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H.Res. 14: Censuring and condemning President Donald J. Trump for attempting to overturn the results of the November 2020 presidential election in the State of Georgia.
H. RES. 14
IN THE HOUSE OF REPRESENTATIVES
Mr. Johnson of Georgia (for himself, Mr. Lieu, Mr. Cicilline, Ms. Escobar, Ms. Dean, Mr. Butterfield, Ms. Jayapal, Ms. Garcia of Texas, Mr. Cohen, Mr. Correa, Mr. Swalwell, Ms. Bass, Ms. Jackson Lee, Mr. Raskin, Ms. Scanlon, Mr. Jones, Ms. Bush, Ms. Adams, Ms. Barragán, Mrs. Beatty, Mr. Beyer, Mr. Bishop of Georgia, Mr. Blumenauer, Ms. Bonamici, Ms. Bourdeaux, Mr. Bowman, Mr. Brendan F. Boyle of Pennsylvania, Mr. Carson, Mr. Casten, Ms. Castor of Florida, Mr. Castro of Texas, Ms. Chu, Ms. Clarke of New York, Mr. Connolly, Mr. Cooper, Mr. Courtney, Ms. DeLauro, Mr. Danny K. Davis of Illinois, Mrs. Dingell, Mr. Doggett, Mr. Espaillat, Mr. Auchincloss, Ms. Eshoo, Mr. Evans, Mr. Foster, Mr. García of Illinois, Mr. Gomez, Mrs. Hayes, Mr. Higgins of New York, Mr. Himes, Mr. Huffman, Mr. Khanna, Mr. Kildee, Mr. Larson of Connecticut, Mrs. Lawrence, Ms. Lee of California, Mr. Levin of Michigan, Mr. Levin of California, Mr. Lowenthal, Mr. Lynch, Ms. McCollum, Mr. McGovern, Mr. McNerney, Mr. Meeks, Ms. Meng, Ms. Newman, Ms. Norton, Ms. Ocasio-Cortez, Ms. Omar, Mr. Pallone, Mr. Panetta, Ms. Pingree, Mr. Pocan, Ms. Pressley, Miss Rice of New York, Mr. Rush, Ms. Schakowsky, Mr. David Scott of Georgia, Ms. Sewell, Mr. Sherman, Ms. Speier, Mr. Suozzi, Mr. Takano, Mr. Thompson of California, Ms. Tlaib, Mrs. Torres of California, Mr. Torres of New York, Ms. Velázquez, Mrs. Watson Coleman, Mr. Welch, Mr. Green of Texas, Mr. McEachin, Ms. Matsui, Mr. Yarmuth, and Mr. Cárdenas) submitted the following resolution; which was referred to the Committee on the Judiciary, and in addition to the Committee on House Administration, for a period to be subsequently determined by the Speaker, in each case for consideration of such provisions as fall within the jurisdiction of the committee concerned
Censuring and condemning President Donald J. Trump for attempting to overturn the results of the November 2020 presidential election in the State of Georgia.
Whereas, on January 2, 2021, President Donald J. Trump called Georgia Secretary of State Brad Raffensperger;
Whereas during that call President Trump repeatedly asked Secretary Raffensperger to overturn the finalized and verified results of the November 2020 presidential election in the State of Georgia;
Whereas President Trump misused the power of his office by threatening an elected official with vague criminal consequences if he failed to pursue the president's false claims;
Whereas President Trump's actions and statements on this call demonstrate an attempt to willfully deprive the citizens of Georgia of a fair and impartial election process in direct contravention of both Federal law and the laws of the State of Georgia;
Whereas President Trump has repeatedly propagated baseless conspiracy theories in statements and on social media, falsely claimed that he won the November 3, 2020, presidential election, and attempted to incite his supporters to undermine our constitutional principles; and
Whereas, as a result of President Trump's words and actions, the lawful results of free and fair elections in the United States have been put in danger: Now, therefore, be it
That the House of Representatives—
publicly states its support for the finalized and verified vote totals in the November 2020 presidential election in the State of Georgia, which recognize Joseph R. Biden as the President-elect and Kamala D. Harris as Vice President-elect of the United States;
censures and condemns President Donald J. Trump for his call to the Georgia Secretary of State on January 2, 2021, during which he asked Secretary Raffensperger to overturn the results of a freely and fairly administered election in the State of Georgia, thereby compromising the very foundation of our Constitution; and
calls on President Trump to retract and disavow this unlawful and unconstitutional behavior and acknowledge President-elect Joseph R. Biden as the victor of the November 2020 presidential election.


Claire J. Kendrick has been awarded through the Provincetown Community Compact, a residency in the Peaked Hill Bars National Register Historic District. She will be residing in one of the 19 well-known Dune Shacks. The Shack is tucked away from civilization, but it has lodged several famous artists and authors throughout time who have been in search of seclusion in which to work.
This is a plein air painting done on location during her residency at the Dune Shack. Painted in early morning light around 5am just before the sun came up, from the C-Scape Dune Shack.
The great rhythms of nature, to-day so dully disregarded, wounded even, have here their spacious and primeval liberty: cloud and shadow of cloud, wind and tide, tremor of night and day. – Henry Beston, The Outermost House.
Beauport Easel has been a great investment – it's been perfect for working on larger plein air. For early morning light I use it right outside the shack looking out the expansive dune scene before me.
Claire J KendrickSeascape SeriesJune 20, 20160 comments36x36, cape cod MA, cjk, claire J Kendrick, dune painting, landscape.


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'Chef Flynn' portrays Justin Bieber of chefs, who started pop-ups at 11
G. Allen Johnson November 19, 2018Updated: November 21, 2018, 12:58 pm
Teenage chef Flynn McGarry in Cameron Yates' documentary "Chef Flynn" (2018). Photo: Kino Lorber
One day, I'd love to eat a 14-course meal prepared by Flynn McGarry. His passion for food is obvious. His passion for life itself — not so obvious.
As portrayed by documentarian Cameron Yates in "Chef Flynn," McGarry — a teenage phenom who began a pop-up restaurant out of his parents' Southern California home at age 11, was profiled by the New Yorker when he was 13 and is a rising star known as the Justin Bieber of chefs — seems to have no life other than food. His success and his approach are fascinating, but I came away from the film really knowing nothing about him. He seems to have no broader interest in anything but himself and his food creations.
McGarry's story is told from ages 11 to 17 (he's now 19) mostly from the point of view of his mother, Meg McGarry, a frustrated filmmaker who became his "stage mother," encouraging his ambition by homeschooling him and becoming his manager and head cheerleader. She has unconditional love for her son, who often during the film seems unappreciative ("Get my mom out of the kitchen!" he barks out during a tense night at a pop-up).
He doesn't seem like a bad kid, but like any teenager who is still growing, Flynn is still gaining life experience. He does show an admirable and mature resilience to a social media backlash by haters who think he is too young for such accolades. But a follow-up documentary, say when he's 30 or 35, might be about a more interesting person.
But the food — wow. Creations involving short ribs, salmon, beets and many others are mouth-watering to look at. He does pop-ups not only in Southern California but New York, where he relocates at age 15, San Francisco (at the Atelier Crenn in 2015) and other places.
Yates' roving camera is also impressive, shining especially during those pop-up restaurant nights where a 14-course meal can go for $160. His camera deftly moves through cramped kitchens and the tiny aisles between customers' tables.
Still, "Chef Flynn" seems more suited for an hour-long show on the Food Network. Its 82-minute running time, although short for a feature film, seems too bloated for this story.
The most interesting character, and worthy of a documentary of her own, is Meg McGarry. Included in "Chef Flynn" are clips of her black-and-white indie short films from the 1980s — she had some talent — and her home videos of Flynn growing up are vital to Yates' film. One also admires this strong woman who, after divorcing Flynn's alcoholic father, was able to not only raise her son and daughter on her own, but fuel Flynn's ambitions as well.
A very remarkable person.
Note: Yates will appear in person at Landmark's Opera Plaza in San Francisco and Shattuck Cinemas in Berkeley on Friday, Nov. 23. www.landmarktheatres.com.
L Chef Flynn: Documentary. With Flynn McGarry. Directed by Cameron Yates. (Not rated. 82 minutes.)
G. Allen Johnson
G. Allen Johnson G. Allen Johnson is a San Francisco Chronicle staff writer. Email: ajohnson@sfchronicle.com Twitter: @BRfilmsAllen

redpajama_set_name: RedPajamaCommonCrawl


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Reviving an age-old story
A review of Neptune Theatre's The Woman in Black
By Gokce On
November 12, 2021/No Comments
Walking into a foggy theatre, audiences already knew this play was going to capture them with its design.
While the story of The Woman in Black isn't a new one, the play is based off a novel written in 1983, the Neptune Theatre's take on this chilling story is one that's worth the time. Neptune is running the show from Oct. 20 to Nov. 14.
At first glance, the set didn't look like anything special – a mostly disheveled room, heavy with abandonment. The lighting was simple; the room was quiet. This all changed as the play progressed. It was almost as if the set itself was revealed along with the plot.
The premise of The Woman in Black is simple – a play within a play. However, there are many layers to the story within. On the surface, it deals with a man who is too afraid to perform his own play. The next layer of the story goes into why he was afraid – a ghost encounter. Lastly, the story delves into why he wanted to tell people his story, revealing his trauma.
Actress Gil Anderson showcased her unique talent as she inhabited the character of the director in one part of the story and Kipps, a lawyer, in the play within the play. She was energetic, enthusiastic and ecstatic. Her energy kept the audience engaged; her character choices were loud and bold but not in an over-the-top distracting way, making the audience move with her character's fluctuating states.
Meanwhile, Gordon Patrick White proved himself as a spectacular character actor. He took on many roles in many forms and never missed a beat within any of them. Even with the minimal costume changes, there was never a doubt in the audience's mind about which character he was playing within the reality of the stage.
However, what really made this production special were the technical elements. The sound was embedded in a way that broke the fourth wall, making it diegetic for one layer of the play and non-diegetic for the other. This use of sound supported White's character acting by adding another layer of realism on to the stage. Whether it was carriage or crowd noises, sound was used to change the atmosphere of the stage without ever really changing the placement of the object and props.
Similarly, while the lighting design was arguably simple, it was very effective in changing the mood of the scene. Using a neater version of rehearsal lights for one layer of the story and specialized coloured lights for the other, the light design helped smooth the transitions between different layers of the story.
The only thing lacking in the production was the titular woman in black. Even though her existence is the main element of horror in the play, she was rather downplayed. The production strived to create suspense and tension through its storytelling, exchanging a solid villain for the idea of one.
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Gokce On
Posted in Arts & Culture, Theatre


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This report provides Verdantix's fifth detailed, fact-based comparison of the most prominent EHS software vendors in the market. Based on the proprietary Verdantix Green Quadrant methodology, the analysis was based on three-hour live product demonstrations with pre-set scenarios as well as vendor responses to a 383-point questionnaire covering 10 technical capabilities, 18 functional capabilities and 11 market momentum categories. Verdantix also leveraged vendor responses from prior questionnaires to maximize the accuracy of our analysis, as well as integrated findings from our recent global survey of 411 EHS decision-makers across 25 industries and 35 countries. The analysis found that 12 vendors currently lead the market: Enablon, Intelex, Cority, VelocityEHS, Sphera, UL, Gensuite, SAI Global, ETQ, Enviance, IsoMetrix and Quentic. Other vendors featured in the 2019 Green Quadrant are Airsweb, Alcumus Group, Dakota Software, DNV GL, INX Software, ProcessMAP, Red-on-line, SAP, SHE Software, TenForce and VisiumKMS.
Yaowen is a Senior Analyst covering Verdantix research on EHS information management technologies, best practices and growth strategies. His current agenda focuses on EHS and sustainability services, quality management, supply chain stewardship as well as chemicals and product compliance. Yaowen has 4-5 years of experience delivering Verdantix research and advisory engagements. He holds a BA degree in environmental management from the University of Pennsylvania.


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Home Circulars / Public Notices Income Tax This
Type: - - All - - Circular Order-Instruction Year -- All -- 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 1995 1994 1993 1992 1991 1990 1989 1988 1987 1986 1985 1984 1983 1982 1981 1980 1979 1978 1977 1976 1975 1974 1973 1972 1971 1970 1969 1968 1967 1965 1960 1959 1955
Income Tax Circulars, Instructions, Public Notices, Trade Notices etc.
01/2023 - 6-1-2023
Extension of time limit for compliance to be made for claiming any exemption under Section 54 to 54GB of the Income-tax Act, 1961 ('Act') in view of the then-Covid-19 pandemic.
25/2022 - 30-12-2022
Clarification for the purposes of clause (c) of Section 269ST of the Income-tax Act, 1961 in respect of dealership/distributorship contract in case of Co-operative Societies
24/2022 - 7-12-2022
INCOME-TAX DEDUCTION FROM SALARIES DURING THE FINANCIAL YEAR 2022-23 UNDER SECTION 192 OF THE INCOME-TAX ACT, 1961.
Finance Act, 2022 - Explanatory Notes to the Provisions of the Finance Act, 2022
Condonation of delay under section 119(2)(b) of the Income-tax Act, 1961 in filing of Form No.10A
CBDT extends due date for filing of TDS statement in Form 26Q for the second quarter of Financial Year 2022-23
Extension of due date for furnishing return of income for the Assessment Year 2022-23
Extension of timeline for filing of various reports of audit for the Assessment Year 2022-23
F. No. 370133/13/2022-TPL - 28-9-2022
Order specifying the Collegium - Explanation to section 158AB of the Income-tax Act, 1961
Additional Guidelines for removal of difficulties under sub-section (2) of section 194R of the Income-tax Act, 1961
Condonation of delay under Section 119(2)(b) of the Income-tax Act, 1961 in filing of Form No. 9A and Form No. 10 for Assessment Year 2018-19 and subsequent years
Condonation of delay under Section 119(2)(b) of the Income-tax Act, 1961 in filing of Form No. 10B for Assessment Year 2018-19 and subsequent years
Condonation of delay under Section 119(2)(b) of the Income-tax Act, 1961 in filing of Form No. 10BB for Assessment Year 2018-19 and subsequent years
Order under section 119 of the Income-tax Act, 1961 (the Act) in relation to tax deduction at source under section 194S of the Act for transactions other than those taking place on or through an Exchange
Guidelines for removal of difficulties under sub-section (6) of section 194S of the Income-tax Act, 1961
Guidelines for removal of difficulties under sub-section (2) of section 194R of the Income-tax Act, 1961
Clarification regarding Form No 10AC issued till the date of this Circular
Circular regarding use of functionality under section 206AB and 206CCA of the Income-tax Act, 1961
Implementation of the judgment of the Hon'ble Supreme Court dated 04.05.2022 (2022 SCC Online SC 543) (Union of India v. Ashish Agarwal).
Guidelines under clause (23FE) of section 10 of the Income-tax Act, 1961
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Etsbôn ou Ozni est un fils de Gad fils de Jacob et de Zilpa. Ses descendants s'appellent les Oznites.

Etsbôn ou Ozni

Etsbôn et Ozni sont le même personnage biblique.

Etsbôn et ses frères

Etsbôn ou Ozni a pour frères Tsiphiôn ou Tsephôn, Haggui, Shouni, Éri, Arodi ou Arod, Aréli.

Etsbôn en Égypte

Etsbôn ou Ozni part avec son père Gad et son grand-père Jacob pour s'installer en Égypte au pays de Goshen dans le delta du Nil.

La famille des Oznites dont l'ancêtre est Ozni ou Etsbôn sort du pays d'Égypte avec Moïse.

Références

Personnage du Tanakh
Personnage de l'Ancien Testament

redpajama_set_name: RedPajamaWikipedia


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Colorado River trouble, rainwater harvesting, private wells, and the future of desalination
By Jeremiah Castelo, originally published by World Water Reserve
The Colorado River has seen a steady decline in flow over the last 3 decades and is predicted to decrease a further 9% in the coming years
Rainwater harvesting and well water pumping are proven methods of self-supply that have seen success in community programs in Zimbabwe and Thailand
Solar-powered desalination is proving to be an effective means for water purification
Preparing for coming water crises may involve water restrictions, conservation, and implementing self-supplying methods
Uncertainty can certainly strip away your peace of mind.
In a developed society, we plan our lives around the certainty we're blessed with.
Many people don't feel the need to grow a vegetable garden due to the expectation that Safeway will always have potatoes in the produce section.
Many of us don't drive more than 15 miles over the speed limit due to the expectation that there probably is a Highway Patrol officer around the corner, ready to enforce the law.
And we don't need to walk many miles to a clean water source because we're fortunate to be able to flip the tap, certain that water will spout forth.
Yes, certainty is a blessing.
But it isn't unreasonable to recognize that many of the certainties that keep our societal structure in place appear to be weakening.
Drought is engulfing the Western half of the United States.
Supply chains are being disrupted and according to financial analysts, inflation isn't stabilizing anytime soon.
HOOVER DAM / RYAN THORPE / UNSPLASH
The obvious, most visceral reaction to all of this is to FEAR. It's easy to feel anxious about the uncertainty of our future but we don't have to be compelled by it.
It's better to recognize the dangers now than to get caught off-guard later.
The truth is, there's still MUCH you can do to secure your future.
Let's get into it.
40 Million Americans Depend on a Declining Colorado River
NPR, Ensia.com
COLORADO RIVER / GABRIEL TOVAR / UNSPLASH
Californians have been dealing with the threat of drought for as long as many can remember, so water issues are nothing new in the West. But to ignore the effect that these water issues will have on the rest of the country's population is a grave mistake.
The Colorado River, which 40 million Americans in the Western United States depend on as their main water source, has seen a decline in flow over the past 3 decades according to the US Bureau of Reclamation (NPR).
A study projects that the river flow would decrease by a further 9% over the next 50 years, which calls for significant restrictions on water usage in order to temper its decline (Ensia).
We can expect to see a rise in restrictions on water usage across the country as an effort to manage these issues. Other strategies such as water reuse and water transfers are being explored by various agencies.
But while these large-scale implementations are certainly vital, an article published by the Global Water Forum indicates how self-supplying can also be an effective practice in times of drought (Global Water Forum).
Self-Supplying as a Method for Community Water Management
CHIANG MAI, THAILAND / DARCEY BEAU / UNSPLASH
Self-supply is identified as the practice of small communities in finding their own water supply rather than relying on municipal sources as large communities and cities do.
According to GWF, rural communities in Zimbabwe and Thailand greatly benefited from self-supplying water in the form of well water pumping and rainwater harvesting amid countrywide drought.
It's worth appreciating GWF's sentiment of highlighting solutions for small communities in the midst of seeking larger, global solutions. While global solutions are certainly the destination, it can be easy to miss how smaller communities are affected and how they can benefit from fairly reasonable living adjustments.
Groundwater and private wells
Some communities in the United States already implement self-supply methods as 13% of the population relies on private wells as their source of water. And 38% of the population relies on groundwater in general, usually from a public source. The rest of the country sources its water from reservoirs or naturally flowing surface water sources such as the Colorado River (Global Water Forum).
Now, urban and city dwellers may be a bit out of luck in terms of groundwater as self-supply as cities have their own public water systems. So, it's the rural areas that can benefit from private wells in a much more practical way.
For those who do have the opportunity to source groundwater, it can be a gold mine. Sourcing groundwater via a private well is optimal for self sufficiency – it's potentially unlimited, unregulated, and free.
There are a lot of critical factors involved with well water pumping. Learn the basics of how a private well works here.
And in areas with adequate rainfall, rainwater harvesting is an increasingly common method of supplementing one's water source.
Despite common misconceptions, collecting rainwater isn't illegal in any of the 50 states.
While some states do have strict regulations on the method that it's collected, some states, in fact, provide incentives to encourage rainwater harvesting.
RAIN BARRELS / JBOLLES / FLICKR
An average-sized rooftop can collect about 600 gallons of rainwater for every inch of rainfall. With the right water pump and filtration system installed, rainwater can provide a significant amount of drinkable water for a household.
Learn more about how to harvest rainwater from this beginner's guide.
OCEAN WATER / JAKOB OWENS / UNSPLASH
But what of areas where groundwater and rainwater aren't an option?
In many areas, a freshwater source such as a lake, river, or stream supplies a cabin or cottage with all its water needs. Each state has its own laws on drawing from freshwater sources, so be sure to check with your state's legislature.
Having a wider variety of purification methods expands one's options for sourcing water. Common methods such as carbon filtration, UV purification, and disinfection can guarantee clean water consumption in most rural areas.
Desalination, the method of purifying saltwater for consumption, has shown promising development in recent years. The main issue with desalination is the extensive energy requirement needed to process the highly-concentrated salt.
RO DESALINATION PLANT / ROPLANT.ORG / CREATIVE COMMONS
But as desalination technology becomes efficient enough to be able to purify water in large quantities, then oceans and saltwater lakes can be used as major water sources.
And many desalination research projects around the world are proving that high-efficiency desalination is just around the corner.
Scientists have discovered a way to improve solar-powered desalination technology with titanium nitric oxide (TiNO), reducing ocean water's salinity by over 97.4% (OGEI).
On September 22, 2021, one of the world's largest desalination projects was implemented in a rural area of Kenya. Bubisa WaterKiosk is a program that provides over 30,000 people with clean water via 100% solar-powered desalination technology (OGEI).
As desalination technology continues to become more efficient, perhaps more communities may soon reap the benefits of it.
How to Prepare for Coming Water Crises
UNCOVERED RAIN BARREL / PIXABAY
Water scarcity is a reality that we'll either learn to manage or be overwhelmed by. On the one hand, allowing ourselves to be gripped by fear and panic won't do any good. On the other hand, completely ignoring reality and acting as if nothing's happening is just as bad.
It's important to have a healthy assessment of the world around us and to make decisions based on what we see. We mustn't make rash decisions but we mustn't be complacent either.
Prepare your household for water restrictions
Water restrictions will likely be a reality for many who live in larger urban areas, so preparation for that is vital. Making the necessary adjustments beforehand will make for an easier transition once restrictions are in full effect.
Begin taking note of the amount of water you and your household currently use and make conservation a priority. Cut out wasteful practices such as leaving the tap on while brushing your teeth or while scrubbing dishes. Systematize your water usage among family members to reduce waste by consolidating laundry. Use water-efficient showerheads and faucets.
Water Education Foundation released some practical water conservation measures that are easy to abide by.
Modify your home for rainwater collection
Regions such as the Pacific Northwest, Northern California, and some parts of Colorado, Utah, and Idaho experience enough rainfall to significantly supplement a household's water supply. Even in areas where rainfall isn't as frequent, installing a rainwater harvesting system can help collect enough water for outdoor usage during the dry seasons. The National Weather Service provides a rainfall map that monitors precipitation across the entire country.
This rainwater harvesting guide will help you get started.
Explore drilling a private well
Those who currently rely on a private well are in a prime position. Those looking to relocate to an area where wells are an option will require a bit of research into aquifer locations, state laws, and well-drilling companies. But once a private well is established in a location where groundwater is sufficient, treat it like a gold mine because it may very well be one.
Learn more about private wells here.
Keep a close eye on water reports
Agencies such as the USGS and USBR regularly publish information on the conditions of aquifers and surface water sources. Maven's Notebook is a great resource for water news in California and is regularly updated. Paying close attention to weather changes can help you stay ahead of the game and make better decisions for yourself and your family.
Familiarize yourself with other water purification methods
While most of us have never considered the need to purify our own water due to the convenience of modern water services, if the tap were to ever fail, knowledge of alternative purification methods may be what saves you. Carbon filtration, UV purification, disinfection, distillation, reverse osmosis, and boiling are among the many effective ways to make water safe.
Learn how to purify water for drinking here.
Perhaps most important of all, don't allow yourself to feel overwhelmed. Much of what's spoken of on media outlets isn't pleasant, and that may partially be due to the fact that good news just doesn't stick.
But that's not to say that there aren't real water issues unfolding before our eyes. Keep your eyes open but don't be blinded by fear. There is still much you can do to secure your own future.
Global Water Forum. (2021, September 14). Self-supply for resilience and water security – World water week, 2021. Global Water Forum | The challenges of water governance in the 21st century. https://globalwaterforum.org/2021/09/14/self-supply-for-resilience-and-water-security-world-water-week-2021/
NPR. (2021, June 9). The drought in the western U.S. is getting bad. Climate change is making it worse. NPR.org. https://www.npr.org/2021/06/09/1003424717/the-drought-in-the-western-u-s-is-getting-bad-climate-change-is-making-it-worse
Off Grid Energy Independence. (2021, September 16). Launch of the largest solar powered water desalination system in Kenya. Off Grid Energy Independence. https://www.offgridenergyindependence.com/articles/24754/launch-of-the-largest-solar-powered-water-desalination-system-in-kenya
Off Grid Energy Independence. (2021, May 3). Solar powered desalination unit shows great promise. https://www.offgridenergyindependence.com/articles/23717/solar-powered-desalination-unit-shows-great-promise
Resilience. (2021, October 6). The future of water in the U.S. west is uncertain, so planning and preparedness are critical. https://www.resilience.org/stories/2021-10-06/the-future-of-water-in-the-u-s-west-is-uncertain-so-planning-and-preparedness-are-critical/
Tags: building resilient water systems, water crises
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A swimming commons
Jeremiah Castelo
I'm Jeremiah Castelo, the owner of World Water Reserve. I'm a writer and researcher with a particular interest in sustainability and rural living, water scarcity, and innovative water purification methods. I utilize my multimedia and communication experience in the NGO and humanitarian fields to bring light to important topics. My passion is to educate others...
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Chair's Circle
Fund Our Scholars
About our Scholarship
Esperanza Fund
Without our volunteers, Esperanza cannot make the impact we have on so many deserving students. Our network of 150 volunteers read applications, run our social media, host fundraising events, interview scholars, mentor scholars and much more. These accomplished professionals hold elite jobs at top organizations by day, and take time to give back to the next generation of leaders in their respective fields by night.
Our volunteer leaders include a scientist at NASA; physicians at the University of Maryland, the Office of the U.S. Global AIDS Coordinator, and NIH; a development engineer at US AID, and an assistant professor of information technology at John Tyler Community College, among others. We'd love you to be one of them!
Meet some of our extraordinary volunteers!
Alice Wang: Co-Founder
Alice Wang, Co-Founder, served as Chair of the Board of Directors from 2009 to 2015. Her work on Esperanza...
Alvaro Bedoya: Co-Founder
Alvaro Bedoya, Co-Founder & Member, Board of Directors, started Esperanza in 2009 alongside Andy Felton and Alice Wang, who...
Ameesha Sampat, Communications Committee Chair
Ameesha Sampat, Communications and Marketing Chair, joined Esperanza as a mentor in 2016, and a volunteer in 2017. Ameesha...
Amilcar Guzman: Mentor & Volunteer
Amilcar Guzman, Mentor & Volunteer, is a member of the Development and the Scholarship Committees. His involvement with Esperanza started...
Birdie Rovner Pieczenik: Mentor
Birdie Rovner Pieczenik, Mentor, chanced to meet an Esperanza mentor at an MIT dinner/lecture who sounded truly inspired by the volunteer...
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Jessica was born and raised in Carson, CA by her two parents who migrated to the U.S. from Nicaragua...
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Jonathan Diaz, Volunteer, worked closely with immigrant communities in Boston, MA and in Rochester, NY. Looking to remain involved...
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Jose was born and raised in Puerto Rico, attended University of Puerto Rico and attained an electrical engineering bachelor...
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Patricia Silva-Santisteban, Mentor, teaches Information Technology at John Tyler Community College in Virginia. Patricia witnessed the creation of Esperanza...
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I am a firm believer in education as the path toward life's achievements as well as contributing to the welfare of our fellow human beings. So many of the young people today have to overcome several hurdles to gain an education, the most formidable of which are faced by immigrant children. As an immigrant myself, I am proud to be part of Esperanza and help make the journey somewhat less insurmountable for our outstanding and well deserving scholars.
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When I read our applications, I am inspired not just by our scholars, but the dedication of mentors—teachers, counselors, community members—who play important roles in encouraging and supporting students who may have fewer resources throughout high school. I am pleased to be part of an organization that provides that same mentorship and support for students in their college years.
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text:
Marcos Heredia
Classic Disney had all the best rom-com and fairy tales that we watched all our childhood. Disney indeed played a significant role in making our childhood memorable. However, today the Disney plus is much more than a classic animation. The Disney plus is a well-developed OTT platform where you can get your hands on a lot of quality work.
The movies, series, and animations of Disney plus are to die for. Recently, Disney plus has bought a number of good movies. At the same time, there is a lot of quality work that Disney is producing or has produced in the last couple of years. There is a lot that you can find there. Thus, we bring you the list of some of the Disney plus movies that you should watch.
Best Movies On Disney Plus To Watch Right Now In 2022
The Pirates Of The Caribbean Trilogy
The Toy Story Trilogy
Thanks to the lockdown, the theatre industry today is exploring a lot of other options to reach the consumer. In all that effort, how can we forget the hype of Hamilton? If you haven't watched it yet, let us tell you that the movie was a record-breaking hit. It broke the first record by grabbing 16 back-to-back nominations from tony, of which it won 11. The cast of the movie was even invited to the White House to perform for Barack Obama.
In the series, Jack Sparrow is primarily concerned with adventures along with mutinous former first mate Barbossa, the fiercely independent Elizabeth Swann, and bland, but altogether quite sweet, love interest Will Turner. The story is rounded out with curses, krakens, maelstroms, British imperialism, and a tentacle-faced Davy Jones. His first film might have been better, but Dead Man's Chest and At World's End are still great movies. The fact that they crammed so much romance and color into a 15-minute film is commendable.
You will love this movie for its soundtrack. The Soul is based on a bit of a different story where the Soul wants a body again. A soul appears in front of supreme power and asks it to reunite it to its pre-birth personality. The unique plot sparks an existential quest and an emotional journey for the Soul. If you are into thought-provoking movies, we recommend you to catch up with this one on Disney plus.
The movie Hocus Pocus focuses on a Halloween-themed story that isn't scary at all. The movie is a good pick to pass your time and not get scared after watching something from the horror genre. It wasn't much of a hit at the time of its release. However, it developed its repute over time. The hardest part to forget in this movie is the Sandersons sisters, who were the child-murdering villains of this movie.
Robert Downey Jr. is the main lead of Iron man. The movie is based on the cocky millionaire who somehow becomes a life-saving superhero. The movie is not like other superhero stories. Rather the story, in comparison, is much more developed and makes a lot of sense. If you are into Superhero movies, we recommend you not to miss Iron Man. It's a must-watch, and you will realize how far iron man has come, unlike its competitor movies.
The documentary free solo is based on the climber Alex Honnold. The guy decided to climb a mountain without any safety precautions. The free solo climbers are the people who do not have any ropes and safety equipment in case they fall. The documentary doesn't only highlight the professional aspect of Honnold's decision of free solo. Rather, it also highlights how his decision affected his personal life and his relationships, especially his relationship with his girlfriend Sanni.
The toy story has 4 parts. The movie is an out-of-the-box genius story. It narrates the concept that all your toys are alive, and they roam around the rooms when you are away. Instead of creeping people out, toy stories brought an amazing work of art for kids. Story 4 is sort of an epilogue and is not quite similar to the first three parts. And, how can we forget buzz lightyear and woody? One of the most entertaining characters of the movie. If you want to have a good time with your kids, we recommend watching the toy story with your kids.
The movie can provide you with the most heartwarming experience. The Isle of Dogs talks about the exiled dogs gathering at the space where they all are liable to live together. The movie is narrated from the mind of Wes Anderson. The young boy goes on a search mission to find his guard dog, where he ends up meeting all the dogs of Megasaki.
Frozen can be the best example of modern Disney cinema. Frozen is a story of two sisters Elsa and Anna. Both of the sisters got separated from each other after the death of their parents. Elsa was kept isolated as she had some ice powers.
The twist in the story takes place when the kingdom of Arendelle gets in danger. With the help of a snow harvester and a snowman, Olaf both the sisters save the kingdom. The story is inspiring yet entertaining. Thus, it is a perfect package. The storyline of Frozen will keep your child hooked.
After Maleficent, Disney brings Cruella, a colorful origin story that explores a young fashion designer's madcap transformation into Cruella de Vil. A visually spectacular feast of two women on the warpath occurs in the film when Emma Stone, as young Cruella, goes toe-to-toe with a renowned English designer, played by Emma Thompson.
The story is about two teenage brothers played by Chris Pratt and Tom Holland. The story portrays the coexistence of modern and medieval times in the perfect way. The boys went on a magical quest so that they could spend just one more day with their dead father. The movie conveys powerful emotions for family and memory of family. If you haven't watched it yet, we suggest you add it to your Wishlist.
This movie is an action-packed thriller. It can be one of the best selections for movie nights. The jungle quest is another addition to the thrilling genre on Disney plus after pirates of the Caribbean. The cast has Emily Blunt, who is a scientist and Dwayne Johnson, who is a skipper. The skipper went down the Amazon in search of life and trees.
The story of this movie revolves around Luca, a sweet boy who becomes friends with another boy named Alberto, an Italian. The two of them discover that when they go into the water, they transform into mermaids. Luca is also about adventure and discovery and keeps you hooked till the very end. The movie is a very good addition to Disney plus. Thus, if you haven't watched it, we recommend you give it a try.
Related More: How to Get Disney Plus On TV
Raya and the Last Dragon is one of the best Walt Disney movies in the last couple of years. It went under the radar due to its lockdown release. However, we believe it is a great watch, and you should consider watching it now.
The movie is an epic fantasy story with an intriguing premise. It focuses on the journey of a young woman named Raya, who aims to find a missing dragon and undo a cataclysm that splits Kumandra's world into five distinct tribes.
The starring role of Awkwafina as the dragon Sisu makes it not only fun and thrilling but also hilarious. Thus, with the movie on your watch list and we bet you would not regret it.
Related More: Top Movies About Pandemics and Viral Diseases
From toy story, one of the most popular movies till Luca and Raya and the last dragon. We tried our best to accumulate the most intriguing and entertaining movies for you. These are no doubt some of the best that you can watch on Disney. Some of them are animated, while others are not. We kept in mind different genres.
The different movies from different genres were chosen so that people can pick and choose the movies according to their choice. The list above provides you with a wide range to choose from. We are certain this article can sort you for the holiday season and movie nights. So, call your friends, spend quality time with your spouse or have a lazy evening while watching all the best movies that you can watch on Disney plus.
Upon graduating from Ash-ford university, Marcos knew that he had his place in the entertainment industry. He frequented the visits to the cinema halls because of his passion for movies and entertainment. Heredia later develops a writing passion for movies and celebrities. He later finds a part-time job as a writer for famous SEO companies. Marcos did benefit from his four-year studies after pursuing mass communication and Journalism. He now works as a writer with over 1000 articles under his name. The readers love him because he delivers timely content that captures details about their favorite athletes, best actors and trending movies. Marcos spends their leisure hours watching horror movies.
It's the holiday season again and, that means more time for friends and family! Christmas ...
By Marcos Heredia
Christmas time is one event that is guaranteed that almost everyone will be at home. ...
As Netflix is eventually gaining popularity among the masses, there is quite a lot of ...


text:
Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer's disease
Grazia D'Onofrio1,
Francesco Panza ORCID: orcid.org/0000-0002-7220-06561,2,3,
Daniele Sancarlo1,
Michele Lauriola1,
Mariangela P. Dagostino1,
Giulia Paroni1,
Madia Lozupone2,
Antonio Mangiacotti1,
Paola Bisceglia1,
Carolina Gravina1,
Maria Urbano1,
Filomena Addante1,
Francesco Paris1,
Leandro Cascavilla1,
Antonio Greco1 &
Davide Seripa1
Translational Neurodegeneration volume 8, Article number: 4 (2019) Cite this article
Serotoninergic pathways underlying delusion symptoms in Alzheimer's disease (AD) have not been fully clarified. 5-Hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) is a variable number tandem repeats in the promoter region of serotonin transporter encoding-gene affecting transcription.
We investigated the association of 5-HTTLPR with delusions in a total of 257 consecutive patients clinically diagnosed as AD according to the National Institute on Aging-Alzheimer's Association criteria. All participants underwent a comprehensive evaluation with a standardized comprehensive geriatric assessment and Neuropsychiatric Inventory.
Delusion symptoms were observed in 171 patients (66.54%). In respect to AD patients without delusions, AD patients with delusions showed a low prevalence of S-plus carriers (5-HTTLPR-L/S + 5-HTTLPR-S/S genotypes) [p < 0.001; odds ratio (OR) = 0.240, 95% confidence interval (CI) = 0.121–0.471]. Logistic regression analysis adjusted for the apolipoprotein E polymorphism showed that in AD patients with delusions the presence of an 5-HTTLPR-S allele may reduce disease duration (p = 0.005; OR = 0.680, 95% CI = 0.522–0.886) and increase aberrant motor activity (p = 0.013; OR = 2.257, 95% CI = 1.195–4.260). The present findings suggested that 5-HTTLPR might be associated with delusions in AD. S-plus carriers might be associated with protective effect against delusions in AD.
More studies on wider samples of high selected demented patients are needed to confirm our results. However, the present findings suggested that a genetic factor related to serotonin metabolism might exert a protective role on the clinical expression of neuropsychiatric clusters in AD with important implications regarding mechanisms underlying delusions and their possible treatment across the AD and dementia spectrum.
Alzheimer's disease (AD) accounts for the 60–70% of cases of dementia. Current estimates indicate 17% of people aged 75–84 years in the US have AD, and the disease costs the country $277 billion per year [1]. Dementia costs in Italy were estimated to be €39.3 billion in 2016 [2]. The prevalence is projected to triple by 2050 to 13.8 million with annual costs of >$1.1 trillion [1]. AD is often complicated by neuropsychiatric symptoms (NPS), which occur in one-third of patients at an early stage of the disease [3, 4]. The possible hypotheses for psychopathology in AD involve selective loss of different neuronal populations, alterations of specific neurotransmitter systems, and genetic risk factors [5, 6]. Delusions appearing with their disabling and persistent features is among the most common NPS characterizing AD course and ranging from 10 to 73% [7]. In a recent study, as compared with AD patients without delusions, it was shown that AD patients with delusion showed higher dementia severity, and higher impairment in cognitive and depressive symptoms, and in several neuropsychiatric domains, and this appeared to be associated with higher multidimensional impairment and increased risk of mortality [8].
Previous studies have shown that NPS in AD were highly heritable [9], increased AD familial risk, and showed significant genome-wide linkage [10], providing evidence that genetic variation does contribute to delusion risk. More rapid cognitive decline was the most consistent correlate of AD with psychosis (AD+P), defined as the occurrence of delusions or hallucinations, compared to AD without psychosis (AD-P) [11]. A recent genome-wide association study (GWAS) showed for the first time an association of AD+P with polygenic risk for a unique set of common variants and inversely associated with polygenic risk for schizophrenia [12]. In this large GWAS, the biological pathways identified by the associations of schizophrenia single nucleotide polymorphisms (SNPs) with AD+P were endosomal trafficking, autophagy, and calcium channel signalling [12].
Investigations of loci in serotonergic gene pathways are among the best studied in association studies of AD with NPS [13, 14]. The 5-hydroxytryptamine (5-HT, serotonin) transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) is a well-characterized variable number of tandem repeat in the promoter region of the serotonin transporter gene, with two major alleles termed long (L) and short (S), suggesting to affect gene transcription [15, 16]. A deeper knowledge of the "5-HTTLPR universe" will be useful to better understand the molecular basis of serotonin homeostasis and the pathological basis underlying serotonin-related NPS conditions and traits.
The association of 5-HTTLPR with delusions in AD was studied in only few studies from Caucasian [17,18,19,20,21] and Japanese patients [22, 23], with contrasting evidence of association. In a recent study, the 5-HTTLPR was associated with delusions in dementia with Lewy bodies (DLB), with important implications regarding the mechanisms underlying this symptom across the AD/DLB/Parkinson disease (PD)-dementia spectrum [24]. The aim of the present study was to determine whether the 5HTTLPR serotonin transporter gene polymorphism was associated with delusions in patients with AD and to determine the association of 5-HTTLPR polymorphisms with other NPS.
This prospective observational study fulfilled the Declaration of Helsinki [25], and the guidelines for Good Clinical Practice [26]. The approval of the study for experiments using human subjects was obtained from the local Ethics Committees on human experimentation. Written informed consent for research was obtained from each patient or from relatives/legal guardian in the case of critically disabled demented patients prior to participation in the study. To avoid bias due to different genetic backgrounds in the population, all patients and subjects included in this study were Caucasians and we did not include people of Jewish, Eastern Europe or Northern Africa descent, with most individuals at least two or more generation living in Central and Southern Italy for at least three generations. Patients consecutively evaluated from March 1, 2015 to December 31, 2016 at the Alzheimer's Evaluation Unit of the Complex Structure of Geriatrics of the IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Foggia, Italy were screened for eligibility.
Inclusion/exclusion criteria
Inclusion criteria were: 1) age ≥ 65 years, 2) ability to provide an informed consent or availability of a relatives or a legal guardian in the case of severe demented patients, 3) diagnosis of AD according to the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria [27], 4) a complete cognitive and neuropsychiatric assessment, 5) a complete Comprehensive Geriatric Assessment (CGA) [28]. Exclusion criteria were: 1) diagnosis of non-AD dementia; 2) presence of serious comorbidity, tumors and other diseases that could be causally related to cognitive impairment (ascertained blood infections, vitamin B12 deficiency, anemia, disorders of the thyroid, kidneys or liver); 3) history of alcohol or drug abuse, head trauma, and other causes that can cause memory impairment; 4) a history of schizophrenia, schizoaffective disorder, delusional disorder or mood disorder with psychotic features, major depressive disorder, substance use disorder, or mental retardation according to Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DMS-5) criteria [29].
Comprehensive geriatric assessment
The CGA [28] was carried out using assessment instruments widely employed in geriatric practice. Functional status was evaluated by activities of daily living (ADL) index [30], and by instrumental activities of daily living (IADL) scale [31]. Cognitive status was screened by the Short Portable Mental Status Questionnaire (SPMSQ) [32]. Comorbidity was examined using the Cumulative Illness Rating Scale Comorbidity Index (CIRS-CI) [33]. Nutritional status was explored with the Mini Nutritional Assessment (MNA) [34]. The Exton-Smith Scale (ESS) [35] was used to evaluate the risk of developing pressure sores. Medication use was defined according to the Anatomical Therapeutics Chemical Classification code system, and the number of drugs used by patients was recorded. Social aspects included household composition, home service, and institutionalization.
In all patients, cognitive status was screened with the Mini-Mental State Examination (MMSE) [36]. Dementia was diagnosed following the DMS-5 criteria [29]. Diagnoses of possible/probable AD were made according to the NIA-AA criteria [27]. Diagnoses of possible/probable VaD were made according to the criteria of the National Institute of Neurological Disorders and Stroke - Association Internationale pour la Recherche et l'Enseignement en Neurosciences Work Group (NINDS-AIREN) [37]. In unclear cases, differential diagnosis between AD and VaD was based also on the Hachinski Ischemic Score: scores ≤4 were considered as probable AD, scores ≥7 were diagnosed as VaD [38]. Diagnosis of AD and VaD was always supported by neuroimaging evidence (computerised tomography scan and/or nuclear magnetic resonance). In particular, the presence of multiple cortical/subcortical infarcts or an infarct in a strategic area such as the thalamus or temporal lobe and/or lesions of the white matter indicated probable VaD; the absence of the above-mentioned cerebrovascular lesions indicated AD. The age at onset of AD symptoms was estimated by semi-structured interviews with the patients' caregivers [39], body mass index(Kg/m2), disease duration, and delusion symptom duration were also calculated for AD patients.
Neuropsychiatric assessment
Neuropsychiatric assessment was performed using the Neuropsychiatric Inventory (NPI) that is based on a structured interview with a caregiver and/or patient's relative [40]. The following 12 neuropsychiatric domains were evaluated: delusions, hallucinations, agitation/aggression, depression mood, anxiety, euphoria, apathy, disinhibition, irritability/lability, aberrant motor activity, sleep disturbances, and eating disorders. For each domain, a screening question is asked to determine if the behavioral change is present or absent. If the answer is positive the domain is explored at greater depth with the sub-questions. If the sub-questions confirm the screening question, frequency is rated from 1 to 4 and severity is scored from 1 to 3. The product (severity x frequency) is calculated for each behavioural change present during the previous month or since the last evaluation. Patients with NPS were identified on the basis of the following parameters: presence of any delusions or hallucinations on the NPI (i.e., a score of ≥1 on either subscale), and/or dysphoria score > 6, anxiety score > 6, disinhibition score > 4, irritability/lability score > 2, and/or score on the apathy, agitation/aggression, euphoria, aberrant motor behavior, sleep disturbance, and eating disorder subscale > 1. In the present study, we used data from individual NPI delusions or hallucinations domains as binary data 0/1 for the definition of the AD-delusion subtype. Thus, a disturbance in the given domain was labelled as 1 = present if there was a score > 0 for hallucinations or delusions domain.
Genomic DNA was purified from fresh/frozen blood samples following salting-out method [41]. Analysis of the 5-HTTLPR and apolipoprotein E (APOE) polymorphisms were made in blinded fashion previously described [42, 43].
Normal distribution of continuous variables was verified by the Shapiro-Wilk normality test. Comparisons between continuous variables were performed by using the Welch Two Sample t-test (Parametric distribution) or the Wilcoxon rank sum test with continuity correction (non-parametric distribution). Categorical variables were compared by using the Pearson's Chi-squared test with Yate's continuity correction or the Fisher exact test for count data. Observed differences in clinical and genetic characteristics were confirmed by a general linear model by using the APOE polymorphism as confounding factor. Relative allelic frequencies were estimated by the gene-counting method [44]. The Hardy-Weinberg (HW) equilibrium was verified for each polymorphism. All statistical analyses were performed using the R Statistical Software Ver. 3.4.0 [45]. Tests in which the p-value was smaller than the Type I error rate α = 0.05 were declared significant.
During the enrolment period, 277 AD patients were screened for the inclusion in the study. Of these, 8 patients were excluded because they were younger than 65 years, 2 patients had an incomplete examination and 10 patients had severe comorbidity associated with cognitive impairment. Thus, the final population included 257 AD patients, 82 men (31.92%) and 175 women (68.09%) with a mean age of 80.21 ± 6.62 years (age range 65–97), of which 171 AD patients with delusions (66.54%) and 86 AD patients without delusions (33.46%).
Demographic and clinical characteristic of patients according to delusion symptom are reported in Table 1. AD patients with delusions showed a different social support network if compared with AD patients without delusions (19.88% living alone, 65.50% living with family, 14.62% institutionalized for AD patients with delusions vs. 2.33, 95.35, and 2.33% for AD patients without delusions; p < 0.001) and a higher number of concomitant treatments (6.60 ± 3.07 vs. 5.08 ± 3.12; p = 0.026). AD patients with delusions also showed a higher risk of malnutrition (MNA score 18.81 ± 5.77 vs. 20.98 ± 5.64; p = 0.011), a greater functional impairment, as measured by ADL (3.27 ± 1.98 vs. 3.89 ± 1.86; p = 0.025) and IADL (2.05 ± 2.39 vs. 2.87 ± 2.81; p = 0.037), a greater number of pressure sores (ESS 14.50 ± 3.29 vs. 15.80 ± 3.29; p = 0.008), and an higher degree of cognitive impairment as measured by MMSE (16.81 ± 5.92 vs. 18.33 ± 5.64; p = 0.017) and SPMSQ (5.29 ± 1.93 vs. 4.75 ± 1.87; p = 0.014), a worse neuropsychiatric condition (NPI score 35.57 ± 20.94 vs. 22.72 ± 17.04; p < 0.001), with an associated greater burden level (NPI-Distress score 15.71 ± 8.08 vs. 9.32 ± 5.96; p < 0.001).
Table 1 Demographic and clinical characteristics of Alzheimer's disease (AD) patients according to the presence of delusion symptom
Prevalence of NPS according to delusion symptom is reported in Table 2. As compared with AD patients without delusions, AD patients with delusions showed a higher prevalence of hallucinations (not observed in AD patients without delusions), agitation/aggression (3.74 ± 3.57 vs. 0.46 ± 1.11; p < 0.001), anxiety (5.34 ± 4.44 vs. 3.42 ± 3.88; p < 0.001), euphoria (not observed in AD patients without delusions), disinhibition (not observed in AD patients without delusions), irritability/liability (4.17 ± 4.17 vs. 0.60 ± 1.28; p < 0.001), and aberrant motor activity (0.86 ± 2.11 vs. 0.43 ± 1.87; p = 0.029). In these patients, a trend towards a higher prevalence of apathy (5.75 ± 4.72 vs. 4.86 ± 4.75; p = 0.072) and sleep disturbance (5.52 ± 4.39 vs. 4.58 ± 4.45; p = 0.094) was also observed.
Table 2 Neuropsychiatric symptoms in Alzheimer's disease (AD) patients according to to the presence of delusion symptoms
Prevalence of 5-HTTLPR genotypes and estimated allele frequencies, as well as those of the APOE polymorphism, are reported in Table 3. As compared with AD patients without delusions, the prevalence of heterozygotes 5-HTTLPR-L/S as well as homozygotes 5-HTTLPR-S/S was lower in AD patients with delusions [37.43% vs. 61.63%, p < 0.001; odds ratio (OR) = 0.226, 95% confidence interval (CI) = 0.111–0.459, and 20.93% vs. 15.79%, p = 0.003; OR = 0.281, 95% CI = 0.115–0.682, respectively). The prevalence of L/L vs. S plus (L/S + S/S) according to delusion symptom is graphically presented in Fig. 1. The estimated frequency of S allele also resulted lower in AD patients with delusions (0.345 vs. 0.517, p < 0.001; OR = 0.415, 95% CI = 0.166–1.038). In the analysis of the APOE polymorphism, no differences in genotype distribution according to delusion symptom was shown, despite a non significant lower frequency of the APOE ε2 allele in AD patients with delusions (0.032 vs. 0.070, p = 0.041; OR = 0.415, 95% CI = 0.166–1.038).
Table 3 Genetic characteristics of patients with Alzheimer's disease (AD) according to the presence of delusion symptom
Carriers of 5-hydroxytriptamine transporter gene-linked polymorphic region (5-HTTLPR) genotypes L/L or L/S + S/S (S-plus) in Alzheimer's disease patients with and without delusions
The APOE-adjusted associations of S-plus carriers with clinical characteristics according to delusion symptom are reported in Table 4 and Additional file 1: Figure S1. S-plus carriers have low disease duration in the overall sample (p = 0.011; OR = 0.740, 95% CI = 0.587–0.933), as well as in AD patients with delusions (p = 0.005; OR = 0.680, 95% CI = 0.522–0.886) (Additional file 1: Figure S1, panel A). In these patients, a trend toward higher NPI-Distress was also suggested (p = 0.074; OR = 9.564, 95% CI = 8.161 × 10− 1-1.121 × 102) (Additional file 1: Figure S1, Panel B). The APOE-adjusted association of S-plus carriers with NPS according to delusion symptom is reported in Table 5 and Additional file 2: Figure S2. S-plus carriers had higher aberrant motor activity in the overall sample (p = 0.050; OR = 1.692, 95% CI = 1.004–2.850), as well as in AD patients with delusions (p = 0.013; OR = 2.257, 95% CI = 1.195–4.260) (Additional file 2: Figure S2, Panel A). In these patients, a trend toward higher irritability/liability was also suggested (p = 0.054; OR = 3.520, 95% CI = 0.988–12.500) (Additional file 2: Figure S2, Panel B).
Table 4 Apolipoprotein E-adjusted estimates of the association of 5-hydroxytriptamine transporter gene-linked polymorphic region (5-HTTLPR) S-plus carriers with clinical characteristics in patients with Alzheimer's disease (AD) according to to the presence of delusion symptom
Table 5 Apolipoprotein E-adjusted estimates of the association of 5-hydroxytriptamine transporter gene-linked polymorphic region (5-HTTLPR) S-plus carriers with neuropsychiatric symptoms in patients with Alzheimer's disease (AD) according to to the presence of delusion symptom
In the present study, investigating the role of 5-HTTLPR in delusion symptom in a large cohort of 257 AD patients, we found a great difference in the distribution of the S-plus carriers (5-HTTLPR-L/S + 5-HTTLPR-S/S genotypes), suggesting an important role of serotonin in delusion symptom physiology. In fact, assuming the L/L genotype as the reference in the statistical analysis, the main finding of the present study was that S-plus carriers were strongly underrepresented in AD with delusions suggesting a possible protective role. Other NPS in AD patients such as apathy and sleep disturbance, which are also associated with dysfunction of the serotonin system, also trended towards a significance difference between the two genotyped cohorts. Furthermore, AD patients with delusions showed a higher prevalence of hallucinations, not observed in AD patients without delusions and also linked to serotonin system dysfunction. Estimating the role of 5-HTTLPR with the other clinical variables, particularly NPS, only minor effects were observed. In fact, 5-HTTLPR S-plus carriers mainly influenced disease duration (lower) and aberrant motor activity (higher). We also adjusted the analyses for the APOE polymorphism, the most important genetic factor influencing risk for AD, thus validating the quality of the present analysis.
In previous studies, the findings on the association of 5HTTLPR polymorphism with delusions in AD were contrasting [17–23]. In particular, a recent study showed that the homozygosis for the 5-HTTLPR-L/L genotype and lower MMSE scores were associated with an increased risk of delusion in DLB, with important implications regarding the mechanisms underlying this symptom across the AD/DLB/PD-dementia spectrum [24]. Similarly to our results, Sweet and colleagues reported an association between the L allele of the 5-HTTLPR polymorphic region with psychosis, as measured using the Empirical Behavioural Pathology in Alzheimer's Disease [17]. However, Rocchi and colleagues did not find an association, using the NPI to investigate 135 Italian AD patients [18]. We can make a comparison with these two studies, because these investigators combined delusions and hallucinations to assess 'psychosis'. In contrast to our results, Borroni and colleagues found that S allele carriers of 5HTTLPR had increased risk for the development of psychosis [19].
Among underlying mechanisms possibly explaining the association between 5-HTTLPR polymorphism and delusions in AD, it is well known that the serotonin system is important in the regulation of memory and thus might be associated with the disease [46, 47]. Serotonin has also been suggested to be responsible for a significant portion of the behavioural aspects of AD. The hypothesis is that transcriptional activity associated to the 5-HTTLPR-L allele is twice that of the S-allele. Thus, the S promoter allelic variant is linked to reduced 5-HTT mRNA expression, resulting in less serotonin reuptake than with the L-allelic variant and an increase of extraneuronal serotonin, contributing to the protective role in AD [48]. The specific mechanism by which the 5-HTTLPR may influence serotonin transmission is not known, but the difference in transcription rate between the two alleles may lead to differences in the number of serotonin reuptake sites and consequently affect serotonin levels [15, 16]. In the present study, AD patients with delusions showed a higher prevalence of hallucinations, not observed in AD patients without delusions. Given the central role of the serotonin system also in hallucinations, a genetic factor related to serotonin metabolism might exert a protective role on the clinical expression of psychotic clusters in AD. On the other hand, also nongenetic factors could influence the development of NPS in AD, i.e., these two cohorts of AD patients (i.e. with or without delusions) also had different social networks (or extent of said networks), and social network size modified the association between AD neuropathology and clinical symptoms of the disease [49]. Social network size may be related to reserve capacity capable of reducing the likelihood that the disease pathology will be clinically expressed [49]. Moreover, there was no influence of sex on the present findings. In fact, gender differences may potentially impact mortality in AD [50], APOE e4 allele effects on amyloid pathology [51], and the development of NPS [11]. However, the two present cohorts of AD patients with and without delusions had similar male/female ratios.
Furthermore, the effects of a 5-HTTLPR gene polymorphism on a functionally related but distinct receptor (5-HT1A receptor) were also evidenced. A study of positron emission tomography imaging has demonstrated the 5-HTTLPR-S/S genotype to be associated with a potential lower serotonin receptor 5HT1A binding than the 5-HTTLPR-L/L genotype [52]. Mechanistically, the lower transcriptional efficiency associated with the S allele of the 5-HTTLPR may lead to decreased 5-HTT function, which in turn may lead to a lifelong increase in 5-HT tone, which may in turn desensitize and downregulate 5-HT1A receptors. Several studies have suggested an association between the 5-HTT genotype and physiological reactivity to acute stressors [53]. According to the plasticity hypothesis, the 5-HTTLPR-S allele has been identified as a genetic invulnerability factor to the negative effects of a preponderance of stressful life events, and also disproportionally benefit from a preponderance of positive environmental influences, which was not found for 5-HTTLPR-L/L homozygotes [54].
In light of these theories, the role of association studies on the neuropharmacology of serotonin in NPS in AD is still not clearly defined. Recently, a study suggested that serotonin receptor inverse agonists of 5-HT2A, such as pimavanserin, might have therapeutic benefits in the treatment of psychosis in AD patients [55], without negative effects on cognition and with no effect on dopamine receptors. Moreover, randomized clinical trials (RCTs) demonstrated that atypical antipsychotic agents which influence serotonin neurotransmission decreased psychosis in AD patients [56, 57]. Furthermore, it has been reported that psychotic disturbances may benefit from selective serotonin reuptake inhibitor treatment in patients with dementia [58]. Thus, a genetic factor related to serotonin metabolism might exert a protective role on the clinical expression of NPS clusters in AD.
We must acknowledge some limitations for the present report. First of all, as a general issue, the present candidate gene approach may have a greater propensity to yield false positives, and to investigate complex traits might be indicate to use a GWAS approach, given also that is highly likely that psychosis in AD is polygenic [12]. Moreover, the study population comprised only Caucasian patients recruited in a single centre, therefore, it could be possible that our findings may not be applicable in other populations. However, the S-plus carriers strongly underrepresented in our AD patients with delusions was a finding also confirmed by the great difference between the observed genotype frequencies in respect to the expected HW frequencies in the two subgroups of patients. In fact, this difference was not present in the entire cohort, being in HWE. This condition is synonymous of strong genetic association with the observed phenotype. It is clear that sampling bias influencing the HW equilibrium or the observed association cannot be excluded, including the relative small number of patients. However, the restricted confidence intervals given back from the analyses certified the sufficient size of the investigated sample.
The present findings suggested that serotonin transporter gene may be associated with delusions in AD patients, providing important mechanistic information to boost the development of new treatment approaches and the prioritization and design of RCTs to manage NPS across the AD/DLB/PD-dementia spectrum.
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This work was fully supported by "Ministero della Salute", I.R.C.C.S. Research Program, Ricerca Corrente 2015–2017, Linea n. 2 "Malattie complesse e terapie innovative" and by the "5 x 1000" voluntary contribution.
Data are available from the authors upon reasonable request.
Fondazione Casa Sollievo della Sofferenza, Department of Medical Sciences, Geriatrics Unit, San Giovanni Rotondo (FG), Foggia, Italy
Grazia D'Onofrio, Francesco Panza, Daniele Sancarlo, Michele Lauriola, Mariangela P. Dagostino, Giulia Paroni, Antonio Mangiacotti, Paola Bisceglia, Carolina Gravina, Maria Urbano, Filomena Addante, Francesco Paris, Leandro Cascavilla, Antonio Greco & Davide Seripa
Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, Bari, Italy
Francesco Panza & Madia Lozupone
Department of Clinical Research in Neurology, University of Bari Aldo Moro, Pia Fondazione Cardinale G. Panico, Tricase, Lecce, Italy
Francesco Panza
Grazia D'Onofrio
Daniele Sancarlo
Michele Lauriola
Mariangela P. Dagostino
Giulia Paroni
Madia Lozupone
Antonio Mangiacotti
Paola Bisceglia
Carolina Gravina
Maria Urbano
Filomena Addante
Francesco Paris
Leandro Cascavilla
Antonio Greco
Davide Seripa
All authors contributed to the design of the study, and interpretation of data, and read and approved the final manuscript. GDO, Francesco Panza, AG, and DS: Study concept and design, data review/comments, interpretation of data, study supervision, manuscript preparation (review and critique). DS, ML, MPD, GP, ML, AM, PB, CG, MU, FA, Francesco Paris, and LC: Study design and organization, execution, and manuscript review/critique.
Correspondence to Grazia D'Onofrio.
The approval of the study for experiments using human subjects was obtained from the local Ethics Committees on human experimentation. Written informed consent for research was obtained from each patient or from relatives/legal guardian in the case of critically disabled demented patients prior to participation in the study. The study was performed in compliance with the principles of Good Clinical Practice, and was designed and conducted in accordance with the principles of the Declaration of Helsinki.
Figure S1 The clinical parameters affected by 5-hydroxytriptamine transporter gene-linked polymorphic region (5-HTTLPR) carrier status disease duration (A) and Neuropsychiatric Inventory (NPI)-Distress (B) in the whole sample (left graphs), Alzheimer's disease (AD) patients with delusions (central graphs), and AD patients without delusions (right graphs). Median, interquartile range, and extremes are presented. (TIF 86 kb)
Figure S2 The neuropsychiatric symptoms affected by 5-hydroxytriptamine transporter gene-linked polymorphic region (5-HTTLPR) carrier status aberrant motor activity (A) and irritability/liability (B) in the whole sample (left graphs), Alzheimer's disease (AD) patients with delusions (central graphs), and AD patients without delusions (right graphs). Median, interquartile range, and extremes are presented. (TIF 84 kb)
D'Onofrio, G., Panza, F., Sancarlo, D. et al. Hydroxytryptamine transporter gene-linked polymorphic region (5HTTLPR) is associated with delusions in Alzheimer's disease. Transl Neurodegener 8, 4 (2019). https://doi.org/10.1186/s40035-019-0144-1
Received: 16 July 2018
Neuropsychiatric inventory
5-HTTLPR


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