Therefore, a protection against the UV radiation-induced photolysis of folate is imperative for the evolution of human populations living in tropical regions where the exposure to UV radiation is high over the year. One body natural adaptation is to elevate the concentration of melanin inside the skin. Melanin works as either an optical filter to disperse the incoming UV radiation rays or free radical to stabilize the hazardous photochemical products. Multiple studies have demonstrated the highly melanized integument as a defense against folate photolysis in Native Americans or African Americans correlates with lower occurrence of NTDs in general. Genetic deficiencies
As reported by Bruno Reversade and colleagues, the inactivation of the NUAK2 kinase in humans leads to anencephaly. This fatal birth defect is believed to arise as a consequence of impaired HIPPO signalling. Other genes such as TRIM36 have also been associated with anencephaly in humans. Gene-environment interaction
A deficiency of folate itself does not cause neural tube defects. The association seen between reduced neural tube defects and folic acid supplementation is due to a gene-environment interaction such as vulnerability caused by the C677T methylenetetrahydrofolate reductase (MTHFR) variant. Supplementing folic acid during pregnancy reduces the prevalence of NTDs by not exposing this otherwise sub-clinical mutation to aggravating conditions. Other potential causes can include folate antimetabolites (such as methotrexate), mycotoxins in contaminated corn meal, arsenic, hyperthermia in early development, and radiation. Maternal obesity has also been found to be a risk factor for NTDs.
Diagnosis
Diagnosis of mittelschmerz is generally made if a woman is mid-cycle and a pelvic examination shows no abnormalities. If the pain is prolonged and/or severe, other diagnostic procedures such as an abdominal ultrasound may be performed to rule out other causes of abdominal pain. The pain of mittelschmerz is sometimes mistaken for appendicitis and is one of the differential diagnoses for appendicitis in women of child-bearing age. Treatment
The pain is not harmful and does not signify the presence of disease. No treatment is usually necessary. Pain relievers (analgesics) such as NSAIDS (Non-steroidal anti inflammatories) may be needed in cases of prolonged or intense pain.Hormonal forms of contraception can be taken to prevent ovulation—and therefore ovulatory pain—but otherwise there is no known prevention. Usefulness
Women charting with some form of fertility awareness may find mittelschmerz to be a helpful secondary sign in detecting ovulation. Because normal sperm life is up to five days, however, mittelschmerz alone does not provide sufficient advance warning to avoid pregnancy. Because other causes of minor abdominal pain are common, mittelschmerz alone also cannot be used to confirm the beginning of the post-ovulatory infertile period. References


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