ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder

Purpose: To identify the molecular cause in five unrelated families with a distinct autosomal dominant ocular systemic disorder we called ROSAH syndrome due to clinical features of retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache. Methods: Independent discovery exome and genome sequencing in families 1, 2, and 3, and confirmation in families 4 and 5. Expression of wild-type messenger RNA and protein in human and mouse tissues and cell lines. Ciliary assays in fibroblasts from affected and unaffected family members. Results: We found the heterozygous missense variant in the ɑkinase gene, ALPK1, (c.710C>T, [p.Thr237Met]), segregated with disease in all five families. All patients shared the ROSAH phenotype with additional low-grade ocular inflammation, pancytopenia, recurrent infections, and mild renal impairment in some. ALPK1 was notably expressed in retina, retinal pigment epithelium, and optic nerve, with immunofluorescence indicating localization to the basal body of the connecting cilium of the photoreceptors, and presence in the sweat glands. Immunocytofluorescence revealed expression at the centrioles and spindle poles during metaphase, and at the base of the primary cilium. Affected family member fibroblasts demonstrated defective ciliogenesis. Conclusion: Heterozygosity for ALPK1, p.Thr237Met leads to ROSAH syndrome, an autosomal dominant ocular systemic disorder

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

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Not AvailableDiversification Approaches for Conventional Rice-Wheat Crop CycleNot Availabl

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CROP RESIDUE: WASTE OR WEALTH?Growing food consumption in developing countries has resulted in a massive increase in global food production. Rice-wheat (RW) cropping systems cover 13 million hectares in South Asia (India, Pakistan, Nepal, Bangladesh, and Bhutan). Rice-wheat cropping systems account for roughly 20% of total cereal production and 40% of wheat production in India. The Indo-Gangetic Plains (IGPs) are home to more than 85 percent of South Asia's RW system. India's IGPs cover around 20% of the country's overall geographical area (329 Mha) and about 27% of the country's net cultivated land, producing about 50% of the country's total food consumption. Continuous rice and rotational wheat agriculture, intensive tillage for both crops, Crop Residue (CR) removal and use of excessive water and chemical has created environmental and ecological imbalance. The CR consists of plant materials left behind after harvesting and threshing crops. These residues were once thought to be waste, but with increased knowledge and further investigation, it is becoming clear that they are not waste but rather an essential natural resource. CR recycling could be used to transform surplus farm waste into usable material. These items can aid in nutrient replenishment, soil fertility enhancement, and ecological balance, all of which are beneficial to crop output. Many farmers utilize wheat straw as animal feed, but rice straw is still a problem because its high silica concentration makes it poor and animal population in rural area is also decreasing. The combine harvester leaves a swath of loose paddy residue, interfering with wheat drill seeding. To meet this difficulty, farmers turn to CR burning, which wastes a lot of biomass and pollutes the environment. On the other hand, National agencies are constantly developing regulations and options for managing these wastes, including their conversion to reusable resources. India creates an average of 500 million tonnes (Mt) of crop residue per year, according to the Indian Ministry of New and Renewable Energy (MNRE). According to the same research, the bulk of crop residue is used for feed, fuel, and other home and industrial reasons. However, there is still a 140 million-tonne surplus, of which 92 million tonnes is burned each year. Table 1 compares the amount of agricultural waste produced in Mt/year by some Asian nations. It's also worth noting that the amount of agricultural waste burned in India is substantially more significant in volume than the total amount of agricultural waste produced in other nations in the region.Not Availabl