Rare loss-of-function mutations in the calcium-sensing receptor (Casr) gene lead to decreased urinary calcium excretion in the context of parathyroid hormone (PTH)-dependent hypercalcemia, but the role of Casr in the kidney is unknown. Using animals expressing Cre recombinase driven by the Six2 promoter, we generated mice that appeared grossly normal but had undetectable levels of Casr mRNA and protein in the kidney. Baseline serum calcium, phosphorus, magnesium, and PTH levels were similar to control mice. When challenged with dietary calcium supplementation, however, these mice had significantly lower urinary calcium excretion than controls (urinary calcium to creatinine, 0.3160.03 versus 0.6360.14; P=0.001). Western blot analysis on whole-kidney lysates suggested an approximately four-fold increase in activated Na + -K + -2Cl 2 cotransporter (NKCC2). In addition, experimental animals exhibited significant downregulation of Claudin14, a negative regulator of paracellular cation permeability in the thick ascending limb, and small but significant upregulation of Claudin16, a positive regulator of paracellular cation permeability. Taken together, these data suggest that renal Casr regulates calcium reabsorption in the thick ascending limb, independent of any change in PTH, by increasing the lumen-positive driving force for paracellular Ca 2+ transport.

A large, ongoing multi-country outbreak of human monkeypox has the potential to cause considerable morbidity and mortality. Therapeutics for the treatment of smallpox, a related Orthopoxvirus, may be used and affect the natural history of monkeypox. We present three patients from our hospitals treated with tecovirimat, a pan-Orthopoxvirus inhibitor currently available under an expanded access investigational new drug protocol for monkeypox.

Context:Screening for ocular manifestations of leukemia, although not a routine practice, is important as they may antedate systemic disease or form an isolated focus of its relapse.Aims:This study evaluates the spectrum of ocular manifestations in acute and chronic leukemias presenting to a tertiary care center in India.Settings and Design:Subjects of leukemia presenting to a tertiary care center in India.Subjects and Methods:A prospective, cross-sectional study looking at the spectrum of ocular manifestations in all inpatients of acute or chronic leukemia.Statistical Analysis Used:The collected data were analyzed using the Statistical Package for Social Sciences for Windows software, version 16 (SPSS Inc., Chicago, Illinois, USA).Results:The study subjects (n = 96) comprised 61 males and 35 females whose age ranged from 18 months to 91 years (mean = 39.73, ±22.1). There were 79 adults and 17 children, 53 new and 43 existing patients, 68 acute and 28 chronic, 61 myeloid and 35 lymphoid patients. Ocular lesions were found in 42 patients (43.8%). The ocular manifestations of leukemia were significantly (P = 0.01467) more frequent in acute 35/68 (51.9%) than chronic 7/28 (25%) leukemias. Primary or direct leukemic infiltration was seen in 8 (8.3%) subjects while secondary or indirect involvement due to anemia, thrombocytopenia, hyperviscosity, total body irradiation, and immunosuppression were seen in 42 (43.8%) subjects. Ocular changes were present in 37/79 (46.8%) adults and 5/17 (29.4%) children (P = 0.09460). Twenty-eight males (28/61) 45.9% and 14/35 (40%) females had ocular manifestations (P = 0.2874). The ocular manifestations were significantly (P = 0.01158) more frequent in myeloid leukemias 32/61 (52.9%) than lymphoid leukemias 10/35 (28.6%).Conclusions:Leukemic ophthalmic lesions were found in 42/96 (43.8%) patients. Ocular involvement is more often seen in adults, acute and myeloid leukemias. All the primary leukemic manifestations were seen in males. A periodic ophthalmic examination should be mandatory for all leukemic patients, as ocular changes are often picked up in asymptomatic patients.

Considering the high true negative rates and reasonably good true positive rates and the wider coverage provided by the program, vision screening in schools by teachers is an effective method of identifying children with low vision. This strategy is also valuable in reducing the workload of the eye care staff.

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The objective of this study was to study the spectrum of neurological manifestations in patients with dengue infection. This was a prospective study undertaken at the Departments of Medicine and Neurology, Christian Medical College, Ludhiana, India. All patients diagnosed with dengue fever during an epidemic (1 September 2010-31 December 2010) were screened for neurological manifestations. There were a total of 799 patients with dengue infection. Neurological manifestations were present in 21 (2.63%), 19 of whom were men with a mean age of 33.7 ± 13.9 years. The neurological diagnoses were hypokalaemia with: quadriparesis (7); myositis (4); encephalopathy (4); Guillain-Barre syndrome (2); acute disseminated encephalomyelitis (2); lumbosacral plexopathy (1); and intracranial haemorrhage (1). Three of these patients died. Clinicians should be aware that neurological manifestations in dengue fever are not uncommon.

Advances in genetic mapping and sequencing techniques have led to substantial progress in the study of rare monogenic (Mendelian) forms of abnormal blood pressure. Many disease-defining pathways for hypertension have been identified in the past two decades. Perturbations in renal salt handling appear to be a common mechanism underlying these rare syndromes of hypertension. Excess activation at various points in the mineralocorticoid signaling pathway and malfunctioning of the autonomic (specifically sympathetic) nervous system have both been implicated in inducing hypertension, while complementary studies examining low blood pressure phenotypes have identified novel pathways exclusively linked to renal salt wasting in either the thick ascending limb or the distal nephron. The genetic defects and the physiological and cellular pathways affected in these various disorders are reviewed here. Importantly, studies have suggested that genetic variation affecting these same genes and pathways may play an important role in explaining the variation of blood pressure levels in the general population. The investigation of rare syndromes of human blood pressure variation has important implications for improving the diagnosis and treatment of hypertension.

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