Two unusual reports of urogenital tuberculosis: One ‘putty’ kidney and another in association with benign prostatic hyperplasia

In India urogenital tuberculosis is the second commonest form of extra-pulmonary tuberculosis. Kidney is the highest and prostate is the least affected urogenital organ. But the extreme stage of renal tuberculosis named as ‘putty’ kidney is a rare manifestation. In general most cases of urogenital tuberculosis are quasi-symptomatic, and therefore an uttermost apprehension is needed from physicians to intercept such cases at the earliest. In this presentation we describe a case of ‘putty’ kidney, and another incidental association of prostate tuberculosis with benign prostatic hyperplasia.     

Regulation of Pain and Itch by TRP Channels

Nociception is an important physiological process that detects harmful signals and results in pain perception. In this review, we discuss important experimental evidence involving some TRP ion channels as molecular sensors of chemical, thermal, and mechanical noxious stimuli to evoke the pain and itch sensations. Among them are the TRPA1 channel, members of the vanilloid subfamily (TRPV1, TRPV3, and TRPV4), and finally members of the melastatin group (TRPM2, TRPM3, and TRPM8). Given that pain and itch are pro-survival, evolutionarily-honed protective mechanisms, care has to be exercised when developing inhibitory/modulatory compounds targeting specific pain/itch-TRPs so that physiological protective mechanisms are not disabled to a degree that stimulus-mediated injury can occur. Such events have impeded the development of safe and effective TRPV1-modulating compounds and have diverted substantial resources. A beneficial outcome can be readily accomplished via simple dosing strategies, and also by incorporating medicinal chemistry design features during compound design and synthesis. Beyond clinical use, where compounds that target more than one channel might have a place and possibly have advantageous features, highly specific and high-potency compounds will be helpful in mechanistic discovery at the structure-function level.     

Dynamic Changes of the Mitochondria in Psychiatric Illnesses: New Mechanistic Insights From Human Neuronal Models

Mitochondria play a crucial role in neuronal function, especially in energy production, the generation of reactive oxygen species, and calcium signaling. Multiple lines of evidence have suggested the possible involvement of mitochondrial deficits in major psychiatric disorders, such as schizophrenia and bipolar disorder. This review will outline the current understanding of the physiological role of mitochondria and their dysfunction under pathological conditions, particularly in psychiatric disorders. The current knowledge about mitochondrial deficits in these disorders is somewhat limited because of the lack of effective methods to dissect dynamic changes in functional deficits that are directly associated with psychiatric conditions. Human neuronal cell model systems have been dramatically developed in recent years with the use of stem cell technology, and these systems may be key tools for overcoming this dilemma and improving our understanding of the dynamic changes in the mitochondrial deficits in patients with psychiatric disorders. We introduce recent discoveries from new experimental models and conclude the discussion by referring to future perspectives. We emphasize the significance of combining studies of human neuronal cell models with those of other experimental systems, including animal models.     

Outcome of thyroglossal duct cyst excision is independent of presenting age or symptomatology

BACKGROUND: Thyroglossal duct cysts (TGDCs) are the most common form of congenital neck cyst, accounting for up to 70% of such lesions. There has been no consensus on which factors predict outcome of thyroglossal duct cyst excision. The objective of the current study is to evaluate the relevance of symptomatology and age at presentation with outcome of TGDCs. METHODS: Retrospective review of patients with TGDC at a tertiary care children's hospital. Data collected included patient's age, gender, clinical presentation, presence or absence of preoperative infection, imaging modality, type of procedure performed, size and location of the lesion, postoperative infection, complications, and recurrence of disease. RESULTS: Twenty-nine patients were identified (59% female, 41% male). Age of presentation was bimodal and ranged from 18 months to 14 years. The most common presenting symptom was the presence of an asymptomatic midline neck mass (76%). A history of preoperative TGDC infection was present in 22% of patients /=5 years of age. Recurrence rate after the Sistrunk procedure was 3.4%. CONCLUSIONS: The finding of a midline neck mass is the most common presentation of TGDCs in toddlers, whereas infection is the most common presenting symptoms in school-aged children. The incidence of preoperative infection was 41% in our series, much higher than previously reported. Independent of presenting age and symptomatology, recurrence of TGDC remains low when the Sistrunk procedure is employed.     

Educational inequalities in mortality of patients with atrial fibrillation in Norway

Objectives: We explored the educational gradient in mortality in atrial fibrillation (AF) patients.

Design: We prospectively followed patients hospitalized with AF as primary discharge diagnosis in the Cardiovascular Disease in Norway 2008-2012 project. The average length of follow-up was 2.4 years. Mortality by educational level was assessed by Cox proportional hazard models. Population attributable fractions (PAF) were calculated. Analyses stratified by age (≤75 and >75 years of age), and adjusted for age, gender, medical intervention, and Charlson Comorbidity Index.

Results: Of 42,138 AF patients, 16% died by end of 2012. Among younger patients, those with low education (≤10 years) had a HR of 2.3 (95% confidence interval 2.0, 2.6) for all-cause mortality relative to those with any college or university education. Similar results were observed for cardiovascular mortality. Disparities in mortality were greater among younger than older patients. A PAF of 35.9% (95% confidence interval 27.9, 43.1) was observed for an educational level of high school/vocational school or less versus higher education in younger patients.

Conclusions: Increasing educational level associated with better prognosis suggesting underlying education-related behavioral and medical determinants of mortality. A considerable proportion of mortality within 5 years following hospital discharge could be prevented.     

Identification of a small molecule inhibitor of the aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib] using mixture-based combinatorial libraries

The aminoglycoside, 6′-N-acetyltransferase type Ib [AAC(6')-Ib] is the most widely distributed enzyme among AAC(6')-I-producing Gram-negative pathogens and confers resistance to clinically relevant aminoglycosides, including amikacin. This enzyme is therefore an ideal target for enzymatic inhibitors that could overcome resistance to aminoglycosides. The search for inhibitors was carried out using mixture-based combinatorial libraries, the scaffold ranking approach, and the positional scanning strategy. A library with high inhibitory activity had pyrrolidine pentamine scaffold and was selected for further analysis. This library contained 738,192 compounds with functionalities derived from 26 different amino acids (R1, R2 and R3) and 42 different carboxylic acids (R4) in four R–group functionalities. The most active compounds all contained S-phenyl (R1 and R3) and S-hydromethyl (R2) functionalities at three locations and differed at the R4 position. The compound containing 3-phenylbutyl at R4 (compound 206) was a robust enzymatic inhibitor in vitro, in combination with amikacin it potentiated the inhibition of growth of three resistant bacteria in culture, and it improved survival when used as treatment of Galleria mellonella infected with aac(6')-Ib-harboring Klebsiella pneumoniae and Acinetobacter baumannii strains.