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Ischemic heart disease, which results from plaque formation in the coronary arteries, hinders the flow of oxygenated blood to the heart, leading to ischemia. Reperfusion injury remains a significant challenge for researchers, and the mechanisms underlying myocardial ischemia-reperfusion injury (MIRI) are not entirely understood. The review directs future research into potential targets in clinical treatment based on our present understanding of the pathophysiological mechanisms of MIRI. The study provides insights into the mechanisms underlying MIRI and offers direction for future research in this area. The use of targeted therapies may hold promise in improving cardiac function in the elderly and minimizing the adverse effects of revascularization therapies. The purpose of this review is to analyze the role of activated protein C (APC) in the pathogenesis of ischemic heart disease, heart failure, and myocardial ischemia-reperfusion injury, and discuss the potential of APC-based therapeutics., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The COVID-19 pandemic has posed a unique challenge to the medical community due to potential co-infections with bacteria and fungi. We report a case of Rhino cerebral mucormycosis infection in a 67-year-old patient after recovery from COVID-19., Objective: To report a case of Rhino cerebral mucormycosis in a 67-year-old patient with preexisting health conditions after recovering from COVID-19 and to highlight the importance of early detection and treatment of co-infections in patients with pre-existing health conditions., Case Presentation: The patient had pre-existing health conditions, including uncontrolled diabetes, hypertension, and Chronic obstructive pulmonary disease (COPD), which made him more vulnerable to complications after COVID-19. He was admitted to the hospital after experiencing a dark discharge from his left eye, later confirmed to be due to mucormycosis. Histopathological examination revealed invasive mucormycosis, highlighting the importance of early detection and treatment. However, the patient experienced Acute kidney injury (AKI) after only 5 days of treatment with conventional amphotericin B, underscoring the need for careful monitoring and adjustment of treatment regimens., Discussion: The case underscores the need for early detection and treatment of co-infections in vulnerable patients. The patient's pre-existing conditions and immunocompromised state made him more susceptible to the infection. The case also highlights the importance of careful monitoring and adjustment of treatment regimens to minimize the risk of adverse effects., Conclusion: While COVID-19 has presented challenges and uncertainties, it has also provided valuable insights into the interactions between infectious agents and the human body. Continued research and vigilance are necessary to mitigate the impact of co-infections and improve outcomes for patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: This comprehensive review aims to examine the reciprocal interplay between Type 2 diabetes mellitus (T2DM) and sarcopenia, identify prevailing research gaps, and discuss therapeutic approaches and measures to enhance healthcare practices within hospital settings., Methods: A thorough literature review was conducted to gather relevant studies and articles on the relationship between T2DM and sarcopenia. Various databases were searched, including Google Scholar, PubMed, Scopus, and Science Direct databases. The search terms included T2DM, sarcopenia, inflammation, insulin resistance, advanced glycation end products, oxidative stress, muscle dimensions, muscle strength, muscle performance, aging, nutrition, hormone levels, and physical activity. The collected articles were critically analysed to extract key findings and identify gaps in current research., Results: The prevalence and incidence of metabolic and musculoskeletal disorders, notably T2DM and sarcopenia, have surged in recent years. T2DM is marked by inflammation, insulin resistance, accumulation of advanced glycation end products, and oxidative stress, while sarcopenia involves a progressive decline in skeletal muscle mass and function. The review underscores the age-related correlation between sarcopenia and adverse outcomes like fractures, falls, and mortality. Research gaps regarding optimal nutritional interventions for individuals with T2DM and sarcopenia are identified, emphasizing the necessity for further investigation in this area., Conclusions: The reciprocal interplay between T2DM and sarcopenia holds significant importance. Further research is warranted to address knowledge gaps, particularly in utilizing precise measurement tools during clinical trials. Lifestyle modifications appear beneficial for individuals with T2DM and sarcopenia. Additionally, practical nutritional interventions require investigation to optimize healthcare practices in hospital settings., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01262-w., Competing Interests: This paper is devoid of any conflict of interest., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of drugs that lower blood glucose levels while decreasing blood pressure, volume loss, and weight loss. SGLT2 inhibitors were studied to determine their effectiveness in treating cardiovascular disease and their side effects. Study outcomes related to cardiovascular and metabolic outcomes were examined in patients on SGLT2 inhibitors by searching PubMed, Embase, Cochrane, and SCOPUS. Articles related to clinical trials, reviews, and meta-analyses were considered. A review of SGLT2 inhibitors' mechanisms of action in preventing cardiovascular (CVS) disease progression was described. We then reviewed the possible effects of SGLT2 inhibitors on CVS dysfunction development, composition, and stability. In the following, we discussed the impact of SGLT2 inhibitors on CVD events, such as ischemic strokes and myocardial infarctions, and their role in treating congestive heart failure and cardiovascular mortality., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

β-blockers have been widely utilized as a part of acute myocardial infarction (AMI) treatment for the past 40 years. Patients receiving β-adrenergic blockers for an extended period following myocardial infarction have a higher chance of surviving. Although many patients benefited from β-blockers, many do not, including those with myocardial infarction, left ventricle dysfunction, chronic pulmonary disease, and elderly people. In individuals with the post-acute coronary syndrome and normal left ventricular ejection fraction (LVEF), the appropriate duration of betablocker therapy is still unknown. There is also no time limit for those without angina and those who do not need β-blockers for arrhythmia or hypertension. Interestingly, β-blockers have been prescribed for more than four decades. The novel mechanism of action on cellular compartments has been found continually, which opens a new way for their potential application in cardiac failure and other cardiac events like post-myocardial infarction. Here, in this review, we studied β-blocker usage in these circumstances and the current recommendations for β-blocker use from clinical practice guidelines., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

OSMF is a precancerous condition of the oral cavity. Cons umption of Areca nut in quid has been proved to be the most consistent factor. To assess middle ear function in OSMF patients by audiometry and tympanometry. Two Hundred patients of < 40 years of age with OSMF were examined and followed by PTA and impedance audiometry. Impaired mobility was seen in 20(10%) ears, and retraction of tympanic membrane was found in 36(18%) ears. Clinical staging was done in four stages. Majority of the patients were males (58%) in the age group of 21-30 years belonging to stage III (38%) and IV (26%) respectively. PTA showed varying degrees of hearing loss in 73 (36.5%) ears. In Grade I, mild hearing loss was seen in 10 (35.71%) ears and moderately severe hearing loss was in 5 (11.36%) ears whereas in Grade II mild hearing loss in 11(25%) ears. Grade III and IV showed mild hearing loss in 11(14.47%) and 12 (23.07%) respectively. Tympanometry revealed type A curve in 126 (63%) ears followed by C curve in 50 (25%) and B curve in 24 (12%) ears. In patients of OSMF, there is involvement of palatal/paratubal muscles in the fibrosis process, which causes eustachian tube malfunction leading to disturbed middle ear functions and negative middle ear pressure. Most patients of oral submucous fibrosis showed direct association with grade of hearing impairment and eustachian tube dysfunction. Higher clinical grades, both clinically and histologically showed similar findings thereby we concluded that if the disease is treated early, preventing patients from having higher grades of disease, involvement of ear can be avoided, and patients can be saved from hearing impairment., Competing Interests: Conflict of interestThe authors declare that they do not have any potential conflict of interest., (© Association of Otolaryngologists of India 2022.)

Monkeypox is an orthopoxvirus-based zoonotic illness that causes symptoms similar to smallpox in humans. Health care workers around the world are making it a priority to educate themselves on the many clinical manifestations and treatment options for this virus as public health agencies strive to stop the current outbreak. The infected do not have access to any treatment at this time. However, information obtained from the smallpox pandemic has led researchers to examine vaccinia immune globulin (IVG), tecovirimat, and cidofovir as viable treatments for monkeypox. Moreover, medication like tecovirimat may be given in extreme circumstances, and supportive therapy can help with symptom relief. The European Medicines Agency (EMA) certified tecovirimat as safe and effective against monkeypox in 2022, per the World Health Organization (WHO). As there are now no established guidelines for alleviating these symptoms, the efficacy of these treatments is highly questionable. Some high-profile cases in recent years have cast doubt on the long-held belief that this illness is rare and always resolves itself without treatment. We aimed to conduct this review to get a deeper comprehension of the evolving epidemiology of monkeypox by analysing such factors as the number of confirmed, probable, and potential cases, the median age at presentation, the mortality rate, and the geographic distribution of the disease. This study offers an updated review of monkeypox and the clinical treatments that are currently available as a result of the worldwide epidemics., Competing Interests: The authors declared no conflict of interest., (© 2022 The Authors. Published by Elsevier Ltd.)

Syringocystadenoma papilliferum (SCAP) is an uncommon, benign adnexal neoplasm that occurs de novo or in an organoid nevus. It usually presents as a skin-coloured to pink, solitary, smooth, hairless plaque, verruca or nodule frequently on the scalp and forehead. SCAP may be present at unusual sites including the arm, forearm, trunk and chest. Diagnosing SCAP arising on uncommon sites is difficult owing to its varied presentation. Mostly, they are wrongly diagnosed clinically and found to be SCAP only on histopathology. We present this study of cases of SCAP with unusual location and varied presentations, which were clinically misdiagnosed. The five cases included in this study were patients attending the dermatology outpatient department in a tertiary care centre in North India. The clinical presentation and the involved sites were noted by the dermatologist, and a clinical diagnosis was made. Biopsy of the lesions was sent for histopathological examination. There are five patients in the series - four are male and one female, with age ranging from 28 to 48 years. Locations included the forearm, arm, anterior chest wall and lateral abdominal wall. The lesions clinically appeared as warty papule or nodules and one lesion appeared within a plaque, with the average duration being 5.3 years. In all five patients, the lesions were clinically suspected to be either tuberculosis verruca cutis or nodular basal cell carcinoma or dermatofibroma sarcoma protuberans (DFSP) or verruca or fibroma or pyogenic granuloma. A confirmatory diagnosis of SCAP was made for all the patients on histopathology. We are presenting five cases which were misdiagnosed clinically due to the unusual location and varied presentation to emphasise the importance of histopathology in diagnosing SCAP arising de novo , which was clinically misdiagnosed. Also, we present this case series to alert the clinicians about the likelihood of SCAP on unusual locations with varied clinical presentation., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Competing Interests: Competing interests: None declared.

A 40-year-old Caucasian man developed excessive thirst and polyuria particularly at night over the preceding 6 months. He had been taking lithium for 16 years for the treatment of bipolar affective disorder. Investigations revealed subnormal maximum urinary concentrating ability after 8 hours of water deprivation and only a borderline response of urine osmolality to exogenous desmopressin given by intramuscular injection. A plasma copeptin concentration was elevated at 23 pmol/L. These results were consistent with partial nephrogenic diabetes insipidus. He was encouraged to increase his water intake as dictated by his thirst. In addition, he received amiloride with some improvement in his symptoms. Clinicians should be aware of the risk of nephrogenic diabetes insipidus with long-term lithium use and seek confirmation by a supervised water deprivation test augmented with a baseline plasma copeptin. If increased water intake is insufficient to control symptoms, amiloride may be considered., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

While vitamin D (vitD) deficiency is thought to contribute to poor health in a variety of ways and should be corrected, there is still concern about giving vitD supplements to patients with a history of nephrolithiasis. The aim is to study the prevalence of vitD deficiency and the effect on stone risk of cholecalciferol (vitD3) supplementation in a cohort of idiopathic stone formers (ISF). We screened for vitD deficiency and urinary measures of stone risk, comparing vitD deficient (serum 25-OH vitD ≤30 nmol/L; ≤12 ng/mL) with vitD insufficient (31-75 nmol/L; 13-30 ng/mL) or vitD replete (>75 nmol/L; >30 ng/mL); we investigated the effect of giving vitD3 (20,000 IU orally, weekly for 4 months) to 37 of the vitD deficients. Thirty-one percent (142/456) were vitD deficient, 57% (259/456) vitD insufficient, and the rest (12%) vitD replete (55/456). Comparison among the groups showed that baseline 24-h urinary measures related to stone risk expressed as concentration ratios over urine creatinine (Cr), such as U. Calcium/Cr, U. Oxalate/Cr, U. Citrate/Cr, and U. Uric acid/Cr were not significantly different. VitD3 supplementation did significantly increase serum 25-OH vitD levels and U. Phosphate/Cr ratios, as well as reduce serum parathyroid hormone (PTH) concentrations. Following vitD3 supplementation, there was an overall rise in 24-h urine calcium excretion, but it failed to reach statistical significance (p = 0.06). U. Calcium/Cr increased in 22 out of 37 patients (average increase +0.07 mmol/mmol), decreased in 14 (average decrease -0.13 mmol/mmol), and remained unchanged in 1; 6 out of 26 initially normocalciuric ISF developed hypercalciuria; and 6 out of 9 patients who became vitD replete were hypercalciuric after supplementation. It is appropriate to monitor urinary Ca excretion in vitD-supplemented stone formers, because it may reveal underlying hypercalciuria in some treated patients.

Introduction: PAX5 is an immunomarker of B-cell origin and useful in the diagnosis of lymphoma. There is hardly any study on PAX5 expression in Indian patients with lymphoma., Aim: To evaluate the diagnostic utility of PAX5 as an adjunct immunohistochemical marker in the diagnosis of Hodgkin Lymphoma (HL) and Non-Hodgkin Lymphoma (NHL)., Materials and Methods: Immunohistochemistry was performed against CD20, CD3, CD15, CD30, and PAX5 on formalin fixed paraffin embedded tissue of 71 cases of lymphoma and CD20, CD3 and PAX5 in control samples of reactive lymph nodes. Frequency, mean values, and percentage were calculated. Fisher's-exact test and test for analysis of variance were applied., Result: For 24 cases of HL and 47 cases of NHL, the mean age of patients was 17.6±14.8 years and 44.1±21.6 years, respectively. The male: female ratio for both HL and NHL were 1.7:1. Among NHL cases, the numbers of B-cell and T-cell types were 39/47 (83%) and 8/47 (17%), respectively. In comparison to control samples, PAX5+ expression was seen in 23/24 (95.8%) cases of HL (p=1.000) and 32/39 (82%) cases of B-NHL (p=0.0834). All the cases of T-NHL showed negative expression of PAX5 (p<0.0001). Analysis of variance between NHL, HL and control samples was statistically significant (p<0.0001)., Conclusion: PAX5 staining between control samples and cases of classical HL and B-NHL was statistically not significant, whereas, statistically significant difference was observed with T-NHL. Thus, PAX5 may be used as an adjunct marker in the diagnosis of classical HL and B-NHL.

Background: Dental anxiety is a widespread phenomenon and a concern for paediatric dentistry. The inability of children to deal with threatening dental stimuli often manifests as behaviour management problems. Nowadays, the use of non-aversive behaviour management techniques is more advocated, which are more acceptable to parents, patients and practitioners. Therefore, this present study was conducted to find out which audio aid was the most effective in the managing anxious children., Aims and Objectives: The aim of the present study was to compare the efficacy of audio-distraction aids in reducing the anxiety of paediatric patients while undergoing various stressful and invasive dental procedures. The objectives were to ascertain whether audio distraction is an effective means of anxiety management and which type of audio aid is the most effective., Materials and Methods: A total number of 150 children, aged between 6 to 12 years, randomly selected amongst the patients who came for their first dental check-up, were placed in five groups of 30 each. These groups were the control group, the instrumental music group, the musical nursery rhymes group, the movie songs group and the audio stories group. The control group was treated under normal set-up & audio group listened to various audio presentations during treatment. Each child had four visits. In each visit, after the procedures was completed, the anxiety levels of the children were measured by the Venham's Picture Test (VPT), Venham's Clinical Rating Scale (VCRS) and pulse rate measurement with the help of pulse oximeter., Results: A significant difference was seen between all the groups for the mean pulse rate, with an increase in subsequent visit. However, no significant difference was seen in the VPT & VCRS scores between all the groups. Audio aids in general reduced anxiety in comparison to the control group, and the most significant reduction in anxiety level was observed in the audio stories group., Conclusion: The conclusion derived from the present study was that audio distraction was effective in reducing anxiety and audio-stories were the most effective.

Background: Fluoridation of drinking water, despite being regarded as one of the top ten public health achievements of the twentieth century, has remained a much debated concept. Various studies on animals and aborted human fetuses have confirmed that excessive fluoride intake during infancy and early childhood, causes a number of irreversible structural and functional changes in the CNS leading to memory, learning and intellectual deficits., Aim: To compare the IQ levels of school children of two different locations, having different fluoride levels in water, and to establish a relationship between fluoride levels, prevalence of fluorosis and its effect on IQ levels., Materials and Methods: A cross-sectional study was conducted among 429 children aged 6 - 12 years, selected by stratified random sampling from two different areas with different levels of fluoride in drinking water in and around Lucknow district. Dental fluorosis was measured using Dean's Fluorosis Index. Intelligence Quotient was measured using Raven's Coloured Progressive Matrices (1998 edition)., Results: Majority of the fluorosis free children (76.3%) had an IQ grade 2 (definitely above the average). Majority of the children suffering from very mild and mild dental fluorosis were found to have IQ grade 3 (Intellectually average). Children with moderate cases of dental fluorosis were found to have IQ grade 4 (Definitely below average). Only 5 children with severe fluorosis were included in the study and they all were found to have an IQ grade 5. Hence, a trend of increase in the IQ grade (decrease in intellectual capacity) was observed indicating a strong correlation between fluorosis grade and IQ grade., Conclusion: Findings of this study suggest that the overall IQ of the children exposed to high fluoride levels in drinking water and hence suffering from dental fluorosis were significantly lower than those of the low fluoride area.

A 72-year-old male presented with urinary symptoms. His serum prostate specific antigen level was 65.2 ng/ml. His radical prostatectomy specimen showed clear cell lesion reminiscent of the clear cell renal cell carcinoma along with acinar type of prostatic adenocarcinoma, Gleason score 4 + 4. The lesional clear cells were positive for pancytokeratin, epithelial membrane antigen, CD10, vimentin, and AMACR while negative for 34βE12, CK7, prostate specific antigen, and PAX8. The final diagnosis was renal-type clear cell carcinoma of the prostate. A follow-up of 20 months did not show metastasis. We herein report fifth case of renal-type clear cell carcinoma of the prostate.

Background: It has been acknowledged that genetics play a significant role in determination of dermatoglyphic patterns. Since caries is a multifactorial disease with the influence of genetic pattern, this study was undertaken to assess dermatoglyphic patterns and correlate them with early childhood caries., Aim: The aim of the study was to determine the association and correlation of dermatoglyphic patterns with early childhood caries., Materials and Methods: The study sample consisted of 100 children aged between 3 and 6 years, divided into two groups of 50 children each. The deft score was evaluated to select the experimental group and control group. Finger and palm prints were recorded using the ink method described by Cummins and Midlo. The handprints obtained were checked for their clarity with a magnifying glass (×2) and coded. The presence of core and the triradii of the dermatoglyphic pattern were checked thoroughly to include the handprint in the study. A total of 1000 digital prints and 200 palmar prints were obtained., Results: The presence of whorls in the index finger of the right hand predicts significantly lower risk of caries in children (male and female; combined). Presence of whorls in the ring finger of the right hand predicts significantly lower risk of caries in female children. Statistically no correlation between atd angle and early childhood caries was obtained from the present data., Conclusion: The results obtained from the present study creates a notion on the validity of the results of the previous studies and point them to be chance findings. Due to increasing acceptability of dermatoglyphics as a diagnostic tool for congenital diseases, further large scale extensive research should be undertaken to evaluate the role of the same in children with Early Childhood Caries (ECC).

Background: Kidney stone disease has an estimated prevalence of around 10%. Genetic as well as environmental factors are thought to play an important role in the pathogenesis of renal stones., Aim: The aim of our study was to analyse and report the main characteristics of patients with kidney stones attending a large UK metabolic stone clinic in London between 1995 and 2012., Design: A cross-sectional study., Methods: Analysis of data from stone formers attending the University College and Royal Free Hospitals' metabolic stone clinic from 1995 to 2012. Demographic, clinical, dietary and biochemical characteristics have been summarized and analysed for men and women separately; trends over time have also been analysed., Results: Of the 2861 patients included in the analysis, 2016 (70%) were men with an average age of 47 years (range 18-87 years) and median duration of disease of 6 years (range 0-60 years). The prevalence of low urine volume, hypercalciuria, hyperoxaluria, hyperuricosuria and hypocitraturia was 5.6%, 38%, 7.9%, 18% and 23%, respectively. The prevalence of several risk factors for stones increased over time. The majority of stones were mixed, with around 90% composed of calcium salts in varying proportion., Conclusion: Our findings in a large cohort of patients attending a London-based stone clinic over the past 20 years show differences in distributions of risk factors for stones for men and women, as well as metabolic profiles and stone composition. The impact of most risk factors for stones appeared to change over time., (© The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The prevalence and incidence of kidney stone disease have increased markedly during the past several decades, and studies have demonstrated that inappropriate dietary habits are leading to more obesity and overweight (OW) in children and adults, which may be important in stone formation. Obese and OW patients share most of the same risk factors for cardiovascular morbidity, while the impact of being OW, rather than obese, on urinary metabolic parameters of kidney stone formers (KSF) is less well known. The aims of this study were to investigate urinary metabolic parameters, stone composition and probability of stone formation (Psf) in OW KSF when compared with normal weight (NW) and obese KSF., Methods: The kidney stone database for KSF attending a large metabolic stone clinic was investigated. Patients with a recorded BMI, confirmed diagnosis of kidney stone disease and full metabolic evaluation were divided into three categories: BMI ≤25.0 kg/m(2) (NW group), BMI 25-30 kg/m(2) (OW group) and BMI >30.0 kg/m(2) (obese group). Twenty-four hour urinary volume (U.Vol), pH (U.pH), calcium (U.Ca), oxalate (U.Ox), citrate (U.Cit), uric acid (U.UA), magnesium (U.Mg), sodium (U.Na) and potassium (U.K) excretions, along with stone composition and Psf, were then compared among the groups., Results: A total of 2132 patients were studied, of whom 833 (39%) were NW, 863 (40.5%) were OW and 436 (20.5%) were obese. OW and obese KSF were older (mean age 43 ± 15 in NW, 48 ± 13 in OW and 50 ± 12 years in obese; P for trend <0.001), demonstrated increased female predominance and higher prevalence of diabetes, hypertension and gout. There were no statistically significant differences in U.Vol and U.Mg among the groups. However, significantly higher levels of U.Ca, U.Ox, U.Cit, by crude analysis, and U.UA (3.3 ± 1.1 versus 3.8 ± 1.2 versus 4.0 ± 1.2 mmol/L; P < 0.001 for trend), U.Na (151 ± 57 versus 165 ± 60 versus 184 ± 63 mmol/L; P < 0.001 for trend), and lower U.pH (6.3 ± 0.5 versus 6.1 ± 0.5 versus 6.0 ± 0.6; P < 0.001 for trend) by both crude and multivariate adjusted analysis models were demonstrated in OW and obese KSF. Stone composition data (N = 640) showed a significantly higher incidence of uric acid stones in OW and obese groups (P for trend < 0.001). In addition, higher Psf for CaOx, UA and CaOx/UA stone types were detected in OW and obese compared with NW KSF., Conclusions: Similar to obese KSF, OW KSF show clear alterations in metabolic urinary profiles that are associated with increased overall risk of stone formation. This greater risk is primarily due to raised U.UA and U.Na, lower U.pH and higher prevalence of hypercalciuria, along with unchanged levels of the commonly measured urinary lithogenesis inhibitors. Moreover, our study established a higher incidence of uric acid, but not calcium, stones in OW KSF. Thus, appropriate evaluation and follow-up may be warranted even in OW patients who are at risk of increased stone formation. Whether modest weight loss in OW KSF will have a favourable impact on their metabolic urinary profiles and thereby diminish the risk of further stone formation needs exploring., (© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Mutations in the 4-hydroxy-2-oxoglutarate aldolase (HOGA1) gene have been recently identified in patients with atypical primary hyperoxaluria (PH). However, it was not clearly established whether these mutations caused disease via loss of function or activation of the gene product., Methods: Whole-gene sequencing of HOGA1 was conducted in 28 unrelated patients with a high clinical suspicion of PH and in whom Types 1 and 2 had been excluded., Results: Fifteen patients were homozygous or compound heterozygous for mutations in HOGA1. In total, seven different mutations were identified including three novel changes: a missense mutation, c.107C > T (p.Ala36Val), and two nonsense mutations c.117C > A (p.Tyr39X) and c.208C > T (p.Arg70X) as well as the previously documented c.860G > T (p.Gly297Val), c.907C > T (p.Arg303Cys) and in-frame c.944&#95;946delAGG (p.Glu315del) mutations. The recurrent c.700 + 5G > T splice site mutation in intron 5 was most common with a frequency of 67%. Expression studies on hepatic messenger RNA demonstrated the pathogenicity of this mutation., Conclusions: The detection of a patient with two novel nonsense mutations within exon 1 of the gene, c.117C > A (p.Tyr39X) and c.208C > T (p.Arg70X), provides definitive proof that PH Type 3 is due to deficiency of the 4-hydroxy-2-oxoglutarate aldolase enzyme.

The heavy metal cadmium (Cd) is known to be a widespread environmental contaminant and a potential toxin that may adversely affect human health. Exposure is largely via the respiratory or gastrointestinal tracts; important non-industrial sources of exposure are cigarette smoke and food (from contaminated soil and water). The kidney is the main organ affected by chronic Cd exposure and toxicity. Cd accumulates in the kidney as a result of its preferential uptake by receptor-mediated endocytosis of freely filtered and metallothionein bound Cd (Cd-MT) in the renal proximal tubule. Internalised Cd-MT is degraded in endosomes and lysosomes, releasing free Cd(2+) into the cytosol, where it can generate reactive oxygen species (ROS) and activate cell death pathways. An early and sensitive manifestation of chronic Cd renal toxicity, which can be useful in individual and population screening, is impaired reabsorption of low molecular weight proteins (LMWP) (also a receptor-mediated process in the proximal tubule) such as retinol binding protein (RBP). This so-called 'tubular proteinuria' is a good index of proximal tubular damage, but it is not usually detected by routine clinical dipstick testing for proteinuria. Continued and heavy Cd exposure can progress to the clinical renal Fanconi syndrome, and ultimately to renal failure. Environmental Cd exposure may be a significant contributory factor to the development of chronic kidney disease, especially in the presence of other co-morbidities such as diabetes or hypertension; therefore, the sources and environmental impact of Cd, and efforts to limit Cd exposure, justify more attention.

Renal stone disease covers kidney and lower urinary tract stones caused by a variety of conditions, including metabolic and inherited disorders, and anatomical defects with or without chronic urinary infection. Most cases are idiopathic, in which there is undoubtedly a genetic predisposition, but where environmental and lifestyle factors play an important role. Indeed, it is becoming apparent that renal stone disease is often part of a larger 'metabolic picture' commonly associated with type 2 diabetes, obesity, dyslipidaemia, and hypertension. Renal stone disease is a growing problem in the UK (and other developed and developing populations) with a cross-sectional prevalence of ∼1.2%. This means that there are currently ∼720,000 individuals with a history of kidney stones in the UK. Almost 40% of first-time stone formers will form a second stone within 3 years of the first episode if no prophylactic measures are instituted to prevent stone recurrence, since removal or disintegration of the first stone does not treat the underlying cause of stones in the majority of patients. The age of onset is getting younger and the sex ratio (until recently more men than women) is becoming almost even. Metabolic screening remains an important part of investigating renal stone disease, but to the disappointment and frustration of many doctors, medical treatment is still essentially pragmatic, except perhaps in cystinuria, and to a limited extent in primary hyperoxaluria (if pyridoxine-sensitive); although newer treatments may be emerging. This review summarizes current thinking and provides a practical basis for the management of renal stone disease., (Copyright © 2010 S. Karger AG, Basel.)

Different groups of mice were infected with various single or repeated doses of larvae of Ancylostoma caninum. Considerable loss of larvae occurred in the immunised groups when compared with their counterpart unimmunised groups. Larval migration and distribution in the different tissues was less in immunised mice, as most larvae were expelled from the gastrointestinal tract. This resulted in a poor onward larval migration to liver, lungs, brain and muscle regions in immunised groups. The heavily immunised group infected five times was most affected and a significant lesser larval distribution in various organs and muscle region observed.