A brighter shade of future climate on Himalayan musk deer Moschus leucogaster.

Himalayan musk deer (Moschus leucogaster) is classified as an endangered species by IUCN with a historically misunderstood distribution due to misidentification with other species of musk deer, Moschus spp. Taking advantage of recent genetic analyses confirming the species of various populations in Nepal and China, we produced an accurate estimate of the species' current and future distribution under multiple climate change scenarios. We collected high-quality occurrence data using systematic surveys of various protected areas of Nepal to train species distribution models. The most influential determinants of the distribution of Himalayan musk deer were precipitation of the driest quarter, temperature seasonality, and annual mean temperature. These variables, and precipitation in particular, determine the vegetation type and structure in the Himalaya, which is strongly correlated with the distribution of Himalayan musk deer. We predicted suitable habitats between the Annapurna and Kanchenjunga region of Nepal Himalaya as well as the adjacent Himalaya in China. Under multiple climate change scenarios, the vast majority (85-89%) of current suitable sites are likely to remain suitable and many new areas of suitable habitat may emerge to the west and north of the current species range in Nepal and China. Two-thirds of current and one-third of future suitable habitats are protected by the extensive network of protected areas in Nepal. The projected large gains in suitable sites may lead to population expansion and conservation gains, only when the threat of overexploitation and population decline is under control.

Multicenter Randomized Trial Assessing MRI and Image-guided Biopsy for Suspected Prostate Cancer: The MULTIPROS Study.

Background The optimal diagnostic pathway for prostate cancer (PCa) is evolving, requiring further evaluation in a randomized controlled trial. Purpose To assess the diagnostic accuracy of prebiopsy multiparametric MRI in the identification of clinically significant PCa (csPCa) using radical prostatectomy (RP) specimens as the reference standard, and to test the diagnostic accuracy of combined US and MRI fusion-targeted biopsy with systematic biopsies. Materials and Methods In a prospective randomized controlled trial including university hospitals, men with suspected PCa were recruited between January 2015 and August 2020 to assess the diagnostic accuracy of multiparametric MRI before biopsy in detection of csPCa at biopsy and RP histopathologic structure (primary outcome). Men with lesions suspicious for cancer (Prostate Imaging and Reporting Data System [PI-RADS] ≥3) at multiparametric MRI were first randomized to either systematic random prostate biopsies alone (control group) or US and MRI fusion-targeted biopsies with systematic random prostate biopsies (intervention group) at a one-to-one ratio to compare the diagnostic accuracy of systematic random versus combined fusion with systematic random biopsies (secondary outcome). A subset of recruited participants (n = 89) underwent RP and histologic sectioning. Results There were 582 participants who were eligible to undergo multiparametric MRI (mean age, 65 years ± 6 [SD]). In total, 413 had a PI-RADS score of at least 3 and were randomized into either the intervention group (207 of 413; 50.1%) or control group (206 of 413; 49.9%). The csPCa detection rate in the intervention group was higher, with an adjusted odds ratio of 1.79 (95% CI: 1.14, 2.79; P = .01). A subgroup of 89 men underwent RP (21.5%; 89 of 413). Multiparametric MRI helped correctly identify 131 of 182 csPCa foci in 89 men (sensitivity, 72%; 95% CI: 65, 78). The specificity, positive predictive value, and negative predictive value were 71% (91 of 128), 78% (131 of 168), and 64% (91 of 142), respectively. Conclusion Prebiopsy multiparametric MRI was accurate in the depiction of clinically significant PCa. Combining US and MRI fusion-targeted biopsies with systematic biopsies helped detect more clinically significant lesions than did systematic biopsies alone. Clinical trial registration no. NCT02745496 © RSNA, 2023 Supplemental material is available for this article.

Fungal alkaline proteases and their potential applications in different industries.

The consumption of various enzymes in industrial applications around the world has increased immensely. Nowadays, industries are more focused on incorporating microbial enzymes in multiple processes to avoid the hazardous effects of chemicals. Among these commercially exploited enzymes, proteases are the most abundantly used enzymes in different industries. Numerous bacterial alkaline proteases have been studied widely and are commercially available; however, fungi exhibit a broader variety of proteases than bacteria. Additionally, since fungi are often recognized as generally regarded as safe (GRAS), using them as enzyme producers is safer than using bacteria. Fungal alkaline proteases are appealing models for industrial use because of their distinct spectrum of action and enormous diversity in terms of being active under alkaline range of pH. Unlike bacteria, fungi are less studied for alkaline protease production. Moreover, group of fungi growing at alkaline pH has remained unexplored for their capability for the production of commercially valuable products that are stable at alkaline pH. The current review focuses on the detailed classification of proteases, the production of alkaline proteases from different fungi by fermentation (submerged and solid-state), and their potential applications in detergent, leather, food, pharmaceutical industries along with their important role in silk degumming, waste management and silver recovery processes. Furthermore, the promising role of alkali-tolerant and alkaliphilic fungi in enzyme production has been discussed briefly. This will highlight the need for more research on fungi growing at alkaline pH and their biotechnological potential.

Primary Definitive Treatment versus Ureteric Stenting in the Management of Acute Ureteric Colic: A Cost-Effectiveness Analysis.

Objectives: To analyze the differences in cost-effectiveness between primary ureteroscopy and ureteric stenting in patients with ureteric calculi in the emergency setting. Patients and Methods: Patients requiring emergency intervention for a ureteric calculus at a tertiary centre were analysed between January and December 2019. The total secondary care cost included the cost of the procedure, inpatient hospital bed days, emergency department (A&E) reattendances, ancillary procedures and any secondary definitive procedure. Results: A total of 244 patients were included. Patients underwent ureteric stenting (62.3%) or primary treatment (37.7%), including primary ureteroscopy (URS) (34%) and shock wave lithotripsy (SWL) (3.6%). The total secondary care cost was more significant in the ureteric stenting group (GBP 4485.42 vs. GBP 3536.83; p = 0.65), though not statistically significant. While mean procedural costs for primary treatment were significantly higher (GBP 2605.27 vs. GBP 1729.00; p < 0.001), costs in addition to the procedure itself were significantly lower (GBP 931.57 vs. GBP 2742.35; p < 0.001) for primary treatment compared to ureteric stenting. Those undergoing ureteric stenting had a significantly higher A&E reattendance rate compared with primary treatment (25.7% vs. 10.9%, p = 0.02) and a significantly greater cost per patient related to revisits to A&E (GBP 61.05 vs. GBP 20.87; p < 0.001). Conclusion: Primary definitive treatment for patients with acute ureteric colic, although associated with higher procedural costs than ureteric stenting, infers a significant reduction in additional expenses, notably related to fewer A&E attendances. This is particularly relevant in the COVID-19 era, where it is crucial to avoid unnecessary attendances to A&E and reduce the backlog of delayed definitive procedures. Primary treatment should be considered concordance with clinical judgement and factors such as patient preference, equipment availability and operator experience.

Emergency Primary Ureteroscopy for Acute Ureteric Colic-From Guidelines to Practice.

OBJECTIVE: To review the factors that may influence the ability to achieve the present guidelines' recommendations in a well-resourced tertiary centre. According to current National Institute for Health and Care Excellence (NICE) guidelines, definitive treatment (primary ureteroscopy (URS) or shock wave lithotripsy (ESWL)) should be offered to patients with symptomatic renal colic that are unlikely to pass the stone within 48 h of diagnosis. METHODS: Retrospective review of all patients presenting to the emergency department between January and December 2019 with a ureteric or renal stone diagnosis. The rate of emergency intervention, risk factors for intervention and outcomes were compared between patients who were treated by primary definitive surgery vs. primary symptom relief by urethral stenting alone. RESULTS: A total of 244 patients required surgical management for symptomatic ureteric colic without symptoms of urinary infection. Of those, 92 patients (37.7%) underwent definitive treatment by either primary URS (82 patients) or ESWL (9 patients). The mean time for the procedure was 25.5 h (range: 1-118). Patients who underwent primary definitive treatment were likelier to have smaller and distally located stones than the primary stenting group. Primary ureteroscopy was more likely to be performed in a supervised setting than emergency stenting. CONCLUSIONS: Although definitive treatment carries high success rates, in a high-volume tertiary referral centre, it may not be feasible to offer it to all patients, with emergency stenting providing a safe and quick interim measure. Factors determining the ability to provide definitive treatment are stone location, stone size and resident supervision in theatre.

Factors Predicting Outcomes of Supine Percutaneous Nephrolithotomy: Large Single-Centre Experience.

Objective: Percutaneous nephrolithotomy (PCNL) is the treatment of choice for large renal calculi. The prone position has been considered the preferred position to obtain renal access. However, the supine position has recently gained popularity, which confers several potential advantages. The current study analyses the prognostic factors for successful supine PCNL procedures in a larger tertiary centre. Subjects: Prospective data were collected from all patients undergoing PCNL in the Galdako modified Valdivia position at our institution between February-2007 and September-2020. Surgical outcomes variables collected included: the rate of Endoscopic-combined intra-renal surgery (ECIRS), operative times, surgical effectiveness (no residuals <2 mm stone fragments) and complications. Results: A total of 592 patients underwent PCNL with a median age of 56 years (IQR: 42−67). The median stone size was 17 mm (IQR: 13−23). Of those, 79% of patients had an effective procedure. Stone size (p < 0.001), location (p < 0.001) and Guys-Stone Score (GSS) (p < 0.001) were associated with effectiveness. A Percutaneous nephrostomy tube was sited at the completion of the procedure in 97.3% of patients and a simultaneous double-J stent in 45.3%. Stent insertion was associated with larger stones (p < 0.001), the performance of ECIRS (p < 0.001) and higher GSS (p < 0.001). The overall complication rate was 21.7%. The main type of complication was an infection in 26.2 of the cases followed by the need for repeated nephrostogram in 12.7%. Conclusions: We demonstrate that PCNL in a high-volume centre is safe and efficacious in the Galdalko modified Valdivia position. Patients with smaller stones in the renal pelvis and a low GSS have the highest chance of a successful procedure.

Himalayan musk deer (Moshcus leucogaster) behavior at latrine sites and their implications in conservation.

Elusive species often use latrines which also serves as communication and information hubs. Thus, studying behavior at latrines may provide critical insights into the species' ecology and behavior. While it is established that musk deer use latrines for defecating, very little is known about the endangered Himalayan musk deer (Moschus leucogaster) and their latrines. We examined musk deer behavior from the various video clips lasting 238 min altogether, captured at latrine sites during both breeding and non-breeding seasons in the Annapurna Conservation Area of Nepal. A total of 428 visits by musk deer and 479 behavioral events by them were captured. We constructed an ethogram to describe musk deer behavior and compared behavior across individuals and sex using parametric and non-parametric tests. We found that musk deer are crepuscular and nocturnal animals. Both male and female musk deer repeatedly and independently visited shared latrine sites as well as exclusively used latrine sites. The proportion of male musk deer visited latrine sites were significantly higher than that of female musk deer. Hence, male musk deer were found more active (>2 times) than females during both seasons. The most frequently observed behavioral activities at the latrine sites were defecating, sniffing and browsing, followed by scrapping and covering, and ignoring the latrine sites. The defecating and sniffing activity were performed throughout breeding and non-breeding seasons to establish communication among peers and to claim territory. Based on the behaviors observed at the latrine sites, we can presume that Himalayan musk deer likely use latrines to convey various messages, including personality, maturity, sexual status, and territory marking among conspecifics. These findings of this study can be used for the conservation of musk deer in its natural habitat and replicated in captivity to enhance breeding performance that improves long-term conservation prospects for this species.

Antioxidant, Antibacterial and Dyeing Potential of Crude Pigment Extract of Gonatophragmium triuniae and Its Chemical Characterization.

Filamentous fungi synthesize natural products as an ecological function. In this study, an interesting indigenous fungus producing orange pigment exogenously was investigated in detail as it possesses additional attributes along with colouring properties. An interesting fungus was isolated from a dicot plant, Maytenus rothiana. After a detailed study, the fungal isolate turned out to be a species of Gonatophragmium belonging to the family Acrospermaceae. Based on the morphological, cultural, and sequence-based phylogenetic analysis, the identity of this fungus was confirmed as Gonatophragmium triuniae. Although this fungus grows moderately, it produces good amounts of pigment on an agar medium. The fermented crude extract isolated from G. triuniae has shown antioxidant activity with an IC50 value of 0.99 mg/mL and antibacterial activity against Gram-positive bacteria (with MIC of 3.91 µg/mL against Bacillus subtilis, and 15.6 µg/mL and 31.25 µg/mL for Staphylococcus aureus and Micrococcus luteus, respectively). Dyeing of cotton fabric mordanted with FeSO4 using crude pigment was found to be satisfactory based on visual observation, suggesting its possible use in the textile industry. The orange pigment was purified from the crude extract by preparative HP-TLC. In addition, UV-Vis, FTIR, HRMS and NMR (1H NMR, 13C NMR), COSY, and DEPT analyses revealed the orange pigment to be "1,2-dimethoxy-3H-phenoxazin-3-one" (C14H11NO4, m/z 257). To our understanding, the present study is the first comprehensive report on Gonatophragmium triuniae as a potential pigment producer, reporting "1,2-dimethoxy-3H-phenoxazin-3-one" as the main pigment from the crude hexane extract. Moreover, this is the first study reporting antioxidant, antibacterial, and dyeing potential of crude extract of G. triuniae, suggesting possible potential applications of pigments and other bioactive secondary metabolites of the G. triuniae in textile and pharmaceutical industry.

Fungal diversity notes 1387-1511: taxonomic and phylogenetic contributions on genera and species of fungal taxa.

This article is the 13th contribution in the Fungal Diversity Notes series, wherein 125 taxa from four phyla, ten classes, 31 orders, 69 families, 92 genera and three genera incertae sedis are treated, demonstrating worldwide and geographic distribution. Fungal taxa described and illustrated in the present study include three new genera, 69 new species, one new combination, one reference specimen and 51 new records on new hosts and new geographical distributions. Three new genera, Cylindrotorula (Torulaceae), Scolecoleotia (Leotiales genus incertae sedis) and Xenovaginatispora (Lindomycetaceae) are introduced based on distinct phylogenetic lineages and unique morphologies. Newly described species are Aspergillus lannaensis, Cercophora dulciaquae, Cladophialophora aquatica, Coprinellus punjabensis, Cortinarius alutarius, C. mammillatus, C. quercoflocculosus, Coryneum fagi, Cruentomycena uttarakhandina, Cryptocoryneum rosae, Cyathus uniperidiolus, Cylindrotorula indica, Diaporthe chamaeropicola, Didymella azollae, Diplodia alanphillipsii, Dothiora coronicola, Efibula rodriguezarmasiae, Erysiphe salicicola, Fusarium queenslandicum, Geastrum gorgonicum, G. hansagiense, Helicosporium sexualis, Helminthosporium chiangraiensis, Hongkongmyces kokensis, Hydrophilomyces hydraenae, Hygrocybe boertmannii, Hyphoderma australosetigerum, Hyphodontia yunnanensis, Khaleijomyces umikazeana, Laboulbenia divisa, Laboulbenia triarthronis, Laccaria populina, Lactarius pallidozonarius, Lepidosphaeria strobelii, Longipedicellata megafusiformis, Lophiotrema lincangensis, Marasmius benghalensis, M. jinfoshanensis, M. subtropicus, Mariannaea camelliae, Melanographium smilaxii, Microbotryum polycnemoides, Mimeomyces digitatus, Minutisphaera thailandensis, Mortierella solitaria, Mucor harpali, Nigrograna jinghongensis, Odontia huanrenensis, O. parvispina, Paraconiothyrium ajrekarii, Parafuscosporella niloticus, Phaeocytostroma yomensis, Phaeoisaria synnematicus, Phanerochaete hainanensis, Pleopunctum thailandicum, Pleurotheciella dimorphospora, Pseudochaetosphaeronema chiangraiense, Pseudodactylaria albicolonia, Rhexoacrodictys nigrospora, Russula paravioleipes, Scolecoleotia eriocamporesi, Seriascoma honghense, Synandromyces makranczyi, Thyridaria aureobrunnea, Torula lancangjiangensis, Tubeufia longihelicospora, Wicklowia fusiformispora, Xenovaginatispora phichaiensis and Xylaria apiospora. One new combination, Pseudobactrodesmium stilboideus is proposed. A reference specimen of Comoclathris permunda is designated. New host or distribution records are provided for Acrocalymma fici, Aliquandostipite khaoyaiensis, Camarosporidiella laburni, Canalisporium caribense, Chaetoscutula juniperi, Chlorophyllum demangei, C. globosum, C. hortense, Cladophialophora abundans, Dendryphion hydei, Diaporthe foeniculina, D. pseudophoenicicola, D. pyracanthae, Dictyosporium pandanicola, Dyfrolomyces distoseptatus, Ernakulamia tanakae, Eutypa flavovirens, E. lata, Favolus septatus, Fusarium atrovinosum, F. clavum, Helicosporium luteosporum, Hermatomyces nabanheensis, Hermatomyces sphaericoides, Longipedicellata aquatica, Lophiostoma caudata, L. clematidis-vitalbae, Lophiotrema hydei, L. neoarundinaria, Marasmiellus palmivorus, Megacapitula villosa, Micropsalliota globocystis, M. gracilis, Montagnula thailandica, Neohelicosporium irregulare, N. parisporum, Paradictyoarthrinium diffractum, Phaeoisaria aquatica, Poaceascoma taiwanense, Saproamanita manicata, Spegazzinia camelliae, Submersispora variabilis, Thyronectria caudata, T. mackenziei, Tubeufia chiangmaiensis, T. roseohelicospora, Vaginatispora nypae, Wicklowia submersa, Xanthagaricus necopinatus and Xylaria haemorrhoidalis. The data presented herein are based on morphological examination of fresh specimens, coupled with analysis of phylogenetic sequence data to better integrate taxa into appropriate taxonomic ranks and infer their evolutionary relationships.

Mercury distribution in the East Himalayas: Elevational patterns in soils and non-volant small mammals.

Mercury (Hg), as a global pollutant, its contamination has been documented in environmental compartments of the Himalayan region. However, little research exists regarding to Hg accumulation in terrestrial wildlife, as well as its driving factors. In this study, surface soil and small mammals were collected in the Lebu Valley, East Himalayas of China, in order to measure the uptake of the long-distance transported Hg along an elevational gradient approximately from 2300 to 5000 m a.s.l. The soil Hg concentrations were measured and predicted mostly by vegetation type as well as soil organic matter, while the Hg in hair of small mammals (Muridae and Cricetidae) showed deeply influenced by soil Hg. Notably, combined with the field survey data, soil and hair Hg were both enhanced in low and mid-elevations, which overlapped the distribution ranges of a majority of mammals. Overall, this indicates that Hg contamination in low- and mid-elevations poses a potential threat to the top predators that consuming small mammals directly or indirectly. Furthermore, our data advances the understanding of Hg dynamics in remote, high mountain ecosystems and provides baseline data for biomonitoring for reduction of Hg emission globally.

Climate-driven elevational variation in range sizes of vascular plants in the central Himalayas: A supporting case for Rapoport's rule.

A fundamental yet controversial topic in biogeography is how and why species range sizes vary along spatial gradients. To advance our understanding of these questions and to provide insights into biological conservation, we assessed elevational variations in the range sizes of vascular plants with different life forms and biogeographical affinities and explored the main drivers underlying these variations in the longest valley in China's Himalayas, the Gyirong Valley. Elevational range sizes of vascular plants were documented in 96 sampling plots along an elevational gradient ranging from 1,800 to 5,400 m above sea level. We assessed the elevational variations in range size by averaging the range sizes of all recorded species within each sampling plot. We then related the range size to climate, disturbance, and the mid-domain effect and explored the relative importance of these factors in explaining the range size variations using the Random Forest model. A total of 545 vascular plants were recorded in the sampling plots along the elevational gradient. Of these, 158, 387, 337, and 112 were woody, herbaceous, temperate, and tropical species, respectively. The range size of each group of vascular plants exhibited uniform increasing trends along the elevational gradient, which was consistent with the prediction of Rapoport's rule. Climate was the main driver of the increasing trends of vascular plant range sizes in the Gyirong Valley. The climate variability hypothesis and mean climate condition hypothesis could both explain the elevation-range size relationships. Our results reinforce the previous notion that Rapoport's rule applies to regions where the influence of climate is the most pronounced, and call for close attention to the impact of climate change to prevent species range contraction and even extinction due to global warming.

Differential HLA Association of GAD65 and IA2 Autoantibodies in North Indian Type 1 Diabetes Patients.

The human leucocyte antigen (HLA) association with type 1 diabetes (T1D) is well known but there are limited studies investigating the association between ß-cell autoantibodies and HLA genes. We evaluated the prevalence of GAD65 and IA-2 autoantibodies (GADA and IA2A) in 252 T1D patients from North India and investigated the genetic association of GADA and IA2A with HLA class I and class II genes/haplotypes. GADA and IA2A were detected in 50.79% and 15.87% of T1D patients, respectively, while only 8.73% had both GADA and IA2A. HLA-DRB1∗03 was observed to be significantly higher in GADA+ T1D patients as compared to GADA- (91.41% vs. 66.13%, Bonferroni-corrected P (P c) = 1.11 × 10-5; OR = 5.45; 95% CI: 2.67-11.08). Similarly, HLA-DQB1∗02 was found to be significantly increased in GADA+ patients (94.53%, P c = 2.19 × 10-5; OR = 6.27; 95% CI: 2.7-14.49) as compared to GADA- (73.39%). The frequencies of HLA-DRB1∗04 and DQB1∗03 were increased in IA2A+ patients (45.0% and 52.5%, respectively) as compared to that in IA2A- (25.94% and 33.96%, respectively). Further, the frequency of DRB1∗03-DQB1∗02 haplotype was found to be significantly increased in GADA+ T1D patients as compared to GADA- (60.55% vs. 41.94%, P = 3.94 × 10-5; OR = 2.13; 95%CI = 1.49-3.03). Similarly, HLA-DRB1∗04-DQB1∗03 haplotype was found to be significantly increased in IA2A+ T1D patients compared to IA2A- patients (22.5% vs. 12.97%; P = 0.041; OR = 1.95; 95%CI = 1.08-3.52). None of the HLA class I genes (HLA-A, B, and Cw) was found to be associated with GADA or IA2A in people with T1D. Our findings suggest that HLA-DRB1∗03/DQB1∗02 and HLA-DRB1∗04/DQB1∗03 might play an important role in the development of GADA and IA2A, respectively.

Author Correction: Projected distribution and climate refugia of endangered Kashmir musk deer Moschus cupreus in greater Himalaya, South Asia.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Projected distribution and climate refugia of endangered Kashmir musk deer Moschus cupreus in greater Himalaya, South Asia.

Kashmir musk deer Moschus cupreus (KMD) are the least studied species of musk deer. We compiled genetically validated occurrence records of KMD to construct species distribution models using Maximum Entropy. We show that the distribution of KMD is limited between central Nepal on the east and north-east Afghanistan on the west and is primarily determined by precipitation of driest quarter, annual mean temperature, water vapor, and precipitation during the coldest quarter. Precipitation being the most influential determinant of distribution suggests the importance of pre-monsoon moisture for growth of the dominant vegetation, Himalayan birch Betula utilis and Himalayan fir Abies spectabilis, in KMD's preferred forests. All four Representative Concentration Pathway Scenarios result an expansion of suitable habitat in Uttarakhand, India, west Nepal and their associated areas in China in 2050s and 2070s but a dramatic loss of suitable habitat elsewhere (Kashmir region and Pakistan-Afghanistan border). About 1/4th of the current habitat will remain as climate refugia in future. Since the existing network of protected areas will only include a tiny fraction (4%) of the climatic refugia of KMD, the fate of the species will be determined by the interplay of more urgent short-term forces of poaching and habitat degradation and long-term forces of climate change.

Fungal Pigments and Their Prospects in Different Industries.

The public's demand for natural, eco-friendly, and safe pigments is significantly increasing in the current era. Natural pigments, especially fungal pigments, are receiving more attention and seem to be in high demand worldwide. The immense advantages of fungal pigments over other natural or synthetic pigments have opened new avenues in the market for a wide range of applications in different industries. In addition to coloring properties, other beneficial attributes of fungal pigments, such as antimicrobial, anticancer, antioxidant, and cytotoxic activity, have expanded their use in different sectors. This review deals with the study of fungal pigments and their applications and sheds light on future prospects and challenges in the field of fungal pigments. Furthermore, the possible application of fungal pigments in the textile industry is also addressed.

A multicentre parallel-group randomised trial assessing multiparametric MRI characterisation and image-guided biopsy of prostate in men suspected of having prostate cancer: MULTIPROS study protocol.

BACKGROUND: There is growing evidence suggesting that multiparametric magnetic resonance imaging (mpMRI) is a marker for prostate cancer (PCa) aggressiveness and could be used to plan treatment. Improving early detection of clinically significant PCa with pre-biopsy mpMRI would very likely have advantages including optimising the diagnosis and treatment of diseases and diminishing patient anxiety. METHODS AND MATERIALS: This is a prospective multicentre study of pre-biopsy mpMRI diagnostic test accuracy with subgroup randomisation at a 1:1 ratio with respect to transrectal ultrasound (TRUS) and MRI/US fusion-guided biopsy or TRUS-only biopsy. It is designed as a single-gate study with a single set of inclusion criteria. The total duration of the recruitment phase was 48 months; however, this has now been extended to 66 months. A sample size of 600 participants is required. DISCUSSION: The primary objective is to determine whether mpMRI can improve PCa detection and characterisation. The key secondary objective is to determine whether MRI/US fusion-guided biopsy can reduce the number of false-negative biopsies. Ethical approval was obtained from the East of Scotland Research Ethics Committee 1 (14/ES/1070) on 20 November 2014. The results of this study will be used for publication and presentation in national and international journals and at scientific conferences. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02745496. Retrospectively registered on 20 April 2016.

Cytokine gene polymorphisms among North Indians: Implications for genetic predisposition?

Variations in the production and activity of cytokines influence the susceptibility and/or resistance to various infectious agents, autoimmune diseases, as well as the post-transplant engraftment/ rejection. Differences in the production of cytokines between individuals have been correlated to single nucleotide polymorphisms (SNPs) in the promoter, coding or non-coding regions of cytokine genes. The present study aimed at understanding distribution of cytokine gene variants among HIV seropositive subjects including HIV + TB+ subjects of Indian origin. Our findings indicate significant association of pro-inflammatory (IL2, IFN-γ, TNF-α) and anti-inflammatory cytokine gene variants (IL4, IL10) with the risk to acquire the HIV infection and development of AIDS related illness in Indian population. Since distribution of genetic polymorphisms varies significantly across different populations, different genotypes might exhibit different disease-modifying effects. An understanding of the immunogenetic factors or AIDS restriction genes is important not only for elucidating the mechanisms of disease pathogenesis but also for vaccine design and its application.

mtDNA analysis confirms the endangered Kashmir musk deer extends its range to Nepal.

Musk deer Moschus spp. are endemic to the high mountain forests of central Asia. The taxonomic status of musk deer in the central and western Himalayas is poorly understood. We investigated the phylogenetic relationship of musk deer from the central and western Himalayas based on mitochondrial genomic data of Cytochrome b (380 bps) and D-loop (1000 bps). Our results distinguished two divergent lineages using higher bootstrap support (bs) values from the Maximum likelihood and Bayesian posterior probabilities (bpp). Both the Manang and Kaski lineages from central Nepal are confirmed as Himalayan musk deer Moschus leucogaster and represent a species complex widespread throughout the central and eastern Himalayan region. The musk deer Mustang lineage was confirmed as Kashmir musk deer Moschus cupreus and has wide distribution in the western Himalayas (from central Nepal to Afghanistan). Our analysis validates that Kashmir musk deer is a genetically distinct species and it clarifies that Himalayan musk deer and Kashmir musk deer are confirmed instead of Alpine musk deer Moschus chrysogaster which has been previously described from the southern parts of Himalayas of Nepal, India and Pakistan.

Diagnostic accuracy of loop-mediated isothermal amplification assay for extra-pulmonary tuberculosis in Indian population.

BACKGROUND: Confirmatory diagnosis of extra-pulmonary tuberculosis remains a true challenge owing to difficulty in procuring appropriate specimen, inefficient laboratory methods and paucibacillary nature of infection. These obstructions become all the very difficult in pediatric EPTB cases, due to non-specific clinical signs and symptoms, low sensitivity of smear microscopy and culture, lack of awareness among clinicians, etc. AIM OF THE STUDY: The present study aimed to evaluate the diagnostic accuracy of rapid and cost-effective loop-mediated isothermal amplification (LAMP) assay for EPTB diagnosis in children. METHODS: A total of 154 cases were analyzed by EPTB-site smear microscopy, culture, PCRs for IS6110, MPB64 & Pab genes, nested PCR and LAMP assay. Single-gene PCRs were performed by custom-synthesized primers. Nested PCR was performed using the 3B BIOTUB Kit and the LAMP assay was done using the Nu-LAMP TB kit. RESULTS: We observed that the molecular tests displayed 4-fold higher positivity rate (minimum 46%) in comparison to the microbiological tests (maximum 11.03%). In contrast to the composite reference standard, LAMP assay was found to be 79.6% sensitive and 78% specific for EPTB diagnosis in childhood cases. CONCLUSIONS: Our results indicate that LAMP assay is a promising technique for efficient diagnosis of EPTB in children belonging to resource-limited regions.

Ecological correlates of Himalayan musk deer Moschus leucogaster.

Himalayan musk deer (Moschus leucogaster; hereafter musk deer) are endangered as a result of poaching and habitat loss. The species is nocturnal, crepuscular, and elusive, making direct observation of habitat use and behavior difficult. However, musk deer establish and repeatedly use the same latrines for defecation. To quantify musk deer habitat correlates, we used observational spatial data based on presence-absence of musk deer latrines, as well as a range of fine spatial-scale ecological covariates. To determine presence-absence of musk deer, we exhaustively searched randomly selected forest trails using a 20-m belt transect in different study sites within the Neshyang Valley in the Annapurna Conservation Area. In a subsequent way, study sites were classified as habitat or nonhabitat for musk deer. A total of 252 plots, 20 × 20 m, were systematically established every 100 m along 51 transects (each ~0.5 km long) laid out at different elevations to record a range of ecological habitat variables. We used mixed-effect models and principal component analysis to characterize relationships between deer presence-absence data and habitat variables. We confirmed musk deer use latrines in forests located at higher elevations (3,200-4,200 m) throughout multiple seasons and years. Himalayan birch (Betula utilis) dominated forest, mixed Himalayan fir (Abies spectabilis), and birch forest were preferred over pure Himalayan fir and blue pine (Pinus wallichiana) forest. Greater crown cover and shrub diversity were associated with the presence of musk deer whereas tree height, diameter, and diversity were weakly correlated. Topographical attributes including aspect, elevation, distance to water source, and slope were also discriminated by musk deer. Over- and understory forest management can be used to protect forests likely to have musk deer as predicted by the models to ensure long-term conservation of this rare deer.