Molecular characterisation of a case of dicentric Y presented as nonobstructive azoospermia with testicular early maturation arrest.

The dicentric Y chromosome is the most common cytogenetically visible structural abnormality of Y chromosome. The sites of break and fusion of dicentric Y are variable, but break and fusion at Yq12 (proximal to the pseudoautosomal region 2/PAR 2) is very rare. Dicentric Y chromosome is unstable during cell division and likely to generate chromosomal mosaicism. Here, we report a case of infertile male with nonmosaic 46,XY where chromosome Y was dicentric with break and fusion at Yq12 (proximal to PAR 2). Clinical presentation of the case was nonobstructive azoospermia due to early maturation arrest at the primary spermatocyte stage. Various molecular techniques such as FISH, STS-PCR and DNA microarray were carried out to characterise genetic defect leading to testicular maturation arrest in the patient. The break and fusion was found at Yq12 (proximal to PAR 2) and resulted in near total duplication of Y chromosome (excluding PAR 2). The reason for maturation arrest seems due to CNVs of PARs (gain in PAR 1 and loss of PAR 2) and azoospermia factors (gain).

Differential expression of THELPER 1 cytokines upon antigen stimulation predicts ex vivo proliferative potential and cytokine production of virus-specific T cells following re-stimulation.

INTRODUCTION: Cytomegalovirus (CMV) and human adenovirus (ADV) infections are causes of morbidity after stem cell transplantation. Antigen (Ag)-specific T cells are essential for the control of viral infections. However, in vivo expansion potential of T-cell subpopulations is hardly predictable in humans. Furthermore, ex vivo identification of human T cells with repopulating capacity for adoptive T-cell transfer has been difficult. METHODS: We analyzed Ag-specific T-cell populations, subdivided according to the expression of different THELPER- 1 (Th1) cytokines. Isolation by flow cytometry was based on interferon-gamma (IFN)-γ, interleukin (IL)-2, or tumor necrosis factor-alpha (TNF-α) secretion of T cells after ex vivo stimulation with the Ags hexon (for ADV) and pp65 (for CMV). Isolated T cells were expanded and examined for functional characteristics, expansion/differentiation potential, and naïve, effector memory, central memory, and late effector phenotypes. RESULTS: Isolation based on IFN-γ production provides a T-cell population with a mixture of early, central memory, and effector memory T cells, high expansion potential, and effective cytokine production. Selection of T cells with Ag-specific expression of IL-2 or TNF-α, however, results in a T-cell population with reduced proliferation and lower effector potential after expansion. CONCLUSION: We conclude that the exclusive secretion of IFN-γ in the human antiviral T-cell responses preferentially leads to higher repopulation capacities of antiviral T cells, compared to IL-2 or TNF-α secreting T-cell populations.

Mode-locked thulium bismuth codoped fiber laser using graphene saturable absorber in ring cavity: reply.

Jung and Lee have made comments [Appl. Opt.53, 553-554 (2014)] on "Mode-locked thulium bismuth codoped fiber laser using Graphene saturable absorber in ring cavity" [Appl. Opt.52, 1226-1229 (2013)]. The answer for the comment is provided in this report.

Dark-coloured semen in nonobstructive azoospermia: a report of four cases.

Dark-coloured semen is rarely observed in men with nonobstructive azoospermia in absence of genital tract bleeding. Dark-coloured semen is also observed rarely in men with spinal cord injury with or without genital tract bleeding. However, this condition has not been reported in the literature in absence of genital tract bleeding or spinal cord injury. Here, we report men with nonobstructive azoospermia with dark-coloured semen and without genital tract bleeding or spinal cord injury. The study included four subjects with dark-coloured semen. All the samples first investigated for the presence of red blood cells as well as haemoglobin. All the cases were examined in details with seminal, hormonal and genetic parameters. In addition, an elemental electron microscopy and inductively coupled plasma-atomic emission spectrometry evaluation for heavy metals was performed. The semen parameters showed normal volume, pH, leucocyte count and azoospermia or oligoazoospermia. Dark-coloured semen specimens contained neither red blood cells nor haeme pigment. Electron microscopy showed presence of platinum in all the cases, whereas inductively coupled plasma-atomic emission spectrometry revealed increased levels of lead, manganese and nickel in serum as compared to controls. The results indicate dark-coloured semen may be linked with heavy metals found in seminal cells.

Mode-locked thulium-bismuth codoped fiber laser using graphene saturable absorber in ring cavity.

We demonstrate mode locking of a thulium-bismuth codoped fiber laser (TBFL) operating at 1901.6 nm, using a graphene-based saturable absorber (SA). In this work, a single layer graphene is mechanically exfoliated using the scotch tape method and directly transferred onto the surface of a fiber pigtail to fabricate the SA. The obtained Raman spectrum characteristic indicates that the graphene on the core surface has a single layer. At 1552 nm pump power of 869 mW, the mode-locked TBFL self starts to generate an optical pulse train with a repetition rate of 16.7 MHz and pulse width of 0.37 ps. This is a simple, low-cost, stable, and convenient laser oscillator for applications where eye-safe and low-photon-energy light sources are required, such as sensing and biomedical diagnostics.

Management of idiopathic granulomatous mastitis: a prospective study.

INTRODUCTION: Idiopathic granulomatous mastitis (IGM) is an evolving problem with varied presentation. No definite treatment guidelines are available at present that may reduce rate of recurrence. Current evidence suggests a ductal pathology behind IGM, which leads to periductal mastitis, leakage and sinus/fistula formation. Thus, excision of the sinus/fistulous tract with en-bloc wide local excision (WLE) of the lesion could be curative. The objective of this study was to look for the basic aetiology of IGM and evaluate the effectiveness of WLE with total or partial duct excision as a curative approach. METHODS: An institutional prospective comparative study was conducted over 4 years (2015-2019), in which 59 cases of IGM were randomly divided into three groups. After necessary investigations, patients in group A received steroid therapy, those in group B received WLE and patients in group C received WLE with total or partial duct excision as the mode of treatment. Postoperative follow-up was between 6 months and 3 years. RESULTS: Histopathological examination (HPE) was found to be the most suitable diagnostic procedure. Patients in group B showed the highest rate of recurrence (73.6%), followed by group A (35.0%) and group C (5.0%). Patients in group C had a significantly lower chance of recurrence compared with both group A and group B (p < 0.05). HPE reports of excised ducts from patients in group C showed ductal disruption and leakage along with periductal granuloma in 70% of cases. CONCLUSIONS: The presence of duct granuloma indicates the association of ductal pathology in IGM. IGM is therefore a disease of the mammary ducts and en-bloc duct excision is curative in non-responding cases.

Phenotyping Superagers Using Resting-State fMRI.

BACKGROUND AND PURPOSE: Superagers are defined as older adults with episodic memory performance similar or superior to that in middle-aged adults. This study aimed to investigate the key differences in discriminative networks and their main nodes between superagers and cognitively average elderly controls. In addition, we sought to explore differences in sensitivity in detecting these functional activities across the networks at 3T and 7T MR imaging fields. MATERIALS AND METHODS: Fifty-five subjects 80 years of age or older were screened using a detailed neuropsychological protocol, and 31 participants, comprising 14 superagers and 17 cognitively average elderly controls, were included for analysis. Participants underwent resting-state-fMRI at 3T and 7T MR imaging. A prediction classification algorithm using a penalized regression model on the measurements of the network was used to calculate the probabilities of a healthy older adult being a superager. Additionally, ORs quantified the influence of each node across preselected networks. RESULTS: The key networks that differentiated superagers and elderly controls were the default mode, salience, and language networks. The most discriminative nodes (ORs > 1) in superagers encompassed areas in the precuneus posterior cingulate cortex, prefrontal cortex, temporoparietal junction, temporal pole, extrastriate superior cortex, and insula. The prediction classification model for being a superager showed better performance using the 7T compared with 3T resting-state-fMRI data set. CONCLUSIONS: Our findings suggest that the functional connectivity in the default mode, salience, and language networks can provide potential imaging biomarkers for predicting superagers. The 7T field holds promise for the most appropriate study setting to accurately detect the functional connectivity patterns in superagers.

Eigenvalue equation and core-mode cutoff of weakly guiding tapered fiber as three layer optical waveguide and used as biochemical sensor.

The core-mode cutoff plays a major role in evanescent field absorption based sensors. A method has been proposed to calculate the core-mode cutoff by solving the eigenvalue equations of a weakly guiding three layer optical waveguide graphically. The variation of normalized waveguide parameter (V) is also calculated with different wavelengths at core-mode cutoff. At the first step, theoretical analysis of tapered fiber parameters has been performed for core-mode cutoff. The taper angle of an adiabatic tapered fiber is also analyzed using the length-scale criterion. Secondly, single-mode tapered fiber has been developed to make a precision sensor element suitable for chemical detection. Finally, the sensor element has been used to detect absorption peak of ethylenediamine. Results are presented in which an absorption peak at 1540 nm is observed.

Depression among Patients Presenting with Gastrointestinal Symptoms: Prevalence and Associated Factors.

Gastrointestinal diseases frequently affect patients' physical and emotional wellbeing as being heavily affected by stress. This study was conducted to find out prevalence and severity of depressive symptoms among patients presenting with gastrointestinal symptoms. This cross sectional study was conducted at Outpatients Department jointly by Department of Gastroenterology and Department of Psychiatry of a tertiary care hospital in north east part of Bangladesh from November 2011 to June 2012. Consecutive patients with gastrointestinal symptoms underwent psychiatric evaluation using HDRS and analyzed. 442 patients, 38(8.6%) were found normal. Among the rest 128(28.96%), 138(31.22%), 72(16.29%) and 66(14.93%) had mild, moderate, severe and very severe depressive symptoms respectively. Female sex (95.03% vs. 89.32%), married people (93.77 vs. 86.13%), older age (98.24%), rural people (94.26% vs. 84.36%), farmers (96.36%) and house wives (96.24%) were more affected. Prevalence of depression was also higher among patients with lower socioeconomic class, less educated people and rural background. Depressive symptoms are very common in patients presenting with gastrointestinal symptoms. Awareness regarding psychiatric assessment and intervention may reduce sufferings and thus improve wellbeing of these patients.

ClimApp-Integrating Personal Factors with Weather Forecasts for Individualised Warning and Guidance on Thermal Stress.

This paper describes the functional development of the ClimApp tool (available for free on iOS and Android devices), which combines current and 24 h weather forecasting with individual information to offer personalised guidance related to thermal exposure. Heat and cold stress assessments are based on ISO standards and thermal models where environmental settings and personal factors are integrated into the ClimApp index ranging from -4 (extremely cold) to +4 (extremely hot), while a range of -1 and +1 signifies low thermal stress. Advice for individuals or for groups is available, and the user can customise the model input according to their personal situation, including activity level, clothing, body characteristics, heat acclimatisation, indoor or outdoor situation, and geographical location. ClimApp output consists of a weather summary, a brief assessment of the thermal situation, and a thermal stress warning. Advice is provided via infographics and text depending on the user profile. ClimApp is available in 10 languages: English, Danish, Dutch, Swedish, Norwegian, Hellenic (Greek), Italian, German, Spanish and French. The tool also includes a research functionality providing a platform for worker and citizen science projects to collect individual data on physical thermal strain and the experienced thermal strain. The application may therefore improve the translation of heat and cold risk assessments and guidance for subpopulations. ClimApp provides the framework for personalising and downscaling weather reports, alerts and advice at the personal level, based on GPS location and adjustable input of individual factors.

[Arthroscopic reconstruction of anterior cruciate ligament with press-fit technique]. / Arthroskopische Rekonstruktion des vorderen Kreuzbandes in Press-fit-Technik.

PURPOSE: Problems related to the use of interference screws for fixation of bone-patellar tendon-bone grafts for anterior cruciate ligament (ACL) replacement have led to increasing interest in press-fit techniques. Most of the described techniques use press-fit fixation on either the femoral or tibial side. Therefore an arthroscopic technique was developed which achieves bone-patellar tendon-bone graft fixation by press-fit on both sides without the need for supplemental fixation material. METHODS: The first consecutive 40 patients were examined clinically with a KT-1000 arthrometer and radiologically after a mean of 28.7 months (range 20-40 months) postoperatively. RESULTS: The mean difference in side-to-side laxity was 1.3 mm (SD 2.2 mm) and the results according to the International Knee Documentation Committee (IKDC) score were as follows: 7 A, 28 B, 5 C, 0 D. CONCLUSIONS: The presented press-fit technique avoids all complications related to the use of interference screws. It achieves primary stable fixation of the bone-patellar tendon-bone graft thereby allowing early functional rehabilitation. However, fixation strength depends on bone quality and the arthroscopic procedure is demanding. The results showed reliable stabilization of the operated knees.

A new uterine suture technique to control PPH in congenitally malformed uterus during caesarean section.

The objective of this prospective study was to evaluate the efficacy of simultaneous devascularisation and compression suture for the control of PPH in a congenitally malformed uterus during caesarean section while classic management failed. The technique adopted for devascularisation was ligation of uterine arteries bilaterally below the hysterotomy wound and for the compression of the uterine musculature, suture passing through and through the anterior and posterior wall above the hysterotomy wound closed to either side, tied anteriorly. The majority (75%) of the women were primigravida and mostly presented with malpresentation of the fetus. Mothers were in the age group of 19-24 years. Out of eight cases, four (50%) cases had a bicornuate uterus, two cases had unicornuate and two had a sub-septate uterus. This procedure was effective in 87.5% (7/8) of cases. In follow-up, normal puerperium, menstruation and pregnancy were observed. This procedure is a simple, effective and safe technique to control PPH in congenitally malformed uterus in the field of conservative surgical approaches.

Finding the structural requirements of diverse HIV-1 protease inhibitors using multiple QSAR modelling for lead identification.

Multiple Quantitative Structure-Activity Relationship (QSAR) analysis is widely used in drug discovery for lead identification. Human Immunodeficiency Virus (HIV) protease is one of the key targets for the treatment of Acquired Immunodeficiency Syndrome (AIDS). One of the major challenges for the design of HIV-1 protease inhibitors (HIV PRIs) is to increase the inhibitory activities against the enzyme to a level where the problem associated to drug resistance may be considerably delayed. Herein, chemometric analyses were performed with 346 structurally diverse HIV PRIs with experimental bioactivities against a sub-type B mutant to develop highly predictable QSAR models and also to identify the effective structural determinants for higher affinity against HIV PR. The QSAR models were developed using OCHEM-based machine learning tools (ASNN, FSMLR, KNN, RF, MANN and XGBoost), with descriptors calculated by eight different software packages. Simultaneously, a Monte Carlo optimization-based QSAR modelling was performed using SMILES and graph-based descriptors to understand fragment and topochemical contributions. To validate the actual predictability of all these models, an additional set of 104 compounds (also with known experimental activities) with slightly different chemical space were employed. This ligand-based study serves as a crucial benchmark for further development of the HIV protease inhibitors with improved activities.

Preparation of colourless phosphate glass by stabilising higher Fe[II] in microwave heating.

Iron impurity in raw material remains a major challenge in producing colourless glass. In this investigation, we report microwave (MW) heating capable of altering Fe-redox ratio (Fe2+/∑Fe) enabling preparation of colourless phosphate glass. The effect of Sn concentration in retention of Fe[II] in glass melted in MW was compared with conventional glasses. Colourimetric study developing Fe2+-ferrozine colour complex reveals Fe-redox ratio ≥0.49 required to obtain colourless phosphate glass. In microwave heating, addition of 1 wt.% Sn metal powder can impart the desired effect whereas addition of 1.9 wt.% Sn metal powder is required in conventional heating. The correlation equation of Fe-redox ratio with concentration of Sn metal is found to be different in microwave and conventional heating. Thus, exploiting this different redox changes in MW heating optical properties can be tailored. Preservation of higher Fe[II] in MW melted glass is also confirmed by XPS and TGA. 31P MAS NMR spectra suggest that transition from cross linked ultra phosphate to linear polymer metaphosphate network in incorporation of Sn is found different in glass prepared adopting microwave irradiation. 27A1 MAS NMR spectra suggest higher relative content of Al6+ in glass obtained from MW heating. Energy consumption analysis revels 3.4 kWh in MW heating while 14 kWh in conventional glass melting using resistance heating. Further, glass melting in MW can be completed within 2 h unlike ~5 h needed in conventional. MW heating plays a significant role in improving properties to make colourless phosphate glass in addition to significant energy and time saving.

Copy number variations in testicular maturation arrest.

Testicular maturation arrest is characterized by interruption of germ cell development and differentiation. Genetic factors play important role in the causation of human disease, including male infertility. The objective was to study copy number variations in testicular maturation arrest using single nucleotide polymorphism (SNP) microarray technique. Conventional cytogenetics, targeted fluorescence in situ hybridization (FISH) and sequence-tagged site (STS) polymerase chain reaction (PCR) were used to confirm some of the SNP microarray findings. SNP microarray on 68 cases of testicular maturation arrest detected copy number variations (CNVs) mostly on sex chromosomes involving pseudoautosomal regions (PAR) 1, 2 and 3 as well as azoospermic factors (AZFs) besides three cases of chromosomal abnormalities (two Klinefelter syndromes and one case of dicentric Y). The AZF deletion was observed in 14 (20.6%) cases and the AZFc gain was observed in 6 (8.8%) cases. PAR 1 and 2 CNVs was observed in 5 (7.3%) cases. PAR 3 CNVs was detected in 19 cases and 2 controls. The TSPY2 gene gain (within PAR 3 CNVs) was observed in 16 cases and 1 control. CNV containing autosomal genes possibly associated with male infertility in this study was SPATA31A2-A5 (9p12) in five cases. In this study, SNP microarray identified possible underlying aetiology in 55.9% (38/68) cases besides identifying minimal critical region of AZFc deletion as 0.51 mb (Y:24356128-24873665) involving TTY5, RBMY2FP, RBMY1F, RBMY1J, TTY6 and PRY genes. SNP microarray seems superior, sensitive, specific as well as cost-effective method and has potential to be the first tier investigations to explore underlying genomic factors of testicular maturation arrest. The present study is an attempt to find out probable genomic factors with idiopathic testicular maturation arrest.

Insight into the structural requirements of pyrimidine-based phosphodiesterase 10A (PDE10A) inhibitors by multiple validated 3D QSAR approaches.

Schizophrenia is a complex disorder of thinking and behaviour (0.3-0.7% of the population is affected). The over-expression of phosphodiesterase 10A (PDE10A) enzyme may be a potential target for schizophrenia and Huntington's disease. Because 3D QSAR analysis is one of the most frequently used modelling techniques, in the present study, five different 3D QSAR tools, namely CoMFA, CoMSIA, kNN-MFA, Open3DQSAR and topomer CoMFA methods, were used on a dataset of pyrimidine-based PDE10A inhibitors. All developed models were validated internally and externally. The non-commercial Open3DQSAR produced the best statistical results amongst 3D QSAR tools. The structural interpretations obtained from different methods were thoroughly analysed and were justified on the basis of information obtained from the crystal structure. Information from one method was mostly validated by the results of other methods and vice versa. In the current work, the use of multiple tools in the same analysis revealed more complete information about the structural requirements of these compounds. On the basis of the observations of the 3D QSAR studies, 12 new compounds were designed for better PDE10A inhibitory activity. The current investigation may help in further designing new PDE10A inhibitors with promising activity.

Healthcare worker and family caregiver hand hygiene in Bangladeshi healthcare facilities: results from the Bangladesh National Hygiene Baseline Survey.

BACKGROUND: Healthcare facility hand hygiene impacts patient care, healthcare worker safety, and infection control, but low-income countries have few data to guide interventions. AIM: To conduct a nationally representative survey of hand hygiene infrastructure and behaviour in Bangladeshi healthcare facilities to establish baseline data to aid policy. METHODS: The 2013 Bangladesh National Hygiene Baseline Survey examined water, sanitation, and hand hygiene across households, schools, restaurants and food vendors, traditional birth attendants, and healthcare facilities. We used probability proportional to size sampling to select 100 rural and urban population clusters, and then surveyed hand hygiene infrastructure in 875 inpatient healthcare facilities, observing behaviour in 100 facilities. FINDINGS: More than 96% of facilities had 'improved' water sources, but environmental contamination occurred frequently around water sources. Soap was available at 78-92% of handwashing locations for doctors and nurses, but just 4-30% for patients and family. Only 2% of 4676 hand hygiene opportunities resulted in recommended actions: using alcohol sanitizer or washing both hands with soap, then drying by air or clean cloth. Healthcare workers performed recommended hand hygiene in 9% of 919 opportunities: more after patient contact (26%) than before (11%). Family caregivers frequently washed hands with only water (48% of 2751 opportunities), but with little soap (3%). CONCLUSION: Healthcare workers had more access to hand hygiene materials and performed better hand hygiene than family, but still had low adherence. Increasing hand hygiene materials and behaviour could improve infection control in Bangladeshi healthcare facilities.

Entrapment efficiency and release characteristics of polyethyleneimine-treated or -untreated calcium alginate beads loaded with propranolol-resin complex.

Propranolol-HCl-loaded calcium alginate (ALG) beads, propranolol-resin complex (resinate)-loaded calcium alginate (RALG) beads and polyethyleneimine (PEI)-treated RALG (RALG-PEI) beads were prepared by ionotropic gelation/polyelectrolyte complexation method. The beads were evaluated and compared in respect of drug entrapment efficiency (DEE) and release characteristics in simulated gastric fluid (SGF, 0.1(N) HCl, pH 1.2) and simulated intestinal fluid (SIF, phosphate buffer, pH 6.8). DEE of RALG beads was considerably higher than that of ALG beads containing unresinated drug. However, DEE of RALG beads decreased with increase in both gelation time and concentration of the gel forming Ca2+ ions due to drug displacement from resinate. PEI treatment of RALG beads further decreased DEE as the polycation also displaced the drug from the resinate. The release of drug from all the beads was slow and incomplete in SGF owing to considerably less swelling of the beads and the decrease in drug release from the beads followed the order: RALG-PEI

Evaluation of mercury toxicity by some cytological indices in leucocyte cultures.

The genotoxicity induced by different levels of inorganic mercury was evaluated by chromosome metaphase analysis in human leucocytes, treated in vitro for 72 hr. Mitotic index gradually decreased with an increase in concentration of mercury but the reverse phenomenon was observed with respect to chromosomal aberration due to its probable interaction with protein and DNA.

Osteodysplastic primordial dwarfism type II with normal intellect but delayed central nervous system myelination.

We describe a 7-year-boy with severe prenatal and postnatal growth retardation, skeletal changes, normal intellect, and unusual facial appearance. The skeletal changes are suggestive of osteodysplastic primordial dwarfism type II (OPD II). He is the first patient of this kind from the Indian subcontinent and the 18th to be reported, based on a literature search (MEDLINE; 1982 to April 1997). He also represents the first case of OPD-II with normal intellect but delayed central nervous system myelination.