Temporal control of neuronal wiring.

Wiring an animal brain is a complex process involving a staggering number of cell-types born at different times and locations in the developing brain. Incorporation of these cells into precise circuits with high fidelity is critical for animal survival and behavior. Assembly of neuronal circuits is heavily dependent upon proper timing of wiring programs, requiring neurons to express specific sets of genes (sometimes transiently) at the right time in development. While cell-type specificity of genetic programs regulating wiring has been studied in detail, mechanisms regulating proper timing and coordination of these programs across cell-types are only just beginning to emerge. In this review, we discuss some temporal regulators of wiring programs and how their activity is controlled over time and space. A common feature emerges from these temporal regulators - they are induced by cell-extrinsic cues and control transcription factors capable of regulating a highly cell-type specific set of target genes. Target specificity in these contexts comes from cell-type specific transcription factors. We propose that the spatiotemporal specificity of wiring programs is controlled by the combinatorial activity of temporal programs and cell-type specific transcription factors. Going forward, a better understanding of temporal regulators will be key to understanding the mechanisms underlying brain wiring, and will be critical for the development of in vitro models like brain organoids.

Coflowing aqueous and oil-based ferrofluid streams exposed to a magnetic field.

We report the transition between stream and droplet regimes in a coflow of an aqueous stream and oil-based ferrofluid. The transition between stream and droplet regimes is typically attained by controlling the capillary numbers (Ca) of the phases. Remarkably, we experimentally evidence a transition between the regimes by adjusting the exposure of the system to a magnetic field, with Ca fixed. We represent the various regimes: stable coflow, interface deformation, and droplet generation, in terms of the magnetic bond number (Bom) and the ratio of capillary numbers of the phases (Car). The different regimes are a consequence of the interplay of the magnetic, viscous, and interfacial tension forces, represented by the two dimensionless numbers. We explain the regimes in terms of the magnetic pinch-off (τmp) and advection (τa) time scales: for τmp ≫ τa a stable coflow is observed, for τmp ∼ τa interface deformation is observed, and for τmp ≪ τa droplet breakup is observed. We study the interface deformation and droplet size from experiments and predict the same from theoretical scaling. We find the interface deformation increases and the droplet size decreases with increases in Bom and Car. The present study may find applications in magnetic field-assisted on-demand droplet generation in microfluidics.

Chronic arsenic poisoning: A sinister cause of peripheral neuropathy in a young couple.

ABSTRACT: Arsenic compounds are colorless and odorless and toxicity can occur either acutely following ingestion of arsenicals with gastrointestinal disturbances or due to chronic exposure usually presenting with dermatologic lesions and peripheral neuropathy. We report a young couple who presented with signs and symptoms of painful sensorimotor peripheral neuropathy in a typical "stocking and glove" pattern. They had raised urinary arsenic levels with normal blood levels and thus, a diagnosis of chronic arsenic poisoning due to contaminated water intake was made after detecting elevated arsenic levels in their home water supply. Both patients underwent chelation therapy with dimercaprol for 14 days and reported subjective and objective improvement in symptoms with the reduction in urinary arsenic levels at the end of therapy.

Correlation of palatal anatomic characteristics with dermatoglyphic heterogeneity in different growth patterns.

AIM AND OBJECTIVE: The study aimed to explore the correlation between dermatoglyphic patterns and quantitative palatal anatomic variables in individuals with different growth patterns. MATERIALS AND METHOD: A cross-sectional study was conducted involving 126 healthy patients aged 17-25 years. Participants were divided into three groups based on growth patterns: average, vertical, and horizontal. Dermatoglyphic patterns were recorded using an optical fingerprint sensor, and palatal characteristics were measured using digital software. Palatal characteristics, including intercanine width, intermolar width, and palatal depth, were measured using digital software. The results were statistically analyzed. RESULTS: Significant differences were observed in ridge counts among the three growth patterns. The average growth pattern showed lower ridge counts compared to the vertical and horizontal growth patterns. Dermatoglyphic patterns, such as double loops and tented arches, were significantly higher in the horizontal growth pattern. Weak correlations were found between certain dermatoglyphic patterns and palatal characteristics, with simple arch patterns showing a negative correlation with inter-canine width and symmetrical whorl patterns showing a positive correlation with palatal depth. Loop patterns, spiral patterns, double loop patterns, symmetrical whorl, and simple arch patterns were significant predictors of growth patterns. CONCLUSION: This study revealed distinct dermatoglyphic patterns and ridge counts among individuals with different growth patterns. Weak correlations were observed between dermatoglyphic patterns and palatal characteristics. However, the predictive value of dermatoglyphics for skeletal malocclusion requires further investigation. Understanding the relationships between dermatoglyphic patterns and craniofacial growth can provide valuable insights into genetic and developmental factors affecting dental and orthodontic conditions.

Trends of surgical-care delivery during the COVID-19 pandemic: A multi-centre study in India (IndSurg Collaboration).

Context: The COVID-19 pandemic and subsequent lockdowns adversely affected global healthcare services to varying extents. To accommodate its added burden, emergency services were affected along-with elective surgeries. Aims: To quantify and analyze the trends of essential surgeries and bellwether procedures during the waxing and waning of the pandemic, across various hospitals in India. Settings and Design: Multi-centric retrospective study. Methods and Material: A research consortium led by World Health Organization (WHO) Collaboration Center (WHOCC) for Research in Surgical Care Delivery in Low-and Middle-Income countries, India, conducted this study with 5 centers. All surgeries performed during April 2020 (Wave I), November 2020 (Recovery I), and April 2021 (Wave II) were compared with those performed in April 2019 (pre-pandemic period). Statistical Analysis Used: Microsoft Excel 2019 and SPSS Version 20. Results: The total number of surgeries reduced by 77% during Wave I, which improved to a 52% reduction in Recovery I compared to the pre-pandemic period. However, surgeries were reduced again during Wave II to 68%, but the reduction was less compared to Wave I. Emergency and essential surgeries were affected along with the elective ones but to a lesser extent. Conclusions: The present study has quantified the effects of the pandemic on surgical-care delivery across a timeline and documented a reduction in overall surgical volumes during the peaks of the pandemic (Wave I and II) with minimal improvement as the surge of COVID-19 cases declined (Recovery II). The surgical volumes improved during the second wave compared to the first one which may be attributable to better preparedness. Cesarean sections were affected the least.

Perspectives of Childhood Cancer Survivors as Young Adults: a Qualitative Study of Illness Education Resources and Unmet Information Needs.

This study investigates the resources used by childhood cancer survivors (CCS) to learn about their cancer histories and evaluates if CCS feel these resources prepare them to manage their health needs as young adults. Young adult participants (aged 18-30 years) were diagnosed with cancer at ≤ 10 years and recruited by word of mouth and from social media and/or non-profit organizations and completed semi-structured interviews. A descriptive thematic analysis guided by an essentialist/realist paradigm combined inductive and deductive approaches to identify key themes. Fourteen participants were interviewed, and six key themes were identified: (1) CCS are aware of general cancer history (age at diagnosis, treating hospital, cancer type), (2) CCS are unaware of treatment regimen (medications and duration), (3) CCS want to learn more about their treatment regimens and (4) potential late effects of treatment, (5) CCS use diverse resources to learn about their cancer histories and potential late effects, and (6) survivors' interests to learn about their cancer histories change over time. Limited knowledge of their cancer treatments leaves some CCS unprepared to manage their health needs as young adults or to address potential risk of late effects. CCS recognize their limited knowledge, but the resources available to them fall short of their information needs. Identifying the shortcomings of resources used by CCS provides evidence for how resources need to be improved to meet survivors' cancer education needs.

Outcomes and complications of Titanium elastic nailing for forearm bones fracture in children: our experience in a district general hospital in the United Kingdom.

Intramedullary Titanium elastic nailing (TENS) is successfully used for irreducible and displaced forearm bone fractures in children. The purpose of this study was to report the potential complications and functional outcomes associated with paediatric forearm fractures treated with TENS nails. We retrospectively reviewed 65 children with displaced forearm bone fractures treated by TENS nailing with a mean follow-up of 5.84 months (4-12). Data detailing patient demographics, fracture characteristics, associated fractures, injury surgery interval, grade of the operating surgeon, methods of fixation, time to union, the timing of removal of the nail, and complications were collected and analysed. The mean age in our study was 9.13 years. 92% had fractures of both radius and ulna, 83.3% had fixation of both bones, and 16.7% had single bone fixation only. Open reduction was required in 38.5% of cases. The average time to fracture union was 10.34 weeks (6-20). The average time of implant removal was 20.12 weeks (9-32). We observed an overall complication rate of 41.5%. We noted a higher (56% vs 32.5%, p=0.059) complication rate in open reduction cases. According to the Price criteria, we had excellent to good results in over 98% of patients despite a slightly higher complication rate. Titanium elastic nailing is a safe, reliable method of internal fixation for irreducible or unstable fractures of both bones of the forearm in children. Open reduction of fracture was associated with higher complications. Despite higher overall complications, we noted excellent functional results in most cases.

LAPAROSCOPIC APPROACH TO A GIANT RUPTURED SPLENIC CYST: A CHALLENGING CASE REPORT.

Splenic cysts are rare; their absence of an epithelial wall determines whether they're real cysts or pseudocysts. Spontaneous nonparasitic actual tumors are those that develop early in life at the anterior pole of the splenic and are typically epidermoid, dermoid, or endodermal. Surgical therapy is suggested for symptomatic, large (more than 5 cm) cysts or complicated. Inhaling splenic excision is a substitute for surgery, depending on the quantity, location, connection to the hilus, and dimension of the tumors. With an emphasis on less invasive treatments that preserve the spleen, laparoscopic methods have already established themselves as the accepted method for treating numerous disorders, including splenic cysts. They describe the effective decapsulation of a massive epidermoid spleen tumor under a prolonged, partially endoscopic technique. Laparoscopy, an operation commonly referred to as surgery with minimally invasive or keyhole surgery, is a technique that makes many tiny incisions in the belly to carry out different surgical procedures.

AN INCREASED RISK OF HORMONAL DISORDERS, PRIMARILY DIABETES, IN INDIVIDUALS WITH Β -THALASSEMIA MAJOR: A RETROSPECTIVE ANALYSIS.

ß-Thalassemia major is an inherited blood condition marked by a serious anemia and a lifetime need for blood transfusions. The effects of ß-thalassemia major on endocrine health, notably the risk of diabetes, remain largely unstudied, despite the fact that its haematological components are established. The purpose of this systematic analysis was to examine the incidence of reduced metabolism of glucose in ß--thalassemia major. The articles were under the inclusion requirements, after which the data was retrieved. The main outcome was determined to be every prevalence (P) of DM (diabetes mellitus) in ß-thalassemia major. In order to examine the percentage of aberrant glucose metabolism (GM) with individuals among ß-thalassemia major, the P with the 95% CI (Confidence Interval) was utilized. In this retrospective investigation, we looked at a cohort of people with ß-thalassemia major diagnoses to determine the incidence and risk of hormonal diseases, particularly diabetes. A specialist thalassemia facility treated 315 individuals with ß-thalassemia major, and their medical records were examined. Age, gender, age at which a main diagnosis of ß-thalassemia was made, the length of transfusion treatment, and concomitant diseases were gathered as part of the demographic and clinical data. Our research, which included 17 studies and 1500 cases altogether, showed that with ß -thalassemia major had a considerably greater frequency of diabetes than people in general. With a mean beginning age of 30 years, diabetes was identified in 28% of the research cohort's participants. The combined meta-analysis showed that each year had a rather stable level of DM P in ß-thalassemia major. In people with major ß-thalassemia, the P of impaired fasting glucose (IFG), DM, and impaired glucose tolerance (IGT) was 17.22% (95% CI: 8.44%-26.02%), (6.57 (95% CI: 5.31%- 7.79%) and 12.47 % (95% CI: 5.97%-18.95%), respectively. Our research suggests that people with ß-thalassemia major have a high chance of acquiring diabetes, particularly if they get extended transfusion treatment. For prompt diagnosis and care, early detection of diabetes and other hormonal problems in this group is crucial. In ß-thalassemia major, there is a high frequency of endocrine problems, including improper GM. To stop growth and endocrine issues, treatment and preventative measures can be required.

Epidemiological and diagnostic aspects of feline leishmaniasis with emphasis on Brazil: a narrative review.

The leishmaniases are a group of diseases caused by the protozoan parasite belonging to the genus Leishmania. In the New World, although dogs are considered the main parasite reservoir, in the last two decades, several studies have confirmed the role of cats (Felis catus) in the epidemiology of the disease and feline leishmaniasis (FeL) is now considered to be an emerging disease. The present review summarizes the current knowledge about FeL, focusing on important immunopathological aspects, epidemiology, and diagnostic methods applied for felines in Brazil. Cats are infected with the same species of Leishmania found in dogs (i.e., Leishmania infantum). Like dogs, skin lesions are the most common in cats with clinical FeL, mainly affecting the cephalic region and less frequently the legs which may be accompanied by generalized signs or visceral involvement. Information on the immune response of cats to Leishmania infection is scarce; however, efficient infection control is seen in most cases. For diagnosis, generally, the same methods as those in dogs are used, mainly serological tools. But there is a lack of studies focusing the performance of these methods for diagnosing FeL. The estimated overall prevalence of FeL in Brazil is 8%, with L. infantum being the most prevalent species. However, infections with Leishmania braziliensis and Leishmania amazonensis have also been reported. In conclusion, although there has been an increase in the publication related to FeL in Brazil in recent years, there is a lack of research relating immune response and diagnosis of these animals. Cats have been shown to be competent hosts for Leishmania parasites, and their role in the epidemiology of the disease cannot be underestimated, especially in areas of Brazil where the disease is historically endemic.

Correlation of arterial PaCO2 to end tidal CO2 in children undergoing laparoscopic abdominal surgery: An observational study.

Background and Aims: The reliability of end tidal carbon dioxide (ETCO2) as a measure of arterial carbon dioxide (PaCO2) in pediatric laparoscopy is unclear. We evaluated the correlation of arterial to end tidal P(a-ET) CO2 during pediatric laparoscopy at two hours of pneumoperitoneum as the primary objective. We also compared P(a-ET) CO2 and alveolar to arterial oxygen gradient P(A-a) O2 and haemodynamics at fixed time points during surgery. Material and Methods: A cross-sectional study was conducted in 25 children undergoing laparoscopic abdominal surgery. Arterial blood gases were drawn at T0, baseline, T10: ten minutes, T1h: 1 hour, T2h: 2 hours of pnuemoperitoneum and T 10d: 10 mins after deflation. The P(a-ET) CO2, P(A-a) O2, were measured from the blood gas and ETCO2 and FiO2 values on the monitor. The Pearson's correlation coefficient, the Wilcoxon rank test and Chi square test were used for statistical analysis. Results: At T2h moderate correlation of P(a-ET) CO2 (r = 0.605, P = 0.001) with 40% children documenting accurate P(a-ET) CO2, -1 to +1 mm Hg was seen. Moderate correlation was also seen at T0, T10, T 10d but poor correlation at T 1h. The P(A-a) O2 increased progressively with surgery and did not correlate with P(a-ET) CO2. Heart rate was stable, but systolic blood pressures at T 10 and diastolic at T10, T 1h, T 2h were higher than baseline. Conclusion: Moderate correlation was seen between PaCO2 and ETCO2 at 2 h of pnuemoperitoneum and at T0, T 10, and T 10d. P(A-a) O2 increased with surgery but did not correlate with P(a-ET) CO2.

Functional characterization of novel variants in SMPD1 in Indian patients with acid sphingomyelinase deficiency.

Pathogenic variations in SMPD1 lead to acid sphingomyelinase deficiency (ASMD), that is, Niemann-Pick disease (NPD) type A and B (NPA, NPB), which is a recessive lysosomal storage disease. The knowledge of variant spectrum in Indian patients is crucial for early and accurate NPD diagnosis and genetic counseling of families. In this study, we recruited 40 unrelated pediatric patients manifesting symptoms of ASMD and subnormal ASM enzyme activity. Variations in SMPD1 were studied using Sanger sequencing for all exons, followed by interpretation of variants based on American College of Medical Genetics and Genomics & Association for Molecular Pathology (ACMG/AMP) criteria. We identified 18 previously unreported variants and 21 known variants, including missense, nonsense, deletions, duplications, and splice site variations with disease-causing potential. Eight missense variants were functionally characterized using in silico molecular dynamic simulation and in vitro transient transfection in HEK293T cells, followed by ASM enzyme assay, immunoblot, and immunofluorescence studies. All the variants showed reduced ASM activity in transfected cells confirming their disease-causing potential. The study provides data for efficient prenatal diagnosis and genetic counseling of families with NPD type A and B.

Addressing Reemergence of Diphtheria among Adolescents through Program Integration in India.

We report a diphtheria outbreak mostly among children (median 12 years; range 4-26 years) of a religious minority in urban India. Case-fatality rate (15%, 19/124) was higher among unimmunized patients (relative risk 4.1, 95% CI 1.5-11.7). We recommend mandating and integrating immunization into school health programs to prevent reemergence.

Differential levels of CHMP2B, LLPH, and SLC25A51 proteins in secondary renal amyloidosis.

OBJECTIVES: Renal amyloidosis (RA) is a rare disease, typically manifested with proteinuria, nephrotic syndrome, and ultimately leads to renal failure. The present study aims to profile the proteomes of renal amyloidosis patient's serum and healthy controls, along with relative quantification to find out robust markers for RA. METHODS: In this study, 12 RA patients and their corresponding age and gender-matched healthy controls were recruited from the Nephrology department of Max Super Specialty Hospital, New Delhi. We employed gel-based proteomic approach coupled with MALDI-TOF MS to compare protein expression patterns in RA patients and controls. Furthermore, validation of differential proteins (selected) was done using bio-layer interferometry. RESULTS: Eleven proteins showed remarkably altered expression levels. Moreover, expression modulation of three proteins (LLPH, SLC25A51, and CHMP2B) was validated which corroborated with two-dimensional gel electrophoresis (2-DE) results showing significant upregulation (p < 0.05) in RA patients followed by ROC analysis which demonstrated the diagnostic potential of these proteins. A protein-protein master network was generated implicating the above identified proteins along with their interactors, fishing out the routes leading to amyloidosis. CONCLUSION: This study indicates that the identified serum proteomic signatures could improve early diagnosis and lead to possible therapeutic targets in RA.

High spatial-density, cladding-pumped 6-mode 7-core fiber amplifier for C-band operation.

We present a C-band 6-mode 7-core fiber amplifier in an all-fiberized cladding-pumped configuration for space division multiplexed transmission supporting a record 42 spatial channels. With optimized fiber components (e.g. passively cooled pump laser diode, pump coupler, pump stripper), high power multimode pump light is coupled to the active fiber without any noticeable thermal degradation and an average gain of 18 dB and noise figure of 5.4 dB are obtained with an average differential modal gain of 3.4 dB.

Particle encapsulation in aqueous ferrofluid drops and sorting of particle-encapsulating drops from empty drops using a magnetic field.

Handling and manipulation of particle-encapsulating droplets (PED) have profound applications in biochemical assays. Herein we report encapsulation of microparticles in aqueous ferrofluid droplets in a primary continuous phase (CP) and sorting of PED from empty droplets (ED) at the interface of the CP in coflow with a second continuous phase using a magnetic field. We find that the encapsulation process results in a size contrast between the PED and ED that depends on the flow regime - squeezing, dripping, or jetting - which in turn is governed by the ratio of the discrete phase to the continuous phase capillary number, Car. The difference between the volume fractions of ferrofluid in the PED and ED, ΔαPED, is utilized for sorting, and is found to depend on the ratio of the capillary numbers, Car. The difference ΔαPED is found to be maximum in the jetting regime, suggesting that the jetting regime is most suitable for encapsulation and sorting. The sorting criterion is represented in terms of a parameter ξ, which is a function of the ratios of the magnetic force to the interfacial force experienced by the PED and ED. Our study revealed that sorting is possible for ξ < 0, which corresponds to ΔαPED > 0.25. The maximum sorting efficiency of our system is found to be ∼95% at a throughput of ∼100 drops per s.

Differential expression of Lumican, Mimecan, Annexin A5 and Serotransferrin in ectopic and matched eutopic endometrium in ovarian endometriosis: a case-control study.

AIM: Endometriosis is a debilitating disease marked by recurrent gynecological proliferations. The present study aimed at performing differential proteomic analysis of matched eutopic and ectopic endometrium from women with ovarian endometriosis. MATERIALS AND METHODS: Proteomes were resolved using nano LC-MS and further identified and quantified using ProteinLynx Global SERVER (PLGS) software. Selected proteins were further chosen for validation by real time-polymerase chain reaction (RT-PCR). RESULTS: The protein profiles uncovered several differentially expressed proteins in the diseased sample (ectopic endometrium) as compared to the reference sample (eutopic endometrium). The study involved an advanced proteomic approach, nano LC-MS, and validates for the first time the upregulation of Mimecan and Lumican proteins in endometriosis. CONCLUSIONS: These proteins may hence prove as potentially useful tools in the search for diagnostic markers for early detection of the disease.

Fluoride Geochemistry and Exposure Risk Through Groundwater Sources in Northeastern Parts of Rajasthan, India.

Exposure to fluoride concentrations above a threshold of 1.5 mg/L can cause joint pains, restricted mobility, skeletal and dental fluorosis. This study aims to determine the hydrochemical evolution of the fluoride-rich groundwater and estimate the risk of fluoride exposure to the residents of semi-arid northeastern part of Rajasthan, India. The methodology involves measurement of fluoride and other ionic concentrations in groundwater using ion chromatography, followed by an estimation of the cumulative density function and fluorosis risk. The fluoride concentration in water samples varied from 0.04 to 8.2 mg/L with 85% samples falling above the permissible limit. The empirical cumulative density function was used to estimate the percentage and degree of health risks associated with the consumption of F- contaminated water. It is found that 55% of the samples indicate risk of dental fluorosis, 42% indicate risk of deformities to knee and hip bones, and 18% indicate risk of crippling fluorosis. In addition, instances of high nitrate concentrations above the permissible limit of 45 mg/L are also found in 13% of samples. The fluoride rich groundwater is mainly associated with the Na-HCO3-Cl type water facies while low fluoride groundwater shows varied chemical facies. The saturation index values indicate a high probability of a further increase in F- concentration in groundwater of this region. The calculated fluoride exposure risk for the general public in the study area is 3-6 times higher than the allowed limit of 0.05 mg/kg/day. Based on the results of this study, a fluorosis index map was prepared for the study area. The northern and northeastern parts are less prone to fluorosis, whereas the south-central and southwestern parts are highly vulnerable to fluorosis. The inferences from this study help to prioritize the regions that need immediate attention for remediation.

Differential expression of MAP3K7 and TROPONIN C proteins and related perturbations in renal amyloidosis.

OBJECTIVES: Renal amyloidosis (RA) is a rare protein misfolding disorder that prompts progressive renal insufficiency. This study aimed to decipher proteomic changes in human sera to understand the pathophysiology and molecular mechanisms underlying the disease development, hence assisting in the diagnosis of RA. METHODS: Serum proteomic analysis was performed using a gel-based approach followed by MALDI-TOF MS. RA patients with age and sex matched healthy volunteers were recruited from Max Super Speciality Hospital, New Delhi, India. RESULTS: Proteome profiles of serum revealed eight differentially expressed proteins namely, Zinc finger protein 624, Protein FAM183A, Calcium-binding mitochondrial carrier protein Scamc-3, V-type proton ATPase 116 kDa subunit A isoforms 2, Protein TXNRD3NB, ATP - dependent RNA helicase, Troponin C and Mitogen-activated protein kinase kinase kinase 7. These proteins were reported first time in RA. The increased levels of MAP3K7 and TROPONIN C were validated by bio-layer interferometry and their diagnostic accuracy was evaluated by ROC curve analysis. The differentially expressed proteins were predominantly associated with vesicular trafficking, transcriptional regulation, metabolic processes, apoptotic process and mitochondrial metabolism. CONCLUSION: The results indicate that these proteomic signatures may be considered as potential molecular targets for RA diagnostics and therapeutics subject to validation on large sample size. Abbreviations: AßP= Amyloid-beta protein, Aß=Amyloid-beta, AL= Light chain amyloidosis, AA= Amyloid A, ALECT2= LECT2 amyloidosis, APS= Ammonium persulfate CKD= Chronic Kidney Diseases, EBRT= external beam radiation therapy, ESRD= End-Stage Kidney Disease, Glis2= Gli-similar 2, JNK= c-Jun NH 2-terminal kinase, MAPK= Mitogen-Activated Protein Kinase, MM=Multiple Myeloma, PHD= Prolyl hydroxylase, RA = Renal Amyloidosis, SAA= Serum Amyloid A, SD= Standard Deviation, Sepp= Selenoprotein, SCC= Squamous cell carcinoma, SDS= Sodium dodecyl sulfate, TEMED = tetramethyl ethylenediamine, TGF-Beta-1=Transforming growth factor- Beta-1, Trx = Thioredoxin, TrxR= Thioredoxin reductase.

Proteomic sift through serum and endometrium profiles unraveled signature proteins associated with subdued fertility and dampened endometrial receptivity in women with polycystic ovary syndrome.

The objective of this study is to discern the proteomic differences responsible for hampering the receptivity of endometrium and subduing the fertility of females with polycystic ovary syndrome in analogy to healthy fertile females. This study was designed in collaboration with Hakeem Abdul Hameed Centenary Hospital affiliated to Jamia Hamdard, New Delhi, India. Serum samples were taken from infertile PCOS subjects (n = 6) and fertile control subjects (n = 6) whereas endometrial tissue samples were recruited from ovulatory PCOS (n = 4), anovulatory PCOS (n = 4) and normal healthy fertile control subjects (n = 4) for proteomic studies. Additionally, endometrial biopsies from healthy fertile control (n = 8), PCOS with infertility (n = 6), unexplained infertility (n = 3) and endometrial hyperplasia (n = 3) were taken for validation studies. Anthropometric, biochemical and hormonal evaluation was done for all the subjects enrolled in this study. Protein profiles were generated through 2D-PAGE and differential proteins analyzed with PD-QUEST software followed by identification with MALDI-TOF MS protein mass fingerprinting. Validation of identified proteins was done through RT-PCR relative expression analysis. Protein profiling of serum revealed differential expression of proteins involved in transcriptional regulation, embryogenesis, DNA repair, decidual cell ploidy, immunomodulation, intracellular trafficking and degradation processes. Proteins involved in cell cycle regulation, cellular transport and signaling, DNA repair, apoptotic processes and mitochondrial metabolism were found to be differentially expressed in endometrium. The findings of this study revealed proteins that hold strong candidature as potential drug targets to regulate the cellular processes implicating infertility and reduced receptivity of endometrium in women with polycystic ovary syndrome.