New Luminescent Pyridine-based Disc type Molecules: Synthesis, Photophysical, Electrochemical, and DFT studies.

The design and synthesis of new conjugated luminescent molecules have attracted the attention of researchers because of their various applications, especially in the field of optoelectronic devices. Most of the applications were mainly based on the intramolecular charge transfer (ICT). For this purpose, we designed and synthesized a series of new donor-acceptor based disc type molecules i.e. 2,4,6-tris(4-(alkyloxy)phenyl)pyridines carrying variable alkoxy chains [i.e. n = 2, 4, 6, 8, 10, 12, 14, 16]. Further, the structures of all the synthesized compounds were confirmed by using ATR-IR, 1H-NMR, 13C-NMR, and ESI-MS analysis. Moreover, the photophysical property study indicated that all the molecules are blue light emitting materials, however the change of alkoxy chain length in phenyl arms does not affect their absorption, emission, and energy levels. Besides, the thermal study revealed that core is stable up to 350 °C. Also, the DFT study showed that the photo induced electron transfer caused by HOMO-LUMO excitation in the studied molecules. Therefore, all the molecules have potential applications in optoelectronic applications.

Efficacy of different surgical treatments for management of anal fistula: a network meta-analysis.

PURPOSE: Currently, the anal fistula treatment which optimises healing and preserves bowel continence remains unclear. The aim of our study was to compare the relative efficacy of different surgical treatments for AF through a network meta-analysis. METHODS: Systematic searches of MEDLINE, EMBASE and CENTRAL databases up to October 2022 identified randomised controlled trials (RCTs) comparing surgical treatments for anal fistulae. Fistulae were classified as simple (inter-sphincteric or low trans-sphincteric fistulae crossing less than 30% of the external anal sphincter (EAS)) and complex (high trans-sphincteric fistulae involving more than 30% of the EAS). Treatments evaluated in only one trial were excluded from the primary analyses to minimise bias. The primary outcomes were rates of success in achieving AF healing and bowel incontinence. RESULTS: Fifty-two RCTs were included. Of the 14 treatments considered, there were no significant differences regarding short-term (6 months or less postoperatively) and long-term (more than 6 months postoperatively) success rates between any of the treatments in patients with both simple and complex anal fistula. Ligation of the inter-sphincteric fistula tract (LIFT) ranked best for minimising bowel incontinence in simple (99.1% of comparisons; 3 trials, n = 70 patients) and complex anal fistula (86.2% of comparisons; 3 trials, n = 102 patients). CONCLUSIONS: There is insufficient evidence in existing RCTs to recommend one treatment over another regarding their short and long-term efficacy in successfully facilitating healing of both simple and complex anal fistulae. However, LIFT appears to be associated with the least impairment of bowel continence, irrespective of AF classification.

Conceptualization of functional single nucleotide polymorphisms of polycystic ovarian syndrome genes: an in silico approach.

PURPOSE: Polycystic ovarian syndrome (PCOS) is a multi-faceted endocrinopathy frequently observed in reproductive-aged females, causing infertility. Cumulative evidence revealed that genetic and epigenetic variations, along with environmental factors, were linked with PCOS. Deciphering the molecular pathways of PCOS is quite complicated due to the availability of limited molecular information. Hence, to explore the influence of genetic variations in PCOS, we mapped the GWAS genes and performed a computational analysis to identify the SNPs and their impact on the coding and non-coding sequences. METHODS: The causative genes of PCOS were searched using the GWAS catalog, and pathway analysis was performed using ClueGO. SNPs were extracted using an Ensembl genome browser, and missense variants were shortlisted. Further, the native and mutant forms of the deleterious SNPs were modeled using I-TASSER, Swiss-PdbViewer, and PyMOL. MirSNP, PolymiRTS, miRNASNP3, and SNP2TFBS, SNPInspector databases were used to find SNPs in the miRNA binding site and transcription factor binding site (TFBS), respectively. EnhancerDB and HaploReg were used to characterize enhancer SNPs. Linkage Disequilibrium (LD) analysis was performed using LDlink. RESULTS: 25 PCOS genes showed interaction with 18 pathways. 7 SNPs were predicted to be deleterious using different pathogenicity predictions. 4 SNPs were found in the miRNA target site, TFBS, and enhancer sites and were in LD with reported PCOS GWAS SNPs. CONCLUSION: Computational analysis of SNPs residing in PCOS genes may provide insight into complex molecular interactions among genes involved in PCOS pathophysiology. It may also aid in determining the causal variants and consequently contributing to predicting disease strategies.

Identification of kisspeptin2 cDNA in the catfish Heteropneustes fossilis: Expression profile, in situ localization and steroid modulation.

Kisspeptin (Kiss) is considered an upstream regulator of gonadotropin-releasing hormone in mammals but its role in non-mammalian vertebrates is not unequivocally established. In the catfish Heteropneustes fossilis, a 605 bp long cDNA was identified from the brain by cloning as well as by retrieving from the catfish transcriptome database. The open reading frame (ORF, 93-405 bp) codes for a 113 amino acids long precursor protein. Homology and phylogenetic analyses showed that the predicted protein belongs to the vertebrate Kiss2 type with a high degree of conservation in the Kiss2-10 region (FNFNPFGLRF). The kiss2 transcripts were expressed highly in the brain and gonads in a dimorphic manner with a female bias. In the brain, kiss2 transcripts showed regional differences with higher expression in the medulla oblongata and forebrain regions. The kiss2 transcripts showed significant seasonal variations with the highest expression in the brain in spawning phase and in the gonads in prespawning phase. The kiss2 transcripts were localized in the brain (nucleus preopticus, habenular nucleus, nucleus recessus posterioris, nucleus recessus lateralis) and stratum periventriculare (radial glial cells) of optic tectum, pituitary and ovary (follicular layer and germinal vesicle). Ovariectomy (1, 2, 3 and 4 weeks) decreased brain kiss2 mRNA levels and a single injection of estradiol-17ß (E2; 0.5 µg/g body weight) in 3- week ovariectomized (OVX) and sham operated fish resulted in an increase in the transcript levels after 24 h. The E2 receptor antagonist Tamoxifen (TMX) produced biphasic effects on the kiss2 expression in the dose- response study. TMX inhibited the expression in the OVX fish, but elicited a stimulatory effect in the OVX + E2-treated fish. Testosterone (T) decreased, and progesterone (P4) inhibited (resting phase) or stimulated (prespawning phase) the transcript level in 3-week OVX fish. In the 3-week sham groups, E2 increased, and TMX, T and P4 inhibited the kiss2 transcript levels. The results suggest that Kiss2 is an important regulator of the brain- pituitary- gonadal- endocrine axis, and in habenular and optic tectum functions.

Expression profile of kisspeptin2 and gonadotropin-releasing hormone2 mRNA during photo-thermal and melatonin treatments in the female air-breathing catfish Heteropneustes fossilis.

In seasonally breeding vertebrates, extrinsic factors like photoperiod and temperature are major determinants, controlling the annual reproductive cycle. In teleosts, kisspeptin, which occurs in two molecular forms: kisspeptin1 (Kiss1) and kisspetin2 (Kiss2), has been reported to alter gonadotropin (Lh and Fsh) secretion but its effect on gonadotropin-releasing hormone (Gnrh) secretion is not unequivocally proved. In the catfish Heteropneustes fossilis, we isolated and characterized kiss2 and gnrh2 cDNAs and the present work reports effects of altered photo-thermal conditions and melatonin (MT, a pineal hormone) on their expressions in the brain. The exposure of the catfish to long photoperiod (LP, 16 h light) at normal temperature (NT) or high temperature (HT, 28 °C) at normal photoperiod (NP) for 14 or 28 days stimulated both kiss2 and gnrh2 expression in both gonad resting and preparatory phases with the combination of LP + HT eliciting maximal effects. Short photoperiod (SP, 8 h light) under NT or HT altered the gene expression according to the reproductive phase and temperature. MT that mediates photo-thermal signals to the brain inhibited brain kiss2 and gnrh2 gene expression in the NP + HT, LP + NT, and SP + NT groups. The altered photo-thermal conditions elicited changes in steroidogenic pathway as evident from changes in plasma E2, progesterone, and testosterone levels. The results show that brain kiss2-gnrh2 signaling is involved in photo-thermal-mediated mechanisms controlling reproduction.

The association of dietary patterns and carotid intima-media thickness: A synthesis of current evidence.

AIMS: Dietary pattern (DP) analysis has emerged as a holistic method to understand the effects of food intake on health outcomes. Though dietary intake has been associated with cardiovascular disease, the association of DPs and carotid intima-media thickness (CIMT), a robust early marker of cardiovascular disease progression has not been comprehensively investigated. This study systematically explores the association of a posteriori and a priori DPs and CIMT. DATA SYNTHESIS: Through a systematic search of MEDLINE, CINAHL, and Web of Science, twenty studies that derived DPs using a posteriori or a priori methods with CIMT as an outcome were included. Four cross-sectional studies and 1 cohort paper reported a statistically significant association between increased consumption of 'unhealthy' foods (i.e processed meat, soda drinks and refined grain) and increased CIMT. While four cross-sectional studies reported a statistically significant association of DPs characterized by increased consumption of 'healthy' foods (i.e fruit and vegetables, fish) and decreased CIMT. DPs derived from each study varied depending on derivation method, study design and use of dietary data collection method. CONCLUSION: Findings from this review are generally supportive of a trend between DPs with higher consumption of 'healthy' foods and lower consumption of 'unhealthy' foods and decreased CIMT; however, the association was largely not statistically significant. Evidence was overwhelmingly heterogeneous due to differences seen in DPs based on location and culture, sample characteristics and adjustment for confounders. Long-term prospective observational and interventional studies with standardized sample selection and dietary data collection are needed to significantly establish the role of DPs on CIMT.

Molecular cloning and characterization of a gonadotropin-releasing hormone 2 precursor cDNA in the catfish Heteropneustes fossilis: Expression profile and regulation by ovarian steroids.

Gonadotropin-releasing hormone 2 (Gnrh2) is one of the three classes of Gnrh distributed in vertebrates and is highly conserved. In the present study, the cDNA encoding Gnrh2 was isolated and characterized in the ostariophysan catfish Heteropneustes fossilis (hf). The cDNA is 611 bp long with an open reading frame (ORF) of 261 bp that encodes a highly conserved protein of 86 amino acids. The deduced Gnrh2 precursor protein clustered with the vertebrate Gnrh2 type. The sequence identity of hfgnrh2 is 94% with African catfish (Clarias gariepinus) gnrh2 mRNA (accession no. X78047). The hfgnrh2 transcripts were expressed only in the brain and gonads with a higher expression in the female brain and ovary in both resting and prespawning phases. The expression was higher in the prespawning phase than the resting phase. The gnrh2 expression in the brain and ovary showed significant seasonal variations but with opposite patterns. In the brain, the expression was the highest in the preparatory phase, decreased progressively to low levels in the postspawning and resting phases. In the ovary, the transcript level was low in the resting and preparatory phases, increased sharply in the prespawning phase reaching the peak level in the spawning phase and declined sharply in the postspawning phase. The gnrh2 mRNA showed the highest expression in the hind brain-medulla oblongata and moderate to low expression in forebrain regions and pituitary. Ovariectomy resulted in a duration-dependent inhibition of hfgnrh2 mRNA levels in the resting and prespawning phases. Steroid (E2, testosterone and progesterone) replacement treatments (0.5 µg/g body weight) in the 3- week ovariectomized fish restored the inhibition due to ovariectomy, elevated the expression over and above the sham level in the resting phase (E2 group), and raised the levels almost to that of the sham group (testosterone and progesterone groups) in the prespawning phase. In the sham control groups, the steroid replacement resulted in a significant reduction in the mRNA levels. The expression of the gnrh2 mRNA in the brain-pituitary-gonadal axis and its regulation by gonadal steroids suggest that Gnrh2 may have a reproductive role in the catfish.

Seven additional families with spondylocarpotarsal synostosis syndrome with novel biallelic deleterious variants in FLNB.

The location and/or type of variants in FLNB result in a spectrum of osteochondrodysplasias ranging from mild forms, like spondylocarpotarsal synostosis syndrome and Larsen syndrome, to severe perinatal lethal forms, such as atelosteogenesis I and III and Boomerang dysplasia. Spondylocarpotarsal synostosis syndrome is characterized by disproportionate short stature, vertebral anomalies and fusion of carpal and tarsal bones. Biallelic loss-of-function variants in FLNB are known to cause spondylocarpotarsal synostosis syndrome and 9 families and 9 pathogenic variants have been reported so far. We report clinical features of 10 additional patients from 7 families with spondylocarpotarsal synostosis syndrome due to 7 novel deleterious variants in FLNB, thus expanding the clinical and molecular repertoire of spondylocarpotarsal synostosis syndrome. Our report validates key clinical (fused thoracic vertebrae and carpal and tarsal coalition) and molecular (truncating variants in FLNB) characteristics of this condition.

Comparison of efficiency of in vitro cloned sheep embryo production by conventional somatic cell nuclear transfer and handmade cloning technique.

Conventional somatic cell nuclear transfer (SCNT) technique of in vitro production of cloned embryos involves use of costly and complicated micromanipulators. Handmade cloning (HMC) technique has been applied as efficient and cost-effective alternative in many livestock species. The aim of the present study was to compare the efficiency of in vitro production and in vitro development of cloned sheep embryos by the two techniques. Cloned embryos were produced by conventional SCNT using micromanipulator apparatus and by HMC technique. Enucleation efficiency and efficiency of fusion with somatic cell (nucleus donor) were compared. Cleavage percentage was observed on day 2 of in vitro culture (IVC), and morula and blastocyst percentages were calculated on day 7 of IVC. Higher enucleation efficiency (96.98 ± 1.01 vs. 93.62 ± 1.03; p > .05) as well as fusion efficiency was obtained with HMC technique than with conventional SCNT (96.26 ± 1.34 vs. 92.63 ± 0.70, p < .05); 181 cloned sheep embryos were produced in vitro by conventional SCNT and 92 by HMC. Cleavage percentage observed on day 2 of in vitro culture was higher in HMC than SCNT (66.92 ± 3.72 vs. 55.97 ± 2.5, respectively, p < .05). Morula percentage obtained was higher in SCNT than HMC (44.12 ± 2.93 vs. 30.43 ± 6.79, respectively, p < .05), whereas blastocyst percentage obtained by HMC was higher (12.46 ± 4.96) than SCNT (5.31 ± 2.25; p > .05). It was inferred that HMC technique provides a cost-effective and efficient method of in vitro production of cloned sheep embryos with a comparatively simpler technique with a possibility of automation. Efficiency of cloned embryo production could be improved further by propagating and standardizing this technique.

NHERF1 in Microvilli of Vomeronasal Sensory Neurons.

In most mammals, the vomeronasal system detects a variety of (semio)chemicals that mediate olfactory-driven social and sexual behaviors. Vomeronasal chemosensation depends on G protein-coupled receptors (V1R, V2R, and FPR-rs) that operate at remarkably low stimulus concentrations, thus, indicating a highly sensitive and efficient signaling pathway. We identified the PDZ domain-containing protein, Na+/H+ exchanger regulatory factor-1 (NHERF1), as putative molecular organizer of signal transduction in vomeronasal neurons. NHERF1 is a protein that contains 2 PDZ domains and a carboxy-terminal ezrin-binding domain. It localizes to microvilli of vomeronasal sensory neurons and interacts with V1Rs. Furthermore, NHERF1 and Gαi2 are closely colocalized. These findings open up new aspects of the functional organization and regulation of vomeronasal signal transduction by PDZ scaffolding proteins.

Synthetic certified DNA reference material for analysis of human erythropoietin transgene and transcript in gene doping and gene therapy.

There is a recognised need for standardisation of protocols for vector genome analysis used in vector manufacturing, to establish dosage, in biodistribution studies and to detect gene doping in sport. Analysis of vector genomes and transgene expression is typically performed by qPCR using plasmid-based calibrants incorporating transgenic sequences. These often undergo limited characterisation and differ between manufacturers, potentially leading to inaccurate quantification, inconsistent inter-laboratory results and affecting clinical outcomes. Contamination of negative samples with such calibrants could cause false positive results. We developed a design strategy for synthetic reference materials (RMs) with modified transgenic sequences to prevent false positives due to cross-contamination. When such RM is amplified in transgene-specific assays, the amplicons are distinguishable from transgene's amplicons based on size and sequence. Using human erythropoietin as a model, we produced certified RM according to this strategy and following ISO Guide 35. Using non-viral and viral vectors, we validated the effectiveness of this RM in vector genome analysis in blood in vitro. The developed design strategy could be applied to production of RMs for other transgenes, genes or transcripts. Together with validated PCR assays, such RMs form a measurement tool that facilitates standardised, accurate and reliable genetic analysis in various applications.

Reverse genetics based rgH5N2 vaccine provides protection against high dose challenge of H5N1 avian influenza virus in chicken.

An inactivated vaccine was developed using the rgH5N2 virus (6 + 2 reassortant) generated by plasmid based reverse genetics system (RGS) with WSN/33/H1N1 as backbone virus. Following mutation of the basic amino acid cleavage site RRRKKR*GLF to IETR*GLF, the H5-HA (haemagglutinin) gene of the selected donor H5N1 virus (A/chicken/West Bengal/80995/2008) of antigenic clade 2.2 was used along with the N2-NA gene from H9N2 field isolate (A/chicken/Uttar Pradesh/2543/2004) for generation of the rgH5N2 virus. A single dose (0.5 ml/bird) of the inactivated rgH5N2 vaccine protected 100% of the vaccinated chickens (n = 10) on 28(th) dpv (early challenge) and 90% of the vaccinated chickens (n = 10) on 200(th) dpv (late challenge) against high dose challenge with HPAI virus (10(9) EID50/bird). Challenge virus shedding via oropharynx and cloaca of the vaccinated chickens was detectable by realtime RT-PCR during 1-5 dpc and 1-9 days dpc in the early and the late challenge, respectively. The protective level of antibodies (mean HI titre > 128) was maintained without booster vaccination for 200 days. The present study provides the experimental evidence about the extent of protection provided by a reverse genetics based vaccine for clade 2.2 H5N1 viruses against challenge with high dose of field virus at two different time points (28 dpv and 200 dpv). The challenge study is uniquely different from the previous similar experiments on account of 1000 times higher dose of challenge and protection at 200 dpv. The protection and virus shedding data of the study may be useful for countries planning to use H5 vaccine in poultry especially against the clade 2.2 H5N1 viruses.

Acute promyelocytic leukaemia with a novel translocation t(16;17)(q12;p13): a case report.

Acute promyelocytic leukaemia (APML) is characterised by the t(15;17)(q22;q21), that results in the fusion of the promyelocytic leukaemia (PML) gene at 15q22 with the retinoic acid α-receptor (RARA) gene at 17q21. The current case report describes a 13-year-old male with APML, who was negative for PML/RARA fusion signal but reported to have an atypical translocation t(16;17). To the best of our knowledge this is the first case report of APML responsive to ATRA with such a translocation.

New insights of superoxide dismutase inhibition of pyrogallol autoxidation.

Autoxidation of pyrogallol in alkaline medium is characterized by increases in oxygen consumption, absorbance at 440 nm, and absorbance at 600 nm. The primary products are H2O2 by reduction of O2 and pyrogallol-ortho-quinone by oxidation of pyrogallol. About 20 % of the consumed oxygen was used for ring opening leading to the bicyclic product, purpurogallin-quinone (PPQ). The absorbance peak at 440 nm representing the quinone end-products increased throughout at a constant rate. Prolonged incubation of pyrogallol in alkali yielded a product with ESR signal. In contrast the absorbance peak at 600 nm increased to a maximum and then declined after oxygen consumption ceased. This represents quinhydrone charge-transfer complexes as similar peak instantly appeared on mixing pyrogallol with benzoquinones, and these were ESR-silent. Superoxide dismutase inhibition of pyrogallol autoxidation spared the substrates, pyrogallol, and oxygen, indicating that an early step is the target. The SOD concentration-dependent extent of decrease in the autoxidation rate remained the same regardless of higher control rates at pyrogallol concentrations above 0.2 mM. This gave the clue that SOD is catalyzing a reaction that annuls the forward electron transfer step that produces superoxide and pyrogallol-semiquinone, both oxygen radicals. By dismutating these oxygen radicals, an action it is known for, SOD can reverse autoxidation, echoing the reported proposal of superoxide:semiquinone oxidoreductase activity for SOD. The following insights emerged out of these studies. The end-product of pyrogallol autoxidation is PPQ, and not purpurogallin. The quinone products instantly form quinhydrone complexes. These decompose into undefined humic acid-like complexes as late products after cessation of oxygen consumption. SOD catalyzes reversal of autoxidation manifesting as its inhibition. SOD saves catechols from autoxidation and extends their bioavailability.

Graphene scavenges free radicals to synergistically enhance structural properties in a gamma-irradiated polyethylene composite through enhanced interfacial interactions.

A unique strategy for scavenging free radicals in situ on exposure to gamma irradiation in polyethylene (PE) nanocomposites is presented. Blends of ultra-high molecular weight PE and linear low-density PE (PEB) and their nanocomposites with graphene (GPEB) were prepared by melt mixing to develop materials for biomedical implants. The effect of gamma irradiation on the microstructure and mechanical properties was systematically investigated. The neat blend and the nanocomposite were subjected to gamma-ray irradiation in order to improve the interfacial adhesion between PE and graphene sheets. Structural and thermal characterization revealed that irradiation induced crosslinking and increased the crystallinity of the polymer blend. The presence of graphene further enhanced the crystallinity via crosslinks between the polymer matrix and the filler on irradiation. Graphene was found to scavenge free radicals as confirmed by electron paramagnetic resonance spectroscopy. Irradiation of graphene-containing polymer composites resulted in the largest increase in modulus and hardness compared to either irradiation or addition of graphene to PEB alone. This study provides new insight into the role of graphene in polymer matrices during irradiation and suggests that irradiated graphene-polymer composites could emerge as promising materials for use as articulating surfaces in biomedical implants.

ALOBAR HOLOPROSENCEPHALY, CLEFT LIP/PALATE, URORECTAL SEPTUM MALFORMATION SEQUENCE AND CONGENITAL PERINEAL HERNIA IN A FETUS.

We report on a fetus with alobar holoprosencephaly, complete cleft lip and palate, urorectal septum malformation sequence and perineal hernia. To our knowledge this appears to be a novel fetal malformation syndrome.

Enhancing photo-induced ultrafast charge transfer across heterojunctions of CdS and laser-sintered TiO2 nanocrystals.

Enhancing the charge transfer process in nanocrystal sensitized solar cells is vital for the improvement of their performance. In this work we show a means of increasing photo-induced ultrafast charge transfer in successive ionic layer adsorption and reaction (SILAR) CdS-TiO2 nanocrystal heterojunctions using pulsed laser sintering of TiO2 nanocrystals. The enhanced charge transfer was attributed to both morphological and phase transformations. At sufficiently high laser fluences, volumetrically larger porous networks of the metal oxide were obtained, thus increasing the density of electron accepting states. Laser sintering also resulted in varying degrees of anatase to rutile phase transformation of the TiO2, producing thermodynamically more favorable conditions for charge transfer by increasing the change in free energy between the CdS donor and TiO2 acceptor states. Finally, we report aspects of apparent hot electron transfer as a result of the SILAR process which allows CdS to be directly adsorbed to the TiO2 surface.

Role of crystal field in mixed alkali metal effect: electron paramagnetic resonance study of mixed alkali metal oxyfluoro vanadate glasses.

The mixed alkali metal effect is a long-standing problem in glasses. Electron paramagnetic resonance (EPR) is used by several researchers to study the mixed alkali metal effect, but a detailed analysis of the nearest neighbor environment of the glass former using spin-Hamiltonian parameters was elusive. In this study we have prepared a series of vanadate glasses having general formula (mol %) 40 V2O5-30BaF2-(30 - x)LiF-xRbF with x = 5, 10, 15, 20, 25, and 30. Spin-Hamiltonian parameters of V(4+) ions were extracted by simulating and fitting to the experimental spectra using EasySpin. From the analysis of these parameters it is observed that the replacement of lithium ions by rubidium ions follows a "preferential substitution model". Using this proposed model, we were able to account for the observed variation in the ratio of the g parameter, which goes through a maximum. This reflects an asymmetric to symmetric changeover of the alkali metal ion environment around the vanadium site. Further, this model also accounts for the variation in oxidation state of vanadium ion, which was confirmed from the variation in signal intensity of EPR spectra.

Opposing effects of pro- and anti-inflammatory cytokine gene polymorphisms on the risk for breast cancer in western Indian women: a pilot study.

In an earlier study, the genotypes associated with higher level of transforming growth factor-ß1 (TGF-ß1) were found to reduce the risk for breast cancer in western Indian women. This observation implied that gene polymorphisms affecting the levels of pro- and anti-inflammatory cytokines may influence the risk for breast cancer in this population. Hence, we performed genotyping for three more functional single-nucleotide polymorphisms (SNPs) responsible for variations in the levels of cytokines associated with inflammation. To that effect, polymorphisms in genes coding for IL-4 (IL-4 C-590T; rs2243250), IFN-γ (IFN-G A + 874T; rs2430561) and MCP-1 (MCP-1 A-2578G; rs1024611) were examined in premenopausal, healthy women (N = 239) and patients with breast cancer (N = 182) from western India. In carriers of the IL-4*590T allele, a reduced risk for the disease (dominant model; OR = 0.61, 95% CI 0.37-0.98) was seen similar to that seen in TGF-B1*10C carriers. An opposite trend was observed with respect to the alleles associated with higher expression of MCP-1 or IFN-γ. In individuals positive for three or more alleles associated with higher levels of either pro- or anti-inflammatory cytokines, an additive effect on the modulation of risk for the disease was evident (for TGF-B1 & IL-4, OR = 0.33, 95% CI 0.12-0.87; for IFN-G & MCP-1, OR = 2.29, 95% CI 0.95-5.51). In the context of contrasting observations in other populations, these results indicate a significant contribution of anti-inflammatory genotypes in the modulation of risk for breast cancer in western Indian women.

Nosocomial infections in the medical ICU: a retrospective study highlighting their prevalence, microbiological profile and impact on ICU stay and mortality.

OBJECTIVES: 1. To study the prevalence of nosocomial infections in the Medical ICU. 2. To determine common microorganisms causing nosocomial infections in the ICU and their antibiotic- sensitivity profile. 3. To study the impact of nosocomial infections on ICU stay and mortality. METHODS: A retrospective 1 year analysis of nosocomial infections in the Medical ICU at Smt. Kashibai Navale Medical College and Hospital, Pune, between January and December 2011 was carried out. Prevalence of nosocomial infections was determined; sites of nosocomial infections and common causative microorganisms were identified; their antibiotic-sensitivity profiles were studied. The group of patients with nosocomial infections was matched with a control group drawn from the pool of patients without nosocomial infections; this matching was done with respect to age, gender and clinical diagnosis. Period of ICU stay and patient mortality rates in the two groups were analysed. RESULTS: A total of 366 ICU patient records were analysed. Of these, 32 patients were found-to have developed 35 nosocomial infections (9.6% prevalence), of which respiratory infections were the commonest (65.8%), followed by urinary infections (17.1%) and dual infections (urinary plus respiratory) (17.1%).The most frequently isolated microorganism causing respiratory infections was Acinetobacter (40.4%), 21% isolates of which were multidrug resistant; whereas the most frequently isolated microorganism causing urinary tract infections was Pseudomonas (38.4%). Average ICU stay in patients with and without nosocomial infections was 16.5 and 6.4 days respectively; whereas mortality in the two groups was 28.1% and 31.2% respectively. Overall ICU mortality was 19.9%. CONCLUSION: The nosocomial infection rate in our ICU was in keeping with the rate in many industrialised countries. The most common site of nosocomial infection was the respiratory tract, followed by the urinary tract. Acinetobacter was the commonest respiratory isolate, whereas Pseudomonas was the commonest urinary isolate. One fourth of Acinetobacter isolates were multidrug resistant. Nosocomial infections resulted in a statistically significant increase in ICU stay; whereas there was no impact on ICU mortality.