A study of prevalence and association of fundus changes in pregnancy induced hypertension

Background: The pathological changes of pregnancy induced hypertension appear to be related to vascular endothelial dysfunction and its consequences. The retinal vascular changes generally, but not always, correlate with the severity of systemic hypertension. To find out the prevalence and association of retinal changes in pregnancy induced hypertension.Methods: A hospital based cross-sectional study was conducted where all antenatal pregnant women who fulfilled the diagnostic criteria of PIH were included in this study. Patients who had pre-existing diabetes or hypertension or renal disease or hazy media which did not permit fundus visualization were excluded from the study.Socio-demogrpahic and obstetric data was collected and all the patients were subjected to detailed clinical examination followed by fundoscopic examination.Results: Out of the total 423 patients of PIH examined, the retinal changes (hypertensive retinopathy changes) were noted in 181 (42.7%) patients. The prevalence of retinopathy changes was more among patients with imminent Eclampsia (76.5%) and eclampsia patients (50%). As the severity of the PIH increased the Odds of women developing retinopathy also increased substantially from OR: 17.6; 95% CI: 3.1-136.3 in severe PIH to OR: 253; 95% CI: 47.2-1935 in Imminent eclampsia and this association between the severity of PIH and the development of retinopathy changes was found to be statistically significant.Conclusions: Fundus examination in cases of PIH is of paramount importance in monitoring and managing cases as it co-relates with the severity of PIH

Safety and efficacy of ferric carboxy maltose in pregnant women- a pilot study

Background: Iron deficiency is a common nutritional deficiency amongst women of childbearing age. It is associated with significant maternal, fetal and infant morbidity. Current options for treatment include oral iron, parenteral iron and red blood cell transfusions. Ferric carboxy maltose is a newer i.v. iron formulation which can be used at high doses with rapid administration. This study was undertaken to assess the safety and efficacy in pregnant women.Methods: Prospective observational study was conducted in VIMS Ballari. 50 pregnant women between 28-36 weeks of gestation having moderate anemia with confirmed iron deficiency were administered with 1000 mg of ferric carboxy maltose (FCM). These women were followed after 2 weeks, 4 weeks and till delivery. Safety and efficacy were assessed.Results: There was significant improvement in both hemoglobin and serum ferritin levels (p<0.01). None of them had significant reactions.Conclusions: Ferric carboxy maltose is well tolerated. Ability to transfuse in single high dose makes it a preferred drug for faster and higher replenishment of iron stores and correction of hemoglobin levels during pregnancy especially in third trimester

High Prevalence of Associated Birth Defects in Congenital Hypothyroidism

Aim. To identify dysmorphic features and cardiac, skeletal, and urogenital anomalies in patients with congenital hypothyroidism. Patients and Methods. Seventeen children with congenital primary hypothyroidism were recruited. Cause for congenital hypothyroidism was established using ultrasound of thyroid and 99mTc radionuclide thyroid scintigraphy. Malformations were identified by clinical examination, echocardiography, X-ray of lumbar spine, and ultrasonography of abdomen. Results. Ten (59%) patients (6 males and 4 females) had congenital malformations. Two had more than one congenital malformation (both spina bifida and ostium secundum atrial septal defect). Five (29%) had cardiac malformations, of whom three had only osteum secundum atrial septal defect (ASD), one had only patent ductus arteriosus (PDA), and one patient had both ASD and PDA. Seven patients (41%) had neural tube defects in the form of spina bifida occulta. Conclusion. Our study indicates the need for routine echocardiography in all patients with congenital hypothyroidism

Use of cetylpyridinium chloride for the storage of sputum samples and isolation of M. tuberculosis

Of 220 sputum specimens collected from pulmonary tuberculosis patients, 85 were culture positive when the sputum aliquots were stored with cetypyridinium chloride (CPC) and processed on 7th day (CPC method), whereas only 70 were culture positive when the aliquots of the same specimens were stored without CPC and processed by sodium hydroxide (NaOH) method. The difference in the culture positivity was statistically significant. The number of positive, cultures obtained by the CPC method (85) was comparable to that obtained by the NaOH method before storage (95) and the difference was not statistically significant

Damage function for historic paper. Part I: Fitness for use

Background In heritage science literature and in preventive conservation practice, damage functions are used to model material behaviour and specifically damage (unacceptable change), as a result of the presence of a stressor over time. For such functions to be of use in the context of collection management, it is important to define a range of parameters, such as who the stakeholders are (e.g. the public, curators, researchers), the mode of use (e.g. display, storage, manual handling), the long-term planning horizon (i.e. when in the future it is deemed acceptable for an item to become damaged or unfit for use), and what the threshold of damage is, i.e. extent of physical change assessed as damage. Results In this paper, we explore the threshold of fitness for use for archival and library paper documents used for display or reading in the context of access in reading rooms by the general public. Change is considered in the context of discolouration and mechanical deterioration such as tears and missing pieces: forms of physical deterioration that accumulate with time in libraries and archives. We also explore whether the threshold fitness for use is defined differently for objects perceived to be of different value, and for different modes of use. The data were collected in a series of fitness-for-use workshops carried out with readers/visitors in heritage institutions using principles of Design of Experiments. Conclusions The results show that when no particular value is pre-assigned to an archival or library document, missing pieces influenced readers/visitors’ subjective judgements of fitness-for-use to a greater extent than did discolouration and tears (which had little or no influence). This finding was most apparent in the display context in comparison to the reading room context. The finding also best applied when readers/visitors were not given a value scenario (in comparison to when they were asked to think about the document having personal or historic value). It can be estimated that, in general, items become unfit when text is evidently missing. However, if the visitor/reader is prompted to think of a document in terms of its historic value, then change in a document has little impact on fitness for use

Novel Molecular Targets of Azadirachta indica Associated with Inhibition of Tumor Growth in Prostate Cancer

Advanced prostate cancer has significant long-term morbidity, and there is a growing interest in alternative and complimentary forms of therapy that will improve the outcomes of patients. Azadirachta indica (common name: neem) contains multiple active compounds that have potent anti-inflammatory and anticancer properties. The present study investigates the novel targets of the anticancer activity of ethanol extract of neem leaves (EENL) in vitro and evaluates the in vivo efficacy in the prostate cancer models. Analysis of the components in the EENL by mass spectrometry suggests the presence of 2′,3′-dehydrosalannol, 6-desacetyl nimbinene, and nimolinone. Treatment of C4-2B and PC-3M-luc2 prostate cancer cells with EENL inhibited the cell proliferation. Genome-wide expression profiling, using oligonucleotide microarrays, revealed genes differentially expressed with EENL treatment in prostate cancer cells. Functional analysis unveiled that most of the up-regulated genes were associated with cell death, and drug metabolism, and the down-regulated genes were associated with cell cycle, DNA replication, recombination, and repair functions. Quantitative PCR confirmed significant up-regulation of 40 genes and immunoblotting revealed increase in the protein expression levels of HMOX1, AKR1C2, AKR1C3, and AKR1B10. EENL treatment inhibited the growth of C4-2B and PC-3M-luc2 prostate cancer xenografts in nude mice. The suppression of tumor growth is associated with the formation of hyalinized fibrous tumor tissue and the induction of cell death by apoptosis. These results suggest that EENL-containing natural bioactive compounds could have potent anticancer property and the regulation of multiple cellular pathways could exert pleiotrophic effects in prevention and treatment of prostate cancer

Revisiting the susceptibility testing of Mycobacterium tuberculosis to ethionamide in solid culture medium.

BACKGROUND & OBJECTIVES Increase in the isolation of drug resistant phenotypes of Mycobacterium tuberculosis necessitates accuracy in the testing methodology. Critical concentration defining resistance for ethionamide (ETO), needs re-evaluation in accordance with the current scenario. Thus, re-evaluation of conventional minimum inhibitory concentration (MIC) and proportion sensitivity testing (PST) methods for ETO was done to identify the ideal breakpoint concentration defining resistance. METHODS Isolates of M. tuberculosis (n=235) from new and treated patients were subjected to conventional MIC and PST methods for ETO following standard operating procedures. RESULTS With breakpoint concentration set at 114 and 156 µg/ml, an increase in specificity was observed whereas sensitivity was high with 80 µg/ml as breakpoint concentration. Errors due to false resistant and susceptible isolates were least at 80 µg/ml concentration. INTERPRETATION & CONCLUSIONS Performance parameters at 80 µg/ml breakpoint concentration indicated significant association between PST and MIC methods

Salvinorin A Regulates Dopamine Transporter Function Via A Kappa Opioid Receptor and ERK1/2-Dependent Mechanism

Salvinorin A (SalA), a selective κ-opioid receptor (KOR) agonist, produces dysphoria and pro-depressant like effects. These actions have been attributed to inhibition of striatal dopamine release. The dopamine transporter (DAT) regulates dopamine transmission via uptake of released neurotransmitter. KORs are apposed to DAT in dopamine nerve terminals suggesting an additional target by which SalA modulates dopamine transmission. SalA produced a concentration-dependent, nor-binaltorphimine (BNI)- and pertussis toxin-sensitive increase of ASP+ accumulation in EM4 cells coexpressing myc-KOR and YFP-DAT, using live cell imaging and the fluorescent monoamine transporter substrate, trans 4-(4-(dimethylamino)-styryl)-N-methylpyridinium) (ASP+). Other KOR agonists also increased DAT activity that was abolished by BNI pretreatment. While SalA increased DAT activity, SalA treatment decreased serotonin transporter (SERT) activity and had no effect on norepinephrine transporter (NET) activity. In striatum, SalA increased the Vmax for DAT mediated DA transport and DAT surface expression. SalA up-regulation of DAT function is mediated by KOR activation and the KOR-linked extracellular signal regulated kinase-½ (ERK1/2) pathway. Co-immunoprecipitation and BRET studies revealed that DAT and KOR exist in a complex. In live cells, DAT and KOR exhibited robust FRET signals under basal conditions. SalA exposure caused a rapid and significant increase of the FRET signal. This suggests that the formation of KOR and DAT complexes is promoted in response to KOR activation. Together, these data suggest that enhanced DA transport and decreased DA release resulting in decreased dopamine signaling may contribute to the dysphoric and pro-depressant like effects of SalA and other KOR agonists

Identification of potential therapeutic targets in prostate cancer through a cross-species approach.

Genetically engineered mouse models of cancer can be used to filter genome-wide expression datasets generated from human tumours and to identify gene expression alterations that are functionally important to cancer development and progression. In this study, we have generated RNAseq data from tumours arising in two established mouse models of prostate cancer, PB-Cre/PtenloxP/loxP and p53loxP/loxPRbloxP/loxP, and integrated this with published human prostate cancer expression data to pinpoint cancer-associated gene expression changes that are conserved between the two species. To identify potential therapeutic targets, we then filtered this information for genes that are either known or predicted to be druggable. Using this approach, we revealed a functional role for the kinase MELK as a driver and potential therapeutic target in prostate cancer. We found that MELK expression was required for cell survival, affected the expression of genes associated with prostate cancer progression and was associated with biochemical recurrence

Intracellular immune sensing promotes inflammation via gasdermin D–driven release of a lectin alarmin

Inflammatory caspase sensing of cytosolic lipopolysaccharide (LPS) triggers pyroptosis and the concurrent release of damage-associated molecular patterns (DAMPs). Collectively, DAMPs are key determinants that shape the aftermath of inflammatory cell death. However, the identity and function of the individual DAMPs released are poorly defined. Our proteomics study revealed that cytosolic LPS sensing triggered the release of galectin-1, a β-galactoside-binding lectin. Galectin-1 release is a common feature of inflammatory cell death, including necroptosis. In vivo studies using galectin-1-deficient mice, recombinant galectin-1 and galectin-1-neutralizing antibody showed that galectin-1 promotes inflammation and plays a detrimental role in LPS-induced lethality. Mechanistically, galectin-1 inhibition of CD45 (Ptprc) underlies its unfavorable role in endotoxin shock. Finally, we found increased galectin-1 in sera from human patients with sepsis. Overall, we uncovered galectin-1 as a bona fide DAMP released as a consequence of cytosolic LPS sensing, identifying a new outcome of inflammatory cell death.Fil: Russo, Ashley J.. UConn Health School of Medicine; Estados UnidosFil: Vasudevan, Swathy O.. UConn Health School of Medicine; Estados UnidosFil: Mendez Huergo, Santiago Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Kumari, Puja. UConn Health School of Medicine; Estados UnidosFil: Menoret, Antoine. UConn Health School of Medicine; Estados UnidosFil: Duduskar, Shivalee. Jena University Hospital; AlemaniaFil: Wang, Chengliang. UConn Health School of Medicine; Estados UnidosFil: Pérez Sáez, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Fettis, Margaret M.. University of Florida; Estados UnidosFil: Li, Chuan. UConn Health School of Medicine; Estados UnidosFil: Liu, Renjie. University of Florida; Estados UnidosFil: Wanchoo, Arun. University of Florida; Estados UnidosFil: Chandiran, Karthik. UConn Health School of Medicine; Estados UnidosFil: Ruan, Jianbin. UConn Health School of Medicine; Estados UnidosFil: Vanaja, Sivapriya Kailasan. UConn Health School of Medicine; Estados UnidosFil: Bauer, Michael. Jena University Hospital; AlemaniaFil: Sponholz, Christoph. Jena University Hospital; AlemaniaFil: Hudalla, Gregory A.. University of Florida; Estados UnidosFil: Vella, Anthony T.. UConn Health School of Medicine; Estados UnidosFil: Zhou, Beiyan. UConn Health School of Medicine; Estados UnidosFil: Deshmukh, Sachin D.. Jena University Hospital; AlemaniaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rathinam, Vijay A.. UConn Health School of Medicine; Estados Unido