Structural and Spectroscopic Characterization of Copper(III) Complexes and Subsequent One-Electron Oxidation Reaction and Reactivity Studies.

The formation of Cu(III) species are often invoked as the key intermediate in Cu-catalyzed organic transformation reactions. In this study, we synthesized Cu(II) (1) and Cu(III) (3) complexes supported by a bisamidate-bisalkoxide ligand consisting of an ortho-phenylenediamine (o-PDA) scaffold and characterized them through an array of spectroscopic techniques, including UV-visible, electron paramagnetic resonance, X-ray crystallography, and 1H nuclear magnetic resonance (NMR) and X-ray absorption spectroscopy. The Cu-N/O bond distances in 3 are ∼0.1 Šreduced compared to 1, implying a significant increase in 3's overall effective nuclear charge. Further, a Cu(III) complex (4) of a bisamidate-bisalkoxide ligand containing a trans-cyclohexane-1,2-diamine moiety exhibits nearly identical Cu-N/O bond distances to that of 3, inferring that the redox-active o-PDA backbone is not oxidized upon one-electron oxidation of the Cu(II) complex (1). In addition, a considerable difference in the 1s → 4p and 1s → 3d transition energy was observed in the X-ray absorption near-edge structure data of 3 vs 1, which is typical for the metal-centered oxidation process. Electrochemical measurements of the Cu(II) complex (1) in acetonitrile exhibited two consecutive redox couples at -0.9 and 0.4 V vs the Fc+/Fc reference electrode. One-electron oxidation reaction of 3 further resulted in the formation of a ligand-oxidized Cu complex (3a), which was characterized in depth. Reactivity studies of species 3 and 3a were explored toward the activation of the C-H/O-H bonds. A bond dissociation free energy (BDFE) value of ∼69 kcal/mol was estimated for the O-H bond of the Cu(II) complex formed upon transfer of hydrogen atom to 3. The study represents a thorough spectroscopic characterization of high-valent Cu complexes and sheds light on the PCET reactivity studies of Cu(III) complexes.

Characterization of Reaction Intermediates Involved in the Water Oxidation Reaction of a Molecular Cobalt Complex.

Molecular cobalt(III) complexes of bis-amidate-bis-alkoxide ligands, (Me4N)[CoIII(L1)] (1) and (Me4N)[CoIII(L2)] (2), are synthesized and assessed through a range of characterization techniques. Electrocatalytic water oxidation activity of the Co complexes in a 0.1 M phosphate buffer solution revealed a ligand-centered 2e-/1H+ transfer event at 0.99 V followed by catalytic water oxidation (WO) at an onset overpotential of 450 mV. By contrast, 2 reveals a ligand-based oxidation event at 0.9 V and a WO onset overpotential of 430 mV. Constant potential electrolysis study and rinse test experiments confirm the homogeneous nature of the Co complexes during WO. The mechanistic investigation further shows a pH-dependent change in the reaction pathway. On the one hand, below pH 7.5, two consecutive ligand-based oxidation events result in the formation of a CoIII(L2-)(OH) species, which, followed by a proton-coupled electron transfer reaction, generates a CoIV(L2-)(O) species that undergoes water nucleophilic attack to form the O-O bond. On the other hand, at higher pH, two ligand-based oxidation processes merge together and result in the formation of a CoIII(L2-)(OH) complex, which reacts with OH- to yield the O-O bond. The ligand-coordinated reaction intermediates involved in the WO reaction are thoroughly studied through an array of spectroscopic techniques, including UV-vis absorption spectroscopy, electron paramagnetic resonance, and X-ray absorption spectroscopy. A mononuclear CoIII(OH) complex supported by the one-electron oxidized ligand, [CoIII(L3-)(OH)]-, a formal CoIV(OH) complex, has been characterized, and the compound was shown to participate in the hydroxide rebound reaction, which is a functional mimic of Compound II of Cytochrome P450.

Effect of Redox-Inactive Metal Ion-Nickel(III) Interactions on the Redox Properties and Proton-Coupled Electron Transfer Reactivity.

Mononuclear nickel(II) and nickel(III) complexes of a bisamidate-bisalkoxide ligand, (NMe4)2[NiII(HMPAB)] (1) and (NMe4)[NiIII(HMPAB)] (2), respectively, have been synthesized and characterized by various spectroscopic techniques including X-ray crystallography. The reaction of redox-inactive metal ions (Mn+ = Ca2+, Mg2+, Zn2+, Y3+, and Sc3+) with 2 resulted in 2-Mn+ adducts, which was assessed by an array of spectroscopic techniques including X-ray absorption spectroscopy (XAS), electron paramagnetic resonance (EPR), and reactivity studies. The X-ray structure of Ca2+ coordinated to Ni(III) complexes, 2-Ca2+T, was determined and exhibited an average Ni-Ca distance of 3.1253 Å, close to the metal ions' covalent radius. XAS analysis of 2-Ca2+ and 2-Y3+ in solution further revealed an additional coordination to Ca and Y in the 2-Mn+ adducts with shortened Ni-M distances of 2.15 and 2.11 Å, respectively, implying direct bonding interactions between Ni and Lewis acids (LAs). Such a short interatomic distance between Ni(III) and M is unprecedented and was not observed before. EPR analysis of 2 and 2-Mn+ species, moreover, displayed rhombic signals with gav > 2.12 for all complexes, supporting the +III oxidation state of Ni. The NiIII/NiII redox potential of 2 and 2-Mn+ species was determined, and a plot of E1/2 of 2-Mn+ versus pKa of [M(H2O)n]m+ exhibited a linear relationship, implying that the NiIII/NiII potential of 2 can be tuned with different redox-inactive metal ions. Reactivity studies of 2 and 2-Mn+ with different 4-X-2,6-ditert-butylphenol (4-X-DTBP) and other phenol derivatives were performed, and based on kinetic studies, we propose the involvement of a proton-coupled electron transfer (PCET) pathway. Analysis of the reaction products after the reaction of 2 with 4-OMe-DTBP showed the formation of a Ni(II) complex (1a) where one of the alkoxide arms of the ligand is protonated. A pKa value of 24.2 was estimated for 1a. The reaction of 2-Mn+ species was examined with 4-OMe-DTBP, and it was observed that the k2 values of 2-Mn+ species increase by increasing the Lewis acidity of redox-inactive metal ions. However, the obtained k2 values for 2-Mn+ species are much lower compared to the k2 value for 2. Such a variation of PCET reactivity between 2 and 2-Mn+ species may be attributed to the interactions between Ni(III) and LAs. Our findings show the significance of the secondary coordination sphere effect on the PCET reactivity of Ni(III) complexes and furnish important insights into the reaction mechanism involving high-valent nickel species, which are frequently invoked as key intermediates in Ni-mediated enzymatic reactions, solar-fuel catalysis, and biomimetic/synthetic transformation reactions.

Determination of heat stress zone for daily milk yield using carryover heat effect model in Murrah buffaloes.

The objective of the present study was to determine heat stress zones (HSZ) in a year for daily milk yield (DMY) of Murrah buffaloes. Data for the study included 2,67,599 daily milk yield records of 445 Murrah buffaloes sired by 171 bulls as well as climatic parameters, viz. dry bulb temperature (Tdb) and wet bulb (Twb) temperatures spanning over 16 years (2001-2016). The regression analysis of DMY on carryover heat effect indicated that the decline in DMY was significant above the carryover heat effect (CHE) 70. April-November were critical for daily milk yield, and maximum decline in daily milk yield was observed during the month of August in Murrah buffaloes. Therefore, two zones in a year were classified as non-heat stress zone (NHSZ) with CHE < 70 for months December-March and heat stress zone (HSZ) with CHE > 70 during April-November.

Genetic analysis of persistency in HF crossbred cattle at an organized farm of northern India.

The present study was undertaken to estimate effect of various genetic and non-genetic factors on persistency of milk production and to identify the most appropriate persistency method that fits best in our environment. In the present study, effects of different non-genetic factors, viz. year, season, days to attain peak yield, and genetic group based on the level of exotic inheritance on persistency of milk yield in crossbred cattle were studied. Data comprised of 686 first lactation daily milk yield records of crossbred cattle that were maintained at GADVASU dairy farm over a period of 25 years from 1991 to 2015 were utilized to calculate persistency coefficients by four methods, viz., Ludwick and Peterson method (P1), Mahadevan method (P2), ratio method (P3), and Prasad et al. method (P4). Overall least squares means for persistency by Ludwick and Peterson method (P1), Mahadevan method (P2), ratio method (P3), and Prasad et al. method (P4) were 0.896 ± 0.096, 1.385 ± 0.224, 187.207 ± 26.398, and 0.621 ± 0.098, respectively. Effect of sires was significant (P < 0.05) on P2 and P4 methods. Effect of genetic group on all four methods was non-significant. Period of calving had significant (P < 0.01) effect on persistency of milk yield (P2, P3, and P4 methods). Effect of season of calving on persistency of milk yield was found to be significant in all estimates obtained by the four methods. Summer and autumn calvers were most persistent whereas spring and winter calvers were least persistent for (P2, P3, and P4 methods). Persistency of milk yield was significantly (P < 0.05) affected by days to attain peak yield in P1 and P2 methods. Maximum persistency was obtained in animals attaining peak at 41-57 days of lactation and minimum in < 41 days for Mahadevan method and ratio method. The highest heritability of persistency and minimum value of standard error was estimated as 0.275 ± 0.11 for the Mahadevan method followed by the Prasad method (0.197 ± 0.10) by half sib correlation method. The maximum coefficient of variation which indicates available variability was estimated as 20.788% for persistency by the Mahadevan method followed by 18.969% for the Prasad method. The highest correlation was also observed between P1 and P3 methods by Spearman's and Pearson's correlation for least squares breeding value of the sires. On the basis of heritability, standard error of heritability, and coefficient of variation, it can be concluded that the Mahadevan method followed by the Prasad method suits best to our environment for animals in first lactation as well as they can be utilized for effective selection for higher persistency in crossbred animals of Punjab.

Cellular thermotolerance is independent of HSF 1 expression in zebu and crossbred non-lactating cattle.

Heat stress is an important domain of research in livestock due to its negative impact on production and disease resistance. The augmentation of stress in the body stimulates the antioxidative activity comprising various enzymes (viz., catalase, superoxide dismutase), metabolites (reduced glutathione, etc.), vitamins, minerals, etc. to combat the situation. The major key players involved in regulation of heat shock response in eukaryotes are the transcription factors, called as heat shock factors (HSF). They activate the heat shock protein (HSP) genes by binding to their promoters. Lymphocytes are considered to be the best model to evaluate the immunity in any living body as it contains plethora of white blood cells (WBCs).In this study, the peripheral blood mononuclear cells (PBMC) obtained from non-lactating Sahiwal vis-à-vis crossbred (Holstein Friesian × Sahiwal) cattle with 75% or more exotic inheritance were subjected to heat shock at 39, 41, and 43 °C in three different incubators, in vitro. The cell count and viability test of pre and post heat stress of concerned PBMCs indicated that the crossbreeds are more prone to heat stress as compared to Sahiwal. The reverse transcription PCR (qRT-PCR) expression data revealed an increment in HSF1 expression at 41 °C which subsequently declined (non-significantly) at 43 °C in both breeds post 1 h heat shock. However, the association between the HSF 1 expression and antioxidative activity through correlation analysis was found to be non-significant (P < 0.05), though enzymatic activity appeared to behave in a similar fashion in both breeds at 5% level of significance (P < 0.05). This rule out the role of HSF1 expression level on the activity of enzymes involved in oxidative stress in vitro in zebu and crossbred cattle.

Biocomputational characterization and evolutionary analysis of bubaline dicer1 enzyme.

Dicer, an ribonuclease type III type endonuclease, is the key enzyme involved in biogenesis of microRNAs (miRNAs) and small interfering RNAs (siRNAs), and thus plays a critical role in RNA interference through post transcriptional regulation of gene expression. This enzyme has not been well studied in the Indian water buffalo, an important species known for disease resistance and high milk production. In this study, the primary coding sequence (5,778 bp) of bubaline dicer (GenBank: AB969677.1) was determined and the bubaline Dicer1 biocomputationally characterized to determine the phylogenetic signature among higher eukaryotes. The evolutionary tree revealed that all the transcript variants of Dicer1 belonging to a specific species were within the same node and the sequences belonging to primates, rodents and lagomorphs, avians and reptiles formed independent clusters. The bubaline dicer1 is closely related to that of cattle and other ruminants and significantly divergent from dicer of lower species such as tapeworm, sea urchin and fruit fly. Evolutionary divergence analysis conducted using MEGA6 software indicated that dicer has undergone purifying selection over the time. Seventeen divergent sequences, representing each of the families/taxa were selected to study the specific regions of positive vis-à-vis negative selection using different models like single likelihood ancestor counting, fixed effects likelihood, and random effects likelihood of Datamonkey server. Comparative analysis of the domain structure revealed that Dicer1 is conserved across mammalian species while variation both in terms of length of Dicer enzyme and presence or absence of domain is evident in the lower organisms.

Catalytic reduction of oxygen to water by non-heme iron complexes: exploring the effect of the secondary coordination sphere proton exchanging site.

In this study, we prepared non-heme FeIII complexes (1, 2, and 3) of an N4 donor set of ligands (H2L, Me2L, and BPh2L). 1 is supported by a monoanionic bispyridine-dioxime ligand (HL). In 2 and 3, the primary coordination sphere of Fe remained similar to that in 1, except that the oxime protons of the ligand were replaced with two methyl groups and a bridging -BPh2 moiety, respectively. X-ray structures of the FeII complexes (1a and 3a) revealed similar Fe-N distances; however, they were slightly elongated in 2a. The FeIII/FeII potential of 1, 2, and 3 appeared at -0.31 V, -0.25 V, and 0.07 V vs. Fc+/Fc, respectively, implying that HL and Me2L have comparable donor properties. However, BPh2L is more electron deficient than HL or Me2L. 1 showed electrocatalytic oxygen reduction reaction (ORR) activity in acetonitrile in the presence of trifluoroacetic acid (TFAH) as the proton source at Ecat/2 = -0.45 V and revealed selective 4e-/4H+ reduction of O2 to H2O. 1 showed an effective overpotential (ηeff) of 0.98 V and turnover frequency (TOFmax) of 1.02 × 103 s-1. Kinetic studies revealed a kcat of 2.7 × 107 M-2 s-1. Strikingly, 2 and 3 remained inactive for electrocatalytic ORR, which established the essential role of the oxime scaffolds in the electrocatalytic ORR of 1. Furthermore, a chemical ORR of 1 has been investigated using decamethylferrocene as the electron source. For 1, a similar rate equation was noted to that of the electrocatalytic pathway. A kcat of 6.07 × 104 M-2 s-1 was found chemically. Complex 2, however, underwent a very slow chemical ORR. Complex 3 chemically enhances the 4e-/4H+ reduction of O2 and exhibits a TOF of 0.24 s-1 and a kcat value of 2.47 × 102 M-1 s-1. Based on the experimental observations, we demonstrate that the oxime backbone of the ligand in 1 works as a proton exchanging site in the 4e-/4H+ reduction of O2. The study describes how the ORR is affected by the tuning of the ligand scaffold in a family of non-heme Fe complexes.

Functional Model of Compound II of Cytochrome P450: Spectroscopic Characterization and Reactivity Studies of a FeIV-OH Complex.

Herein, we show that the reaction of a mononuclear FeIII(OH) complex (1) with N-tosyliminobenzyliodinane (PhINTs) resulted in the formation of a FeIV(OH) species (3). The obtained complex 3 was characterized by an array of spectroscopic techniques and represented a rare example of a synthetic FeIV(OH) complex. The reaction of 1 with the one-electron oxidizing agent was reported to form a ligand-oxidized FeIII(OH) complex (2). 3 revealed a one-electron reduction potential of -0.22 V vs Fc+/Fc at -15 °C, which was 150 mV anodically shifted than 2 (Ered = -0.37 V vs Fc+/Fc at -15 °C), inferring 3 to be more oxidizing than 2. 3 reacted spontaneously with (4-OMe-C6H4)3C• to form (4-OMe-C6H4)3C(OH) through rebound of the OH group and displayed significantly faster reactivity than 2. Further, activation of the hydrocarbon C-H and the phenolic O-H bond by 2 and 3 was compared and showed that 3 is a stronger oxidant than 2. A detailed kinetic study established the occurrence of a concerted proton-electron transfer/hydrogen atom transfer reaction of 3. Studying one-electron reduction of 2 and 3 using decamethylferrocene (Fc*) revealed a higher ket of 3 than 2. The study established that the primary coordination sphere around Fe and the redox state of the metal center is very crucial in controlling the reactivity of high-valent Fe-OH complexes. Further, a FeIII(OMe) complex (4) was synthesized and thoroughly characterized, including X-ray structure determination. The reaction of 4 with PhINTs resulted in the formation of a FeIV(OMe) species (5), revealing the presence of two FeIV species with isomer shifts of -0.11 mm/s and = 0.17 mm/s in the Mössbauer spectrum and showed FeIV/FeIII potential at -0.36 V vs Fc+/Fc couple in acetonitrile at -15 °C. The reactivity studies of 5 were investigated and compared with the FeIV(OH) complex (3).

Subfertility problems leading to disposal of breeding bulls.

Subfertility problems are encountered frequently in the cattle and buffalo bulls commercially maintained for semen production in dairy farms and under field conditions for natural insemination. Reports are scarce on the incidence of subfertility in breeding bulls, especially in India. The objective of the present study was to assess the incidence of the male reproductive anomalies leading to disposal of bovine bulls at GADVASU dairy farm, Ludhiana, Punjab (India). Data on frequency of various subfertility and disposal pattern of bulls maintained at the dairy farm, GADVASU, were collected for 12 yrs (1999 to 2010) and compiled from different record registers. Percentage of bulls that produced freezable semen (out of reserved ones) was less in cattle (25.641%) as compared to that of buffalo (30.4%). Various subfertility traits like poor libido and unacceptable seminal profile were found to be the significant reasons (p<0.01) for culling of the breeding bulls. Inadequate sex drive and poor semen quality were the main contributing factors for bull disposal in cattle whereas poor semen freezability was most frequently observed in buffalo bulls. All the male reproductive traits were significantly different (p<0.05) for the periods of birth, except for semen volume, initial motility (IM), age at last semen collection (ALSC) and age at disposal. The ages at first and last semen collection as well as freezing (i.e. AFSC, ALSC and AFSF, ALSF, respectively) and age at disposal (AD) were higher in buffalo. The spermatological parameters and semen production period (SPP) were higher in cattle. The age at first semen donation and breeding period could be reduced by introducing the bulls to training at an early age. The results revealed an increasing trend in individual motility (IM) while semen volume, AFSC, AFSF, AD, FSPP, SPP, ALSC and ALSF showed a decreasing, however, not a definite trend, over the periods. The semen donation traits like, AFSF, of the cattle and buffalo bulls could be predicted from the AFSC, using prediction equation derived in the present study.

Efficacy and Safety of Brolucizumab, Aflibercept, and Ranibizumab for the Treatment of Patients with Visual Impairment Due to Diabetic Macular Oedema: A Systematic Review and Network Meta-Analysis.

INTRODUCTION: Key clinical guidelines recommend anti-vascular endothelial growth factor (VEGF) therapy as first-line treatment for visual impairment due to diabetic macular oedema (DMO). A systematic literature review (SLR) and network meta-analysis (NMA) were conducted comparing the relative efficacy of the anti-VEGF brolucizumab with a focused network of the most relevant comparator dosing regimens approved in countries other than the USA (aflibercept, ranibizumab). The safety and tolerability of brolucizumab were also assessed. METHODS: A broad SLR was conducted to identify randomised controlled trials to ensure all relevant potential comparators were captured. Identified studies were refined to those appropriate for inclusion in the NMA. A Bayesian NMA was conducted comparing brolucizumab 6 mg (every 12 [Q12W]/every 8 weeks [Q8W]) with relevant aflibercept 2 mg and ranibizumab 0.5 mg regimens. RESULTS: Fourteen studies were included in the NMA. At 1-year follow-up, the various aflibercept 2 mg and ranibizumab 0.5 mg regimens were mostly comparable with brolucizumab 6 mg Q12W/Q8W across key visual and anatomical outcomes, except brolucizumab 6 mg was favoured over ranibizumab 0.5 mg every 4 weeks (Q4W) for the change from baseline (CFB) in best-corrected visual acuity (BCVA), and BCVA loss/gain of pre-specified numbers of letters, and over ranibizumab 0.5 mg pro re nata for CFB in diabetic retinopathy severity scale, and retinal thickness. At year 2, where data were available, brolucizumab 6 mg showed similar results across efficacy outcomes versus all other anti-VEGFs. In most cases, discontinuation rates (all cause, and due to adverse events [AE]) and serious and overall rates of AEs excluding ocular inflammatory events were similar (in unpooled and pooled-treatment analyses) versus comparators. CONCLUSION: Brolucizumab 6 mg Q12W/Q8W was comparable or superior to aflibercept 2 mg and ranibizumab 0.5 mg regimens for various visual and anatomical efficacy outcomes and discontinuation rates.

Extracting time-dependent obese-diabetic specific networks in hepatic proteome analysis.

Molecular mechanism governing biological processes leading to dietary obesity and diabetes are largely unknown. Here we study the liver proteome differentially expressed in a long-term high-fat and high-sucrose diet (HFHSD)-induced obesity and diabetes mouse model. Changes in mouse liver proteins were identified using iTRAQ, offline 2D LC (SCX and RP) and MALDI-TOF/TOF MS. A total of 1639 proteins was quantified during 3-15 weeks of disease progression and a pronounced proteome change was captured by incorporating the statistical analysis and network analysis. This underscores the importance of protein expression profiles involved in different biological processes that correlate well with the disease progression. The functionally important modules with key hub proteins such as Egfr, Pklr, Suclg1, and Pcx (Carbohydrate metabolism), Cyp2e1, Fasn, Acat1, and Hmgcs2 (Lipid metabolism and ketogenesis), and Gpx1, Mgst1, and Sod2 (ROS metabolism) can be linked to a physiological state of obesity and T2D. Multiple proteins involved in glucose catabolism and lipogenesis were down-regulated, whereas proteins involved in lipid peroxidation and oxidative phosphorylation were up-regulated. In conclusion, this proteomic study provides targets for future mechanistic and therapeutic studies in relation to development and prevention of obesity and Type 2 Diabetes.

Efficacy of Lecture cum demonstration versus video-based teaching regarding active management of third stage of labor in terms of knowledge and skills of GNM students: An interventional study.

INTRODUCTION: Educational interventions have been associated with improved performance and significant changes, especially in perinatal outcomes. Teaching is one of the main components in educational planning which is a key factor in conducting educational plans through various teaching strategies such as simulation, demonstration and video teaching. AIM: The study aimed to assess lecture cum demonstration (LCD) versus video-based teaching (VBT) regarding active management of the third stage of labor (AMTSL) in terms of knowledge and skills of General Nursing Midwifery (GNM) students. METHODS: This was a quasi-experimental study conducted on 100 GNM third-year students selected by purposive sampling and randomly assigned to LCD (n = 50) and VBT (n = 50) groups. Sample characteristics performa, Structured Knowledge Questionnaire, and observational checklist were used to collect data from GNM students through self-report and observational technique. RESULTS: The study results showed that the mean posttest knowledge scores of LCD (17.32 ± 2.14) and VBT group (16.90 ± 2.41) were nearly equal and mean rank posttest skills score of LCD group (54.40) was slightly higher than VBT group (49.51), but computed " t " value of mean posttest knowledge and computed " Z " value of skill score of both LCD and VBT group (0.47, 0.54) were found to be statistically non-significant at 0.05 level of significance. CONCLUSION: It can be concluded that both LCD and VBT were found to be effective in improving knowledge and skills of GNM students regarding AMTSL.

Peer learning versus conventional teaching regarding antenatal assessment among nursing students in terms of knowledge, skills, and satisfaction: An interventional study.

INTRODUCTION: Eaching methods are the stimulation, guidance, direction, and encouragement for learning and also the means to achieve the desired educational objectives. AIM: This study aimed to assess peer learning (PL) versus conventional teaching (CT) regarding antenatal assessment in terms of knowledge, skills, and satisfaction among nursing students. METHODS: This was a quasi-experimental study conducted on 51 B.Sc.Nursing 3rd-year students who were selected by convenient sampling and randomly assigned to PL (n = 21) and CT (n = 30) group. Sample characteristics pro forma, structured knowledge questionnaire, observational checklist, and satisfaction rating scale wereused to collect data from nursing students through self-report and observational technique. RESULTS: The study results revealed that the mean posttest knowledge score (19.1 ± 0.75) in PL group was higher than that in CT group (17.0 ± 0.741) and the mean rank skill score of PL group (44.90) was higher than that in the CT group (20.30). There was no significant difference (t = 1.08, P > 0.05) in mean posttest knowledge score, whereas the significant difference was found in posttest skill score (Z = 5.00, P ≤ 0.01) among nursing students. Most of the nursing students were satisfied with the CT method. There was a mild positive correlation (r = 0.25) between knowledge and skills regarding antenatal assessment among nursing students. CONCLUSION: Based on the findings of the study, it can be concluded that both PL and CT groups were found to be equally effective in improving knowledge and skills of nursing students regarding antenatal assessment.

Effectiveness of Warm Compression on Lumbo-Sacral Region in Terms of Labour Pain Intensity and Labour Outcomes among Nulliparous: an Interventional Study.

Introduction: Childbirth is a distinctive and joyous moment in every mother's life. Giving birth is one of the powerful and vital event. This study aimed to assess and evaluate the effectiveness of warm compression (moist heat) on lumbo-sacral region in terms of labor pain intensity and labor outcomes Methods: An experimental research design was carried out on 88 nulliparous mothers with normal singleton term pregnancy (44 participants in each group) who were admitted in the labor room. Mothers who had high-risk pregnancy were excluded. Warm compression was given to nulliparous mothers of the experimental group with hydrochollator pack at 70◦C temperature for 20 minutes for 3 times with one-hour interval on lumbo sacral region starting from 4-5 cm of cervical dilatation. Labor pain intensity score, fetal heart rate, frequency and duration of uterine contractions were assessed before and immediately of warm compression and again after 30 minutes only labor pain was assessed. Results: Study results revealed that immediately after first, second and third time of warm compression labor pain intensity score in experimental group was lower than control group respectively ( t= 3.20; P< 0.001; t =4.45; P< 0.001; t= 6.18; P< 0.001). But no significant difference found in fetal heart rate and labor outcomes in terms of duration of labor, type of delivery, baby born alive/ not and cried immediately after birth. Conclusion: Warm compression was useful method to decrease the labour pain among nulliparous mothers in the first stage of labour and mothers reported satisfaction with intervention.

Health-related quality of life and economic burden of chronic lymphocytic leukemia in the era of novel targeted agents.

OBJECTIVE: To quantify the health-related quality of life (HRQoL) and economic burden of chronic lymphocytic leukemia (CLL). METHODS: Studies were searched through Embase, MEDLINE, PubMed, and Cochrane Library, as well as conference abstracts (1 January 2000-2 June 2019). RESULTS: Overall, 12 and 17 primary studies were included in the HRQoL and economic burden reviews, respectively. Patients with CLL reported impairment in various quality of life domains when compared with healthy controls, including fatigue, anxiety, physical functioning, social functioning, depression, sleep disturbance, and pain interference. Key factors associated with a negative impact on the HRQoL burden of CLL included female gender, increased disease severity, and the initiation of multiple lines of therapy. Economic burden was assessed for patients with CLL based on disease status and the treatment regimen received. The main cost drivers related to CLL were outpatient and hospitalization-related costs, primarily incurred as a result of chemo/chemoimmunotherapy, adverse events (AEs), and disease progression. Treatment with targeted agents, i.e. ibrutinib and venetoclax, was associated with lower medical costs than chemoimmunotherapy, although ibrutinib was associated with some increased AE costs related to cardiac toxicities. Cost studies of targeted agents were limited by short follow-up times that did not capture the full scope of treatment costs. CONCLUSIONS: CLL imposes a significant HRQoL and economic burden. Our systematic review shows that an unmet need persists in CLL for treatments that delay progression while minimizing AEs. Studies suggest targeted therapies may reduce the economic burden of CLL, but longer follow-up data are needed.

MicroRNA expression profiling in PBMCs of Indian water Buffalo (Bubalus bubalis) infected with Brucella and Johne's disease.

BACKGROUND: MicroRNAs play key roles in host-pathogen-interactions and disease pathogenesis. Our aim was to characterize the differentially expressed miRNAs in the blood cells of diseased (Brucellosis-positive, Johne's disease-positive) and healthy- water buffaloes. The pooled small-RNA samples of each group were sequenced on Ion Torrent Personal Genome Machine (PGM) sequencer and the data were analyzed for differential expression. RESULTS: Here we identified 274 known miRNAs with bovine homologs and 36 novel mature-star miRNAs from the sequnces of small RNA libraries. Overall 195 miRNAs were common to all the three groups. Certain miRNAs such as bta-miR-21-5p, -26a, -29a/b, -30d - 103, - 140, - 150, - 191, - 374, - 1434-5p,-1260b, - 2484 and let-7 members were abundantly expressed in diseased groups. Bta-miR-1434-5p, - 188, -200c were up-regulated (> 1.5 folds) while bta-miR-27a-5p, -34b and -2285x were down-regulated (> 100 folds) in Brucellosis group. In Johne's Disease group, only 3 miRNAs (bta-miR-1434-5p, - 2340 and - 2484) were up-regulated (> 1.5 folds). The functional classification of miRNA target genes into gene ontology (GO) terms indicated their involvement in innate immunity and cellular process of disease pathogenesis. Expression profile of four differentially expressed miRNAs (bta-miR-9-5p, - 677, - 331-3p and - 2440) and eight predicted target-genes were validated through reverse transcriptase qPCR. CONCLUSION: This study provides a valuable frame of reference for elucidation of regulatory roles of miRNAs associated with disease pathogenesis in water buffaloes as well as identification of miRNA biomarkers for disease diagnosis and treatment.

Knowledge and attitude regarding reproductive and sexual health among school teachers: a descriptive survey.

BACKGROUND: Adolescence is a time of evolving from the immaturity of childhood into the maturity of adulthood. This is a stage which requires extra care and protection. Physiologically and physically, adolescents go through a series of transformations as they grow and develop. METHOD: A descriptive study design was adopted with 70 teachers selected using a convenience sampling technique from five different government schools of the Ambala District, Haryana. Knowledge and attitude were assessed using a structured knowledge questionnaire and a 5-point Likert scale, respectively. The reliability coefficient of the structured knowledge questionnaire was found to be 0.67 by the Kuder-Richardson method and for the attitude scale, it was found to be 0.7 by Cronbach's α. RESULTS: More than one third (37.1%) of the teachers were between 31 and 35 years of age. Out of 70 the majority (75.7%) of the teachers were female. More than half (62.9%) of the teachers had an average level of knowledge and the majority (71.4%) of the teachers had moderately favorable attitudes regarding reproduction and sexual health. Furthermore, teachers had more knowledge about the reproductive organs and the concept of puberty followed by the concept of reproductive and sexual health and had the least knowledge in the area of contraception. CONCLUSION: This study highlights the need for special training and awareness programs regarding reproduction and sexual health among school teachers.

Lack of Treatment Persistence and Treatment Nonadherence as Barriers to Glycaemic Control in Patients with Type 2 Diabetes.

Treatment persistence (continuing to take medication for the prescribed period) and treatment adherence (complying with the prescription in terms of drug schedules and dosage) are both important when treating chronic diseases such as type 2 diabetes (T2D). They can be indicators of patient satisfaction with treatment. In T2D, the achievement of optimal outcomes requires both persistence with and adherence to prescribed therapy. Poor persistence with and adherence to T2D medication can have profound consequences for the patient, including non-achievement of glycaemic goals and an increased risk of long-term complications and mortality. Therefore, poor treatment persistence and adherence may also have economic consequences, including increased healthcare resource utilization and healthcare costs. Treatment persistence and adherence are affected by several factors, including the mode of administration, administration frequency/regimen complexity, and patient expectations. The aims of this review are as follows: to provide an overview of persistence with and adherence to different antidiabetes therapies for patients with T2D in the real-world setting; examine factors contributing to poor treatment persistence and adherence; and assess available data on the impact of poor treatment persistence and/or adherence on clinical and economic outcomes. Numerous potential targets for improving treatment persistence and/or adherence are identified, including developing less complex treatment regimens with lower pill burdens or less frequent injections, improving the convenience of drug-delivery systems, such as the use of insulin pen devices rather than the conventional vial and syringe, and developing therapies with an improved safety profile to alleviate patient fears of adverse effects, such as weight gain and risk of hypoglycaemia.Funding: Sanofi.

Identification of the MicroRNA Repertoire in TLR-Ligand Challenged Bubaline PBMCs as a Model of Bacterial and Viral Infection.

In the present study, we used high-throughput sequencing, miRNA-seq, to discover and explore the expression profiles of known and novel miRNAs in TLR ligand-stimulated vis-à-vis non-stimulated (i.e. Control) peripheral blood mononuclear cells (PBMCs) isolated from blood of healthy Murrah buffaloes. Six small RNA (sRNA) libraries were multiplexed in Ion Torrent PI chip and sequenced on Ion Proton System. The reads obtained were aligned to the Bos taurus genome (UMD3.1 assembly), which is phylogenetically closest species to buffalo (Bubalus bubalis). A total of 160 bovine miRNAs were biocomputationally identified in buffalo PBMCs and 130 putatively novel miRNAs (not enlisted in the bovine mirBase) were identified. All of these 290 miRNAs identified across the six treatment and control samples represent the repertoire of novel miRNAs for the buffalo species. The expression profiles of these miRNAs across the samples have been represented by sample dendrogram and heatmap plots. The uniquely expressed miRNAs in each treatment and control groups were identified. A few miRNAs were expressed at very high levels while the majority of them were moderately expressed. The miRNAs bta-miR-103 and -191 were found to be highly abundant and expressed in all the samples. Other abundantly expressed miRNAs include bta-miR-19b, -29b, -15a, -19a, -30d, -30b-5p and members of let family (let 7a-5p, let 7g & let 7f) in LPS and CpG treated PBMCS and bta-miR-191, -103 & -19b in Poly I:C stimulated PBMCs. Only one novel miRNA (bta-miR-11039) out of 130 identified putatively novel miRNAs, was expressed in all the six samples and differentially expressed (>2- fold) miRNAs were identified. Six of the differentially expressed miRNAs across the groups (bta-miR-421, bta-let-7i, bta-miR-138, bta-miR-21-5p, bta-miR-222 and bta-miR-27b) were subsequently confirmed by TaqMan quantitative reverse transcription polymerase chain reaction (qRT-PCR). Furthermore, the target genes of differentially expressed miRNAs were enriched for the roles in innate immunity and TLR signaling pathways. This maiden study on profiling and cataloguing of bubaline miRNAs expressed in TLR-ligand stimulated PBMCs will provide an important reference point for future studies on regulatory roles of miRNAs in immune system of buffaloes.