Testing the waters: A pilot trial of acceptance and commitment therapy (ACT) for alcohol use disorder.

Background: Psychosocial interventions help maintain alcohol abstinence. Third-wave psychotherapies have emerged as an alternative to cognitive behavioral therapies for Alcohol Use Disorder (AUD) treatment. However, third-wave therapies have not been tested in non-western settings or via telehealth. Aim: We assessed the acceptability and feasibility of Acceptance and Commitment Therapy (ACT) in moderate/severe AUD. Methods: This was a pre- and post-study design. All those who met the eligibility (n = 40) criteria consented to participate. A trained nurse delivered four sessions of ACT, either in-person or via video-conferencing, per participants' preference. Alcohol use, craving, relapse signs, and psychological flexibility were assessed three months post-intervention. Results: Twenty-eight participants (70%) attended all four sessions. There was a significant increase in abstinence and a decrease in alcohol use, frequency of drinking/heavy drinking, craving, relapse signs, and improved psychological flexibility. Outcomes were positive for either mode of delivery. Conclusion: ACT is feasible, acceptable, and probably effective in AUD.

Zuranolone, a neuroactive drug, used in the treatment of postpartum depression by modulation of GABAA receptors.

BACKGROUND: Postpartum depression [PPD] is a prevalent and debilitating mood disorder that affects mothers in the weeks to months after childbirth. Zuranolone (Zurzuvae) is a novel pharmaceutical agent that was approved by the US FDA on 4 August 2023 for the management of PPD. This review article provides a comprehensive overview of zuranolone, focusing on its dosing, chemistry, mechanism of action, clinical trials, adverse drug reaction, and overall conclusion regarding its utility in the management of PPD. It also discusses the recommended dosing strategies to achieve optimal efficacy while minimizing adverse effects as the dosage regimen of zuranolone is critical for its therapeutic application. Moreover, it gives insights into neurobiological pathways involved in PPD. METHODOLOGY: Data from randomized controlled trials and observational studies was collected to provide a comprehensive understanding of zuranolone in the management and treatment of PPD. CONCLUSION: Zuranolone represents a promising therapeutic option for women suffering from postpartum depression. However, ongoing research and post-marketing surveillance are essential to further elucidate its long-term safety and efficacy. The integration of zuranolone into clinical practice may significantly improve the quality of life for mothers facing the challenges of postpartum depression.

Newborns with congenital complete heart block: Advice for perinatal care providers.

Congenital complete heart block (CCHB) is a rare, but a potentially life-threatening manifestation of autoimmune diseases in neonates. Bradycardia in CCHB can be misdiagnosed as foetal distress in utero and thus precipitating a Caesarean section. We report a case series of three neonates with bradycardia without any electrolyte abnormalities and structurally normal hearts with favourable outcomes.

Kisspeptin stimulates oestradiol biosynthesis by upregulating steroidogenic transcripts and proliferation markers in the bubaline granulosa cells in vitro.

Kisspeptin (Kp), an upstream regulator of GnRH release, is essential for the development and function of reproductive axis. Previously, we demonstrated the localization of Kp and its receptor (Kiss1r) in the active follicle in the bubaline ovary. Present study aimed to determine the effect of Kp on granulosa cell (GCs) functions, especially oestradiol (E2 ) and progesterone (P4 ) production, and differential expression of genes regulating the proliferation, apoptosis and steroidogenesis in the buffalo. The ovaries with 6-10 mm size follicles obtained from the cyclic buffaloes after slaughtering were used for isolation of GCs for in vitro study. The primary GCs culture was treated with Kp (0, 10, 50 and 100 nM) and incubated for 48 h. Production of E2 and P4 was estimated in the culture supernatant by ELISA. The expression of gonadotropin receptors (FSHR and LHR), steroidogenic genes (STAR, 3ß-HSD, CYP19A1), proliferation marker (PCNA), apoptotic factors (CASP3 and BCL2) and Kp signalling molecule (extracellular signal-regulated kinase 1/2, ERK1/2 and p-ERK1/2) was studied in the GCs by qPCR. Significant E2 production was found in the Kp 50 and 100 nM groups (p < .05), whereas P4 production was reduced in Kp 100 nM group (p < .05). There was concomitant upregulation of FSHR, ERK1/2, STAR and CYP19A1 in the Kp 100 nM treated GCs. In addition, Kp at 100 nM stimulated the proliferation of GCs by upregulating the expression of BCL2 (5.0 fold) and PCNA (94.9 fold). Further, high immunoreactivity of p-ERK1/2 was observed in the Kp-treated GCs. It was concluded that Kp at 100 nM concentration stimulated E2 production by upregulating the steroidogenic pathway through ERK1/2, STAR and CYP19A1 and modulating PCNA and BCL2 expressions in the GCs. Further experiments are warranted using Kp antagonist in different combinations to establish the signalling pathway in Kp-mediated steroidogenesis in the GCs for developing strategies to control ovarian functions.

Atomic Dynamics of Multi-Interfacial Migration and Transformations.

Redox-induced interconversions of metal oxidation states typically result in multiple phase boundaries that separate chemically and structurally distinct oxides and suboxides. Directly probing such multi-interfacial reactions is challenging because of the difficulty in simultaneously resolving the multiple reaction fronts at the atomic scale. Using the example of CuO reduction in H2 gas, a reaction pathway of CuO → monoclinic m-Cu4 O3 → Cu2 O is demonstrated and identifies interfacial reaction fronts at the atomic scale, where the Cu2 O/m-Cu4 O3 interface shows a diffuse-type interfacial transformation; while the lateral flow of interfacial ledges appears to control the m-Cu4 O3 /CuO transformation. Together with atomistic modeling, it is shown that such a multi-interface transformation results from the surface-reaction-induced formation of oxygen vacancies that diffuse into deeper atomic layers, thereby resulting in the formation of the lower oxides of Cu2 O and m-Cu4 O3 , and activate the interfacial transformations. These results demonstrate the lively dynamics at the reaction fronts of the multiple interfaces and have substantial implications for controlling the microstructure and interphase boundaries by coupling the interplay between the surface reaction dynamics and the resulting mass transport and phase evolution in the subsurface and bulk.

Perspective and prospects of in situ transmission/scanning transmission electron microscopy.

In situ transmission/scanning transmission electron microscopy (TEM/STEM) measurements have taken a central stage for establishing structure-chemistry-property relationship over the past couple of decades. The challenges for realizing 'a lab-in-gap', i.e. gap between the objective lens pole pieces, or 'a lab-on-chip', to be used to carry out experiments are being met through continuous instrumental developments. Commercially available TEM columns and sample holder, that have been modified for in situ experimentation, have contributed to uncover structural and chemical changes occurring in the sample when subjected to external stimulus such as temperature, pressure, radiation (photon, ions and electrons), environment (gas, liquid and magnetic or electrical field) or a combination thereof. Whereas atomic resolution images and spectroscopy data are being collected routinely using TEM/STEM, temporal resolution is limited to millisecond. On the other hand, better than femtosecond temporal resolution can be achieved using an ultrafast electron microscopy or dynamic TEM, but the spatial resolution is limited to sub-nanometers. In either case, in situ experiments generate large datasets that need to be transferred, stored and analyzed. The advent of artificial intelligence, especially machine learning platforms, is proving crucial to deal with this big data problem. Further developments are still needed in order to fully exploit our capability to understand, measure and control chemical and/or physical processes. We present the current state of instrumental and computational capabilities and discuss future possibilities.

Exploring the mechanisms and impacts of melatonin on fish colouration.

The pineal hormone melatonin is a multi-functional molecule with a recognized role in pigment aggregation in chromatophores, mediating its actions through binding to subtypes of its specific receptors. Since its discovery, melatonin has been known to be responsible for pigment aggregation towards the cell centre in fishes, including their embryos, as an adaptation to reduced light and thus results in pale body colouration. Diversity exists in the sensitivity of melanophores towards melatonin at interspecies, intraspecific levels, seasons, and amongst chromatophores at different regions of the animal body. In most of the fishes, melatonin leads to their skin paling at night. It is indicated that the melatonin receptors have characteristically maintained to show the same aggregating effects in fishes and other vertebrates in the evolutionary hierarchy. However, besides this aggregatory effect, melatonin is also responsible for pigment dispersion in certain fishes. Here is the demand in our review to explore further the nature of the dispersive behaviour of melatonin through the so-called ß-melatonin receptors. It is clear that the pigment translocations in lower vertebrates under the effect of melatonin are mediated through the melatonin receptors coupled with other hormonal receptors as well. Therefore, being richly supplied with a variety of receptors, chromatophores and melanocytes can be used as in vitro test models for pharmacological applications of known and novel drugs. In this review, we present diverse effects of melatonin on chromatophores of fishes in particular with appropriate implications on most of the recent findings.

Infiltrating duct cell carcinoma in lactating adenoma: A rare case in pair.

Lactating adenomas, though considered being benign, sometimes turn out to be malignant. We are hereby presenting two cases of lactating adenomas which turned out to be harboring infiltrating duct cell carcinoma (DCC). Two lactating women with mass in the breast were referred from surgery for fine-needle aspiration cytology and biopsy. On histopathology, it was found that both had infiltrating DCC (either as collision tumor or as a malignant transformation of lactating adenoma). These cases point toward some association between lactating adenoma and DCC, however, small it may be. Therefore, any mass lesion in the breast should be followed up under strict vigilance for an early diagnosis and management of this deadly disease. A large sample size and elaborate study are required to frame its prognostic relevance. Like estrogen receptor and progesterone receptor, prolactin and prolactin receptor expression can be exploited for developing newer receptor-targeted therapy.

Evaluation of sexed semen-based artificial insemination in Tharparkar cattle under organized farm condition.

Sexed semen facilitates additional female calf production for the expansion of a herd at a faster rate and also curtails the surplus production of unwanted male calves. A study was conducted to evaluate the performance of sexed semen in indigenous Tharparkar cows based on 114 artificial inseminations (AI) performed at natural oestrus using two protocols i.e., single AI (n = 48) and double AI (n = 66). Overall, the first service conception rate (CR) was significantly higher in double (53.0%) than single (33.3%) AI protocol. The odds ratio of conception rate in double AI was 2.26 (χ2 = 4.4, df = 1, p = .04) with respect to single AI. The time that elapsed since the detection of oestrus to insemination was also analysed. In a single AI protocol, the CR was higher (p < .05) at 16 h (54.6%) than insemination at 8 h (27.0%) following the onset of oestrus. Yet, the CR using double AI protocol did not differ (p = .73) significantly when AIs were performed either at 8 h and 24 h (51.9%) or 16 h and 24 h (57.1%) post onset of oestrus. Besides, like the single AI protocol, the parity of the animals also influenced the CR, being higher in heifers (n = 22) than those of parous (n = 92) cows (72.73 vs. 40.43%, χ2 = 7.48, df = 1, p = .006) in the present study. The odds ratio of conception in heifers was 3.93 with respect to parous cows. Overall, the birth of female calf was 91.7%. In conclusion, the present study indicates a future promise of the sexed semen for the production of more female offspring from Tharparkar cattle.

Evolutionary Dynamics of FLC-like MADS-Box Genes in Brassicaceae.

MADS-box genes encode transcription factors that play important roles in the development and evolution of plants. There are more than a dozen clades of MADS-box genes in angiosperms, of which those with functions in the specification of floral organ identity are especially well-known. From what has been elucidated in the model plant Arabidopsis thaliana, the clade of FLC-like MADS-box genes, comprising FLC-like genes sensu strictu and MAF-like genes, are somewhat special among the MADS-box genes of plants since FLC-like genes, especially MAF-like genes, show unusual evolutionary dynamics, in that they generate clusters of tandemly duplicated genes. Here, we make use of the latest genomic data of Brassicaceae to study this remarkable feature of the FLC-like genes in a phylogenetic context. We have identified all FLC-like genes in the genomes of 29 species of Brassicaceae and reconstructed the phylogeny of these genes employing a Maximum Likelihood method. In addition, we conducted selection analyses using PAML. Our results reveal that there are three major clades of FLC-like genes in Brassicaceae that all evolve under purifying selection but with remarkably different strengths. We confirm that the tandem arrangement of MAF-like genes in the genomes of Brassicaceae resulted in a high rate of duplications and losses. Interestingly, MAF-like genes also seem to be prone to transposition. Considering the role of FLC-like genes sensu lato (s.l.) in the timing of floral transition, we hypothesize that this rapid evolution of the MAF-like genes was a main contributor to the successful adaptation of Brassicaceae to different environments.

Secretory leucocyte protease inhibitor (SLPI) as an adjunct prognostic biomarker for canine pyometra.

Pyometra is a potentially life-threatening condition that affects intact female dogs in their middle to advance age. Timely diagnosis and appropriate treatment are critical for the survival of patients, especially when pyometra advances to sepsis. This study aimed to investigate the prognostic potential of certain haematology, serum biochemical and inflammatory biomarker, secretory leucocyte protease inhibitor (SLPI) for pyometra in bitches (n = 41). Blood samples were collected after clinical diagnosis of pyometra for haematology and serum biochemistry. Based on the prognosis following medical/surgical treatment, animals were retrospectively categorized into survivor (n = 29) and dead (n = 12). Endometrial tissue sections were obtained from the bitches undergoing ovariohysterectomy (n = 21). Serum concentration of SLPI was quantified using sandwich ELISA and its expression in the endometrium was investigated using RT-qPCR. A marked increase in the total leucocyte count (TLC), neutrophils, blood urea nitrogen (BUN) and serum creatinine was observed in the female dogs that did not survive. Significant elevation in the serum SLPI concentration (3.49 ± 0.44 vs. 2.38 ± 0.13 ng/mL) was observed in the bitches those died after the treatment, in comparison to those survived (p < .01). Additionally, there was a notable upregulation of SLPI in the endometrium in the bitches those died due to pyometra. Based on the ROC analysis results, it was observed that a cut-off concentration of 2.93 ng/mL for SLPI, 27.77 mg/dL for BUN and 16.3 × 103 /µL for TLC could effectively distinguish the prognosis of pyometra-affected dogs. From this study, it can be concluded that upregulation of SLPI in the endometrium and its elevated concentration in peripheral circulation along with TLC and BUN concentration could serve as valuable indicators for predicting the prognosis of pyometra in bitches.

Effective corrosion inhibition of mild steel using novel 1,3,4-oxadiazole-pyridine hybrids: Synthesis, electrochemical, morphological, and computational insights.

An easy synthesis of two 1,3,4-oxadiazole derivatives, namely, 2-phenyl-5-(pyridin-3-yl)-1,3,4-oxadiazole (POX) and 2-(4-methoxyphenyl)-5-(pyridin-3-yl)-1,3,4-oxadiazole (4-PMOX), and their corrosion-inhibition efficacy against mild steel corrosion in 1 N HCl, is evaluated using weight loss from 303 to 323 K, Electrochemical Impedance Spectroscopy (EIS), Potentiodynamic Polarization (PDP), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray (EDX), UV-Vis spectroscopy, along with theoretical evaluation. Both POX and 4-PMOX exhibit excellent inhibition efficiency, with values reaching 97.83% and 98% at 500 ppm, respectively. The PDP analysis reveals that both derivatives act as mixed-type inhibitors. The Langmuir adsorption isotherm provides insights into the adsorption phenomena, demonstrating that 4-PMOX exhibits superior adsorption behavior on the mild steel surface compared to POX. This finding is further supported by SEM, DFT, RDF, and MSD analyses. Quantum mechanical parameters, including EHOMO, ELUMO, dipole moment (µ), energy gap (ΔE), etc., are in good agreement with the effectiveness of inhibition performance revealing ΔE values of 3.10 and 2.75 for POX and 4-PMOX, respectively. The results obtained from this study hold significant implications for researchers aiming to design more efficient organic inhibitors to combat metal corrosion.

Therapeutic Benefits of Melatonin against COVID-19.

The assumption of the pineal hormone melatonin as a therapeutic use for COVID-19-affected people seems promising. Its intake has shown significant improvement in the patients' conditions. Higher melatonin titers in children may provide a protective shield against this disease. The hormone melatonin works as an anti-inflammatory, antioxidant, immunomodulator, and strategically slows down the cytokine release which is observed in the COVID-19 disease, thereby improving the overall health of afflicted patients. The medical community is expected shortly to use remedial attributes like anti-inflammatory, antioxidant, antivirals, etc., of melatonin in the successful prevention and cure of COVID-19 morbidity. Thus, the administration of melatonin seems auspicious in the cure and prevention of this COVID-19 fatality. Moreover, melatonin does not seem to reduce the efficiency of approved vaccines against the SARS-CoV-2 virus. Melatonin increases the production of inflammatory cytokines and Th1 and enhances both humoral and cell-mediated responses. Through the enhanced humoral immunity, melatonin exhibits antiviral activities by suppressing multiple inflammatory products such as IL-6, IL1ß, and tumor necrosis factor α, which are immediately released during lung injury of severe COVID-19. Hence, the novel use of melatonin along with other antivirals as an early treatment option against COVID-19 infection is suggested. Here, we have chalked out the invasion mechanisms and appropriate implications of the latest findings concerned with melatonin against the virus SARS-CoV-2. Nevertheless, within the setting of a clinical intervention, the promising compounds must go through a series of studies before their recommendation. In the clinical field, this is done in a time-ordered sequence, in line with the phase label affixed to proper protocol of trials: phase I-phase II and the final phase III. Nevertheless, while medical recommendations can only be made on the basis of reassuring evidence, there are still three issues worth considering before implementation: representativeness, validity, and lastly generalizability.

Recent Advancement in Multicomponent Synthesis of Fused Coumarin Derivatives.

The synthesis of coumarin derivatives has been an essential topic since its discovery in 1820. In bioactive compounds, the coumarin moiety serves as a backbone, as many such bioactive compounds with the coumarin moiety play a significant role in their bioactivities. Given this moiety's relevance, several researchers are developing fused-coumarin derivatives to create new drugs. Mostly the approach done for this purpose was a multicomponent reaction based. Over the years, the multicomponent reaction has gained enormous popularity, and this approach has evolved as a replacement for conventional synthetic methods. Because of all these perspectives, we have reported the various fused-coumarin derivatives synthesized using multicomponent reactions in recent years.

Antibacterial and antioxidant assay of novel heteroaryl-substituted methane derivatives synthesized via ceric ammonium nitrate (CAN) catalyzed one-pot green approach.

Individually, hydroxycoumarin and amino pyrimidine derivatives are of significant biological interest owing to their importance in drugs and pharmaceuticals. To access their combined biological impact into one molecule, we designed a novel, one-pot green approach for synthesizing trisubstituted methanes. A series of new heteroaryl-substituted methanes have been synthesized and subjected to in vitro antibacterial and antioxidant evaluation. Tests against clinical isolates of Escherichia coli (gram-negative) and Staphylococcus aureus showed potent activity of the derivatives 4a, 4b, 4d, 4e, 4f, 4l, and 5 against the former, and 4a, 4e, 4j, and 4l against the later one. Further, antioxidant assay for these TRSMs was also studied where 4a, 4b, 4f, 4j, and 4l exhibited the most promising results. These preliminary bioassay evaluations strongly suggest the promise and scope of these molecules in medical science. A one pot methodology for the synthesis of coumarin and uracil tethered trisubstituted methanes has been reported. The synthesized derivatives were further analyzed for their antibacterial and antioxidant properties to explore their medicinal applications. The salient features of this methodology are operational simplicity, short reaction time, good to moderate yields of the products, easy purification method. Biochemical assay of the synthesized TRSMs a reveals their utility in medicinal & pharma industry.

Adverse Childhood Experiences, Aggression, Empathy, and Psychopathology in Adult Males Accused of Rape.

Background: Investigating the underlying psychosocial factors is a cornerstone of planning need-based intervention for adult males accused of rape. Unresolved debates on its etiology, mediation, or interaction among causal psychosocial variables fuel curiosity to scrutinize it further. Hence, we studied potential influence of and relation between adverse childhood experiences, aggression, empathy, and psychopathology in adult males accused of rape in India and investigated the risk factors for the same. Methods: With a correlational research design, 40 literate and consenting adult males medically confirmed for rape were recruited using convenient sampling. The assessment was done on Adverse Childhood Experiences, Aggression Questionnaire, Symptom Checklist-90, and Interpersonal Reactivity Index. Descriptive statistics, Pearson's product-moment correlation, and stepwise linear regression analysis were calculated. Results: Approximately 75% of the participants experienced at least one category of Adverse Childhood Experiences. Scores above cut-off points were obtained on anger, hostility, fantasy, and personal distress. Significant correlations were obtained between adverse childhood experiences and psychopathology; between hostility and psychopathology, perspective taking, and personal distress; and in case of indirect aggression, with perspective taking and empathetic concerns. Regression analysis revealed that an increase in Symptom Checklist-90 global scores increases hostility and that lower personal distress predicts higher scores on hostility on Aggression Questionnaire. Conclusions: Adverse childhood experiences, aggression, and psychopathology play a critical role and, therefore, should be included as core components of the prevention of rape or relapse prevention programs at the community level.

A comprehensive yoga programme for weight reduction in children & adolescents with obesity: A randomized controlled trial.

Background & objectives: Obesity is a rising pandemic in childhood. There is scarcity of evidence on the efficacy of yoga in achieving weight loss in overweight/obese children. The objective of this study was to assess the efficacy of family-based comprehensive yoga intervention in the reduction of body mass index (BMI) in overweight/obese children, in comparison to standard dietary and lifestyle counselling and control group. Methods: This was an open-label randomized controlled study. Children aged 8-15 yr who were overweight or had obesity were randomized to one of the three arms for 18 wk; standard weight management (group 1), yoga with dietary modification (group 2) and control (no intervention; group 3). Reduction in BMI and improvement in physiological, biochemical and psychological parameters from baseline to 18 wk was compared between the three arms. Late follow up was also done at 6-12 months. Results: A total of 165 children with mean±standard deviation (SD) age of 11.6±1.8 yr and mean BMI 26.3±4.2 kg/m2 were enrolled. Outcome analysis at 18 wk was performed for 109 children. Improved diet quality and reduced intake were observed in both intervention arms. The median (IQR) reduction in BMI in standard and yoga arms was similar [-1.4 (-3.1, -0.5) kg/m2 and -1.2 (-2.3, -0.6) kg/m2, respectively], while it increased by +0.3 (-0.3, 0.1) in the control arm. In the yoga arm, mean systolic BP reduced from 118 (10) to 114 (8) mmHg, (P=0.019). In the standard arm, significant improvement in psychological scores was noted. In group 3, the mean fasting glucose increased from 93±10 to 102±12 mg/dl (P<0.001). Interpretation & conclusions: The findings of the present study suggest that yoga in conjunction with dietary modification is equally effective as the standard weight management for BMI reduction in the paediatric age group.

Reducing Perinatal Mortality in India: Two-Years Results of the IRIA Fetal Radiology Samrakshan Program.

Aim The aim of the study is to determine improvements in perinatal mortality at the end of the first 2 years from the initiation of the Samrakshan program of the Indian Radiological and Imaging Association. Methods Samrakshan is a screening program of pregnant women that uses trimester-specific risk assessment protocols including maternal demographics, mean arterial pressure, and fetal Doppler studies to classify women as high risk or low risk for preterm preeclampsia (PE) and fetal growth restriction (FGR). Low dose aspirin 150 mg daily once at bedtime was started for pregnant women identified as high risk in the 11-13 6/7 weeks screening. The third-trimester screening focused on the staging of FGR and protocol-based management for childbirth and risk assessment for PE. Outcomes of childbirth including gestational age at delivery, development of PE, and perinatal mortality outcomes were collected. Results Radiologists from 38 districts of 16 states of India participated in the Samrakshan program that screened 2,816 first trimester, 3,267 second trimester, and 3,272 third trimester pregnant women, respectively. At 2 years, preterm PE was identified in 2.76%, preterm births in 19.28%, abnormal Doppler study in 25.76% of third trimester pregnancies, and 75.32% of stage 1 FGR delivered at term. The neonatal mortality rate was 9.86/1,000 live births, perinatal mortality rate was 18.97/1,000 childbirths, and maternal mortality was 58/100,000 live births compared with 29.5, 36, and 113, respectively in 2016. Conclusion Fetal Doppler integrated antenatal ultrasound studies in Samrakshan led to a significant reduction in preterm PE rates, preterm birth rates, and a significant improvement in mean birth weights. Perinatal, neonatal, and maternal mortality rates are significantly better than the targets for 2030 set by the Sustainable Development Goals-3.