A Single-Center Study on Clinico-Radiological Evaluation of Inguino-Scrotal or Labial Swellings Presenting to a Tertiary Care Set-Up in Central India.

Introduction The inguino-scrotal/labial region, anatomically defined as the juncture where the thigh meets the lower abdomen, encompassing the ipsilateral scrotal area in men and the inguino-labial area in women, exhibits a broad spectrum of masses. Traditionally, these swellings were clinically diagnosed with high accuracy, primarily due to the prevalence of simple hernias and hydroceles. However, contemporary observations reveal a surge in complex inguino-scrotal/labial swellings, particularly in referral hospitals, necessitating additional radiological and imaging modalities for precise diagnosis. Our interest in this subject was sparked by the escalating numbers of intricate inguino-scrotal/labial masses encountered in our medical setting, posing challenges for clinical diagnosis in both pediatric and adult populations. Materials and methods A prospective, observational study was conducted over two years (August 2021 to March 2023) involving 210 patients presenting with inguino-scrotal/labial swellings at our institute. Clinical data were meticulously collected using a designed pro forma, following informed consent procedures. Results Among the 210 patients with inguino-scrotal/labial swellings, males predominated (194) compared to females (16). The paediatric age group comprised 84 patients, while 126 were adults. Radiological investigations played a crucial role in diagnosing 40 patients and provided significant additional information in 12 cases. Radiological investigations contributed to the diagnosis in 52 patients (24.76%). The study revealed a spectrum of new entities in the inguino-scrotal/labial region, including malignancies, lymph nodal masses in the groin, and vascular, inflammatory, and congenital lesions, which might have been overlooked if solely relying on clinical parameters for diagnosis. Conclusion Inguino-scrotal/labial swelling patients, especially those facing diagnostic dilemmas or harbouring complex lesions, should undergo radiological assessment as an indispensable criterion, particularly when such facilities are readily accessible.

Optimization and characterization of hybrid bio-briquettes produced from the mixture of sawdust, sugarcane bagasse, and paddy straw.

Biomass briquetting is a viable densification technique that converts waste biomass materials into useful products and alternative energy. This work explores the characteristics and optimization of hybrid bio-briquette production by combining crop residues (paddy straw) and solid biomass materials (sawdust and sugarcane bagasse). A total number of 20 briquettes were fabricated with three input factors: sawdust (SD), sugarcane bagasse (SB), and paddy straw (PS) based on the faced-centered central composite design (FCCCD) approach in the laboratory to investigate the calorific value (CV) and ash content (AC). The bomb calorimeter technique was used to evaluate the briquette's calorific value and ash content. The proposed work focused on optimizing the briquette input parameters (SD, SB, and PS) and output responses (CV and AC) using analysis of variance (ANOVA) and response surface methodology (RSM) and hybrid artificial neural network-integrated with multi-objective genetic algorithms (ANN-MOGA). This study shows that the MOGA-ANN-based model results in the best value of CV (17.07 MJ/kg) and AC (1.95%) with optimal input parameters SD (39.99 g), SB (29.02 g), and PS (69.02 g). The optimal results observed from the MOGA-ANN model have also been validated experimentally. The Fourier transform infrared (FTIR) spectroscopy investigation reveals that biomass briquettes are the sustainable and environment-friendly option of fossil fuels for power generation and indoor cooking. The study suggests a strategy for minimizing agro-waste, which may be converted into future fuel in the form of briquettes.

Synthesis, characterization, biological activity and computation-based efficacy of cobalt(II) complexes of biphenyl-2-ol against SARS-CoV-2 virus.

Cobalt(II) complexes of biphenyl-2-ol of composition, CoCl2-n(OC6H4C6H5-2)n(H2O)4 (where n = 1 or 2), were prepared by reacting cobaltous(II) chloride with equi- and bimolar ratios of sodium salt of biphenyl-2-ol. The structural characterization of the synthesized complexes was accomplished by NMR, FTIR, thermogravimetry (TGA), high resolution mass spectroscopy (HRMS), electronic spectroscopic techniques coupled with density functional theory (DFT). The stability of the complexes in different pH media of solvent was studied. Chemical reactivity parameters of the newly synthesized complexes, computed using DFT, indicated greater reactivity of complex 2 over complex 1 and free ligand as indicated by its low HOMO-LUMO energy gap corresponding to 1.71 eV. Molecular docking (MD) studies were carried out in order to study the binding affinities between amino acid residues of DNA duplex (PDB ID: 1BNA) and SARS-CoV-2 (PDB ID: 7T9K) with newly synthesized complexes. Complex 2 has shown promising antivirus behaviour with an inhibition constant value of 0.0423 µmol-1 with amino acid residues of SARS-CoV-2 virus. Toxicity of the complexes was predicted using ProTox-II online server. Antibacterial studies have indicated the complexes to exhibit greater efficacy than the free ligand, while the antioxidant activities have suggested them to display enhanced antioxidant behaviour as compared to reference compounds.Communicated by Ramaswamy H. Sarma.

Partnership status and positive DNA methylation age acceleration across the adult lifespan in the UK.

Although a significant body of research has shown that married people are healthier and live longer, empirical research on sex differences in the link between marital status and health suggests results are mixed. Moreover, the sex disparities in marital status and health relationships vary across adulthood. The literature on partnership status and measures of ageing is largely focused on older age groups and is limited in its view of early adulthood. Data from waves 2 and 3 (2010-2012) of Understanding Society: UKHLS were used to examine the association of current partnership status with epigenetic age acceleration (AA) assessed with DNA methylation (DNAm) algorithms 'Phenoage' and ' DunedinPACE ' in 3492 participants (aged 16-97). Regression models were estimated separately for men and women, and further stratified by age groups. Divorced/separated and widowed people showed positive age acceleration compared to the married/cohabiting people (reference group). Some sex differences were apparent, especially, among the single and divorced/separated groups. Age differences were also apparent, for example in men, being single was negatively associated with DNAmAA in the youngest group, but positively in the oldest group compared to partnered counterparts. These findings illustrate the importance of partnerships on the ageing process, in particular marital change through divorce and widowhood for positive age acceleration in adults. For single groups, observations were heterogenous by age and sex.

Are housing circumstances associated with faster epigenetic ageing?

BACKGROUND: Numerous aspects of housing are associated with health. However, the pathways between housing and health, particularly the psychosocial elements of housing, are less well understood. Epigenetic information alongside social survey data offers an opportunity to explore biological ageing, measured using DNA methylation, as a potential pathway through which housing affects health. METHODS: We use data on housing and DNA methylation from the UK Household Longitudinal Study, linked with prior survey responses from the British Household Panel Survey, covering adults in Great Britain. We explore the association between epigenetic ageing and housing circumstances, both contemporary and historical, using hierarchical regression. RESULTS: We find that living in a privately rented home is related to faster biological ageing. Importantly, the impact of private renting (coefficient (SE) 0.046 years (0.011) vs owned outright, p<0.001) is greater than the impact of experiencing unemployment (coefficient 0.027 years (0.012) vs employed, p<0.05) or being a former smoker (coefficient 0.021 years (0.005) vs never smoker, p<0.001). When we include historical housing circumstances in the analysis, we find that repeated housing arrears and exposure to pollution/environmental problems are also associated with faster biological ageing. CONCLUSION: Our results suggest that challenging housing circumstances negatively affect health through faster biological ageing. However, biological ageing is reversible, highlighting the significant potential for housing policy changes to improve health.

Comparison of success rate of abducted and neutral arm position for right infraclavicular subclavian vein cannulation under real-time ultrasound guidance in patients undergoing elective neurosurgery under general anesthesia.

Background: Classically subclavian vein catheterization is done in neutral arm position; recently, it has been done in different arm positions to compare success rate and catheter misplacement. There is a paucity of literature for comparing abducted and neutral arm position for right infraclavicular subclavian vein cannulation. Aim: Comparison of success rate of abducted and neutral arm position for right infraclavicular subclavian vein cannulation under real-time ultrasound guidance in patients undergoing elective neurosurgery under general anesthesia. Design: Randomized comparative study. Materials and Methods: After approval from Institutional Review Board and Ethical Committee, 100 patients of 18-70 years of age, of either sex, posted for elective neurosurgery under general anesthesia, requiring right subclavian vein cannulation were included in our study. They were randomly divided into two groups: abducted arm position (group 1-AG) and neutral arm position (group 2-NG) using sealed envelope technique. Results: First attempt success rate was higher in AG group compared to NG group (P value- 0.741). Times taken (seconds) for cannulation in NG and AG group, catheter misplacement and hematoma (P value- 0.37, P value- 0.37, P value- 1, respectively) were lesser in AG Group. Conclusion: For USG-guided infraclavicular subclavian vein cannulation, abducted arm position, and neutral arm position in terms of first attempt success rate, number of attempts and associated complications has comparable results; however, further studies with larger group of patients are required to assess the overall advantage of abducted arm position over neutral arm position.

Theoretical insights into the structural, optoelectronic, thermoelectric, and thermodynamic behavior of novel quaternary LiZrCoX (X = Ge, Sn) compounds based on first-principles study.

The structural, magnetic, electronic, elastic, vibrational, optical, thermodynamic as well as thermoelectric properties of newly predicted quaternary LiZrCoX (X = Ge, Sn) Heusler compounds are evaluated intricately with the aid of ab initio techniques developed under the framework of density functional theory. The computed structural properties are found to be in tandem with the existing analogous theoretical and experimental facts. Structural optimization has been carried out in three different structural arrangements, i.e., Type-1, Type-2, and Type-3. Further analysis of the optimization curves reveals that the Type-3 phase, which has the least amount of energy, is the most stable structure for the compounds under consideration. The tabulated cohesive energy and formation energy of these compounds depict their chemical as well as thermodynamic stability. The absence of negative phonon frequencies in the phonon band spectrum of the studied compounds depicts their dynamic stability. Similarly, the tabulated second-order elastic constants (Cij) and the linked elastic moduli show their stability in the cubic phase. The calculated value of Pugh's ratio and Cauchy pressure reveal that LiZrCoGe is brittle whereas LiZrCoSn is ductile. Additionally, the optical characteristics of the compounds are studied in terms of the dielectric function, refractive index, extinction coefficient, absorption coefficient, reflectivity, energy loss function, and optical conductivity. The obtained high value of power factor and figure of merit of the studied lithium-based quaternary compounds predict good thermoelectric behavior in these compounds. Thus, LiZrCoX (X = Ge, Sn) compounds can therefore be used to create innovative and intriguing thermoelectric materials as well as optoelectronic and energy-harvesting equipment.

Unlocking the Potential of Immunotherapy in Cardiovascular Disease: A Comprehensive Review of Applications and Future Directions.

Immunotherapy has emerged as a pioneering therapeutic approach that harnesses the immune system's abilities to combat diseases, particularly in the field of oncology where it has led to significant advancements. However, despite its significant impact in the field of oncology, the potential of immunotherapy in the context of cardiovascular disease (CVD) has not been thoroughly investigated. The purpose of this narrative review is to address the existing knowledge and potential uses of immunotherapy in the field of cardiovascular disease (CVD), with the intention of filling the existing gap in understanding. Furthermore, the review thoroughly examines the future prospects of this swiftly advancing field, providing insights into the aspects that necessitate further investigation and addressing the forthcoming challenges. The review is organized into four distinct sections to enhance comprehension. The first section introduces immunotherapy, presenting the fundamental concepts and principles. The second section explores the immunomodulatory mechanisms in cardiovascular disease (CVD), with a specific focus on the intricate interplay between the immune system and the development of cardiovascular pathogenesis. The utilization of immunotherapy in specific cardiovascular conditions will be examined, investigating the application of immunotherapy in the context of different cardiovascular diseases. The future prospects and challenges in immunotherapy for cardiovascular diseases will be discussed, highlighting the potential areas for future research and addressing the barriers that must be overcome to effectively implement immunotherapeutic interventions in the management of cardiovascular diseases.

Triangulating evidence from observational and Mendelian randomization studies of ketone bodies for cognitive performance.

BACKGROUND: Ketone bodies (KBs) are an alternative energy supply for brain functions when glucose is limited. The most abundant ketone metabolite, 3-ß-hydroxybutyrate (BOHBUT), has been suggested to prevent or delay cognitive impairment, but the evidence remains unclear. We triangulated observational and Mendelian randomization (MR) studies to investigate the association and causation between KBs and cognitive function. METHODS: In observational analyses of 5506 participants aged ≥ 45 years from the Whitehall II study, we used multiple linear regression to investigate the associations between categorized KBs and cognitive function scores. Two-sample MR was carried out using summary statistics from an in-house KBs meta-analysis between the University College London-London School of Hygiene and Tropical Medicine-Edinburgh-Bristol (UCLEB) Consortium and Kettunen et al. (N = 45,031), and publicly available summary statistics of cognitive performance and Alzheimer's disease (AD) from the Social Science Genetic Association Consortium (N = 257,841), and the International Genomics of Alzheimer's Project (N = 54,162), respectively. Both strong (P < 5 × 10-8) and suggestive (P < 1 × 10-5) sets of instrumental variables for BOHBUT were applied. Finally, we performed cis-MR on OXCT1, a well-known gene for KB catabolism. RESULTS: BOHBUT was positively associated with general cognitive function (ß = 0.26, P = 9.74 × 10-3). In MR analyses, we observed a protective effect of BOHBUT on cognitive performance (inverse variance weighted: ßIVW = 7.89 × 10-2, PIVW = 1.03 × 10-2; weighted median: ßW-Median = 8.65 × 10-2, PW-Median = 9.60 × 10-3) and a protective effect on AD (ßIVW = - 0.31, odds ratio: OR = 0.74, PIVW = 3.06 × 10-2). Cis-MR showed little evidence of therapeutic modulation of OXCT1 on cognitive impairment. CONCLUSIONS: Triangulation of evidence suggests that BOHBUT has a beneficial effect on cognitive performance. Our findings raise the hypothesis that increased BOHBUT may improve general cognitive functions, delaying cognitive impairment and reducing the risk of AD.

A randomised study of nurse collected venous blood and self-collected dried blood spots for the assessment of cardiovascular risk factors in the Understanding Society Innovation Panel.

Dried blood spot (DBS) sample collection has been suggested as a less invasive, cheaper and more convenient alternative to venepuncture, which requires trained personnel, making it a potentially viable approach for self-collection of blood on a large scale. We examine whether participants in a longitudinal survey were willing to provide a DBS sample in different interview settings, and how resulting cardiovascular risk biomarkers compared with those from venous blood to calculate clinical risk. Participants of the Understanding Society Innovation Panel, a representative sample of UK households, were randomly assigned to three modes of interview. Most participants (84%) were interviewed in their allocated mode. Participants (n = 2162) were interviewed by a nurse who collected both a blood sample by venepuncture and a DBS card ('nurse collection') or participants were seen by an interviewer or took part in the survey online to self-collect a DBS card ('self-collection'). All DBS cards were returned in the post after the sample had dried. Lipids (total cholesterol, HDL-cholesterol, triglycerides), HbA1c and C-reactive protein were measured in venous and DBS samples and equivalence was calculated. The resultant values were used to confirm equivalent prevalence of risk of cardiovascular disease in each type of blood sample by mode of participation. Of participants interviewed by a nurse 69% consented to venous blood sample and 74% to a DBS sample, while in the self-collection modes, 35% consented to DBS collection. Demographic characteristics of participants in self-collection mode was not different to those in nurse collection mode. The percentage of participants with clinically raised biomarkers did not significantly differ between type of blood collection (for example, 62% had high cholesterol (> 5 mmol/l) measured by venepuncture and 67% had high cholesterol within the self-collected DBS sample (p = 0.13)). While self-collected DBS sampling had a lower response rate to DBS collected by a nurse, participation did not vary by key demographic characteristics. This study demonstrates that DBS collection is a feasible method of sample collection that can provide acceptable measures of clinically relevant biomarkers, enabling the calculation of population levels of cardiovascular disease risk.

Management Dilemma in a Large Fungating Squamous Cell Carcinoma Over a Marjolin's Ulcer on the Chest Wall Coexisting With Severe Post-Burn Contracture of the Neck.

Marjolin's ulcer is a premalignant condition occurring over scars and chronically inflamed tissue. Squamous cell carcinoma is the most common malignancy associated with Marjolin's ulcer. The progression of disease and metastasis is relatively slow due to scarring and meagre lymphatic and vascular supply over these scars. We present a case of a large fungating squamous cell carcinoma in a patent having a burn scar over his chest as well as having post-burn contracture of the neck, posing problems in management due to intubation issues. We managed him unconventionally with serial excision under local anesthesia and skin grafting of the wound.

A case report: Management dilemma in a large fungating squamous cell carcinoma over a Marjolin's ulcer on the chest wall coexisting with severe post burn contracture of the neck.

INTRODUCTION AND IMPORTANCE: Marjolin's ulcer is a premalignant condition occurring over scars and chronically inflamed tissue. Squamous cell carcinoma is the most common malignancy associated with Marjolin's ulcer. These are rare tumors which spread locally and once infiltrating, may lead to distant spread. In our case recurrent bleeding causing severe anaemia and foul smelling discharge, mandated an early resection, the problem in this case was due to his chest condition and severe post-burn neck contracture and he was unfit for general anesthesia. He was subjected to serial local excisions as well as subsequent serial skin grafts. CASE PRESENTATION: We present a case of a large fungating squamous cell carcinoma in a patent having burn scar over his chest as well has having post-burn contracture of the neck, posing problems in management due to intubation issues. DISCUSSION: The progression of disease and metastasis is relatively slow due to scarring and meager lymphatic and vascular supply over these scars. Owing to the complexities and urgency, we managed him unconventionally with serial excision under local anesthesia and skin grafting of the wound. CONCLUSION: Some alterations in management may be a gift of life in such patients is the message through this case.

Does the feedback of blood results in observational studies influence response and consent? A randomised study of the Understanding Society Innovation Panel.

BACKGROUND: While medical studies generally provide health feedback to participants, in observational studies this is not always the case due to logistical and financial difficulties, or concerns about changing observed behaviours. However, evidence suggests that lack of feedback may deter participants from providing biological samples. This paper investigates the effect of offering feedback of blood results on participation in biomeasure sample collection. METHODS: Participants aged 16 and over from a longitudinal study - the Understanding Society Innovation Panel-were randomised to three arms - nurse interviewer, interviewer, web survey - and invited to participate in biomeasures data collection. Within each arm they were randomised to receive feedback of their blood results or not. For those interviewed by a nurse both venous and dried blood samples (DBS) were taken in the interview. For the other two arms, they were asked if they would be willing to take a sample, and if they agreed a DBS kit was left or sent to them so the participant could take their own sample and return it. Blood samples were analysed and, if in the feedback arms, participants were sent their total cholesterol and HbA1c results. Response rates for feedback and non-feedback groups were compared: overall; in each arm of the study; by socio-demographic and health characteristics; and by previous study participation. Logistic regression models of providing a blood sample by feedback group and data collection approach controlling for confounders were calculated. RESULTS: Overall 2162 (80.3% of individuals in responding households) took part in the survey; of those 1053 (48.7%) consented to provide a blood sample. Being offered feedback had little effect on overall participation but did increase consent to provide a blood sample (unadjusted OR 1.38; CI: 1.16-1.64). Controlling for participant characteristics, the effect of feedback was highest among web participants (1.55; 1.11-2.17), followed by interview participants (1.35; 0.99 -1.84) and then nurse interview participants (1.30; 0.89-1.92). CONCLUSIONS: Offering feedback of blood results increased willingness to give samples, especially for those taking part in a web survey.

Effect of the Polypill on Adherence and Prevention of Cardiovascular Diseases in Patients With or at High Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials.

It is important to understand the role of polypills on medication adherence and clinical outcomes in patients with or at high risk of cardiovascular diseases (CVD) to help decision-makers make robust guidelines on using polypills in these people. Therefore, the current meta-analysis was conducted to assess the impact of polypills on medication adherence and clinical outcomes in patients with or at high risk of CVD. The present meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We searched the electronic databases PubMed, Embase, and the Cochrane Library for randomized control trials (RCTs) from inception to January 1, 2023. The outcomes assessed in the present meta-analysis were adherence to prescribed drugs at the study end, the incidence of cardiovascular events, and change in low-density lipoprotein cholesterol (LDL-C), total cholesterol, and high-density lipoprotein (HDL) from baseline to the study end in mmol/l. A total of six studies were included in the present meta-analysis, with a total sample size of 13139 (6577 in the polypill group and 6562 in the control group). Meta-analysis showed that medication adherence was significantly higher in patients receiving polypills compared to the control group (relative risk (RR): 1.38, 95% confidence interval (CI): 1.22-1.56, p-value: 0.001). The risk of a cardiovascular event was significantly lower in the polypill group (RR: 0.72, 95% CI: 0.63-0.82, p-value: 0.001). No significant differences were found in the changes in LDL-C and total cholesterol between the two groups. This meta-analysis shows a significant impact of polypills on medication adherence. We also found that polypills can reduce the incidence of cardiovascular events in patients with or at high risk of CVD. Our study has also shown that regardless of the history of CVD, polypills play an important role in promoting medication adherence in patients with and without a history of CVD.

Exosomes induce neurogenesis of pluripotent P19 cells.

Exosomes play a role in tissue/organ development and differentiation. Retinoic acid induces differentiation of P19 cells (UD-P19) to P19 neurons (P19N) that behave like cortical neurons and express characteristic neuronal genes such as NMDA receptor subunits. Here we report P19N exosome-mediated differentiation of UD-P19 to P19N. Both UD-P19 and P19N released exosomes with characteristic exosome morphology, size, and common protein markers. P19N internalized significantly higher number of Dil-P19N exosomes as compared to UD-P19 with accumulation in the perinuclear region. Continuous exposure of UD-P19 to P19N exosomes for six days induced formation of small-sized embryoid bodies that differentiated into MAP2-/GluN2B-positive neurons recapitulating RA-induction of neurogenesis. Incubation with UD-P19 exosomes for six days did not affect UD-P19. Small RNA-seq identified enrichment of P19N exosomes with pro-neurogenic non-coding RNAs (ncRNAs) such as miR-9, let-7, MALAT1 and depleted with ncRNAs involved in maintenance of stem cell characteristics. UD-P19 exosomes were rich with ncRNAs required for maintenance of stemness. P19N exosomes provide an alternative method to genetic modifications for cellular differentiation of neurons. Our novel findings on exosomes-mediated differentiation of UD-P19 to P19 neurons provide tools to study pathways directing neuron development/differentiation and develop novel therapeutic strategies in neuroscience.

Social mobility across the lifecourse and DNA methylation age acceleration in adults in the UK.

Disadvantaged socio-economic position (SEP) is associated with greater biological age, relative to chronological age, measured by DNA methylation (positive 'age acceleration', AA). Social mobility has been proposed to ameliorate health inequalities. This study aimed to understand the association of social mobility with positive AA. Diagonal reference modelling and ordinary least square regression techniques were applied to explore social mobility and four measures of age acceleration (first-generation: 'Horvath', 'Hannum' and second-generation: 'Phenoage', DunedinPoAm) in n = 3140 participants of the UK Household Longitudinal Study. Disadvantaged SEP in early life is associated with positive AA for three (Hannum, Phenoage and DunedinPoAm) of the four measures examined while the second generation biomarkers are associated with SEP in adulthood (p < 0.01). Social mobility was associated with AA measured with Hannum only such that compared to no mobility, upward mobility was associated with greater age independently of origin and destination SEP. Compared to continuously advantaged groups, downward mobility was associated with positive Phenoage (1.06y [- 0.03, 2.14]) and DunedinPoAm assessed AA (0.96y [0.24, 1.68]). For these two measures, upward mobility was associated with negative AA (Phenoage, - 0.65y [- 1.30, - 0.002]; DunedinPoAm, - 0.96y [- 1.47, - 0.46]) compared to continually disadvantaged groups. While we find some support for three models of lifecourse epidemiology with early life as a sensitive period, SEP across the lifecourse and social mobility for age acceleration measured with DNA methylation, our findings suggest that disadvantaged SEP across the lifecourse is most consistently associated with positive AA.

A decennary update on diverse heterocycles and their intermediates as privileged scaffolds for cathepsin B inhibition.

The identification of x-ray crystal structure of cathepsin B (CTSB) in the early 90's enabled researchers to embark on a journey to understand and demystify its multiple catalytic mechanisms (endopeptidase/carboxypeptidase/peptidyl-dipeptidase) in diverse physiological processes and their switching into one another under different conditions. The engagement of CTSB in different pathological conditions due to its over-expression further highlighted the enhanced research interest around the domain. The occurrence of over-expressed CTSB in various diseases like Alzheimer's, cancer, arthritis, cardiovascular, etc., and the use of CTSB inhibitors for the treatment of these diseases have established its involvement in different pathological conditions. Such an understanding tempted researchers to design, synthesize, and screen diverse classes of compounds against CTSB. This in turn, helped in understanding their interactions with the active sites of the enzyme. Heterocyclic compounds comprise a very rich and broad class of medicinally important compounds that also hold great potential for CTSB inhibition. This review covers the CTSB inhibition potential of various natural and synthetic heterocyclic scaffolds. Researchers working in the fields of molecular modeling, drug design and development, and enzyme inhibitors can benefit significantly from this review.

Density functional theory studies on molecular geometry, spectroscopy, HOMO-LUMO and reactivity descriptors of titanium(IV) and oxidozirconium(IV) complexes of phenylacetohydroxamic acid.

The molecular geometry of new titanium(IV) and oxidozirconium(IV) phenylacetohydroxamate complexes [TiCl2 (L1)2 ] (I) and [ZrO(L1)2 ] (II) (where L1 = Potassium phenylacetohydroxamate = C6 H5 CH2 CONHOK) computed by B3LYP/6-311++G(d,p) method has shown these to be distorted octahedral and square pyramidal, respectively. A comparison of computed characteristic bond lengths (CO, CN, and NO) of complexes with that of free ligand has shown chelation through carbonyl and hydroxamic oxygen atoms (O, O coordination). The TiO/ZrO bond lengths in complexes are suggestive of weak coordination through (carbonyl CO) and strong covalent (hydroxamic NO) bonding of the ligand. The magnitude of ClTiCl bond angle involving two chloride atoms is suggestive of cis-conformation at titanium metal in (I). The thermodynamic parameters Gibbs free energy, enthalpy, entropy, nuclear internal energy, constant volume heat capacity, and internal energy of ligand and complexes have been computed. From the energies of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), the global reactivity descriptors such as ionization potential (IP), electron affinity (EA), chemical potential (µ), hardness (η), softness (S), electronegativity (χ), electrophilicity index (ω), and dipole moment have been calculated. The computed vibrational frequencies, 1 H and 13 C NMR spectra have substantiated the molecular structure of complexes. The thermal behavior of complexes has been studied by thermogravimetric techniques (TGA, DTG, and DTA) in N2 atmosphere has shown complexes are thermally stable.

Trends in Weight Gain Among Breastfed Infants Versus Bottle-Fed Infants at a Tertiary Care Hospital in Karachi, Pakistan.

Background Infants need to be exclusively breastfed up to six months of age, and breastfeeding should be continued up to two years of age along with complementary food. In Pakistan, the majority of newborns are not exclusively breastfed. This study was done to compare weight gain between breastfed infants and non-breastfed infants at a tertiary care hospital in Karachi, Pakistan. Methodology This observational cohort study was conducted at the well-baby clinic and vaccination center of the National Institute of Child Health, Karachi, Pakistan, from January 2021 to December 2021. A total of 360 normal term babies (180 in each group) with age below 11 months on either exclusively breastfeeding or other milk feed were included. Data were collected by the duty senior staff nurse of the well-baby clinic and monitored on daily basis by the researchers. The sociodemographic characteristics of mothers of breastfed and non-breastfed babies and birth weight, length, and BMI Z scores of babies in both groups were compared. Results In a total of 360 babies, there were 192 (53.3%) boys and 168 (46.7%) girls. Overall, the mean maternal age was calculated to be 28.1±6.2 years, ranging between 18 and 37 years. The employment status of mothers (p=0.0117) and monthly income of parents (p=0.0388) were significantly different between groups. The mean weight gain in the exclusively breastfeeding group was 4.0±0.5 kg between the first and fifth visit (final visit) in comparison with 4.5±0.5 kg in the non-breastfeeding group (p<0.0001). Conclusion Non-breastfed babies gained significantly more weight in comparison with exclusively breastfed babies. More multicenter trials involving a large proportion of populations are needed to further verify the findings of the present study.

Evaluation of nanopore sequencing for epigenetic epidemiology: a comparison with DNA methylation microarrays.

Most epigenetic epidemiology to date has utilized microarrays to identify positions in the genome where variation in DNA methylation is associated with environmental exposures or disease. However, these profile less than 3% of DNA methylation sites in the human genome, potentially missing affected loci and preventing the discovery of disrupted biological pathways. Third generation sequencing technologies, including Nanopore sequencing, have the potential to revolutionize the generation of epigenetic data, not only by providing genuine genome-wide coverage but profiling epigenetic modifications direct from native DNA. Here we assess the viability of using Nanopore sequencing for epidemiology by performing a comparison with DNA methylation quantified using the most comprehensive microarray available, the Illumina EPIC array. We implemented a CRISPR-Cas9 targeted sequencing approach in concert with Nanopore sequencing to profile DNA methylation in three genomic regions to attempt to rediscover genomic positions that existing technologies have shown are differentially methylated in tobacco smokers. Using Nanopore sequencing reads, DNA methylation was quantified at 1779 CpGs across three regions, providing a finer resolution of DNA methylation patterns compared to the EPIC array. The correlation of estimated levels of DNA methylation between platforms was high. Furthermore, we identified 12 CpGs where hypomethylation was significantly associated with smoking status, including 10 within the AHRR gene. In summary, Nanopore sequencing is a valid option for identifying genomic loci where large differences in DNAm are associated with a phenotype and has the potential to advance our understanding of the role differential methylation plays in the etiology of complex disease.