Effects of Hormonal Replacement Therapy and Mindfulness-Based Stress Reduction on Climacteric Symptoms Following Risk-Reducing Salpingo-Oophorectomy.

Breast Cancer Associated Susceptibility Proteins Type 1/2 (BRCA1/2) promote cellular functioning by modulating NRF2-mediated antioxidant signaling. Redox failure in women with BRCA1/2 insufficiency increases the risk for breast/ovarian/uterine cancers. Risk-reducing salpingo-oophorectomy (RRSO) is a prophylactic surgery of the reproductive organs, which is frequently conducted by the age of 40 to lower the occurrence of cancer in women with BRCA1/2 mutations. However, abrupt estrogen decline following RRSO causes ovarian failure, which implicates various cellular physiological processes, resulting in the increased release of free radicals and subsequent severe onset of menopausal symptoms. Comfort measures (e.g., hormonal replacement therapy (HRT) and mindfulness-based stress reduction (MBSR)) may improve chronological menopause-related quality of life, but their specific effects are not clear in women with gene mutations. Aiming to fill the gap, this study used path analysis to examine the effects of HRT and MBSR on menopausal symptoms among RRSO patients (N = 199, mean age = 50.5 ± 6.7 years). HRT directly alleviated the levels of urogenital symptoms (ß = -0.195, p = 0.005), which mediated its indirect significant effects on the somatic-vegetative and psychological symptoms of menopause (ß = -0.046, -0.067; both p values = 0.004, respectively), especially in BRCA2 carriers and in women who were currently physically active, premenopausal at the time of RRSO, had a high BMI, and had no history of breast cancer. It increased the severity of urogenital symptoms in women with a history of cancer. MBSR, on the other hand, was associated with indirect increases in the intensity of the somatic-vegetative and psychological symptoms of menopause (ß = 0.108, 0.029; p = 0.003, 0.033, respectively). It exerted positive direct effects on different menopausal symptoms in multigroup analysis. The results suggest that young women undergoing recent RRSO may benefit from HRT at an individual level, while their need for extensive measures to optimize their psychological wellbeing is ongoing. The adverse effects of MBSR, which are captured in the present study, imply that MBSR may interfere with redox sensitivity associated with estradiol fluctuations in BRCA1/2 carriers. Investigations are needed to test this hypothesis and elaborate on the underlying mechanisms in these women.

Exome sequencing revealed variants in SGCA and SIL1 genes underlying limb girdle muscular dystrophy and Marinesco-Sjögren syndrome patients.

BACKGROUND: Inherited neuromuscular (NMD) and neurodegenerative diseases (NDD) belong to two distinct categories that disturb different components of the nervous system, leading to a variety of different symptoms and clinical manifestations. Both NMD and NDD are a heterogeneous group of genetic conditions. Genetic variations in the SGCA and SIL1 genes have been implicated in causing Limb Girdle Muscular Dystrophy (LGMD), a type of neuromuscular disorder, and Marinesco-Sjögren Syndrome (MSS) which is a neurodegenerative disorder. METHODS: In the present study, we have investigated four patients presenting LGMD and five patients with MSS features. After collecting detailed clinical and family history, necessary laboratory investigations, including estimation of a skeletal muscle marker enzyme serum creatine kinase (CK), nerve conduction study (NCS), electromyography (EMG), echocardiography (Echo), Magnetic resonance imaging (MRI -brain), CT-brain and X-rays were performed. Whole exome followed by Sanger sequencing was employed to search for the disease-causing variants. RESULTS: Physical examination in LGMD patients revealed poor muscle tone and facing difficulty in straightening up from the floor. Clinical history revealed frequent falls and strenuousness in climbing stairs. They started toe-walking in early childhood. Laboratory investigations confirmed elevated CK levels and abnormal NCS and EMG. The MSS patients showed abnormalities in gate and jerking movement, abnormal speech, and strabismus with cataract. MRI-brain showed cerebral atrophy in some MSS patients with elevated CK levels. Whole exome sequencing revealed a nonsense variant [c.C574T, p.(Arg192*)] in the SGCA gene and a frameshift [c.936dupG, p.(Leu313AlaFs*39)] in the SIL1 gene in LGMD and MSS patients, respectively. CONCLUSION: Our study emphasizes the significance of integrating clinical and genetic analyses for precise diagnosis and tailored management strategies in inherited NMD and NDD disorders. To the best of our knowledge, this is the first study documenting SGCA and SIL1 recurrent variants in subcontinent populations with few rare clinical features. The recurrent mutations expanding the global understanding of the mutation's geographic and ethnic distribution and contributing valuable epidemiological data. The study will facilitate genetic counseling for families experiencing similar clinical features, both within Pakistani populations and in other regions.

Effect of medication adherence on quality of life, activation measures, and health imagine in the elderly people: a cross-sectional study.

BACKGROUND: Usually, old age brings a poor quality of life due to illness and frailty. To prolong their lives and ensure their survival, all elderly patients with chronic diseases must adhere to their medications. In our study, we investigate medication adherence for elderly patients and its impact on the general health of the patient. METHODS: We implemented a cross-sectional survey-based study with four sections in April 2022 in Saudi Arabia. Data about the participants' demographic characteristics, the Morisky Medication Adherence Scale, Patient Activation Measure (PAM) 13, and EQ-5D-5 L. RESULTS: A total of 421 patients participated in this study, their mean age was 60.4 years, and most of them were males. Most of our population is living independently 87.9%. The vast majority of people have a low adherence record in the Morisky Medication Adherence Scale (8-MMAS) classes (score = < 6). Moreover, the average PAM13 score is 51.93 (Level2) indicating a low level of confidence and sufficient knowledge to take action. Our analysis showed a significant correlation between socioeconomic status and medication adherence. Also, there was an association between housing status and medication adherence. On the other hand, we found no correlation between medication adherence and quality of life (QOL) by EQ-5D-5 L. CONCLUSION: Medication adherence is directly affected by living arrangements, as patients who live with a caretaker who can remind them to take their medications at the appropriate times have better medication adherence than those who live alone. Medication adherence was also significantly influenced by socioeconomic status, perhaps as a result of psychological effects and the belief of the lower-salaried population that they would be unable to afford the additional money required to cure any comorbidities that arose as a result of the disease. On the other hand, we did not find any correlation between medication adherence and quality of life. Finally, awareness of the necessity of adherence to medication for the elderly is essential.

Exercise-based gaming in patients with multiple sclerosis: A systematic review and meta-analysis.

Background: Multiple sclerosis presents a significant burden, with balance disturbances impacting patients' daily living. Conventional therapies have been supplemented with technological advancements like virtual reality (VR) and exergaming, providing engaging, multisensory rehabilitation options. Objective: This study aimed to synthesize evidence on exergaming's role in multiple sclerosis treatment, particularly to evaluate the impact of exergaming on cognitive, motor, and psychological outcomes in patients with multiple sclerosis. Methods: A systematic review and subsequent meta-analysis design were employed. An extensive search was conducted up to June 2023 across five electronic databases - Web of Science, Scopus, PubMed, Cochrane, and EMBASE. The data extraction process from the selected studies was conducted independently. The risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool 1 (ROB1) and the National Institutes of Health (NIH) assessment tool. Continuous outcomes were consolidated as mean differences (MD) with 95% confidence intervals (CIs). Meta-analyses were performed using RevMan ver. 5.4. Results: Out of 1,029 studies, 27 were included for meta-analysis. There were no significant differences in cognitive outcomes between the exergaming and the no-intervention group or the Conventional Physiotherapy and Rehabilitation interventions (CPRh) subgroups. However, the Symbol Digit Modalities Test (SDMT) showed a statistically significant difference in favor of exergaming in the no-intervention subgroup (MD = 5.40, 95% CI [0.08, 10.72], p = 0.05). In motor outcomes, exergaming only demonstrated better results in the 6-minute walking test compared to the no-intervention group (MD = 25.53, 95% CI [6.87, 44.19], p = 0.007). The Berg Balance Scale score in both studied subgroups and the Timed Up and Go (TUG) test in the no-intervention group favored exergaming. In terms of psychological outcomes, the Beck Depression Inventory did not reveal any significant differences, while the Modified Fatigue Impact Scale (MFIS) score favored exergaming in the CPRh subgroup. Conclusion: Exergaming shows promise for enhancing cognitive and motor functions, motivation, adherence, and quality of life in MS patients, which is beneficial for nurses. It can be tailored to individual preferences and easily conducted at home, potentially serving as a viable alternative to traditional rehab programs, especially during relapses. However, further research is necessary to fully understand its optimal and lasting benefits.

Exploring nanoarchitectonics and optical properties of PAA-ZnO@BCP wide-band-gap organic semiconductors.

This work reports the formation of polyacrylic acid (PAA)-zinc oxide (ZnO)-bromocresol purple (BCP), (PAA-ZnO@ (0.00-0.01) BCP wide-bandgap organic semiconductors deposited onto glass substrates via a sol-gel polymerization process. These semiconductor films were deposited on glass substrates using a spin coating and then dried at 60 °C. The PAA-ZnO film appeared to be of amorphous phase, and films loaded with BCP revealed semicrystalline behavior. The surface of the films exhibited adherence and extended grains. The hydrogen bonds formed between PAA-ZnO and the BCP dye within the PAA-ZnO@BCP films was performed using FTIR-spectroscopy. The prepared nanocomposites demonstrate an indirect band transition which is affected slightly by adding ZnO and BCP dye. Optical parameters such as the absorption coefficient, the refractive index, the dielectric constant, optical conductivity, optical depth, and optical electronegativity of the prepared nanocomposites were studied as functions of incident light energy (wavelength). The PAA carbonyl group n-π* transition and BCP aromatic ring π-π* transitions were detected at about 285 (for all samples) and 432 nm (for BCP loaded samples), respectively. The superior photoluminescence characteristics observed in the BCP/PAA-Zn films excited with a wavelength of 250 nm indicated the successful loading of the BCP dye during the self-aggregation of the PAA-Zn film.

Quantum Efficiency Measurement and Modeling of Silicon Sensors Optimized for Soft X-ray Detection.

Hybrid pixel detectors have become indispensable at synchrotron and X-ray free-electron laser facilities thanks to their large dynamic range, high frame rate, low noise, and large area. However, at energies below 3 keV, the detector performance is often limited because of the poor quantum efficiency of the sensor and the difficulty in achieving single-photon resolution due to the low signal-to-noise ratio. In this paper, we address the quantum efficiency of silicon sensors by refining the design of the entrance window, mainly by passivating the silicon surface and optimizing the dopant profile of the n+ region. We present the measurement of the quantum efficiency in the soft X-ray energy range for silicon sensors with several process variations in the fabrication of planar sensors with thin entrance windows. The quantum efficiency for 250 eV photons is increased from almost 0.5% for a standard sensor to up to 62% as a consequence of these developments, comparable to the quantum efficiency of backside-illuminated scientific CMOS sensors. Finally, we discuss the influence of the various process parameters on quantum efficiency and present a strategy for further improvement.

Exploration of nonlinear optical properties of 4-methyl-4H-1,2,4-triazol-3-yl)thio)-N-phenylpropanamide based derivatives: experimental and DFT approach.

Triazoles, nitrogen-containing heterocycles, have gained attention for their applications in medicinal chemistry, drug discovery, agrochemicals, and material sciences. In the current study, we synthesized novel derivatives of N-substituted 2-((5-(3-bromophenyl)-4-methyl-4H-1,2,4-triazol-3-yl)thio)-N-phenylpropanamide and conducted a comprehensive investigation using density functional theory (DFT). These novel structural hybrids of 1,2,4-triazole were synthesized through the multi-step chemical modifications of 3-bromobenzoic acid (1). Initially, compound 1 was converted into its methyl-3-bromobenzoate (2) which was then transformed into 3-bromobenzohydrazide (3). The final step involved the cyclization of compound 3, producing its 1,2,4-triazole derivative (4). This intermediate was then coupled with different electrophiles, resulting in the formation of the final derivatives (7a-7c). Additionally, the characterization of these triazole-based compounds (7a, 7b, and 7c) were carried out using techniques such as IR, HNMR, and UV-visible spectroscopy to understand their structural and spectroscopic properties. The DFT study utilized M06/6-311G(d,p) functional to investigate geometrical parameters, HOMO-LUMO energies, natural bond orbital analyses, transition density matrix (TDM), density of states, and nonlinear optical (NLO) properties. The FMO analysis revealed that compound 7c exhibited the lowest band gap value (4.618 eV). Notably, compound 7c exhibited significant linear polarizability (4.195 > × 10-23) and first and second hyperpolarizabilities (6.317 > × 10-30, 4.314 × 10-35), signifying its potential for nonlinear optical applications. These NLO characteristics imply that each of our compounds, especially 7c, plays a crucial part in fabricating materials showing promising NLO properties for optoelectronic applications.

A pediatric HIV outbreak in Pakistan

Background:Following reports of an outbreak of HIV infection among children in Larkana District, Pakistan, an international team investigated the extent and cause of the outbreak between April and June 2019.Aims:To investigate the incidence of HIV among children in Larkana District, Pakistan and describe the distribution of cases by time, place and person.Methods:Self-referred persons were tested for HIV using the national testing protocol. Local epidemiology of HIV was reviewed to generate hypotheses. An infection prevention and control (IPC) team conducted site visits and reviewed IPC practices.Results:Between 25 April and 27 June 2019, a total of 30 191 persons were tested for HIV in Larkana District, and 876 of them tested positive. Of those who tested positive, 719 (82%) were children aged <15 years. Traditional skin piercing procedures and transmission from high-risk populations to children were ruled out during the investigation. Informative interviews with parents or guardians of a convenience sample of 211 children aged <15 years showed that 99% of children had an injection or infusion for medical treatment within the past 12 months. Our investigation identified lack of HIV prevalence data for the general population including tuberculosis patients and those who attended antenatal care services.Conclusions:Investigations indicate that unsafe healthcare practices in formal and informal healthcare settings as the most likely cause of the 2019 outbreak of HIV infection in Larkana, Pakistan. Measures should be taken to improve IPC practices at the facility level, especially in pediatric and antenatal care clinics.

Humidity sensing using Zn(1.6 - x)Na0.4CuxTiO4 spinel nanostructures.

In this paper, we present a humidity sensing material based on nanostructured Zn(1.6 - x)Na0.4CuxTiO4 spinel to enhance optical and sensitivity performance. Nano-porous of Zn (1.6 - x) Na0.4CuxTiO4 spinel were synthesized using sol gel reactions and calcined at 700 °C. The nanostructures of Zn(1.6 - x)Na0.4CuxTiO4 spinel underwent thorough characterization through multiple techniques. X-ray diffractometry (XRD) coupled with Rietveld refinement using FullProf software, transmission electron microscopy (TEM), Raman Spectroscopy, and optical analysis were employed to assess various aspects of the nanostructures. These techniques were utilized to determine the phase composition, particle size distribution, chemical bonding, and the tunable band gap of the nanostructures. The X-ray diffraction (XRD) analysis of Zn(1.6 - x)Na0.4CuxTiO4 samples revealed well-defined and prominent peaks, indicating a highly crystalline cubic spinel structure. The lattice parameter was decreased from 8.4401 to 8.4212 Å with increasing Cu content from 0 to 1.2 mol%. UV-visible diffuse reflectance spectra were employed to investigate the optical characteristics of copper-doped Zn1.6Na0.4TiO4. The applicability of Cu@NaZT spinel nanostructures in humidity sensors was evaluated at ambient conditions. The fabricated sensor was investigated in a wide span of humidity (11-97%). The examined sensor demonstrates a low hysteresis, excellent repeatability, fast response and recovery. The response and recovery times were estimated to be 20 s and 6 s respectively. The highest sensitivity was achieved at 200 Hz. The proposed sensor can be coupled easily with electronic devices as the humidity-impedance relationship is linear.

Advancing energy storage and supercapacitor applications through the development of Li+-doped MgTiO3 perovskite nano-ceramics.

Perovskite oxide materials, specifically MgTiO3 (MT) and Li-doped MgTiO3 (MTxLi), were synthesized via a sol-gel method and calcination at 800 °C. This study explores the impact of varying Li doping levels (x = 0, 0.01, 0.05, and 0.1) on the crystalline structure and properties of MgTiO3. X-ray diffraction analysis revealed a well-defined rhombohedral MgTiO3 phase. Optical diffuse reflectance measurements provided insights into energy gap values, refractive index, and dielectric constant. Li+ doping enhanced the electrical properties of MgTiO3, with a notable phase transition observed at 50 °C. The study investigated impedance and AC conductivity under varying temperature and frequency conditions (25-120 °C, 4 Hz to 8 MHz). Electrochemical analysis through cyclic voltammetry and electrochemical impedance spectroscopy confirmed highly electrocatalytic properties for MTxLi, particularly when modified onto screen-printed electrodes. This work not only advances the understanding of Li-doped MgTiO3 nanostructures but also highlights their significant potential for direct electrochemical applications, particularly in the realm of energy storage.

Optimizing magnetic, dielectric, and antimicrobial performance in chitosan-PEG-Fe2O3@NiO nanomagnetic composites.

There is a growing interest in eco-friendly and cost-effective organic-inorganic nanocomposites due to their alignment with the principles of "green" chemistry, as well as their biocompatibility and non-toxicity. This study focused on producing Chitosan-PEG-Fe2O3@NiO nanomagnetic composites to improve the stability, dielectric properties, and antimicrobial effectiveness of these nanocomposite materials. The process involved synthesizing Fe2O3@NiO via sol-gel and polymerizing chitosan-PEG. The nanocomposites were characterized by XRD, TEM, FTIR, optical, dielectric, and VSM. Incorporating Fe2O3@NiO significantly improved stability, and the interaction with Fe2O3 during the sol-gel process facilitated the formation of NiFe2O4 with an increase in the crystallinity within the chitosan-PEG matrix. The study examined optical and dielectric properties, highlighting that the 3 NiO-doped chitosan-PEG-Fe2O3 composites had high electrical conductivity (1.8 ∗ 10-3 S/cm) and a significant dielectric constant (106 at low frequencies). As the ratio of NiO NPs within the chitosan-PEG-Fe2O3 increases, the energy band gap of chitosan-PEG-Fe2O3 films decreases up to 3.7 eV. This decrease is owing to the quantum confinement effect. These composites also demonstrated improved antimicrobial activity against E. coli and S. aureus and higher activity in the presence of nanomagnetic particles. The minimum inhibitory concentrations of CS-PEG-Fe2O3/NiO NPs against (Bacillus cereus, M. luteus, S. aureus and (S. enterica, H. pylori, E. coli) were (22-35 mm) and (21-34 mm), respectively.

Immunotherapy: Constructive Approach for Breast Cancer Treatment.

A novel and rapid therapeutic approach is the treatment of human breast cancer by enhancing the host's immune system. In initial findings, program death one (PD-1) and program cell death ligand one (PD-L1) showed positive results towards solid tumors, but tumor relapse and drug resistance are the major concerns. Breast cancer therapy has been transformed by the advent of immune checkpoint blockades (ICBs). Triple-negative breast cancers (TNBCs) have exhibited enduring responses to clinical usage of immune checkpoint inhibitors (ICBs) like atezolizumab and pembrolizumab. Nonetheless, a notable proportion of individuals with TNBC do not experience advantages from these treatments, and there is limited comprehension of the resistance mechanisms. Another approach to overcome resistance is cancer stem cells (CSCs), as these cells are crucial for the initiation and growth of tumors in the body. Various cancer vaccines are created using stem cells (dendritic, whole cell, bacterial) and focus primarily on targeting tumor-related antigens. The ultimate objective of cancer vaccines is to immunize the patients by active artificial immunity against cancer, though. In this review, we primarily focused on existing immunotherapeutic options, immune checkpoint blockers, the latest progress in understanding the molecular mechanisms underlying resistance to immune checkpoint inhibitors (ICBs), advanced strategies to overcome resistance to ICBs, cancer stem cell antigens and molecular markers, ongoing clinical trials for BCs and cancer vaccines for breast cancer.

Application of Virtual Reality-Assisted Exergaming on the Rehabilitation of Children with Cerebral Palsy: A Systematic Review and Meta-Analysis.

BACKGROUND: Rehabilitation programs for children with cerebral palsy (CP) aim to improve their motor and cognitive skills through repeated and progressively challenging exercises. However, these exercises can be tedious and demotivating, which can affect the effectiveness and feasibility of the programs. To overcome this problem, virtual reality VR-assisted exergaming has emerged as a novel modality of physiotherapy that combines fun and motivation with physical activity. VR exergaming allows children with CP to perform complex movements in a secure and immersive environment, where they can interact with virtual objects and scenarios. This enhances their active engagement and learning, as well as their self-confidence and enjoyment. We aim to provide a comprehensive overview of the current state of research on VR exergaming for CP rehabilitation. The specific objectives are: To identify and describe the existing studies that have investigated the effects of VR exergaming on motor function and participation outcomes in children with CP. In addition, we aim to identify and discuss the main gaps, challenges, and limitations in the current research on VR exergaming for CP rehabilitation. Finally, we aim to provide recommendations and suggestions for future research and practice in this field. METHODS: In June 2023, we conducted a systematic search on Scopus, Web of Science, PubMed, Cochrane, and Embase for randomized trials and cohort studies that applied VR-assisted exergaming to rehabilitating patients with CP. The inclusion criteria encompassed the following: (1) Randomized controlled trials (RCTs) and cohort studies involving the rehabilitation of children with CP; (2) the application of VR-based exergaming on the rehabilitation; (3) in comparison with conventional rehabilitation/usual care. The quality of the selected RCTs was evaluated using Cochrane's tool for risk of bias assessment bias includes. Whereas the quality of cohort studies was assessed using the National Institutes of Health (NIH) tool. RESULTS: The systematic search of databases retrieved a total of 2576 studies. After removing 863 duplicates, 1713 studies underwent title and abstract screening, and 68 studies were then selected as eligible for full-text screening. Finally, 45 studies were involved in this review (n = 1580), and 24 of those were included in the quantitative analysis. The majority of the included RCTs had a low risk of bias regarding study reporting, participants' attrition, and generating a random sequence. Nearly half of the RCTs ensured good blinding of outcomes assessors. However, almost all the RCTs were unclear regarding the blinding of the participants and the study personnel. The 2020 retrospective cohort study conducted at Samsung Changwon Hospital, investigating the effects of virtual reality-based rehabilitation on upper extremity function in children with cerebral palsy, demonstrated fair quality in its methodology and findings. VR-assisted exergaming was more effective than conventional physiotherapy in improving the Gross Motor Function Measurement (GMFM)-88 score (MD = 0.81; 95% CI [0.15, 1.47], p-value = 0.02) and the GMFM walking and standing dimensions (MD = 1.45; 95% CI [0.48, 2.24], p-value = 0.003 and MD = 3.15; 95% CI [0.87, 5.42], p-value = 0.007), respectively. The mobility and cognitive domains of the Pediatric Evaluation of Disability Inventory score (MD = 1.32; 95% CI [1.11, 1.52], p-value < 0.001) and (MD = 0.81; 95% CI [0.50, 1.13], p-value < 0.0001) were also improved. The Canadian Occupational Performance Measure performance domain (MD = 1.30; 95% CI [1.04, 1.56], p-value < 0.001), the WeeFunctional Independence Measure total score (MD = 6.67; 95% CI [6.36, 6.99], p-value < 0.0001), and the Melbourne Assessment of Unilateral Upper Limb Function-2 score (p-value < 0.001) improved as well. This new intervention is similarly beneficial as conventional therapy in improving other efficacy measures. CONCLUSIONS: Our findings suggest that VR-assisted exergaming may have some advantages over conventional rehabilitation in improving CP children's functioning and performance in daily life activities, upper and lower limb mobility, and cognition. VR-assisted exergaming seems to be as effective as conventional physiotherapy in the other studied function measures. With its potential efficacy, better feasibility, no reported side effects, and entertaining experience, VR-assisted exergaming may be a viable complementary approach to conventional physiotherapy in rehabilitating children with CP.

The anticancer and anti-inflammatory activity screening of pyridazinone-based analogs against human epidermoid skin cancer with detailed mechanistic analyses.

3(2H)-Pyridazinone derivatives based on 4-biphenyl, naphtha-2-yl, pyridine, or piperidine moiety were synthesized and characterized using I-R and 1HNMR spectra. The activity and cytotoxicity of some synthesized compounds on the skin epidermoid cancer cell proliferation and progression were investigated. The pyridazine isomer with pyridine revealed a significant decrease in the level of nitric oxide p < 0.01 than the activity of caffeine phenecyl ester. The activity of the three active isomers recorded significant activity for their total antioxidant content that triggers their ability for the scavenging the oxygen free radicals significantly p < 0.01. Moreover, revealing the pharmaceutical activity of the isomers as anti-inflammatory agents, IL-6, IL10, and IL12 have been decreased by variable significant values. Additionally, the active isomers revealed variable actions on the skin cancer cell to induce apoptosis using annexin V-FITC/PI. Pyridine was the highest isomer to induce late apoptosis and necrosis for the skin cancer cells against the use of cisplatin. Importantly, Molecular modeling experiments including docking and dynamic simulations were done for the most active 3 analogs to explore the ligand binding and stability leading to exploring the structure-activity relationship with biological target PARP1 which showed a good binding propensity to pyridazine binding site which supports the in vitro data. In conclusion, the pyridazine moieties with piperdine, naphthayl, and pyridine have pharmacological activities against skin cancer epidermoid by triggering action in inhibition of the proliferation and progression with an up-regulated apoptotic mechanism that evades the emergence of cisplatin resistance among different cancer cells.Communicated by Ramaswamy H. Sarma.

Application of coliphage as biocontrol agent in combination with gamma irradiation to eliminate multi-drug-resistant E. coli in minimally processed vegetables.

Biofilm formation is a rising concern in the food industry. Escherichia coli (E. coli) is one of the most important food-borne pathogens that can survive in food and food-related environments and eventually produce biofilms. This study suggested that both coliphages used were successful in preventing the creation of new biofilms as well as removing existing ones. Confocal laser scanning microscopy verified these findings. According to the findings, neither coliphage survived at 37 °C, but both remained stable at 4 °C and - 20 °C for extended periods of time. The study revealed that both coliphages demonstrated a greater degree of gamma irradiation resistance when compared to E. coli. The study's results indicate that the implementation of a dual method, which incorporates gamma irradiation (1.5 kGy) and coliphage treatment, on various kinds of vegetables that were infected with E. coli, resulted in a significant reduction in bacterial count (surpassing 99.99%) following a 24-h incubation period. Combining gamma irradiation and the coliphage approach was significantly effective at lowering polysaccharide concentrations and proteins in the biofilm matrix. The results revealed that the pairing of gamma irradiation and coliphages acted in conjunction to cause disruptions in the matrix of biofilm, thereby promoting cell removal compared with either of the individual treatments. Ca+ ions strengthen the weak virion interaction with the relevant bacterial host cell receptors during the adsorption process. In conclusion, use of coliphage in combination with gamma irradiation treatment can be applied to improve fresh produce's microbial safety and enhance its storability in supermarkets.

Development of Novel Class of Phenylpyrazolo[3,4-d]pyrimidine-Based Analogs with Potent Anticancer Activity and Multitarget Enzyme Inhibition Supported by Docking Studies.

Phenylpyrazolo[3,4-d]pyrimidine is considered a milestone scaffold known to possess various biological activities such as antiparasitic, antifungal, antimicrobial, and antiproliferative activities. In addition, the urgent need for selective and potent novel anticancer agents represents a major route in the drug discovery process. Herein, new aryl analogs were synthesized and evaluated for their anticancer effects on a panel of cancer cell lines: MCF-7, HCT116, and HePG-2. Some of these compounds showed potent cytotoxicity, with variable degrees of potency and cell line selectivity in antiproliferative assays with low resistance. As the analogs carry the pyrazolopyrimidine scaffold, which looks structurally very similar to tyrosine and receptor kinase inhibitors, the potent compounds were evaluated for their inhibitory effects on three essential cancer targets: EGFRWT, EGFRT790M, VGFR2, and Top-II. The data obtained revealed that most of these compounds were potent, with variable degrees of target selectivity and dual EGFR/VGFR2 inhibitors at the IC50 value range, i.e., 0.3-24 µM. Among these, compound 5i was the most potent non-selective dual EGFR/VGFR2 inhibitor, with inhibitory concentrations of 0.3 and 7.60 µM, respectively. When 5i was tested in an MCF-7 model, it effectively inhibited tumor growth, strongly induced cancer cell apoptosis, inhibited cell migration, and suppressed cell cycle progression leading to DNA fragmentation. Molecular docking studies were performed to explore the binding mode and mechanism of such compounds on protein targets and mapped with reference ligands. The results of our studies indicate that the newly discovered phenylpyrazolo[3,4-d]pyrimidine-based multitarget inhibitors have significant potential for anticancer treatment.

Introducing of novel class of pyrano[2,3-c]pyrazole-5-carbonitrile analogs with potent antimicrobial activity, DNA gyrase inhibition, and prominent pharmacokinetic and CNS toxicity profiles supported by molecular dynamic simulation.

Microbiological DNA gyrase is recognized as an exceptional microbial target for the innovative development of low-resistant and more effective antimicrobial drugs. Hence, we introduced a one-pot facile synthesis of a novel pyranopyrazole scaffold bearing different functionalities; substituted aryl ring, nitrile, and hydroxyl groups. All new analogs were characterized with full spectroscopic data. The antimicrobial screening for all analogs was assessed against standard strains of Gm + ve and Gm-ve through in vitro considers. The screened compounds displayed very promising MIC/MBC values against some of the bacterial strains with broad or selective antibacterial effects. Of these, 4j biphenyl analog showed 0.5-2/2-8 µg/mL MIC/MBC for suppression and killing of Gm + ve and Gm-ve strains. Moreover, the antimicrobial screening was assessed for the most potent analogs against certain highly resistant microbial strains. Consequently, DNA gyrase supercoiling assay was done for all analogs using ciprofloxacin as reference positive control. Obviously, the results showed a different activity profile with potent analog 4j with IC50 value 6.29 µg/mL better than reference drug 10.2 µg/mL. Additionally, CNS toxicity testing was done using the HiB5 cell line for attenuation of GABA/NMDA expression to both 4j and ciprofloxacin compounds that revealed better neurotransmitter modulation by novel scaffold. Importantly, docking and dynamic simulations were performed for the most active 4j analog to investigate its interaction with DNA binding sites, which supported the in vitro observations and compound stability with binding pocket. Finally, a novel scaffold pyranopyrazole was introduced as a DNA gyrase inhibitor with prominent antibacterial efficacy and low CNS side effect toxicity better than quinolones.Communicated by Ramaswamy H. Sarma.

A systematic review and meta-analysis on the efficacy and safety of the Baska mask versus other laryngeal mask airways during general anaesthesia.

BACKGROUND: The Baska mask is a supraglottic airway device used during general anaesthesia that combines features from various other devices. This systematic review aims to compare its efficacy and safety with other laryngeal mask airways. METHODS: Randomised controlled trials were identified by searching PubMed, Scopus, Web of Science and Cochrane Library. RevMan software was used for meta-analysis, with mean difference and risk ratios calculated for continuous and dichotomous data, respectively, along with a 95% confidence interval. RESULTS: The meta-analysis found that the Baska mask provides a better oropharyngeal seal pressure (mean difference = 7.03; 95% confidence interval = [6.00, 8.07], p < 0.00001) and a higher rate of maximal seal pressure (risk ratio = 18.38; 95% confidence interval = [2.53, 133.47], p = 0.004) compared to other laryngeal mask airways. However, the Baska mask had lower success rates in first-attempt insertion (risk ratio = 0.79; 95% confidence interval = [0.72, 0.86], p < 0.00001) and higher rates of insertion manipulation (risk ratio = 16.64; 95% confidence interval = [5.86, 47.24], p < 0.00001). CONCLUSION: The Baska mask offers better oropharyngeal seal pressure, but may be more difficult to insert than other laryngeal mask airways, without causing significant delays. The Baska mask appears as safe as other laryngeal mask airways, but larger trials are needed to support these findings.

Synthesis and characterization of chitosan-corn starch-SiO2/silver eco-nanocomposites: Exploring optoelectronic and antibacterial potential.

This work discusses the physicochemical and antimicrobial characteristics of chitosan-corn starch eco-nanocomposites integrated with silica@Ag nano-spheres. These composites were synthesized through sol-gel polymerization and subsequently exposed to simulated body fluid (SBF). The incorporation of Ag into the eco-nanocomposites led to a decrease in diffuse reflectance across the entire wavelength range. The dielectric permittivity exhibited an increase up to 52.1 at a frequency of 100 kHz, while the ac conductivity reached a value of 5.2 ∗ 10-6 (S cm-1) at the same frequency for the sample with the highest Ag content. The study utilized XRD and FTIR techniques to examine the materials before and after in vitro testing and evaluated the antibacterial properties of the eco-nanocomposites against several pathogenic microorganisms, including Staphylococcus haemolyticus, Staphylococcus aureus, Klebsiella pneumoniae, and Escherichia coli, using the agar diffusion method. The eco-nanocomposites demonstrated bioactivity by forming a hydroxy appetite layer on their surfaces and were capable of releasing silver (Ag) at concentrations of 1.3, 1.9, and 2.5 mol%. This study suggests that chitosan-corn starch-SiO2-based doped with Ag eco-nanocomposite has the potential for various applications, including biomedical and environmental fields, where their antibacterial properties can be utilized to combat harmful microorganisms.

Calibration method and performance of a time-of-flight detector to measure absolute beam energy in proton therapy.

BACKGROUND: The beam energy is one of the most significant parameters in particle therapy since it is directly correlated to the particles' penetration depth inside the patient. Nowadays, the range accuracy is guaranteed by offline routine quality control checks mainly performed with water phantoms, 2D detectors with PMMA wedges, or multi-layer ionization chambers. The latter feature low sensitivity, slow collection time, and response dependent on external parameters, which represent limiting factors for the quality controls of beams delivered with fast energy switching modalities, as foreseen in future treatments. In this context, a device based on solid-state detectors technology, able to perform a direct and absolute beam energy measurement, is proposed as a viable alternative for quality assurance measurements and beam commissioning, paving the way for online range monitoring and treatment verification. PURPOSE: This work follows the proof of concept of an energy monitoring system for clinical proton beams, based on Ultra Fast Silicon Detectors (featuring tenths of ps time resolution in 50 µm active thickness, and single particle detection capability) and time-of-flight techniques. An upgrade of such a system is presented here, together with the description of a dedicated self-calibration method, proving that this second prototype is able to assess the mean particles energy of a monoenergetic beam without any constraint on the beam temporal structure, neither any a priori knowledge of the beam energy for the calibration of the system. METHODS: A new detector geometry, consisting of sensors segmented in strips, has been designed and implemented in order to enhance the statistics of coincident protons, thus improving the accuracy of the measured time differences. The prototype was tested on the cyclotron proton beam of the Trento Protontherapy Center (TPC). In addition, a dedicated self-calibration method, exploiting the measurement of monoenergetic beams crossing the two telescope sensors for different flight distances, was introduced to remove the systematic uncertainties independently from any external reference. RESULTS: The novel calibration strategy was applied to the experimental data collected at TPC (Trento) and CNAO (Pavia). Deviations between measured and reference beam energies in the order of a few hundreds of keV with a maximum uncertainty of 0.5 MeV were found, in compliance with the clinically required water range accuracy of 1 mm. CONCLUSIONS: The presented version of the telescope system, minimally perturbative of the beam, relies on a few seconds of acquisition time to achieve the required clinical accuracy and therefore represents a feasible solution for beam commission, quality assurance checks, and online beam energy monitoring.