Feed aggregator

Lancet Reg Health Eur. 2024 Apr 24;40:100903. doi: 10.1016/j.lanepe.2024.100903. eCollection 2024 May.

ABSTRACT

BACKGROUND: Second primary cancers (SPCs) after breast cancer (BC) present an increasing public health burden, with little existing research on socio-demographic, tumour, and treatment effects. We addressed this in the largest BC survivor cohort to date, using a novel linkage of National Disease Registration Service datasets.

METHODS: The cohort included 581,403 female and 3562 male BC survivors diagnosed between 1995 and 2019. We estimated standardized incidence ratios (SIRs) for combined and site-specific SPCs using incidences for England, overall and by age at BC and socioeconomic status. We estimated incidences and Kaplan-Meier cumulative risks stratified by age at BC, and assessed risk variation by socio-demographic, tumour, and treatment characteristics using Cox regression.

FINDINGS: Both genders were at elevated contralateral breast (SIR: 2.02 (95% CI: 1.99-2.06) females; 55.4 (35.5-82.4) males) and non-breast (1.10 (1.09-1.11) females, 1.10 (1.00-1.20) males) SPC risks. Non-breast SPC risks were higher for females younger at BC diagnosis (SIR: 1.34 (1.31-1.38) <50 y, 1.07 (1.06-1.09) ≥50 y) and more socioeconomically deprived (SIR: 1.00 (0.98-1.02) least deprived quintile, 1.34 (1.30-1.37) most).

INTERPRETATION: Enhanced SPC surveillance may benefit BC survivors, although specific recommendations require more detailed multifactorial risk and cost-benefit analyses. The associations between deprivation and SPC risks could provide clinical management insights.

FUNDING: CRUK Catalyst Award CanGene-CanVar (C61296/A27223). Cancer Research UK grant: PPRPGM-Nov 20∖100,002. This work was supported by core funding from the NIHR Cambridge Biomedical Research Centre (NIHR203312)]. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

PMID:38745989 | PMC:PMC11092881 | DOI:10.1016/j.lanepe.2024.100903

Proc Natl Acad Sci U S A. 2024 May 21;121(21):e2322923121. doi: 10.1073/pnas.2322923121. Epub 2024 May 13.

ABSTRACT

The ubiquitin-proteasome system is essential to all eukaryotes and has been shown to be critical to parasite survival as well, including Plasmodium falciparum, the causative agent of the deadliest form of malarial disease. Despite the central role of the ubiquitin-proteasome pathway to parasite viability across its entire life-cycle, specific inhibitors targeting the individual enzymes mediating ubiquitin attachment and removal do not currently exist. The ability to disrupt P. falciparum growth at multiple developmental stages is particularly attractive as this could potentially prevent both disease pathology, caused by asexually dividing parasites, as well as transmission which is mediated by sexually differentiated parasites. The deubiquitinating enzyme PfUCHL3 is an essential protein, transcribed across both human and mosquito developmental stages. PfUCHL3 is considered hard to drug by conventional methods given the high level of homology of its active site to human UCHL3 as well as to other UCH domain enzymes. Here, we apply the RaPID mRNA display technology and identify constrained peptides capable of binding to PfUCHL3 with nanomolar affinities. The two lead peptides were found to selectively inhibit the deubiquitinase activity of PfUCHL3 versus HsUCHL3. NMR spectroscopy revealed that the peptides do not act by binding to the active site but instead block binding of the ubiquitin substrate. We demonstrate that this approach can be used to target essential protein-protein interactions within the Plasmodium ubiquitin pathway, enabling the application of chemically constrained peptides as a novel class of antimalarial therapeutics.

PMID:38739798 | DOI:10.1073/pnas.2322923121

Proc Natl Acad Sci U S A. 2024 May 21;121(21):e2322923121. doi: 10.1073/pnas.2322923121. Epub 2024 May 13.

ABSTRACT

The ubiquitin-proteasome system is essential to all eukaryotes and has been shown to be critical to parasite survival as well, including Plasmodium falciparum, the causative agent of the deadliest form of malarial disease. Despite the central role of the ubiquitin-proteasome pathway to parasite viability across its entire life-cycle, specific inhibitors targeting the individual enzymes mediating ubiquitin attachment and removal do not currently exist. The ability to disrupt P. falciparum growth at multiple developmental stages is particularly attractive as this could potentially prevent both disease pathology, caused by asexually dividing parasites, as well as transmission which is mediated by sexually differentiated parasites. The deubiquitinating enzyme PfUCHL3 is an essential protein, transcribed across both human and mosquito developmental stages. PfUCHL3 is considered hard to drug by conventional methods given the high level of homology of its active site to human UCHL3 as well as to other UCH domain enzymes. Here, we apply the RaPID mRNA display technology and identify constrained peptides capable of binding to PfUCHL3 with nanomolar affinities. The two lead peptides were found to selectively inhibit the deubiquitinase activity of PfUCHL3 versus HsUCHL3. NMR spectroscopy revealed that the peptides do not act by binding to the active site but instead block binding of the ubiquitin substrate. We demonstrate that this approach can be used to target essential protein-protein interactions within the Plasmodium ubiquitin pathway, enabling the application of chemically constrained peptides as a novel class of antimalarial therapeutics.

PMID:38739798 | DOI:10.1073/pnas.2322923121

Food Chem X. 2024 Apr 30;22:101418. doi: 10.1016/j.fochx.2024.101418. eCollection 2024 Jun 30.

ABSTRACT

Purpose of current study was to determine physicochemical, triglyceride composition, and functional groups of wild adlay accessions (brown, black, yellow, grey, green, off white, and purple) to find out its scope as cereal crop. Triglycerides, minerals and functional groups were determined through Gas chromatography, spectrophotometer and Fourier Transform Infrared (FTIR) spectrophotometer respectively. Results revealed variation among bulk densities, specific densities, percent empty spaces, and corresponding grain counts per 10 g of sample are useful in distinguishing brown, black, yellow, grey, green, off white, and purple wild adlay accessions. Specific density and grain count per 10 g sample was significantly related. No statistical relationship exists among the pronounced physical characteristics. Brown adlay expressed the highest protein, fat, and fiber contents 15.82%, 4.76% and 2.37% respectively. Protein, fat, ash, and fiber percent contents were found comparable to cultivated adlay. Spectrophotometric analysis revealed macro elements including phosphorus, potassium, calcium, and sodium in the range 0.3% - 2.2% and micro elements boron, iron, copper, zinc, and manganese in the range 1.6 mg/kg - 20.8 mg/kg. Gas chromatography showed polyunsaturated fatty acids (PUFA) constitute the primary fraction (39% ± 7.2) of wild adlay triglycerides. Linoleic and palmitic acids were present as prominent fatty acids, 43.5% ±1.4 and 26.3% ±1.4 respectively. Infra-red frequencies distinguished functional groups in narrow band and fingerprint region of protein in association with out of plane region leading to structural differences among adlay accessions. Comparison of major distinguishing vibrational frequencies among different flours indicated black adlay containing highest functional groups appeared promising for varietal development.

PMID:38736980 | PMC:PMC11087951 | DOI:10.1016/j.fochx.2024.101418

Cureus. 2024 Apr 9;16(4):e57905. doi: 10.7759/cureus.57905. eCollection 2024 Apr.

ABSTRACT

Ocular tuberculosis (TB) can affect various eye structures and may manifest independently of systemic TB. Typically, it arises from hematogenous dissemination from a primary focus; however, in exceptional instances, it may originate as a primary infection after epithelial injury. Diagnosing TB in an extrapulmonary site presents a significant clinical challenge. We present the case of a 33-year-old Bangladeshi female who presented with a deteriorating loss of vision in her left eye. A thorough neurologic examination and serological tests, the tuberculin skin test, a CT scan of the chest, ocular fundus photography, and optical coherence tomography were performed. Based on the clinical features and the outcome of appropriate tests, a presumptive diagnosis of ocular TB was made and later confirmed after initiating antitubercular therapy, which resulted in a marked improvement in the patient's vision a week later. This case is an illustration of the rare nature and unusual presentation of extrapulmonary TB in the form of tubercular chorioretinitis, diagnosed in a resource-limited setting. Tubercular chorioretinitis, characterized by inflammation of the choroid and retina due to TB infection, presents a diagnostic challenge, especially in resource-limited environments where access to advanced diagnostic tools may be restricted. Therefore, this case highlights the importance of considering TB as a potential cause of ocular manifestations, even in settings where TB prevalence might not be high, and underscores the need for increased awareness and diagnostic capacity for extrapulmonary TB in resource-limited areas. This case exemplifies the infrequent occurrence and atypical manifestation, presenting a learning opportunity for future clinicians.

PMID:38725761 | PMC:PMC11081081 | DOI:10.7759/cureus.57905

J Mammary Gland Biol Neoplasia. 2024 May 9;29(1):10. doi: 10.1007/s10911-024-09561-5.

ABSTRACT

Signal transducers and activators of transcription (STAT) proteins regulate mammary development. Here we investigate the expression of phosphorylated STAT3 (pSTAT3) in the mouse and cow around the day of birth. We present localised colocation analysis, applicable to other mammary studies requiring identification of spatially congregated events. We demonstrate that pSTAT3-positive events are multifocally clustered in a non-random and statistically significant fashion. Arginase-1 expressing cells, consistent with macrophages, exhibit distinct clustering within the periparturient mammary gland. These findings represent a new facet of mammary STAT3 biology, and point to the presence of mammary sub-microenvironments.

PMID:38722417 | DOI:10.1007/s10911-024-09561-5

J Mammary Gland Biol Neoplasia. 2024 May 9;29(1):10. doi: 10.1007/s10911-024-09561-5.

ABSTRACT

Signal transducers and activators of transcription (STAT) proteins regulate mammary development. Here we investigate the expression of phosphorylated STAT3 (pSTAT3) in the mouse and cow around the day of birth. We present localised colocation analysis, applicable to other mammary studies requiring identification of spatially congregated events. We demonstrate that pSTAT3-positive events are multifocally clustered in a non-random and statistically significant fashion. Arginase-1 expressing cells, consistent with macrophages, exhibit distinct clustering within the periparturient mammary gland. These findings represent a new facet of mammary STAT3 biology, and point to the presence of mammary sub-microenvironments.

PMID:38722417 | DOI:10.1007/s10911-024-09561-5

Mechanobiol Med. 2024 Mar;2(1):100038. doi: 10.1016/j.mbm.2024.100038. Epub 2024 Jan 5.

ABSTRACT

Accumulating evidence strongly suggests that cell chirality plays a pivotal role in driving left-right (LR) symmetry breaking, a widespread phenomenon in living organisms. Whole embryos and excised organs have historically been employed to investigate LR symmetry breaking and have yielded exciting findings. In recent years, in vitro engineered platforms have emerged as powerful tools to reveal cellular chiral biases and led to uncovering molecular and biophysical insights into chiral morphogenesis, including the significant role of the actin cytoskeleton. Establishing a link between observed in vivo tissue chiral morphogenesis and the determined chiral bias of cells in vitro has become increasingly important. In this regard, computational mathematical models hold immense value as they can explain and predict tissue morphogenic behavior based on the chiral biases of individual cells. Here, we present the formulations and discoveries achieved using various computational models spanning different biological scales, from the molecular and cellular levels to tissue and organ levels. Furthermore, we offer insights into future directions and the role of such models in advancing the study of asymmetric cellular mechanobiology.

PMID:38721590 | PMC:PMC11078094 | DOI:10.1016/j.mbm.2024.100038

Sci Total Environ. 2024 May 6:172942. doi: 10.1016/j.scitotenv.2024.172942. Online ahead of print.

ABSTRACT

Biochar is increasingly used in climate-smart agriculture, yet its impact on greenhouse gas (GHG) emissions and soil carbon (C) sequestration remains poorly understood. This study examined biochar-mediated changes in soil properties and their contribution to C stabilization and GHG mitigation by evaluating four types of biochar. Soil carbon dioxide (CO2) and nitrous oxide (N2O) emissions, soil chemical and biological properties, and soil organic carbon (SOC) mineralization kinetics were monitored using greenhouse, laboratory, and modeling experiments. Three pine wood biochars pyrolyzed at 460 °C (PB-460), 500 °C (PB-500), 700 °C (PB-700), and one pine bark biochar from gasification at 760 °C (GB-760) were added into soil at 1 % w/w basis. Soils amended with biochar were used to cultivate sorghum for three months in a greenhouse, followed by three months of laboratory incubation. Data obtained from laboratory incubation was modeled using various statistical approaches. The PB-500 and PB-700 reduced cumulative N2O-N emissions by 68.5 % and 73.9 % and CO2 equivalent C emissions by 66.9 % and 72.4 %, respectively, compared to unamended control. The N2O emissions were positively associated with soil nitrate N, available P, and biochar ash content while negatively associated with SOC. The CO2 emission was negatively related to biochar C:N ratio and volatile matter content. Biochar amended soils had 49.2 % (PB-500) to 87.7 % (PB-700) greater SOC and 22.9 % (PB-700) to 48.1 % (GB-760) greater sorghum yield than the control. While PB-700 had more saprophytes than the control, the GB-760 yielded a greater yield than biochars prepared by pyrolysis. Microbial biomass C was 7.23 to 23.3 % greater in biochar amended soils than in control. The double exponential decay model best explained the dynamics of C mineralization, which was associated with initial soil nitrate N and available P positively and total fungi and protozoa biomass negatively. Biochar amendment could be a climate smart agricultural strategy. Pyrolysis pine wood biochar showed the greatest potential to reduce GHG emissions and enhance SOC storage and stability, and gasification biochar contributed more to SOC storage and increased crop yield.

PMID:38719032 | DOI:10.1016/j.scitotenv.2024.172942

Br J Surg. 2024 May 3;111(5):znae115. doi: 10.1093/bjs/znae115.

NO ABSTRACT

PMID:38717922 | DOI:10.1093/bjs/znae115

Nat Nanotechnol. 2024 May 6. doi: 10.1038/s41565-024-01655-9. Online ahead of print.

ABSTRACT

Defending against future pandemics requires vaccine platforms that protect across a range of related pathogens. Nanoscale patterning can be used to address this issue. Here, we produce quartets of linked receptor-binding domains (RBDs) from a panel of SARS-like betacoronaviruses, coupled to a computationally designed nanocage through SpyTag/SpyCatcher links. These Quartet Nanocages, possessing a branched morphology, induce a high level of neutralizing antibodies against several different coronaviruses, including against viruses not represented in the vaccine. Equivalent antibody responses are raised to RBDs close to the nanocage or at the tips of the nanoparticle's branches. In animals primed with SARS-CoV-2 Spike, boost immunizations with Quartet Nanocages increase the strength and breadth of an otherwise narrow immune response. A Quartet Nanocage including the Omicron XBB.1.5 'Kraken' RBD induced antibodies with binding to a broad range of sarbecoviruses, as well as neutralizing activity against this variant of concern. Quartet nanocages are a nanomedicine approach with potential to confer heterotypic protection against emergent zoonotic pathogens and facilitate proactive pandemic protection.

PMID:38710880 | DOI:10.1038/s41565-024-01655-9

Nat Nanotechnol. 2024 May 6. doi: 10.1038/s41565-024-01655-9. Online ahead of print.

ABSTRACT

Defending against future pandemics requires vaccine platforms that protect across a range of related pathogens. Nanoscale patterning can be used to address this issue. Here, we produce quartets of linked receptor-binding domains (RBDs) from a panel of SARS-like betacoronaviruses, coupled to a computationally designed nanocage through SpyTag/SpyCatcher links. These Quartet Nanocages, possessing a branched morphology, induce a high level of neutralizing antibodies against several different coronaviruses, including against viruses not represented in the vaccine. Equivalent antibody responses are raised to RBDs close to the nanocage or at the tips of the nanoparticle's branches. In animals primed with SARS-CoV-2 Spike, boost immunizations with Quartet Nanocages increase the strength and breadth of an otherwise narrow immune response. A Quartet Nanocage including the Omicron XBB.1.5 'Kraken' RBD induced antibodies with binding to a broad range of sarbecoviruses, as well as neutralizing activity against this variant of concern. Quartet nanocages are a nanomedicine approach with potential to confer heterotypic protection against emergent zoonotic pathogens and facilitate proactive pandemic protection.

PMID:38710880 | DOI:10.1038/s41565-024-01655-9

Epilepsy Behav Rep. 2024 Apr 1;26:100665. doi: 10.1016/j.ebr.2024.100665. eCollection 2024.

ABSTRACT

Neonatal seizures can lead to long-term neurodevelopmental problems. This study aims to identify predictors of poor developmental outcomes in neonates with seizures to aid in early intervention and referral for follow-up and rehabilitation. This observational study was conducted in the Department of Neonatology and Institute of Paediatric Neurodisorder and Autism, Bangabandhu Sheikh Mujib Medical University. Among 75 study cases of neonatal seizure, 23 died, and 46 were followed-up at 6 and 9 months after discharge. EEGs were performed on every patient. A comprehensive neurological examination and developmental evaluation were performed using Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III). Three-fourths of neonates were born at term (76.1 %), and over half were male (56.5 %). The majority were appropriate for gestational age (79.7 %) and had an average birth weight of 2607 ± 696 g (±SD). Over half of the neonates (52.2 %) had adverse neurodevelopmental outcomes, with global developmental delay being the most common. Recurrent seizures, the number of anticonvulsants needed to control seizures, and abnormal Electroencephalograms were identified as independent predictors of adverse neurodevelopmental outcomes. The study highlights the need for early referral for follow-up and rehabilitation of neonates with seizures having abnormal electroencephalograms, recurrent seizures and requiring more anticonvulsants to control seizures.

PMID:38708367 | PMC:PMC11068513 | DOI:10.1016/j.ebr.2024.100665

ACS Omega. 2024 Apr 17;9(17):19108-19116. doi: 10.1021/acsomega.3c10112. eCollection 2024 Apr 30.

ABSTRACT

Biopolymers have gained significant importance in the field of biomedicine, particularly in addressing organ and tissue loss in living organisms. These polymers exhibit temporary functionality during treatment and undergo biodegradation once their intended purpose is fulfilled. The diverse characteristics of these biopolymers expand their range of applications, albeit necessitating extensive experimentation and a time commitment for thorough investigation. Computational models have emerged as a promising avenue for predictive analysis, complementing traditional experimental methods. In this study, we delve into the degradation dynamics of polyester materials with a specific emphasis on the hydrolysis process. We employed an appropriate reaction diffusion model to unveil the underlying mechanisms governing material weight loss and erosion within a two-dimensional framework for a rectangular slice of the implant. By bridging computational modeling with empirical research, this study provides valuable insights into the behavior of biopolymers, contributing to a deeper understanding of these materials and their potential for advanced biomedical applications. To illustrate this framework's effectiveness, we conducted a case study using experimental data from the literature, focusing on poly(d,l-lactic acid) material.

PMID:38708230 | PMC:PMC11063999 | DOI:10.1021/acsomega.3c10112

Heliyon. 2024 Apr 16;10(9):e29506. doi: 10.1016/j.heliyon.2024.e29506. eCollection 2024 May 15.

ABSTRACT

Public transportation plays a critical role in meeting transportation demands, particularly in densely populated areas. The COVID-19 pandemic has highlighted the importance of public health measures, including the need to prevent the spread of the virus through public transport. The spreading of the virus on a passenger ship is studied using the Computational Fluid Dynamic (CFD) model and Monte Carlo simulation. A particular focus was the context of Bangladesh, a populous maritime nation in South Asia, where a significant proportion of the population utilizes passenger ships to meet transportation demands. In this regard, a turbulence model is used, which simulates the airflow pattern and determines the contamination zone. Parameters under investigation are voyage duration, number of passengers on board, social distance, the effect of surgical masks, and others. This study shows that the transmission rate of SARS-CoV-2 infection on public transport, such as passenger ships, is not necessarily directly proportional to voyage duration or the number of passengers onboard. This model has the potential to be applied in various other modes of transportation, including public buses and airplanes. Implementing this model may help to monitor and address potential health risks effectively in the public transport networks.

PMID:38698983 | PMC:PMC11064074 | DOI:10.1016/j.heliyon.2024.e29506

J Neurosci. 2024 May 1:e2148232024. doi: 10.1523/JNEUROSCI.2148-23.2024. Online ahead of print.

ABSTRACT

Aberrant condensation and localisation of the RNA-binding protein (RBP) fused in sarcoma (FUS) occur in variants of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Changes in RBP function are commonly associated with changes in axonal cytoskeletal organisation and branching in neurodevelopmental disorders. Here, we asked whether branching defects also occur in vivo in a model of FUS-associated disease. We use two reported Xenopus models of ALS/FTD (of either sex), the ALS-associated mutant FUS(P525L) and a mimic of hypomethylated FUS, FUS(16R). Both mutants strongly reduced axonal complexity in vivo. We also observed an axon looping defect for FUS(P525L) in the target area, which presumably arises due to errors in stop cue signalling. To assess whether loss of axon complexity also had a cue-independent component, we assessed axonal cytoskeletal integrity in vitro Using a novel combination of fluorescence and atomic force microscopy, we found that mutant FUS reduced actin density in the growth cone, altering its mechanical properties. Therefore, FUS mutants may induce defects during early axonal development.Significance statement This study demonstrates that mutation of the ALS/FTD (amyotrophic lateral sclerosis/frontotemporal dementia)-associated RNA-binding protein Fused in Sarcoma (FUS) can result in changes in axonal development. These changes occur both axon-autonomously in cytoskeletal organisation during axon extension and context-dependently during axonal branching. This indicates pre-symptomatic, developmental changes in axonal organisation may occur in familial disease variants.

PMID:38692734 | DOI:10.1523/JNEUROSCI.2148-23.2024

Health Sci Rep. 2024 Apr 29;7(5):e2075. doi: 10.1002/hsr2.2075. eCollection 2024 May.

ABSTRACT

BACKGROUND AND AIMS: Diabetic Foot Ulcers (DFUs) are a significant health concern, particularly in Low- and Middle-Income Countries (LMICs). This review explores key strategies for managing DFUs in LMICs, including integrating podiatry, endocrinology, and wound care services, educating patients, promoting self-care, and preventive measures to reduce amputation rates.

METHODS: A comprehensive literature review was conducted, focusing on studies conducted in Low and Middle Income Countries to facilitate a qualitative analysis. The review examined the aetiology and risk factors to developing DFUs, clinical presentation, multidisciplinary management and evidence based interventions, challenges to the provision of care and future directions, all pertaining to DFUs in low and middle income countries.

RESULTS: The aetiology and risk factors contributing to the development of DFUs are complex and multifaceted. Factors such as limited access to health care, inadequate diabetes management, and socioeconomic disparities significantly influence the incidence of DFUs. Clinical presentation varies, with patients often presenting at advanced stages of the disease due to delayed or missed diagnoses. Multidisciplinary management, incorporating podiatry, endocrinology, and wound care services, has exhibited substantial promise in enhancing patient outcomes. Evidence-based interventions, including offloading techniques, wound debridement, and the use of advanced wound dressings, have proven effective in promoting ulcer healing.

CONCLUSION: The burden of DFUs in LMICs requires comprehensive strategies. Integrating podiatry, endocrinology, and wound care services, along with patient education and self-care practices, is essential for reducing amputations and improving patients' quality of life. Regular follow-up and early detection are vital for effective DFU management, emphasizing the need for ongoing research and investment in LMIC health care infrastructure. Embracing these multidisciplinary, patient-centered approaches can effectively address the challenge of DFUs in LMICs, leading to better patient outcomes and improved quality of life.

PMID:38690005 | PMC:PMC11058085 | DOI:10.1002/hsr2.2075

J Integr Neurosci. 2024 Apr 12;23(4):80. doi: 10.31083/j.jin2304080.

ABSTRACT

Parkinson's disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, including hallucinations. The use of antipsychotic medications is a common strategy to manage hallucinations associated with Parkinson's disease psychosis (PDP). However, careful consideration is necessary when selecting the most appropriate drug due to the potential risks associated with the available treatment options. Atypical antipsychotics (AAPs), such as Pimavanserin and Clozapine, have effectively controlled PDP symptoms. On the contrary, the support for utilizing quetiapine is not as substantial as other antipsychotics because research studies specifically investigating its application are still emerging and relatively recent. The broad mechanisms of action of AAPs, involving dopamine and serotonin receptors, provide improved outcomes and fewer side effects than typical antipsychotics. Conversely, other antipsychotics, including risperidone, olanzapine, aripiprazole, ziprasidone, and lurasidone, have been found to worsen motor symptoms and are generally not recommended for PDP. While AAPs offer favorable benefits, they are associated with specific adverse effects. Extrapyramidal symptoms, somnolence, hypotension, constipation, and cognitive impairment are commonly observed with AAP use. Clozapine, in particular, carries a risk of agranulocytosis, necessitating close monitoring of blood counts. Pimavanserin, a selective serotonin inverse agonist, avoids receptor-related side effects but has been linked to corrected QT (QTc) interval prolongation, while quetiapine has been reported to be associated with an increased risk of mortality. This review aims to analyze the benefits, risks, and mechanisms of action of antipsychotic medications to assist clinicians in making informed decisions and enhance patient care.

PMID:38682215 | DOI:10.31083/j.jin2304080

Energy Res Soc Sci. 2023 Jul;101:103092. doi: 10.1016/j.erss.2023.103092. Epub 2023 May 30.

ABSTRACT

Energy insecurity research has described the prevalence and circumstances of household energy unaffordability, as well as its outcomes for health. Previous studies have also noted coping strategies that result from energy insecurity. We provide evidence advancing our understanding of the nature and extent of these coping strategies. In 2020, we conducted in-depth interviews with 30 energy insecure household members enrolled in one or more energy assistance programs in Washington D.C. We asked about their home conditions, utility usage, cost-reducing strategies, understanding of environmental concerns, and main sources of expenses and income. Qualitative analysis revealed two key themes that characterize how individuals experience energy insecurity and navigate energy assistance services: 1) vigilant conservation refers to the duty to conserve utility resources and strictly manage the household's financial affairs by saving across various categories, and 2) administrative burden includes the hardships attached to seeking help and managing the bureaucratic processes of formal support. Our study connects energy insecurity to broader questions on sustainability and clarifies a need to relieve households of administrative burdens.

PMID:38680547 | PMC:PMC11052585 | DOI:10.1016/j.erss.2023.103092

Pharmaceuticals (Basel). 2024 Apr 15;17(4):505. doi: 10.3390/ph17040505.

ABSTRACT

In the present work, an efficient isocratic HPLC method was developed for the precise and accurate estimation of vitamin D3 in tablet form. The chromatographic conditions comprised an L3 silica column (5 µm in particle size, 4.6 mm × 250 mm) with a mobile phase n-hexane/ethyl acetate (85:15 v/v) with a flow rate of 2.0 mL/min and a detection wavelength of 292 nm. The new methodology was validated for accuracy, precision, specificity, robustness, and quantification limits according to an official monograph of USP/BP and ICH guidelines. The peak areas of the six replicates of the homogeneous sample were recorded. The mean value obtained was 67,301, and the relative standard deviation (RSD) was 0.1741. The linearity and range were in the acceptable bounds, i.e., 0.999, which was calculated using regression line analysis. The results show that the method is truly acceptable as the RSD, as the flow rate was 0.81%, while for the mobile phase composition, it was 0.72%, which lies in the acceptable range. The limit of detection (LOD) and the limit of quantification (LOQ) values were 0.0539 µg/mL and 0.1633 µg/mL, respectively. The % RSD of the intra and inter-day precision of the method was deemed acceptable according to the international commission for harmonization guidelines. The developed method has potential to be used for the detection and quantification of vitamin D3 during routine analysis for tablets in dosage form.

PMID:38675464 | DOI:10.3390/ph17040505