Revolutionizing Chronic Heart Disease Management: The Role of IoT-Based Ambulatory Blood Pressure Monitoring System.

Chronic heart disease (CHD) is a widespread and persistent health challenge that demands immediate attention. Early detection and accurate diagnosis are essential for effective treatment and management of this condition. To overcome this difficulty, we created a state-of-the-art IoT-Based Ambulatory Blood Pressure Monitoring System that provides real-time blood pressure readings, systolic, diastolic, and pulse rates at predefined intervals. This unique technology comes with a module that forecasts CHD's early warning score. Various machine learning algorithms employed comprise Naïve Bayes, K-Nearest Neighbors (K-NN), random forest, decision tree, and Support Vector Machine (SVM). Using Naïve Bayes, the proposed model has achieved an impressive 99.44% accuracy in predicting blood pressure, a vital aspect of real-time intensive care for CHD. This IoT-based ambulatory blood pressure monitoring (IABPM) system will provide some advancement in the field of healthcare. The system overcomes the limitations of earlier BP monitoring devices, significantly reduces healthcare costs, and efficiently detects irregularities in chronic heart diseases. By implementing this system, we can take a significant step forward in improving patient outcomes and reducing the global burden of CHD. The system's advanced features provide an accurate and reliable diagnosis that is essential for treating and managing CHD. Overall, this IoT-based ambulatory blood pressure monitoring system is an important tool for the early identification and treatment of CHD in the field of healthcare.

Model-Informed Development of a Cost-Saving Dosing Regimen for Sacituzumab Govitecan.

BACKGROUND: The antibody-drug conjugate sacituzumab govitecan is approved for metastatic triple-negative breast cancer and has shown promising results in various other types of cancer. Its costs may limit patient access to this novel effective treatment modality. OBJECTIVE: The purpose of this study was to develop an evidence-based rational dosing regimen that results in targeted drug exposure within the therapeutic range while minimizing financial toxicity, to improve treatment access. PATIENTS AND METHODS: Exposure equivalent dosing strategies were developed based on pharmacokinetic modeling and simulation by using the published pharmacokinetic model developed by the license holder. The alternative dose was based on the principle of using complete vials to prevent spillage and on the established non-linear relationship between body weight and systemic exposure. Equivalent exposure compared to the approved dosing regimen of 10 mg/kg was aimed for. Equivalent exposure was conservatively defined as calculated geometric mean ratios within the 0.9-1.11 boundaries for area under the concentration-time curve (AUC), trough concentration (Ctrough) and maximum concentration (Cmax) of the alternative dosing regimen compared to the approved dosing regimen. Since different vial sizes are available for the European Union (EU) and United States (US) market, because body weight distributions differ between these populations, we performed our analysis for both scenarios. RESULTS: Dosing regimens of sacituzumab govitecan for the EU (< 50 kg: 400 mg, 50-80 kg: 600 mg, and > 80 kg: 800 mg) and US population (< 40 kg: 360 mg, 40-65 kg: 540 mg, 65-90 kg: 720 mg, and > 90 kg: 900 mg) were developed, based on weight bands. The geometric mean ratios for all pharmacokinetic outcomes were within the predefined equivalence boundaries, while the quantity of drug used was 21.5% and 19.0% lower for the EU and US scenarios, respectively. CONCLUSIONS: With the alternative dosing proposal, an approximately 20% reduction in drug expenses for sacituzumab govitecan can be realized while maintaining an equivalent and more evenly distributed exposure throughout the body weight range, without notable increases in pharmacokinetic variability.

Prolonged Grief Disorder, but Not Death From COVID-19, Elicits Public Stigma: A Vignette-Based Experiment.

We investigated the effects of cause of death (COVID-19 with an underlying medical condition vs. without) and prolonged grief disorder status (PGD present or absent) on participants' reported public stigma towards the bereaved. Participants (N = 304, 66% women; Mage = 39.39 years) were randomly assigned to read one of four vignettes describing a bereaved man. Participants completed stigma measures assessing negative attributions, desired social distance, and emotional reactions. Participants reported significantly stronger stigmatizing responses towards an individual with PGD (vs. without PGD) across all stigma measures. There was no significant difference in stigma based on cause of death; however, stigma was reported regardless of cause of death. There was no significant interaction between cause of death and PGD on stigma. This study supports the robust finding of public stigma being reported toward an individual with PGD, suggesting these individuals are at risk of public stigma and not receiving adequate bereavement support.

Engineering dynamic covalent bond-based nanosystems for delivery of antimicrobials against bacterial infections.

Nanodrug delivery systems (NDDS) continue to be explored as novel strategies enhance therapy outcomes and combat microbial resistance. The need for the formulation of smart drug delivery systems for targeting infection sites calls for the engineering of responsive chemical designs such as dynamic covalent bonds (DCBs). Stimuli response due to DCBs incorporated into nanosystems are emerging as an alternative way to target infection sites, thus enhancing the delivery of antibacterial agents. This leads to the eradication of bacterial infections and the reduction of antimicrobial resistance. Incorporating DCBs on the backbone of the nanoparticles endows the systems with several properties, including self-healing, controlled disassembly, and stimuli responsiveness, which are beneficial in the delivery and release of the antimicrobial at the infection site. This review provides a comprehensive and current overview of conventional DCBs-based nanosystems, stimuli-responsive DCBs-based nanosystems, and targeted DCBs-based nanosystems that have been reported in the literature for antibacterial delivery. The review emphasizes the DCBs used in their design, the nanomaterials constructed, the drug release-triggering stimuli, and the antibacterial efficacy of the reported DCBs-based nanosystems. Additionally, the review underlines future strategies that can be used to improve the potential of DCBs-based nanosystems to treat bacterial infections and overcome antibacterial resistance.

Financial scarcity, psychological well-being and perceptions: an evaluation of the Nigerian currency redesign policy outcomes.

BACKGROUND: The relationship between insufficient financial resources and psychological health has been extensively studied and established in various contexts. However, there remains uncertainty regarding the potential impact of the Nigerian naira currency redesign policy on the psychological well-being of Nigerians. This policy, which aimed to demonetize the economy and promote economic stability, involved changes to the physical appearance of some naira denominations (200, 500 and 1000). Understanding the effects of this policy on psychological health is essential for evaluating its overall societal impact and identifying potential areas for improvement in future currency redesign initiatives. METHODS: The study is a cross-sectional mixed-methods study involving 2237 respondents across the six geopolitical zones of Nigeria. Utilizing the simple random, snowball and convenience sampling technique, social media platforms (Facebook and WhatsApp) were used to recruit respondents. Variables were analyzed at descriptive and inferential levels. The qualitative component comprised seven (7) in-depth interviews with participants across the geo-political zones. RESULTS: The perceptions of respondents towards the policy were diverse across different demographic groups. It was widely perceived that the timing of the policy was inappropriate, considering the challenges faced in utilizing online payment platforms and the significant inaccessibility of cash. Furthermore, the analysis revealed that demographic variables played a role in explaining systematic variations in the experience of financial scarcity and its effect on psychological health during the cash crunch that ensued as a result of the Nigerian naira currency redesign policy. CONCLUSIONS: This study identified a significant association between the psychological inventory of financial scarcity and psychological well-being among residents in Nigeria during the cash crunch resulting from the Naira redesign policy. The findings suggest that the financial scarcity experienced by Nigerians due to the policy had a substantial impact on individuals' psychological well-being. We recommend that a holistic approach be undertaken by policymakers to ensure that policy actions not only address economic objectives but also safeguard the mental health and overall well-being of the population.

Prevalence of anaerobic bacteria in surgical site infections in Lagos University Teaching Hospital.

Background: Surgical site infection (SSI) is the second most common cause of nosocomial infection, after urinary tract infection. Sequelae of SSI include increased healthcare costs and worse patient outcomes. There is a paucity of research studies on the impact of anaerobic organisms on SSIs in Nigeria. The aim of this study was to determine the role of anaerobic bacteria in SSI encountered at the Lagos University Teaching Hospital (LUTH). Materials and Methods: A total of 438 patients were consecutively recruited into this study from general surgery, obstetrics and gynaecology and paediatric units of the LUTH from 1 July through 31 December 2019. Two surgical wound specimens were collected from all patients with suspected SSIs. One was for anaerobic culture using Brucella blood agar incubated in an anaerobic jar that secured anaerobiosis using the anaerobic gas pack. The other swab was used for aerobic culture on blood agar incubated on air at 37oC. Identifications and antibiotic sensitivity testing were performed according to standard laboratory procedures. Result: The overall incidence of SSI in the study was 12.3%. The incidence of anaerobic SSI was 1.1%. The distribution of anaerobic infections by medical specialty unit was as follows; general surgery (1.6%), obstetrics and gynaecology (0.8%) and paediatrics (0.9%). Bacteroides species was the only anaerobic isolate. The risk factors associated with the development of SSI by multiple logistic regression analysis were duration of surgery greater than 2 h (OR 1.418; 95% CI 1.834-9.286; P = 0.001) and NNIS risk index 2 and 3 - (OR 2.165; 95% CI 2.366-32.086; P = 0.001). Conclusions: The prevalence of anaerobic SSI was 1.1%. Duration of surgery greater than 2 h and NNIS risk index 2 and 3 were independent predictors of SSI.

Storage and time course effects on the quality of oil extracted from Phyllanthus amarus Schumach and Annona muricata Linn and their antidiabetic potentials.

With the advent of modern technology, advancements in processing and storage techniques, and increasing medical knowledge, people are becoming aware of deterioration in the quality of medicinal products due to storage methods and time. In most cases, herbal products are not consumed immediately after production; as such, improper storage can result in physical, chemical, and microbiological changes. The study evaluated the effect of storage methods and time on the quality of oil extracted from Phyllanthus amarus Schumach and Annona muricata Linn and assessed their antidiabetic and antioxidative effects. Plants were air-dried, pulverized, and then subjected to Soxhlet extraction in petroleum ether. The oil was evaluated for phytochemical constituents and the effects of time and storage methods on its physicochemical properties. Characterization of the oil was done by spectroscopic techniques. Oils from both plants contained tannins, flavonoids, alkaloids, steroids, glycosides, terpenoids, phlobotannins, resins, reducing sugar, phenols, and saponins in different proportions. The oil from A. muricata had higher phenolic (3.11 ± 0.31 mg GAE/g), flavonoid (11.82 ± 0.08 mg QUE/g), alkaloid (16.37 ± 0.56 mg APE/g), and tannin (7.13 ± 0.47 mg CE/g) contents than the oil from P. amarus, which had 0.54 ± 0.08 mg GAE/g, 7.83 ± 0.13 mg QUE/g, 9.87 ± 0.15 mg APE, and 3.16 ± 0.12 mg CE/g for total phenolic, flavonoids, alkaloids, and tannins, respectively. Initial acid, iodine, peroxide, and saponification values recorded for P. amarus were 5.63 ± 0.82 mg KOH/g, 97.17 ±0.53 Wijis, 9.31 ± 0.15 mEq/kg, and 116.11 ± 0.74 mg KOH/g, respectively, significantly different from those of A. muricata , which had values of 1.17 ± 0.08 mg KOH, 76.23 ± 0.03 Wijis, 6.75 ± 0.47 mEq/kg, and 193.31 ± 0.52 mg KOH/g, respectively. FT-IR characterization of the oils revealed the presence of carboxylic acid, alkyl, alkene, alkane, haloalkane, aldehyde, aromatic amine, α-unsaturated and ß-unsaturated esters, and phenol functional groups. P. amarus oil inhibited α-amylase (IC50 0.17 ± 0.03 mg/ml), α-glucosidase (IC50 0.64 ± 0.03 mg/ml), and xanthine oxidase (0.70 ± 0.01 mg/ml) to a greater extent than A. muricata oil, with IC50 values of 0.43 ± 0.05 mg/ml (α-amylase), 2.25 ± 0.31 mg/ml (α-glucosidase), and 0.78 ± 0.07 mg/ml (xanthine oxidase). This study showed that oils from the tested plants have low rancidity with a moderate shelf life. The extracts contained essential phytoconstituents that significantly inhibited α-glucosidase and xanthine oxidase. These effects of the oil indicate their potential to prevent diabetes, gout, and oxidative stress. Consequently, the supply of P. amarus and A. muricata in homemade diets is strongly encouraged for healthy living.

Survey of Animal Neoplastic Cases Diagnosed in Nigerian Veterinary Teaching Hospitals, 2000-2017.

Incidence data from 17-year veterinary neoplasm surveillance and registration were reviewed. Most of the neoplastic cases diagnosed in Nigerian veterinary teaching hospitals (VTHs) were in the avian (49%) and canine species (44%). Fewer cases were recorded in the equine (3.2%), bovine (2.4%), ovine (1.5%), caprine (0.3%) and porcine (0.15%) species. Marek's disease was the most prevalently diagnosed neoplastic disease of domestic animals in Nigerian VTHs from 2000-2017. Also, the Nigerian local breed had a higher mean distribution than any other dog breed and this was statistically significant (p < 0.05). Nearly all of the neoplastic cases diagnosed, were found in females (60.4%) and so the mean distribution of sex was statistically significant (p < 0.05). The digestive system, with 296 (46.25%) cases, was the anatomic location where the majority of the neoplastic cases were found. However, the mean distribution of different neoplastic anatomic sites was not statistically significant (p > 0.05). In conclusion, little emphasis is given to the appropriate diagnosis and recording of neoplastic cases that are diagnosed. The study provides information regarding the prevalence and distribution of tumours in different animal species consulted in Nigeria veterinary teaching hospitals. To illustrate all of this, ArcGIS software was used. Veterinary clinicians, pathologists and epidemiologists from Nigeria may benefit from the results of this study by freely accessing some specific data regarding the breed, the age group or the gender of some animal species diagnosed with different tumours.

Efficacy of a Single Oral Dose of Artesunate plus Sulfalene-Pyrimethamineversus Praziquantel in the Treatment of Schistosoma mansoni in Kenyan Children: An Open-Label, Randomized, Exploratory Trial.

Unlike praziquantel, artemisinin derivatives are effective against juvenile schistosome worms. We assessed the efficacy and safety of a single oral dose of artesunate plus sulfalene-pyrimethamine versus praziquantel in the treatment of Schistosoma mansoni. Seventy-three schoolchildren (aged 9-15 years) with confirmed S. mansoni infection in Rarieda, western Kenya, were randomly assigned to receive either a single oral dose of artesunate plus sulfalene-pyrimethamine (n = 39) or a single dose of praziquantel (n = 34). The cure and egg reduction rates at 4 weeks posttreatment were 69.4% (25/36) versus 80.6% (25/31) (P = 0.297) and 99.1% versus 97.5% (P = 0.607) in the artesunate plus sulfalene-pyrimethamine group versus praziquantel group, respectively. Fourteen children developed adverse events, and there were no serious adverse events. A single oral dose of artesunate plus sulfalene-pyrimethamine has efficacy comparable to that of praziquantel in the treatment of S. mansoni, but these results should be confirmed in larger randomized controlled trials.

Multi-functional pH-responsive and biomimetic chitosan-based nanoplexes for targeted delivery of ciprofloxacin against bacterial sepsis.

Bacterial sepsis is a mortal syndromic disease characterized by a complex pathophysiology that hinders effective targeted therapy. This study aimed to develop multifunctional, biomimetic and pH-responsive ciprofloxacin-loaded chitosan (CS)/sodium deoxycholic acid (SDC) nanoplexes (CS/SDC) nanoplexes with the ability to target and modulate the TLR4 pathway, activated during sepsis. The formulated nanoplexes were characterized in terms of physicochemical properties, in silico and in vitro potential biological activities. The optimal formulation showed good biocompatibility and stability with appropriate physicochemical parameters. The surface charge changed from negative at pH 7.4 to positive at pH 6.0 accompanied with a significantly faster release of CIP at pH 6.0 compared to 7.4. The biomimicry was elucidated by in silico tools and MST and results confirmed strong binding between the system and TLR4. Furthermore, the system revealed 4- and 2-fold antibacterial enhancement at acidic pH, and 3- and 4-fold better antibiofilm efficacy against Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa) respectively, compared to bare CIP. In addition, enhanced bacterial efflux pump inhibition was demonstrated by CS/SDC nanoplexes. Finally, the developed nanosystem showed excellent antioxidant activity against DPPH radicals. Taken together, the study confirmed the multi-functionalities of CS/SDC nanoplexes and their potential benefits in improving bacterial sepsis therapy.

Public stigma toward prolonged grief and COVID-19 bereavement: A vignette-based experiment.

We investigated the effects of cause of death and the presence of prolonged grief disorder (PGD) on eliciting public stigma toward the bereaved. Participants (N = 328, 76% female; Mage = 27.55 years) were randomly assigned to read one of four vignettes describing a bereaved man. Each vignette differed by his PGD status (PGD diagnosis or no PGD diagnosis) and his wife's cause of death (COVID-19 or brain hemorrhage). Participants completed public stigma measures assessing negative attributions, desired social distance, and emotional reactions. Bereavement with PGD (versus without PGD) elicited large and significantly stronger responses across all stigma measures. Both causes of death elicited public stigma. There was no interaction between cause of death and PGD on stigma. With increased PGD rates expected during the pandemic, the potential for public stigma and reduced social support for people bereaved via traumatic deaths and people with PGD requires mitigation.

Systematic Review and Meta-Analysis: Early Irritability as a Transdiagnostic Neurodevelopmental Vulnerability to Later Mental Health Problems.

OBJECTIVE: Irritability is a transdiagnostic indicator of child and adolescent internalizing and externalizing problems that is measurable from early life. The objective of this systematic review was to determine the strength of the association between irritability measured from 0 to 5 years and later internalizing and externalizing problems, to identify mediators and moderators of these relationships, and to explore whether the strength of the association varied according to irritability operationalization. METHOD: Relevant studies published in peer-reviewed, English-language journals between the years 2000 and 2021 were sought from EMBASE, PsycINFO, MEDLINE, CINAHL, and ERIC. We synthesized studies that included a measure of irritability within the first 5 years of life and reported associations with later internalizing and/or externalizing problems. Methodological quality was assessed using the JBI-SUMARI Critical Appraisal Checklist. RESULTS: Of 29,818 identified studies, 98 met inclusion criteria, with a total number of 932,229 participants. Meta-analysis was conducted on 70 studies (n = 831,913). Small, pooled associations were observed between infant irritability (0-12 months) and later internalizing (r = 0.14, 95% CI = 0.09, 0.20) and externalizing symptoms (r = 0.16, 95% CI = 0.11, 0.21) symptoms. For toddler/preschool irritability (13-60 months), small-to-moderate pooled associations were observed for internalizing (r = 0.21, 95% CI = 0.14, 0.28) and externalizing (r = 0.24, 95% CI = 0.18, 0.29) symptoms. These associations were not moderated by the lag between irritability and outcome assessment, although the strength of the associations varied according to irritability operationalization. CONCLUSION: Early irritability is a consistent transdiagnostic predictor of internalizing and externalizing symptoms in childhood and adolescence. More work is required to understand how to accurately characterize irritability across this developmental period, and to understand mechanisms underlying the relationship between early irritability and later mental health problems. DIVERSITY & INCLUSION STATEMENT: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as living with a disability. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. STUDY PREREGISTRATION INFORMATION: Early irritability as a transdiagnostic neurodevelopmental vulnerability to early onset mental health problems: A systematic review; https://www.crd.york.ac.uk/prospero/; CRD42020214658.

Psychosocial wellbeing, parental concerns, and familial impact of children with developmental coordination disorder.

BACKGROUND: Developmental Coordination Disorder (DCD) is a neurodevelopmental condition impacting motor skill acquisition and competence. While previous studies have identified adverse psychosocial outcomes in DCD, they are limited by small or population-screened, community-based samples. AIMS: To understand the psychosocial difficulties, parental concerns, and familial impacts of childhood DCD in a large population-based sample. METHODS AND PROCEDURES: Parents of 310 children aged 4 - 18 years with a diagnosis of DCD (or synonymous term) completed the Impact for DCD survey. Parent-rated measures of emotional problems, peer problems, and prosocial behaviour were compared to normative data. Parental concerns for the impact of DCD on participation, interaction, emotional well-being, and the family system were examined. OUTCOMES AND RESULTS: Compared to typically developing children, children with DCD were rated significantly higher for emotional and peer problems, and significantly lower for prosocial behaviours. Parents most commonly reported concerns for their child's future and withdrawal from physical activity. The presence of one or more co-occurring disorders did not significantly influence outcomes. CONCLUSION AND IMPLICATIONS: Findings highlight the poor psychosocial outcomes for children with DCD. Crucially, poor psychosocial outcomes were just as likely in those with a single diagnosis of DCD as those with DCD and multiple co-occurring diagnoses. Parents reported concerns for their child (i.e., non-participation and social withdrawal) that are not targeted in existing DCD intervention modalities and emphasised the impact of DCD on the whole family unit. WHAT THIS PAPER ADDS: This paper presents data from the largest parent-reported survey of children with a known diagnosis of DCD (or synonymous labels). It highlights the significant impact of DCD on psychosocial outcomes in children across age groups. The children in this study were rated by their parents to have significantly higher levels of emotional and peer problems, and lower prosocial behaviours, than similarly aged Australian children without DCD. It also challenges the misconception that poor psychosocial outcomes in DCD are the result of co-occurring disorders, with outcomes observed to be as poor in children with a sole diagnosis of DCD in this sample. Furthermore, findings highlighted the significant worry and concern that parents with DCD face, particularly around their child's participation and their emotional health. Finally, parents reported on the considerable impact that DCD had on their family unit, regularly causing worry and concern, influencing their choice of activities, and causing financial strain. These concerns and impacts are not addressed in current intervention models for DCD and highlight the need for support mechanisms moving forward.

SCHISTOACT: a protocol for an open-label, five-arm, non-inferiority, individually randomized controlled trial of the efficacy and safety of praziquantel plus artemisinin-based combinations in the treatment of Schistosoma mansoni infection.

BACKGROUND: Schistosomiasis control relies on praziquantel for preventive chemotherapy. Alternative drugs are needed for the treatment and control of schistosomiasis. Praziquantel is effective against adult schistosome worms but ineffective against larval stages of the parasite and cannot prevent re-infection or interrupt the transmission of infection. Continued reliance on praziquantel for wide-scale schistosomiasis control will likely accelerate the emergence of drug resistance. Artemisinin derivatives are effective against the juvenile stages but ineffective against adult worms. The SCHISTOACT study aimed to evaluate the efficacy and safety of praziquantel plus one of four artemisinin-based combinations in treating Schistosoma mansoni infection in Kenya. METHODS: The SCHISTOACT study is an open-label, head-to-head, five-arm, proof-of-concept, non-inferiority, individually randomized controlled trial with a follow-up of 12 weeks. A total of 540 primary school-aged children from the Mwea area, Kirinyaga County in central Kenya, diagnosed with S. mansoni infection (by Kato-Katz method) are randomly allocated (1:1:1:1:1) to a single dose of praziquantel plus a 3-day course of artesunate-sulfalene/pyrimethamine, or artesunate-amodiaquine, or artesunate plus mefloquine, or dihydroartemisinin-piperaquine, or praziquantel control arm. The primary endpoints are efficacy (cure rate, assessed by microscopy) and safety (adverse events) of each study arm 6 weeks after treatment. Secondary endpoints include cumulative cure rate, egg reduction rate, and re-infection 12 weeks after treatment. The non-inferiority margin is set at - 10 for the risk difference in cure rates between praziquantel and the combined treatment. DISCUSSION: This study assesses a strategy for repurposing artemisinin-based combination therapies (ACTs) for treating schistosomiasis. It adopts a head-to-head comparison of four different ACTs to test a non-inferiority hypothesis and to strengthen local capacity to conduct clinical trials for interventions against neglected tropical diseases. TRIAL REGISTRATION: Pan-African Clinical Trials Registry PACTR202001919442161 . Retrospectively registered on 6 January 2020.

Cortisol as Biomarker for CYP17-Inhibition is Associated with Therapy Outcome of Abiraterone Acetate.

BACKGROUND: Abiraterone acetate is an irreversible 17α-hydroxylase/C17, 20-lyase (CYP17) inhibitor approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients. Inhibition of this enzyme leads to low testosterone and cortisol levels in blood. There is growing evidence that clinical efficacy of abiraterone is related to the rate of suppression of serum testosterone. However, quantification of very low levels of circulating testosterone is challenging. We therefore aimed to investigate whether circulating cortisol levels could be used as a surrogate biomarker for CYP17 inhibition in patients with mCRPC treated with abiraterone acetate. PATIENTS AND METHODS: mCRPC patients treated with abiraterone acetate were included. Abiraterone and cortisol levels were measured with a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). On treatment cortisol and abiraterone concentrations were related to treatment response and progression free survival. RESULTS: In total 117 patients were included with a median cortisol concentration of 1.13 ng/ml (range: 0.03 - 82.2) and median abiraterone trough concentration (Cmin) of 10.2 ng/ml (range: 0.58 - 92.1). In the survival analyses, abiraterone Cmin ≥ 8.4 ng/mL and cortisol < 2.24 ng/mL were associated with a longer prostate-specific antigen (PSA) independent progression-free survival than patients with an abiraterone concentration ≥ 8.4 ng/mL and a cortisol concentration ≥ 2.24 ng/mL (13.8 months vs. 3.7 months). CONCLUSION: Our study shows that cortisol is not an independent predictor of abiraterone response in patients with mCRPC, but it is of added value in combination with abiraterone levels, to predict a response on abiraterone.

The whole-genome molecular epidemiology of sequential isolates of Acinetobacter baumannii colonizing the rectum of patients in an adult intensive care unit of a tertiary hospital.

IMPORTANCE: Acinetobacter baumannii is a multidrug-resistant nosocomial pathogen that colonizes and infects debilitated patients in the ICU. There is very little information on the genomic characteristics of colonizing strains. This information is important to understand the evolution of lineages of A. baumannii that develop resistance while patients receive antibiotic treatment in the ICU. Our study demonstrated different patterns of colonization of the rectum of ICU patients with different STs of A. baumannii while one ST colonized all patients. Some STs carried more antibiotic resistance genes compared to others. However, there was a correlation between ST and a particular resistance gene profile. Our results further elucidate the dynamics of enteric colonization of this opportunistic pathogen.

A mixed method study exploring gender differences in dementia caregiving.

Few studies have investigated the experience of male carers of people with dementia and fewer specifically examined whether male and female carers of people with dementia differ in their approach to the caring role. As such, this research set-out to investigate whether male carers of people with dementia approach the caring role differently to female carers. Data from 167 survey participants (24 males and 143 females) were analysed using a mixed research methodology. Participants' demographics and scores on standardised burden and coping scales were analysed using linear regression. Participants' written responses to open-ended questions were analysed using thematic analysis anchored in theories of hegemonic masculinity. No significant gender differences were identified in carers' coping strategies or self-reported carer burden. However, qualitative analysis revealed strong thematic gender differences like: gendered barriers to help-seeking; gendered service preference; gendered considerations about residential care; gendered expression of burden; and themes of the absent son and exhausted daughter. This research identified that male carers of people with dementia approach help-seeking differently to female carers, typically focusing on addressing functional tasks and refraining from showing emotions, this despite reporting similar carer burden. Rapport building with male carers should start with conversations around functional issues rather than assessing the emotional impact of the caring role. The findings reinforce the need for more qualitative research into the unmet needs of male carers of people with dementia, to inform the design of male-friendly interventions which could facilitate timely access to services by male carers.

Inflammation-responsive drug delivery nanosystems for treatment of bacterial-induced sepsis.

Sepsis, a complication of dysregulated host immune systemic response to an infection, is life threatening and causes multiple organ injuries. Sepsis is recognized by WHO as a big contributor to global morbidity and mortality. The heterogeneity in sepsis pathophysiology, antimicrobial resistance threat, the slowdown in the development of antimicrobials, and limitations of conventional dosage forms jeopardize the treatment of sepsis. Drug delivery nanosystems are promising tools to overcome some of these challenges. Among the drug delivery nanosystems, inflammation-responsive nanosystems have attracted considerable interest in sepsis treatment due to their ability to respond to specific stimuli in the sepsis microenvironment to release their payload in a precise, targeted, controlled, and rapid manner compared to non-responsive nanosystems. These nanosystems posit superior therapeutic potential to enhance sepsis treatment. This review critically evaluates the recent advances in the design of drug delivery nanosystems that are inflammation responsive and their potential in enhancing sepsis treatment. The sepsis microenvironment's unique features, such as acidic pH, upregulated receptors, overexpressed enzymes, and enhanced oxidative stress, that form the basis for their design have been adequately discussed. These inflammation-responsive nanosystems have been organized into five classes namely: Receptor-targeted nanosystems, pH-responsive nanosystems, redox-responsive nanosystems, enzyme-responsive nanosystems, and multi-responsive nanosystems. Studies under each class have been thematically grouped and discussed with an emphasis on the polymers used in their design, nanocarriers, key characterization, loaded actives, and key findings on drug release and therapeutic efficacy. Further, this information is concisely summarized into tables and supplemented by inserted figures. Additionally, this review adeptly points out the strengths and limitations of the studies and identifies research avenues that need to be explored. Finally, the challenges and future perspectives on these nanosystems have been thoughtfully highlighted.

Cracking the Code: Unveiling the Diversity of Carbapenem-Resistant Klebsiella pneumoniae Clones in the Arabian Peninsula through Genomic Surveillance.

The rise of antimicrobial resistance is a global challenge that requires a coordinated effort to address. In this study, we examined the genetic similarity of carbapenem-resistant Klebsiella pneumoniae (CRKP) in countries belonging to the Gulf Cooperation Council (GCC) to gain a better understanding of how these bacteria are spreading and evolving in the region. We used in silico genomic tools to investigate the occurrence and prevalence of different types of carbapenemases and their relationship to specific sequence types (STs) of CRKP commonly found in the region. We analyzed 720 publicly available genomes of multi-drug resistant K. pneumoniae isolates collected from six GCC countries between 2011 and 2020. Our findings showed that ST-14 and ST-231 were the most common STs, and 51.7% of the isolates carried blaOXA-48-like genes. Additionally, we identified rare carbapenemase genes in a small number of isolates. We observed a clonal outbreak of ST-231 in Oman, and four Saudi isolates were found to have colistin resistance genes. Our study offers a comprehensive overview of the genetic diversity and resistance mechanisms of CRKP isolates in the GCC region that could aid in developing targeted interventions to combat this pressing global issue.

Melt Processible Biodegradable Blends of Polyethylene Glycol Plasticized Cellulose Diacetate with Polylactic Acid and Polybutylene Adipate-Co-Terephthalate.

Enhancing the melt processability of cellulose is key to broadening its applications. This is done via derivatization of cellulose, and subsequent plasticization and/or blending with other biopolymers, such as polylactic acid (PLA) and polybutylene adipate terephthalate (PBAT). However, derivatization of cellulose tends to reduce its biodegradability. Moreover, traditional plasticizers are non-biodegradable. In this study, we report the influence of polyethylene glycol (PEG) plasticizer on the melt processibility and biodegradability of cellulose diacetate (CD) and its blends with PLA and PBAT. CD was first plasticized with PEG (PEG-200) at 35 wt%, and then blended with PLA and PBAT using a twin-screw extruder. Blends of the PEG plasticized CD with PLA at 40 wt% and with PBAT at 60 wt% were studied in detail. Dynamic mechanical analysis (DMA) showed that PEG reduced the glass transition of the CD from ca. 220 °C to less than 100 °C, indicating effective plasticization. Scanning electron microscopy revealed that the CD/PEG-PBAT blend had a smoother morphology implying some miscibility. The CD/PEG-PBAT blend at 60 wt% PBAT had an elongation-to-break of 734%, whereas the CD/PEG-PLA blend had a tensile strength of 20.6 MPa, comparable to that of the PEG plasticized CD. After a 108-day incubation period under simulated aerobic composting, the CD/PEG-PBAT blend at 60 wt% PBAT exhibited a biodegradation of 41%, whereas that of the CD/PEG-PLA at 40 wt% PLA was 107%. This study showed that melt processible, biodegradable CD blends can be synthesized through plasticization with PEG and blending with PBAT or PLA.