Search

Abstract Background Caregivers often undertake medication management for people living with dementia without formal training. There is a need to evaluate caregiver medication management practices for people living with dementia to identify and address the key issues that contribute to caregiver burden. Objectives This study aimed to identify and summarize approaches that evaluate medication management for caregivers of people living with dementia and appraise caregiver's involvement in aspects of medication management. Search Strategy A systematic search was undertaken in five databases: Medline, Embase, PsycINFO, Scopus and International Pharmaceutical Abstracts. Studies written in English that contained tools and surveys that evaluated aspects of medication management for caregivers of PWD were included. Results A total of 10 studies were included. Medication selection was assessed in six studies, supply and monitoring/review was captured in seven studies, with administration assessed in nine studies. Caregivers were commonly involved in decision‐making for medication changes (77.1%–86.8%) and in the ordering (55.9%–86.0%) and collection (87.0%–92.4%) of medications. Reported caregiver involvement in medication administration showed a wide range (44%–94.7%) between the studies. Challenges in administration were commonly related to polypharmacy and dosage regimen complexity. Conclusions Current tools capture specific aspects of medication management, with medication administration the most evaluated aspect of medication management. Future research is needed to develop a tool to holistically evaluate the complexities of medication management for caregivers of people living with dementia to minimize adverse events at transitions of care. Public Contribution From the authors' previous research, caregivers highlighted the need to address key issues in medication management for people living with dementia.

Objective Medication management guidance for carers of people with dementia at hospital discharge is important to prevent medication-related harm during transitions of care. This study aimed to develop a tool to evaluate medication management guidance provided to carers of people with dementia at hospital discharge.Design The tool was developed using mixed methods involving two stages. Stage 1 involved item generation and content validation. Items were based on a previous qualitative study and systematic review. Content validation involved experts and consumers with knowledge or experience of medication management guidance in the acute care setting, and rating each item on importance and relevance. Stage 2 involved conducting cognitive interviews with carers of people with dementia to pretest the tool.Setting For stage 1, experts and consumers from Australia, USA and New Zealand were included. For stage 2, carers of people with dementia were recruited across Australia.Participants 18 experts and consumers participated in round 1 of content validation, and 13 experts and consumers completed round 2. Five carers of people with dementia participated in cognitive interviews.Results The final tool contained 30 items capturing information across five domains: (1) provision of medication management guidance at hospital discharge; (2) carer understanding of medication management guidance provided at discharge; (3) carer engagement in discussing the safe use of medications at discharge; (4) carer preparedness to conduct medication management activities after discharge; and (5) co-ordination of medication management guidance after discharge.Conclusions We developed the first tool to assess medication management guidance provided for carers of people with dementia at hospital discharge. The tool may be useful to inform future research strategies to improve the delivery of medication management guidance at discharge.

Objectives: Among residents who had a residential medication management review (RMMR), there is a lack of studies assessing exposure to polypharmacy and potentially inappropriate medications (PIMs) in people with dementia. This study compared the exposure to polypharmacy and PIMs in residents with dementia and without dementia receiving RMMR. Methods: A retrospective analysis was performed using data of 16,261 residents living in 343 Australian residential aged care facilities who had an RMMR in 2019. Medication use was assessed as polypharmacy (defined as ≥9 medications) and use of ≥1 PIMs using the 2019 updated Beers criteria. Dementia diagnosis was determined with ICD‐10 coding from medical records. Descriptive analyses reported resident demographics and patterns of medication use. Pearson's χ2 tests and logistic regression analysis were conducted to compare medication exposure between residents with and without dementia. Results: Among 16,261 residents, 6781 (42%) had dementia. Residents with dementia were significantly more likely to be exposed to polypharmacy and PIMs, compared to those without dementia (74% vs. 70% and 83% vs. 73%, p <.001 respectively). Residents with dementia had 1.31 times the odds of exposure to polypharmacy (adjusted OR: 1.31, 95% CI: 1.22–1.41, p <.001) and 1.88 times the odds of being prescribed ≥1 PIMs than people without dementia (adjusted OR: 1.88, 95% CI: 1.73–2.04, p <.001). Conclusions: In a study of residents receiving RMMR, polypharmacy and PIMs were highly common, and those with dementia were more likely to be exposed to inappropriate polypharmacy. There is a need for targeted deprescribing strategies to immediately address inappropriate prescribing in residents, particularly those living with dementia. [ABSTRACT FROM AUTHOR]

Background People living with dementia and their carers often experience difficulties in effectively managing medications and have indicated they lack necessary support, information and guidance. Recognising the medication management information needs of this population is an important first step in addressing these issues. Objectives To identify the priorities for information on medication management expressed by people living with dementia and their carers. Methods A scoping review with systematic search was conducted from inception to 12 May 2023 for any original studies that reported the information needs of people living with dementia and their carers (informal, i.e. unpaid or within an existing relationship) regarding medication management. Two authors independently screened the abstracts, full-texts and extracted data. Study characteristics were described descriptively, and themes of information need were extracted using an iterative approach. Results Of the 11 367 records screened, 35 full-texts were included. All studies (n = 35) involved carers, with 17 also including people living with dementia. Most studies (n = 30) were conducted in the community and used qualitative methods (n = 32). Five major themes of information need were identified: critical medication information; medication effects; medication indication(s); disease progression and impact on medications; and safe and appropriate administration of medications. People living with dementia and their carers indicated they need more medication management information generally and want it simple, tailored and relevant. Conclusions This review highlights the key medication information priorities for people living with dementia and their carers and will help guide the provision of medication management guidance and development of new information resources. [ABSTRACT FROM AUTHOR]

Abstract Background The introduction of antibody–drug conjugates represents a significant advancement in targeted therapy of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Our study aims to investigate the role of the DNA damage response pathway and the impact of PARP1 inhibition, utilizing talazoparib, on the response of AML and ALL cells to Gemtuzumab ozogamicin (GO) and Inotuzumab ozogamicin (INO), respectively. Methods AML and ALL cells were treated with GO, INO and γ-calicheamicin in order to induce severe DNA damage and activate the G2/M cell-cycle checkpoint in a dose- and time-dependent manner. The efficacy of PARP1 inhibitors and, in particular, talazoparib in enhancing INO or GO against ALL or AML cells was assessed through measurements of cell viability, cell death, cell cycle progression, DNA damage repair, accumulation of mitotic DNA damage and inhibition of clonogenic capacity. Results We observed that both ALL and AML cell lines activate the G2/M cell-cycle checkpoint in response to γ-calicheamicin-induced DNA damage, highlighting a shared cellular response mechanism. Talazoparib significantly enhanced the efficacy of INO against ALL cell lines, resulting in reduced cell viability, increased cell death, G2/M cell-cycle checkpoint override, accumulation of mitotic DNA damage and inhibition of clonogenic capacity. Strong synergism was observed in primary ALL cells treated with the combination. In contrast, AML cells exhibited a heterogeneous response to talazoparib in combination with GO. Our findings suggest a potential link between the differential responses of ALL and AML cells to the drug combinations and the ability of talazoparibto override G2/M cell-cycle arrest induced by antibody–drug conjugates. Conclusion PARP1 emerges as a key player in the response of ALL cells to INO and represents a promising target for therapeutic intervention in this leukemia setting. Our study sheds light on the intricate interplay between the DNA damage response pathway, PARP1 inhibition, and response of γ-calicheamicin-induced DNA damages in AML and ALL. These findings underscore the importance of targeted therapeutic strategies and pave the way for future research aimed at optimizing leukemia treatment approaches.

Ultrasound-guided vascular access is a medical procedure that is becoming increasingly common in daily practice and is recommended to avoid iatrogenic complications. One of the procedures with a high-risk rate of complications is the vascular puncture. However, training on this technique can be challenging due to the limited availability of simulation models. We propose a simple, cost-effective, and effective ultrasound-guided vascular access simulation model that utilizes chicken breast and a urine catheter to address this need.

Abstract This paper aims to introduce a novel family of probability distributions by the well-known method of the T–X family of distributions. The proposed family is called a “Novel Generalized Exponent Power X Family” of distributions. A three-parameters special sub-model of the proposed method is derived and named a “Novel Generalized Exponent Power Weibull” distribution (NGEP-Wei for short). For the proposed family, some statistical properties are derived including the hazard rate function, moments, moment generating function, order statistics, residual life, and reverse residual life. The well-known method of estimation, the maximum likelihood estimation method is used for estimating the model parameters. Besides, a comprehensive Monte Carlo simulation study is conducted to assess the efficacy of this estimation method. Finally, the model selection criterion such as Akaike information criterion (AINC), the correct information criterion (CINC), the Bayesian information criterion (BINC), the Hannan–Quinn information criterion (HQINC), the Cramer–von-Misses (CRMI), and the ANDA (Anderson–Darling) are used for comparison purpose. The comparison of the NGEP-Wei with other rival distributions is made by Two COVID-19 data sets. In terms of performance, we show that the proposed method outperforms the other competing methods included in this study.

Peritonitis is a severe complication in peritoneal dialysis (PD) patients, contributing to technique failure and patient mortality. Tunisia lacks a national dialysis registry, making the incidence of peritonitis unclear. The International Society for Peritoneal Dialysis (ISPD) published guidelines from 2016 to 2022, outlining effective strategies for preventing infections in PD patients. This study was conducted between June and July 2022 to assess Tunisian nephrologists’ knowledge and practices for preventing infections. Using an online questionnaire, 44 participants (67.69% response rate) provided insights. Findings revealed an average score of 4.45 out of 7, indicating significant confusion among respondents. Many incorrectly believe that protecting the catheter under the skin until renal replacement therapy is initiated reduces infections. Questions also addressed nasal Staphylococcus aureus screening, antibiotic prophylaxis, surgical techniques, timing of dressing changes, and local antibiotic use. Responses varied, with 59.1% supporting systematic nasal screening but differing concerning eradication strategies. The study highlights discrepancies between current practices and ISPD guidelines among young Tunisian nephrologists. Recommendations include establishing a national dialysis registry to enhance surveillance and developing tailored national guidelines. A working group from the Tunisian Society of Nephrology, Dialysis, and Transplantation is already developing protocols to address identified gaps and improve PD patient outcomes.

Citrus fruits, revered for their nutritional value, face significant threats from diseases like citrus canker, particularly impacting global citrus cultivation, notably in Pakistan. This study delves into the critical role of NPR1-like genes, the true receptors for salicylic acid (SA), in the defense mechanisms of citrus against Xanthomonas axonopodis pv. citri (Xcc). By conducting a comprehensive genome-wide analysis and phylogenetic study, the evolutionary dynamics of Citrus limon genes across diverse citrus cultivars are elucidated. Structural predictions unveil conserved domains, such as the BTB domain and ankyrin repeat domains, crucial for the defense mechanism. Motif analysis reveals essential conserved patterns, while cis-regulatory elements indicate their involvement in transcription, growth, response to phytohormones, and stress. The predominantly cytoplasmic and nuclear localization of NPR1-like genes underscores their pivotal role in conferring resistance to various citrus species. Analysis of the Ks/Ka ratio indicates a purifying selection of NPR1-like genes, emphasizing their importance in different species. Synteny and chromosomal mapping provide insights into duplication events and orthologous links among citrus species. Notably, Xac infection stimulates the expression of NPR1-like genes, revealing their responsiveness to pathogenic challenges. Interestingly, qRT-PCR profiling post-Xac infection reveals cultivar-specific alterations in expression within susceptible and resistant citrus varieties. Beyond genetic factors, physiological parameters like peroxidase, total soluble protein, and secondary metabolites respond to SA-dependent PR genes, influencing plant characteristics. Examining the impact of defense genes (NPR1) and plant characteristics on disease resistance in citrus, this study marks the inaugural investigation into the correlation between NPR1-associated genes and various plant traits in both susceptible and resistant citrus varieties to citrus bacterial canker.

The fungal endophytes are an understudied area of research with great potential for new bioactive compounds’ discovery. These are the fungal strains that live within the inner compartments of the host plant without causing it any kind of harm. These fungal endophytes, in combination with the host organisms, synthesize many compounds with a range of pharmaceutical values. Most recently, the discovery of fungal endophyte genes which are linked with the biosynthesis of plant metabolites has opened a new field of research. These plant partners assist plants against biotic stress and protect them from pathogenic attacks or diseases with the presence of some important gene families like WRKY and MYB. The bioactive metabolites from this group are known for their anticancer, antimicrobial, antioxidant, antidiabetic, and anti-tubercular properties. Therefore, these bioactive compounds offer new routes for discovering novel drugs, which can boost the pharmaceutical industry in times of great demand for novel drugs. Extracellular enzymes are also produced within the members of this distinct group which are crucial for several industrial sectors, including the biofuel production industry. Furthermore, fungal endophytes are capable of synthesizing silver nanoparticles, which exhibit significant potential in fields like biomedical imaging and water purification. This article aims to document all the available data on this group of fungi living in medicinal plants and the major compounds produced by members of this distinct group that are in use for the therapy of various ailments.

Simulation-based medical education is becoming a cornerstone in health education. Simulators are commonly expensive and not available in developing countries.We propose a very low-cost simulator that any educator can realize. We describe here the steps to follow to develop this proposed simulator.

Abstract Aims Management of patients with recently decompensated heart failure by hospital services is expensive, complicated to plan, and not always effective. Telemedicine programmes in heart failure may improve the quality of care, but their effectiveness is poorly documented in real‐world settings. The study aims to evaluate the impact of patient engagement in home‐based telemonitoring for heart failure (SCAD programme) on rehospitalization and mortality rates. Methods and results A retrospective observational study was performed in 659 SCAD participants. SCAD is a patient‐oriented service of home‐based interactive telemonitoring offered to heart failure patients during hospitalization who agree to participate in a therapeutic education programme. Patients were telemonitored for at least 3 months, and rehospitalization and mortality were documented at 12 months and 5 years. During the telemonitoring period, patients provided daily information on health and lifestyle through an internet‐based interface. Data were linked on a patient‐by‐patient basis between the SCAD database and the French national health insurance database (Système National des Données de Santé). Outcomes were compared as a function of use of the programme. Low, intermediate, and high users were classified by tercile of data return during telemonitoring. Patients were followed for a median of 32.9 months. Rehospitalization rates for cardiovascular disease decreased from 79.4% in the year preceding enrolment to 41.1% in the following year and from 52.8% to 18.8% for hospitalizations for heart failure. The 12 month mortality rate was 11.2%. Significant associations were observed between level of use of the SCAD programme and all‐cause rehospitalization (P = 0.0085), rehospitalization for cardiovascular disease (P = 0.0010), rehospitalization for heart failure (27.8% in low users, 12.9% in intermediate users, and 13.5% in high users; P

Chalcone synthase (CHS) is the pivotal enzyme that catalyzes the first committed step of the phenylpropanoid pathway leading to flavonoids. Herein, we identified twenty-seven OsCHS genes from the rice genome database. The bioinformatics analysis, including conserved motif, domain, interactive proteins, gene ontology (GO), target micro RNAs (miRNA) prediction, and the OsCHS physiochemical properties, highlight the key aspects of OsCHS genes in Oryza sativa L. The OsCHS proteins' phylogeny was further clustered into 4 sub-groups (Group I- Group IV) based on the structural similarities and functional diversities. The GO analysis of OsCHS proteins showed they are highly stress-responsive (biotic/abiotic) and involved in various growth and developmental processes. The microarray expression analysis showed transcription in twelve rice tissues, and the differential expression pattern of OsCHS genes revealed their possible involvement against salinity and drought. The higher expression of OsCHS15 in the OsWRKY65-OE line indicates its potential in hormonal-mediated stress response. The predicted miRNA that includes miR2260, miR167, miR11337, and miR2232 families further the engagement of OsCHS genes in the post-translational regulation of rice growth and stress-responsive. Owing to the above-mentioned outcomes, we speculate that OsCHS genes in the O. sativa genome play an essential role not only in growth and development but also in fine-tuning the immune responses to various environmental stresses and provide major indications for further functional studies.

Root cysts are inflammatory odontogenic cysts of the dental areas of the jaws. Most of these lesions involve the apex of the offending tooth and present as well-defined radiolucencies. Because of their similar clinical features to other more common lesions of the oral cavity, the differential diagnosis should include dentinal cyst, ameloblastoma, odontogenic keratocyst, periapical cementoma, and Pindborg tumor. The present case report documents a root cyst associated with non-carious tooth originating from an old defective gold thodontic treatment. On the basis of clinical, radiographic, and histopathologic findings, the present case was diagnosed as a root cyst. The clinical characteristics of this cyst can be considered interesting and rare owing to the unusual origin. The tooth was treated with endodontic therapy, then the lesion was enucleated surgically associated with apical resection; all other teeth and vital structures were preserved, without any postoperative complications and with satisfactory healing with total disappearance of the lesion after one year.

Vibriosis is one of the major diseases leading to massive fish mortality. Probiotics may provide a potential alternative method to protect fish from pathogens and to promote a balanced environment minimizing the use of antibiotics and chemotherapy. The aims of this study were to (i) isolate and purify marine spore-former strains from Sardine and shrimp intestine, (ii) screen for bacteria with potential probiotic properties, and (iii) carry out their in vitro safety assessment using a subtractive procedure. Among 108 spore-former strains, five strains exhibited a strong antibacterial activity against Vibriosis such as Vibrio harveyi and Vibrio anguillarum. These selected strains were unaffected by high-temperature and gastrointestinal conditions; produced amylase, protease, and lipase activities; and showed high percentages of auto-aggregation and co-aggregation with pathogens, as well as a strong adhesion to fish mucus. Partial 16S rDNA gene sequencing and MALDI-TOF MS revealed that isolates are Bacillus amyloliquefaciens or Bacillus subtilis. All of them were susceptible to antibiotics, while hydrolic enzymes and virulence factors were not detected for B. subtilis S17. In conclusion, based on their proprieties and their safety assessment, B. subtilis S17 could serve as a potential probiotic candidate for aquaculture.

Abstract Background Karyomegalic interstitial nephritis (KIN) is a rare disease entity first described by Burry in 1974. The term KIN was introduced by Mihatsch et al. in 1979. KIN is characterized by chronic tubulointerstitial nephritis associated with enlarged tubular epithelial cell nuclei, which leads to a progressive decline of renal function. The prevalence of this disease is less than 1% of all biopsies, and its pathogenesis is unclear. KIN results from mutations in FAN1 (FANCD2/FANCI-Associated Nuclease 1), a gene involved in the DNA damage response pathway, particularly in the kidney. In this study, we report two Tunisian consanguineous families with KIN caused by mutations in the FAN1 gene. Methods Direct sequencing of the coding regions and flanking intronic sequences of the FAN1 gene was performed in three affected members. Three prediction programs (Polyphen-2 software, SIFT, and MutationTaster) were used to predict the functional effect of the detected variations. Results Two causative frameshift variants in the FAN1 gene were identified in each family: The previously described frameshift mutation c.2616delA (p.Asp873ThrfsTer17) and a novel mutation c.2603delT (p.Leu868ArgfsTer22) classified as "pathogenic" according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Conclusion To our best knowledge, this is the first Tunisian study involving familial cases of KIN with mutations in the FAN1 gene. We hypothesize that these findings can expand the mutational spectrum of KIN and provide valuable information on the genetic cause of KIN.

Among all available antimicrobials, antibiotics hold a prime position in the treatment of infectious diseases. However, the emergence of antimicrobial resistance (AMR) has posed a serious threat to the effectiveness of antibiotics, resulting in increased morbidity, mortality, and escalation in healthcare costs causing a global health crisis. The overuse and misuse of antibiotics in global healthcare setups have accelerated the development and spread of AMR, leading to the emergence of multidrug-resistant (MDR) pathogens, which further limits treatment options. This creates a critical need to explore alternative approaches to combat bacterial infections. Phytochemicals have gained attention as a potential source of alternative medicine to address the challenge of AMR. Phytochemicals are structurally and functionally diverse and have multitarget antimicrobial effects, disrupting essential cellular activities. Given the promising results of plant-based antimicrobials, coupled with the slow discovery of novel antibiotics, it has become highly imperative to explore the vast repository of phytocompounds to overcome the looming catastrophe of AMR. This review summarizes the emergence of AMR towards existing antibiotics and potent phytochemicals having antimicrobial activities, along with a comprehensive overview of 123 Himalayan medicinal plants reported to possess antimicrobial phytocompounds, thus compiling the existing information that will help researchers in the exploration of phytochemicals to combat AMR.

This study aims to evaluate the diagnostic accuracy of artificial intelligence in detecting apical pathosis on periapical radiographs. A total of twenty anonymized periapical radiographs were retrieved from the database of Poznan University of Medical Sciences. These radiographs displayed a sequence of 60 visible teeth. The evaluation of the radiographs was conducted using two methods (manual and automatic), and the results obtained from each technique were afterward compared. For the ground-truth method, one oral and maxillofacial radiology expert with more than ten years of experience and one trainee in oral and maxillofacial radiology evaluated the radiographs by classifying teeth as healthy and unhealthy. A tooth was considered unhealthy when periapical periodontitis related to this tooth had been detected on the radiograph. At the same time, a tooth was classified as healthy when no periapical radiolucency was detected on the periapical radiographs. Then, the same radiographs were evaluated by artificial intelligence, Diagnocat (Diagnocat Ltd., San Francisco, CA, USA). Diagnocat (Diagnocat Ltd., San Francisco, CA, USA) correctly identified periapical lesions on periapical radiographs with a sensitivity of 92.30% and identified healthy teeth with a specificity of 97.87%. The recorded accuracy and F1 score were 96.66% and 0.92, respectively. The artificial intelligence algorithm misdiagnosed one unhealthy tooth (false negative) and over-diagnosed one healthy tooth (false positive) compared to the ground-truth results. Diagnocat (Diagnocat Ltd., San Francisco, CA, USA) showed an optimum accuracy for detecting periapical periodontitis on periapical radiographs. However, more research is needed to assess the diagnostic accuracy of artificial intelligence-based algorithms in dentistry.