Treatment Strategies Research Articles

Expert consensus on clinical application of next-generation sequencing in advanced breast cancer (2024 edition)

Breast cancer is the most common malignant tumor among women in the world. According to data from the World Health Organization, in 2020, there were approximately 2.26 million new breast cancer cases worldwide, accounting for 11.7% of all new cancer cases. In recent years, with the rapid development of molecular biology and gene detection technology, the research on advanced breast cancer continues to deepen, and the treatment methods are constantly enriched. Gene targeted therapy significantly prolongs the survival period of patients with advanced breast cancer, which is of great significance for molecular pathological diagnosis, targeted drug selection and treatment mode optimization of patients with advanced breast cancer. Based on the development of literature and clinical research, the consensus expert committee formulated the "Expert consensus on clinical application of next-generation sequencing in advanced breast cancer (2024 edition)". Compared with the "Chinese Expert Consensus on Hot Issues of Gene Testing for Advanced breast cancer (2021)", the 2024 consensus adopts new evidence-based medical evidence, aiming to provide more comprehensive gene testing information for patients with advanced breast cancer, so as to develop more accurate treatment strategies.

Understanding the human element in scams: a multidisciplinary approach

ABSTRACT Scams are a widespread and persistent issue that have existed for thousands of years, evolving into a significant problem in modern society with the advancement of new media and communication technologies. This editorial attempts to provide a comprehensive understanding of the social and psychological mechanisms in scams through a multidisciplinary lens, drawing insights from communication studies, information systems, psychology, sociology, and economics. We aim to not only provide a robust framework for future scientific research, but also to map potential directions for developing effective scam prevention and intervention strategies in the future.

Understanding the Complexities of Tuberculosis: A Comprehensive Review of Drug-Resistant Strains in Pakistan

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a critical global health challenge, claiming over one million lives annually. Despite substantial progress in reducing TB incidence in developed countries post-World War II, it persists as a major cause of mortality, particularly in low-income populations. Socio-economic disparities significantly contribute to TB prevalence, exacerbating the uneven distribution of resources and healthcare access. Pakistan is among the nations severely impacted by TB, with eradication targets still unmet. All forms of TB are prevalent in the region, presenting symptoms such as fever, chronic cough, chills, and weight loss. This review assesses treatment outcomes and the prevalence of pulmonary TB in diagnosed patients in Pakistan. The airborne transmission of TB significantly drives its global burden. According to the World Health Organization (WHO), 2021 witnessed 1.2 million TB-related deaths and 9.9 million new cases. Diagnostic methods include immunological assays and molecular techniques, requiring sputum and blood sample analyses. Early diagnosis is crucial to prevent the emergence of drug-resistant strains. Pulmonary TB primarily spreads via respiratory pathways, with MTB infecting alveolar macrophages, leading to disease progression. Although studies on genetic susceptibility to TB have been conducted, conclusive evidence remains elusive. Computed Tomography (CT) provides detailed insights into TB manifestations but demands automation due to the high volume of data generated. The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB presents serious challenges to control and treatment. This review offers a comprehensive analysis of the epidemiology, pathogenesis, diagnosis, treatment, and prevention strategies for MDR and XDR TB. It highlights existing research gaps and proposes future directions to address these challenges. Advances in Artificial Intelligence (AI) and Computer Vision (CV) provide novel approaches for automating TB image analysis, facilitating scalable pre-clinical trials and improving disease management.

Petrous bone cholesteatoma (PBC): report of 94 cases of PBC with focus on intraoperative endoscopic assistance, and systematic review of the literature.

The aim of this study is to assess the clinical characteristics, classification, surgical approaches, interventional strategies, and treatment outcomes of patients with petrous bone cholesteatoma (PBC). Observational retrospective study of patients with PBC managed by the senior author of this paper between 1995 and 2024 in a tertiary referral center. A literature review was made, identifying 16 articles. Clinical presentations, Sanna's classification, pre- and post-surgical facial function and audiometry, surgical approach and intraoperative endoscopic assistance, postoperative complications, and recurrence rates were reported. We report on a large series of 94 cases managed by the senior author. The most common type was supralabyrinthine PBCs (40.43%; 38 cases), followed by massive (18.09%; 17). Hearing loss was present in almost all the patients (98.91%). The most frequent approaches were the modified translabyrinthine approach (24.51%; 25), the subtotal petrosectomy (22.55%; 23) and the transotic approach (18.63%; 19). In 11 patients the approach was assisted by the use of an endoscope. Recurrence of PBC was identified in 8 cases (8.51%) that were surgically resolved. Additionally, we report a review of the literature (16 articles). We focus on the introduction of endoscopic assisted techniques that may help in reducing the rate of residual and avoid rerouting of the facial nerve. At the same time, we encourage techniques that include elimination of the middle ear through a subtotal petrosectomy, as they are essential to protect vital structures that have been exposed by the disease or by the surgical technique.

Adapting the HSE-MS Indicator Tool for Academia: A Psychometric Evaluation of the Academic Teacher Stress Indicator Tool in Italian.

The assessment of work-related stress is mandatory in Italy, according to Legislative Decree 81/2008. The Academic Teacher Stress Indicator Tool (ATS-IT) was developed to address stress in academic teaching staff by adapting the Health and Safety Executive Management Standards Indicator Tool (HSE-MS IT). An online ATS-IT survey was administered to all teaching staff at the University of Trieste, yielding 334 valid responses. The survey also included a measure of psychosomatic complaints and demographic questions. Confirmatory factor analysis (CFA) was performed to test the six-factor structure, and reliability was assessed using Cronbach's alpha. CFA confirmed an excellent fit for the six-factor structure (CFI = .99; TLI = .99; RMSEA = .034). Reliability analysis mainly showed acceptable values (Cronbach's α ranging from .66 to .91). Significant gender differences were found in the Demands and Control scales, with additional differences based on age and academic role across multiple scales. The ATIS-IT scales were significantly intercorrelated and negatively correlated with psychosomatic complaints. The ATS-IT demonstrates good potential as a valid and reliable instrument for assessing work-related stress among Italian academic teaching staff. Its use can facilitate better stress management and intervention strategies in educational institutions.

Statin Use and Hyperglycemia: Do Statins Cause Diabetes?

Atherosclerotic cardiovascular disease (ASCVD) and diabetes are leading causes of morbidity and mortality in the United States and globally. Statin medications, a cornerstone of ASCVD prevention and treatment strategies, have been demonstrated to cause hyperglycemia and new onset diabetes mellitus (NODM). The purpose of this review is to summarize existing and emerging knowledge around the intersection of statins and these two important clinical problems. Since initial reporting of statin-induced hyperglycemia and NODM, the totality of available data corroborates an association between incident diabetes and statin use. A consensus that high-intensity statin and individuals with obesity or glycemic parameters approximating diabetes thresholds constitute the majority of risk exists. Alterations in insulin signaling, glucose transport and gastrointestinal microbiota are leading hypotheses underlying the mechanisms of statin-induced hyperglycemia. The probability of NODM based on an individual's risk factors and statin specific properties can be anticipated. This risk needs to be contextualized with the risk of ASCVD. In order to effectively adjudicate the risk of NODM, improvement in formulating and ultimately conveying a comprehensive ASCVD risk assessment to patients is necessary.

The Value of a Tooth for Alveolar Ridge Management; Strategies to Manage Ankylosed Maxillary Anterior Teeth in Young Patients.

In the young and growing patient, tooth ankylosis impedes alveolar growth and presents a serious dilemma regarding the best treatment approach. Two common treatment approaches, extraction of the ankylosed tooth or a "wait and see" will result in a compromised alveolar ridge that can affect future prosthetic rehabilitation. The purpose of this article is to discuss five treatment strategies that can be utilized in the management of tooth ankylosis in the growing patient: (1) extraction, (2) decoronation or root submergence, (3) socket shield (partial extraction), (4) segmental osteotomy and (5) replacement with tooth autotransplantation. It is important to understand the biologic sequelae of ankylosis and the value of the tooth for alveolar ridge management. Strategies will be discussed with an emphasis on alveolar ridge management using a natural tooth and root. With an interdisciplinary team, treatment options can then be developed, to achieve more favorable long-term outcomes. An understanding of each of these procedures and the proper time for implementation will help the clinician achieve the most optimal long-term outcomes for these growing patients. There are several treatment options for traumatized ankylosed incisors in growing patients. This article will describe the details of these treatment strategies, emphasize the value of the tooth for ridge management and present guidelines about selecting the most optimal strategy based on age, rate of growth, condition of the traumatized tooth, and the definitive prosthetic plan.

A prognostic model for predicting functional impairment in youth mental health services.

Functional impairment is a major concern among those presenting to youth mental health services and can have a profound impact on long-term outcomes. Early recognition and prevention for those at risk of functional impairment is essential to guide effective youth mental health care. Yet, identifying those at risk is challenging and impacts the appropriate allocation of indicated prevention and early intervention strategies. We developed a prognostic model to predict a young person's social and occupational functional impairment trajectory over 3 months. The sample included 718 young people (12-25years) engaged in youth mental health care. A Bayesian random effects model was designed using demographic and clinical factors and model performance was evaluated on held-out test data via 5-fold cross-validation. Eight factors were identified as the optimal set for prediction: employment, education, or training status; self-harm; psychotic-like experiences; physical health comorbidity; childhood-onset syndrome; illness type; clinical stage; and circadian disturbances. The model had an acceptable area under the curve (AUC) of 0.70 (95% CI, 0.56-0.81) overall, indicating its utility for predicting functional impairment over 3 months. For those with good baseline functioning, it showed excellent performance (AUC=0.80, 0.67-0.79) for identifying individuals at risk of deterioration. We developed and validated a prognostic model for youth mental health services to predict functional impairment trajectories over a 3-month period. This model serves as a foundation for further tool development and demonstrates its potential to guide indicated prevention and early intervention for enhancing functional outcomes or preventing functional decline.

Malignant vasovagal syncope in children.

Malignant vasovagal syncope (VVS) is a unique form of cardioinhibitory VVS, characterized by prolonged asystole. To deepen the understanding of this distinct type of VVS in children, this article reviews advancements in the potential pathogenesis, diagnostic approaches, clinical significance, and treatment controversies of malignant VVS in pediatric patients. This article was developed by reviewing the literature and studies in databases including PubMed and Chinese Journal Full-text Database up to September 2024. Search terms included "malignant vasovagal syncope" AND "children" or "vasovagal syncope" AND "asystole" AND "children". To date, studies focused on malignant VVS in children remain limited. Theoretically, children with malignant VVS are at risk of physical or mental impairment due to this cardiac asystole, though no definite conclusions have been reached. The mechanism underlying the significant cardiac inhibition in malignant VVS remains unclear, and the treatment strategy of malignant VVS is debatable. The understanding of children with malignant VVSis insufficient. Further research is required to evaluate the clinical features and the pathogenesis of pediatric VVS with cardiac asystole and to establish effective management strategies for malignant VVS. Video Abstract.

Effect of goal-directed perceptual-motor exercise on children with specific learning difficulties: a randomized controlled trial

BackgroundAlthough perceptual interventions focus on sensory and cognitive skills, they significantly enhance the effectiveness of motor interventions by improving coordination, decision-making, and overall engagement in physical activities. A comprehensive literature review has demonstrated that incorporating perceptual interventions into motor exercises is beneficial. While there are several treatment strategies for SLD-diagnosed children, the potential role of goal-directed perceptual-motor exercises has not been studied. This study examined the effectiveness of goal-directed perceptual-motor training on attention, motor skills, and quality of life in children with Specific Learning Disorder (SLD).MethodsThis was a randomized clinical study with 38 children diagnosed with SLD between September 2021 and April 2022. The control group (n = 19) received a standard intervention protocol, and the intervention group (n = 19) additionally received a perceptual-motor training program. Bourdon Attention Test, the Bruininks-Oseretsky Test 2–Short Form (BOT2- SF), and the Pediatric Quality of Life Inventory (PEDSQL) were used as outcome measures.ResultsThe intervention significantly improved attention, fine and gross motor skills, and life quality as evidenced by the within- and between-group comparisons at the end of therapy.ConclusionsGoal-directed perceptual-motor physical training with cognitive aspects may enhance academic performance, social participation, and life quality for children with SLD by improving basic motor skills. Therefore, the inclusion of physical and task-specific perceptual-motor exercises in educational programs may offer several avenues for cognitive skill development in SLD children.Trial registrationThe protocol is retrospectively registered with http://clinicaltrials.gov/ (16/August/2023, Clinical Trial, NCT05998083).

The radiohumeral synovial plica: anatomy, histology, and implications in chronic lateral epicondylitis.

Our study aimed to elucidate synovial plica (SP) of the elbow histological characteristics and the anatomical relationship with adjacent structures. Subsequently, we sought to assess the relationship between SP and clinical symptoms as well as magnetic resonance imaging (MRI) features in patients with chronic lateral epicondylitis. MRI was performed on eight cadaveric elbows specimens. The MRI findings were compared with those in anatomic sections and histologic preparations. In addition, ninety-nine patients with chronic lateral epicondylitis who underwent preoperative elbow MRI and arthroscopic surgery were included. The patients were divided into SP and without SP groups. The differences in clinical symptoms and MRI features between the two groups were compared. SP is located proximal to the annular ligament that extends into the joint cavity, then moves to the lateral collateral ligament (LCL) complex, and finally attaches to the lateral epicondyle of the elbow along with the common extensor tendon (CET). The SP, ligament, and tendon blend imperceptibly without distinct boundaries. Furthermore, in a study of patients with chronic lateral epicondylitis, we found that compared to the without SP group, patients in the SP group had higher preoperative and 3-week postoperative VAS scores and more severe abnormalities in LCL complex and CET. The SP is distinct from the annular ligament and closely correlates with the LCL complex and CET enthesis at the lateral epicondyle. Chronic lateral epicondylitis patients with SP have more severe abnormalities of the LCL complex and CET, more severe pain, and longer postoperative recovery times. Question Synovial plica (SP) cause lateral elbow pain, but few studies regarding histological and imaging features of SP and its relationship to chronic lateral epicondylitis exist. Findings The presence of SP leads to more severe common extensor tendon abnormalities and higher visual analog scale scores in patients with chronic lateral epicondylitis. Clinical relevance The combination of magnetic resonance imaging and clinical symptoms to further understand the effect of SP on the clinical symptoms and postoperative recovery in chronic lateral epicondylitis can help refine treatment strategies and improve the prognosis of patients.

Exploring the value of multiparametric quantitative MRI in the assessment of pancreatic ductal adenocarcinoma fibrosis grading.

To analyze the performance of multiparametric magnetic resonance imaging (MRI) in quantification of pancreatic ductal adenocarcinoma (PDAC) fibrosis grading. This prospective study enrolled 79 patients with PDAC confirmed by pathology. Multiparametric MRI including native T1 mapping, intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), diffusion kurtosis imaging diffusion-weighted imaging (DKI-DWI), and enhanced T1 mapping were performed before surgery. Masson staining was used to evaluate intratumoral fibrosis content and classified into low- and high-fibrosis groups. MRI parameters were compared between the two groups using multivariable logistic regression analysis. The correlations between fibrosis content and MRI parameters were evaluated using Pearson's correlation. D, f, mean diffusion (MD), and enhanced T1 mapping were lower in the high-fibrosis group than in the low-fibrosis group (p < 0.001, p < 0.001, p < 0.001, p = 0.026, respectively). Native T1 mapping and extracellular volume (ECV) were opposite (All p < 0.001). No significant differences in the rest. Multivariable logistic regression revealed that native T1 mapping, MD, and ECV were independent discriminators for PDAC fibrosis grading (p = 0.037, p = 0.031, p = 0.014, respectively); the area under the curve (AUC) of native T1 mapping, MD and ECV was 0.863, 0.798, and 0.929. Among them, ECV had an extremely strong positive correlation with intratumoral fibrosis content. Native T1 mapping and MD were correlated strongly with fibrosis content (positive and negative, respectively). ECV had the highest assessing performance for grading fibrosis in PDAC compared to other MRI parameters, and has the potential to be an imaging biomarker for predicting the fibrosis content of PDAC. Question The relationship between fibrosis grade of PDAC and quantitative MRI parameters based on T1 mapping and diffusion imaging has not been fully investigated. Findings ECV performed the best in distinguishing between fibrosis grade and increased as interstitial fibrosis increased; clinical indicators offered no added value. Clinical relevance Quantitative MRI parameters provide significant value in evaluating the fibrosis grade of PDAC, which bears significant implications for preoperative risk stratification and the selection of personalized treatment strategies for patients.

Sagittal Split Ramus Osteotomy Without Segmental Fixation in Skeletal Class II.

The new orthognathic treatment strategy of non-segmental fixation (non-fix) sagittal split ramus osteotomy (SSRO) with jaw exercise initiation on the second postoperative day, the so-called physiological positioning strategy (PPS), induces good skeletal stability with few temporomandibular joint (TMJ) symptoms after surgery in skeletal class III. This study aimed to clarify whether non-fix SSRO with modified PPS can be applied to skeletal class II. This retrospective study included skeletal class II patients who underwent non-fix SSRO to correct mandibular retrognathia. Jaw exercise was initiated within 10 postoperative days. Cephalometric analyses were performed before (T1), immediately after (T2), and more than 6 months after (T3) surgery. Skeletal and dental stability, and TMJ symptoms were evaluated. Twelve patients (2 men, 10 women; mean age 22.9±7.1y) were included. The mean mandibular advancement was 6.8±1.8mm. angle between S-N and N-B. was 73.6±4.5, 77.1±3.9, and 75.1±4.4 degrees at T1, T2, and T3, meaning 60.5% relapse. The Menton moved forward by 6.3mm from T1 to T2 and relapsed by 4.6mm at T3. The duration of intermaxillary traction showed a moderate negative correlation with angle between S-N and N-B. relapse (r=-0.42, P=0.1787). Only 2 TMJ symptoms (2/24, 8.3%) developed postoperatively. This study suggests that non-fix SSRO with modified PPS is a suitable method for skeletal class II malocclusion. Further research with a larger sample size and detailed analysis of the effect of intermaxillary traction on skeletal stability after surgery is needed.

Does Epstein-Barr virus and intracellular Toll-like receptors affect the course of Hashimoto disease? Findings from studies on newly-diagnosed patients.

Epstein‑Barr virus (EBV) reactivation is increasingly recognized as a potential exacerbator of autoimmune diseases, including Hashimoto thyroiditis (HT). This study examined the association between EBV reactivation and intracellular Toll‑like receptor (TLR) expression in newly‑diagnosed, untreated HT patients. Its aim was to determine whether EBV reactivation and expression of specific TLRs (TLR3, TLR7, TLR8, and TLR9) contribute to the pathogenesis and progression of HT. The study involved a cohort was 54 newly‑diagnosed, untreated patients with HT and 20 healthy volunteers (HVs) matched for age and sex. Blood samples were collected to assess EBV viral load and intracellular expression levels of TLR3, TLR7, TLR8, and TLR9 using flow cytometry. The levels of specific anti‑EBV antibodies (eg, viral capsid A [VCA] immunoglobulin [Ig] M, VCA IgG, Epstein‑Barr nuclear antigen 1 [EBNA‑1] IgM, EBNA‑1 IgG) were measured to identify signs of EBV reactivation, while soluble TLRs (sTLR3, sTLR7, sTLR8, and sTLR9) were quantified in serum using enzyme‑linked immunosorbent assay. Notably, our HT patients were not euthyroid, as they exhibited significantly lower thyroid‑stimulating hormone levels and elevated free triiodothyronine and free thyroxine levels in comparison with the HVs. The study showed a significant increase in EBV reactivation among the HT patients, with 26 of 54 (48.1%) testing positive for EBV DNA, as compared with none of the HVs. The HT patients with reactivated EBV showed significantly higher intracellular expression of TLR3, TLR7, and TLR9, with TLR3+ cells constituting an average of 4.72% of CD4+ lymphocytes (vs 0.69% in the HVs), suggesting a potential synergistic effect. In addition, sTLR levels increased in the HT patients with reactivated EBV, suggesting a possible role of these receptors in potentiating autoimmune responses. These findings highlight the importance of considering both viral reactivation and TLR activity in the treatment of HT. Understanding the interplay between EBV and intracellular TLRs may lead to development of new therapeutic approaches to mitigate the impact of these factors on the disease progression. Further research is warranted to investigate the mechanisms underlying this interaction and its implications for treatment strategies.

Biomimetic astrocyte cell membrane-fused nanovesicles for protecting neurovascular units in hypoxic ischemic encephalopathy

Hypoxic ischemic encephalopathy (HIE) refers to neonatal hypoxic brain injury caused by severe asphyxia during the perinatal period. With a high incidence rate and poor prognosis, HIE accounts for 2.4% of the global disease burden, imposing a heavy burden on families and society. Current clinical treatment for HIE primarily focuses on symptomatic management and supportive care. Therefore, the developments of effective treatment strategies and new drug formulations are critical for improving the prognosis of HIE patients. In order to protect the compromised neurovascular units after HIE, we prepared membrane-fused nanovesicles for delivering rapamycin and si EDN1 (TRCAM@RAPA@si EDN1). Due to the homotypic targeting feature of membrane-fused nanovesicles, we employed astrocyte membranes as synthetic materials to improve the targeting of astrocytes in brain while reducing the clearance of nanovesicles by circulatory system. Additionally, the surface of cell membrane was modified with CXCR3 receptors, enhancing the homing of nanovesicles to infarcted lesions. Lipid vesicles were modified with TK and RVG29 transmembrane peptides, enabling responsive release of internal drugs and blood-brain barrier penetration. Internally loaded rapamycin could promote protective autophagy in astrocytes, improve cellular oxidative stress, while si EDN1 could reduce the expression level of endothelin gene, thereby reducing secondary damage to neurovascular units.Graphical

Impact of psychological stress on ovarian function: Insights, mechanisms and intervention strategies (Review)

Impact of psychological stress on ovarian function: Insights, mechanisms and intervention strategies (Review)

Protocol: the American Women: Assessing Risk Epidemiologically (AWARE) cohort study

BackgroundWhile progress has been made in reducing HIV incidence rates among cisgender women, it continues to fall short of reaching the goal of ending the HIV epidemic with no new cases.ObjectiveThis study aims to use innovative electronic methods (e.g., social media with community-informed advertisements) to recruit and retain a large (N = 1,800), diverse national sample of women at higher risk for HIV seroconversion who are 14 years of age and older to better understand the predictors of HIV-related sexual risk and HIV incidence within the context of a theoretically-grounded social-ecological framework.MethodsA US-based national longitudinal cohort study was launched among cisgender women with greater likelihood of HIV seroconversion Participants complete a survey with items related to demographics, substance use, mental health symptoms, interpersonal violence and other social factors. Biospecimens include self-collected vaginal and rectal swabs, and blood in microtainers to test for HIV, syphilis, chlamydia, gonorrhea, and trichomoniasis every 6 months for 2 years.ResultsParticipant recruitment began in June 2023 and baseline enrollment is scheduled to finish in July 2025.DiscussionInnovative and culturally sensitive strategies to improve access to HIV prevention and treatment services for cisgender women are vital to curb the burden of the HIV epidemic for this key population. Findings from this study will inform future research, intervention strategies, and public policies.

Prevalence and influencing factors of medication-related burden among patients with late-life depression in typical city of eastern China: a cross-sectional study

AimTo evaluate the medication-related burden (MRB) of patients with late-life depression (LLD) and its influencing factors in China using the Living with Medicines Questionnaire-3 (LMQ-3), providing reference for reducing the MRB of those patients.MethodA cross-sectional study was conducted between September 2023 and January 2024 on 588 patients with LLD. LMQ-3 and MRB factors questionnaire were used for data collection. The distribution of variables was assessed using descriptive analysis, while analyses of Mann-Whitney and Kruskal-Wallis were performed to evaluate inter-group differences. To explore the MRB among patients with LLD and influencing factors, multiple linear regression analysis was performed.ResultsThe median (IQR) LMQ-3 score of 588 participants was 102 (18), indicating a moderate MRB level. Regression analysis revealed a significant trend toward higher perceived burden among patients aged 70–79 years old, living in rural areas, receiving more medical insurance settlements, using all cash, taking more than 5 drugs each time, and taking medicine more than 3 times a day (p < 0.05), which were risk factors for higher MRB. Conversely, patients who lived with their children, had an annual household income (including adult children) more than 50,000 Chinese Yuan, and no adverse drug reactions had lower LMQ-3 scores (p < 0.05), which were protective factors. Patients’ concerns about medicine, their lack of autonomy in medicine regimens, and the lack of communication between patients and doctors on treatment regimens were the main causes of the burden.ConclusionsResults of this study provided preliminary evidence of the MRB among patients with LLD. Age, residence, living status, annual household income, type of drug payment, quantity and frequency of medication, and adverse reactions significantly affected the perceived medication burden. It is advisable for health policy makers and health care providers to implement appropriate intervention strategies and burden reduction programs for this vulnerable group.

Comparison of fine-scale malaria strata derived from population survey data collected using RDTs, microscopy and qPCR in South-Eastern Tanzania

BackgroundMalaria-endemic countries are increasingly adopting data-driven risk stratification, often at district or higher regional levels, to guide their intervention strategies. The data typically comes from population-level surveys collected by rapid diagnostic tests (RDTs), which unfortunately perform poorly in low transmission settings. Here, a high-resolution survey of Plasmodium falciparum prevalence rate (PfPR) was conducted in two Tanzanian districts using rapid diagnostic tests (RDTs), microscopy, and quantitative polymerase chain reaction (qPCR) assays, enabling the comparison of fine-scale strata derived from these different diagnostic methods.MethodsA cross-sectional survey was conducted in 35 villages in Ulanga and Kilombero districts, south-eastern Tanzania between 2022 and 2023. A total of 7,628 individuals were screened using RDTs (SD-BIOLINE) and microscopy, with two thirds of the samples further analysed by qPCR. The data was used to categorize each district and village as having very low (PfPR < 1%), low (1%≤PfPR < 5%), moderate (5%≤PfPR < 30%), or high (PfPR ≥ 30%) parasite prevalence. A generalized linear mixed model was used to analyse infection risk factors. Other metrics, including positive predictive value (PPV), sensitivity, specificity, parasite densities, and Kappa statistics were computed for RDTs or microscopy and compared to qPCR as reference.ResultsSignificant fine-scale variations in malaria risk were observed within and between the districts, with village prevalence ranging from 0% to > 50%. Prevalence varied by testing method: Kilombero was low risk by RDTs (PfPR = 3%) and microscopy (PfPR = 2%) but moderate by qPCR (PfPR = 9%); Ulanga was high risk by RDTs (PfPR = 39%) and qPCR (PfPR = 54%) but moderate by microscopy (PfPR = 26%). RDTs and microscopy classified majority of the 35 villages as very low to low risk (18–21 villages). In contrast, qPCR classified most villages as moderate to high risk (29 villages). Using qPCR as the reference, PPV for RDTs and microscopy ranged from as low as < 20% in very low transmission villages to > 80% in moderate and high transmission villages. Sensitivity was 62% for RDTs and 41% for microscopy; specificity was 93% and 96%, respectively. Kappa values were 0.7 for RDTs and 0.5 for microscopy. School-age children (5–15 years) had higher malaria prevalence and parasite densities than adults (P < 0.001). High-prevalence villages also had higher parasite densities (Spearman r = 0.77, P < 0.001 for qPCR; r = 0.55, P = 0.003 for microscopy).ConclusionThis study highlights significant fine-scale variability in malaria burden within and between the study districts and emphasizes the variable performance of the testing methods when stratifying risk at local scales. While RDTs and microscopy were effective in high-transmission areas, they performed poorly in low-transmission settings; and classified most villages as very low or low risk. In contrast, qPCR classified most villages as moderate or high risk. The findings emphasize that, where precise mapping and effective targeting of malaria are required in localized settings, tests must be both operationally feasible and highly sensitive. Furthermore, when planning microstratification efforts to guide local control measures, it is crucial to carefully consider both the strengths and limitations of the available data and the testing methods employed.

Mechanisms and Potential Benefits of Neuroprotective Agents in Neurological Health

The brain contains many interconnected and complex cellular and molecular mechanisms. Injury to the brain causes permanent dysfunctions in these mechanisms. So, it continues to be an area where surgical intervention cannot be performed except for the removal of tumors and the repair of some aneurysms. Some agents that can cross the blood–brain barrier and reach neurons show neuroprotective effects in the brain due to their anti-apoptotic, anti-inflammatory and antioxidant properties. In particular, some agents act by reducing or modulating the accumulation of protein aggregates in neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Amyotrophic lateral sclerosis, and prion disease) caused by protein accumulation. Substrate accumulation causes increased oxidative stress and stimulates the brain’s immune cells, microglia, and astrocytes, to secrete proinflammatory cytokines. Long-term or chronic neuroinflammatory response triggers apoptosis. Brain damage is observed with neuronal apoptosis and brain functions are impaired. This situation negatively affects processes such as motor movements, memory, perception, and learning. Neuroprotective agents prevent apoptosis by modulating molecules that play a role in apoptosis. In addition, they can improve impaired brain functions by supporting neuroplasticity and neurogenesis. Due to the important roles that these agents play in central nervous system damage or neurodegenerative diseases, it is important to elucidate many mechanisms. This review provides an overview of the mechanisms of flavonoids, which constitute a large part of the agents with neuroprotective effects, as well as vitamins, neurotransmitters, hormones, amino acids, and their derivatives. It is thought that understanding these mechanisms will enable the development of new therapeutic agents and different treatment strategies.