Browse Articles

Determination of the solubility of methyldopa in supercritical carbon dioxide for drug delivery applications: thermal analysis

Stability of refractive outcomes after hyperopic LASIK with and without Mitomycin C application: a randomized controlled trial

AbstractTo assess the efficacy, safety, and stability of refractive outcomes in hyperopic Laser-Assisted in Situ Keratomileusis (LASIK) with and without the application of Mitomycin C (MMC). This randomized, parallel group, controlled multicenter trial included 140 hyperopic eyes. The participants were randomly assigned to two groups: one receiving LASIK with mitomycin C (MMC) (n = 70) and the other receiving LASIK without MMC (n = 70). The primary outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and safety parameters at six months postoperatively. The statistical analysis employed t-tests, Mann-Whitney tests, and Fisher’s Exact Test, with a significance level of p < 0.05. All 140 eyes (70 per group) were analyzed. No statistically significant differences were identified between the two groups in postoperative UDVA, CDVA, or safety parameters (p > 0.05). Both groups demonstrated highly effective and safe refractive outcomes. No intraoperative complications or postoperative adverse events were observed. Age and preoperative spherical equivalent did not significantly affect outcomes. Hyperopic LASIK with and without MMC showed comparable efficacy, safety, and stability of refractive outcomes at the six-month postoperative interval. Although MMC use in hyperopic LASIK appears to be a safe procedure, it was not found to be significantly superior to conventional LASIK. Further investigation with longer follow-up periods and larger cohorts is necessary to confirm these results.

MAP4 kinase-regulated reduced CLSTN1 expression in medulloblastoma is associated with increased invasiveness

Abstract De-regulated protein expression contributes to tumor growth and progression in medulloblastoma (MB), the most common malignant brain tumor in children. MB is associated with impaired differentiation of specific neural progenitors, suggesting that the deregulation of proteins involved in neural physiology could contribute to the transformed phenotype in MB. Calsynthenin 1 (CLSTN1) is a neuronal protein involved in cell-cell interaction, vesicle trafficking, and synaptic signaling. We previously identified CLSTN1 as a putative target of the pro-invasive kinase MAP4K4, which we found to reduce CLSTN1 surface expression. Herein, we explored the expression and functional significance of CLSTN1 in MB. We found that CLSTN1 expression is decreased in primary MB tumors compared to tumor-free cerebellum or brain tissues. CLSTN1 is expressed in laboratory-established MB cell lines, where it localized to the plasma membrane, intracellular vesicular structures, and regions of cell-cell contact. The reduction of CLSTN1 expression significantly increased growth factor-driven invasiveness. Pharmacological inhibition of pro-migratory MAP4 kinases caused increased CLSTN1 expression and CLSTN1 accumulation in cell-cell contacts. Co-culture of tumor cells with astrocytes increased CLSTN1 localization in cell-cell contacts, which was further enhanced by MAP4K inhibition. Our study revealed a repressive function of CLSTN1 in growth-factor-driven invasiveness in MB, identified MAP4 kinases as repressors of CLSTN1 recruitment to cell-cell contacts, and points towards CLSTN1 implication in the kinase-controlled regulation of tumor-microenvironment interaction.

A comparative study of mini-monovision, crossed mini-monovision, and emmetropia with enhanced monofocal intraocular lenses

Targeting mutant p53: Evaluation of novel anti-p53R175H monoclonal antibodies as diagnostic tools

Abstract About 50% of all cancers carry a mutation in p53 that impairs its tumor suppressor function. The p53 missense mutation p53 R175H (p53 R172H in mice) is a hotspot mutation in various cancer types. Therefore, monoclonal antibodies selectively targeting clinically relevant mutations like p53 R175H could prove immensely value. We aimed to evaluate the in vitro and in vivo binding properties of two novel anti-p53 R175H monoclonal antibodies and to assess their performance as agents for molecular imaging. In vitro, 125 I-4H5 and 125 I-7B9 demonstrated long shelf life and antigen-specific binding. Our in vivo study design allowed head-to-head comparison of the antibodies in a double tumor model using repeated SPECT/CT imaging, followed by biodistribution and autoradiography. Both tracers performed similarly, with marginally faster blood clearance for 125 I-7B9. Repeated molecular imaging demonstrated suitable imaging characteristics for both antibodies, with the best contrast images occurring at 48 h post-injection. Significantly higher uptake was detected in the mut-p53-expressing tumors, confirmed by ex vivo autoradiography. We conclude that molecular imaging with an anti-p53 R175H tracer could be a promising approach for cancer diagnostics and could be further applied for patient stratification and treatment response monitoring of mutant p53-targeted therapeutics.

Subtype-specific prognostic impact of Bcl-2 in HER2-positive and HER2-negative breast cancer

Vitiligo detection capabilities of 1D photonic crystal biosensing design

Daily briefing: Sleeping mice hint at why new memories don’t overwrite old ones

Is executive attention affected by environmental lighting conditions?

Bright daylight has various positive influences, such as the long-term synchronization of circadian rhythms and an associated alertness that creates optimal conditions for attentional performance. However, the short-term effects of light on attention have not yet been sufficiently researched. Studies of these short-term effects on selective attention also showed partly contradictory effects. To investigate these short-term effects, 95 participants completed the Attention Network Test, under conditions of bright daylight or warm-white light. The focus of the present study was on executive attention, because this construct comes closest to the ANT short form of selective attention used. A significant enhancement of executive attention was observed under bright daylight conditions. This specifically means a short term effect of bright daylight on executive attention and thus selective attention in young adults.

Chlorogenic acid inhibits NLRP3 inflammasome activation through Nrf2 activation in diabetic nephropathy

Diabetic nephropathy (DN) is the single largest cause of end-stage renal disease (ESRD). Inflammation reaction mediated by NLRP3 inflammasome and Nrf2-related oxidative stress have been considered to play a very important role in the progress of diabetic nephropathy (DN). Effective drugs for the treatment of diabetic nephropathy still need to be explored. Chlorogenic acid (CGA) is a kind of polyphenol with a Nrf2 activation property widely existed in nature. The aims of this study were to evaluate the renoprotective effect of CGA and to elucidate the anti-inflammation mechanisms involved. In the present study, we established a diabetic rat model to investigate the renoprotective effect of CGA in vivo. The results show that the level of serum creatinine (Scr), blood urea nitrogen (BUN), and urinary protein excretion in diabetic rats were significantly decreased after CGA intervention. CGA administration can active the Nrf2 pathway and inhibit NLRP3 inflammasome activation. Notably, Nrf2 siRNA transfection nullified the inhibitory effects of CGA on NLRP3 inflammasome activation in vitro. To summarize, our present study provided evidence that chlorogenic acid can slow the progression of diabetic nephropathy progression, and the effect is associated with suppression of NLRP3 inflammasome activation via through modulation of the Nrf2 pathway, suggesting its therapeutic implications for diabetic nephropathy.

Adherence to antiretroviral therapy and its associated factors among children living with HIV in Eastern and Southern Africa: A systematic review and meta-analysis

Background Children living with HIV in low-income settings, such as in Eastern and Southern Africa, are at a high risk for poor adherence to antiretroviral therapy. However, various primary studies presented inconsistent and inconclusive estimates of adherence and its associated factors among children living with HIV in Eastern and Southern Africa. Therefore, we were aimed to determine the pooled prevalence of adherence and its associated factors, and to guide interventions efforts to support adherence, this comprehensive systematic review and meta-analysis was conducted. Methods We have comprehensively searched PubMed, Google Scholar, EMBASE, Scopus, and Hinari databases for all primary studies. Unpublished studies were also searched manually and accessed from university repositories. Additional searches were conducted by examining the references in the included articles to further identify relevant studies. Data were extracted and analyzed using Microsoft Excel spreadsheet and STATA version 17 software, respectively. A random-effects DerSimonian-Laird model was used to compute the pooled prevalence of adherence to antiretroviral therapy among children living in Eastern and Southern Africa. We have used Cochran’s Q test (χ2) and Higgins I2 statistics to identify heterogeneity. Subgroup and sensitivity analysis were conducted to investigate the potential sources of heterogeneity. Publication bias was assessed by the funnel plot and Egger’s test. An association was expressed through the pooled adjusted odds ratio and statistical significance was considered at a p-value < 0.05. Results This meta-analysis combined the effect estimates of 29 primary studies with 7414 study participants. The pooled prevalence of adherence to antiretroviral therapy among children living in Eastern and Southern Africa was 76.2% (95% CI: 71.4, 81.1) [I2 = 97.06%, P < 0.001 and Q test (χ2) = 953.83, p-value < 0.001]. Being a biological caregiver [AOR = 1.93 (95% CI: 1.34, 2.73)], receiving first-line antiretroviral treatment [AOR = 2.7 (95% CI: 1.39, 5.25)], and having social support [AOR = 1.88 (95% CI: 1.33, 2.66)] were significantly associated with adherence to antiretroviral therapy. Conclusion The pooled prevalence of adherence to antiretroviral therapy among children living with HIV is low. Biological caregiver, first-line antiretroviral treatment, and social support were factors associated with adherence to ART among children living with HIV. Therefore, healthcare providers, adherence counselors, supporters, as well as governmental and non-governmental organizations, should emphasize a multi-component intervention approach to address the multifaceted challenges associated with adherence to ART, thereby improving counseling efforts to enhance adherence. Moreover, clinicians should prioritize the selection and utilization of regimens for individuals in this age group on robust first-line options.

Are the 2009 Institute of Medicine gestational weight gain recommendations applicable in a contemporary South-East Asian pregnancy cohort? Results of a prospective analysis

Gestational Weight Gain (GWG) modulates pregnancy outcomes and long-term offspring metabolic health. The 2009 Institute of Medicine (IOM) GWG recommendations have largely been validated in Caucasian and mono-ethnic East Asian cohorts. Asians are at higher metabolic risk at a lower body mass index (BMI), and this has prompted the World Health Organization (WHO) to identify lower BMI cut-offs for risk evaluation amongst Asians. This prospective observational cohort study aimed to determine if 2009 IOM GWG thresholds are applicable in a contemporary multi-ethnic South-East Asian cohort. We recruited 875 mothers from an urban Malaysian tertiary clinic during screening for gestational diabetes mellitus (GDM) from 2014–2021. Data collected included measures of insulin-sensitivity, total GWG (maternal weight at delivery–self-reported pre-gravid weight), and neonatal anthropometrics (birthweight and skinfold-thickness measured with Harpenden calipers). BMI was stratified by Caucasian (overweight ≥25kg/m2, obese ≥30kg/m2) as well as Asian (overweight ≥23kg/m2, obese ≥27.5kg/ m2) cut-offs, and patients categorized by 2009 IOM GWG reference ranges. The cohort comprised 67% Malay-, 23% Chinese- and 10% Indian-descent mothers with a high prevalence of overweight/obesity (Asian cut-offs 56.9% vs Caucasian 44%). When Asian BMI cut-offs were deployed, excessive GWG incidence increased (34.1% → 40.6%) whilst inadequate GWG declined (30% → 24.8%) (p<0.05). Upon multivariate-analysis (adjusting for age, parity, race, GDM, insulin-sensitivity, baby-gender) excessive GWG categorized with Caucasian BMI cut-offs was significantly associated with increased risk of macrosomia (adjusted odds ratio (aOR) 8.65, 95% confidence interval (CI) 1.07–70.01), Neonatal-Fat-Mass (NFM) >90th centile (aOR 2.14, 95% CI 1.02–4.45) and Sum-of-Skinfold Thickness (SSFT) >90th centile (aOR 3.88, 95% CI 1.77–8.51). Excessive GWG by Asian cut-offs was also associated with increased risk of SSFT >90th centile (aOR 5.75, 95% CI 2.35–14.10). Inadequate GWG by both Caucasian and Asian BMI cut-offs was associated with Small-for-Gestational-Age (SGA) status (aOR 4.30, 95% CI 2.48–7.45 and aOR 3.66, 95% CI 2.13–6.30 respectively). In conclusion, the 2009 IOM GWG recommendations, using either Caucasian or regional Asian BMI cut-offs, are applicable in a contemporary Malay majority South-East Asian cohort in terms of predicting abnormal neonatal adiposity. Importantly, the association with neonatal adiposity is independent of increased maternal insulin resistance characteristic of Asians.

Revising the definition of “demand satisfied for modern methods of family planning:” A cross-sectional study to explore incorporating person-centered constructs of demand, choice, and satisfaction

Several challenges to validity have been identified with standard approaches used to measure “demand satisfied for modern methods of family planning.” This study explored construct validity of the widely used indicator for “demand satisfied” by comparing the standard definition to alternative definitions of the indicator highlighting dimensions of women’s own perceived demand, choice, and satisfaction. This cross-sectional study of women aged 15–49 years was conducted in Argentina (n = 1492), Ghana (n = 1600), and India (n = 1702) using a two-staged random sampling design. Women were directly asked about their: 1) demand, whether they wanted to use a contraceptive method to prevent pregnancy; 2) choice, whether they had autonomy in decision-making during their last family planning visit; and 3) satisfaction, whether they were satisfied with their method. The values of the standard and alternative indicators were compared. Convergent validity was assessed using logistic regression to explore the association between indicator definition and use of a preferred contraceptive method. In Argentina and India, the percentage of women with demand satisfied after incorporating constructs of demand, choice, and satisfaction was substantially lower than that obtained using the standard definition—a reduction of ~70% in Argentina and ~40% in India. Women who were categorized as having their “demand satisfied” for family planning according to the person-centered dimensions of the alternative indicator were significantly more likely to be using their preferred method of contraception in all three countries (OR: 7.7, 95% CI: 5.31–11.07 in Argentina, OR: 4.83, 95% CI: 2.27–10.27 in Ghana, and OR: 2.07 95% CI: 1.11–3.86 in India) compared to those whose demand was satisfied by only the standard indicator definition. Revising the definition of demand satisfied to reflect the principles of person-centered care offers an opportunity to improve construct validity by ensuring that global measurement efforts align with women’s reproductive rights.

Dialysate and plasma meropenem concentrations in continuous intraperitoneal regimen during peritoneal-dialysis-related peritonitis

Background A single dose of intraperitoneal (IP) meropenem is recommended for peritoneal-dialysis (PD)-related peritonitis stemming from extended-spectrum β-lactamase-producing organisms. However, data on IP meropenem is limited. Methods This prospective, descriptive study was conducted to examine plasma and dialysate meropenem levels during continuous IP meropenem administration in five patients with PD-related peritonitis. All patients received an IP meropenem loading dose of 500 mg, followed by IP meropenem at 125 mg/L, with four exchanges daily. The plasma and dialysate meropenem concentrations were measured at specified intervals for a 24-hour period utilizing a high-performance, liquid chromatography method. Results Five patients with PD related peritonitis were studied. The mean-maximum dialysate and plasma meropenem levels were 158.1 mg/L (standard deviation [SD] ± 62.9) and 29.4 mg/L (SD ± 15.9), respectively. The mean dialysate meropenem level was at its minimum of 32.6 mg/L (SD ± 19.1) at 24 hours. Throughout the period, the dialysate meropenem levels exceeded the minimal inhibitory concentration of the pathogenic resistance organism (> 8 mg/L). Four patients responded to the treatment, whereas one developed treatment failure from fungal peritonitis. Conclusion An IP meropenem loading of 500 mg, followed by 125 mg/L every 6 hours, provided an adequate dialysate meropenem concentration and is an effective treatment for PD related peritonitis. Trial registration Thai Clinical Trials Registry (TCTR20191121002) with date of first registration at 21/11/2019 (retrospectively registered).

The synergistic effects of microcredit access and agricultural technology adoption on maize farmer’s income in Kenya

Addressing global food security demands urgent improvement in agricultural productivity, particularly in developing economies where market imperfections are perverse and resource constraints prevail. While microcredit is widely acknowledged as a tool for economic empowerment, its role in facilitating agricultural technology adoption and improving agricultural incomes remains underexplored. This study examines the synergistic effects of microcredit access and agricultural technology adoption on the incomes of maize farmers in Kenya. Using household-level data, we employ an endogenous switching regression framework to control possible endogeneity in access to microcredit. Our findings shows that microcredit access positively influences the adoption of advanced agricultural technologies. Key determinants, including marital status, use of fertilizer application, access to extension services, and cooperative membership, are identified as significant determinants of microcredit access. Notably, the Average Treatment Effect on the Treated (ATT) indicates a 40.52% increase in income among farmers who access microcredit, mainly driven by the timely adoption of high-quality seeds, improved agricultural technologies, and enhanced inputs. These results highlight microcredit’s role in promoting allocative efficiency and enhancing Total Factor Productivity (TFP) within agricultural systems. Robustness checks, including propensity score matching and sensitivity analyses, corroborate these findings. The study recommends the implementation of targeted financial policies and educational initiatives meant to promote credit access, encourage savings, and enhancing financial literacy, particularly for credit-constrained households. Integrating these measures could strengthen rural financial markets and drive sustainable agricultural development across the regions.

Construction of management tools for early warning of prevacuum steam sterilization failure

Objective The aim of this study is to develop a set of management tools for early warning of steam sterilization failure, including a failure risk checklist and a calculation model for assessing early sterilization failure risk, and to verify the early warning effectiveness of the management tools through check experiment. Methods This study included two stages. The first stage involved the construction of a failure risk checklist and the development of a computational formula for early sterilization failure risk by expert consultation. In the second stage, the early warning effectiveness of the sterilization failure management tools was verified through a comparative verification method based on the consultation results of two experts. Results The evaluation system comprised a total of 10 early warning indicators divided into 3 categories: "Staff", "Steam sterilizer" and "Medical devices". The Cronbach’s α coefficient for internal consistency reliability was 0.837, the total content validity index (S-CVI) was 0.884, and the item-content validity (I-CVI) ranged from 0.762 to 1. In management practices, the sterilization qualification rate of the experimental group was 100%, compared to 99.78% in the control group. There were significant differences between the two groups in terms of accidental downtime (hours) and the normal operation rate of the equipment caused by equipment failure. Conclusion This study constructed an early warning model for the vacuum steam sterilization process failures. This model facilitates more accurate identification of sterilization failure risks, which helps medical institutions in enhancing sterilization quality control and early interventions.

Effects of two training workshops upon university students’ learning of critical thinking

We evaluated the effect of two workshops on learning about critical thinking amongst first- year university students. 66 Chilean pedagogy students participated, all female, with ages ranging between 18 and 37 years. Two experimental groups were organized, one with direct teaching (n = 22) and another one with semi-directed teaching (n = 19), plus a control group (n = 25). Pre- and post-tests were applied with an abbreviated Pencrisal critical thinking questionnaire. The results showed statistically significant differences in both experimental groups between the pre- and post-test, with a greater difference in experimental group 1, while the control showed no significant differences. The covariables evaluated were age and academic performance upon entering university, observing that even after controlling for the aforementioned variables, there are differences between the experimental groups and the control. We discuss the possible positive effect of direct teaching in critical thinking as a more effective strategy.

Effect of case management on viral load in adult clients enrolled due to non-suppression in Capricorn District, South Africa: A case control study

Background Case management is a structured, client centered approach that incorporates various strategies such as employing lay counsellors to provide psychosocial and adherence support to strengthen antiretroviral (ART) adherence, improve retention in care and viral load (VL) suppression. This study aimed to evaluate the effects of case management on VL in clients enrolled due to non-suppression (> = 50 copies/ml) in Capricorn District, Limpopo Province. Methods We conducted a case control study using two datasets (1) cases were selected from case management data collected from June 2021 to November 2022 at 35 facilities and captured on the REDCap system. (2) controls were identified from TIER.Net data from facilities where case management is not available and with at least two VLs on record since June 2021. Our study was restricted to clients with an unsuppressed (> = 50 copies) VL at enrollment, over the age of 18 years and excluded clients with a missing VL at enrollment. Using similar age, gender, and VL characteristics, an equal number of clients not receiving case management was randomly sampled from the TIER.Net data. Descriptive and multivariate logistic regression analysis were used to determine the factors associated with viral suppression. Results Our final study sample consisted of 3 256 clients, half of which received case management (N = 1 628), 1084 (33%) with a first VL in study of 50–399 copies/ml, 404 (12%) 400–999 copies/ml and 1768 (54%) >1000 copies/ml. Post case management intervention results showed that 49% had a VL below 50 copies/ml amongst those receiving case management and 44% among those who did not receive case management. In the adjusted model we found that case management (Odds ratio [OR] 1.25; 95% Confidence Interval [CI] 1.08–1.44) versus no case management, 35–54 years old (1.43; 1.07–1.91) and 55+ year old (1.88; 1.35–2.61) versus 18–24-year-old increased odds of VL suppression whilst being male (0.72; 0.61–0.84) versus being female has decreased odd of VL suppression. Conclusion Close to half of the clients had a VL below 50 copies/ml after case management. Factors that increased the odds of VL suppression were case management and older age, whilst being male was associated with reduced odds of VL suppression. Differentiated services for virally unsuppressed clients would be helpful for men. Case management was associated with viral suppression in those with a starting VL > 1000 copies/ml and not for those starting with low level viremia (50–999 copies/ml).

Determining the perceptions and practices of oncologists regarding venous thromboembolism risk assessment in ambulatory cancer patients: A qualitative study

Cancer-associated thrombosis (CAT) can increase morbidity and mortality for cancer patients. Therefore, guidelines recommend predicting VTE risk and thromboprophylaxis for high-risk patients. Many studies critique oncologists’ adherence to thromboprophylaxis guidelines for cancer patients. Meanwhile, most of these studies did not discuss in detail the reasons and facilitators for oncologists’ adherence to thromboprophylaxis guidelines. Therefore, the current study aimed to explore in depth the perceptions and practices of oncologists working in oncology centers in Baghdad, Iraq, regarding VTE and its risk assessment among ambulatory cancer patients. A qualitative study with face-to-face individual-based interviews was conducted with oncologists working in four major oncology centers in Baghdad, Iraq using a semi-structured interview guide. The guide was developed based on previous relevant literature and validated by a panel of experts. The interviews were conducted from November 2023 to January 2024. Thematic analysis approach was used for data analysis. Thirty-one oncologists were interviewed in this study. Twenty-two of the interviewed oncologists reported that they detect VTE among their cancer patients. 64% of participating oncologists reported that they did not conduct VTE risk assessments for their cancer patients. Only four oncologists reported assessing VTE risk using the Khorana score. 58% of oncologists reported that they prescribe thromboprophylaxis for high-risk patients; meanwhile, only 11% of them reported prescribing anticoagulants in a dose similar to that reported by thromboprophylaxis guidelines. 77% of participating oncologists reported that pharmacists have a significant role in preventing cancer-related thrombosis by helping physicians prescribe a safe and effective prophylactic anticoagulant and in calculating VTE risk scores. In conclusion, CAT is commonly diagnosed among Iraqi cancer patients. VTE risk assessment for ambulatory cancer patients is rarely conducted by oncologists working at Oncology centers in Baghdad, Iraq. The prophylactic anticoagulants were rarely prescribed in appropriate dose and/or duration for patients at high risk of VTE. Pharmacists can help oncologists follow thromboprophylaxis guidelines by calculating VTE risk score and recommending a safe and effective dose of appropriate prophylactic anticoagulant.Educating and training oncologists about VTE risk assessment is recommended to enhance their practice in thromboprophlaxis.

Telehealth equity and access communication skills pilot simulation for practicing clinicians

Objectives This pilot study evaluated a telehealth training simulation program for practicing clinicians, specifically focused on addressing patient issues of equity and access to healthcare via improving telehealth communication. Methods Participants participated in a one-hour simulation experience with two cases. Performance was assessed pre- and post-intervention using a checklist measuring communication domains related to equity and access in telehealth. Participant satisfaction was secondarily measured via survey. Results Results showed measurable gains in clinicians’ abilities to effectively incorporate equity and access communication skills. Participants found the session useful and recommended the training experience. Conclusions The findings of this pilot study highlight the potential of simulation-based telehealth training for practicing clinicians, emphasizing clinicians’ attention to patients’ equitable access to healthcare. Future studies should aim to explore the durability of learning and investigate the generalizability of this training approach to other telehealth competencies and settings.