Self-reported urinary tract infection and bacterial vaginosis symptoms among indigenous adolescents during seasonal periods of water scarcity: A cross-sectional study in Bandarban Hill District of Bangladesh.

Background and Aims: Water scarcity and poor water quality could lead to suboptimum menstrual hygiene practices, and subsequently urinary tract infection (UTI) and bacterial vaginosis (BV). In this study, we estimate the prevalence of self-reported UTI and BV among indigenous adolescent girls during the water scarcity period in the Bandarban Hill Districts in south-eastern Bangladesh. Methods: Using a cross-sectional design, a total of 242 indigenous adolescent girls were selected and interviewed during the seasonal water scarcity period (from February to May 2022) in Bandarban. The difference in prevalence of any self-reported UTI or BV symptoms by respondents' characteristics was assessed by χ 2 test. Multivariable logistic regression model was used to observe the associated factors. Results: The prevalence of self-reported UTI, BV, and any symptoms of UTI or BV among the respondents were 35.54%, 28.93%, and 43.80%, respectively. Ethnicity, studentship status, source of water used for menstrual hygiene, and perceived water quality were significantly associated with the prevalence of any self-reported UTI or BV symptoms. Conclusion: Findings recommend further research to cross-check the validity of self-reported prevalence and investigate if the episodes of UTI or BV could be attributable to water scarcity and poor water quality in study areas during dry period.

On the Mechanism of Self-Assembly of Fibrinogen in Thrombin-free Aqueous Solution.

Fibrinogen dissolved in 0.12 M aqueous NaCl solution at a pH of 6.6 exhibits self-assembly in response to a lowering of the NaCl concentration to values equal to or lower than 60 mM. As has been established in a preceding work (Langmuir 2019, 35, and 12113), a characteristic signature of the self-assembly triggered by a drop in ionic strength is the formation of large globular particles. Growth of these particles most likely obeys a coalescence-like process also termed a step growth process. In order to extend this knowledge, the present work first optimized the protocol, leading to highly reproducible self-assembly experiments. Based on this optimization, the work succeeded in identifying an initial stage, not yet accessible, during which rigid short fibrils grow in close analogy to the thrombin-catalyzed polymerization of fibrin. In addition, first suggestions could be made on the transformation of these fibrils into larger aggregates, which upon drying turn into thick fiber-like ropes.

Ciprofloxacin Derivative-Loaded Nanoparticles Synergize with Paclitaxel Against Type II Human Endometrial Cancer.

Combinations of chemotherapeutic agents comprise a clinically feasible approach to combat cancers that possess resistance to treatment. Type II endometrial cancer is typically associated with poor outcomes and the emergence of chemoresistance. To overcome this challenge, a combination therapy is developed comprising a novel ciprofloxacin derivative-loaded PEGylated polymeric nanoparticles (CIP2b-NPs) and paclitaxel (PTX) against human type-II endometrial cancer (Hec50co with loss of function p53). Cytotoxicity studies reveal strong synergy between CIP2b and PTX against Hec50co, and this is associated with a significant reduction in the IC50 of PTX and increased G2/M arrest. Upon formulation of CIP2b into PEGylated polymeric nanoparticles, tumor accumulation of CIP2b is significantly improved compared to its soluble counterpart; thus, enhancing the overall antitumor activity of CIP2b when co-administered with PTX. In addition, the co-delivery of CIP2b-NPs with paclitaxel results in a significant reduction in tumor progression. Histological examination of vital organs and blood chemistry was normal, confirming the absence of any apparent off-target toxicity. Thus, in a mouse model of human endometrial cancer, the combination of CIP2b-NPs and PTX exhibits superior therapeutic activity in targeting human type-II endometrial cancer.

The prevalence and influencing factors of coexisting prediabetes and prehypertension among Bangladeshi adults.

BACKGROUND: Early detection of diabetes and hypertension is helpful to prevent and/or delay the onset of these diseases through proper interventions. Therefore, it is a prerequisite to know the prevalence of prediabetes and prehypertension and the factors associated with these conditions but people from developing countries including Bangladesh often remain undiagnosed and unaware of these conditions. In this study we investigate the prevalence of prediabetes and prehypertension and their associated factors in Bangladesh using nationally representative data. METHOD: We used nationally representative Bangladesh Demographic and Health Survey (BDHS) 2017-18 survey data, which included a total sample of 14,704 adults aged 18 years and more from whom blood pressure and fasting plasma glucose were collected. Chi-square test was used to examine the differences between sociodemographic and outcome variables. The univariate and multivariate logistic regression was performed to identify the factors associated with prediabetes and prehypertension. RESULTS: Overall, the prevalence of prediabetes and prehypertension was 8.6% with 14% of the sampled population having from prediabetes and prehypertension separately. Among the prediabetic and prehypertensive participants, one-fourth of the participant were from the richest families and around one-third were overweight/obese, while more than fifty percent had normal Body Mass Index (BMI) and completed secondary and higher education. In the univariate analysis, the richest wealth status (UOR 3.3, 95% CI: 2.46 -4.35) and overweight/obesity (UOR 3.2, 95% CI: 2.62-3.85) are the highest predictors for prediabetes and prehypertension. After adjusting the other variables, overweight/obesity remains the largest predictor for prediabetes and prehypertension (AOR:2.5, 95% CI:2.05-3.05). Further, people aged 31 and above and from the richest family had around 2 times and 1.8 times higher risk of being prediabetic and prehypertensive compared to the younger age people (18-30 years) and the poorest family (respectively). CONCLUSION: The coexistence of prediabetes and prehypertension is an early sign of a greater burden of noncommunicable diseases (NCDs) in the near future for Bangladesh. To reduce the higher burden of NCDs, our findings call for a multisectoral approach to identify the precondition of NCDs with particular attention to maintaining body weight.

ADU-Net: An Attention Dense U-Net based deep supervised DNN for automated lesion segmentation of COVID-19 from chest CT images.

An automatic method for qualitative and quantitative evaluation of chest Computed Tomography (CT) images is essential for diagnosing COVID-19 patients. We aim to develop an automated COVID-19 prediction framework using deep learning. We put forth a novel Deep Neural Network (DNN) composed of an attention-based dense U-Net with deep supervision for COVID-19 lung lesion segmentation from chest CT images. We incorporate dense U-Net where convolution kernel size 5×5 is used instead of 3×3. The dense and transition blocks are introduced to implement a densely connected network on each encoder level. Also, the attention mechanism is applied between the encoder, skip connection, and decoder. These are used to keep both the high and low-level features efficiently. The deep supervision mechanism creates secondary segmentation maps from the features. Deep supervision combines secondary supervision maps from various resolution levels and produces a better final segmentation map. The trained artificial DNN model takes the test data at its input and generates a prediction output for COVID-19 lesion segmentation. The proposed model has been applied to the MedSeg COVID-19 chest CT segmentation dataset. Data pre-processing methods help the training process and improve performance. We compare the performance of the proposed DNN model with state-of-the-art models by computing the well-known metrics: dice coefficient, Jaccard coefficient, accuracy, specificity, sensitivity, and precision. As a result, the proposed model outperforms the state-of-the-art models. This new model may be considered an efficient automated screening system for COVID-19 diagnosis and can potentially improve patient health care and management system.

A ciprofloxacin derivative with four mechanisms of action overcomes paclitaxel resistance in p53-mutant and MDR1 gene-expressing type II human endometrial cancer.

Dysfunction of the p53 gene and the presence of the MDR1 gene are associated with many malignant tumors including endometrial cancer and are responsible for cancer therapeutic resistance and poor survival. Thus, there is a critical need to devise novel combinatorial therapies with multiple mechanisms of action to overcome drug resistance. Here, we report a new ciprofloxacin derivative (CIP2b) tested either alone or in combination with taxanes against four human endometrial cancer cell lines. In vitro studies revealed that a combination of paclitaxel + CIP2b had synergistic cytotoxic effects against MDR1-expressing type-II human endometrial cancer cells with loss-of-function p53 (Hec50co LOFp53). Enhanced antitumor effects were confirmed by substantial increases in caspase-3 expression, cell population shifts toward the G2/M phase, and reduction of cdc2 phosphorylation. It was found that CIP2b targets multiple pathways including the inhibition of MDR1, topoisomerase I, and topoisomerase II, as well as enhancing the effects of paclitaxel (PTX) on microtubule assembly. In vivo treatment with the combination of PTX + CIP2b also led to significantly increased accumulation of PTX in tumors (compared to CIP2b alone) and reduction in tumor growth. Enhanced in vivo cytotoxic effects were confirmed by histological and immunohistochemical examination of the tumor tissues. Complete blood count and blood biochemistry data confirmed the absence of any apparent off-target toxicity. Thus, combination therapy involving PTX and CIP2b targeted multiple pathways and represents an approach that could result in improved tolerance and efficacy in patients with type-II endometrial cancer harboring the MDR1 gene and p53 mutations.

How is parental education associated with infant and young child feeding in Bangladesh? a systematic literature review.

BACKGROUND: Education is expected to bring about positive behavioral changes which could lead to improved health behaviors. Parental education is a primary determinant of child health and development. However, some evidence showed inverse associations between high parental education and recommended infant and young child feeding (IYCF) in Bangladesh. How the association of parental education differs with specific IYCF components has not been reviewed. Therefore, the role of parental education on optimal IYCF practices in Bangladesh appears to be inconclusive. The objective of this review is to summarize how parental education is associated with IYCF practices in Bangladesh. METHOD: This review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A systematic literature search was conducted in PubMed, Web of Science, Embase, and Google Scholar. Record searching, study selection, and data extraction was performed using Endnote online and Covidence tool, respectively. The Newcastle-Ottawa scale was used for quality assessment of the included studies. RESULTS: Out of 414 initial hits, 34 studies were included for this review. Of the included studies, 32 were cross-sectional, one was a randomized controlled trial, and one was a retrospective cohort. Most of the studies (n = 24) were nationally representative whereas 10 studies had populations from district and sub-district level. Included studies considered different IYCF-related indicators, including breastfeeding (n = 22), complementary feeding (n = 8), both breastfeeding and complementary feeding (n = 2), both breastfeeding and bottle feeding (n = 1), and pre-lacteal feeding (n = 1). Parental education was found to be positively associated with complementary feeding practices. However, the role of parental education on breastfeeding, in general, was ambiguous. High parental education was associated with bottle-feeding practices and no initiation of colostrum. CONCLUSION: Public health interventions need to focus not only on non- and/or low-educated parents regarding complementary feeding but also on educated mothers for initiation of colostrum and proper breastfeeding practices. TRIAL REGISTRATION: This systematic review is registered to PROSPERO ( https://www.crd.york.ac.uk/prospero/ ) with registration ID: CRD42022355465.

An Overview of Systematic Reviews and Meta-Analyses on the Effect of Medication Interventions Targeting Polypharmacy for Frail Older Adults.

Frailty refers to the lack of resilience and a reduction in a person's ability to recover following a health problem, and it is increasingly becoming a challenging aspect of ageing populations. Many older adults are exposed to polypharmacy; i.e., they continue to be on medications without timely re-evaluation. Medication reviews have proven successful in managing polypharmacy in the general population, but there is uncertainty regarding their effect among frail older adults. This overview of published systematic reviews assesses the impact of medication reviews on polypharmacy in frail older adults. Embase was searched from its inception to January 2021 and 28 systematic reviews were identified, out of which 10 were included in the overview. Medication reviews were the most common intervention in 8 out of 10 systematic reviews. The frailty score was reported as an outcome in one systematic review that found no evidence for fundamental pharmacological effects on frailty. Six systematic reviews reported a statistically significant reduction in the number of inappropriately prescribed medications. Four systematic reviews reported on hospital admissions, with two of them reporting a decrease in hospitalisations. The quality assessment was moderate in six and critically low in four of the systematic reviews. We conclude that medication reviews help in reducing the use of inappropriate medications in frail older adults, but that there is insufficient evidence in terms of frailty score and hospital admissions.

Selective androgen receptor modulator microparticle formulation reverses muscle hyperalgesia in a mouse model of widespread muscle pain.

ABSTRACT: Chronic pain is a significant health problem associated with disability and reduced quality of life. Current management of chronic pain is inadequate with only modest effects of pharmacological interventions. Thus, there is a need for the generation of analgesics for treating chronic pain. Although preclinical and clinical studies demonstrate the analgesic effects of testosterone, clinical use of testosterone is limited by adverse androgenic effects. Selective androgen receptor modulators (SARMs) activate androgen receptors and overcome treatment limitations by minimizing androgenic side effects. Thus, we tested whether daily soluble SARMs or a SARM-loaded microparticle formulation alleviated muscle hyperalgesia in a mouse-model of widespread pain (male and female C57BL/6J mice). We tested whether the analgesic effects of the SARM-loaded microparticle formulation was mediated through androgen receptors by blocking androgen receptors with flutamide pellets. In vitro and in vivo release kinetics were determined for SARM-loaded microparticles. Safety and toxicity of SARM treatment was determined using serum cardiac and liver toxicity panels, heart histology, and conditioned place preference testing. Subcutaneous daily SARM administration, and 2 injections, 1 week apart, of SARM-loaded microparticles alleviated muscle hyperalgesia in both sexes and was prevented with flutamide treatment. Sustained release of SARM, from the microparticle formulation, was observed both in vitro and in vivo for 4 weeks. Selective androgen receptor modulator treatment produced no cardiac or liver toxicity and did not produce rewarding behaviors. These studies demonstrate that SARM-loaded microparticles, which release drug for a sustained period, alleviate muscle pain, are safe, and may serve as a potential therapeutic for chronic muscle pain.

Value of Nonpharmacological Interventions for People With an Acquired Brain Injury: A Systematic Review of Economic Evaluations.

OBJECTIVES: Acquired brain injury (ABI) has long-lasting effects, and patients and their families require continued care and support, often for the rest of their lives. For many individuals living with an ABI disorder, nonpharmacological rehabilitation treatment care has become increasingly important care component and relevant for informed healthcare decision making. Our study aimed to appraise economic evidence on the cost-effectiveness of nonpharmacological interventions for individuals living with an ABI. METHODS: This systematic review was registered in PROSPERO (CRD42020187469), and a protocol article was subject to peer review. Searches were conducted across several databases for articles published from inception to 2021. Study quality was assessed according the Consolidated Health Economic Evaluation Reporting Standards checklist and Population, Intervention, Control, and Outcomes criteria. RESULTS: Of the 3772 articles reviewed 41 publications met the inclusion criteria. There was a considerable heterogeneity in methodological approaches, target populations, study time frames, and perspectives and comparators used. Keeping these issues in mind, we find that 4 multidisciplinary interventions studies concluded that fast-track specialized services were cheaper and more cost-effective than usual care, with cost savings ranging from £253 to £6063. In 3 neuropsychological studies, findings suggested that meditated therapy was more effective and saved money than usual care. In 4 early supported discharge studies, interventions were dominant over usual care, with cost savings ranging from £142 to £1760. CONCLUSIONS: The cost-effectiveness evidence of different nonpharmacological rehabilitation treatments is scant. More robust evidence is needed to determine the value of these and other interventions across the ABI care pathway.

Cost Effectiveness of the Use of Prophylactic Mesh To Prevent Parastomal Hernia After Urinary Diversion with an Ileal Conduit.

Background: Prophylactic lightweight mesh in the sublay position reduced the cumulative incidence of parastomal hernia (PSH) after cystectomy with ileal conduit diversion in a randomised controlled trial. Objective: To investigate whether the use of prophylactic mesh is cost-effective in comparison to no mesh from the health care provider perspective. Design setting and participants: Data on health care resource utilisation (outpatient care and inpatient care) were obtained for 159 patients included in a randomised trial. The patients underwent surgery at Skåne University Hospital or Helsingborg County Hospital (80 with a prophylactic mesh and 79 without) and information about care was ascertained from the regional health care register. The patients underwent surgery between 2012 and 2017 and were followed until death or August 2020. Outcome measurements and statistical analyses: The primary outcome measure was the clinical incidence of PSH. Costs are reported in Euro in 2020 prices (€1 = 10.486 Swedish Krona) and presented as the incremental cost-effectiveness ratios (ICERs) with confidence intervals (CIs) calculated using a nonparametric bootstrap procedure. Sensitivity analyses and subgroup analyses were performed to capture the uncertainty for ICERs. Results and limitations: The mean difference in total costs between the mesh and no-mesh groups was -€2047 (95% CI -€16 441 to €12 348). Seventeen patients (21.5%) in the no-mesh group developed clinical PSH versus six patients (7.5%) in the mesh group (p = 0.001). This indicates that mesh is less costly and more effective compared to no mesh from the health care provider perspective. Subgroup analyses showed that results were more advantageous for women and for patients younger than 71 yr and with less comorbidity than for their counterparts. Conclusions: The use of prophylactic mesh during ileal conduit reconstruction to prevent PSH is cost-effective from the health care provider perspective. Patient summary: In patients having their bladder surgically removed, a mesh implant can be inserted when a portion of the intestine is used to create an opening to drain urine from the body. Our results show that mesh use to prevent development of a hernia at the opening where urine exits the body is cost-effective from the perspective of health care providers.

Short Term Economic Evaluation of the Digital Platform "Support, Monitoring and Reminder Technology for Mild Dementia" (SMART4MD) for People with Mild Cognitive Impairment and their Informal Caregivers.

BACKGROUND: A randomized controlled trial of the SMART4MD tablet application was conducted for persons with mild cognitive impairment (PwMCI) and their informal caregivers to improve or maintain quality of life. OBJECTIVE: The objective was to conduct economic evaluation of SMART4MD compared to standard care in Sweden from a healthcare provider perspective based on a 6-month follow-up period. METHODS: Three hundred forty-five dyads were enrolled: 173 dyads in the intervention group and 172 in standard care. The primary outcome measures for PwMCI and informal caregivers were quality-adjusted life years (QALY). The results are presented as incremental cost-effectiveness ratios, and confidence intervals are calculated using non-parametric bootstrap procedure. RESULTS: For PwMCI, the mean difference in total costs between intervention and standard care was € 12 (95% CI: -2090 to 2115) (US$ = € 1.19) and the mean QALY change was -0.004 (95% CI: -0.009 to 0.002). For informal caregivers, the cost difference was - € 539 (95% CI: -2624 to 1545) and 0.003 (95% CI: -0.002 to 0.008) for QALY. The difference in cost and QALY for PwMCI and informal caregivers combined was -€ 527 (95% CI: -3621 to 2568) and -0.001 (95% CI: -0.008 to 0.006). Although generally insignificant differences, this indicates that SMART4MD, compared to standard care was: 1) more costly and less effective for PwMCI, 2) less costly and more effective for informal caregivers, and 3) less costly and less effective for PwMCI and informal caregivers combined. CONCLUSION: The cost-effectiveness of SMART4MD over 6 months is inconclusive, although the intervention might be more beneficial for informal caregivers than PwMCI.

Healthcare costs of dementia diseases before, during and after diagnosis: Longitudinal analysis of 17 years of Swedish register data.

INTRODUCTION: This study examines health-care costs attributed to dementia diseases in the 10 years prior to, during, and 6 years after diagnosis. METHODS: Using administrative register data for people diagnosed with dementia (2010-2016) in southern Sweden (n = 21,184), and a comparison group without dementia, health-care costs over 17 years were examined using longitudinal regression analysis. RESULTS: Average annual health-care costs per person were consistently higher before diagnosis in the dementia group (10 years before: Swedish krona (SEK) 2063, P < .005 and 1 year before: SEK8166, P < .005). At diagnosis, health-care costs were more than twice as high (SEK44,410, P < .005). Four to 6 years after diagnosis, there was no significant different in costs compared to comparators. DISCUSSION: Excess health-care cost arise as early as 10 years before a formal diagnosis of dementia, and while there is a spike in cost after diagnosis, health-care costs are no different 4 years after. These findings question currently accepted assumptions on costs of dementia.

In search of an appropriate mix of taxes and subsidies on nutrients and food: A modelling study of the effectiveness on health-related consumption and mortality.

Taxes and subsidies on foods and nutrients have the potential to promote healthier diets and thereby reduce mortality. In this study, we examine the effects of such policy instruments on Swedish public health. Specifically, we estimate the effects of food and nutrient taxes and subsidies on mortality averted and postponed in Sweden, using both demand system estimations and simulation models. We evaluate different Value Added Tax (VAT) reforms. The VAT is raised on food products that are particularly rich in saturated fat or salt and lowered on fruit and vegetables. Our models predict that an increase in the current VAT of 12% on food, to 25% VAT on products rich in saturated fat plus a 0% VAT on fruits and vegetables would result in almost 1100 deaths (95% CI: -832; -1363) averted or postponed in a year in Sweden, while the combination of a 34.4% VAT on products rich in saturated fat and a -10.4% VAT (i.e. a subsidy) on fruits and vegetables would result in almost 2100 (95% CI: -1572; -2311) deaths averted or postponed corresponding to a 4.8% reduction in diet-related annual death. Most of the deaths averted or delayed from this reform would be deaths from coronary heart disease (-1,148, 95% CI: -728; -1586), followed by stroke -641 (95% CI: -408; -887) and diet-related cancer deaths (-288, 95% CI: -11; -435). We find that health-related food taxes and subsidies improve dietary habits as well as reduce the mortality of the Swedish population. However, the effect of these reforms on different socioeconomic classes and which reforms provide the best value for money, i.e., cost-effectiveness of these reforms needs to be established first before implementation.

Maternal health status and household food security on determining childhood anemia in Bangladesh -a nationwide cross-sectional study.

BACKGROUND: The aim of this study was to examine the effect of household food security on childhood anemia in Bangladesh while controlling for socioeconomic and demographic factors. METHODS: We used nationally representative Bangladesh Demographic Health Survey (BDHS) 2011 data for this study, the only existing survey including anemia information and household food security. The sample included 2171 children aged 6-59 months and their mothers. Differences between socioeconomic and demographic variables were analyzed using Chi-square test. Univariate and multivariate logistic regression analyses were performed to estimate the effects of different socioeconomic and demographic factors on childhood anemia. We also performed mediation analysis to examine the direct and indirect effect of household food security on childhood anemia. RESULTS: In Bangladesh, 53% male (95% CI: 50-56) and 51% female (95% CI: 47-54) children aged 6-59 months were anemic in 2011. The food insecure households have 1.20 times odds (95% CI: 0.97-1.48) of having anemic children comparing to food secure households in the unadjusted model. On the other hand, anemic mothers have 2 times odds (95% CI: 1.67-2.44) of having anemic children comparing to non-anemic mothers. However, household food security is no longer significantly associated with childhood anemia in the adjusted model while mothers' anemia remained a significant factor (OR 1.87: 95% CI: 1.53-2.29). Age of children is the highest associated factor, and the odds are 4.89 (95% CI: 3.21-7.45) for 6-12 months old children comparing to 49-59 months in the adjusted model. Stunting and household wealth are also a significant factor for childhood anemia. Although food security has no significant direct effect on childhood anemia, maternal anemia and childhood stunting mediated that relationship. CONCLUSIONS: Future public health policies need to focus on improving mothers' health with focusing on household food security to eliminate childhood anemia.

Solubilized ubiquinol for preserving corneal function.

Defective cellular metabolism, impaired mitochondrial function, and increased cell death are major problems that adversely affect donor tissues during hypothermic preservation prior to transplantation. These problems are thought to arise from accumulated reactive oxygen species (ROS) inside cells. Oxidative stress acting on the cells of organs and tissues preserved in hypothermic conditions before surgery, as is the case for cornea transplantation, is thought to be a major reason behind cell death prior to surgery and decreased graft survival after transplantation. We have recently discovered that ubiquinol - the reduced and active form of coenzyme Q10 and a powerful antioxidant - significantly enhances mitochondrial function and reduces apoptosis in human donor corneal endothelial cells. However, ubiquinol is highly lipophilic, underscoring the need for an aqueous-based formulation of this molecule. Herein, we report a highly dispersible and stable formulation comprising a complex of ubiquinol and gamma cyclodextrin (γ-CD) for use in aqueous-phase ophthalmic products. Docking studies showed that γ-CD has the strongest binding affinity with ubiquinol compared to α- or ß-CD. Complexed ubiquinol showed significantly higher stability compared to free ubiquinol in different aqueous ophthalmic products including Optisol-GS® corneal storage medium, balanced salt solution for intraocular irrigation, and topical Refresh® artificial tear eye drops. Greater ROS scavenging activity was noted in a cell model with high basal metabolism and ROS generation (A549) and in HCEC-B4G12 human corneal endothelial cells after treatment with ubiquinol/γ-CD compared to free ubiquinol. Furthermore, complexed ubiquinol was more effective at lowering ROS, and at far lower concentrations, compared to free ubiquinol. Complexed ubiquinol inhibited lipid peroxidation and protected HCEC-B4G12 cells against erastin-induced ferroptosis. No evidence of cellular toxicity was detected in HCEC-B4G12 cells after treatment with complexed ubiquinol. Using a vertical diffusion system, a topically applied inclusion complex of γ-CD and a lipophilic dye (coumarin-6) demonstrated transcorneal penetrance in porcine corneas and the capacity for the γ-CD vehicle to deliver drug to the corneal endothelium. Using the same model, topically applied ubiquinol/γ-CD complex penetrated the entire thickness of human donor corneas with markedly greater ubiquinol retention in the endothelium compared to free ubiquinol. Lastly, the penetrance of ubiquinol/γ-CD complex was assayed using human donor corneas preserved for 7 days in Optisol-GS® per standard industry practices, and demonstrated higher amounts of ubiquinol retained in the corneal endothelium compared to free ubiquinol. In summary, ubiquinol complexed with γ-CD is a highly stable composition that can be incorporated into a variety of aqueous-phase products for ophthalmic use including donor corneal storage media and topical eye drops to scavenge ROS and protect corneal endothelial cells against oxidative damage.

Cost-effectiveness analysis of negative pressure wound therapy dressings after open inguinal vascular surgery - The randomised INVIPS-Trial.

AIM: While the scientific evidence in favour of negative pressure wound therapy (NPWT) dressings on sutured incisions in the prevention of surgical site infections (SSIs) has increased, the cost-effectiveness after vascular surgery has not been evaluated. The aim of this study was to evaluate the cost-effectiveness of NPWT compared to standard dressings for the prevention of SSIs after open inguinal vascular surgery. MATERIALS AND METHODS: Patient data were retrieved from the randomised INVIPS-trial's open arm, which included patients randomised to either NPWT or standard dressings. The patients were surveyed for SSIs for 90 days postoperatively. The patients' individual cost data were included and analysed from a healthcare perspective. The patients' quality of life was measured using the Vascuqol-6 questionnaire pre- and 30 days postoperatively. Cost-effectiveness of NPWT was determined by decreased or equal total costs and a significant reduction in SSI incidence. RESULTS: The mean vascular procedure-related costs at 90 days were €16,621 for patients treated with NPWT (n = 59) and €16,285 for patients treated with standard dressings (n = 60), p = 0.85. The SSI incidence in patients treated with NPWT was 11.9% (n = 7/59) compared to 30.0% (n = 18/60) with standard dressings, p = 0.015. This corresponds to an increased mean cost of €1,853 per SSI avoided. The cost-effectiveness plane of incremental vascular procedure-related costs and difference in Vascuqol-6 score showed that 42% of estimates were in the quadrant where NPWT was dominant. CONCLUSION: NPWT is considered cost-effective over standard dressings in patients undergoing open inguinal vascular surgery due to reduced SSI incidence at no higher costs.

Isolation, detection, and quantification of hydrolyzable tannins of the biosynthetic pathway by liquid chromatography coupled with tandem mass spectrometry.

RATIONALE: Hydrolyzable tannins (HTs) are widely distributed complex secondary metabolites with potential bioactivities and health-promoting benefits. A highly sensitive compound-specific ultrahigh-performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS) method is required for their successful detection and quantification in order to advance the study of these compounds. METHODS: In this study, 36 HTs belonging to the HT biosynthetic pathway covering 13 major branches were extracted by cold extraction and fractionated by Sephadex LH-20 size-exclusion chromatography. Followed fractionation, the HTs were purified by semipreparative HPLC so that they could be used for the development of a UHPLC/QqQ-MS/MS multiple reaction monitoring (MRM) method for their characterization. The cone voltage and collision energy for each HT were extensively optimized during the development of the MRM method. RESULTS: The developed method was very useful for the detection and quantification of marker tannins with a low limit of detection (LOD) and limit of quantification (LOQ), depending on the size and complexity of the structures of the HTs. Each isolated compound was successfully identified and characterized by UHPLC/ESI-Orbitrap-MS/MS analysis. In addition, a new methodology for cold extraction and fractionation by Sephadex LH-20 chromatography has been developed for the targeted extraction of HTs. CONCLUSIONS: This study has provided a compound-specific MRM method for the detection and quantification of representative HTs from diverse phytochemical samples that can thus be used in large-scale screening tests to pinpoint the major biosynthetic branches of HTs utilized by plants to accumulate specific types of HTs.