Medicinal Mushroom Supplements in Cancer: A Systematic Review of Clinical Studies.

PURPOSE OF REVIEW: Patients seek clinical guidance on mushroom supplements that can be given alongside conventional treatments, but most research on such fungi has been preclinical. The current systematic review focused on clinical studies of mushrooms in cancer care conducted in the past 10 years. We searched Medline (Ovid), Embase (Ovid), Scopus (Wiley), and Cochrane Library to identify all mushroom studies conducted in humans published from January 2010 through December 2020. Two authors independently assessed papers for inclusion. RECENT FINDINGS: Of 136 clinical studies identified by screening 2349, 39 met inclusion criteria. The studies included 12 different mushroom preparations. A survival benefit was reported using Huaier granules (Trametes robiniophila Murr) in 2 hepatocellular carcinoma studies and 1 breast cancer study. A survival benefit was also found in 4 gastric cancer studies using polysaccharide-K (polysaccharide-Kureha; PSK) in the adjuvant setting. Eleven studies reported a positive immunological response. Quality-of-life (QoL) improvement and/or reduced symptom burden was reported in 14 studies using various mushroom supplements. Most studies reported adverse effects of grade 2 or lower, mainly nausea, vomiting, diarrhea, and muscle pain. Limitations included small sample size and not using randomized controlled trial design. Many of the reviewed studies were small and observational. Most showed favorable effects of mushroom supplements in reducing the toxicity of chemotherapy, improving QoL, favorable cytokine response, and possibly better clinical outcomes. Nevertheless, the evidence is inconclusive to recommend the routine use of mushrooms for cancer patients. More trials are needed to explore mushroom use during and after cancer treatment.

Treatment of primitive myxoid mesenchymal tumour of infancy: a management paradigm focusing on surgical nuances.

Primitive myxoid mesenchymal tumour of infancy (PMMTI) is a rare mesenchymal tumour that typically appears in those under 6 months of age and preferentially affects the deep soft tissues of the trunk and paravertebral spinal regions. PMMTI has only recently been described, and there is scarce literature reporting cases regarding the management paradigm of the tumour. We report the case of an 11-week-old male who presented with bilaterally reduced movement and brisk reflexes in his lower limbs, and irritability. Despite numerous radiological investigations, including MRI, PMMTI was only diagnosed upon biopsy and histopathology. Although PMMTI is known to be relatively unresponsive to chemotherapy, we observed a notable decrease in tumour size after a series of chemotherapy sessions. After two-staged surgical resection of the tumour, the patient is currently stable and under close follow-up. In this article, we aim to report on the patient's clinical presentation, investigations, diagnosis, and treatment, while also discussing the findings from a review of the literature pertaining to future approaches in managing PMMTI. Overall, this case highlights the importance of considering PMMTI in the differential diagnosis of deep soft tissue tumours in young infants and the potential for a combination of chemotherapy and surgical resection to be effective in treating this rare tumour.

A peek behind the curtain in the diagnosis and management of COVID­19­Associated Mucormycosis (CAM).

Coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) is responsible for a high mortality rate due to its unique and severe host-pathogen interactions. Critically ill or immunocompromised COVID-19 patients are more prone to suffer from aggressive mycoses. Probable victims include those with uncontrolled diabetes mellitus (DM), metabolic acidosis, prolonged neutropenia, increased ferritin levels, hypoxia, and prolonged hospitalization with/without mechanical ventilators and corticosteroids administration. The current review aims to outline the journey of patients with CAM as well as the advantages and disadvantages of the currently available diagnostic techniques. It also discussed the current status of treatment options and caveats in the management of mucormycosis. Multidisciplinary team, early diagnosis, controlling the predisposing condition(s), complete surgical debridement, effective antifungal therapies (e.g., amphotericin B, isavuconazole, and posaconazole), and implementing antifungal stewardship programs are imperative in CAM cases.

Rise of the natural red pigment 'prodigiosin' as an immunomodulator in cancer.

Cancer is a heterogeneous disease with multifaceted drug resistance mechanisms (e.g., tumour microenvironment [TME], tumour heterogeneity, and immune evasion). Natural products are interesting repository of bioactive molecules, especially those with anticancer activities. Prodigiosin, a red pigment produced by Serratia marcescens, possesses inherent anticancer characteristics, showing interesting antitumour activities in different cancers (e.g., breast, gastric) with low or without harmful effects on normal cells. The present review discusses the potential role of prodigiosin in modulating and reprogramming the metabolism of the various immune cells in the TME, such as T and B lymphocytes, tumour-associated macrophages (TAMs), natural killer (NK) cells, and tumour-associated dendritic cells (TADCs), and myeloid-derived suppressor cells (MDSCs) which in turn might introduce as an immunomodulator in cancer therapy.

Combining CuAAC reaction enables sialylated Bi- and triantennary pseudo mannose N-glycans for investigating Siglec-7 interactions.

Naturally occurring N-glycans display much diversity in modifications, linkages, and peripheral presentation of the oligosaccharide chain. Despite continued advancements in oligosaccharide synthesis, synthetic access to these natural glycans remains challenging. Biologically relevant complex N-glycan mimetics with various natural and unnatural modifications are an alternate way for investigating glycan-protein interactions. Further supporting this pattern, we report here a new class of sialylated bi- and triantennary pseudo mannose N-glycans reproducing orientation of the underlying glycan chain and branching patterns and replacing the two inner mannopyranosyl units with 1,2,3-triazole rings. Such mimetics are straightforwardly generated by implementing multiple intermolecular Cu(I)-catalyzed azide-alkyne cycloaddition between chemoenzymatically synthesized azido sialosides and rationally designed C-3 and C-6 di-O- or C-2, C-3, and C-6 tri-O-alkynylated mannoside. Human recombinant Siglec-7-Fc fusion protein recognizes almost all sialylated pseudo mannose N-glycans in the microarray. However, a differential Sia-binding pattern was also observed. Given the library size, comparison of pairwise mannose N-glycan combinations showed that biantennary linear α(2,3)α(2,8)- and α(2,6)α(2,8)- or branched α(2,3)α(2,6)-, and triantennary branched α(2,3)α(2,6)-sialyl pseudo N-glycans possess similar binding capabilities and affinity to recombinant Siglec-7-Fc. While the full range of topological mannose arms remain elusive, the bi- and triantennary mimics are simpler structures for interrogating Siglec interactions.

Effect of Different Heat Treatments on the Quality and Flavor Compounds of Black Tibetan Sheep Meat by HS-GC-IMS Coupled with Multivariate Analysis.

There are limited reports about the effect of different heat treatments on the quality and flavor of Black Tibetan sheep meat. The current study examined the effect of pan-frying, deep-frying, baking, and boiling treatment on the quality of Black Tibetan sheep meat; the amino acid, fatty acid, and volatile flavor compounds (VFCs) were investigated by a texture analyzer, ultra-high-performance liquid chromatography (UHPLC), gas chromatography (GC), and headspace-gas chromatography-ion mobility (HS-GC-IMS). The key VFCs were identified through orthogonal partial least squares discrimination analysis (OPLS-DA), and variable importance projection (VIP) values. In addition, Pearson's correlations between meat quality parameters and key VFCs were examined. The sensory scores, including texture, color, and appearance, of baked and pan-fried meat were higher than those of deep-fried and boiled meat. The protein (40.47%) and amino acid (62.93 µmol/g) contents were the highest in pan-fried meat (p < 0.05). Additionally, it contained the highest amounts of monounsaturated and polyunsaturated fatty acids, such as oleic, linoleic, and α-linolenic acids (p < 0.05). Meanwhile, pan-fried and deep-fried meat had higher amounts of VFCs than baked meat. The OPLS-DA similarity and fingerprinting analyses revealed significant differences between the three heat treatment methods. Aldehydes were the key aroma compounds in pan-fried meat. Importantly, 3-methylbutyraldehyde and 2-heptanone contents were positively correlated with eicosenoic, oleic, isooleic, linoleic, α-Linolenic, and eicosadiene acids (p < 0.05). To sum up, pan-fried Black Tibetan sheep meat had the best edible, nutritional, and flavor quality.

The role of 5-lipoxygenase in the pathophysiology of COVID-19 and its therapeutic implications.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, known as coronavirus disease 2019 (COVID-19) causes cytokine release syndrome (CRS), leading to acute respiratory distress syndrome (ARDS), acute kidney and cardiac injury, liver dysfunction, and multiorgan failure. Although several studies have discussed the role of 5-lipoxygenase (5-LOX) in viral infections, such as influenzae and SARS, it remains unexplored in the pathophysiology of COVID-19. 5-LOX acts on free arachidonic acid (AA) to form proinflammatory leukotrienes (LTs). Of note, numerous cells involved with COVID-19 (e.g., inflammatory and smooth muscle cells, platelets, and vascular endothelium) widely express leukotriene receptors. Moreover, 5-LOX metabolites induce the release of cytokines (e.g., tumour necrosis factor-α [TNF-α], interleukin-1α [IL-1α], and interleukin-1ß [IL-1ß]) and express tissue factor on cell membranes and activate plasmin. Since macrophages, monocytes, neutrophils, and eosinophils can express lipoxygenases, activation of 5-LOX and the subsequent release of LTs may contribute to the severity of COVID-19. This review sheds light on the potential implications of 5-LOX in SARS-CoV-2-mediated infection and the anticipated therapeutic role of 5-LOX inhibitors.

Parenteral versus enteral fluid therapy for children hospitalised with bronchiolitis.

BACKGROUND: The main focus of treatment for children hospitalised with bronchiolitis is supportive, including oxygen supplementation, respiratory support, and fluid therapy. Up to half of infants hospitalised with bronchiolitis require non-oral fluid therapy due to dehydration or concerns related to the safety of oral feeding. The two main modalities used for non-oral fluid therapy are parenteral (intravenous (IV)) and enteral tube (nasogastric (NG) or orogastric (OG)). However, it is not known which mode is optimal in young children. OBJECTIVES: To systematically review randomised clinical trials (RCTs) of the effectiveness and safety of parenteral and enteral tube fluid therapy for children under two years of age hospitalised with bronchiolitis. SEARCH METHODS: We conducted a search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, Web of Science, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform on 8 March 2021. We handsearched conference proceedings, conducted forward and backward searching of citation lists of relevant articles, and contacted experts. SELECTION CRITERIA: We included RCTs and quasi-RCTs of children aged up to two years admitted to hospital with a clinical diagnosis of bronchiolitis who required fluid therapy. The trials compared enteral tube fluid therapy with parenteral fluid therapy. The primary outcome was difference in length of hospital stay in hours after each non-oral fluid therapy modality. As actual time of discharge can be impacted by various factors, we also assessed theoretical length of stay (i.e. time when a patient is safe for discharge). We assessed several secondary outcomes. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.  MAIN RESULTS: The searches yielded 615 unique records, of which four articles underwent full-text screening. We included two trials (810 children). Oakley 2013 was an open, non-blinded RCT of infants aged two to 12 months admitted to hospitals in Australia and New Zealand with a clinical diagnosis of bronchiolitis during three bronchiolitis seasons. The trial enrolled 759 children, of which 381 were randomised to NG tube therapy and 378 to IV therapy. Risk of bias was low in most domains. Kugelman 2013 was an open, non-blinded RCT that enrolled infants aged less than six months with a clinical diagnosis of "moderate bronchiolitis" at a single hospital in Israel. The study enrolled 51 infants, of which 31 were assigned to NG or OG tube therapy and 20 to IV therapy. Risk of bias was unclear in most domains. The application of enteral tube fluid therapy compared to IV fluid therapy probably makes little to no difference for actual length of hospital stay (mean difference (MD) 6.8 hours, 95% confidence interval (CI) -4.7 to 18.4 hours; 2 studies, 810 children, moderate certainty evidence). There was also little to no difference for theoretical length of stay (MD 4.4 hours, 95% CI -3.6 to 12.4 hours; 2 studies, 810 children, moderate certainty evidence). For the secondary outcomes, enteral tube fluid therapy probably makes little to no difference for time to resume full oral feeding compared to IV fluid therapy (MD 2.8 hours, 95% CI -3.6 to 9.2 hours; 2 studies, 810 children, moderate certainty evidence). The use of enteral tube for fluid therapy probably results in a large increase in the success of insertion of fluid modality at first attempt (risk ratio (RR) 1.52, 95% CI 1.36 to 1.69; 1 study, 617 children, moderate certainty evidence), and probably largely reduces the chances of change in fluid therapy modality (RR 0.52, 95% CI 0.38 to 0.71; 1 study, 759 children, moderate certainty evidence) compared to IV fluid.  Oakley 2013 reported 47 local complication events after discharge in the IV fluid group compared to 30 events in the NG tube group. They also evaluated parental satisfaction, which was high with both modalities. Enteral tube fluid therapy makes little to no difference to the duration of oxygen supplementation (MD 2.2 hours, 95% CI -5.0 to 9.5 hours; 2 studies, 810 children, moderate certainty evidence). Compared with the IV fluid therapy group, there was a 17% relative reduction in the number of intensive care unit admissions (RR 0.83, 95% CI 0.47 to 1.46; 1 study, 759 children, moderate certainty evidence) and a 19% relative reduction in number of readmissions to hospital (RR 0.81, 95% CI 0.33 to 2.04; 1 study, 678 children, moderate certainty evidence) in the enteral tube fluid therapy group. Adverse events were uncommon in both trials, with likely little to no differences between groups. AUTHORS' CONCLUSIONS: Based on two RCTs, enteral tube feeding likely results in little to no difference in length of hospital stay compared with the IV fluid group. However, enteral tube fluid therapy likely results in a large increase in the success of insertion of fluid modality at first attempt, and a large reduction in change in modality of fluid therapy. It also probably reduces local complications compared to the IV fluid group. Despite bronchiolitis being one of the most prevalent childhood conditions, we identified only two studies with under 1000 participants in total, which highlights the need for multicentre trials. Future studies should explore type of fluid administered, parent-reported outcomes and preferences, and the role of shared decision-making.

Effectiveness of a nutrition education and intervention programme on nutrition knowledge and dietary practice among Princess Nourah Bint Abdulrahman University's population.

OBJECTIVE: The study sought to assess the influence of nutrition education and intervention programmes on nutrition knowledge and dietary practice among both students and staff (including faculty) of Princess Nourah Bint Abdulrahman University in Saudi Arabia. DESIGN: A pretest-posttest, non-randomised experimental study design was implemented at Princess Nourah Bint Abdulrahman University in Riyadh City between September 2019 and February 2020. SETTING: Princess Nourah Bint Abdulrahman University is the largest women's university in the world and has eighteen colleges and institutions and around ninety academic programmes. PARTICIPANTS: The survey was completed by 1824 participants (1350 students and 474 staff/faculty) before the intervention and by a different cohort of 1731 participants (1317 students and 414 staff/faculty) after the intervention. In total, an independent sample of 3555 staff and students participated. Participants were asked about dietary knowledge and practices. Dietary knowledge entailed food variety and nutrients, fast food and its poor nutritional value, and the influence of cooking style on the nutritional quality of food. Dietary practices involved eating breakfast; consuming salt/sugar, eating high-salt food; eating pre-packaged food and consumption of vegetables, fruits, supplements, water and caffeine. RESULTS: The majority of the sample consisted of students (75·1 %) and had not been diagnosed with any disease (73·7 %). The result of the current study showed that nutrition knowledge improved after completion of the nutrition programme. CONCLUSIONS: The nutrition awareness programme improved students' nutritional knowledge; however, there was no significant effect on their dietary practices. Future nutrition awareness programmes should separate activities for students and staff, focusing on one target population at a time.

Can facility-based transitional care improve patient flow? Lessons from four Canadian regions.

Units providing transitional, subacute, or restorative care represent a common intervention to facilitate patient flow and improve outcomes for lower acuity (often older) inpatients; however, little is known about Canadian health systems' experiences with such "transition units." This comparative case study of diverse units in four health regions (48 interviews) identified important success factors and pitfalls. A fundamental requirement for success is to clearly define the unit's intended population and design the model around its needs. Planners must also ensure that the unit be resourced and staffed to deliver truly restorative care. Finally, streamlined processes must be developed to help patients access and move through the unit. Units that were perceived as more effective appeared to have satisfactorily addressed these population, capacity, and process issues, whereas those perceived as less effective continued to struggle with them. Findings suggest principles to support optimal design and implementation of transition units.

Knowledge and involvement of husbands in maternal and newborn health in rural Bangladesh.

BACKGROUND: Access to skilled health services during pregnancy, childbirth and postnatal period for obstetric care is one of the strongest determinants of maternal and newborn health (MNH) outcomes. In many countries, husbands are key decision-makers in households, effectively determining women's access to health services. We examined husbands' knowledge and involvement regarding MNH issues in rural Bangladesh, and how their involvement is related to women receiving MNH services from trained providers. METHODS: We conducted a cross-sectional survey in two rural sub-districts of Bangladesh in 2014 adopting a stratified cluster sampling technique. Women with a recent birth history and their husbands were interviewed separately with a structured questionnaire. A total of 317 wife-husband dyads were interviewed. The associations between husbands accompanying their wives as explanatory variables and utilization of skilled services as outcome variables were assessed using multiple logistic regression analyses. RESULTS: In terms of MNH knowledge, two-thirds of husbands were aware that women have special rights related to pregnancy and childbirth and one-quarter could mention three or more pregnancy-, birth- and postpartum-related danger signs. With regard to MNH practice, approximately three-quarters of husbands discussed birth preparedness and complication readiness with their wives. Only 12% and 21% were involved in identifying a potential blood donor and arranging transportation, respectively. Among women who attended antenatal care (ANC), 47% were accompanied by their husbands. Around half of the husbands were present at the birthplace during birth. Of the 22% women who received postpartum care (PNC), 67% were accompanied by their husbands. Husbands accompanying their wives was positively associated with women receiving ANC from a medically trained provider (AOR 4.5, p < .01), birth at a health facility (AOR 1.5, p < .05), receiving PNC from a medically trained provider (AOR 48.8, p < .01) and seeking care from medically trained providers for obstetric complications (AOR 3.0, p < 0.5). CONCLUSION: Husbands accompanying women when receiving health services is positively correlated with women's use of skilled MNH services. Special initiatives should be taken for encouraging husbands to accompany their wives while availing MNH services. These initiatives should aim to increase men's awareness regarding MNH issues, but should not be limited to this.

Synthesis and characterization of novel carboxymethyl Assam Bora rice starch for the controlled release of cationic anticancer drug based on electrostatic interactions.

Carboxymethyl Assam Bora rice starch (CM-ABRS) was chemically synthesized in non-aqueous medium with the optimum degree of substitution (DS) of 1.23, and physicochemically characterized by FT-IR, DSC, XRD, and SEM analysis. Comparative evaluation of CM-ABRS with native starch (ABRS) for powder flow characteristics, swelling index, apparent solubility, rheological properties, textural properties, and mucoadhesive studies were carried out. The aim of the current work was to investigate the potential of CM-ABRS as a novel carrier for the water-soluble chemotherapeutic, doxorubicin hydrochloride (DOX). Formation of drug/polymer complex (DOX-CM-ABRS) via electrostatic interaction has been evaluated for the controlled release of DOX in three different pH media (phosphate-buffered saline (PBS), pH 7.4, 6.8, and 5.5). In vitro drug release studies illustrated faster release of drug in PBS at pH 5.5 as compared to pH 6.8 and pH 7.4, respectively, indicating the importance of pH-sensitive drug release from the DOX-CM-ABRS complex in malignant tissues.

Enhanced anti-tumor efficacy of paclitaxel with PEGylated lipidic nanocapsules in presence of curcumin and poloxamer: In vitro and in vivo studies.

Cancer chemotherapeutic drug containing PEGylated lipidic nanocapsules (D-LNCs) were formulated by the controlled addition of organic phase (combined solution of paclitaxel and curcumin in a mixture of oleic acid and MPEG2000-DSPE (90:2.5 molar ratio) in acetone) to the aqueous phase (consist of Poloxamer 407 as emulsifying agents and glycerol as a co-solvent) at a temperature of 55-60°C followed by evaporation of organic solvent. The obtained pre-colloidal dispersion of D-LNCs was processed through high pressure homogenization to get more uniformly and nano-sized particles. Effect of concentration of emulsifying agent and process variables of high pressure homogenization (pressure and number of cycles) on average particle size and entrapment efficiency was further investigated by constructing Box-Behnken experimental design to achieve the optimum manufacturing process. D-LNCs were characterized by dynamic light scattering, scanning and transmission electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. In vitro release studies showed a sustained release pattern of drug from the PEGylated D-LNCs, whereas in vivo pharmacokinetic studies after a single-dose intravenous (i.v.) administration of paclitaxel (15mg/kg) in Ehrlich ascites tumor (EAT)-bearing female Swiss albino mice showed a prolonged circulation time and slower elimination of paclitaxel from D-LNCs as compared with marketed formulation (Paclitec®). From the plasma concentration vs. time profile, i.v. bioavailability (AUC0-∞) of paclitaxel from D-LNCs was found to be increased approximately 2.91-fold (P<0.001) as compared to Paclitec®. In vitro cell viability assay against MCF-7 and MCF-7/ADR cell lines, in vivo biodistribution studies and tumor inhibition study in EAT-bearing mice, all together prove its significantly improved potency towards cancer therapy.

Transungual Delivery of Ketoconazole Nanoemulgel for the Effective Management of Onychomycosis.

Ketoconazole (KCZ) nanoemulgel containing permeation enhancer was formulated as a vehicle for transungual drug delivery, and its efficacy to inhibit the growth of onychomycotic dermatophytes was investigated in vitro. Different components of oil-in-water nanoemulsions were moderately agitated by classical titration method and passed through a high-pressure homogenizer to formulate various nanoemulsions, which were further identified by constructing pseudo-ternary phase diagrams. Stress-stability testing was carried out for the nanoemulsions, and those that passed these tests were characterized for mean droplet size, zeta potential, morphology, pH, refractive index, viscosity and transmittance. Mean droplet size and zeta potential of the optimized nanoemulsion (NE3) were found to be 77.52 ± 0.92 nm (polydispersity index (PDI) = 0.128 ± 0.035) and -5.44 ± 0.67 mV, respectively. Optimized nanoemulsion was converted into nanoemulgel (NEG1) with 1% (w/w) of gelling agent (Carbopol® Ultrez 21) and 1%-2% (v/v) thioglycolic acid as permeation enhancer, and evaluated for pH, viscosity, spreadability, extrudability, tensile strength and bio-adhesion measurement. In vitro cumulative drug released at the end of 24 h from NE3, NEG1 and drug suspension were found to be 98.87 ± 1.29, 84.42 ± 2.78% and 54.86 ± 2.19%, respectively. Ex vivo transungual permeation values for KCZ through goat hooves from NE3, NEG1 and drug suspension were found to be 62.49 ± 2.98, 77.54 ± 2.88% and 38.54 ± 2.54%, respectively, in 24 h. The antifungal effect of NEG1 on Trichophyton rubrum and Candida albicans showed a significant (p < 0.05) zone of inhibition as compared to drug solution. Skin irritation and histopathology studies on rat skin showed the safe topical use and enhanced permeation of formulated nanoemulgel.

A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives.

In the modern world, a number of therapeutic proteins such as vaccines, antigens, and hormones are being developed utilizing different sophisticated biotechnological techniques like recombinant DNA technology and protein purification. However, the major glitches in the optimal utilization of therapeutic proteins and peptides by the oral route are their extensive hepatic first-pass metabolism, degradation in the gastrointestinal tract (presence of enzymes and pH-dependent factors), large molecular size and poor permeation. These problems can be overcome by adopting techniques such as chemical transformation of protein structures, enzyme inhibitors, mucoadhesive polymers and permeation enhancers. Being invasive, parenteral route is inconvenient for the administration of protein and peptides, several research endeavors have been undertaken to formulate a better delivery system for proteins and peptides with major emphasis on non-invasive routes such as oral, transdermal, vaginal, rectal, pulmonary and intrauterine. This review article emphasizes on the recent advancements made in the delivery of protein and peptides by a non-invasive (peroral) route into the body.

Cost-effectiveness of malaria diagnosis using rapid diagnostic tests compared to microscopy or clinical symptoms alone in Afghanistan.

BACKGROUND: Improving access to parasitological diagnosis of malaria is a central strategy for control and elimination of the disease. Malaria rapid diagnostic tests (RDTs) are relatively easy to perform and could be used in primary level clinics to increase coverage of diagnostics and improve treatment of malaria. METHODS: A cost-effectiveness analysis was undertaken of RDT-based diagnosis in public health sector facilities in Afghanistan comparing the societal and health sector costs of RDTs versus microscopy and RDTs versus clinical diagnosis in low and moderate transmission areas. The effect measure was 'appropriate treatment for malaria' defined using a reference diagnosis. Effects were obtained from a recent trial of RDTs in 22 public health centres with cost data collected directly from health centres and from patients enrolled in the trial. Decision models were used to compare the cost of RDT diagnosis versus the current diagnostic method in use at the clinic per appropriately treated case (incremental cost-effectiveness ratio, ICER). RESULTS: RDT diagnosis of Plasmodium vivax and Plasmodium falciparum malaria in patients with uncomplicated febrile illness had higher effectiveness and lower cost compared to microscopy and was cost-effective across the moderate and low transmission settings. RDTs remained cost-effective when microscopy was used for other clinical purposes. In the low transmission setting, RDTs were much more effective than clinical diagnosis (65.2% (212/325) vs 12.5% (40/321)) but at an additional cost (ICER) of US$4.5 per appropriately treated patient including a health sector cost (ICER) of US$2.5 and household cost of US$2.0. Sensitivity analysis, which varied drug costs, indicated that RDTs would remain cost-effective if artemisinin combination therapy was used for treating both P. vivax and P. falciparum. Cost-effectiveness of microscopy relative to RDT is further reduced if the former is used exclusively for malaria diagnosis. In the health service setting of Afghanistan, RDTs are a cost-effective intervention compared to microscopy. CONCLUSIONS: RDTs remain cost-effective across a range of drug costs and if microscopy is used for a range of diagnostic services. RDTs have significant advantages over clinical diagnosis with minor increases in the cost of service provision. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov under identifier NCT00935688.

The role of adding metformin in insulin-resistant diabetic pregnant women: a randomized controlled trial.

PURPOSE: The aim of the present study is to assess the impact of adding oral metformin to insulin therapy in pregnant women with insulin-resistant diabetes mellitus. METHODS: The current non-inferiority randomized controlled trial was conducted at Ain Shams University Maternity Hospital. The study included pregnant women with gestational or pre-existing diabetes mellitus at gestations between 20 and 34 weeks, who showed insulin resistance (defined as poor glycemic control at a daily dose of ≥1.12 units/kg). Recruited women were randomized into one of two groups: group I, including women who received oral metformin without increasing the insulin dose; and group II, including women who had their insulin dose increased. The primary outcome was maternal glycemic control. Secondary outcomes included maternal bouts of hypoglycemia, need for another hospital admission for uncontrolled diabetes during pregnancy, gestational age at delivery, mode of delivery, birth weight, birth trauma, congenital anomalies, 1- and 5-min Apgar score, neonatal hypoglycemia, need for neonatal intensive care unit (NICU) admission and adverse neonatal outcomes. RESULTS: A total number of 154 women with diabetes mellitus with pregnancy were approached; of them 90 women were eligible and were randomly allocated and included in the final analysis. The recruited 90 women were randomized into one of two groups: group I (metformin group) (n = 46), including women who received oral metformin in addition to the same initial insulin dose; and group II (control group) (n = 44), including women who had their insulin dose increased according to the standard protocol. The mean age of included women was 29.84 ± 5.37 years (range 20-42 years). The mean gestational age at recruitment was 28.7 ± 3.71 weeks (range 21-34 weeks). Among the 46 women of group I, 17 (36.9 %) women reached proper glycemic control at a daily metformin dose of 1,500 mg, 18 (39.2 %) at a daily dose of 2,000 mg, while 11 (23.9 %) received metformin at a daily dose of 2,000 mg without reaching proper glycemic control and needed raising the dose of insulin dose. CONCLUSION: Adding metformin to insulin therapy in women with insulin-resistant diabetes mellitus with pregnancy seems to be effective in proper glycemic control in a considerable proportion of women, along with benefits of reduced hospital stay, reduced frequency of maternal hypoglycemia as well as reduced frequency of neonatal hypoglycemia, NICU admission and neonatal respiratory distress syndrome.

Push-out bond strength of fiber posts to root canal dentin using a one-step self-etching adhesive: the effect of solvent removal and light-curing methods.

PURPOSE: To evaluate the effect of solvent removal and light-curing methods on the push-out bond strength of fiber posts to root canal dentin using a one-step self-etching adhesive. MATERIALS AND METHODS: Eighty single-rooted, single-canal human mandibular premolars were used in this study. After removal of the crown, the pulp was extirpated and the post space was prepared. The teeth were divided into two main groups according to the solvent removal method, either using the paper point or the air-drying method. Each of the above main groups was further subdivided into 4 subgroups according to the light-curing method: group 1: both adhesive and resin cement were cured from the top of the post in the same step (cocuring) for 40 s; group 2: the adhesive was light cured for 20 s and the resin cement for 40 s; group 3: the adhesive was light cured for 40 s as was the resin cement; group 4: an intracanal tip was used to cure the adhesive inside the post space for 20 s. In groups 1 to 4, the solvent was evaporated using oil-free compressed air for 5 s from the root surface and excess adhesive was removed from inside the canal using a paper point. In groups 5 to 8, the adhesive and cement were applied and light cured as in groups 1 to 4, except the solvent was evaporated (air dried) from inside the post space using an intra-canal disposable plastic tip attached to the tip of a 3-way syringe. After 24 hours, three 2-mm-thick root slices were obtained from each root. Each slice was subjected to the push-out bond strength test at a crosshead speed of 0.5 mm/min. Factorial analysis (two-way ANOVA) was run to test the effect of solvent evaporation method, light-curing method, and their interactions on bond strength. One-way ANOVA followed by Duncan's Multiple Range Test were used to test the effect of lightcuring method on bond strength within each solvent evaporation method. Student's t-test was performed to compare the effect of solvent evaporation method on bond strength within each light-curing method. RESULTS: Two-way ANOVA revealed that the solvent removal method had a significant effect on the bond strength of fiber post to root canal dentin. Neither the light-curing method nor the interaction between the two independent variables had a significant effect on the push-out bond strength. CONCLUSIONS: Only air drying the one-step self-etching adhesive could influence the bond strength of the fiber post to root canal dentin.

Flap blood glucose measurement for flap monitoring and early detection of circulatory problems.

Postoperative monitoring of skin flaps is subjective and cannot detect early circulatory problems in the flap. Early detection and rapid remedial re-exploration are important for flap salvage. We evaluated flap glucose measurement to monitor the flaps for early detection of circulatory problems. In total, 30 patients underwent cutaneous flap reconstruction. This is an easy, economic, objective, and reliable method for flap monitoring and can detect early venous congestion requiring remedial measures.

Estimating the Global and Regional Burden of Streptococcus pneumoniae Meningitis in Children: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: Streptococcus pneumoniae (Spn) has been a leading cause of bacterial meningitis in children. The most recent estimation of the global burden of Spn meningitis indicates a positive trajectory in eliminating Spn through the implementation of pneumococcal conjugate vaccines. However, continuous monitoring and assessment of the disease burden are necessary due to the evidence of serotype replacement, antibiotic resistance, and the impact of the recent COVID-19 pandemic. OBJECTIVE: The aim of this systematic review is to provide an updated and focused assessment of the global and regional burden of Spn meningitis in children, which can guide policies and strategies to reduce the disease burden. METHODS: Population-based studies published from January 1, 2000, to January 1, 2022, were preliminarily searched from the electronic databases PubMed, Embase, Global Health (CABI), and CINAHL Plus without any language restrictions. Studies were included if they reported the incidence, prevalence, mortality, or case-fatality ratio (CFR) for Spn meningitis in children aged 0-4 years; meningitis was confirmed by cerebrospinal fluid culture; the study period was a minimum of 1 year; the number of reported cases was at least 10; and the study had no methodological ambiguities. The article screening process follows the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Characteristics including study period, setting, World Health Organization region, income level, vaccination information, and participant data (age, number of cases, deaths, sequelae, and risk factors) will be extracted from the included studies. Search results will be updated and incorporated into our review prior to finalizing the extraction of data. Generalized linear mixed models meta-analysis will be performed to estimate the pooled incidence and CFR. We will further assess the risk of bias and heterogeneity, and will perform subgroup and sensitivity analyses to provide a meaningful interpretation of the current burden and literature for pneumococcal meningitis. RESULTS: Our preliminary search in December 2021 yielded 9295 articles. Out of 275 studies that were assessed with our eligibility criteria, 117 articles were included. Data extraction and analysis are expected to be complete by January 2025. We plan to publish the results from the full study, including an updated search in 2024, by March 2025. CONCLUSIONS: Given that the major burden of Spn meningitis affects children under the age of 5 years, this systematic review will provide a thorough understanding of the global burden of Spn meningitis in this vulnerable population over a span of 2 decades. Insights into incidence trends, geospatial distribution, risk factors, and sequelae will be valuable for stakeholders, policy makers, and the academic community. This information will aid in the ongoing monitoring of the disease and in enhancing targeted vaccine programs to further mitigate the impact of the disease on children worldwide. TRIAL REGISTRATION: PROSPERO CRD42021293110; https://tinyurl.com/kc3j5k4m. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50678.