[Preventing relapse of acute leukemias and myelodysplastic syndromes in post-allograft transplantation: Prophylactic and preemptive strategies (SFGM-TC)]. / Prévention de la rechute des leucémies aiguës et syndromes myélodysplasiques en post-allogreffe : stratégies prophylactique et préemptive (SFGM-TC).

Disease relapse remains the first cause of mortality of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HCT) for acute myeloid and lymphoid leukemia (AML and ALL) and for myelodysplastic syndroms (MDS). More and more patients are eligible for allo-HCT over the years and for many of them, only reduced intensity conditioning is possible, which is associated with a higher risk of relapse. Knowledge and biotechnology allow us to better identify diseases at very high risk of relapse and to measure residual disease before allo-HCT. Planning post-transplant maintenance treatment as part of a prophylaxis strategy is now feasible. Monitoring biomarkers of residual disease and post-transplant chimerism after allo-HCT allows a preemptive strategy. Within the frame of the 14th annual workshops of the Francophone Society for Bone Marrow Transplantation and Cell Therapy, the working group reviewed the literature and discussed novel strategies and therapies used to prevent relapse post-allo-HCT. Innovative drugs have been developed recently. Their toxicity profile allows their use post-allo-HCT, albeit with precaution. We reviewed the use of FLT3 inhibitors for AML, BCR::ABL inhibitors for Philadelphia chromosome for ALL, hypomethylating agents and Bcl-2 inhibitors for AML and MDS. The indications of immunomodulation and infusion of donor lymphocytes have been reviewed. Finally, we outlined methods of follow-up and support for patients receiving these prophylactic treatments.

Metabolic associated fatty liver disease (MAFLD): assessing the knowledge and practice of primary care doctors in Seremban District, Negeri Sembilan.

Introduction: Metabolic-associated fatty liver disease (MAFLD) is the liver manifestation of metabolic syndrome, which is commonly seen in primary care settings. This study aimed to determine the knowledge and practice of primary care physicians regarding MAFLD in Seremban District, Negeri Sembilan. Methods: This cross-sectional study was conducted among medical officers in 14 health clinics in Seremban District, using a validated, self-administered online questionnaire. Results: A total of 240 medical officers from 14 health clinics in Seremban District, participated in this study. Most participants (85.4%) passed the knowledge test. Their practice was acceptable, but only a minority were familiar with non-invasive testing of liver fibrosis (e.g. APRI or FIB-4), medication and specific diet for the treatment of MAFLD. Conclusion: Most primary care physicians in Seremban District are knowledgeable in identifying risk factors and managing patients with MAFLD. However, there are still areas to improve in terms of management, particularly regarding the use of silymarin, vitamin E and pioglitazone.

Awake Tracheal Intubation: An Update.

Awake tracheal intubation (ATI) remains the "gold standard" technique in securing a definitive airway in conscious, self-ventilating patients with predicted or known difficult airways and the procedure is associated with a low failure rate. Since its inception a variety of techniques to achieve ATI have emerged and there have been accompanying advancements in pharmaceuticals and technology to support the procedure. In recent years there has been a growing focus on the planning, training and human factors involved in performing the procedure. The practice of ATI, does however, remain low around 1% to 2% of all intubations despite an increase in those with head and neck pathology. ATI, therefore, presents a skill that is key for the safety of patients but may not be practised with regularity by many anesthetists. In this article we therefore aim to highlight relevant guidance, recent literature and provide an update on the practical methods fundamental for successful ATI. We also discuss the crucial aspects of a safe airway culture and how this can help to embed training and maintenance of skills.

Prevalence and severity of anaemia among the Temiar sub-ethnic indigenous Orang Asli communities in Kelantan, Peninsular Malaysia.

Introduction: Anaemia remains a primary concern of public health in developing countries. Indigenous populations are a significant and frequently underreported group at risk for anaemia. This study aimed to assess the prevalence of anaemia and identify its determinants in the Temiar sub-ethnic indigenous Orang Asli (OA) community in Peninsular Malaysia. Methodology: A community-based cross-sectional study was conducted among 640 indigenous Temiar OA participants from a remote settlement in Gua Musang, Kelantan, Malaysia. Data was collected using face-to-face interviews with a standardised pretested questionnaire and through blood samples collected for haemoglobin (Hb) testing. Anaemia status was determined using the Hb level cut-off established by the World Health Organization (WHO). Descriptive analysis was used to determine the prevalence of anaemia, while multiple logistic regression was used to determine factors associated with anaemia. Results: The overall anaemia prevalence was 44.7% (286/640), and the prevalence rates of mild, moderate and severe anaemia were 42.7, 50.7 and 6.6%, respectively. Anaemia-specific prevalence varied significantly by age group (p < 0.001) and was highest in the ≤5 group for both moderate anaemia (43.4%) and severe (42.1%), followed by the 6-17 age group for mild anaemia (39.3%). The prevalence of anaemia was also highest among students (53.9%), with a significant difference observed between the three anaemia severity classifications (p = 0.002). In the multivariate logistic regression, only age groups of 6-17 (adjusted odds ratio [aOR] 0.38, p < 0.001), 18-40 (aOR 0.18, p < 0.001) and > 40 (aOR 0.25, p < 0.001) were significantly associated with the lower odds of anaemia in the population. Conclusion: This study has highlighted the high prevalence of anaemia among indigenous OA in Peninsular Malaysia and revealed that younger children were positively associated with childhood anaemia. Effective interventions and special attention to this indigenous population need to be implemented to reduce the risk of anaemia.

The Importance of Being Grade 3: A Plea for a Three-tier Hybrid Classification System for Grade in Primary Non-muscle-invasive Bladder Cancer.

Grade is an important determinant of progression in non-muscle-invasive bladder cancer. Although the World Health Organization (WHO) 2004/2016 grading system is recommended, other systems such as WHO1973 and WHO1999 are still widely used. Recently, a hybrid (three-tier) system was proposed, separating WHO2004/2016 high grade (HG) into HG/grade 2 (G2) and HG/G3 while maintaining low grade. We assessed the prognostic performance of HG/G3 and HG/G2. Three independent cohorts with 9712 primary (first diagnosis) Ta-T1 bladder tumors were analyzed. Time to progression was analyzed with cumulative incidence functions and Cox regression models. Harrell's C-index was used to assess discrimination. Time to progression was significantly shorter for HG/G3 than for HG/G2 in multivariable analyses (cohort 1: hazard ratio [HR] = 1.92; cohort 2: HR = 2.51, and cohort 3: HR = 1.69). Corresponding progression risks at 5 yr were 18%, 20%, and 18% for HG/G3 versus 7.3%, 7.5%, and 9.3% for HG/G2, respectively. Cox models using hybrid grade performed better than models with WHO2004/2016 (all cohorts; p < 0.001). For the three cohorts, C-indices for WHO2004/2016 were 0.69, 0.62, and 0.75, while, for hybrid grade, C-indices were 0.74, 0.68, and 0.78, respectively. Subdividing the HG category into HG/G2 and HG/G3 stratifies time to progression and supports the recommendation to adopt the hybrid grading system for Ta/T1 bladder cancers.

Vermi-remediation impacts on growth and metals bioaccumulation in tomato irrigated with wastewater.

Due to their persistence in the environment, and their highly toxic and bioaccumulative nature, heavy metals are well known to the environment. Vermicompost has gained popularity because it improves soil properties and, most importantly, remediates and immobilizes heavy metals. The present study assessed vermicompost effects on heavy metal bioaccumulation in tomato plants irrigated with wastewater. A plastic bag experiment was carried out with 5 kg of growing media in each bag. Growing media contain garden soil with four levels of vermicompost mixed at 0%, 5%, 15%, and 25%. The pots were irrigated with wastewater from different industries and tap water, which was taken as control. Wastewater was collected from the pharmaceutical industry, plastic industry, and sewage water of Hayatabad Industrial Estate, Peshawar. Vermicompost application significantly affected all tomatoes' growth attributes and heavy metals concentration. Results revealed that minimum Cd (2.48 mg kg-1), Cr (1.27 mg kg-1), Cu (4.10 mg kg-1), and Pb (0.62 mg kg-1) concentrations were recorded in tomatoes cultivated in 25 % vermicompost amended soil, while, maximum Cd (5.23 mg kg-1), Cr (2.29 mg kg-1), Cu (8.84 mg kg-1) and Pb (2.18 mg kg-1) concentrations were reported in sewage water irrigated plants., Overall, vermicompost applied at 25% significantly enhanced plant growth and yield, reducing the bioavailability and bioaccumulation of heavy metals. From the finding of this study, it is observed that wastewater irrigation of plants should be avoided because of the high level of heavy metals; in contrast, the application of vermicompost is highly recommended as compost reduces heavy metals bioaccumulation and enhances productivity.

Abstracts of the Cell Therapy Transplant Canada 2023 Annual Conference.

On behalf of Cell Therapy Transplant Canada (CTTC), we are pleased to present the Abstracts of the CTTC 2023 Annual Conference. The conference was held in-person, 31 May-2 June 2023, in Halifax, Nova Scotia at the Westin Nova Scotian hotel. Poster authors presented their work during a lively and engaging welcome reception on Thursday, 1 June, and oral abstract authors were featured during the oral abstract session in the afternoon of Friday, 2 June 2023. Twenty-three (23) abstracts were selected for presentation as posters and four (4) as oral presentations. Abstracts were submitted within four categories: (1) Basic/Translational Sciences, (2) Clinical Trials/Observations, (3) Laboratory/Quality, and (4) Pharmacy/Nursing/Other Transplant Support. The top four (4) oral abstracts and top four (4) poster abstracts were selected to receive an award. All of these were marked as "Award Recipient" within the relevant category. We congratulate all the presenters on their research and contributions to the field.

Influence of agro-wastes derived biochar and their composite on reducing the mobility of toxic heavy metals and their bioavailability in industrial contaminated soils.

The agro-waste derived valuable products are prime interest for effective management of toxic heavy metals (THMs). The present study investigated the efficacy of biochars (BCs) on immobilization of THMs (Cr, Zn, Pb, Cu, Ni and Cd), bioaccumulation and health risk. Agro-wastes derived BCs including wheat straw biochar (WSB), orange peel biochar (OPB), rice husk biochar (RHB) and their composite biochar (CB) were applied in industrial contaminated soil (ICS) at 1% and 3% amendments rates. All the BCs significantly decreased the bioavailable THMs and significantly (p < 0.001) reduced bioaccumulation at 3% application with highest efficiency for CB followed by OPB, WSB and RHB as compared to control treatment. The bioaccumulation factor (BAF), concentration index (CI) and ecological risk were decreased with all BCs. The hazard quotient (HQ) and hazard index (HI) of all THMs were <1, except Cd, while carcer risk (CR) and total cancer risk index (TCRI) were decreased through all BCs. The overall results depicted that CB at 3% application rate showed higher efficacy to reduce significantly (p < 0.001) the THMs uptake and reduced health risk. Hence, the present study suggests that the composite of BCs prepared from agro-wastes is eco-friendly amendment to reduce THMs in ICS and minimize its subsequent uptake in vegetables.

The present study has a scientific research scope, based on reduction of bioavailability and bioaccumulation of toxic heavy metals (THMs) by the addition of biochars derived from agro-wastes and their composite biochar (CB), thereby decreasing the potential health risk. Limited study has been conducted, especially on the impact of CB in THMs-contaminated soil. This study could fill the scientific research gap and provides useful information for mitigation of THMs present in contaminated soil, which could be followed by the Environmental Protection Agency, Ministry of Agriculture and farmers in degraded lands.

Giant Cell Tumor of the Tendon Sheath of the Hand: Analysis of Factors Impacting Recurrence.

Background Giant cell tumors of the tendon sheath (GCTTS) of the hand are considered the second most common benign tumors of the hand after ganglion cysts. Excision biopsy is considered the standard treatment at present. They are notorious for having a very high rate of recurrence as given in many studies. Many factors are said to be associated with recurrence of the tumors. The goal of this study is to evaluate the long-term results of a series of 48 patients operated on at a single institute and to find out if there is any correlation between the proposed risk factors with recurrence. Methods A retrospective analysis was done in cases of GCTTS operated on between 2015 and 2021. The patients were invited for follow-up for a minimum of 2 years, and the patient files were reviewed. Further data were collected at follow-up including recurrence, range of movement, sensation, skin necrosis, scarring, and digital neuropathy. A data analysis was done. The correlation between the proposed risk factors and recurrence was calculated with the Pearson correlation coefficient. A p -value of less than 0.05 was considered statistically significant. Results During the 6 years, 48 patients were operated on. Recurrence was observed in eight patients (16%) at an average of 38.7 months from the time of surgery. Of the risk factors, tumors with satellite nodules and tumor adjacency to joint correlated significantly with recurrence. No complications were observed during follow-up. Conclusion GCTTS of the hand has a high propensity to recur. The presence of satellite nodules and proximity to interphalangeal joints are two important risk factors for recurrence. Magnification during surgery ensures complete excision of the tumor and reduces the chance of recurrence.

Multifaceted Applications of Luminescent Metalloporphyrin Derivatives: Fluorescence Turn-On Sensing of Nicotine and Antimicrobial Activity.

In this study, we designed and synthesized metalloporphyrin derivatives (with Ni and Zn) specifically intended for the fluorescence detection of nicotine in aqueous solutions. Our results showcased a notable selectivity for nicotine over other naturally occurring food toxins, exhibiting an exceptional sensitivity with a limit of detection as low as 7.2 nM. Through mechanistic investigations (1H NMR, FT-IR, etc.), we elucidated the binding mechanism, revealing the specific interaction between the pyridine ring of nicotine and the metal center, while the N atom pyrrolidine unit engaged in the hydrogen bonding with the side chain of the porphyrin ring. Notably, we observed that the nature of the metal center dictated the extent of interaction with nicotine; particularly, Zn-porphyrin demonstrated a superior response compared to Ni-porphyrin. Furthermore, we performed the quantitative estimation of nicotine in commercially available tobacco products. Additionally, we conducted the antibacterial (Staphylococcus aureus and Escherichia coli) and antifungal (Candida albicans) activities of the porphyrin derivatives.

Treatment with nanosomal paclitaxel lipid suspension versus conventional paclitaxel in metastatic breast cancer patients - a multicenter, randomized, comparative, phase II/III clinical study.

Background: A novel nanosomal paclitaxel lipid suspension (NPLS), free from Cremophor EL (CrEL) and ethanol, was developed to address the solvent-related toxicities associated with conventional paclitaxel formulation. Objective: To evaluate the efficacy and safety of NPLS versus CrEL-based paclitaxel (conventional paclitaxel) in patients with metastatic breast cancer (MBC). Design: A prospective, open-label, randomized, multiple-dose, parallel, phase II/III study. Methods: Adult (18-65 years) female patients with MBC who had previously failed at least one line of chemotherapy were randomized (2:2:1) to NPLS 175 mg/m2 every 3 weeks (Q3W, n = 48, arm A), NPLS 80 mg/m2 every week (QW, n = 45, arm B) without premedication or conventional paclitaxel (Taxol®, manufactured by Bristol-Myers Squibb, Princeton, NJ, USA) 175 mg/m2 Q3W (n = 27, arm C) with premedication. In the extension study, an additional 54 patients were randomized (2:1) to arm A (n = 37) or arm C (n = 17). Results: Pooled data from the primary study and its extension phase included 174 patients. The primary endpoint was the overall response rate (ORR). As per intent-to-treat analysis, ORR was significantly better in the NPLS QW arm as compared to conventional paclitaxel [44.4% (20/45) versus 22.7% (10/44), (p = 0.04)]. An improvement in ORR with NPLS Q3W versus conventional paclitaxel arm [29.4% (25/85) versus 22.7% (10/44)] (p = 0.53) was observed. Disease control rates observed were improved with NPLS Q3W versus conventional paclitaxel Q3W (77.7% versus 72.7%, p = 0.66) and with NPLS QW versus conventional paclitaxel Q3W (84.4% versus 72.7%, p = 0.20), although not significant. A lower incidence of grade III/IV peripheral sensory neuropathy, vomiting, and dyspnea was reported with NPLS Q3W versus conventional paclitaxel Q3W arms. Conclusion: NPLS demonstrated an improved tumor response rate and a favorable safety profile versus conventional paclitaxel. NPLS 80 mg/m2 QW demonstrated a significantly better response versus conventional paclitaxel 175 mg/m2 Q3W. Trial registration: Clinical Trial Registry-India (CTRI), CTRI/2010/091/001344 Registered on: 18 October 2010 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MjEzNQ==&Enc=&userName=CTRI/2010/091/001344), CTRI/2015/07/006062 Registered on: 31 July 2015 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTE2Mjc=&Enc=&userName=CTRI/2015/07/006062).

Role of nanosomal paclitaxel lipid suspension (NPLS) in the treatment of patients with metastatic breast cancer (MBC) Why was the study done? Paclitaxel is a commonly used drug for the treatment of breast cancer. Conventional formulation of paclitaxel is known to cause side effects like injection site reactions. A newer formulation named NPLS was developed to overcome the limitations of the conventional paclitaxel. The current study was done to compare the safety and effectiveness of NPLS and conventional paclitaxel in patients with advanced breast cancer. What did the researchers do? The research team conducted a large study in multiple hospitals across India, involving women with advanced breast cancer who had experienced treatment failure with previous chemotherapy. A total of 174 patients were randomly assigned to receive either of the three treatment schedules: (1) NPLS every 3 weeks, (2) NPLS every week, (3) conventional paclitaxel every 3 weeks. What did the researchers find? The results showed that NPLS, in a weekly schedule, led to better tumor response rates compared to conventional paclitaxel given every 3 weeks. Additionally, NPLS demonstrated a favorable safety profile, as compared to conventional paclitaxel. What do the findings mean? These findings suggest that NPLS could be a promising alternative for women with advanced breast cancer. NPLS improved the response to treatment, with a better safety profile compared to conventional paclitaxel.

Modification of 4-(4-chlorothiophen-2-yl)thiazol-2-amine derivatives for the treatment of analgesia and inflammation: synthesis and in vitro, in vivo, and in silico studies.

Inflammation is a protective response to a variety of infectious agents. To develop a new anti-inflammatory drug, we explored a pharmacologically important thiazole scaffold in this study. In a multi-step synthetic approach, we synthesized seven new thiazole derivatives (5a-5g). Initially, we examined the in vitro anti-inflammatory potentials of our compounds using COX-1, COX-2, and 5-LOX enzyme assays. After in vitro confirmation, the potential compounds were subjected to in vivo analgesic and anti-inflammatory studies. The hot plate method was used for analgesia, and carrageenan-induced inflammation was also assayed. Overall, all our compounds proved to be potent inhibitors of COX-2 compared to celecoxib (IC50 0.05 µM), exhibiting IC50 values in the range of 0.76-9.01 µM .Compounds 5b, 5d, and 5e were dominant and selective COX-2 inhibitors with the lowest IC50 values and selectivity index (SI) values of 42, 112, and 124, respectively. Similarly, in the COX-1 assay, our compounds were relatively less potent but still encouraging. Standard aspirin exhibited an IC50 value of 15.32 µM. In the 5-LOX results, once again, compounds 5d and 5e were dominant with IC50 values of 23.08 and 38.46 µM, respectively. Standard zileuton exhibited an IC50 value of 11.00 µM. Based on the COX/LOX and SI potencies, the compounds 5d and 5e were subjected to in vivo analgesic and anti-inflammatory studies. Compounds 5d and 5e at concentrations of 5, 10, and 20 mg/kg body weight were significant in animal models. Furthermore, we explored the potential role of compounds 5d and 5e in various phlogistic agents. Similarly, both compounds 5d and 5e were also significantly potent in the anti-nociceptive assay. The molecular docking interactions of these two compounds with the target proteins of COX and LOX further strengthened their potential for use in COX/LOX pathway inhibitions.

Recent advances in modified starch based biodegradable food packaging: A review.

This study reviews the importance of resistant starch (RS) as the polymer of choice for biodegradable food packaging and highlights the RS types and modification methods for developing RS from native starch (NS). NS is used in packaging because of its vast availability, low cost and film forming capacity. However, application of starch is restricted due to its high moisture sensitivity and hydrophilic nature. The modification of NS into RS improves the film forming characteristics and extends the applications of starch into the formulation of packaging. The starch is blended with other bio-based polymers such as guar, konjac glucomannan, carrageenan, chitosan, xanthan gum and gelatin as well as active ingredients such as nanoparticles (NPs), plant extracts and essential oils to develop hybrid biodegradable packaging with reduced water vapor permeability (WVP), low gas transmission, enhanced antimicrobial activity and mechanical properties. Hybrid RS based active packaging is well known for its better film forming properties, crystalline structures, enhanced tensile strength, water resistance and thermal properties. This review concludes that RS, due to its better film forming ability and stability, can be utilized as polymer of choice in the formulation of biodegradable packaging.

Novel and Innovative Surgical Strategies for Recurrent Rectal Cancer: Uncommon Resections, Local Interventions for Pelvic Reoccurrence, and Intraoperative Radiation Therapy.

The frequency of recurrent rectal cancer has dropped significantly with improved surgical approaches and adjunctive therapies. These recurrences have proven challenging to obtain R0 resection with salvage operations. Meticulous planning, clear understanding of anatomy with imaging, and multispecialty support have become essential in local control and long-term survival with pelvic recurrence of rectal cancer. Technical considerations and prognosis indicators along with role of intraoperative radiation or boost radiation are discussed within.

Breaking barriers to climate finance: Asymmetric nexus between green investment and energy innovation in Europe.

Growing concerns regarding climate change and the necessity to shift towards a low-carbon economy have resulted in a significant rise in the worth of green finance for developing energy technology. This growing emphasis on green finance underscores the urgency for a nuanced exploration of the asymmetric nexus between green investment and energy innovation in Europe. The present article investigates the asymmetric relationship between green investment and energy innovation in the top ten European nations with the highest green investment (France, Netherlands, Germany, Italy, Spain, Denmark, Austria, Finland, the UK, and Sweden). Formerly, panel data methodologies were employed to observe the link between green investment and energy innovation despite the absence of an exclusive connection in certain economies. On the other hand, this study uses 'Quantile-on-Quantile' approach for econometric estimation using the annual data from 2007 to 2022. This unique methodology enables a detailed and specific analysis of time-series interdependence in every economy, providing valuable perceptions of the nuanced relationship between these variables. Investment in renewable energy is employed as a proxy for green investment, while energy-related patents represent energy innovation. The study employs a quantile cointegration test to assess the variables long-run relationship. The results indicate a positive correlation between green investment and energy innovation in many countries at certain data points. Additionally, the analysis demonstrates that the extent of asymmetry between these variables varies across countries, stressing policymakers' need to closely monitor fluctuations in green investment and energy innovation.

Design, synthesis, in-vitro biological profiling and molecular docking of some novel oxazolones and imidazolones exhibiting good inhibitory potential against acetylcholine esterase.

Heterocyclic compounds with oxazole and imidazole rings in their structure have disclosed momentous biological aptitudes. Taking into account their superlative attributes, the present study was designed to introduce a new synthetic scheme to make new derivatives with tremendous futuristic pharmacological potentialities. Series of Oxazolones were synthesized by using substituted benzaldehyde with benzyl halides to produce respective benzaldehyde derivatives 1 (a-d) which further reacted with hippuric acid to yield oxazolones 2 (a-e). Newly synthesized oxazolones then reacted with 4-chloroaniline to yield corresponding imidazolones 3 (a-e). All the compounds were characterized by using FTIR and NMR spectroscopic techniques. Docking studies of Compounds were conducted using AutoDock Vina and analyzed with PYMOL. All synthesized oxazolone and imidazolone derivatives exhibited antioxidant potential, demonstrated by their IC50 values compared to ascorbic acid standard. Oxazolone derivatives (2a-2e) exhibited good acetyl cholinesterase inhibitory potential whereas Imidazolone series did not show significant inhibition as shown by their IC50 values compared to donepezil as a standard. Docking studies of all compounds against acetylcholinesterase demonstrated favorable binding affinity, indicating their potential for further in-vivo studies. It is notable that novel compounds of both oxazolones and Imidazolone series exhibited antioxidant potential with maximum percentage inhibition of 75.9 (IC50 12.9 ± 0.0573 µM/mL) by compound 2d while compound 2a showed AChE inhibitory potential with maximum %age inhibition of 75.49 (IC50 7.8 ± 0.0218 µM/mL).Communicated by Ramaswamy H. Sarma.

In Silico Insights into the Arsenic Binding Mechanism Deploying Application of Computational Biology-Based Toolsets.

An assortment of environmental matrices includes arsenic (As) in its different oxidation states, which is often linked to concerns that pose a threat to public health worldwide. The current difficulty lies in addressing toxicological concerns and achieving sustained detoxification of As. Multiple conventional degradation methods are accessible; however, they are indeed labor-intensive, expensive, and reliant on prolonged laboratory evaluations. Molecular interaction and atomic level degradation mechanisms for enzyme-As exploration are, however, underexplored in those approaches. A feasible approach in this case for tackling this accompanying concern of As might be to cope with undertaking multivalent computational methodologies and tools. This work aimed to provide molecular-level insight into the enzyme-aided As degradation mechanism. AutoDock Vina, CABS-flex 2.0, and Desmond high-performance molecular dynamics simulation (MDS) were utilized in the current investigation to simulate multivalent molecular processes on two protein sets: arsenate reductase (ArsC) and laccase (LAC) corresponding arsenate (ART) and arsenite (AST), which served as model ligands to comprehend binding, conformational, and energy attributes. The structural configurations of both proteins exhibited variability in flexibility and structure framework within the range of 3.5-4.5 Å. The LAC-ART complex exhibited the lowest calculated binding affinity, measuring -5.82 ± 0.01 kcal/mol. Meanwhile, active site residues ILE-200 and HIS-206 were demonstrated to engage in H-bonding with the ART ligand. In contrast to ArsC, the ligand binding affinity of this bound complex was considerably greater. Additional validation of docked complexes was carried out by deploying Desmond MDS of 100 ns to capture protein and ligand conformation behavior. The system achieved stability during the 100 ns simulation run, as confirmed by the average P-L RMSD, which was ∼1 Å. As a preliminary test of the enzyme's ability to catalyze As species, corresponding computational insights might be advantageous for bridging gaps and regulatory consideration.

Achieving Benchmarks for National Quality Indicators Reduces Recurrence and Progression in Non-muscle-invasive Bladder Cancer.

BACKGROUND: Noncompliance with evidence-based interventions and guidelines contributes to significant and variable recurrence and progression in patients with non-muscle-invasive bladder cancer (NMIBC). The implementation of a quality performance indicator (QPI) programme in Scotland's National Health Service (NHS) aimed to improve cancer outcomes and reduce nationwide variance. OBJECTIVE: To evaluate the effect of hospitals achieving benchmarks for two specific QPIs on time to recurrence and progression in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: QPIs for bladder cancer (BC) were enforced nationally in April 2014. NHS health boards collected prospective data on all new BC patients. Prospectively recorded surveillance data were pooled from 12 collaborating centres. INTERVENTION: QPIs of interest were (1) hospitals achieving detrusor muscle (DM) sampling target at initial transurethral resection of bladder tumour (TURBT) and (2) use of single instillation of mitomycin C after TURBT (SI-MMC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary and secondary endpoints were time to recurrence and progression, respectively. Kaplan-Meier and Cox multivariable regression analyses were performed. KEY FINDINGS AND LIMITATIONS: Between April 1, 2014 and March 31, 2017, we diagnosed 3899 patients with new BC, of which 2688 were NMIBC . With a median follow up of 60.3 mo, hospitals achieving the DM sampling target had a 5.4% lower recurrence rate at 5 yr than hospitals not achieving this target (442/1136 [38.9%] vs 677/1528 [44.3%], 95% confidence interval [CI] = 1.6-9.2, p = 0.005). SI-MMC was associated with a 20.4% lower recurrence rate (634/1791 [35.4%] vs 469/840 [55.8%], 95% CI = 16.4-24.5, p < 0.001). On Cox multivariable regression, meeting the DM target and SI-MMC were associated with significant improvement in recurrence (hazard ratio [HR] 0.81, 95% CI = 0.73-0.91, p = 0.0002 and HR 0.66, 95% CI = 0.59-0.74, p < 0.004, respectively) as well as progression-free survival (HR 0.62, 95% CI = 0.45-0.84, p = 0.002 and HR 0.65, 95% CI = 0.49-0.87, p = 0.004, respectively). We did not have a national multicentre pre-QPI control. CONCLUSIONS: Within a national QPI programme, meeting targets for sampling DM and SI-MMC in the real world were independently associated with delays to recurrence and progression in NMIBC patients. PATIENT SUMMARY: Following the first 3 yr of implementing a novel quality performance indicator programme in Scotland, we evaluated compliance and outcomes in non-muscle-invasive bladder cancer. In 2688 patients followed up for 5 yr, we found that achieving targets for sampling detrusor muscle and the single instillation of mitomycin C during and after transurethral resection of bladder tumour, respectively, were associated with delays in cancer recurrence and progression.

[Unrelated donor selection for allogeneic hematopoietic stem cell transplantation: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Choix d'un donneur non apparenté en vue d'une allogreffe de cellules souches hématopoïétiques : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

The selection of a donor is an essential element in allogeneic hematopoietic stem cell transplantation. In the absence of an HLA-matched related donor, the selection of an unrelated donor is considered, and is currently the most common type of allogenic donor used in practice. Many criteria are considered for the selection when multiple donors are available, particularly in case of partial match. The aim of this workshop is to assist in the selection of an unrelated donor, in keeping with recent data from the literature.