Factors Associated with Opting Out of an Unrelated Hematopoietic Stem Cell Donor Registry: Differences and Similarities across Five Key Groups of Young Race/Ethnically Diverse Potential Donors in the United States.

Young adults from underserved racial/ethnic groups are critically needed as unrelated hematopoietic stem cell (HSC) donors, yet they are more likely than other groups to opt out of donation after having matched a patient. Understanding which factors are most strongly associated with opting out among young underserved racial/ ethnic registered donors compared with their White counterparts will provide the basis for specific interventions to improve donor retention. We sought to determine the key, modifiable psychosocial, registry-related, and donation-related characteristics that are uniquely associated with opting out across 5 key racial/ethnic groups of young HSC donor registry members who had been contacted as a potential match for a patient. This study examines data from a large cross-sectional survey of young (age 18 to 30) registry members shortly after they preliminarily matched a patient (CT-stage) and continued toward or opted out of donation (CT-C and CT-NI), stratified by racial/ethnic group and sex. We assessed psychosocial, registry-related, and donation-related characteristics for all participants. We used chi-squared and F tests to assess differences between racial/ethnic groups. A separate logistic regression analysis for each racial/ethnic group was conducted to quantify adjusted associations between each variable and opting out. Then, we compared these associations across the racial/ethnic groups by evaluating the interaction effect between each variable and racial/ethnic group, with the same outcome (CT-C versus CT-NI) in question. Nine hundred thirty-five participants were surveyed, including 284 White, 165 Hispanic, 191 Black, 192 Asian/Pacific Islander, and 103 Multiracial/multiethnic participants. There were significant differences across racial/ethnic groups in values/goals, religious objections to donation, HSC-related medical mistrust, and parental involvement in donation decisions. Adjusted logistic regression subgroup analyses indicated that ambivalence was strongly associated with opting out across all racial/ethnic groups. Greater focus on intrinsic life goals (e.g., raising a family, becoming a community leader, influencing social values) was associated with opting out in the Multiracial/multiethnic, Hispanic, and Asian/Pacific Islander groups. Healthcare mistrust and insufficient registry contact was a significant factor for Hispanic participants. Protective factors against opting out included remembering joining the registry (Black participants), and parental support for donation decision (Asian/Pacific Islander participants). The performance of each logistic regression model was strong, with area-under-the curve ≥.88, CT-stage outcome classification accuracy ≥89%, and good fit between expected and observed opt-out probabilities. In the analysis across different racial/ethnic groups, the only significant interaction was race/ethnicity by whether more contact with the registry would have changed the decision at CT-stage; this variable was significant only for the Hispanic group. In the within-group analysis for Hispanic participants, the "more registry contact" variable was strongly associated with opting out (odds ratio 5.8, P = .03). Consistent with a growing body of HSC donor research, ambivalence was a key factor associated with opting-out for all racial/ethnic groups. Other key variables were differentially associated with opting-out depending on racial/ethnic group. Our study highlights key variables that registries should focus on as they develop targeted and tailored strategies to enhance commitment and reduce attrition of potential donors.

Structural insights into respiratory complex I deficiency and assembly from the mitochondrial disease-related ndufs4-/- mouse.

Respiratory complex I (NADH:ubiquinone oxidoreductase) is essential for cellular energy production and NAD+ homeostasis. Complex I mutations cause neuromuscular, mitochondrial diseases, such as Leigh Syndrome, but their molecular-level consequences remain poorly understood. Here, we use a popular complex I-linked mitochondrial disease model, the ndufs4-/- mouse, to define the structural, biochemical, and functional consequences of the absence of subunit NDUFS4. Cryo-EM analyses of the complex I from ndufs4-/- mouse hearts revealed a loose association of the NADH-dehydrogenase module, and discrete classes containing either assembly factor NDUFAF2 or subunit NDUFS6. Subunit NDUFA12, which replaces its paralogue NDUFAF2 in mature complex I, is absent from all classes, compounding the deletion of NDUFS4 and preventing maturation of an NDUFS4-free enzyme. We propose that NDUFAF2 recruits the NADH-dehydrogenase module during assembly of the complex. Taken together, the findings provide new molecular-level understanding of the ndufs4-/- mouse model and complex I-linked mitochondrial disease.

Colonoscopy screening for colorectal cancer in Egypt: a nationwide cross-sectional study.

BACKGROUND: Current guidelines advocate for colorectal cancer (CRC) screening in adults who are at risk by using direct visualization methods such as colonoscopy. However, in Egypt, there is a paucity of data regarding the current practice of colonoscopy screening. Moreover, more information is needed about the knowledge and attitudes of potential participants regarding the procedure and possible barriers that can limit their participation. METHODS: We conducted a nationwide cross-sectional study using an interview-based survey of patients aged 45 years or above who presented to outpatient clinics of nine university hospitals throughout Egypt. Participants were surveyed to assess their compliance with CRC colonoscopy screening guidelines, their knowledge of and attitude towards colonoscopy screening, and their perspective on potential barriers to colonoscopy screening. RESULTS: A total of 1,453 participants responded to our survey in the nine study centers. Only a minority of participants (2.3%) were referred for CRC screening. Referral rates were higher among those who knew someone with a history of CRC (5.3% vs 1.5%, p < 0.001) or had a discussion with their physician about CRC (25.8% vs 0.7%, p < 0.001). Few responders (3.2%) had good knowledge regarding CRC screening. After introducing the concept of CRC screening to all participants, most patients (66.7%) showed a positive attitude towards having the procedure. Financial burden and fear of results were the two most frequently cited barriers to undergoing CRC screening (81.1%; and 60.1%, respecteively). CONCLUSIONS: Despite the positive attitude, there is insufficient knowledge about CRC screening among eligible participants in Egypt. This has probably contributed to low compliance with current CRC screening guidelines and needs to be addressed at the national level.

Rubus moluccanus L.: a valuable medicinal plant of traditional system of medicine.

Rubus moluccanus L., commonly known as Molucca bramble or broad-leaf bramble is a member of family Rosaceae which occurs mainly in tropical Asia and Australia. It has applications in indigenous medicines and is used in the treatment of number of ailments like headache, diarrhoea, dysentery, abdominal pain, nocturnal micturition of children and enhancement of female fertility. This plant is a rich and valuable source of bioactive flavonoids, terpenes and other chemical compounds. The presence of these active chemical compounds exerts antibacterial, antifungal, antihelminthic and antioxidant activities. Regardless of its use in various diseases and disorders, the information about this plant is scanty. So the present review assessed and summarised the knowledge on taxonomy, morphology, geographical distribution, nutritional value, ethnobotany, phytochemistry and biological activities of R. moluccanus.

A graphene oxide/polyaniline nanocomposite biosensor: synthesis, characterization, and electrochemical detection of bilirubin.

The level of free bilirubin is a considerable index for the characterization of jaundice-related diseases. Herein, a biosensor was fabricated via the immobilization of bilirubin oxidase (BOx) on graphene oxide (GO) and polyaniline (PANI) that were electrochemically co-precipitated on indium tin oxide (ITO) conductive glass. The structural enzyme electrode was characterized by FTIR, XRD, and Raman spectroscopy, while the spectral and thermal properties were investigated by UV-vis and thermogravimetric analysis (TGA). Owing to the activity of the fabricated BOx/GO@PANI/ITO biosensor, it could detect free bilirubin with good selectivity and sensitivity in a low response time. The electrochemical response was studied using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). At polarization potential 0.2 V vs. Ag/AgCl, the fabricated sensor illustrated a response in only 2 s at 30 °C and pH 7.5. The LOD and LOQ for the BOx/GO@PANI/ITO biosensor were calculated and found to be 0.15 nM and 2.8 nM, respectively. The electrochemical signal showed a linear response in the concentration range 0.01-250 µM. At 5 °C, the biosensor demonstrated a half-time of 120 days, through which it could be utilized 100 times at this temperature conditions. By using a common colorimetric method, the data on bilirubin levels in serum showed a determination coefficient (R2) of 0.97.

Investigation of hydrated channels and proton pathways in a high-resolution cryo-EM structure of mammalian complex I.

Respiratory complex I, a key enzyme in mammalian metabolism, captures the energy released by reduction of ubiquinone by NADH to drive protons across the inner mitochondrial membrane, generating the proton-motive force for ATP synthesis. Despite remarkable advances in structural knowledge of this complicated membrane-bound enzyme, its mechanism of catalysis remains controversial. In particular, how ubiquinone reduction is coupled to proton pumping and the pathways and mechanisms of proton translocation are contested. We present a 2.4-Å resolution cryo-EM structure of complex I from mouse heart mitochondria in the closed, active (ready-to-go) resting state, with 2945 water molecules modeled. By analyzing the networks of charged and polar residues and water molecules present, we evaluate candidate pathways for proton transfer through the enzyme, for the chemical protons for ubiquinone reduction, and for the protons transported across the membrane. Last, we compare our data to the predictions of extant mechanistic models, and identify key questions to answer in future work to test them.

Perioperative truncal peripheral nerve blocks for bariatric surgery: an opioid reduction strategy.

BACKGROUND: Bariatric surgical patients are vulnerable to cardiopulmonary depressant effects of opioids. The enhanced recovery after surgery (ERAS) protocol to improve postoperative morbidity recommends regional anesthesia for postoperative pain management. However, there is limited evidence that peripheral nerve blocks (PNB) have added benefit. OBJECTIVE: Study the effect of PNB on postoperative pain and opioid use following bariatric surgery. SETTING: Academic medical center, United States. METHODS: We conducted a cohort study of patients who underwent sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) surgery. A total of 44 patients received the control ERAS protocol with preoperative oral extended-release morphine sulfate (MS), while 45 patients underwent a PNB with either intrathecal morphine (IM) or oral MS per local ERAS protocol. The PNB group either underwent preoperative bilateral T7 paravertebral (PVT) PNBs (27 patients) with IM or postoperative transversus abdominis plane (TAP) PNBs (18 patients) with oral MS. The primary outcome compared total opioid consumption between the ERAS control group and the PNB group up to 48 hours postoperatively. Secondary outcomes included comparison by block type and postoperative pain scores. RESULTS: PVT or TAP PNB patients had a reduction in mean postoperative oral morphine equivalent (OME) requirements compared with the ERAS protocol cohort at 24 hours (93.9 versus 42.8 mg), P < .0001; at 48 hours (72.6 versus 40.5 mg); and in pain scores at 24 hours (5.64/10 versus 4.46/10), P = .02. OME and pain scores were higher in the SG cohort. CONCLUSION: Addition of truncal PNB to standard ERAS protocol for bariatric surgical patients reduces postoperative total opioid consumption.

Cryo-EM structures of mitochondrial respiratory complex I from Drosophila melanogaster.

Respiratory complex I powers ATP synthesis by oxidative phosphorylation, exploiting the energy from NADH oxidation by ubiquinone to drive protons across an energy-transducing membrane. Drosophila melanogaster is a candidate model organism for complex I due to its high evolutionary conservation with the mammalian enzyme, well-developed genetic toolkit, and complex physiology for studies in specific cell types and tissues. Here, we isolate complex I from Drosophila and determine its structure, revealing a 43-subunit assembly with high structural homology to its 45-subunit mammalian counterpart, including a hitherto unknown homologue to subunit NDUFA3. The major conformational state of the Drosophila enzyme is the mammalian-type 'ready-to-go' active resting state, with a fully ordered and enclosed ubiquinone-binding site, but a subtly altered global conformation related to changes in subunit ND6. The mammalian-type 'deactive' pronounced resting state is not observed: in two minor states, the ubiquinone-binding site is unchanged, but a deactive-type π-bulge is present in ND6-TMH3. Our detailed structural knowledge of Drosophila complex I provides a foundation for new approaches to disentangle mechanisms of complex I catalysis and regulation in bioenergetics and physiology.

Experimental evaluation of the influence of combined particle size pretreatment and Fe3O4 additive on fuel yields of Arachis Hypogea shells.

A smart energy recovery process can achieve maximum energy recovery from organic wastes. Pretreatment of feedstock is essential to biogas and methane yields during the anaerobic digestion process. This work combined particle size reduction with Fe3O4 nanoparticles to investigate their influence on biogas and methane yields from anaerobic digestion of Arachis hypogea shells. Twenty milligrams per litre of Fe3O4 nanoparticles was implemented with 2, 4, 6 and 8 mm particle sizes and a single treatment of Fe3O4 for 35 days. The treatments were compared with each other and were discovered to significantly (p < 0.05) enhance biogas yield by 37.40%, 50.10%, 54.40%, 51.40% and 35.50% compared with control, respectively. Specific biogas yield recorded was 966.2, 1406, 1552.7, 1317.4, 766.2 and 413 mL g-1 volatile solid. This study showed the combination of Fe3O4 with 6 mm particle size of Arachis hypogea shells produced the optimum biogas and methane yields. The addition of Fe3O4 to particle sizes below 6 mm resulted in over-accumulation of volatile fatty acids and lowered the gas yield. This can be applied on an industrial scale.

LW-CovidNet: Automatic covid-19 lung infection detection from chest X-ray images.

Coronavirus Disease 2019 (Covid-19) overtook the worldwide in early 2020, placing the world's health in threat. Automated lung infection detection using Chest X-ray images has a ton of potential for enhancing the traditional covid-19 treatment strategy. However, there are several challenges to detect infected regions from Chest X-ray images, including significant variance in infected features similar spatial characteristics, multi-scale variations in texture shapes and sizes of infected regions. Moreover, high parameters with transfer learning are also a constraints to deploy deep convolutional neural network(CNN) models in real time environment. A novel covid-19 lightweight CNN(LW-CovidNet) method is proposed to automatically detect covid-19 infected regions from Chest X-ray images to address these challenges. In our proposed hybrid method of integrating Standard and Depth-wise Separable convolutions are used to aggregate the high level features and also compensate the information loss by increasing the Receptive Field of the model. The detection boundaries of disease regions representations are then enhanced via an Edge-Attention method by applying heatmaps for accurate detection of disease regions. Extensive experiments indicate that the proposed LW-CovidNet surpasses most cutting-edge detection methods and also contributes to the advancement of state-of-the-art performance. It is envisaged that with reliable accuracy, this method can be introduced for clinical practices in the future.

Cryo-electron microscopy reveals how acetogenins inhibit mitochondrial respiratory complex I.

Mitochondrial complex I (NADH:ubiquinone oxidoreductase), a crucial enzyme in energy metabolism, captures the redox potential energy from NADH oxidation/ubiquinone reduction to create the proton motive force used to drive ATP synthesis in oxidative phosphorylation. High-resolution single-particle electron cryo-EM analyses have provided detailed structural knowledge of the catalytic machinery of complex I, but not of the molecular principles of its energy transduction mechanism. Although ubiquinone is considered to bind in a long channel at the interface of the membrane-embedded and hydrophilic domains, with channel residues likely involved in coupling substrate reduction to proton translocation, no structures with the channel fully occupied have yet been described. Here, we report the structure (determined by cryo-EM) of mouse complex I with a tight-binding natural product acetogenin inhibitor, which resembles the native substrate, bound along the full length of the expected ubiquinone-binding channel. Our structure reveals the mode of acetogenin binding and the molecular basis for structure-activity relationships within the acetogenin family. It also shows that acetogenins are such potent inhibitors because they are highly hydrophobic molecules that contain two specific hydrophilic moieties spaced to lock into two hydrophilic regions of the otherwise hydrophobic channel. The central hydrophilic section of the channel does not favor binding of the isoprenoid chain when the native substrate is fully bound but stabilizes the ubiquinone/ubiquinol headgroup as it transits to/from the active site. Therefore, the amphipathic nature of the channel supports both tight binding of the amphipathic inhibitor and rapid exchange of the ubiquinone/ubiquinol substrate and product.

Modelling the effects of particle size pretreatment method on biogas yield of groundnut shells.

Optimising biogas yields from anaerobic digestion of organic wastes is significant to maximum energy recovery in the biodigestion process and has become an important topic of interest. Substrate particle size is an important process parameter in biogas production, and it precedes other pretreatments methods for the majority of the lignocellulose materials. Optimisation of biogas yield using Response Surface Methodology (RSM) was done, and temperature, hydraulic retention time and particle size were considered variables to develop the predictive models. Pretreatment of groundnut shells was investigated using particle size reduction of mechanical pretreatment methods. After pretreatment, 30 samples were digested in a batch digester at mesophilic temperature. The experimental results showed that the temperature, hydraulic retention time and particle size had significant effects of interaction (p < 0.05). The optimum experimental and predicted yields are: 44.70 and 42.92 (lNkgoDM) organic dry matter biogas yield, 20.80 and 19.09 (lN/kgFM) fresh mass biogas yield, 24.00 and 22.68 (lNCH4oDM) organic dry methane yield and 12.30 and 15.59 (lNCH4FM) fresh mass methane yield, respectively. The R2 recorded for the four yield components were 0.6268, 0.5875, 0.6109 and 0.5547. These values seem to be lower and a sign of the average fit of the model. Biogas production from groundnut shells was significantly improved with statistical optimisation and the pretreatment method.

Effect of Hijama (wet cupping), Dalk (massage) and Bukhur (medicated steam) in amelioration of Waja al-Zahr (non-specific low back pain) - an open prospective clinical trial.

OBJECTIVES: Low back pain is the most widespread musculoskeletal ailment and a common cause of disability worldwide. Conventional medicine typically treats low back pain with a combination of physical therapy; activity modification and rest; pain-relieving and anti-inflammatory medications which are associated with huge socioeconomic implications and adverse drug reactions. In contrast Hijama, Dalk and Bukhur are ancient medical techniques recommended in the management of musculoskeletal disorders with little or no adverse effects. To evaluate the safety and effectiveness of Hijama bi'l Shart (wet cupping), followed by Dalk (Massage) with Roghan Dafli and Bukhur (medicated steam) with Tukhm Soya (Anethum graveolens Linn) in patients of Waja al-Zahr (Non-specific Low back pain). METHODS: Patients of either gender in the age group of 18-50 years with low back pain persisting for four weeks or more as chief complaint were recruited in the trial. The study was GCP compliant. The duration of the protocol therapy carried out was 14 days. RESULTS: Ninty two patients of NSLBP were screened, of which 34 who fulfilled the inclusion criteria and were willing to participate in the study were recruited. Three participants were lost to follow-ups due to personal reasons and 31 patients completed the trial during the study period. Overall therapeutic response observed in this study was 97% while 3% of the patients did not respond to intervention. CONCLUSIONS: The study findings imply that there is a credible evidence to ensure that the regimens intervened are safe and effective in ameliorating the symptoms of Waja al-Zahr.

Optimization of biogas yield from lignocellulosic materials with different pretreatment methods: a review.

Population increase and industrialization has resulted in high energy demand and consumptions, and presently, fossil fuels are the major source of staple energy, supplying 80% of the entire consumption. This has contributed immensely to the greenhouse gas emission and leading to global warming, and as a result of this, there is a tremendous urgency to investigate and improve fresh and renewable energy sources worldwide. One of such renewable energy sources is biogas that is generated by anaerobic fermentation that uses different wastes such as agricultural residues, animal manure, and other organic wastes. During anaerobic digestion, hydrolysis of substrates is regarded as the most crucial stage in the process of biogas generation. However, this process is not always efficient because of the domineering stableness of substrates to enzymatic or bacteria assaults, but substrates' pretreatment before biogas production will enhance biogas production. The principal objective of pretreatments is to ease the accessibility of the enzymes to the lignin, cellulose, and hemicellulose which leads to degradation of the substrates. Hence, the use of pretreatment for catalysis of lignocellulose substrates is beneficial for the production of cost-efficient and eco-friendly process. In this review, we discussed different pretreatment technologies of hydrolysis and their restrictions. The review has shown that different pretreatments have varying effects on lignin, cellulose, and hemicellulose degradation and biogas yield of different substrate and the choice of pretreatment technique will devolve on the intending final products of the process.

Chlorine inhalation induces acute chest syndrome in humanized sickle cell mouse model and ameliorated by postexposure hemopexin.

Triggering factors of Acute Chest Syndrome (ACS) is a leading cause of death in patients with Sickle Cell Disease (SCD) and targeted therapies are limited. Chlorine (Cl2) inhalation happens frequently, but its role as a potential trigger of ACS has not been determined. In this study, we hypothesized that Cl2 exposure resembling that in the vicinity of industrial accidents induces acute hemolysis with acute lung injury, reminiscent of ACS in humanized SCD mice. When exposed to Cl2 (500 ppm for 30 min), 64% of SCD mice succumbed within 6 h while none of the control mice expressing normal human hemoglobin died (p<0.01). Surviving SCD mice had evidence of acute hemolysis, respiratory acidosis, acute lung injury, and high concentrations of chlorinated palmitic and stearic acids (p<0.05) in their plasmas and RBCs compared to controls. Treatment with a single intraperitoneal dose of human hemopexin 30 min after Cl2 inhalation reduced mortality to around 15% (p<0.01) with reduced hemolysis (decreased RBCs fragility (p<0.001) and returned plasma heme to normal levels (p<0.0001)), improved oxygenation (p<0.0001) and reduced acute lung injury scores (p<0.0001). RBCs from SCD mice had significant levels of carbonylation (which predisposes RBCs to hemolysis) 6 h post-Cl2 exposure which were absent in RBCs of mice treated with hemopexin. To understand the mechanisms leading to carbonylation, we incubated RBCs from SCD mice with chlorinated lipids and identified sickling and increased hemolysis compared to RBCs obtained from control mice and treated similarly. Our study indicates that Cl2 inhalation induces ACS in SCD mice via induction of acute hemolysis, and that post exposure administration of hemopexin reduces mortality and lung injury. Our data suggest that SCD patients are vulnerable in Cl2 exposure incidents and that hemopexin is a potential therapeutic agent.

Effects of co-administration of Unani pharmacopoeia formulations Qurs Tabasheer Sartani and Arq Hara Bhara with CAT-I antitubercular drugs in rats.

OBJECTIVES: Tuberculosis continues to be a major public health problem globally, despite incredible advancements in healthcare system. In Unani system of medicine, Qurs Tabasheer Sarthani (QTS) and Arq Hara Bhara (AHB) have been traditionally used for tuberculosis like conditions. The study was aimed to investigate the effects of co-administration of QTS and AHB with category I first line antitubercular drugs (CAT-I) on the indices of liver and kidney function in rats. METHODS: QTS and AHB were prepared individually and mixed to achieve final compound Unani pharmacopoeia formulation (UPF). The human equivalent doses for rats were calculated and administered with and without CAT-I. The effects of the formulations on serum indices of kidney and liver function, hematological markers and plasma CAT-I drug levels were estimated at 14th, 60th & 180th days of treatment. RESULTS: The administration of UPF, CAT-I and UPF + CAT-I altered the levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT) and haematological markers. These alterations were within permissible range and randomly distributed among groups during various time points. Administration of CAT-I alone resulted in moderate histopathological changes which were completely abrogated in CAT-I + UPF co-administered animals. The co-administration of UPF with CAT-I improved the plasma peak rifampicin (RIF) levels, without altering the liver and kidney functions. CONCLUSIONS: The co-administration of UPF with ATT improved liver and kidney functions and increased the plasma levels of RIF. These beneficial findings provide a scope to evaluate the pharmacokinetic studies in humans.

Electrochemical corrosion behavior of copper in graphene-based thermal fluid with different surfactants.

This study investigates the effect of different surfactant-dispersed graphene nanofluid on the electrochemical behavior of copper. This study was achieved by measuring the open circuit potential and potentiodynamic polarization of copper in the nanofluids at room temperature. The test media includes surfactant-free graphene nanofluid and graphene nanofluid dispersed using four different surfactants, which are sodium dodecyl sulfate, sodium dodecylbenzene sulfonate, Gum Arabic, and Tween 80. The surface characterization and elemental composition of the copper sample before and after the corrosion tests were determined using a scanning electron microscope coupled with energy-dispersive X-ray spectroscopy. The phase formation after corrosion was also evaluated by measuring X-ray diffraction. The quantity of copper dissolved in the test media was evaluated using an inductively coupled plasma mass spectrometry (ICP-MS). The open-circuit potential measurements revealed that the current free corrosion potential of copper in the different surfactant-aided graphene nanofluids are different. The electrochemical corrosion potential, Tafel slopes, and corrosion rates revealed the better corrosion performance of copper in the nanofluid of different surfactants in the increasing order GA, SDS, Tween 80, and SDBS. Copper in GA-based graphene nanofluid was found to have the lowest corrosion rate while that of SDBS has the highest corrosion rate. However, the ICP-MS result revealed a discrepancy in the corrosion behavior and quantity of copper dissolved in the different test media. This could be attributed to the dissimilar dissolution-redeposition rate of copper in different media.

Factors Impeding Health-Care Professionals to Effectively Treat Coronavirus Disease 2019 Patients in Pakistan: A Qualitative Investigation.

The coronavirus disease 2019 (COVID-19) pandemic, first reported in late December 2019, is regarded as the most significant public health emergency of the century. According to the World Health Organization (WHO), the current outbreak of COVID-19 has affected millions of people and killed hundreds of thousands in more than 200 countries, including Pakistan. Health-care professionals (HCPs) cannot minimize human interactions or isolate themselves from patients due to their jobs and moral duties. Hence, the outbreak needed HCPs to work in adverse and challenging conditions with possible mental health problems. In light of the stated background, this study aims to explore and understand the factors that impede HCPs to effectively treat COVID-19 patients in Karachi, Pakistan. Based on qualitative methods, a phenomenological approach was considered to record the true experiences of HCPs. Twelve doctors and nurses were recruited from five COVID-19 designated hospitals in Karachi, Sindh Province, using purposive and snowball sampling. Semi-structured in-depth telephone interviews were conducted from April 6 to 14, 2020, and analyzed through thematic analysis. The findings suggest that there were two types of constraints, institutional and personal, which were impeding HCPs to treat COVID-19 patients effectively. Institutional constraints include the poor condition of isolation wards, inadequate availability of personal protective equipment (PPE), excessive and uneven workload, and absence of emotional and psychological support in hospitals. Besides, personal constraints include nervousness due to the novel virus, a constant fear of becoming infected, fear of taking virus to family, extreme isolation and loneliness, and feeling of powerlessness. The study found that HCPs in Pakistan have been dealing with a high risk of infection, causing mental health problems such as stress, anxiety, and depressive symptoms. These mental health problems not only affect attention, understanding, and decision-making capacity of HCPs, which could hinder the fight against COVID-19, but they could also have a continuous effect on their overall well-being on a long-term basis. Therefore, the present study outlines important clinical and policy strategies that are needed to support HCPs as the pandemic continues.

Structure of inhibitor-bound mammalian complex I.

Respiratory complex I (NADH:ubiquinone oxidoreductase) captures the free energy from oxidising NADH and reducing ubiquinone to drive protons across the mitochondrial inner membrane and power oxidative phosphorylation. Recent cryo-EM analyses have produced near-complete models of the mammalian complex, but leave the molecular principles of its long-range energy coupling mechanism open to debate. Here, we describe the 3.0-Å resolution cryo-EM structure of complex I from mouse heart mitochondria with a substrate-like inhibitor, piericidin A, bound in the ubiquinone-binding active site. We combine our structural analyses with both functional and computational studies to demonstrate competitive inhibitor binding poses and provide evidence that two inhibitor molecules bind end-to-end in the long substrate binding channel. Our findings reveal information about the mechanisms of inhibition and substrate reduction that are central for understanding the principles of energy transduction in mammalian complex I.