Mitochondrial disease presenting in childhood is characterized by clinical, biochemical and genetic complexity. Some children are affected by canonical syndromes, but the majority have nonclassical ...multisystemic disease presentations involving virtually any organ in the body. Each child has a unique constellation of clinical features and disease trajectory, leading to enormous challenges in diagnosis and management of these heterogeneous disorders. This review discusses the classical mitochondrial syndromes presenting most frequently in childhood and then presents an organ‐based perspective including systems less frequently linked to mitochondrial disease, such as skin and hair abnormalities and immune dysfunction. An approach to diagnosis is then presented, encompassing clinical evaluation and biochemical, neuroimaging and genetic investigations, and emphasizing the problem of phenocopies. The impact of next‐generation sequencing is discussed, together with the importance of functional validation of novel genetic variants never previously linked to mitochondrial disease. The review concludes with a brief discussion of currently available and emerging therapies. The field of mitochondrial medicine has made enormous strides in the last 30 years, with approaching 400 different genes across two genomes now linked to primary mitochondrial disease. However, many important questions remain unanswered, including the reasons for tissue specificity and variability of clinical presentation of individuals sharing identical gene defects, and a lack of disease‐modifying therapies and biomarkers to monitor disease progression and/or response to treatment.
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Candida auris is an emerging yeast pathogen that can cause invasive infections, particularly candidemia, in healthcare settings. Candida auris is characterized by resistance to multiple classes of ...antifungal drugs and high mortality.
To describe the risk factors, clinical characteristics, antifungal susceptibility pattern and outcomes of Candida auris blood stream infection.
We conducted a retrospective review of electronic medical records of C. auris fungemia cases in the facilities under Hamad Medical corporation, Qatar from 1/11/2018 to 31/7/2021. Demographic data, risk factors, antibiogram and 30-day outcome are described.
We identified 36 patients with C. auris fungemia. Most of the patients were in intensive care unit following severe COVID-19 pneumonia and had received steroids and broad-spectrum antibiotics. Most cases were central line related. Over 90% of isolates were non-susceptible to fluconazole, while amphotericin B resistance reached 85%. Factors associated with high mortality included initial SOFA score of 9 or above and absence of source control.
Our study reveals a concerning 41.6% mortality rate within 30 days of C. auris candidemia. Furthermore, the prevalence of amphotericin B resistance in Qatar exceeds what has been reported in the literature necessitating further exploration. Echinocandins retains nearly 100% susceptibility and should be prioritized as the treatment of choice. These findings emphasize the need for vigilant monitoring and appropriate management strategies to combat C. auris infections and improve patient outcomes.
GeneXpert MTB/RIF (Xpert) and Genotype MTBDRplus (DRplus) are two World Health Organization (WHO) endorsed probe based molecular drug susceptibility testing (DST) methods for rapid diagnosis of drug ...resistant tuberculosis. Both methods target the same 81 bp Rifampicin Resistance Determining Region (RRDR) of bacterial RNA polymerase β subunit (rpoB) for detection of Rifampicin (RIF) resistance associated mutations using DNA probes. So there is a correspondence of the probes of each other and expected similarity of probe binding.
We analyzed 92 sputum specimens by Xpert, DRplus and LJ proportion method (LJ-DST). We compared molecular DSTs with gold standard LJ-DST. We wanted to see the agreement level of two molecular methods for detection of RIF resistance associated mutations. The 81bp RRDR region of rpoB gene of discrepant cases between the two molecular methods was sequenced by Sanger sequencing.
The agreement of Xpert and DRplus with LJ-DST for detection of RIF susceptibility was found to be 93.5% and 92.4%, respectively. We also found 92.4% overall agreement of two molecular methods for the detection of RIF susceptibility. A total of 84 out of 92 samples (91.3%) had agreement on the molecular locus of RRDR mutation by DRplus and Xpert. Sanger sequencing of 81bp RRDR revealed that Xpert probes detected seven of eight discrepant cases correctly and DRplus was erroneous in all the eight cases.
Although the overall concordance with LJ-DST was similar for both Xpert and DRplus assay, Xpert demonstrated more accuracy in the detection of RIF susceptibility for discrepant isolates compared with DRplus. This observation would be helpful for the improvement of probe based detection of drug resistance associated mutations especially rpoB mutation in M. tuberculosis.
Many tumors increase uptake and dependence on glucose, cystine or glutamine. These basic observations on cancer cell metabolism have opened multiple new diagnostic and therapeutic avenues in cancer ...research. Recent studies demonstrated that smoking could induce the expression of xCT (SLC7A11) in oral cancer cells, suggesting that overexpression of xCT may support lung tumor progression. We hypothesized that overexpression of xCT occurs in lung cancer cells to satisfy the metabolic requirements for growth and survival. Our results demonstrated that 1) xCT was highly expressed at the cytoplasmic membrane in non-small cell lung cancer (NSCLC), 2) the expression of xCT was correlated with advanced stage and predicted a worse 5-year survival, 3) targeting xCT transport activity in xCT overexpressing NSCLC cells with sulfasalazine decreased cell proliferation and invasion in vitro and in vivo and 4) increased dependence on glutamine was observed in xCT overexpressed normal airway epithelial cells. These results suggested that xCT regulate metabolic requirements during lung cancer progression and be a potential therapeutic target in NSCLC.
Rapid and early detection of drug susceptibility among multidrug-resistant tuberculosis (MDR-TB) patients could guide the timely initiation of effective treatment and reduce transmission of ...drug-resistant TB. In the current study, we evaluated the diagnostic performance of GenoType MTBDRsl (MTBDRsl) ver1.0 assay for detection of resistance to ofloxacin (OFL), kanamycin (KAN) and ethambutol (EMB), and additionally the XDR-TB among MDR-TB patients in Bangladesh.
The MTBDRsl assay was performed directly on 218 smear-positive sputum specimens collected from MDR-TB patients and the results were compared with the phenotypic drug susceptibility testing (DST) performed on solid Lowenstein-Jensen (L-J) media. We also analyzed the mutation patterns of gyrA, rrs, and embB genes for detection of resistance to OFL, KAN and EMB, respectively.
The sensitivity and specificity of the MTBDRsl compared to phenotypic L-J DST were 81.8% (95% CI, 69.1-90.9) and 98.8% (95% CI, 95.6-99.8), respectively for OFL (PPV: 95.7% & NPV: 94.1%); 65.1% (95% CI, 57.5-72.2) and 86.7% (95% CI, 73.2-94.9), respectively for EMB (PPV: 94.9% & NPV: 39.4%); and 100% for KAN. The diagnostic accuracy of KAN, OFL and EMB were 100, 94.5 and 69.6%, respectively. Moreover, the sensitivity, specificity and diagnostic accuracy of MtBDRsl for detection of XDR-TB was 100%. The most frequently observed mutations were at codon D94G (46.8%) of gyrA gene, A1401G (83.3%) of rrs gene, and M306V (41.5%) of the embB gene.
Considering the excellent performance in this study we suggest that MTBDRsl assay can be used as an initial rapid test for detection of KAN and OFL susceptibility, as well as XDR-TB directly from smear-positive sputum specimens of MDR-TB patients in Bangladesh.
In Bangladesh, about 80% of healthcare is provided by the private sector. Although free diagnosis and care is offered in the public sector, only half of the estimated number of people with ...tuberculosis are diagnosed, treated, and notified to the national program. Private sector engagement strategies often have been small scale and time limited. We evaluated a Social Enterprise Model combining external funding and income generation at three tuberculosis screening centres across the Dhaka Metropolitan Area for diagnosing and treating tuberculosis.
The model established three tuberculosis screening centres across Dhaka Metropolitan Area that carried the icddr,b brand and offered free Xpert MTB/RIF tests to patients visiting the screening centres for subsidized, digital chest radiographs from April 2014 to December 2017. A network of private and public health care providers, and community recommendation was formed for patient referral. No financial incentives were offered to physicians for referrals. Revenues from radiography were used to support screening centres' operation. Tuberculosis patients could choose to receive treatment from the private or public sector. Between 2014 and 2017, 1,032 private facilities networked with 8,466 private providers were mapped within the Dhaka Metropolitan Area. 64, 031 patients with TB symptoms were referred by the private providers, public sector and community residents to the three screening centres with 80% coming from private providers. 4,270 private providers made at least one referral. Overall, 10,288 pulmonary and extra-pulmonary tuberculosis cases were detected and 7,695 were bacteriologically positive by Xpert, corresponding to 28% of the total notifications in Dhaka Metropolitan Area.
The model established a network of private providers who referred individuals with presumptive tuberculosis without financial incentives to icddr,b's screening centres, facilitating a quarter of total tuberculosis notifications in Dhaka Metropolitan Area. Scaling up this approach may enhance national and international tuberculosis response.
The sustainability of the ship recycling industry strongly linked with the global shipping market and international commodity flows. More than 80% of the End of Life (EoL) ships are dismantled in ...South Asian countries, namely Bangladesh, India, and Pakistan. Due to measures taken to minimize the propagation of the Coronavirus disease (COVID-19), an international supply chain is broken to a historic low, except for certain medical-related urgencies. Due to the disruption of global supply chains, the industry may submerge into uncertainty due to, perhaps, lack of adequate labor force to dismantle increased EoL ships and due to disturbances of vessel transportation to the recycling nations amid strong precautionary measures. Our estimate suggests that about 300 million Gross Tonnage (GT) available for demolition in the next five years and the inability to get them recycled would cost about 20 billion dollars. More importantly, South Asian recycling nations would suffer from economic losses and employment opportunities. In this study, we also apply a scenario analysis technique to understand the impact range of COVID-19 in the short term and in the long term. The disruption is viewed through a circular economy framework, identifying a critical lack of ‘global scale’ acknowledgment in the circular economy framework. This article suggests that a formalized global scale, paralleled with favorable policies, may reduce supply chain disruption and improve sustainable development in the receiving nations.
We conducted a systematic review and meta‐analysis of population‐based cohort studies of maternal body mass index (BMI) and risk of adverse birth and health outcomes in low‐ and middle‐income ...countries. PubMed, Embase, CINAHL and the British Nursing Index were searched from inception to February 2014. Forty‐two studies were included. Our study found that maternal underweight was significantly associated with higher risk of preterm birth (odds ratio OR, 1.13; 95% confidence interval CI, 1.01–1.27), low birthweight (OR, 1.66; 95% CI, 1.50–1.84) and small for gestational age (OR, 1.85; 95% CI, 1.69–2.02). Compared with mothers with normal BMI, overweight or obese mothers were at increased odds of gestational diabetes, pregnancy‐induced hypertension, pre‐eclampsia, caesarean delivery and post‐partum haemorrhage. The population‐attributable risk (PAR) indicated that if women were entirely unexposed to overweight or obesity during the pre‐pregnancy or early pregnancy period, 14% to 35% fewer women would develop gestational diabetes, pre‐eclampsia or pregnancy‐induced hypertension in Brazil, China, India, Iran or Thailand. The highest PAR of low birthweight attributable to maternal underweight was found in Iran (20%), followed by India (18%), Thailand (10%) and China (8%). Treatment and prevention of maternal underweight, overweight or obesity may help reduce the burden on maternal and child health in developing countries.
Research on alternative fuels is increasing due to environmental concerns and diminishing fossil fuel reserves. Biodiesel is one of the best renewable replacements for petroleum-based fuels. This ...paper examines the potential of biodiesel obtained from Jatropha curcas and Moringa oleifera oils. The physico-chemical properties of J. curcas and M. oleifera methyl esters were presented, and their 10% by volume blends (JB10 and MB10) were compared with diesel fuel (B0). The performance of these fuels and their emissions were assessed in a fully loaded multi-cylinder diesel engine at various engine speeds. The properties of J. curcas and M. oleifera biodiesels and their blends agreed with ASTM D6751 and EN 14214 standards. Engine performance test results indicated that the JB10 and the MB10 fuels produced slightly lower brake powers and higher brake specific fuel consumption values compared to diesel fuel over the entire range of speeds. Engine emission results indicated that the JB10 and MB10 fuels reduced the average emissions of carbon monoxide by 14 and 11%, respectively; and hydrocarbons by 16 and 12%, respectively. However, the JB10 and MB10 fuels slightly increased nitrous oxides emissions by 7 and 9%, respectively, and carbon dioxide by 7 and 5%, respectively compared to B0. In conclusion, J. curcas and M. oleifera are potential feedstock for biodiesel production, and the JB10 and MB10 blends can replace diesel fuel without modifying engines to produce cleaner exhaust emissions.
•Potential of methylester production from crude Moringa oleifera oil.•Potential of methylester production from crude Jatropha curcas oil.•Evaluation of M. oleifera methylester in a diesel engine.•Evaluation of J. curcas methylester in a diesel engine.
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