Post-mortem pulmonary tuberculosis: comparison of available diagnostic methods.

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a serious public health threat with the World Health Organisation (WHO) reporting 5.8 million cases and 1.3 million deaths in the year 2020 due to TB. TB can be diagnosed by imaging, histopathological and bacteriological methods with culture remaining the gold standard. This study was performed to look at the sensitivity and specificity of post-mortem computed tomography (PMCT) imaging when compared to culture in diagnosing pulmonary tuberculosis. This was a retrospective comparative study looking at post mortem cases where lung tissue samples sent for TB culture at Hospital Kuala Lumpur were compared against PMCT imaging. Exclusion criteria included contaminated samples, decomposed cases, immunocompromised subjects and those below 18 years of age. Subjects included 80 medico-legal autopsy cases at the National Institute of Forensic Medicine, Hospital Kuala Lumpur, Malaysia who had whole body PMCT done in accordance with the Institute's protocol and tissue samples sent for bacteriology culture for tuberculosis. PMCT findings were positively associated with acid-fast organisms in 23.5 out of 33 cases (71.2%). Our study also showed that PMCT had a sensitivity of 71.3% and specificity of 54.3% (95% CI: 39.5-68.4) in diagnosing TB based on the protocol set in this study. This study showed that there was relatively good agreement between radiological PMCT findings and bacterial culture, suggesting that radiological examination is a relatively reliable tool for preliminary screening and possible diagnosis of TB prior to a postmortem examination which would be beneficial in reducing the risk of transmission of TB to health workers during autopsy.

Diabetes and dental caries in US adults: an analysis of data from the National Health and Nutrition Examination Survey, 2011-2018.

OBJECTIVES: To determine the relationship between diabetes and dental caries among US adults participating in the 2011-2018 National Health and Nutrition Examination Survey (NHANES). BASIC RESEARCH DESIGN: The NHANES was a cross-sectional study including clinical assessments, laboratory analysis, and interviews. The sample included 16,635 participants aged 20 years and older that represent 187,596,215 individuals in the US in a probability weighted sample. Outcome variables included overall total caries score (or number of decayed, missing, filled permanent teeth - DMFT index) and the presence of caries. Bivariate analysis, Poisson regression for total caries score, logistic regression for the presence of caries were used for analysis. RESULTS: Controlling for covariates, multiple Poisson regression revealed that total DMFT scores were associated with diabetes status (adjusted relative risk ratio (RR)controlled diabetes = 1.13, RRuncontrolled diabetes = 1.18; p⟨0.001), no college education, female sex, white race, elderly (≥ 65 years), cigarette smoking, obesity, yearly dental visits, seeing a dentist only for treatment. Similarly, multiple logistic regression shows that the odds of adults with diabetes having dental caries were higher than among those without diabetes (adjusted risk ratio (OR)controlled diabetes = 1.84, ORuncontrolled diabetes = 1.87; p⟨0.05). CONCLUSIONS: Diabetes was associated with a higher caries score and a greater risk for dental caries among US adults.

High-Throughput Generation, Manipulation, and Degradation of Magnetic Nanoparticle-Laden Alginate Core-Shell Beads for Single Bacteria Culturing Analysis.

Microbes could be found almost everywhere around us and have significant impacts on our human society. The treatment of microorganisms has long been seen as a complex problem. Till now, most of the genetic and phenotypic information regarding rare species is buried in the bulk microbial colony due to a lack of efficient tools to screen live bacteria. Droplet microfluidics offers a powerful approach to address this problem. However, the interactions among bacteria and their living environment are entirely restricted by the water/oil interfaces in conventional water/oil single emulsion-based microfluidic systems. Here, we demonstrate an oil-mediated all-aqueous microfluidic workflow that can overcome this drawback. In contrast to the previous works, our all-aqueous culturing environment allows cell-cell and cell-environment interactions, thus facilitating the growth of bacteria. Fe3O4 magnetic nanoparticles added into the alginate beads enables on-chip manipulation of the microcapsules. The core-shell structure separately encapsulates bacteria and magnetic particles in the core and shell to avoid contamination. We demonstrate the feasibility of this approach by single bacterium culturing in droplet-templated alginate beads. Finally, a new approach is proposed to degrade the alginate beads for post-treatment. This novel microfluidic workflow can create new opportunities for microbial applications, such as bacteria culturing and screening.

Post-mortem pulmonary tuberculosis: comparison of available diagnostic methods

@#Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a serious public health threat with the World Health Organisation (WHO) reporting 5.8 million cases and 1.3 million deaths in the year 2020 due to TB. TB can be diagnosed by imaging, histopathological and bacteriological methods with culture remaining the gold standard. This study was performed to look at the sensitivity and specificity of post-mortem computed tomography (PMCT) imaging when compared to culture in diagnosing pulmonary tuberculosis. This was a retrospective comparative study looking at post mortem cases where lung tissue samples sent for TB culture at Hospital Kuala Lumpur were compared against PMCT imaging. Exclusion criteria included contaminated samples, decomposed cases, immunocompromised subjects and those below 18 years of age. Subjects included 80 medico-legal autopsy cases at the National Institute of Forensic Medicine, Hospital Kuala Lumpur, Malaysia who had whole body PMCT done in accordance with the Institute’s protocol and tissue samples sent for bacteriology culture for tuberculosis. PMCT findings were positively associated with acid-fast organisms in 23.5 out of 33 cases (71.2%). Our study also showed that PMCT had a sensitivity of 71.3% and specificity of 54.3% (95% CI: 39.5–68.4) in diagnosing TB based on the protocol set in this study. This study showed that there was relatively good agreement between radiological PMCT findings and bacterial culture, suggesting that radiological examination is a relatively reliable tool for preliminary screening and possible diagnosis of TB prior to a postmortem examination which would be beneficial in reducing the risk of transmission of TB to health workers during autopsy.

Biophysical analysis of gelatin and PLGA nanoparticle interactions with complex biomimetic lung surfactant models.

Biocompatible materials are increasingly used for pulmonary drug delivery, and it is essential to understand their potential impact on the respiratory system, notably their effect on lung surfactant, a monolayer of lipids and proteins, responsible for preventing alveolar collapse during breathing cycles. We have developed a complex mimic of lung surfactant composed of eight lipids mixed in ratios reported for native lung surfactant. A synthetic peptide based on surfactant protein B was added to better mimic the biological system. This model was used to evaluate the impact of biocompatible gelatin and poly(lactic-co-glycolic acid) nanoparticles. Surface pressure-area isotherms were used to assess lipid packing, film compressibility and stability, whereas the lateral organization was visualized by Brewster angle microscopy. Nanoparticles increased film fluidity and altered the monolayer collapse pressure. Bright protruding clusters formed in their presence indicate a significant impact on the lateral organization of the surfactant film. Altogether, this work indicates that biocompatible materials considered to be safe for drug delivery still need to be assessed for their potential detrimental impact before use in therapeutic applications.

Novel frameshift variant in the PCNT gene associated with Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) Type II and small kidneys.

BACKGROUND: Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) Type II is an autosomal recessive condition encompassing a heterogeneous group of disorders characterized by symmetrical growth retardation leading to dwarfism, microcephaly, and a range of multiple medical complications including neurovascular diseases. Biallelic pathogenic variants in the pericentrin gene (PCNT) have been implicated in its pathogenesis. CASE PRESENTATION: We performed whole-exome sequencing to ascertain the diagnosis of a 2 year and 6 months old boy who presented with severe failure to thrive, microcephaly, and facial gestalt suggestive of MOPD Type II which included features such as retrognathia, small ears, prominent nasal root with a large nose, microdontia, sparse scalp hair, bilateral fifth finger clinodactyly. He had a small ostium secundum atrial septal defect and bilaterally small kidneys. Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) Type II was confirmed based on a pathogenic compound heterozygous frameshift variant in the PCNT gene c.5059_5060delAA | p. Asn1687fs (novel variant) and c.9535dup (p. Val3179fs). His parents were found to be heterozygous carriers for the variants. CONCLUSION: We report a novel frameshift variant in the PCNT gene and a previously unreported phenotype for Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) Type II.

Monocarboxylate transporter 1-mediated lactate accumulation promotes nucleus pulposus degeneration under hypoxia in a 3D multilayered nucleus pulposus degeneration model.

During intervertebral disc degeneration (IVDD), due to endplate calcification, diminished oxygen and nutrient concentrations and accumulated lactate are present in the microenvironment of the nucleus pulposus (NP). The disadvantages of 3D layered culture include uneven oxygen and nutrient gradients. In the present study, to mimic the in vivo microenvironment of the NP, a 5-layered 3D culture was constructed using clinical haemostatic gelatine sponges and developed as a NP degeneration (NPD) model. Subsequently, cell distribution as well as expression of NP chondrogenic markers (type II collagen and aggrecan), glycosaminoglycan (GAG) and degeneration markers [e.g. matrix metalloproteinase (MMP) 3] were measured from the top to the bottom layer. However, in a single NP-cell-loaded disc model, the chondrogenic potency in the middle or bottom layer was higher than that in the top layer. To further study the mechanism underlying the degeneration of NP cells in this NPD model, the contribution of secreted metabolites was examined. Lactate identified in the supernatant modulated GAG accumulation and MMP3 expression. Inhibition of lactate influx by the monocarboxylate transporter (MCT)-1 inhibitor, AZD3965, reversed the effect of lactate on GAG accumulation and MMP3 expression and further improved NP cell degeneration in the NPD model. Thanks to the homogenous expression of lactate in the model, it was possible to further identified that the combination of lactate and hypoxia enhanced MMP3 expression. Taken together, multilayered cell-loaded sponges, with oxygen and nutrient gradients as well as lactate accumulation, can represent a 3D multilayered NPD model for exploring potential agents for IVDD.

Predictive Validity of the Physical Resilience Instrument for Older Adults (PRIFOR).

This study aimed at evaluating the predictive ability of the Physical Resilience Instrument for Older Adults (PRIFOR) for the recovery of frailty, activity of daily living (ADL), and quality of life in older adults suffering from acute health stressors. The longitudinal study was adopted and patients aged 65 and older with Clinical Frailty Scale (CFS) scores between 4 and 6 were included. The PRIFOR was used to assess physical resilience at baseline. Katz ADL, CFS and EuroQoL 5-dimension Questionnaire (EQ5D) scores were all assessed at baseline and one month after discharge. The mean age of the 192 participants was 76.29 ± 6.53 years, and 50.5% were female. After adjusting for the baseline condition, the PRIFOR was only significantly associated with the CFS (ß=-0.183, p<0.001) at one month after discharge. Our study results provide evidence of the predictive capacity of the PRIFOR for recovery from frailty.

Acute kidney injury following hepatectomy and its impact on long-term survival for patients with hepatocellular carcinoma.

BACKGROUND: Acute kidney injury (AKI) is increasingly being recognized after hepatectomy. This study aimed to identify factors predicting its occurrence and its impact on long-term outcome among patients with hepatocellular carcinoma (HCC). METHODS: This was a retrospective analysis of the incidence of AKI, factors predicting its occurrence, and its impact on patients undergoing hepatectomy between September 2007 and December 2018. A subgroup analysis included patients with histologically proven HCC. RESULTS: The incidence of AKI was 9.2 per cent in 930 patients. AKI was associated with increased mortality, morbidity, posthepatectomy liver failure (PHLF), and a longer hospital stay. On multivariable analysis, study period December 2013 to December 2018, diabetes mellitus, mean intraoperative BP below 72.1 mmHg, operative blood loss exceeding 377ml, high Model for End-Stage Liver Disease (MELD) score, and PHLF were predictive factors for AKI. Among 560 patients with HCC, hypertension, BP below 76.9 mmHg, blood loss greater than 378ml, MELD score, and PHLF were predictive factors. The 1-, 3-, and 5-year overall survival rates were 74.1, 59.2, and 51.6 per cent respectively for patients with AKI, and 91.8, 77.9, and 67.3 per cent for those without AKI. Corresponding 1-, 3-, and 5-year disease-free survival rates were 56.9, 42.3, and 35.4 per cent respectively in the AKI group, and 71.7, 54.5, and 46.2 per cent in the no-AKI group. AKI was an independent predictor of survival in multivariable analysis. CONCLUSION: AKI is associated with longer hospital stay, and higher morbidity and mortality rates. It is also associated with shorter long-term survival among patients with HCC. To avoid AKI, control of blood loss and maintaining a reasonable BP (72-77 mmHg) during hepatectomy is important.

Global association between satellite-derived nitrogen dioxide (NO2) and lockdown policies under the COVID-19 pandemic.

The COVID-19 pandemic has severely affected various aspects of life, at different levels and in different countries on almost every continent. In response, many countries have closed their borders and imposed lockdown policies, possibly bringing benefits to people's health with significantly less emission from air pollutants. Currently, most studies or reports are based on local observations at the city or country level. There remains a lack of systematic understanding of the impacts of different lockdown policies on the air quality from a global perspective. This study investigates the impacts of COVID-19 pandemic towards global air quality through examining global nitrogen dioxide (NO2) dynamics from satellite observations between 1 January and 30 April 2020. We used the Apriori algorithm, an unsupervised machine learning method, to investigate the association among confirmed cases of COVID-19, NO2 column density, and the lockdown policies in 187 countries. The findings based on weekly data revealed that countries with new cases adopted various lockdown policies to stop or prevent the virus from spreading whereas those without tended to adopt a wait-and-see attitude without enforcing lockdown policies. Interestingly, decreasing NO2 concentration due to lockdown was associated with international travel controls but not with public transport closure. Increasing NO2 concentration was associated with the "business as usual" strategy as evident from North America and Europe during the early days of COVID-19 outbreak (late January to early February 2020), as well as in recent days (in late April) after many countries have started to resume economic activities. This study enriches our understanding of the heterogeneous patterns of global associations among the COVID-19 spreading, lockdown policies and their environmental impacts on NO2 dynamics.

Six Novel ATM Gene Variants in Sri Lankan Patients with Ataxia Telangiectasia.

INTRODUCTION: Ataxia telangiectasia is a rare genetic condition with an estimated prevalence of 1 in 40,000-100,000 live births. This condition predominantly affects the nervous and immune systems. It is characterized by progressive ataxia beginning from early childhood. The neurological deficit associated with this condition affects one's balance, coordination, walking, and speech and can be accompanied by chorea, myoclonus, and neuropathy. They may also have ocular telangiectasias and high levels of blood alpha-fetoprotein (AFP). The ataxia telangiectasia mutated gene (ATM) is associated with this condition and codes for the ATM protein which is a phosphatidylinositol 3-kinase. This gene occupies 150 kb on chromosome 11q22-23 and contains 66 exons encoding a 13 kb transcript. ATM is a relatively large protein with a molecular weight of 350 kDa and 3,056 amino acids. METHODS: Four patients of Sri Lankan origin presenting with features suggestive of ataxia telangiectasia were referred to our genetics center for specialized genetic counseling and testing. Whole-exome sequencing followed by Sanger sequencing was used to confirm the candidate variants. Protein modeling and genotype to phenotype correlation was performed in the identified variants. RESULTS: We observed 6 novel ATM gene variants in four patients with ataxia telangiectasia. The identified variants are as follows: homozygous c.7397C > A (p.Ala2466Glu) and c.510_511delGT (p.Tyr171fs) and compound heterozygous c.5347_5350delGAAA (p.Glu1783fs), c.8137A > T (p.Arg2713 ∗ ) and c.1163A > C (p.Lys388Thr), and c.5227A > C (p.Thr1743Pro). Variant analysis was followed by modeling of the native and altered protein structures. CONCLUSION: We report novel ATM gene variants that have implications on the molecular diagnosis of ataxia telangiectasia.

Novel variant in NSDHL gene associated with CHILD syndrome and syndactyly- a case report.

BACKGROUND: Congenital hemidysplasia with ichthyosiform erythroderma and limb defects also known as CHILD syndrome is an X-linked dominant, male lethal genodermatosis with a prevalence of 1 in 100,000 live births. Mutations in NSDHL gene located at Xq28 potentially impair the function of NAD(P) H steroid dehydrogenase-like protein and is responsible for its pathogenesis. CASE PRESENTATION: The proband was a 9-month-old twin (T2) girl with a healthy twin sister (T1) of Sri Lankan origin born to non-consanguineous parents. She presented with right sided continuous icthyosiform erythroderma and ipsilateral limb defects and congenital hemidysplasia since birth. Notably the child had ipsilateral hand hypoplasia and syndactyly. There were other visceral abnormalities. We performed whole exome sequencing and found a novel heterozygous variant (NSDHL, c.713C > A, p.Thr238Asn). CONCLUSION: We report a novel missense variant in the NSDHL gene that resides in a highly-conserved region. This variant affects the NAD(P) H steroid dehydrogenase-like protein function via reduction in the number of active sites resulting in the CHILD syndrome phenotype and syndactyly.

Immediate and long-term impact of the COVID-19 pandemic on delivery of surgical services.

BACKGROUND: The ongoing pandemic is having a collateral health effect on delivery of surgical care to millions of patients. Very little is known about pandemic management and effects on other services, including delivery of surgery. METHODS: This was a scoping review of all available literature pertaining to COVID-19 and surgery, using electronic databases, society websites, webinars and preprint repositories. RESULTS: Several perioperative guidelines have been issued within a short time. Many suggestions are contradictory and based on anecdotal data at best. As regions with the highest volume of operations per capita are being hit, an unprecedented number of operations are being cancelled or deferred. No major stakeholder seems to have considered how a pandemic deprives patients with a surgical condition of resources, with patients disproportionally affected owing to the nature of treatment (use of anaesthesia, operating rooms, protective equipment, physical invasion and need for perioperative care). No recommendations exist regarding how to reopen surgical delivery. The postpandemic evaluation and future planning should involve surgical services as an essential part to maintain appropriate surgical care for the population during an outbreak. Surgical delivery, owing to its cross-cutting nature and synergistic effects on health systems at large, needs to be built into the WHO agenda for national health planning. CONCLUSION: Patients are being deprived of surgical access, with uncertain loss of function and risk of adverse prognosis as a collateral effect of the pandemic. Surgical services need a contingency plan for maintaining surgical care in an ongoing or postpandemic phase.

ANTECEDENTES: La pandemia en curso tiene un efecto colateral sobre la salud en la prestación de atención quirúrgica a millones de pacientes. Se sabe muy poco sobre el manejo de la pandemia y sus efectos colaterales en otros servicios, incluida la prestación de servicios quirúrgicos. MÉTODOS: Se ha realizado una revisión de alcance de toda la literatura disponible relacionada con COVID-19 y cirugía utilizando bases de datos electrónicas, páginas web de sociedades, seminarios online y repositorios de pre-publicaciones. RESULTADOS: Se han publicado varias guías perioperatorias en un corto período de tiempo. Muchas recomendaciones son contradictorias y, en el mejor de los casos, se basan en datos anecdóticos. A medida que las regiones con el mayor volumen de operaciones per cápita se ven afectadas, se cancela o difiere un número sin precedentes de operaciones. Ninguna de las principales partes interesadas parece haber considerado cómo una pandemia priva de recursos a los pacientes que necesitan una intervención quirúrgica, con pacientes afectados de manera desproporcionada debido a la naturaleza del tratamiento (uso de anestesia, quirófanos, equipo de protección, contacto físico y necesidad de atención perioperatoria). No existen recomendaciones sobre cómo reanudar la actividad quirúrgica. La evaluación tras la pandemia y la planificación futura deben incluir a los servicios quirúrgicos como una parte esencial para mantener la atención quirúrgica adecuada para la población también durante un brote epidémico. La prestación de servicios quirúrgicos, debido a su naturaleza transversal y a sus efectos sinérgicos en los sistemas de salud en general, debe incorporarse a la agenda de la OMS para la planificación nacional de la salud. CONCLUSIÓN: Los pacientes se ven privados de acceso a la cirugía con una pérdida de función incierta y riesgo de un pronóstico adverso como efecto colateral de la pandemia. Los servicios quirúrgicos necesitan un plan de contingencia para mantener la atención quirúrgica durante la pandemia y en la fase post-pandemia.

Methanol related death in National Institute of Forensic Medicine, Hospital Kuala Lumpur: A case series.

INTRODUCTION: Methanol is a widely available chemical with a range of uses including as solvent, as a fuel, in chemical synthesis and anti-freeze preparations. Most of the cases are accidental exposures to drinking beverages contaminated with methanol. MATERIALS AND METHODS: In mid-September 2018, there was a single outbreak of methanol poisoning in Malaysia especially involving the state of Federal Territory Kuala Lumpur and Selangor. There were 33 reported deaths suspected due to methanol poisoning in this current outbreak where 11 of them were brought in to the Institute of Forensic Medicine (NIFM), Kuala Lumpur. The last outbreak was in the year 2013 with 29 deaths reported out of 44 cases. RESULTS: There were 3 cases (27.2%) died in hospital and the remaining 8 cases (72.8%) were found dead at home and were later brought in dead to the hospital. A full autopsy was carried out for each case. Autopsy findings, as well as lab results pertaining to cases that survived and directly brought in dead, were of a different spectrum. CONCLUSION: Methanol related deaths are almost always as a result of greed. The running truism is 'methanol poisoning is a result of deliberate addition/adulteration with industrial methanol'. Prevention of the illegal production of methanol and methylated spirits should be established to curb this matter in the future.

Air pollution interventions and respiratory health: a systematic review.

BACKGROUND: Indoor and ambient air pollution exposure is a major risk to respiratory health worldwide, particularly in low- and middle-income countries (LMICs). Interventional trials have mainly focused on alternatives to cooking stoves, with mixed results. Beyond cooking, additional sources of particulate matter also contribute to the burden of air pollution exposure. This review explores evidence from current randomised controlled trials (RCTs) on the clinical effectiveness of interventions to reduce particulate matter in LMICs.METHODS: Twelve databases and the grey literature (e.g., Government reports and policy papers) were searched. Eligible studies were RCTs conducted in LMICs aiming to reduce particulate exposure from any source and reporting on at least one clinical respiratory outcome (respiratory symptoms, lung function or clinical diagnoses). Data from relevant studies were systematically extracted, the risk of bias assessed and narrative synthesis provided.RESULTS: Of the 14 included studies, 12 tested 'improved' cookstoves, most using biomass, but solar and bioethanol cookers were also included. One trial used solar lamps and another was an integrated intervention incorporating behavioural and environmental components for the treatment and prevention of chronic obstructive pulmonary disease. Of the six studies reporting child pneumonia outcomes, none demonstrated significant benefit in intention-to-treat analysis. Ten studies reported respiratory symptom outcomes with some improvements seen, but self-reporting made these outcomes highly vulnerable to bias. Substantial inter-study clinical and methodological heterogeneity precluded calculation of pooled effect estimates.CONCLUSION: Evidence from the RCTs performed to date suggests that individual household-level interventions for air pollution exposure reduction have limited benefits for respiratory health. More comprehensive approaches to air pollution exposure reduction must be developed so their potential health benefits can be assessed.