A 40-year-old male with Becker muscular dystrophy presented with severe mitral regurgitation and underwent mitral valve repair. Following the surgery, the patient became tachycardic, and developed a continuous high grade-fever and hyperbilirubinemia. The patient's condition worsened and we eventually tested his thyroid levels and discovered abnormally high thyroid levels. After diagnosing a severe thyroid storm, the patient was treated with oral administration of Lugol's iodine and thiamazole, as well as an intravenous steroid, which led to an immediate improvement of symptoms. The incidence of thyroid storm after open-heart surgery is extremely rare but highly life-threatening if unrecognized.

Background: Sickle cell disease (SCD), the commonest monogenic disorder, affects more than 300,000 births annually, with 44,000 in India. While the clinical phenotype of SCD is considered to be milder in aboriginal populations in India, there is a paucity of data on outcomes. To determine the severity of SCD in this population, we studied mortality rates and causes of mortality in a longitudinal cohort of patients with SCD in a remote aboriginal community in India receiving community-based comprehensive care. Procedures: Causes of death in this cohort from January 2008 to December 2018 were analyzed. Details were collected from hospital records and in case of deaths at home, by utilizing the WHO verbal autopsy questionnaire. Results: The cohort consisted of 157 patients belonging to the Paniya, Betta Kurumba, Kattunyakan, and Mullu Kurumba tribes. During the study period, there were 22 deaths, all from the Paniya tribe. Twelve deaths (54.5%) occurred in the hospital and the remaining at home (45.5%) reflecting a crude mortality rate of 140 per 1000 population. 25% of deaths occurred in the 6-18 age group. There were no deaths in the 0-5 age group. The median age of death was 25 years, which was 20 years less than in the non-SCD aboriginal population. The leading causes of death were acute chest syndrome, anemia, and sepsis among the SCD patients and stroke and suicides in the non-SCD aboriginal population Conclusion: SCD is a severe disease among the Gudalur Valley’s aboriginal population with a significant risk of premature mortality.

The United States produces more than 10 million tons of waste oils and fats each year. This paper aims to establish a new biomanufacturing platform that convert waste oils or fats into a series of value-added products. Our research employs the oleaginous yeast Yarrowia lipolytica as a case study for citrate production from waste oils. First, we conducted the CFD simulation of the bioreactor system and identified that the extracellular mixing and mass transfer is the first limiting factor of an oil fermentation process due to the insolubility of oil in water. Based on the CFD simulation results, bioreactor design and operating conditions were optimized and successfully enhanced oil uptake and bioconversion in fed-batch fermentation experiments. After that, we investigated the impacts of cell morphology on oil uptake, intracellular lipid accumulation, and citrate formation by overexpressing and deleting the MHY1 gene in the wild type Y. lipolytica. Fairly good correlations were achieved between cell morphology and productivities of biomass, lipid, and citrate. Finally, fermentation kinetics with both glucose and oil substrates were compared and the oil fermentation process was carefully evaluated. Our research results suggest that waste oils or fats can be economical feedstocks for biomanufacturing of many high-value products.

Esophageal perforation is most commonly caused by endoscopic instrumentation of the upper GI tract and most commonly presents with chest pain in more than 70% of patients, vomiting, and subcutaneous emphysema.

Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in profound health challenges across the globe. Pharmacists’ readiness to cope with the pandemic is critical in supporting and sustaining the healthcare workforce to meet the challenges.Objective This study aims to examine community pharmacists’ views on their work environment, policies, and preparedness for safe retail patronage to prevent the transmission of COVID-19 and assess the variables influencing coping strategies during the pandemic.Setting An online survey of pharmacists practicing in community pharmacy setting in Malaysia.Method A questionnaire-based, cross-sectional study was conducted in Malaysia to evaluate coping strategies of community pharmacists and pharmaceutical services provided during COVID-19 pandemic. Between May 1 and July 31, 2020, the questionnaire was distributed to pharmacists working in community setting nationwide utilizing a snowball sampling method. Main outcome measure Community pharmacists’ perceptions on safety, resilience, organizational support, and pharmaceutical services offered during COVID-19 pandemic.Results A total of 217 pharmacists participated in the study. The vast majority of community pharmacists reported a positive outlook and were able to balance working with self-care during this period. Most reported to have access to personal protective equipment such as gloves and hand sanitizers. A large proportion of community pharmacies also installed physical barriers in doorways or in front of the counter, put markings on the ground to section areas to ensure physical distancing, and controlled the number of customers who could access the pharmacy during this period. Innovations reported to be implemented included teleconsultations and providing curb-side or drive-through delivery and pickup services.  Conclusion The findings suggest the frontline and essential roles of community pharmacists in delivering pandemic responses, creating the opportunity to determine areas where community pharmacy services can be incorporated to strengthen the public health system and improve patient health outcomes.

Cryptococcus neoformans infection is a known cause of meningoencephalitis in immunocompromised patients. However, it is less frequent in immunocompetent individuals. Here we report a case of a 60 years old COVID-19 patient with a history of several co-morbidities who received tocilizumab and corticosteroids, which lead to Cryptococcemia.

SVEIR epidemic model; age-dependence; basic reproduction number; local and global stability; uniform persistence

Non-Hodgkin's lymphoma of the female genital system is extremely rare. It may be confused with cervix uteri malignancies when being diagnosed.

Purpose Only 25% of oesophageal adenocarcinoma (OAC) patients have a pathological response to neo-adjuvant therapy (NAT) before oesophagectomy. Early response assessment using PET imaging may help guide management of these patients. We performed a systematic review and meta-analysis to synthesise the evidence detailing response rate and diagnostic accuracy of early PET-CT assessment. Methods We systematically searched several databases including MEDLINE and Embase. Studies with mixed cohorts of histology, tumour location, and a repeat PET-CT assessment after more than one cycle of NAT were excluded. Reference standard was pathological response, defined by Becker or Mandard classifications. Primary outcome was metabolic response rate after one cycle of NAT defined by a reduction in maximum standardised uptake value (SUVmax) of 35%. Secondary outcome was diagnostic accuracy of treatment response prediction, defined as the sensitivity and specificity of early PET-CT using this threshold. Quality of evidence was also assessed. Random-effects meta-analysis pooled response rates and diagnostic accuracy. This study was registered with PROSPERO (CRD42019147034). Results Overall, 1341 articles were screened, and six studies were eligible for analysis. These studies reported data for 518 patients (aged 27-78 years; 452 [87.3%] were male) between 2005-2020. Pooled sensitivity of early metabolic response to predict pathological response was 77.2% (95%CI 53.2%-100%). Significant heterogeneity existed between studies (I2=80.6% (95%CI 38.9%-93.8%), p=0.006). Pooled specificity was 75.0% (95%CI 68.2%-82.5%), however no significant heterogeneity between studies existed (I2=0.0% (95%CI 0.0%-67.4%), p=0.73). Conclusion High-quality evidence is lacking, and few studies met the inclusion criteria of this systematic review. The sensitivity of PET using a SUVmax reduction threshold of 35% was suboptimal and varied widely. However, specificity was consistent across studies with a pooled value of 75.0%, suggesting early PET assessment is a better predictor of treatment resistance than of pathological response. Further research is required to define optimal PET-guided treatment decisions in OAC.

Multi-domain proteins are not only formed through natural evolution but can also be generated by recombinant DNA technology. Because many fusion proteins can enhance the selectivity of cell targeting, these artificially produced molecules, called multi-specific biologics, are promising drug candidates, especially for immunotherapy. Moreover, the rational design of domain linkers in fusion proteins is becoming an essential step toward a quantitative understanding of the dynamics in these biopharmaceutics. We developed a computational framework to characterize the impacts of peptide linkers on the dynamics of multi-specific biologics. We constructed a benchmark containing six types of linkers that represent various lengths and degrees of flexibility and used them to connect two natural proteins as a test system. The microsecond dynamics of these proteins generated from Anton were projected onto a coarse-grained conformational space. The similarity of dynamics among different proteins in this low-dimensional space was further analyzed by a neural network model. Finally, hierarchical clustering was applied to place linkers into different subgroups based on the neural network classification results. The clustering results suggest that the length of linkers used to spatially separate different functional modules plays the most important role in regulating the dynamics of this fusion protein. Given the same number of amino acids, linker flexibility functions as a regulator of protein dynamics. In summary, we illustrated that a new computational strategy can be used to study the dynamics of multi-domain fusion proteins by a combination of long timescale molecular dynamics simulation, coarse-grained modeling, and artificial intelligence.

A 60-year-old man presented to our hospital with pericardial effusion. He died of respiratory failure 13 months later. Autopsy revealed right atrial angiosarcoma extending into the right lung. To the best of our knowledge, this is the first case report of a primary cardiac angiosarcoma that displayed direct lung invasion.

Background: Intravenous immunoglobulin (IVIG) resistance prediction remains substantial in Kawasaki disease (KD), with limited data on the predictive value of coagulation profile for IVIG resistance, particularly for repeated IVIG resistance. Therefore, the aim of our study was to testify the predictive validity of coagulation profile for both initial and repeated IVIG resistance in KD. Methods: A total of 385 KD patients were prospectively recruited between April in 2015 and May in 2019. Coagulation and other profiles were evaluated between IVIG-responsive and IVIG-resistant groups. Multivariate logistic regression analysis was applied to determine the association between coagulation profiles and IVIG resistance. ROC curves analysis was further performed to assess validity of coagulation profiles in predicting both initial and repeated IVIG resistance. Results: PT, APTT and D-dimer were significantly increased in initial IVIG-resistant group with ATIII significantly reduced. Meanwhile, ATIII was declined markedly in repeated IVIG-resistant patients. PT, APTT, D-dimer and ATIII cutoff values of 13.95 s, 41.15 s, 1.48 mg/l, and 89.5% yielded sensitivities of 73%, 32%, 71%, 81%; specificities of 55%, 88%, 62%, 51% for predicting initial IVIG resistance, respectively. The cutoff value of ATIII for predicting repeated IVIG resistance was 68.5%, with sensitivity of 71% and specificity of 55%. Multivariate logistic regression analysis showed that PT, APTT, D-dimer and ATIII were independent risk factors for initial IVIG resistant patients with KD. Conclusions: Coagulation profiles were significantly dysregulated in KD patients. Some of them particularly ATIII may serve as complementary laboratory markers for prediction of both initial and repeated IVIG resistance.

In this work the flow behavior of granular material in flat-bottomed funnel flow silos was investigated through 3D Discrete Element Method (DEM) simulations. It is observed that particles in the flowing zone move collectively, manifested by the oscillatory fluctuations of the averaged particle vertical velocity and the non-Gaussian characteristics of the fluctuations of individual velocity around average. The delayed correlations of velocity fluctuation and the Fourier spectrums of velocity and contact force between particles were analyzed to characterize the propagation of flow fluctuation. It is found that there exist two special vertical positions in the converging zone. The lower one corresponds to the emission source from which the velocity wave propagates both upwards and downwards. The higher one locates at the upper boundary of converging zone and is characterized by the most violent fluctuation of contact force. Possible mechanisms of the appearances of these two vertical positions are discussed.

A computation analysis is performed to study double-diffusive natural convection in a right-angle trapezoidal cavity packed with a porous medium. The horizontal top and bottom boundaries are insulated and impermeable. The vertical left sidewall is kept at a constant heat flux and high concentration, whereas the temperature and concentration of the mixture at the inclined sidewall are held at lower temperatures and lower concentration. The dimensionless nonlinear system is solved by employing finite difference method along Successive Under Relaxation technique. The findings are compared and validated with the existing literature for the Darcy flow driven through a single buoyancy effect (difference in density is only due to temperature variations) in a porous square enclosure. The numerical results are expressed in the form of dimensionless temperature, concentration, streamlines, isotherms and iso-concentrations, local and average Nusselt and Sherwood numbers. It is demonstrated that the Rayleigh number and buoyancy parameter enhance both surface heat and concentration rates.

In this paper, we deal with a new approximation of a diffusive predator--prey model with Leslie--Gower term and social behavior for the prey subject to Neumann boundary conditions. A new approach for a predator-prey interaction in the presence of prey social behavior has been considered. Our main topic in this work is to study the influence of the prey's herd shape on the predator-prey interaction in the presence of Leslie--Gower term. First of all, we examine briefly the system without spatial diffusion. By analyzing the distribution of the eigenvalues associated with the constant equilibria, the local stability of the equilibrium points and the existence of Hopf bifurcation have been investigated. Then, the spatiotemporal dynamics introduced by self diffusion was determined, where the existence of the positive solution, Hopf bifurcation, Turing driven instability, Turing-Hopf bifurcation point have been derived. Further, the effect of the prey's herd shape rate on the prey and predator equilibrium densities as well as on the Hopf bifurcating points has been discussed. Finally, by using the normal form theory on the center manifold, the direction and stability of the bifurcating periodic solutions have also been obtained. To illustrate the theoretical results, some graphical representations are given.

This article comments on: ‘Short- and long-term effects of fire on stem hydraulics in Pinus ponderosa saplings’ by Partelli-Feltrin et al. (2020), https://doi.org/10.1111/pce.13881.

Radiologic evidence of aortic disease is not always consistent with the diagnosis. With lack of accompanying symptoms or with an atypical presentation, diagnosis of aortic pathology relies greatly on imaging techniques. We report the case of a 58 year-old female who presented with incidental radiographic findings consistent with a type A aortic intramural hematoma and a vague left-sided chest discomfort. After follow-up imaging was consistent with disease progression and hematoma expansion, the affected segment was resected and pathology reported lymphoplasmacytic aortitis as the underlying etiology of the imaging findings rather than an intramural hematoma. The patient lacked symptoms or serology consistent with rheumatologic disease and the postoperative course was uneventful. The management of a suspected ascending intramural hematoma is controversial, especially when the patient presents with atypical signs and symptoms. Features of disease progression may warrant urgent surgical intervention.

Rationale Prescribed opioids are major contributors to the current international public health opioid crisis. Such iatrogenic calamities usually result from collective decision failures of healthcare organizations rather than solely of individual organizations or professionals. Findings from a system-wide safety analysis of the iatrogenic opioid crisis that includes roles of pertinent healthcare organizations may help avoid or mitigate similar future tragedies. In this exploratory study, we report on such an analysis. Methods Root cause analysis, incorporating recent suggestions for improvement, was used to retrospectively identify possible causal factors from the literature. Based on their mandated roles and potential influences to prevent or mitigate the iatrogenic crisis, relevant organizations were grouped and stratified from most to least influential. Results The analysis identified a chain of multiple interrelated causal factors within and between organizations. The most influential organizations were: pharmaceutical, political and drug regulatory; next: experts and their related societies, and publications. Less influential: accreditation, professional licensing and regulatory, academic and healthcare funding bodies. Collectively, their views and decisions influenced prescribing practices of frontline healthcare professionals and advocacy groups. Financial associations between pharmaceutical and all other organizations/groups were common. Ultimately, patients were adversely affected. There was a complex association with psychosocial variables. Limitations Our analysis suggests associations not causality. Conclusions The iatrogenic crisis has multiple intricately linked interacting roots. The major catalyst: pervasive pharma-linked financial conflicts of interest (CoIs) involving most of the other healthcare organizations. These extensive financial CoIs were likely triggers for a cascade of erroneous decisions and actions that adversely affected patients. The actions and decisions of pharma ranged from unethical to illegal. The iatrogenic opioid crisis exemplifies widespread “institutional corruption of pharmaceuticals.”