Global Health Commodities Supply Chain in the Era of COVID-19 Pandemic: Challenges, Impacts, and Prospects: A Systematic Review.

Background: The COVID-19 pandemic led to the most substantial health crisis in the 21st Century. This pandemic interrupted the supply of essential commodities for human beings. Among the essential commodities for human survival, disruption of the supply of essential health commodities has become a global concern. Objective: The study aimed to systematically analyze published articles on the challenges, impacts, and prospects of the global health commodities' supply chain in the era of the COVID-19 pandemic. Methods: A standard searching strategy was conducted in seven research databases to retrieve pertinent articles. Finally, 459 articles were retrieved for further screening, and only 13 articles were selected for final synthesis. Results: Almost 38.5% of the studies targeted the supply chain of health commodities used to treat HIV, TB, and malaria. Lockdown policies, travel restrictions, lack of transportation, low manufacturing capacity, and rising costs were the significant challenges indicated for the supply interruption of essential health commodities and COVID-19 vaccines. Findings indicated that the supply interruption of essential health commodities leads to a devastating impact on global health. Conclusion: Global medicine shortages due to the pandemic crisis can have a devastatingly harmful impact on patient outcomes and might result in a devastatingly long-lasting effect on the health of the world community. Supply-related challenges of the COVID-19 vaccine affect countries' ambitions for achieving herd immunity quickly. Monitoring the pandemic's effect on the health commodities' supply system and designing a short-term and long-term resilient health supply chain system that can cope with current and future health catastrophes is pivotal.

MerTK-dependent efferocytosis by monocytic-MDSCs mediates resolution of post-lung transplant injury.

Rationale: Patients with end stage lung diseases require lung transplantation (LTx) that can be impeded by ischemia-reperfusion injury (IRI) leading to subsequent chronic lung allograft dysfunction (CLAD) and inadequate outcomes. Objectives: We examined the undefined role of MerTK (receptor Mer tyrosine kinase) on monocytic myeloid-derived suppressor cells (M-MDSCs) in efferocytosis (phagocytosis of apoptotic cells) to facilitate resolution of lung IRI. Methods: Single-cell RNA sequencing of lung tissue and BAL from post-LTx patients was analyzed. Murine lung hilar ligation and allogeneic orthotopic LTx models of IRI were used with Balb/c (WT), cebpb -/- (MDSC-deficient), Mertk -/- or MerTK-CR (cleavage resistant) mice. Lung function, IRI (inflammatory cytokine and myeloperoxidase expression, immunohistology for neutrophil infiltration), and flow cytometry of lung tissue for efferocytosis of apoptotic neutrophils were assessed in mice. Measurements and Main Results: A significant downregulation in MerTK-related efferocytosis genes in M-MDSC populations of CLAD patients compared to healthy subjects was observed. In the murine IRI model, significant increase in M-MDSCs, MerTK expression and efferocytosis was observed in WT mice during resolution phase that was absent in cebpb -/- Land Mertk -/- mice. Adoptive transfer of M-MDSCs in cebpb -/- mice significantly attenuated lung dysfunction, and inflammation leading to resolution of IRI. Additionally, in a preclinical murine orthotopic LTx model, increases in M-MDSCs were associated with resolution of lung IRI in the transplant recipients. In vitro studies demonstrated the ability of M-MDSCs to efferocytose apoptotic neutrophils in a MerTK-dependent manner. Conclusions: Our results suggest that MerTK-dependent efferocytosis by M-MDSCs can significantly contribute to the resolution of post-LTx IRI.

Guidelines to inform the generation of clinically relevant and realistic blast loading conditions for primary blast injury research.

'Primary' blast injuries (PBIs) are caused by direct blast wave interaction with the human body, particularly affecting air-containing organs. With continued experimental focus on PBI mechanisms, recently on blast traumatic brain injury, meaningful test outcomes rely on appropriate simulated conditions. Selected PBI predictive criteria (grouped into those affecting the auditory system, pulmonary injuries and brain trauma) are combined and plotted to provide rationale for generating clinically relevant loading conditions. Using blast engineering theory, explosion characteristics including blast wave parameters and fireball dimensions were calculated for a range of charge masses assuming hemispherical surface detonations and compared with PBI criteria. While many experimental loading conditions are achievable, this analysis demonstrated limits that should be observed to ensure loading is clinically relevant, realistic and practical. For PBI outcomes sensitive only to blast overpressure, blast scaled distance was demonstrated to be a useful parameter for guiding experimental design as it permits flexibility for different experimental set-ups. This analysis revealed that blast waves should correspond to blast scaled distances of 1.75

Allocation of funding into blast injury-related research and blast traumatic brain injury between 2000 and 2019: analysis of global investments from public and philanthropic funders.

INTRODUCTION: There is little systematic tracking or detailed analysis of investments in research and development for blast injury to support decision-making around research future funding. METHODS: This study examined global investments into blast injury-related research from public and philanthropic funders across 2000-2019. Research databases were searched using keywords, and open data were extracted from funder websites. Data collected included study title, abstract, award amount, funder and year. Individual awards were categorised to compare amounts invested into different blast injuries, the scientific approaches taken and analysis of research investment into blast traumatic brain injury (TBI). RESULTS: A total of 806 awards were identified into blast injury-related research globally, equating to US$902.1 million (m, £565.9m GBP). There was a general increase in year-on-year investment between 2003 and 2009 followed by a consistent decline in annual funding since 2010. Pre-clinical research received $671.3 m (74.4%) of investment. Brain-related injury research received $427.7 m (47.4%), orthopaedic injury $138.6 m (15.4%), eye injury $63.7 m (7.0%) and ear injury $60.5m (6.7%). Blast TBI research received a total investment of $384.3 m, representing 42.6% of all blast injury-related research. The U.S. Department of Defense funded $719.3 m (80%). CONCLUSIONS: Investment data suggest that blast TBI research has received greater funding than other blast injury health areas. The funding pattern observed can be seen as reactive, driven by the response to the War on Terror, the rising profile of blast TBI and congressionally mandated research.

Defining blast loading 'zones of relevance' for primary blast injury research: A consensus of injury criteria for idealised explosive scenarios.

Blast injuries remain a serious threat to defence and civilian populations around the world. 'Primary' blast injuries (PBIs) are caused by direct blast wave interaction with the human body, particularly affecting air-containing organs. Work to define blast loading conditions for injury research has received relatively little attention, though with a continued experimental focus on PBIs and idealised explosion assumptions, meaningful test outcomes and subsequent clinical applications, rely on appropriate simulated conditions. This paper critically evaluates and combines existing PBI criteria (grouped into those affecting the auditory system, pulmonary injuries and brain trauma) as a function of idealised blast wave parameters. For clinical blast injury researchers, analysis of the multi-injury criteria indicates zones of appropriate loading conditions for human-scale test items and demonstrates the importance of simulating blast conditions that are both realistic and relevant to the injury type. For certain explosive scenarios, spatial interpretation of the 'zones of relevance' could support emergency response and hazard preparedness by informing triage, patient management and resource allocation, thus leading to improved health outcomes. This work will prove useful to clinical blast injury researchers, blast protection engineers and clinical practitioners involved in the triage, diagnosis, and treatment of PBIs.

Phenome-wide association study identifies dsDNA as a driver of major organ involvement in systemic lupus erythematosus.

In systemic lupus erythematosus (SLE), dsDNA antibodies are associated with renal disease. Less is known about comorbidities in patients without dsDNA or other autoantibodies. Using an electronic health record (EHR) SLE cohort, we employed a phenome-wide association study (PheWAS) that scans across billing codes to compare comorbidities in SLE patients with and without autoantibodies. We used our validated algorithm to identify SLE subjects. Autoantibody status was defined as ever positive for dsDNA, RNP, Smith, SSA and SSB. PheWAS was performed in antibody positive vs. negative SLE patients adjusting for age and race and using a false discovery rate of 0.05. We identified 1097 SLE subjects. In the PheWAS of dsDNA positive vs. negative subjects, dsDNA positive subjects were more likely to have nephritis ( p = 2.33 × 10-9) and renal failure ( p = 1.85 × 10-5). After adjusting for sex, race, age and other autoantibodies, dsDNA was independently associated with nephritis and chronic kidney disease. Those patients negative for dsDNA, RNP, SSA and SSB negative subjects were all more likely to have billing codes for sleep, pain and mood disorders. PheWAS uncovered a hierarchy within SLE-specific autoantibodies with dsDNA having the greatest impact on major organ involvement.

The inter-tester repeatability of a model for analysing elbow flexion-extension during overhead sporting movements.

This study investigates the inter-tester repeatability of an upper limb direct kinematic (ULDK) model specifically for the reporting of elbow flexion-extension (FE) during overhead sporting movements, such as cricket bowling. The ULDK model consists of an upper arm and a forearm connected with a 6° of freedom elbow joint. The ULDK model was assessed for inter-tester repeatability by calculating elbow FE during cricket bowling in two sessions, with unique testers applying the kinematic marker set in each session. Analysis of both elbow FE time-varying waveforms (statistical parametric mapping = 0% time different) and extracted discrete events (no statistical differences, strong correlations > 0.9) support that this model is inter-tester repeatable at assessing elbow FE within the context of cricket bowling. This model is recommended as a framework in future studies for measuring elbow kinematics during other overhead sporting tasks, with recommendations for further participant-specific considerations. Graphical abstract ᅟ.

Role of the Inducible Adhesin CpAls7 in Binding of Candida parapsilosis to the Extracellular Matrix under Fluid Shear.

The yeast Candida parapsilosis is an increasingly common cause of systemic fungal infections among immunocompromised individuals, including premature infants. Adhesion to host surfaces is an important step in pathogenesis, but this process has not been extensively studied in this organism. A microfluidics assay was developed to test the ability of C. parapsilosis to adhere to immobilized host extracellular matrix proteins under physiological fluid shear conditions. Growth in mammalian tissue culture medium at 37°C for 3 to 6 h led to the induction of an adhesive phenotype at shear forces of 1 to 5 dynes/cm2 in some isolates of C. parapsilosis Glutamic acid, proline, and calcium appeared to be the minimally necessary requirements for increased adhesion in these assays. To determine whether genes homologous to the ALS gene family of C. albicans were important for the adhesive phenotype, the expression levels of 5 homologous C. parapsilosis genes were quantified by using quantitative PCR (qPCR) under conditions leading to increased adhesion. CPAR2_404800 (CpALS7) and CPAR2_404780 showed increased expression levels compared to those in control yeast. The extent of adhesion was variable among different isolates, and linear regression identified the expression of CpALS7 but not CPAR2_404780 as having a strong positive correlation with adhesion. A homozygous CpALS7 deletion strain was deficient in adhesion, whereas the expression of CpALS7 in Saccharomyces cerevisiae resulted in increased adhesion. Together, these data provide strong evidence that CpAls7 aids in the adherence of C. parapsilosis to the extracellular matrix under shear forces and support its previously reported role in virulence.

Representing Knowledge Consistently Across Health Systems.

Objectives: Electronic health records (EHRs) have increasingly emerged as a powerful source of clinical data that can be leveraged for reuse in research and in modular health apps that integrate into diverse health information technologies. A key challenge to these use cases is representing the knowledge contained within data from different EHR systems in a uniform fashion. Method: We reviewed several recent studies covering the knowledge representation in the common data models for the Observational Medical Outcomes Partnership (OMOP) and its Observational Health Data Sciences and Informatics program, and the United States Patient Centered Outcomes Research Network (PCORNet). We also reviewed the Health Level 7 Fast Healthcare Interoperability Resource standard supporting app-like programs that can be used across multiple EHR and research systems. Results: There has been a recent growth in high-impact efforts to support quality-assured and standardized clinical data sharing across different institutions and EHR systems. We focused on three major efforts as part of a larger landscape moving towards shareable, transportable, and computable clinical data. Conclusion: The growth in approaches to developing common data models to support interoperable knowledge representation portends an increasing availability of high-quality clinical data in support of research. Building on these efforts will allow a future whereby significant portions of the populations in the world may be able to share their data for research.

Septotomía endoscópica del divertículo de Zenker / Endoscopy septotomy in zenker diverticulum

Introducción: La Diverticulotomía o Septotomía endoscópica en el divertículo de Zenker, es una alternativa a otros abordajes terapéuticos. El presente estudio muestra nuestra experiencia de esta técnica endoscópica. Pacientes y Métodos: Análisis retrospectivo, entre el 2009 y 2017 en pacientes con divertículo de Zenker. La septotomía se realizó utilizando videoendoscopio flexible, esfinterótomo aguja, electrobisturi para DSE tipo Hibridknife, mediante una técnica ya estandarizada. Resultados: Se trataron 25 pacientes con edad promedio de 71 años (rango etario de 45 a 84 años). En una paciente su mejoría fue muy poca, por lo que se sometió a intervención quirúrgica, donde tampoco hubo resultados consistentes. Veintiún pacientes mostraron un alivio completo de la disfagia. Tres pacientes que tuvieron recurrencia sintomática fueron tratados con el mismo método endoscópico entre 2 y 4 sesiones evolucionando de forma satisfactoria. Conclusiones: La septotomía endoscópica del divertículo de Zenker es un método eficaz y seguro, por lo tanto representa una alternativa real a la cirugía.

Introduction: Diverticulotomy or Endoscopic septotomy in Zenker's diverticulum is an alternative to others therapeutics approaches. The present study shows our experience of this endoscopic technique. Patients and methods: Retrospective analysis between 2009 and 2017 in patients with Zenker's diverticulum. The procedure was performed using a flexible video endoscope and a needle knife, Erbe hybrid knife probe, using an already standardized technique. Results: Twenty-five patients with an average age of 71 years (age range 45-84 years) were treated. In one patient his improvement was very little, therefore surgical procedure was performed, nevertheless this procedure had not consistent results. Twenty-one patients showed complete relief of dysphagia. Three patients who had symptomatically relapsed were retreated with the same endoscopic method between 2 and 4 sessions with good results. Conclusions: Zenker's endoscopic septotomy of the diverticulum is an effective and safe method; thereby it represents a real alternative to surgical treatment.

Angiolipofibroma de ciego: A propósito de un caso / Angiolipofibroma of cecum: case report

Paciente femenino de 61 años de edad con enfermedad actual de 22 días de evolución caracterizado por evacuaciones liquidas en 05 oportunidades/día sin moco ni sangre. Dolor Abdominal tipo cólico de aparición insidiosa, de leve intensidad, en flanco y fosa iliaca derecha, sin acalmias, ni horario, no irradiado, sin concomitantes, motivo por el cual acude a consulta de gastroenterología. Antecedentes Personales: Niega de Importancia. Antecedentes Familiares: Padre fallecido a los 65 años de edad IAM, Madre viva 60 años HTA. Hábitos Psicobiológicos: Niega de importancia Exploración Funcional: No contributarios. Al Examen Físico: Talla: 1.60 mts FC: 72 Lpm Peso: 55 kg IMC: 21.5 kg/m2 FR: 16 rpm TABI: 120/66mmhg (acostada). Colonoscopia 16/05/16: Lipoma Para-apendicular Vs Apéndice Evertida. RME 21/07/16 con similar impresión diagnóstica macroscópica. Reporte Histopatológico: Angiofibrolipoma de Ciego. Un tipo infrecuente pólipo colorrectal, se forman pólipos subepiteliales hamartomatosas mesenquimales por más de un tipo de tejido mesenquimatoso. Presentamos los hallazgos patológicos de una presentación inusual de una proliferación polipoide en ciego con tejido vascular, adiposo maduro, fibroso y tejido conectivo. En la literatura solo hay 3 reportes previos en colon y recto.

The “Gastric Bypass” is one of the most performed bariatric Female patient 61 years old with 22 days of current diseases, characterized by liquid evacuations in 05 opportunities / day without mucus and blood. Cramping abdominal pain type of insidious onset, mild, skinny in flank y right iliac fossa, without acalmias, non-irradiated, without concomitant, that’s the reason because she consult to our center. Personal Background: Importance diseases deny. Family history: Father died at 65 years old of heart attack, Mother live 60 years old with arterial hypertension. Psychobiological habits: non important. Functional Exploration important symptoms Denies. Physical Exams: Size: 1.60 mts heart frequency: 72 x min Weight: 55 kg BMI: 21.5 kg / m2 breathing frequency: 16 x min Blood pressure 120 / 66mmhg (lying). Colonoscopy 5/16/16: Lipoma next to appendix Vs Appendix everted. 21/07/16 RME similarly macroscopic diagnostic impression. Histopathological report: Angiofibrolipoma of Cecum. A rare type colorectal polyps, polyps subepithelial mesenchymal Hamartomatous are formed by more than one mesenchymal tissue type. We present the pathological findings of an unusual presentation of a polypoid vascular proliferation in Cecum, with fat mature, fibrous tissue and connective tissue. In the literature there are only 3 previous reports in colon and rectum.

Stigma-related barriers and facilitators to help seeking for mental health issues in the armed forces: a systematic review and thematic synthesis of qualitative literature.

A recent quantitative review in the area of stigma and help seeking in the armed forces has questioned the association between these factors (Sharp et al. 2015). To date, the contribution of qualitative literature in this area has largely been ignored, despite the value this research brings to the understanding of complex social constructs such as stigma. The aim of the current systematic review of qualitative studies was to identify appropriate literature, assess the quality and synthesize findings across studies regarding evidence of stigma-related barriers and facilitators to help seeking for mental health issues within the armed forces. A multi-database text word search incorporating searches of PsycINFO, MEDLINE, Social Policy and Practice, Social Work Abstracts, EMBASE, ERIC and EBM Review databases between 1980 and April 2015 was conducted. Literature was quality assessed using the Critical Appraisal Skills Programme tool. Thematic synthesis was conducted across the literature. The review identified eight studies with 1012 participants meeting the inclusion criteria. Five overarching themes were identified across the literature: (1) non-disclosure; (2) individual beliefs about mental health; (3) anticipated and personal experience of stigma; (4) career concerns; and (5) factors influencing stigma. The findings from the current systematic review found that unlike inconsistent findings in the quantitative literature, there was substantial evidence of a negative relationship between stigma and help seeking for mental health difficulties within the armed forces. The study advocates for refinement of measures to accurately capture the complexity of stigma and help seeking in future quantitative studies.

The effect of genetic variation in PCSK9 on the LDL-cholesterol response to statin therapy.

Statins (HMG-CoA reductase inhibitors) lower low-density lipoprotein cholesterol (LDL-C) and prevent cardiovascular disease. However, there is wide individual variation in LDL-C response. Drugs targeting proprotein convertase subtilin/kexin type 9 (PCSK9) lower LDL-C and will be used with statins. PCSK9 mediates the degradation of LDL receptors (LDLRs). Therefore, a greater LDL-C response to statins would be expected in individuals with PCSK9 loss-of-function (LOF) variants because LDLR degradation is reduced. To examine this hypothesis, the effect of 11 PCSK9 functional variants on statin response was determined in 669 African Americans. One LOF variant, rs11591147 (p.R46L) was significantly associated with LDL-C response to statin (P=0.002). In the three carriers, there was a 55.6% greater LDL-C reduction compared with non-carriers. Another functional variant, rs28362261 (p.N425S), was marginally associated with statin response (P=0.0064).The effect of rs11591147 was present in individuals of European ancestry (N=2388, P=0.054). The therapeutic effect of statins may be modified by genetic variation in PCSK9.

Resección mucosal endoscópica de hiperplasia linfoide reactiva de colon: Presentación de un caso / Endoscopic mucosal resection of reactive lymphoid hyperplasia of colon: One case presentation

La hiperplasia linfoide de colon es una patología gastrointestinal muy poco frecuente. Su tamaño y su forma macroscópica es variable. Se presenta un caso de hiperplasia linfoide reactiva en paciente femenina de 53 años de edad con aspecto macroscópico de una lesión polipoidea sésil tipo IIa ubicada en el ángulo hepático de colon la cual fue tratada con resección mucosal endoscópica. No había evidencia de lesión en otras áreas de la paciente y su evolución fue favorable.

Colon Lymphoid Hyperplasia is a rare gastrointestinal pathology. Its size and its macroscopic form is variable. We present a case of reactive Lymphoid Hyperplasia in a female patient of 53 years old with macroscopic appearance of a sessile polypoid lesion type IIa in the hepatic flexure of colon which was treated with Endoscopic mucosal resection. There was no evidence of the same pathology in other areas of the patient and the evolution of this patient has been favourable.

Disección submucosal endoscópica en cáncer gástrico temprano: Experiencia inicial / Endoscopic submucosal dissection in early gastric cancer: Initial experience

La disección submucosal endoscópica es una técnica endoluminal que nos permite resecciones amplias en un solo bloque en el tratamiento endoscópico del cáncer gástrico temprano.En este trabajo se presenta la experiencia inicial en la aplicación de la disección submucosal endoscópica en el tratamiento minimamente invasivo del cáncer gástrico temprano. Realizamos este procedimiento en 21 casos de cáncer gástrico temprano Y un caso de adenoma plano con displasia de bajo grado.La edad promedio de los pacientes fue de 67 años. Macroscópicamente 11 casos fueron Tipo IIc, 9 casos de cáncer gástrico temprano Tipo IIa y el otro caso fue una forma combinada Tipo IIa+II. 14 casos estaban localizados en antro próximal y 8 casos en cuerpo gástrico.21 casos fueron resecados en un solo bloque. Hubo una perforación y observamos hemorragia durante 7 casos que fueron controladas por vía endoscópica.

Endoscopic submucosal dissection (ESD) is a new endoluminal endoscopic procedure that allowed resection for early gastric cancer(EGC) in one bloc. In this paper we present 21 cases of EGC and one case of flat adenoma treated by ESD in our institution.Median age of our patients was 67 years.Macroscopically 11 cases were Tipe IIC, 9 case was Tipe IIa and the other case was Tipe IIa+IIc. According to localization 14 cases were located in the proximal antrum and 8 cases were located in gastric body .there was one perforation that it was solved by surgical procedure and we observed 7 cases with bleeding that were endosc opically treated.