Notes

Predicting specific skills following stopping cerebrovascular event: Development and approval involving prognostic designs.
Osteomyelitis is relatively frequent in young pigs and a few bacterial species have been postulated to be potential causative agents. Although Actinobacillus (A.) pleuropneumoniae has been sporadically described to cause osteomyelitis, typically, actinobacillosis is characterized by respiratory symptoms. Nevertheless, subclinical infections are a challenging problem in pig herds. To the authors' knowledge, this is the first case description that reports clinical, diagnostic imaging, pathological and histopathological findings of vertebral osteomyelitis in a pig and first describes A. pleuropneumoniae as the causative agent identified by advanced molecular methods.

An eight-week-old female weaner was presented with a non-ambulatory tetraparesis. The neurological signs were consistent with a lesion in the C6-T2 spinal cord segments. Imaging studies revealed a collapse of the seventh cervical vertebral body (C7) with a well demarcated extradural space-occupying mass ventrally within the vertebral canal severely compressing the spinal cord. Post-mortem examination identified an abscess and osteomyelitis of C7 and associated meningitis and neuritis with subsequent pathological fracture of C7 and compression of the spinal cord. In the microbiological analysis, A. pleuropneumoniae was identified using PCR and DNA sequence analysis.

A. pleuropneumoniae can be responsible for chronic vertebral abscess formation with subsequent pathological fracture and spinal cord compression in pigs.
A. pleuropneumoniae can be responsible for chronic vertebral abscess formation with subsequent pathological fracture and spinal cord compression in pigs.Glioblastoma multiforme (GBM) is the most common malignant brain cancer that invades normal brain tissue and impedes surgical eradication, resulting in early local recurrence and high mortality. In addition, most therapeutic agents lack permeability across the blood brain barrier (BBB), further reducing the efficacy of chemotherapy. Thus, effective treatment against GBM requires tumor specific targets and efficient intracranial drug delivery. With the most recent advances in immunotherapy, genetically engineered T cells with chimeric antigen receptors (CARs) are becoming a promising approach for treating cancer. By transducing T lymphocytes with CAR constructs containing a tumor-associated antigen (TAA) recognition domain linked to the constant regions of a signaling T cell receptor, CAR T cells may recognize a predefined TAA with high specificity in a non-MHC restricted manner, and is independent of antigen processing. Active T cells can travel across the BBB, providing additional advantage for drug delivery and tumor targeting. Here we review the CAR design and technical innovations, the major targets that are in pre-clinical and clinical development with a focus on GBM, and multiple strategies developed to improve CAR T cell efficacy.
The yeast Kluyveromyces marxianus offers unique potential for industrial biotechnology because of useful features like rapid growth, thermotolerance and a wide substrate range. As an emerging alternative platform, K. marxianus requires the development and validation of metabolic engineering strategies to best utilise its metabolism as a basis for bio-based production.

To illustrate the synthetic biology strategies to be followed and showcase its potential, we describe a comprehensive approach to rationally engineer a metabolic pathway in K. marxianus. We use the phenylalanine biosynthetic pathway both as a prototype and because phenylalanine is a precursor for commercially valuable secondary metabolites. First, we modify and overexpress the pathway to be resistant to feedback inhibition so as to overproduce phenylalanine de novo from synthetic minimal medium. Second, we assess native and heterologous means to increase precursor supply to the biosynthetic pathway. Finally, we eliminate branch points and competing reactions in the pathway and rebalance precursors to redirect metabolic flux to a specific product, 2-phenylethanol (2-PE). As a result, we are able to construct robust strains capable of producing over 800mg L
2-PE from minimal medium.

The strains we constructed are a promising platform for the production of aromatic amino acid-based biochemicals, and our results illustrate challenges with attempting to combine individually beneficial modifications in an integrated platform.
The strains we constructed are a promising platform for the production of aromatic amino acid-based biochemicals, and our results illustrate challenges with attempting to combine individually beneficial modifications in an integrated platform.
Designing public health policies to target the needs of specific places requires highly granular data. When geographic health statistics from official sources are absent or lacking in spatial detail, Sanitary Vulnerability metrics derived from Census and other georeferenced public data can be used to identify areas in particular need of attention. With that aim, a Vulnerability Map was developed, identifying areas with a substantial deficit in its population health coverage. As a result a novel methodology for measuring Sanitary Vulnerability is presented, that can potentially be applied to different time periods or geographies.

Census, official listings of public health facilities and crowdsourced georeferenced data are used. The Vulnerability Index is built using dimensionality reduction techniques such as Autoencoders and Non-parametric PCA.

The high resolution map shows the geographical distribution of a Sanitary Vulnerability Index, produced using official and crowdsourced open data sources, overcoming the lack of official sources on health indicators at the local level.

The Sanitary Vulnerability Map's value as a tool for place specific policymaking was validated by using it to predict local health related metrics such as health coverage. Further lines of work contemplate using the Map to study the interaction between Sanitary Vulnerability and the prevalence of different diseases, and also applying its methodology in the context of other public services such as education, security, housing, etc.
The Sanitary Vulnerability Map's value as a tool for place specific policymaking was validated by using it to predict local health related metrics such as health coverage. Further lines of work contemplate using the Map to study the interaction between Sanitary Vulnerability and the prevalence of different diseases, and also applying its methodology in the context of other public services such as education, security, housing, etc.
In Kenya, pre-exposure prophylaxis (PrEP) for HIV prevention is almost exclusively delivered at HIV clinics. Developing novel PrEP delivery models is important for increasing the reach of PrEP. Delivery of PrEP through pharmacies is one approach utilized in the US to improve accessibility. Retail pharmacies are commonly used as a first-line access point for medical care in Kenya, but have not been utilized for PrEP delivery. We conducted a collaborative consultative meeting of stakeholders to develop a care pathway for pharmacy-based PrEP delivery in Kenya.

In January 2020, we held a one-day meeting in Nairobi with 36 stakeholders from PrEP regulatory, professional, healthcare service delivery, civil society, and research organizations. Attendees reviewed a theory of change model, results from formative qualitative research with pharmacy providers and clients, and anticipated core components of pharmacy-based PrEP delivery counseling, HIV testing, prescribing, and dispensing. Stakeholders participated in for pilot testing that has the potential to expand PrEP delivery options in Kenya and other similar settings.
PrEP delivery stakeholders in Kenya were strongly supportive of developing and testing a model for pharmacy-based PrEP delivery to increase PrEP access. We collaboratively developed a care pathway for pilot testing that has the potential to expand PrEP delivery options in Kenya and other similar settings.
The Revised Short McGill Pain Questionnaire Version-2 (SF-MPQ-2) is a multidimensional outcome measure designed to capture, evaluate and discriminate pain from neuropathic and non-neuropathic sources. A recent systematic review found insufficient psychometric data with respect to musculoskeletal (MSK) health conditions. This study aimed to describe the reproducibility (test-retest reliability and agreement) and internal consistency of the SF-MPQ-2 for use among patients with musculoskeletal shoulder pain.

Eligible patients with shoulder pain from MSK sources completed the SF-MPQ-2 at baseline (n = 195), and a subset did so again after 3-7days (n = 48), if their response to the Global Rating of Change (GROC) scale remained unchanged. Cronbach alpha (α) and intraclass correlation coefficient (ICC
), and their related 95% CI were calculated. Standard error of measurement (SEM), group and individual minimal detectable change (MDC90), and Bland-Altman (BA) plots were used to assess agreement.

Cronbach α ran pain assessment, with the total scale displaying the best reproducibility coefficients. Additional research on the validity and responsiveness of the SF-MPQ-2 is still required in this population.
Health workers' compliance with outpatient malaria case-management guidelines has been improving, specifically regarding the universal testing of suspected cases and the use of artemisinin-based combination therapy (ACT) only for positive results (i.e., 'test and treat'). Whether the improvements in compliance with 'test and treat' guidelines are consistent across different malaria endemicity areas has not been examined.

Data from 11 national, cross-sectional, outpatient malaria case-management surveys undertaken in Kenya from 2010 to 2016 were analysed. Four primary indicators (i.e., 'test and treat') and eight secondary indicators of artemether-lumefantrine (AL) dosing, dispensing, and counselling were measured. Mixed logistic regression models were used to analyse the annual trends in compliance with the indicators across the different malaria endemicity areas (i.e., from highest to lowest risk being lake endemic, coast endemic, highland epidemic, semi-arid seasonal transmission, and low risk).

Compllling tasks significantly changed over time.

There is variability in health workers' compliance with outpatient malaria case-management guidelines across different malaria-risk areas in Kenya. Major improvements in areas of the highest risk have not been seen in low-risk areas. Interventions to improve practices should be targeted geographically.
There is variability in health workers' compliance with outpatient malaria case-management guidelines across different malaria-risk areas in Kenya. Major improvements in areas of the highest risk have not been seen in low-risk areas. Interventions to improve practices should be targeted geographically.
Herba Siegesbeckiae (HS), the dried aerial parts of Siegesbeckia orientalis L., S. pubescens Makino, or S. glabrescens Makino, is traditionally used for treating chronic diseases in China. However, there is no information about the chronic toxicity of HS. The objective of this study is to evaluate the 24-week oral dosing toxicities of HS aqueous extract (HSE) in rats.

S. orientalis-originated HS was reflux-extracted with distilled water. Sprague-Dawley rats were randomly divided into four groups, with 10 males and 10 females in each group. The rats were intragastrically administered with HSE at 5, 1.67 and 0.56 g/kg (experimental groups) or an equal volume of distilled water (control group), 6 days a week, for 24 weeks. The high dose of HSE (5 g/kg) was its maximum tolerated dose. Body weight was recorded every 2 days during the experimental period. Chemical, hematological and histopathological parameters, as well as organ weights, were measured at the end of the experiment.

Decreased body weight gain; increased liver and lung relative weights; histopathological alterations in liver and lung tissues; elevated serum levels of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase were found after HSE treatments.
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