Assessment of diabetes and prediabetes prevalence and predictors by HbA1c in a population from sub-Saharan Africa with a high proportion of anemia: a prospective cross-sectional study

Epidemiological data about diabetes mellitus (DM) for sub-Saharan Africa (SSA) are scarce and the utility of glycated hemoglobin (HbA1c) to diagnose DM is uncertain in African populations with a high proportion of anemia.; In a cross-sectional study, age-adjusted prevalence rates and predictors for DM and pre-DM were prospectively assessed by HbA1c in a semirural walk-in population of Tanzania (n=992). Predictors for DM were calculated by logistic regression. Correlations between HbA1c, hemoglobin, and blood glucose levels were done by Pearson's correlation.; Overall, DM and pre-DM prevalence rates were 6.8% (95% CI 5.3 to 8.5) and 25% (95% CI 22.8 to 28.3), respectively. There was an increase in DM prevalence in patients 50-59 (14.9%; 95% CI 9.1 to 22.5), ≥60 years old (18.5%; 95% CI 12.2 to 26.2) and in patients with overweight (9.3%; 95% CI 5.9 to 13.7), obesity (10.9%; 95% CI 6.9 to 16) compared with patients 18-29 years old (2.2%; 95% CI 0.9 to 4.4) (p<0.001) and to normal-weight patients (3.6%; 95% CI 2.1 to 5.6) (p<0.01), respectively. Age (OR 1.08, 95% CI 1.05 to 1.12; p<0.001), body mass index (BMI) (OR 1.10, 95% CI 1.04 to 1.16; p<0.001), and acute infection (OR 3.46, 95% CI 1.02 to 10.8; p=0.038) were predictors for DM. Comparing patients with a BMI of 20 kg/m; 2; and a BMI of 35 kg/m; 2; , the relative risk for DM increases in average by 2.12-fold (range 1.91-2.24) across the age groups. Comparing patients 20 years old with patients 70 years old, the relative risk for DM increases in average 9.7-fold (range 8.9-10.4) across the BMI groups. Overall, 333 patients (36%) suffered from anemia. Pearson's correlation coefficients (r) between HbA1c and hemoglobin was -0.009 (p=0.779), and between HbA1c and fasting blood glucose and random blood glucose, it was 0.775 and 0.622, respectively (p<0.001).; We observed a high prevalence of DM and pre-DM, mainly triggered by increasing age and BMI, and provide evidence that HbA1c is suitable to assess DM also in populations of SSA with high proportions of anemia.; NCT03458338

Pennsylvania Folklife Vol. 25, No. 1

• Pennsylvania German Tombstone Art of Lebanon County, Pennsylvania • Rain Day in Waynesburg, Pennsylvania • Non-Ordinary Stoneware Pieces from New Geneva and Greensboro, Pennsylvania • Pennsylvania German Astronomy and Astrology XIII: Conjunctions of 1683, 1694, and 1743 • The Social Context of Musical Instruments within the Pennsylvania German Culture • Tourism and the Amish Way of Life • Home Brewing Techniques: Folk-Cultural Questionnaire No. 41https://digitalcommons.ursinus.edu/pafolklifemag/1065/thumbnail.jp

Nucleocytoplasmic transport: a thermodynamic mechanism

The nuclear pore supports molecular communication between cytoplasm and nucleus in eukaryotic cells. Selective transport of proteins is mediated by soluble receptors, whose regulation by the small GTPase Ran leads to cargo accumulation in, or depletion from the nucleus, i.e., nuclear import or nuclear export. We consider the operation of this transport system by a combined analytical and experimental approach. Provocative predictions of a simple model were tested using cell-free nuclei reconstituted in Xenopus egg extract, a system well suited to quantitative studies. We found that accumulation capacity is limited, so that introduction of one import cargo leads to egress of another. Clearly, the pore per se does not determine transport directionality. Moreover, different cargo reach a similar ratio of nuclear to cytoplasmic concentration in steady-state. The model shows that this ratio should in fact be independent of the receptor-cargo affinity, though kinetics may be strongly influenced. Numerical conservation of the system components highlights a conflict between the observations and the popular concept of transport cycles. We suggest that chemical partitioning provides a framework to understand the capacity to generate concentration gradients by equilibration of the receptor-cargo intermediary.Comment: in press at HFSP Journal, vol 3 16 text pages, 1 table, 4 figures, plus Supplementary Material include

Fashioning Entitlements: A Comparative Law and Economic Analysis of the Judicial Role in Environmental Centralization in the U.S. and Europe

This paper identifies and evaluates, from an economic point of view, the role of the judiciary the steady shift of environmental regulatory authority to higher, more centralized levels of government in both the U.S. and Europe. We supply both a positive analysis of how the decisions made by judges have affected the incentives of both private and public actors to pollute the natural environment, and normative answers to the question of whether judges have acted so as to create incentives that move levels of pollution in an efficient direction, toward their optimal, cost-minimizing (or net-benefit-maximizing) levels. Highlights of the analysis include the following points: 1) Industrial-era local (state or national) legislation awarding entitlements to pollute was almost certainly inefficient due to a fundamental economic obstacle faced by those who suffer harm from the over-pollution of publicly owned natural resources: the inability to monetize and credibly commit to repay the future economic value of reducing pollution. 2) When industrial era pollution spilled across state lines in the US, the federal courts, in particular the Supreme Court, fashioned a federal common law of interstate nuisance that set up essentially the same sort of blurry, uncertain entitlements to pollute or be free of pollution that had been created by the state courts in resolving local pollution disputes. We argue that for the typical pollution problem, a legal regime of blurry interstate entitlements - with neither jurisdiction having a clear right either to pollute or be free of pollution from the other - is likely to generate efficient incentives for interjursidictional bargaining, even despite the public choice problems besetting majority-rule government. Interestingly, a very similar system of de facto entitlements arose and often stimulated interjursidictional bargaining in Europe as well as in the U.S. 3) The US federal courts have generally interpreted the federal environmental statutes in ways that give clear primacy to federal regulators. Through such judicial interpretation, state and local regulators face a continuing risk of having their decisions overridden by federal regulators. This reduces the incentives for regulatory innovation at the state and local level. Judicial authorization of federal overrides has thus weakened the economic rationale for cooperative federalism suggested by economic models of principal-agent relationships. As a result of the principle of attribution, there is less risk in Europe that (like in the US) courts would enlarge the federal purview and thereby limit the powers of the Member States. Despite this principle, the power of the European bureaucracy (that is, the European Commission) has steadily increased and led to a steady shift of environmental regulatory competencies to the European level. This shift is only sometimes normatively desirable, and yet there is little that the ECJ can or will do to slow it

Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis

BACKGROUND: Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. METHODS: We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. RESULTS: We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27-32]. The hazard of death was comparatively lower for patients in the WHO European region. INTERPRETATION: Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission

Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis

Background Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. Methods We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. Results We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67–82]), than encephalopathy (54% [42–65]). Intensive care use was high (38% [35–41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27–32]. The hazard of death was comparatively lower for patients in the WHO European region. Interpretation Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission

Haematological consequences of acute uncomplicated falciparum malaria: a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data

Background: Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods: Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7. Results: A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0–19.7 g/dL) in Africa, 11.6 g/dL (range 5.0–20.0 g/dL) in Asia and 12.3 g/dL (range 6.9–17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to ≥ 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39–3.05], p < 0.001). Conclusions: In patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis.

BackgroundNeurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome.MethodsWe conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models.ResultsWe included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27-32]. The hazard of death was comparatively lower for patients in the WHO European region.InterpretationNeurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission