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Measles is a highly infectious, vaccine-preventable disease that can cause severe illness, hospitalization, and death. A measles outbreak associated with a migrant shelter in Chicago occurred during February-April 2024, in which a total of 57 confirmed cases were identified, including 52 among shelter residents, three among staff members, and two among community members with a known link to the shelter. CDC simulated a measles outbreak among shelter residents using a dynamic disease model, updated in real time as additional cases were identified, to produce outbreak forecasts and assess the impact of public health interventions. As of April 8, the model forecasted a median final outbreak size of 58 cases (IQR = 56-60 cases); model fit and prediction range improved as more case data became available. Counterfactual analysis of different intervention scenarios demonstrated the importance of early deployment of public health interventions in Chicago, with a 69% chance of an outbreak of 100 or more cases had there been no mass vaccination or active case-finding compared with only a 1% chance when those interventions were deployed. This analysis highlights the value of using real-time, dynamic models to aid public health response, set expectations about outbreak size and duration, and quantify the impact of interventions. The model shows that prompt mass vaccination and active case-finding likely substantially reduced the chance of a large (100 or more cases) outbreak in Chicago.
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Brotes de Enfermedades , Sarampión , Humanos , Brotes de Enfermedades/prevención & control , Chicago/epidemiología , Sarampión/epidemiología , Sarampión/prevención & control , Modelos Epidemiológicos , Salud Pública , Factores de Tiempo , Predicción , Adolescente , Niño , Preescolar , Vacunación Masiva , AdultoRESUMEN
Glutathione (GSH) is a major endogenous antioxidant, and its depletion has been observed in several brain diseases including epilepsy. Previous studies in our laboratory have shown that dimercaprol (DMP) can elevate GSH via post-translational activation of glutamate cysteine ligase (GCL), the rate limiting GSH biosynthetic enzyme and inhibit neuroinflammation in vitro. Here we determined 1) the role of cysteamine as a new mechanism by which DMP increases GSH biosynthesis and 2) its ability to inhibit neuroinflammation and neuronal injury in the rat kainate model of epilepsy. DMP depleted cysteamine in a time- and concentration-dependent manner in a cell free system. To guide the in vivo administration of DMP, its pharmacokinetic profile was determined in the plasma, liver, and brain. The results confirmed DMP's ability to cross the blood-brain-barrier. Treatment of rats with DMP (30 mg/kg) depleted cysteamine in the liver and hippocampus that was associated with increased GCL activity in these tissues. GSH levels were significantly increased (20 %) in the hippocampus 1 h after 30 mg/kg DMP administration. Following DMP (30 mg/kg) administration once daily, a marked attenuation of GSH depletion was seen in the SE model. SE-induced inflammatory markers including cytokine release, microglial activation, and neuronal death were significantly attenuated in the hippocampus with DMP treatment. Taken together, these results highlight the importance of restoring redox status with rescue of GSH depletion by DMP in post epileptogenic insults.
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Glutatión , Enfermedades Neuroinflamatorias , Estrés Oxidativo , Estado Epiléptico , Animales , Ratas , Glutatión/metabolismo , Estado Epiléptico/metabolismo , Estado Epiléptico/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/etiología , Masculino , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Cisteamina/farmacología , Antioxidantes/farmacología , Antioxidantes/metabolismo , Glutamato-Cisteína Ligasa/metabolismo , Hígado/metabolismo , Hígado/patología , Hígado/efectos de los fármacosRESUMEN
Bedaquiline fumarate (BQF) is classified as a BCS class II drug and has poor water solubility and dissolution rate, which ultimately compromises bioavailability. The objective of this study is to improve the biopharmaceutical properties of BQF through a solid dispersion system by using Soluplus®. Two solid dispersion systems were prepared i.e. binary solid dispersion (BSD) and ternary solid dispersion (TSD) where 14.31-fold and 20.43-fold increase in solubility of BQF was observed with BSD and TSD in comparison to BQF. In our previous research work, we explored the BSD and TSD of BQF with a crystalline polymer, poloxamer 188, which showed an increment in the solubility of BQF. In the current research, amorphous Soluplus® polymer was selected to formulate BSD and TSD with BQF and showed higher solubility than poloxamer 188. The various solid and liquid state characterization results confirmed the presence of an amorphous form of BQF inside solid dispersion. The Fourier transform infrared spectroscopy showed no chemical interactions between BQF and polymer. The cellular uptake results demonstrated higher uptake in Caco-2 cell lines. Pharmacokinetic studies showed enhanced solubility and bioavailability of TSDs. Hence, the present research shows a promising formulation strategy for enhancing the biopharmaceutical performance of BQF by increasing its solubility.
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Disponibilidad Biológica , Diarilquinolinas , Polietilenglicoles , Polivinilos , Solubilidad , Polivinilos/química , Células CACO-2 , Humanos , Animales , Diarilquinolinas/farmacocinética , Diarilquinolinas/química , Diarilquinolinas/farmacología , Polietilenglicoles/química , Masculino , Ratas , Composición de Medicamentos/métodos , Química Farmacéutica/métodos , Antituberculosos/farmacocinética , Antituberculosos/química , Antituberculosos/farmacología , Antituberculosos/administración & dosificación , Poloxámero/químicaRESUMEN
Herein, we report an in-situ mild and metal-free protocol for thiomethylation of heteroarenes in high yields. The thiomethylation of various chloropurines, nucleosides, and chloroheteroarenes has been accomplished offering easy access to agrochemicals and synthetic molecules useful for drug discovery.
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Reactive oxygen species have an emerging role in the pathologic consequences of status epilepticus. We have previously demonstrated the efficacy of a water-for-injection formulation of the meso-porphyrin catalytic antioxidant, manganese (III) meso-tetrakis (N-N-diethylimidazole) porphyrin (AEOL10150) against oxidative stress, neuroinflammation, and neuronal death initiated by kainic acid, pilocarpine, diisopropylflurophosphate (DFP), and soman. This previous dose and dosing strategy of AEOL10150 required smaller multiple daily injections, precluding our ability to test its efficacy against delayed consequences of nerve agent exposure such as neurodegeneration and cognitive dysfunction. Therefore, we developed formulations of AEOL10150 designed to deliver a larger dose once daily with improved brain pharmacodynamics. We examined four new formulations of AEOL10150 that resulted in 8 times higher subcutaneous dose with lower acute toxicity, slower absorption, longer half-life, and higher maximal plasma concentrations compared with our previous strategy. AEOL10150 brain levels exhibited improved pharmacodynamics over 24 hours with all four formulations. We tested a subcutaneous dose of 40 mg/kg AEOL10150 in two formulations (2% carboxymethyl cellulose and 4% polyethylene glycol-4000) in the DFP rat model, and both formulations exhibited significant protection against DFP-induced oxidative stress. Additionally, and in one formulation (4% polyethylene glycol-4000), AEOL10150 significantly protected against DFP-induced neuronal death, microglial activation, delayed memory impairment, and mortality. These results suggest that reformulation of AEOL10150 can attenuate acute and delayed outcomes of organophosphate neurotoxicity. SIGNIFICANCE STATEMENT: Reformulation of manganese (III) meso-tetrakis (N-N-diethylimidazole) porphyrin allowed higher tolerated doses of the compound with improved pharmacodynamics. Specifically, one new formulation allowed fewer daily doses and improvement in acute and delayed outcomes of organophosphate toxicity.
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Disfunción Cognitiva , Metaloporfirinas , Agentes Nerviosos , Ratas , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Ratas Sprague-Dawley , Agentes Nerviosos/toxicidad , Enfermedades Neuroinflamatorias , Manganeso , Estrés Oxidativo , Metaloporfirinas/farmacología , Metaloporfirinas/uso terapéutico , Organofosfatos , PolietilenglicolesRESUMEN
Lithium is commonly prescribed as a mood stabilizer in a variety of mental health conditions, yet its molecular mode of action is incompletely understood. Many cellular events associated with lithium appear tied to mitochondrial function. Further, recent evidence suggests that lithium bioactivities are isotope specific. Here we focus on lithium effects related to mitochondrial calcium handling. Lithium protected against calcium-induced permeability transition and decreased the calcium capacity of liver mitochondria at a clinically relevant concentration. In contrast, brain mitochondrial calcium capacity was increased by lithium. Surprisingly, 7Li acted more potently than 6Li on calcium capacity, yet 6Li was more effective at delaying permeability transition. The size distribution of amorphous calcium phosphate colloids formed in vitro was differentially affected by lithium isotopes, providing a mechanistic basis for the observed isotope specific effects on mitochondrial calcium handling. This work highlights a need to better understand how mitochondrial calcium stores are structurally regulated and provides key considerations for future formulations of lithium-based therapeutics.
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An efficient ex-situ method for the amidation of carboxylic acids mediated by CDI has been disclosed herewith. This metal-free strategy is performed at ambient temperature and can be applied effectively for late-stage modification of amino acids and APIs.
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Glutathione (GSH) depletion, and impaired redox homeostasis have been observed in experimental animal models and patients with epilepsy. Pleiotropic strategies that elevate GSH levels via transcriptional regulation have been shown to significantly decrease oxidative stress and seizure frequency, increase seizure threshold, and rescue certain cognitive deficits. Whether elevation of GSH per se alters neuronal hyperexcitability remains unanswered. We previously showed that thiols such as dimercaprol (DMP) elevate GSH via post-translational activation of glutamate cysteine ligase (GCL), the rate limiting GSH biosynthetic enzyme. Here, we asked if elevation of cellular GSH by DMP altered neuronal hyperexcitability in-vitro and in-vivo. Treatment of primary neuronal-glial cerebrocortical cultures with DMP elevated GSH and inhibited a voltage-gated potassium channel blocker (4-aminopyridine, 4AP) induced neuronal hyperexcitability. DMP increased GSH in wildtype (WT) zebrafish larvae and significantly attenuated convulsant pentylenetetrazol (PTZ)-induced acute 'seizure-like' swim behavior. DMP treatment increased GSH and inhibited convulsive, spontaneous 'seizure-like' swim behavior in the Dravet Syndrome (DS) zebrafish larvae (scn1Lab). Furthermore, DMP treatment significantly decreased spontaneous electrographic seizures and associated seizure parameters in scn1Lab zebrafish larvae. We investigated the role of the redox-sensitive mammalian target of rapamycin (mTOR) pathway due to the presence of several cysteine-rich proteins and their involvement in regulating neuronal excitability. Treatment of primary neuronal-glial cerebrocortical cultures with 4AP or l-buthionine-(S,R)-sulfoximine (BSO), an irreversible inhibitor of GSH biosynthesis, significantly increased mTOR complex I (mTORC1) activity which was rescued by pre-treatment with DMP. Furthermore, BSO-mediated GSH depletion oxidatively modified the tuberous sclerosis protein complex (TSC) consisting of hamartin (TSC1), tuberin (TSC2), and TBC1 domain family member 7 (TBC1D7) which are critical negative regulators of mTORC1. In summary, our results suggest that DMP-mediated GSH elevation by a novel post-translational mechanism can inhibit neuronal hyperexcitability both in-vitro and in-vivo and a plausible link is the redox sensitive mTORC1 pathway.
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Glutatión , Pez Cebra , Animales , Humanos , Pez Cebra/metabolismo , Glutatión/metabolismo , Glutamato-Cisteína Ligasa/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Butionina Sulfoximina/farmacología , Mamíferos/metabolismoRESUMEN
Background: Anemia is the most common nutritional disease in pregnancy with significant adverse maternofetal outcome. The objective of the present study is to study the impact of COVID-19 pandemic on the pregnancy outcomes of women with severe anemia. Methodology: A retrospective observational study was conducted in the Department of Obstetrics and Gynaecology at LHMC and SSK Hospital, Delhi. The study included all antenatal women admitted at a gestational age of >26 weeks (third trimester) with severe anemia and hemoglobin level of 7 g/dL. In our study, a total of 4031 women were included as cases during study period (July to December 2022) and 6659 women as controls from pre-COVID-19 period (July to December 2019). Results: In present study, a total of 4031 women delivered during study period as compared to 6659 in control period. In the present study, the prevalence of anemia was observed to be 74.7% in the study group and 51.6% in the control group (P < 0.001). Mean hemoglobin level was significantly lower in study group as compared to the control groups P<0.05. Microcytic hypochromic anemia was the most common morphological type of anemia in both groups. Serum ferritin, serum iron, serum B12, and folic acid levels among cases were significantly (P < 0.05) lower as compared to controls. Odds of fetal growth restriction were 1.4 times higher among study group as compared to control groups. The odds of newborn complications such as low birth weight were 2.49 (95% CI: 1.04-5.91) and need for nursery or NICU admission were 4.84 times (95% CI: 0.48-48.24) higher in cases as compared to controls. Low birth rate was higher in cases and was found to be statistically significant. Conclusion: COVID-19 pandemic had indirect impact on adverse maternal and fetal outcome in women with severe anemia.
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Streptococcus mutans, found in the human oral cavity, is a significant contributor to the pathogenesis of dental caries. This bacterium expresses three genetically distinct types of glucosyltransferases named GtfB (GTF-I), GtfC (GTF-SI) and GtfD (GTF-S) that play critical roles in the development of dental plaque. The catalytic domains of GtfB, GtfC and GtfD contain conserved active-site residues for the overall enzymatic activity that relate to hydrolytic glycosidic cleavage of sucrose to glucose and fructose, release of fructose and generation of a glycosyl-enzyme intermediate in the reducing end. In a subsequent transglycosylation step, the glucosyl moiety is transferred to the nonreducing end of an acceptor to form a growing glucan polymer chain made up of glucose molecules. It has been proposed that both sucrose breakdown and glucan synthesis occur in the same active site of the catalytic domain, although the active site does not appear to be large enough to accommodate both functions. These three enzymes belong to glycoside hydrolase family 70 (GH70), which shows homology to glycoside hydrolase family 13 (GH13). GtfC synthesizes both soluble and insoluble glucans (α-1,3 and α-1,6 glycosidic linkages), while GtfB and GtfD synthesize only insoluble or soluble glucans, respectively. Here, crystal structures of the catalytic domains of GtfB and GtfD are reported. These structures are compared with previously determined structures of the catalytic domain of GtfC. With this work, apo structures and inhibitor-complex structures with acarbose are now available for the catalytic domains of GtfC and GtfB. The structure of GtfC with maltose allows further identification and comparison of active-site residues. A model of sucrose binding to GtfB is also included. The new structure of the catalytic domain of GtfD affords a structural comparison of the three S. mutans glycosyltransferases. Unfortunately, the catalytic domain of GtfD is not complete since crystallization resulted in the structure of a truncated protein lacking approximately 200 N-terminal residues of domain IV.
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Caries Dental , Streptococcus mutans , Humanos , Dominio Catalítico , Cristalografía por Rayos X , Glucosiltransferasas/química , Glucosa , Sacarosa , Fructosa , GlucanosRESUMEN
Mitochondrial dysfunction is an early event in the pathogenesis of neurologic disorders and aging. Sirtuin 3 (SIRT3) regulates mitochondrial function in response to the cellular environment through the reversible deacetylation of proteins involved in metabolism and reactive oxygen species detoxification. As the primary mitochondrial deacetylase, germline, or peripheral tissue-specific deletion of SIRT3 produces mitochondrial hyperacetylation and the accelerated development of age-related diseases. Given the unique metabolic demands of neurons, the role of SIRT3 in the brain is only beginning to emerge. Using mass spectrometry-based acetylomics, high-resolution respirometry, video-EEG, and cognition testing, we report targeted deletion of SIRT3 from select neurons in the cortex and hippocampus produces altered neuronal excitability and metabolic dysfunction in female mice. Targeted deletion of SIRT3 from neuronal helix-loop-helix 1 (NEX)-expressing neurons resulted in mitochondrial hyperacetylation, female-specific superoxide dismutase-2 (SOD2) modification, increased steady-state superoxide levels, metabolic reprogramming, altered neuronal excitability, and working spatial memory deficits. Inducible neuronal deletion of SIRT3 likewise produced female-specific deficits in spatial working memory. Together, the data demonstrate that deletion of SIRT3 from forebrain neurons selectively predisposes female mice to deficits in mitochondrial and cognitive function.SIGNIFICANCE STATEMENT Mitochondrial SIRT3 is an enzyme shown to regulate energy metabolism and antioxidant function, by direct deacetylation of proteins. In this study, we show that neuronal SIRT3 deficiency renders female mice selectively vulnerable to impairment in redox and metabolic function, spatial memory, and neuronal excitability. The observed sex-specific effects on cognition and neuronal excitability in female SIRT3-deficient mice suggest that mitochondrial dysfunction may be one factor underlying comorbid neuronal diseases, such as Alzheimer's disease and epilepsy. Furthermore, the data suggest that SIRT3 dysfunction may predispose females to age-related metabolic and cognitive impairment.
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Sirtuina 3 , Masculino , Ratones , Femenino , Animales , Sirtuina 3/genética , Neuronas/metabolismo , Mitocondrias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Envejecimiento/metabolismo , AcetilaciónRESUMEN
The dimethylamino functionality has significant importance in industrially relevant molecules and methodologies to install these efficiently are highly desirable. We report herein a highly efficient, room-temperature dimethylamination of chloroheteroarenes performed via the in-situ generation of dimethylamine using N,N-dimethylformamide (DMF) as precursor wiith a large substrate scope that includes various heteroarenes, purines as well as commercially relevant drugs such as altretamine, ampyzine and puromycin precursor.
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Dimetilformamida , Temperatura , Dimetilformamida/química , CatálisisRESUMEN
BACKGROUND: Pulmonary microbial infection is mainly caused by microbes like atypical bacteria, viruses, and fungi, on both the upper and lower respiratory tracts. One of the demands of the present is the use of nanotechnology-based treatments to fight various lung infections. AIM: The main aim of the study is to explore all pulmonary infectious diseases and to compare the advanced and novel treatment approaches with the conventional methods which are available to treat infections. METHODS: This work sheds light on pulmonary infectious diseases with their conventional and present treatment approaches along with a focus on the advantageous roles of nano-based formulations. In the literature, it has been reported that the respiratory system is the key target of various infectious diseases which gives rise to various challenges in the treatment of pulmonary infections. RESULTS: The present review article describes the global situation of pulmonary infections and the different strategies which are available for their management, along with their limitations. The article also highlights the advantages and different examples of nanoformulations currently combating the limitations of conventional therapies. CONCLUSION: The content of the present article further reflects on the summary of recently published research and review works on pulmonary infections, conventional methods of treatment with their limitations, and the role of nano-based approaches to combat the existing infectious diseases which will jointly help the researchers to produce effective drug formulations with desired pharmacological activities.
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Enfermedades Transmisibles , Nanotecnología , Humanos , Nanotecnología/métodos , Hongos , Pulmón , Bacterias , Enfermedades Transmisibles/tratamiento farmacológicoRESUMEN
The International League Against Epilepsy/American Epilepsy Society (ILAE/AES) Joint Translational Task Force established the TASK3 working groups to create common data elements (CDEs) for various preclinical epilepsy research disciplines. This is the second in a two-part series of omics papers, with the other including genomics, transcriptomics, and epigenomics. The aim of the CDEs was to improve the standardization of experimental designs across a range of epilepsy research-related methods. We have generated CDE tables with key parameters and case report forms (CRFs) containing the essential contents of the study protocols for proteomics, lipidomics, and metabolomics of samples from rodent models and people with epilepsy. We discuss the important elements that need to be considered for the proteomics, lipidomics, and metabolomics methodologies, providing a rationale for the parameters that should be documented.
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The roles of both neuroinflammation and oxidative stress in the pathophysiology of epilepsy have begun to receive considerable attention in recent years. However, these concepts are predominantly studied as separate entities despite the evidence that neuroinflammatory and redox-based signaling cascades have significant crosstalk. Oxidative post-translational modifications have been demonstrated to directly influence the function of key neuroinflammatory mediators. Neuroinflammation can further be controlled on the transcriptional level as the transcriptional regulators NF-KB and nrf2 are activated by reactive oxygen species. Further, neuroinflammation can induce the increased expression and activity of NADPH oxidase, leading to a highly oxidative environment. These factors additionally influence mitochondria function and the metabolic status of neurons and glia, which are already metabolically stressed in epilepsy. Given the implication of this relationship to disease pathology, this review explores the numerous mechanisms by which neuroinflammation and oxidative stress influence one another in the context of epilepsy. We further examine the efficacy of treatments targeting oxidative stress and redox regulation in animal and human epilepsies in the literature that warrant further investigation. Treatment approaches aimed at rectifying oxidative stress and aberrant redox signaling may enable control of neuroinflammation and improve patient outcomes.
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The International League Against Epilepsy/American Epilepsy Society (ILAE/AES) Joint Translational Task Force established the TASK3 working groups to create common data elements (CDEs) for various preclinical epilepsy research disciplines. The aim of the CDEs is to improve the standardization of experimental designs across a range of epilepsy research-related methods. Here, we have generated CDE tables with key parameters and case report forms (CRFs) containing the essential contents of the study protocols for genomics, transcriptomics, and epigenomics in rodent models of epilepsy, with a specific focus on adult rats and mice. We discuss the important elements that need to be considered for genomics, transcriptomics, and epigenomics methodologies, providing a rationale for the parameters that should be collected. This is the first in a two-part series of omics papers with the second installment to cover proteomics, lipidomics, and metabolomics in adult rodents.
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Proliferation of blaNDM-1 in water and wastewater is particularly concerning because of multidrug-resistance and horizontal transfer of the gene. In the present study, a pathogenic NDM-1-positive Escherichia coli strain (named E. coli NDM-1) and the blaNDM-1 gene were treated with titanium dioxide (TiO2)/ultraviolet A (UVA) photocatalysis. Effects of catalyst dose, UVA intensity, and phosphate on bacteria and intracellular and extracellular blaNDM-1 genes were determined. With increases in TiO2 dose and UVA intensity, the inactivation rate of E. coli NDM-1 increased greatly in saline solution. However, phosphate in water hindered adsorption of bacteria to TiO2 and partly changed the TiO2 photocatalytic pathway, resulting in low degradation efficiency. Although inactivation of E. coli NDM-1 was highly efficient, TiO2/UVA photocatalysis had little effect on removal of the blaNDM-1 gene. During the 2-h photocatalytic experiments, E. coli cells decreased by 4.7-log, while the blaNDM-1 gene decreased by 0.7- ~ 1.5-log. Moreover, the degradation rate of extracellular blaNDM-1 was ~2.7 times higher than that of intracellular genes. Abundance and transformation frequency of residual blaNDM-1 genes remained high, even when bacteria were completely inactivated, indicating potential health risks. Increases in treatment time and UVA irradiation intensity are needed to remove the blaNDM-1 gene to sufficiently low levels.
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Escherichia coli , beta-Lactamasas , Antibacterianos/farmacología , Bacterias , Escherichia coli/genética , Fosfatos , Titanio/farmacología , Rayos Ultravioleta , Agua , beta-Lactamasas/genéticaRESUMEN
INTRODUCTION: To date, COVID-19 has claimed 4.9 million lives. Diabetes has been identified as an independent risk factor of serious outcomes in people with COVID-19 infection. Whether that holds true across world regions uniformly has not been previously assessed. METHODS: This study offers the first umbrella systematic review and meta-analysis to analyse the collective and geographically stratified mortality, ICU admission, ventilation requirement, illness severity and discharge rate amongst patients with diabetes. Five databases (EMBASE, MEDLINE, CAB Abstracts, PsychInfo and Web of Science) and 3 additional sources (SSRN's eLibrary, Research Square and MedRxiv) were searched from inception to 30 August 2021. Prospective and retrospective cohort studies, reporting the association between diabetes and one or more COVID-19 hospitalization outcomes, were included. This meta-analysis was registered on PROSPERO, CRD42021278579. Abbreviated MeSH terms used for search were as follows: (Diabetes) AND (2019 Novel Coronavirus Disease), adapted per database requirements. Exclusion criteria exclusion criteria were as follows: (1) none of the primary or secondary outcomes of meta-analysis reported, (2) no confirmed COVID-19 infection (laboratory or clinical) and (3) no unexposed population (solely patients with diabetes included). Quality of the included studies were assessed using the Newcastle-Ottawa Scale (NOS) whilst quality of evidence by the GRADE framework. Studies that were clinically homogeneous were pooled. Summative data and heterogeneity were generated by the Cochrane platform RevMan (V. 5.4). RESULTS: Overall, 158 observational studies were included, with a total of 270,212 of participants, median age 59 [53-65 IQR] of who 56.5% were male. A total of 22 studies originated from EU, 90 from Far East, 16 from Middle East and 30 from America. Data were synthesized with mixed heterogeneity across outcomes. Pooled results highlighted those patients with diabetes were at a higher risk of COVID-19-related mortality, OR 1.87 [95%CI 1.61, 2.17]. ICU admissions increased across all studies for patients with diabetes, OR 1.59 [95%CI 1.15, 2.18], a result that was mainly skewed by Far East-originating studies, OR 1.94 [95%CI 1.51, 2.49]. Ventilation requirements were also increased amongst patients with diabetes worldwide, OR 1.44 [95%CI 1.20, 1.73] as well as their presentation with severe or critical condition, OR 2.88 [95%CI 2.29, 3.63]. HbA1C levels under <70 mmol and metformin use constituted protective factors in view of COVID-19 mortality, whilst the inverse was true for concurrent insulin use. CONCLUSIONS: Whilst diabetes constitutes a poor prognosticator for various COVID-19 infection outcomes, variability across world regions is significant and may skew overall trends.
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COVID-19 , Diabetes Mellitus , COVID-19/epidemiología , Diabetes Mellitus/epidemiología , Femenino , Hospitales , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Respiración Artificial , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Using external illumination cues, we induce the formation and dissolution of laboratory swarms of the nonbiting midge Chironomus riparius and study their behavior during these transient processes. In general, swarm formation is slower than swarm dissolution. We find that the swarm property that appears most rapidly during formation and disappears most rapidly during dissolution is an emergent mean radial acceleration pointing toward the center of the swarm. Our results strengthen the conjecture that this central effective force may be used as an indicator to distinguish when the midges are swarming from when they are not.