Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

KAJIAN KARAKTERISTIK HABITAT RAFFLESIA (Rafflesia patma BLUME.) DI CAGAR ALAM BOJONGLARANG JAYANTI, CIANJUR, JAWA BARAT

<p><em>Bojonglarang Jayanti Nature Reserve one of habitat Rafflesia patma. The purpose of this research  to identify biotic and abiotic habitat characteristic of R. patma in Bojonglarang Jayanti Nature Reserve. Research conducted in March until April, using single plot analysis habitat to take physical and biotic data as well as the study of literature for climate data retrieval. R. patma habitat have lowland and coastal forest vegetation types  with dominant species Cyathocalys biovulatus. Fauna that be a benefit to the life of Rafflesia are 19 species from 15 Family. There are 90 individual R.patma found at altitude 0-100 m above sea level, slope average 14.73%, the distance from the coast beach 758 m, a distance from the water 12 m, litter thickness 1.7 cm, and the type of soil is Podsolic with low nutrient content and acidic pH. R. patma habitat has C climate type. </em></p><p><em> </em></p><p><em>Key word : </em><em>A</em><em>biotic, </em><em>B</em><em>iotic, </em><em>H</em><em>abitat, </em><em>Population, </em><em>R. Patma</em></p

KAJIAN KARAKTERISTIK HABITAT RAFFLESIA (Rafflesia patma BLUME.) DI CAGAR ALAM BOJONGLARANG JAYANTI, CIANJUR, JAWA BARAT

Bojonglarang Jayanti Nature Reserve one of habitat Rafflesia patma. The purpose of this research  to identify biotic and abiotic habitat characteristic of R. patma in Bojonglarang Jayanti Nature Reserve. Research conducted in March until April, using single plot analysis habitat to take physical and biotic data as well as the study of literature for climate data retrieval. R. patma habitat have lowland and coastal forest vegetation types  with dominant species Cyathocalys biovulatus. Fauna that be a benefit to the life of Rafflesia are 19 species from 15 Family. There are 90 individual R.patma found at altitude 0-100 m above sea level, slope average 14.73%, the distance from the coast beach 758 m, a distance from the water 12 m, litter thickness 1.7 cm, and the type of soil is Podsolic with low nutrient content and acidic pH. R. patma habitat has C climate type.  Key word : Abiotic, Biotic, Habitat, Population, R. Patm

Utilization of a DC brushless hub motor as an alternator in drive train of fuel efficient series hybrid urban class vehicle

While designing the drive train of a Series Hybrid Vehicle fuel efficient vehicle for Shell Eco Marathon Asia 2010, The most important issue was the coupling of Engine and Alternator. The major problem faced while doing so is the compatibility check of alternator with the engine as most locally available alternators were not capable enough to provide 48V at rated power of the engine required for operation of hub motors used in the drive train. In order to overcome this problem, it was decided that Magic Pie DC Brushless Hub motors may be used as improvised alternators, as the regenerative abilities of these motors provide an excellent platform to use it as an alternator and are fairly efficient as well. Many small mechanical modifications and mathematical calculations were done in order to achieve this goal

Computational-Model-Based Biopharmaceutics for p53 Pathway Using Modern Control Techniques for Cancer Treatment

The p53 pathway has been the focus of many researchers in the last few decades owing to its pivotal role as a frontline cancer suppressant protein. It plays a vital role in maintaining cell cycle checkpoints and cell apoptosis in response to a broken DNA strand. This is why it is found in the mutated form in more than 50% of malignant tumors. To overcome this, various drugs have been proposed to revive the p53 pathway in cancer patients. Small-molecule-based drugs, such as Nutlin 3a, which are capable of performing this stimulation, are at the fore of advanced clinical trials. However, the calculation of their dosage is a challenge. In this work, a method to determine the dosage of Nutlin 3a is investigated. A control-systems-based model is developed to study the response of the wild-type p53 protein to this drug. The proposed strategy regulates the p53 protein along with negative and positive feedback loops mediated by the MDM2 and MDM2 mRNA, respectively, along with the reversible repression of MDM2 caused by Nutlin 3a. For a broader perspective, the reported PBK dynamics of Nutlin 3a are also incorporated. It has been reported that p53 responds to stresses in two ways in terms of concentration to this drug: either it is a sustained (constant) or an oscillatory response. The claimed dosage strategy turned out to be appropriate for sustained p53 response. However, for the induction of oscillations, inhibition of MDM2 is not enough; rather, anti-repression of the p53&ndash;MDM2 complex is also needed, which opens new horizons for a new drug design paradigm

Computational-Model-Based Biopharmaceutics for p53 Pathway Using Modern Control Techniques for Cancer Treatment

The p53 pathway has been the focus of many researchers in the last few decades owing to its pivotal role as a frontline cancer suppressant protein. It plays a vital role in maintaining cell cycle checkpoints and cell apoptosis in response to a broken DNA strand. This is why it is found in the mutated form in more than 50% of malignant tumors. To overcome this, various drugs have been proposed to revive the p53 pathway in cancer patients. Small-molecule-based drugs, such as Nutlin 3a, which are capable of performing this stimulation, are at the fore of advanced clinical trials. However, the calculation of their dosage is a challenge. In this work, a method to determine the dosage of Nutlin 3a is investigated. A control-systems-based model is developed to study the response of the wild-type p53 protein to this drug. The proposed strategy regulates the p53 protein along with negative and positive feedback loops mediated by the MDM2 and MDM2 mRNA, respectively, along with the reversible repression of MDM2 caused by Nutlin 3a. For a broader perspective, the reported PBK dynamics of Nutlin 3a are also incorporated. It has been reported that p53 responds to stresses in two ways in terms of concentration to this drug: either it is a sustained (constant) or an oscillatory response. The claimed dosage strategy turned out to be appropriate for sustained p53 response. However, for the induction of oscillations, inhibition of MDM2 is not enough; rather, anti-repression of the p53–MDM2 complex is also needed, which opens new horizons for a new drug design paradigm

Computational-Model-Based Biopharmaceutics for p53 Pathway Using Modern Control Techniques for Cancer Treatment

The p53 pathway has been the focus of many researchers in the last few decades owing to its pivotal role as a frontline cancer suppressant protein. It plays a vital role in maintaining cell cycle checkpoints and cell apoptosis in response to a broken DNA strand. This is why it is found in the mutated form in more than 50% of malignant tumors. To overcome this, various drugs have been proposed to revive the p53 pathway in cancer patients. Small-molecule-based drugs, such as Nutlin 3a, which are capable of performing this stimulation, are at the fore of advanced clinical trials. However, the calculation of their dosage is a challenge. In this work, a method to determine the dosage of Nutlin 3a is investigated. A control-systems-based model is developed to study the response of the wild-type p53 protein to this drug. The proposed strategy regulates the p53 protein along with negative and positive feedback loops mediated by the MDM2 and MDM2 mRNA, respectively, along with the reversible repression of MDM2 caused by Nutlin 3a. For a broader perspective, the reported PBK dynamics of Nutlin 3a are also incorporated. It has been reported that p53 responds to stresses in two ways in terms of concentration to this drug: either it is a sustained (constant) or an oscillatory response. The claimed dosage strategy turned out to be appropriate for sustained p53 response. However, for the induction of oscillations, inhibition of MDM2 is not enough; rather, anti-repression of the p53–MDM2 complex is also needed, which opens new horizons for a new drug design paradigm.</jats:p

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population

Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4&nbsp;% presented with RS, while 13.6&nbsp;% had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7&nbsp;% vs RS: 37.5&nbsp;%). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1&nbsp;% vs. RS 32.0&nbsp;%), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83-0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders