Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Only 3 cases of coronavirus disease 2019 (COVID-19) were identified in Italy in the first half of February 2020 and all involved people who had recently traveled to China. On February 20, 2020, a severe case of pneumonia due to SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) was diagnosed in northern Italy’s Lombardy region in a man in his 30s who had no history of possible exposure abroad. Within 14 days, many other cases of COVID-19 in the surrounding area were diagnosed, including a substantial number of critically ill patients.1 On the basis of the number of cases and of the advanced stage of the disease it was hypothesized that the virus had been circulating within the population since January. Another cluster of patients with COVID-19 was simultaneously identified in Veneto, which borders Lombardy. Since then, the number of cases identified in Italy has rapidly increased, mainly in northern Italy, but all regions of the country have reported having patients with COVID-19. After China, Italy now has the second largest number of COVID-19 cases2 and also has a very high case-fatality rate.3 This Viewpoint reviews the Italian experience with COVID-19 with an emphasis on fatalities.

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Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy.

A vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to control the coronavirus disease 2019 (COVID-19) global pandemic. Structural studies have led to the development of mutations that stabilize Betacoronavirus spike proteins in the prefusion state, improving their expression and increasing immunogenicity1. This principle has been applied to design mRNA-1273, an mRNA vaccine that encodes a SARS-CoV-2 spike protein that is stabilized in the prefusion conformation. Here we show that mRNA-1273 induces potent neutralizing antibody responses to both wild-type (D614) and D614G mutant2 SARS-CoV-2 as well as CD8+ T cell responses, and protects against SARS-CoV-2 infection in the lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a phase III trial to evaluate its efficacy.

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SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness.

Major depression is characterized by diverse debilitating symptoms that include hopelessness and anhedonia. Dopamine neurons involved in reward and motivation are among many neural populations that have been hypothesized to be relevant, and certain antidepressant treatments, including medications and brain stimulation therapies, can influence the complex dopamine system. Until now it has not been possible to test this hypothesis directly, even in animal models, as existing therapeutic interventions are unable to specifically target dopamine neurons. Here we investigated directly the causal contributions of defined dopamine neurons to multidimensional depression-like phenotypes induced by chronic mild stress, by integrating behavioural, pharmacological, optogenetic and electrophysiological methods in freely moving rodents. We found that bidirectional control (inhibition or excitation) of specified midbrain dopamine neurons immediately and bidirectionally modulates (induces or relieves) multiple independent depression symptoms caused by chronic stress. By probing the circuit implementation of these effects, we observed that optogenetic recruitment of these dopamine neurons potently alters the neural encoding of depression-related behaviours in the downstream nucleus accumbens of freely moving rodents, suggesting that processes affecting depression symptoms may involve alterations in the neural encoding of action in limbic circuitry.

Dopamine neurons modulate neural encoding and expression of depression-related behaviour

Zakljucno, potrebno je i nadalje svakodnevno raditi na prevenciji demencije, osiguravati resurse i osmisljavati strategije borbe protiv demencije, jer ce broj osoba s demencijom i u Hrvatskoj u buducnosti biti veci. No, s obzirom da se u svijetu ulažu znatna sredstva u podrucju istraživanja demencije, za ocekivati je pozitivnih pomaka, kako na podrucju terapije, rane dijagnostike, tako i na podrucju rehabilitacije osoba s demencijom. Stoga - vrijeme je na nasoj strani!

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Dementia: a public health priority

The Coronavirus (CoV) is a large family of viruses known to cause illnesses ranging from the common cold to acute respiratory tract infection The severity of the infection may be visible as pneumonia, acute respiratory syndrome, and even death Until the outbreak of SARS, this group of viruses was greatly overlooked However, since the SARS and MERS outbreaks, these viruses have been studied in greater detail, propelling the vaccine research On December 31, 2019, mysterious cases of pneumonia were detected in the city of Wuhan in China's Hubei Province On January 7, 2020, the causative agent was identified as a new coronavirus (2019-nCoV), and the disease was later named as COVID-19 by the WHO The virus spread extensively in the Wuhan region of China and has gained entry to over 210 countries and territories Though experts suspected that the virus is transmitted from animals to humans, there are mixed reports on the origin of the virus There are no treatment options available for the virus as such, limited to the use of anti-HIV drugs and/or other antivirals such as Remdesivir and Galidesivir For the containment of the virus, it is recommended to quarantine the infected and to follow good hygiene practices The virus has had a significant socio-economic impact globally Economically, China is likely to experience a greater setback than other countries from the pandemic due to added trade war pressure, which have been discussed in this paper

COVID-19: Emergence, Spread, Possible Treatments, and Global Burden

Antidiabetic, antihyperlipidemic and antioxidant effects of the flavonoid rich fraction of Pilea microphylla (L.) in high fat diet/streptozotocin-induced diabetes in mice.

Objectives. Aluminium, a neurotoxic agent in humans, has been implicated in the pathogenesis of neurodegenerative disorders. In this study, we examined the behavioral and biochemical effects of aluminium in rats with special emphasis on memory centres, namely, hippocampus and frontal cortex. Further, the effect of simvastatin treatment on aluminium intoxication was evaluated. Methods. Rats were exposed to aluminium chloride (AlCl3) for 60 days. Simvastatin (10 mg/kg/p.o.) and rivastigmine (1 mg/kg/p.o.) were administered daily prior to AlCl3. Behavioral parameters were assessed using Morris water maze test and actophotometer followed by biochemical investigations, namely, acetylcholinesterase (AChE) activity, TNF-α level, antioxidant enzymes (GSH, catalase), lipid peroxidation, and nitrite level in hippocampus and frontal cortex. Triglycerides, total cholesterol, LDL, and HDL levels in serum were also determined. Key Findings. Simvastatin treatment improved cognitive function and locomotor activity in rats. Simvastatin reversed hyperlipidemia and significantly rectified the deleterious effect of AlCl3 on AChE activity. Further, in hippocampus and frontal cortex, aluminium-induced elevation in nitrite and TNF-α and reduction in antioxidant enzymes were inhibited by simvastatin. Conclusion. To conclude, the present study suggests that simvastatin per se protects the neurons in hippocampus and frontal cortex from AlCl3, an environmental toxin.

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Modulatory role of simvastatin against aluminium chloride-induced behavioural and biochemical changes in rats.

Objective

Literature favours the in vitro neuroprotective role of caffeic acid, a naturally derived polyphenolic compound. This study was aimed to investigate the role of caffeic acid in experimental model of Alzheimer's disease.



Methods

Firstly, caffeic acid was tested for in vitro anticholinesterase potential using rat brain homogenate. Later, in vivo antidementia activity of caffeic acid was assessed against aluminium chloride (AlCl3)-induced dementia in rats. Behavioural (Morris water maze test) and brain biochemical parameters (acetylcholinesterase (AChE), catalase, glutathione-S-transferase (GST) activity, glutathione (GSH) and nitrite levels) were assessed to correlate the cognitive function with cholinergic transmission and oxidative stress.



Key findings

Rats administered with caffeic acid showed improved cognitive function in Morris water maze test. The antidementia activity of caffeic acid was confirmed by the reduction in brain AChE activity and nitrite levels. Further, caffeic acid corrected the diminished level of antioxidant enzymes such as catalase, GSH and GST in brain.



Conclusion

These findings suggest the antidementia activity of caffeic acid against AlCl3-induced dementia in rats. The outcome of present study offers a wider scope to screen caffeic acid against neurodegeneration associated disorders.

Jayesh Mudgal

Papers

COVID-19: Emergence, Spread, Possible Treatments, and Global Burden

Antidiabetic, antihyperlipidemic and antioxidant effects of the flavonoid rich fraction of Pilea microphylla (L.) in high fat diet/streptozotocin-induced diabetes in mice.

Modulatory role of simvastatin against aluminium chloride-induced behavioural and biochemical changes in rats.

Impact of caffeic acid on aluminium chloride-induced dementia in rats

Anti-inflammatory activity of Terminalia paniculata bark extract against acute and chronic inflammation in rats