Changes in mood instability, episode and symptom density among bipolar patients living under strict lockdown: insights from a third-world country with a never-ending quarantine

Introduction: During 2020, measures to contain the global health crisis caused by the coronavirus disease (COVID-19) included social confinement, with the consequent interruption of normal activities. In Argentina, particularly, the confinement was one of the longest and strictest in the world. Within this context, the current study was aimed at exploring changes in illness severity among bipolar disorder (BD) patients living under strict lockdown. Method: Ninety BD outpatients under naturalistic conditions were followed from March (when the lockdown measures were imposed in our country) to September 2020. Thirteen variables of illness severity were assessed during this period, which were compared with the results obtained during the same 28-week period of the previous year (i.e., from March to September 2019). Results: No significant differences were observed between periods in the rate of patients that remained euthymic during the entire follow-up (28.9% before the pandemic versus 41.1% during the pandemic, p = 0.09). For most variables, no significant differences were observed. A small decrease was found in depressive episode density (from 0.39 ± 0.74 to 0.22 ± 0.63, p = 0.003). Symptom and episode density during the pre-pandemic period and the number of previous depressive episodes at study entry predicted worse outcomes during the pandemic. Conclusion: Findings from a large sample of BD individuals indicate that illness severity variables have not worsened as a result of the lockdown. In addition, our findings suggest an important degree of positive coping among BD patients and emphasize the effectiveness of telepsychiatry in treating this clinical population.

A crystallographic snapshot of SARS-CoV-2 main protease maturation process

SARS-CoV-2 is the causative agent of COVID-19. The dimeric form of the viral Mpro is responsible for the cleavage of the viral polyprotein in 11 sites, including its own N- and C-terminus. The lack of structural information for intermediary forms of Mpro is a setback for the understanding its self-maturation process. Herein, we used X-ray crystallography combined with biochemical data to characterize multiple forms of SARS-CoV-2 Mpro. For the immature form, we show that extra N-terminal residues caused conformational changes in the positioning of domainthree over the active site, hampering the dimerization and diminishing its activity. We propose that this form preludes the cis and trans-cleavage of N-terminal residues. Using fragment screening, we probe new cavities in this form which can be used to guide therapeutic development. Furthermore, we characterized a serine site-directed mutant of the Mpro bound to its endogenous Nand C-terminal residues during dimeric association stage of the maturation process. We suggest this form is a transitional state during the C-terminal trans-cleavage. This data sheds light in the structural modifications of the SARS-CoV-2 main protease during its self-maturation process.

Graphene BioFET sensors for SARS-CoV-2 detection: a multiscale simulation approach.

Biological Field-Effect Transistors (BioFETs) have already demonstrated enormous potential for detecting minute amounts of ions and molecules. The use of two-dimensional (2D) materials has been shown to boost their performance and to enable the design of new applications. This combination deserves special interest in the current pandemic caused by the SARS-CoV-2 virus which demands fast, reliable and cheap detection methods. However, in spite of the experimental advances, there is a lack of a comprehensive and in-depth computational approach to capture the mechanisms underlying the sensor behaviour. Here, we present a multiscale platform that combines detailed atomic models of the molecules with mesoscopic device-level simulations. The fine-level description exploited in this approach accounts for the charge distribution of the receptor, its reconfiguration when the target binds to it, and the consequences in terms of sensitivity on the transduction mechanism. The results encourage the further exploration of improved sensor designs and 2D materials combined with diverse receptors selected to achieve the desired specificity.

Stenosis of large lower limb arteries in a teenager after COVID-19 infection

The aim of the present study is to report a COVID-19 infection sequel in large lower limb arteries in adolescent. An 18-year-old female adolescent those two weeks after COVID- 19 she had severe pain in her right leg that limited her walking and was admitted to hospital. Upon admission, a clinical history and physical examination were performed and the absence of pulses in the femoral was detected. An angiotomography was requested, which revealed thrombosis in a portion of the external iliac artery, femoral, popliteal and tibial. She underwent an embolectomy that progressed well and is discharged from the hospital with anticoagulation using sodium warfarin. In outpatient follow-up, she underwent a control examination with arterial duplex of the right lower limb, eight months after the event, with a finding of stenosis greater than 50% of the diameter, suggesting an inflammatory process in the iliac femoral artery and a significant reduction in the diameter of the artery posterior tibial artery. The clinical evolution of post COVID-19 patients who had arterial thrombotic events should be monitored for possible sequelae that may occur.

[Adaptation of psychiatric practice in public and private mental health institutions of the City of Buenos Aires during the COVID-19 pandemic]

BACKGROUND: One of the most significant indirect impacts of the COVID-19 pandemic will be seen on the mental health of the population. On this study, we will take into account the adapting capacity that the most representative mental health services (MHS) of Buenos Aires (BA) City have had as to this new situation. METHODS: We designed an online survey including 10 self-administered closed questions, strictly anonymous. It has been sent to targeted professionals who work in public and private MHS of BA after 2 months of the beginning of the lockdown. RESULTS: We got 38 answers. 2 professionals rejected to answer. 34% belonged to private institutions and 66% to public ones. 81% of the total were able to implement online assistance but only 24% had been trained on how to treat patients in this context. 69% of the private and 12% of the public sector professionals informed to have been trained on telemedicine tools. 69% of the private and 36% of the public sector professionals informed to have prepared materials for the users on telemedicine resources. 68% mentioned that their service was properly organized. 40% of the public sector professionals may have been reassigned to work on tasks related to the pandemic. 40% of the total informed a reduced capacity of assistance. CONCLUSIONS: The MHS of BA may have been able to migrate their assistance to telemedicine, however we have noticed differences in the training levels. A better capacity of training on this modality might be needed.

Medical reasoning: Not sustained activation of neuronal circuits

Background and aims: For a physician, it is essential to extract relevant information from a patient's history and identify abnormal findings of the physical examination to select exams for an accurate diagnosis. We checked the performances of medical students in different steps of the clinical reasoning. Methods: Twenty-five medical students that finished the first two years of basic training, gave us written approval and were tested. We presented 3 different clinical cases: colon cancer (CC), pneumonia (Pn) and stroke (St). For each case, 4 findings of the history and 2 of the examination were informed. They had to choose 2 supplementary exams. Then, we asked which other 2 exams they would require. Finally, diagnosis was required. Results: For CC, 52% chose the blood count and 44% a scopy as the first exams. The other exams: scopy (32%) and blood count (28%). Diagnosis: CC (36%) and lower gastrointestinal hemorrhage (12%). For Pn, 92% chose Chest X-ray or tomography and 38% blood count. Further exams were: gasometry (54%) and blood count (29%). Diagnosis: Pn (54%) and COVID-19 (33%). For St, 79% chose Head tomography and 54% blood count. The other exams: blood glucose (37.5%) and electrolytes (29%). Diagnosis: St (88%) and brain tumor (4%). Conclusions: Our data show that, no matter the clinical case, the students strongly disagree the second set of exams they would ask to make a diagnosis. Data from the medical consultation can activate neuronal circuits on a standardized way at an initial step of the clinical reasoning, but that activation cannot be sustained.

A Crystallographic Snapshot of SARS-CoV-2 Main Protease Maturation Process.

SARS-CoV-2 is the causative agent of COVID-19. The dimeric form of the viral Mpro is responsible for the cleavage of the viral polyprotein in 11 sites, including its own N and C-terminus. The lack of structural information for intermediary forms of Mpro is a setback for the understanding its self-maturation process. Herein, we used X-ray crystallography combined with biochemical data to characterize multiple forms of SARS-CoV-2 Mpro. For the immature form, we show that extra N-terminal residues caused conformational changes in the positioning of domain-three over the active site, hampering the dimerization and diminishing its activity. We propose that this form preludes the cis and trans-cleavage of N-terminal residues. Using fragment screening, we probe new cavities in this form which can be used to guide therapeutic development. Furthermore, we characterized a serine site-directed mutant of the Mpro bound to its endogenous N and C-terminal residues during dimeric association stage of the maturation process. We suggest this form is a transitional state during the C-terminal trans-cleavage. This data sheds light in the structural modifications of the SARS-CoV-2 main protease during its self-maturation process.