Trace Elements Zinc and Selenium: Their Significance in the Conditions of the Covid-19 Pandemic

Within the conditions of the ongoing COVID-19 pandemic, when many questions regarding prevention and treatment strategies remain unsolved and the search for the best antiviral agents is underway, attention should be paid to the role of trace elements zinc and selenium in increasing the body's resistance to viral infections and their direct antiviral activity against SARS-CoV-2. Experimental data show that trace elements zinc and selenium not only actthrough regulating the immune response at all levels of humoral and cellular immunity, but also can play a significant role in adjuvant therapy for viral diseases. This is especially relevant in the case of COVID-19. Studies of the direct antiviral effect of these micro-elements testify to its 3 main ways to SARS-Cov-2: I - counteraction to virus replication and its transcription through: (i) their covalent binding to the SH-group of the cysteine of the main protease M(Pro) of the virus;(ii) inhibition of its RNA polymerase activity by zinc;II - preventing the penetration of the virus into cells due to blocking SH-groups of protein disulfide isomerase (RDI) of the protein of its spikes (peplomers);III - decreasing the adsorption capacity of the virus due to the blocking of the electrostatic interaction of SARS-CoV-2 peplomers and angiotensin-converting enzyme (ACE-2) in ultra-low, uncharacteristic oxidation states (Zn+1and Se-2). The intensity of the antiviral action of these trace elements may depend on their chemical form. It was found that zinc citrate (a five-membered complex of zinc with citric acid) and monoselenium citric acid obtained with the help of nanotechnology have a greater intensity of action and higher chemical purity. Taking into account the immunostimulating and direct antiviral effect of zinc and selenium, their use in the form of pharmaceuticals and dietary supplements should be considered as adjunctive therapy for SARS-CoV-2 in patients, or as a preventive strategy for uninfected people from risk groups during the spread of COVID-19.Copyright © Publisher PH <<Akademperiodyka>> of the NAS of Ukraine, 2023.

The Effect of FOXP3+Regulatory T Cells on Infectious and Inflammatory Diseases

CD4+CD25+FOXP3+regulatory T cells (Tregs) contribute to the maintenance of immune homeostasis and tolerance in the body. The expression levels and functional stability of FOXP3 control the function and plasticity of Tregs. Tregs critically impact infectious diseases, especially by regulating the threshold of immune responses to pathogenic microorganisms. The functional regulatory mechanism and cell-specific surface markers of Tregs in different tissues and inflammatory microenvironments have been investigated in depth, which can provide novel ideas and strategies for immunotherapies targeting infectious diseases.Copyright © 2021. All rights reserved.

DYNAMICS IN MATURATION OF SARS-CoV-2 RBD-SPECIFIC IgG ANTIBODY AVIDITY DEPENDING ON IMMUNIZATION TIMEFRAME AND TYPE.

The aim is to examine dynamics of avidity maturation of IgG antibodies against SARS-CoV-2 RBD depending on the type of immunization (vaccination or infection), as well as on the duration and frequency of immunization. Materials and methods. The study was performed on two sample cohorts collected at two time points during COVID-19 pandemic. The first cohort (group No. 1) consisted of 87 samples of blood sera obtained from COVID-19 convalescents in the period from March to September 2020. The second cohort included 204 samples obtained in September 2021 from two patient groups. Group No. 2 (n = 64) - patients immunized with a full course of Gam-Covid-Vac, group No. 3 (n = 140) - COVID-19 convalescent patients and subjects vaccinated with Gam-Covid-Vac ("hybrid immunity"). Results and conclusion. The dynamics of avidity maturation for SARS-CoV-2 RBD IgG antibodies depending on the method and frequency of immunization, showed that the most effective immunity was formed in COVID-19 convalescent patients and subjects vaccinated with a full course of Gam-Covid-Vac. The "hybrid" immunity showed not only a significantly higher (compared with groups No. 1 and No. 2) level of IgG antibodies (median 228 BAU/ml vs 75 or 119 BAU/ml, p < 0.001), but also a higher level of avidity (IA 90.5% vs 54.5 and 76.6, respectively, p < 0.001, 4M urea). In the test for assessing the avidity index with the denaturing agent 8M urea in patients with "hybrid immunity", the median level of IA was 25% versus 14.8% and 16% in COVID-19 convalescents and vaccinated subjects (p < 0.001), only in 8 patients IA was higher than 50%. While comparing a single infection of COVID-19 with a full course of Gam-Covid-Vac, it was shown that vaccination leads to higher IgG levels (median values in groups 119 and 75 BAU/ml, p < 0.001) and to a higher avidity index (median 76.6% vs 54.5%). Thus, the more rapid induction of high-avidity antibodies was in vaccinated individuals at early stages of immunization (up to 4 months), during the period when IgG avidity maturation has not yet been completed. Our results showed that during this period vaccination leads to production of antibodies with avidity index at median level of 82% versus 36% in COVID-19 convalescents at similar time point.Copyright © 2023 Saint Petersburg Pasteur Institute. All rights reserved.

Development of a Lymphoid Organ-Chip to Evaluate Covid Vaccine Boosting Strategies

Background: Secondary lymphoid organs provide the adequate microenvironment for the development of antigen (Ag)-specific immune responses. The tight collaboration between CD4+ T cells and B cells in germinal centers is crucial to shape B cell fate and optimize antibody maturation. Dissecting these immune interactions remains challenging in humans, and animal models do not always recapitulate human physiology. To address this issue, we developed an in vitro 3D model of a human lymphoid organ. The model relies on a microfluidic device, enabling primary human cells to self-organize in an extracellular matrix (ECM) under continuous fluid perfusion. We applied this Lymphoid Organ-Chip (LO chip) system to the analysis of B cell recall responses to SARS-CoV-2 antigens. Method(s): We used a two-channel microfluidic Chip S1 from Emulate, where the top channel is perfused with antigen (spike protein or SARS-CoV-2 mRNA vaccine), while the bottom channel contains PBMC (n = 14 independent donors) seeded at high-density in a collagen-based ECM. Immune cell division and cluster formation were monitored by confocal imaging, plasmablast differentiation and spike-specific B cell amplification by flow cytometry, antibody secretion by a cell-based binding assay (S-flow). Result(s): Chip perfusion with the SARS-CoV-2 spike protein for 6 days resulted in the induction CD38hiCD27hi plasmablast maturation compared to an irrelevant BSA protein (P< 0.0001). Using fluorescent spike as a probe, we observed a strong amplification of spike-specific B cell (from 3.7 to 140-fold increase). In line with this rapid memory B cell response, spike-specific antibodies production could be detected as early as day 6 of culture. Spike perfusion also induced CD4+ T cell activation (CD38+ ICOS+), which correlated with the level of B cell maturation. The magnitude of specific B cell amplification in the LO chip was higher than in 2D and 3D static cultures at day 6, showing the added value of 3D perfused culture for the induction of recall responses. Interestingly, the perfusion of mRNA-based SARS-CoV-2 vaccines also led to strong B cell maturation and specific B cell amplification, indicating that mRNA-derived spike could be expressed and efficiently presented in the LO chip. Conclusion(s): We developed a versatile Lymphoid Organ-Chip model suitable for the rapid evaluation of B cell recall responses. The model is responsive to protein and mRNA-encoded antigens, highlighting its potential in the evaluation of SARS-CoV-2 vaccine boosting strategies.

SARS-CoV-2 antibody avidity responses in natural infection and vaccination

Background: In ongoing SARS CoV-2 pandemic, understanding antibody responses have played a key role in measuring extent of exposure, protection from reinfection, vaccine efficacy and serodiagnosis. Antibody avidity is total binding strength of immunoglobulin G (IgG) toward its target epitope. High antibody avidity has been correlated with effective neutralization of the SARSCoV-2 virus. However, the data on avidity responses against COVID-19 infection and vaccination are limited. Objective(s): To understand the avidity responses among sera of naturally infected, recovered COVID-19 patients;naive Covaxin, Covishield vaccinees and breakthrough infections. Material(s) and Method(s): In this study, we utilized an in-house developed SARS-CoV-2 anti-spike receptor binding domain (SRBD) IgG ELISA to optimize the avidity assay. A panel of anti-SARS-CoV- 2 SRBD IgG positive serum samples were treated with known concentration of a chaotropic agent (urea) for disruption of the noncovalent interactions of the antigen-antibody complex. This disruption causes low avidity antibodies to dissociate which gives the percentage of high avidity antibodies present in a serum sample. Additionally, the optimized assay was used to understand the avidity responses among sera belonging to individuals naturally infected and recovered after COVID-19, naive Covaxin and Covishield vaccinees;followed by breakthrough infections. Result(s) and Conclusion(s): The anti-SRBD avidity progressively elevated over a period of twelve months. Moreover, overall antibody avidity responses were similar in the case of natural infection and naive two doses of Covaxin and Covishield vaccinated individuals. However, avidity responses were high among individuals with a breakthrough infection as compared to naive vaccinees.

Sirna-A Potential Therapy for Covid-19 Infection

Background: The deadly virus COVID-19 has affected more than 1 crore people and claimed more than 5 lakh lives worldwide according to the World health organization. Though there are numerous treatment modalities available including anti-bacterials, antivirals, vaccines etc., none of them can be considered as effective cure for SARS CoV-2 virus as they are mostly non-specific in action. Aim(s): siRNA therapy can be considered as a significant treatment modality due to its specificity in action. The aim of this review is to explore siRNA as a potential treatment strategy for the treatment of COVID-19. Material(s) and Method(s): In this review we shall explore the targets of siRNA therapy which includes viral RNA-dependent RNA polymerase, helicase, protease and nucleoprotein N. siRNA related patents provide solutions for novel RNAi techniques, high expense of chemically synthetic siRNA, techniques for restraining SARS-CoV by disturbing RNA etc., siRNA-based drug delivery systems and limitations of nanocarrier delivery system were reviewed. siRNA is a gene silencer that targets highly conserved sequences which codes for protease 3CL (nsp5) and viral helicase (from 16-18 kbp). Conclusion(s): Thus, siRNA-based therapy is considered highly efficacious as it can hit the highly conserved regions of SARS-CoV-2 RNA.Copyright © 2023, Advanced Scientific Research. All rights reserved.

Embryology and Clinical Development of the Human Olfactory System

The olfactory system is unique as a special sensory system in its developmental neuroanatomy and function. Neonatal olfactory reflexes can be detected in the fetus from 30 weeks gestation and can be tested in term and preterm neonates and older children. Most efferent axons from the olfactory bulb terminate in the anterior olfactory nucleus within the olfactory tract, with secondary projections to the amygdala, hypothalamus, hippocampus, and entorhinal cortex (parahippocampal gyrus), with tertiary projections also to the insula and other cortical regions. The olfactory bulb and tract incorporate an intrinsic thalamic equivalent. The olfactory bulb may be primary in generating olfactory auras in some cases of temporal lobe epilepsy. Developmental malformations may involve the olfactory bulb and tract, isolated or as part of complex cerebral malformations and genetic syndromes. Primary neural tumors may arise in the olfactory bulb or nerve. Impaired olfaction occurs in neonatal hypoxic/ischemic and some metabolic encephalopathies. Loss of sense of smell are early symptoms in some neurodegenerative diseases and in some viral respiratory diseases including coronavirus disease 2019. Testing cranial nerve I is easy and reliable at all ages, and is recommended in selected neonates with suspected brain malformations or encephalopathy.

Increased frequency of central precocious puberty during the coronavirus disease (COVID-19) pandemic at a single center in the Osaka Metropolitan Area of Japan

As environmental factors are known to affect the timing of puberty, self-isolation during the coronavirus disease (COVID-19) pandemic may affect the incidence of central precocious puberty (CPP). This study aimed to evaluate the frequency of CPP during the COVID-19 pandemic at a single center in the Osaka metropolitan area of Japan. We retrospectively analyzed the annual frequency of CPP occurrence before and after the first declaration of COVID-19 state of emergency in Japan at our hospital. We performed an interrupted time-series analysis to investigate the frequency of patients with CPP at our hospital from 2016 to 2021. There was a significant increase in the frequency of patients with CPP before and after the state of emergency declaration, both overall and among females. However, there was no significant increase in the number of males. There were no significant differences in the clinical, auxological, and endocrinological features between those diagnosed before and after the state of emergency. Overall, the frequency of CPP significantly increased during the COVID-19 pandemic at a single center in the Osaka metropolitan area of Japan.

DYNAMICS IN MATURATION OF SARS-CoV-2 RBD-SPECIFIC IgG ANTIBODY AVIDITY DEPENDING ON IMMUNIZATION TIMEFRAME AND TYPE

The aim is to examine dynamics of avidity maturation of IgG antibodies against SARS-CoV-2 RBD depending on the type of immunization (vaccination or infection), as well as on the duration and frequency of immunization. Materials and methods. The study was performed on two sample cohorts collected at two time points during COVID-19 pandemic. The first cohort (group No. 1) consisted of 87 samples of blood sera obtained from COVID-19 convalescents in the period from March to September 2020. The second cohort included 204 samples obtained in September 2021 from two patient groups. Group No. 2 (n = 64) — patients immunized with a full course of Gam-Covid-Vac, group No. 3 (n = 140) — COVID-19 convalescent patients and subjects vaccinated with Gam-Covid-Vac ("hybrid immunity”). Results and conclusion. The dynamics of avidity maturation for SARS-CoV-2 RBD IgG antibodies depending on the method and frequency of immunization, showed that the most effective immunity was formed in COVID-19 convalescent patients and subjects vaccinated with a full course of Gam-Covid-Vac. The "hybrid” immunity showed not only a significantly higher (compared with groups No. 1 and No. 2) level of IgG antibodies (median 228 BAU/ml vs 75 or 119 BAU/ml, p < 0.001), but also a higher level of avidity (IA 90.5% vs 54.5 and 76.6, respectively, p < 0.001, 4M urea). In the test for assessing the avidity index with the denaturing agent 8M urea in patients with "hybrid immunity”, the median level of IA was 25% versus 14.8% and 16% in COVID-19 convalescents and vaccinated subjects (p < 0.001), only in 8 patients IA was higher than 50%. While comparing a single infection of COVID-19 with a full course of Gam-Covid-Vac, it was shown that vaccination leads to higher IgG levels (median values in groups 119 and 75 BAU/ml, p < 0.001) and to a higher avidity index (median 76.6% vs 54.5%). Thus, the more rapid induction of high-avidity antibodies was in vaccinated individuals at early stages of immunization (up to 4 months), during the period when IgG avidity maturation has not yet been completed. Our results showed that during this period vaccination leads to production of antibodies with avidity index at median level of 82% versus 36% in COVID-19 convalescents at similar time point. © 2023 Saint Petersburg Pasteur Institute. All rights reserved.

The Challenge Of Covid19 In The Management Of Vascular Access For Hemodialysis In An Universitary Hospital.

INTRODUCTION: Chronic kidney disease prevalence has been increasing worldwide, with an increasing need to deliver an effective treatment. During the first months of the coronavirus disease 2019 (COVID-19) pandemic healthcare systems around the world were under stress. Therefore, the aim of this study is to report a single center experience with arteriovenous fistula (AVF) creation while also evaluating the impact of COVID-19. METHODS: Procedures for AVF creation in a tertiary hospital between March 2017 and December 2020 were included in this study and their case records were retrospectively analyzed and data retrieved. RESULTS: A total of 582 procedures were performed and a total of 568 accesses were created (506 being made pre-COVID onset and 62 post-COVID onset). The period between the referral to the vascular surgery consultation was significantly longer for the COVID group [18 (23) days vs 28 (44) days; p<0,001] while the period between the consultation to the surgery was significantly shorter [76 (77) days vs 40 (57) days; p<0,001]. This resulted in significantly less time between referral to surgery in the COVID group [103 (77) days vs 88 (55) days; p=0,008]. CONCLUSION: The ability of hospitals to adapt their resources was paramount to mitigate COVID impact. In the institution where the study took place, the time from referral to consultation was increased significantly during the first months of COVID but the time from consultation to surgery was significantly reduced. Overall, these results show that there was a successful effort to expedite the creation of a vascular access.

Vancomycin-Induced Maturation Arrest with Reactive Promyelocyte Proliferation: A Diagnostic and Therapeutic Challenge.

Drug-induced leukopenia is a diagnostic and therapeutic challenge. A detailed clinical history is a must to come to a right diagnosis. Certain drugs are known to cause bone marrow suppression, leukopenia, myeloid maturation arrest, and reactive promyelocyte proliferation. Here, we report an unusual case of vancomycin-induced maturation arrest with marked promyelocyte proliferation in a 47-year-old male patient who was being treated for novel coronavirus disease 2019 (COVID-19) infection. Most times, this reactive promyelocyte proliferation is confused with neoplastic promyelocytes, leading to incorrect diagnosis and management.

Maternal and Fetal Effects of COVID-19 Virus on a Complicated Triplet Pregnancy: a Case Report

Background: Coronavirus disease 2019 (COVLD-19), the global pandemic that has spread throughout the world, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the limited scientific evidence on the manifestations and potential impact of this virus on pregnancy, we decided to report this case. Case presentation: The patient was a 38 year-old Iranian woman with a triplet pregnancy and a history of primary infertility, as well as hypothyroidism and gestational diabetes. She was hospitalized at 29 weeks and 2 days gestational age due to elevated liver enzymes, and finally, based on a probable diagnosis of gestational cholestasis, she was treated with ursodeoxycholic acid. On the first day of hospitalization, sonography was performed, which showed that biophysical scores and amniotic fluid were normal in all three fetuses, with normal Doppler findings in two fetuses and increased umbilical artery resistance (pulsatility index [PI] > 95%) in one fetus. On day 4 of hospitalization, she developed fever, cough and myalgia, and her COVID-19 test was positive. Despite mild maternal symptoms, exacerbated placental insufficiency occurred in two of the fetuses leading to the rapid development of absent umbilical artery end-diastolic flow. Finally, 6 days later, the patient underwent cesarean section due to rapid exacerbation of placental insufficiency and declining biophysical score in two of the fetuses. Nasopharyngeal swab COVID-19 tests were negative for the first and third babies and positive for the second baby. The first and third babies died 3 and 13 days after birth, respectively, due to collapsed white lung and sepsis. The second baby was discharged in good general condition. The mother was discharged 3 days after cesarean section. She had no fever at the time of discharge and was also in good general condition. Conclusion(s): This was a complicated triplet pregnancy, in which, after maternal infection with COVID-19, despite mild maternal symptoms, exacerbated placental insufficiency occurred in two of the fetuses, and the third fetus had a positive COVID-19 test after birth. Therefore, in cases of pregnancy with COVID-19 infection, in addition to managing the mother, it seems that physicians would be wise to also give special attention to the possibility of acute placental insufficiency and subsequent fetal hypoxia, and also the probability of vertical transmission.Copyright © 2022 Goldstein and Associates. All rights reserved.

An Automated Patient Bed Cleaner Using UV Rays

Coronavirus (COVID-19) is an infectious illness due to serious respiratory trouble. It is impacted numerous humans and has asserted the living expectancy of a greater number of persons from all over the planet. The maturation period of this virus, on typically about 5-6 days but it might also be up to 2 weeks. Throughout this period, the individual may not feel any indications but could still be transmissible. A person could develop this disease if he/ she inhales the virus while a diseased person/ virus carrier within close vicinity sneezes or coughs otherwise tapping an infected place in addition to afterward again his/ her eyes, nose or mouth. To prevent this, the region of the COVID-19 patient must be decontaminated with virucidal disinfectants, such as and 0.05% sodium hypochlorite (NaClO) and ethanol-based products (at least 70%) an optional technique used is UV light sterilization. Ultraviolet (UV) sterilization technology is used to help reduce micro-organisms that can remain on surfaces after basic sprinkling to the minimum amount. The proposed work has established an UV robot or UV bot to perform decontamination in an operating room or in-patients room. Three 19.3-watt UV lights are positioned in a 360-degree circle on the UV bot platform. It used an integrated system based on a microprocessor and a metal frame to aid in navigation in a fixed path to avoid barriers. In addition, a sanitizer dispenser is also included to clean the viral organisms, which is spread through the water droplets of the patient. © 2022 IEEE.

Antigen presentation dynamics shape the antibody response to variants like SARS-CoV-2 Omicron after multiple vaccinations with the original strain.

The Omicron variant of SARS-CoV-2 is not effectively neutralized by most antibodies elicited by two doses of mRNA vaccines, but a third dose increases anti-Omicron neutralizing antibodies. We reveal mechanisms underlying this observation by combining computational modeling with data from vaccinated humans. After the first dose, limited antigen availability in germinal centers (GCs) results in a response dominated by B cells that target immunodominant epitopes that are mutated in an Omicron-like variant. After the second dose, these memory cells expand and differentiate into plasma cells that secrete antibodies that are thus ineffective for such variants. However, these pre-existing antigen-specific antibodies transport antigen efficiently to secondary GCs. They also partially mask immunodominant epitopes. Enhanced antigen availability and epitope masking in secondary GCs together result in generation of memory B cells that target subdominant epitopes that are less mutated in Omicron. The third dose expands these cells and boosts anti-variant neutralizing antibodies.

Discovery and Optimization of Neutralizing SARS-CoV-2 Antibodies Using ALTHEA Gold Plus Libraries™.

We recently reported the isolation and characterization of anti-SARS-CoV-2 antibodies from a phage display library built with the VH repertoire of a convalescent COVID-19 patient, paired with four naïve synthetic VL libraries. One of the antibodies, called IgG-A7, neutralized the Wuhan, Delta (B.1.617.2) and Omicron (B.1.1.529) strains in authentic neutralization tests (PRNT). It also protected 100% transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE-2) from SARS-CoV-2 infection. In this study, the four synthetic VL libraries were combined with the semi-synthetic VH repertoire of ALTHEA Gold Libraries™ to generate a set of fully naïve, general-purpose, libraries called ALTHEA Gold Plus Libraries™. Three out of 24 specific clones for the RBD isolated from the libraries, with affinity in the low nanomolar range and sub-optimal in vitro neutralization in PRNT, were affinity optimized via a method called "Rapid Affinity Maturation" (RAM). The final molecules reached sub-nanomolar neutralization potency, slightly superior to IgG-A7, while the developability profile over the parental molecules was improved. These results demonstrate that general-purpose libraries are a valuable source of potent neutralizing antibodies. Importantly, since general-purpose libraries are "ready-to-use", it could expedite isolation of antibodies for rapidly evolving viruses such as SARS-CoV-2.

Antibody Avidity Maturation Following Recovery From Infection or the Booster Vaccination Grants Breadth of SARS-CoV-2 Neutralizing Capacity.

BACKGROUND: Cross-neutralizing capacity of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is important in mitigating (re-)exposures. Role of antibody maturation, the process whereby selection of higher affinity antibodies augments host immunity, to determine SARS-CoV-2 neutralizing capacity was investigated. METHODS: Sera from SARS-CoV-2 convalescents at 2, 6, or 10 months postrecovery, and BNT162b2 vaccine recipients at 3 or 25 weeks postvaccination, were analyzed. Anti-spike IgG avidity was measured in urea-treated ELISAs. Neutralizing capacity was assessed by surrogate neutralization assays. Fold change between variant and wild-type neutralization inferred the breadth of neutralizing capacity. RESULTS: Compared with early-convalescent, avidity indices of late-convalescent sera were significantly higher (median, 37.7 [interquartile range 28.4-45.1] vs 64.9 [57.5-71.5], P < .0001). Urea-resistant, high-avidity IgG best predicted neutralizing capacity (Spearman r = 0.49 vs 0.67 [wild-type]; 0.18-0.52 vs 0.48-0.83 [variants]). Higher-avidity convalescent sera better cross-neutralized SARS-CoV-2 variants (P < .001 [Alpha]; P < .01 [Delta and Omicron]). Vaccinees only experienced meaningful avidity maturation following the booster dose, exhibiting rather limited cross-neutralizing capacity at week 25. CONCLUSIONS: Avidity maturation was progressive beyond acute recovery from infection, or became apparent after the booster vaccine dose, granting broader anti-SARS-CoV-2 neutralizing capacity. Understanding the maturation kinetics of the 2 building blocks of anti-SARS-CoV-2 humoral immunity is crucial.

Exploring the role of framework mutations in enabling breadth of a cross-reactive antibody (CR3022) against the SARS-CoV-2 RBD and its variants of concern.

Cross-reactive and broadly neutralizing antibodies against surface proteins of diverse strains of rapidly evolving viral pathogens like SARS-CoV-2 can prevent infection and therefore are crucial for the development of effective universal vaccines. While antibodies typically incorporate mutations in their complementarity determining regions during affinity maturation, mutations in the framework regions have been reported as players in determining properties of broadly neutralizing antibodies against HIV and the Influenza virus. We propose an increase in the cross-reactive potential of CR3022 against the emerging SARS- CoV-2 variants of concern through enhanced conformational flexibility. In this study, we use molecular dynamics simulations, in silico mutagenesis, structural modeling, and docking to explore the role of light chain FWR mutations in CR3022, a SARS-CoV anti-spike (S)-protein antibody cross-reactive to the S-protein receptor binding domain of SARS-CoV-2. Our study shows that single substitutions in the light chain framework region of CR3022 with conserved epitopes across SARS-CoV strains allow targeting of diverse antibody epitope footprints that align with the epitopes of recently-categorized neutralizing antibody classes while enabling binding to more than one strain of SARS-CoV-2. Our study has implications for rapid and evolution-based engineering of broadly neutralizing antibodies and reaffirms the role of framework mutations in effective change of antibody orientation and conformation via improved flexibility.Communicated by Ramaswamy H. Sarma.

Multidisciplinary management of a quickly growing pediatric atypical Spitz nevus, mimicking melanoma, during the COVID-19 pandemic

Spitzoid melanoma is very rare tumour in the pediatric population, with clinical and non-uniform behaviour, different from adult melanoma [1]. It can be difficult to differentiate an atypical Spitz nevus from a Spitzoid melanoma, resulting in diagnostic problems. In addition, in our clinical case, the COVID-19pandemiccaused significant delays both in the diagnosis and in the surgical treatment of our patient. We present the clinical case of a 4-year-old child suffering from a localized polypoid cutaneous neoformation on the dorsum of the left hand, which started immediately before the lockdown and steadily increased during the COVID-19 pandemic. After a general clinical framing, the child underwent an excisional biopsy at our Department of Plastic and Reconstructive Surgery, at the Policlinico of Foggia. Subsequently, two independent anatomic pathology groups examined the specimen. Definitive diagnosis was made only after careful genetic analysis in combination with supporting histological and immunohistochemical examinations. This clinical case shows how during the pandemic we have been facing advanced forms of tumours, compared to the previous period and highlight show an interdisciplinary and multicenter collaboration allowed a quick diagnosis of certainty, demonstrating the utility of molecular pathology as a fundamental aid in clinical/surgical practice. © 2022 The Authors

Adolescent brain maturation and the neuropathological effects of binge drinking: A critical review.

Adolescence is a transitional stage marked by continued brain development. This period is accompanied by physical and neurochemical modifications in the shape and function of the hippocampus, prefrontal cortex, and other limbic system structures. Brain maturation during adolescence, which is typically governed by intrinsic factors, can be dramatically altered by environmental influences such as drugs and alcohol. Unlike many other addictive substances, binge drinking is very common and normative among teenagers and young adults. This repeated pattern of excessive alcohol consumption in adolescents has been shown to cause behavioral changes and neurocognitive impairments that include increased anxiety, risky decision-making, and learning deficits, which could lead to the development of alcohol use disorder (AUD). This manuscript highlights factors that lead to adolescent binge drinking, discusses maturational changes that occur in an adolescent's brain, and then evaluates the effect of adolescent alcohol consumption on brain structure, function, and neurocognitive abilities in both human studies and animal models. The impact of gender/sex and COVID-19 are briefly discussed. Understanding the factors that promote the onset of adolescent binge drinking and its undesirable consequences could serve as a catalyst for developing therapeutic agents that would decrease or eradicate the damaging effects of alcohol on an adolescent brain.