Determining the Effect of KmtR Mutants, E101Q, H102Q, and H111Q on the Metal Binding Affinities

Mycobacterium tuberculosis is the second leading infectious killer after COVID-19. The bacteria utilizes several metal transport systems to help it survive in the host.With an increase in the number of multiresistant, extensively resistant and totally drug-resistant strains, the development of new therapeutic strategies that target other essential pathways in the bacteria is critical. The bacteria contain several metal transport systems which are necessary for its survival. Additionally, the bacteria has two metalloregulators that are associated with nickel and cobalt export, NmtR and KmtR. The focus of this research is on KmtR, which represses the expression of the genes, cdf (which encodes the export protein) and kmtR. The goal of our research is to identify the residues that are responsible for binding the cognate metals, nickel and cobalt, as well as the noncognate metal, zinc, to KmtR. Mutagenesis studies coupled with metal binding experiments will be used to determine how KmtR binds these metals. The E101Q, H102Q, and H111Q mutants, among others, have been made, expressed, and purified in our lab. Data obtained from Isothermal Titration Calorimetry determined that all three mutant proteins bind cobalt with nanomolar affinities and the H111Q mutant KmtR proteins binds cobalt an order of magnitude weaker than the other two mutant proteins. Research reported as supported fully by the RI Institutional Development Award (IDeA) Network for Biomedical Research Excellence (RI-INBRE) from the National Institute of General Medical Sciences of the National Institutes of Health under grant #P20GM103430.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Otolaryngology Conditions and Diseases in Migrants: The Experience of the PROTECT Project

Introduction: The number of migrants living in Europe is growing rapidly. The PROTECT project is a national study conducted among refugees and migrants in the Lazio region, Italy from February 2018 to September 2021 to evaluate their otolaryngological, dental, and ophthalmic health status. This article reports the results of this study with a special focus on otolaryngological conditions and diseases. Materials and methods: A total of 3023 participants were included in the project. Data on the participants' demographic factors, migration status, and otolaryngological history were collected using a questionnaire. Each patient underwent clinical ear, nose, and throat examination, and the main otolaryngological conditions and diseases were noted. Results: nearly two-thirds of participants were males (68.1%). The mean age was 31.6 +/- 13.1. Most of the participants were born in Nigeria, followed by Bangladesh, Pakistan, Somalia, Mali, and Gambia. The prevalence of chronic noise exposure was 5.2%. Unilateral hearing loss was reported by 6.5% of the subjects, and bilateral hearing loss by 3.6%. The most frequent symptoms reported in the questionnaire were snoring (10.4%), nasal obstruction (5.9%), vertigo (5.0%), otalgia (4.5%), and tinnitus (4.2%). At the clinical examination, the most frequent findings were nasal septum deviation (25.2%), ear wax (6.5%), hypertrophic palatine tonsils (5.3%), and tympanic membrane perforation (1.3%). Conclusions: the PROTECT project allowed for the evaluation of otolaryngological, dental, and ophthalmological conditions in over 3000 migrants, giving them the possibility to access specialist care.

Vitamin D and interferon-γ co-operate to increase the ACE-2 receptor expression in primary cultures of human thyroid cells.

BACKGROUND: A more severe course of COVID-19 was associated with low levels of Vitamin D (VitD). Moreover in vitro data showed that VitD up-regulates the mRNA of the Angiotensin Converting Enzyme 2 (ACE-2), the SARS-COV-2 receptor in different type of cells. ACE-2 is expressed in several type of tissues including thyroid cells, on which its mRNA was shown to be up-regulated by interferon-gamma (IFN-γ). The aim of the present study was to investigate if treatment with VitD alone or in combination with IFN-γ would increase ACE-2 both at mRNA and protein levels in primary cultures of human thyrocytes. MATERIALS AND METHODS: Primary thyroid cell cultures were treated with VitD and IFN-γ alone or in combination for 24 h. ACE-2 mRNA levels were measured by Real-time Polymerase Chain Reaction (RT-PCR). The presence of ACE-2 on thyroid cell membrane was assessed by immunocytochemistry basally and after the previous mentioned treatments. RESULTS: ACE-2 mRNA levels increased after treatment with VitD and IFN-γ alone. The combination treatment (VitD + IFN-γ) showed an additive increase of ACE-2-mRNA. Immunocytochemistry experiments showed ACE-2 protein on thyroid cells membrane. ACE-2 expression increased after treatment with VitD and IFN-γ alone and further increased by the combination treatment with VitD + IFN-γ. CONCLUSIONS: VitD would defend the body by SARS-COV2 both by regulating the host immune defense and by up-regulating of the expression of the ACE-2 receptor. The existence of a co-operation between VitD and IFN-γ demonstrated in other systems is supported also for ACE-2 up-regulation. These observations lead to an increased interest for the potential therapeutic benefits of VitD supplementation in COVID-19.

Otolaryngology adverse events following COVID-19 vaccines.

OBJECTIVE: Since the outbreak of COVID-19 pandemic, the international scientific community aimed at developing a vaccine to protect against the infection and prevent serious forms of the disease. To date, various adverse events of COVID-19 vaccines have been reported, mostly mild to moderate. MATERIALS AND METHODS: In this short communication, we reviewed available literature and described the most frequent otolaryngology adverse events reported after COVID-19 vaccination. RESULTS: The most frequent adverse events following COVID-19 vaccine described in the literature are represented by audiovestibular symptoms, such as tinnitus, sudden sensorineural hearing loss, vertigo, and dizziness. Other side effects include facial nerve palsy, epistaxis, and oral manifestations (lichen planus, bleeding, ulcers, and vesicles). CONCLUSIONS: COVID-19 vaccine is of utmost importance in limiting the spread of SARS-CoV-2. Otolaryngology-related side effects have been described, but none was severe or life threatening. The mechanisms underlying these effects are still mostly unknown.

Attention-based Gender Recognition on Masked Faces

Gender recognition from face images can be profitably used in several vertical markets, such as targeted advertising and cognitive robotics. However, in the last years, due to the COVID-19 pandemic, the unreliability of such systems when dealing with faces covered by a mask has emerged. In this paper, we propose a novel architecture based on attention layers and trained with a domain specific data augmentation technique for reliable gender recognition of masked faces. The proposed method has been experimentally evaluated on a huge dataset, namely VGGFace2-M, a masked version of the well known VGGFace2 dataset, and the achieved results confirm an improvement of around 4% with respect to traditional gender recognition algorithms, while preserving the performance on unmasked faces.

Evaluation of olfactory dysfunction persistence after COVID-19: a prospective study.

OBJECTIVE: Alterations of the olfactory function in patients affected by COVID-19 often have an early onset and a variable duration ranging from a few weeks to months. The aim of this study was to evaluate olfactory dysfunction persistence after recovery from COVID-19, and potential related clinical-demographic conditions. PATIENTS AND METHODS: A total of 76 patients recovered from COVID-19 from at least 20 days with olfactory dysfunction during the infection were included in the study. For the subjective evaluation of olfactory function, a visual analogic scale (VAS) was used. The objective evaluation was performed with the use of the Sniffin' Sticks test. RESULTS: Objective assessment of olfactory function revealed that 48 (63.16%) patients were found to be normosmic (TDI ≥ 30.5), 26 (34.21%) were hyposmic (TDI from 30.5 to 16.5) and two (2.63%) were anosmic (TDI ≤ 16.5) at the time of the evaluation. These results did not show a significant difference between subjective and objective tests (p = 0.45). Most patients recovered their sense of smell within the first two months after recovery while a portion (22.2%) still experienced olfactory alterations 4-6 months after SARS-CoV-2 infection. Patients who had not recovered their sense of smell had a significantly longer period of SARS-CoV-2 positivity compared to patients that fully recovered (36.07 ± 7.78 days vs. 29 ± 7.89 days; p = 0.04). CONCLUSIONS: Our results suggest that the duration of the infection negatively correlates with the recovery of olfactory function.

COVID-19 pandemic and days of absence from work in workers with flu-like symptoms in the City of Rome, Italy.

ABSTRACT: COVID-19 has dramatically affected working forces. We aim to report our occupational medicine service's experience in managing suspected COVID-19 cases during the pandemic through a retrospec-tive observational study. We compared the number of days employees were absent from work due to flu-like symptoms from March 2020 to February 2021 to the same period the previous year (2019-2020). Two hundred thirty-four patients (+47.2% compared to the previous year) who tested negative for SARS-CoV-2 reported flu-like symp-toms; the number of days of absence from work was 2812 (+190.2% compared to the previous year). On average, employees with flu-like symptoms lost 12.07 working days compared to 6.12 in the previous year (p<0.0001). In conclusion, in our sample COVID-19 has increased the number of working day loss. However, our approach proved to be important, especially during the first months of the pandemic, to limit SARS-CoV-2 spread in workplaces.

Managing Covid-19 crisis: The Locarno hospital “La Carità” as a relevant case in the Ticino's hospital system response to the pandemic

In Switzerland, Ticino was one of the Cantons most affected by the Covid-19 pandemic and the reconfiguration of its hospital system relied on the creation of Covid-centers. This paper analyzes how the hospital “La Carità” in Locarno (ODL), appointed as reference Covid-center at the cantonal level in mid-March, has reorganized itself, playing a central active role in the response of the Ticino hospital system. The analysis, based on semi-structured interviews administered to six key actors of the hospital management, shed light on the main success factors of the response to the emergency. In particular, case study indicates some important drivers: the EOC multisite hospital model, an agile and coordinated structure at the institutional and operational level (fostering both unity of command and flexibility), the importance of public-private cooperation in a context of network governance, the management according to a logic of learning by doing and the orientation toward managerial and operational innovation. Copyright © FrancoAngeli

Effects of COVID-19 pandemic on head and neck oncology activity: the experience of our University Hospital

OBJECTIVE: The COVID-19 pandemic has severely affected otolaryngology and head and neck activities, also involving diagnosis and treatment of patients with oncology diseases with consequent delays and tumor upstaging. The aim of this study was to describe the experience of our otolaryngology unit during the pandemic on patients with cancer of the head and neck, comparing data on anatomical site of origin and preferred treatment with pre-pandemic data. PATIENTS AND METHODS: This study retrospectively analyzed the clinical records of patients treated for oncology disorders of the head and neck in the Otolaryngology Unit of the Policlinico Umberto I, Sapienza University of Rome, between March 10, 2020, and March 9, 2021. Data were compared with the same period of the previous year (March 10, 2019 - March 9, 2020). RESULTS: During the pandemic, we treated 92 patients with malignant tumor of the head and neck, compared to 101 patients treated during the same period of 2019 (-8.91%). The most common anatomical sites of origin of the neoplasms were larynx, oral cavity, and oropharynx. Surgical approach was preferred in 57 patients (61.95%);non-surgical treatments were performed in 35 cases (38.05%). Compared to the same period of the previous year, we found a 12.90% decrease in the number of oncology patients undergoing surgery. while patients treated exclusively with non-surgical approaches increased by 18.42%. CONCLUSIONS: Despite the impact of COVID-19 on the activity of our otolaryngology unit and on the whole healthcare system, diagnostic and therapeutic procedures for patients affected by malignancy of head and neck region were only minimally impacted.

Ist Gesundheit Alles?

Can psychology be defined "only" as a health profession? The presence of psychology in health contexts is indispensable, but reducing it to this presence is inappropriate and impossible;in fact, "objects", "issues" and "contexts" relevant to health are not reducible to the health system and seem to require multidisciplinary and multisectoral approaches. Covid-19 makes it clear that a sectoral view is insufficient to address the devastating impact on society;Covid- 19 represents a challenge that seems to require a reorientation to a psychology which, while dutifully exercising an action to support individual traumas and frailties, cannot afford to reduce its presence and ability to intervene to. It is also along these problematic nuclei that a reterritorialization of psychology develops;in this way, through a not short process of revisiting the epistemological and methodological foundations of the practices and operationalities typical of the profession, psychology can assume a role of autonomous presence and influence in the system of health and social services. We therefore appeal to the Postgraduate Schools in Health Psychology to recognize themselves in the task of guiding this necessary transition towards a full transformative responsibility for psychology. © 2021 Franco Angeli Edizioni. All rights reserved.

Microencapsulated wharton jelly-derived adult mesenchymal stem cells as a potential new therapeutic tool for patients with covid-19 disease: An in vitro study

Background: The recent newly appeared Coronavirus disease (COVID-19), caused by an enveloped RNA virus named “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)”, is associated with severe respiratory morbidity and mortality. Recent studies have shown that lymphopenia and a cytokine mass release represent important pathogenic features, with clinical evidence of dyspnea and hypoxemia, often leading to acute respiratory distress syndrome (ARDS), in severely ill patients, with a high death toll. Currently, stem cells are actively being investigated for their potential use in many “untreatable” diseases. In this regard and in particular, Mesenchymal Stem Cells (MSC), due to their intrinsic features, including either ability to impact on regulation of the immune system, or association with both anti-viral and anti-inflammatory properties, or potential for differentiation into several cell lineages, have become a promising tool for cell and molecular-based therapies. On this background, we wished to explore whether human umbilical cord-derived mesenchymal stem cells (hUCMS) would represent a potential viable therapeutic approach for the management of critically ill COVID19 patients. Methods: We tested the hUCMS effects on peripheral blood mononuclear cell (PBMCs) retrieved from patients with COVID19 (Ethical Committee CEAS Umbria, Italy CER N°3658/20 7, May, 2020), both as free cell monolayers and after envelopment in sodium alginate microcapsules. Both cell systems, after priming with IFN-γ, proved able to produce several immu-nomodulatory molecules such as IDO1 and HLAG5, although only the microencapsulated hUCMS were associated with massive and dose-dependent production of these factors. Results: The microencapsulated hUCMS improved allo-suppression in mixed lymphocytes reactions (MLRs), while also blunting T helper 1 and T helper 17 responses, that are involved with the cytokine storm and greatly contribute to the patient death. Moreover, we observed that both free and microencapsulated hUCMS permitted 5 days survival of in vitro culture maintained PBMCs extracted from very ill patients. Conclusion: We have provided evidence that microencapsulated hUCMS in vitro, seem to represent a powerful tool to impact on several immune pathways, clearly deranged in COVID19 patients. Further study is necessary to begin in vivo assessment of this experimental system, upon determining both, the most appropriate time of the disease onset for intervention, and cell dosage/patient of our experimental product.

Staying tuned for post-COVID-19 syndrome: looking for new research to sniff out.

Post-COVID-19 syndrome was defined as a persistent and protracted illness, which follows acute COVID-19 infection. This condition continues for more than 12 weeks and cannot be attributed to other clinical situations. Researchers and clinicians are allied in unraveling the molecular pathogenetic mechanisms and the clinical development of this unexpected SARS-CoV-2 infectious evolution. Anosmia, dysgeusia, fatigue, dyspnea, and 'brain fog' are common symptoms observed in the Post-COVID-19 syndrome, depicting a multiorgan involvement associated with injuries involving mainly cardiovascular, pulmonary, musculoskeletal, and neuropsychiatric systems. This commentary analyzes the state of the art of Post-COVID-19 interdisciplinary studies, confirming that we are facing a truly intricate biomedicine story.

Treatment of cll relapsed/refractory patients in covid-19 pandemic: A real-life experience with venetoclax-rituximab combination in southern Italy

Background: Given the multifactorial immune defect characterizing chronic lymphocytic leukemia (CLL), it appears conceivable that these patients have risk factors that increase their likelihood of complications and death from COVID-19. Aims: To evaluate incidence and severity of COVID-19 cases in a well-defined cohort of patients with CLL receiving venetoclax-based combinations. Methods: We administered a survey to a cohort of CLL treating hematologists from hematological centers in southern Italy. Participants were asked: a) to indicate whether they had offered a test for detection of COVID-19 infection (mainly nasopharyngeal swabs) only to CLL patients who reported symptoms or universally;b) to provide information on the incidence of COVID-19 infection and its severity;c) to specify reasons of possible treatment modifications. The survey was restricted to relapsed-refractory (R/R) CLL patients treated from Feb 1st to Dec 31th 2020 with time-limited venetoclax/rituximab (VR) combination as recommended by MURANO protocol (venetoclax for up to 2 years plus rituximab for the first 6 months), within their clinical practice. Results: A specific questionnaire was sent to 30 CLL hematologists, but only 26 responded to all questions. We considered suitable for the present analysis the 24 questionnaires compiled by hematologists who declared to have treated at least one patient with VR combination in the observation period. Of those, 20.8% worked in academic hospitals. Overall, the survey allowed to collect data on 124 patients who were treated with VR combination. The median number of patients treated in each center was 5 (range,1-15).COVID-19 surveillance tests consisted of viral RNA reverse transcriptase PCR (RT-PCR) on nasopharyngeal swabs. Generally, a policy of universal SARS-CoV-2 testing to be performed on patients at different time-points of therapy was used. Most patients (83/124, 66.9%) were tested before beginning the ramp-up with venetoclax;moreover 66/124 (53.2%) were regularly tested before each rituximab infusion (Fig 1).Reasons for potential change of the schedule of treatment were also investigated. The survey revealed that adherence to treatment was relatively high (70.8%). Only 29.1% physicians modified the therapeutic program mainly because of grade 3 neutropenia. Changes consisted of transient interruption of venetoclax, reduction of doses, and delay of rituximab infusion.Only 2/124 patients (1.6%) had a symptomatic RT-PCR proven diagnosis of COVID-19 infection and required hospitalization. Both patients needed oxygen therapy and admission into an intensive care unit. Of those, 1 patient who was receiving VR combination at the time of COVID infection, eventually died. The second patient developed COVID-19 infection while receiving venetoclax monotherapy (after the VR combination period). He recovered from COVID-19 infection and after 21 days of treatment interruption, he was able to restart venetoclax. Summary/Conclusion: Results of the present survey provide information, thus far lacking, on the use in real-world clinical practice of VR combination during the COVID19 pandemic in 2020. Current literature on the prevalence of COVID-19 infection in CLL, has some limitations (i.e., small size sample, heterogeneity of treatment, restriction to only the first pandemic wave);this survey, performed on a large number of CLL patients treated with VR combination only seems to provide additional information on safe management of CLL treatment during the COVID19 pandemic.

Performance assessment of face analysis algorithms with occluded faces

In retail environments, it is important to acquire information about customers entering in a selling area, by counting them, but also by understanding stable traits (such as gender, age, or ethnicity) and temporary feelings (such as the emotion). Anyway, in the last year, due to the COVID-19 pandemic, it is becoming mandatory to wear a mask, covering at least half of the face, thus making the above mentioned face analysis tasks definitely more challenging. In this paper, we evaluate the drop in the performance of these analytics when the face is partially covered by a mask, in order to evaluate how existing face analysis applications can perform with occluded faces. According to our knowledge, this is the first time a similar analysis has been performed. Furthermore, we also propose two new datasets, designed as extensions with masked faces of the widely adopted VGG-Face and RAF-DB datasets, that we make publicly available for benchmarking purposes. The analysis we conducted demonstrates that, except for gender and ethnicity recognition whose accuracy drop is quite limited (less than 10%), further investigations are necessary for increasing the performance of methods for age estimation (MAE drop between 4 and 10 years) and emotion recognition (accuracy decrease between 45% and 55%). © Springer Nature Switzerland AG 2021.

Lessons learned from COVID-19 pandemic in Italy - A commentary

Since the COVID-19 outbreak, Italy has been one of the most affected countries in Europe and the second for number of deaths. In this commentary, we discuss some lessons that we learned as health-care providers working in a large public hospital during the pandemic, with a special focus on the importance of infection containment and early diagnosis, the role of swab, serological tests, home isolation and individual protection devices, and the available therapies and management indications to better face a possible new outbreak in the near future. These comments should stimulate a more diffused, efficient, and efficacious management of COVID-19 patients, also reducing the number of admissions to hospital emergency departments and the related spread of the infection.

Challenges for Midwives' Healthcare Practice in the Next Decade: COVID-19 - Global Climate Changes - Aging and Pregnancy - Gestational Alcohol Abuse.

Midwives are multifaceted healthcare professionals whose competence spectrum includes a large variety of knowledge and skills going from antenatal care to education and research. The aim of this review is to suggest the future challenges midwives are going to face in the upcoming decade of this Century. COVID-19 and other infections will reasonably impact healthcare workers all over the world. Midwives are frontline healthcare professionals who are constantly at risk of contagion as their job implies close contact with women, physical support and hand touch. Also, menstruation waste plays a large role in the pollution of waters, severely impacting hygiene in the developing countries and fueling climate change. Appropriate disposal of used menstrual material is still insufficient in many countries of the world especially because of lack of sanitary education on girls. As educators, midwives will be more involved into preventing inappropriate disposal of menstrual hygiene devices by educating girls around the world about the green alternatives to the commercial ones. Despite the evidences about the fertility decrement that occurs with aging, women keep postponing reproduction and increasing their chance being childless or suffering complications related to the advanced maternal age. Teen pregnancies are as well an important issue for midwives who will be called to face more age-related issues and use a tailored case to case approach, enhancing their family planning skills. Another crucial role of midwifery regards the information about the risk of drinking alcohol during gestation. Alcohol assumption during pregnancy is responsible for serious damage to the fetus causing a wide range of pathological conditions related to Fetal Alcoholic Spectrum Disorder, leading cause of mental retardation in children of western countries. On the whole, midwives have demonstrated their willingness to expand their practice through continuing professional development, and through specialist and advanced roles especially in preventive and educational positions.