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A syndrome occurring after adenoviral vector anti-SARS-CoV-2 vaccination, characterized by thrombocytopenia, venous thrombosis, and circulating anti-PF4 antibodies, known as vaccine-induced immune thrombotic thrombocytopenia (VITT), is well described. Data on the long-term course of this syndrome are lacking. Our aim is to report the clinical and laboratory features of a patient with VITT from diagnosis and during 21 months of follow-up. Cerebral venous thrombosis associated with elevated D-dimer, low fibrinogen, thrombocytopenia, and anti-PF4 antibodies positivity occurred in this patient after ChAdOx1 nCoV-19 vaccination. Cerebral thrombosis required a revascularization procedure and decompressive craniectomy. Upon dexamethasone and anticoagulant treatment initiation, the platelet count recovered. However, a persistently high anti-PF4 antibody titer, without thrombosis recurrence, was observed. Little is known about the long-term persistence of anti-PF4 antibodies, their clinical significance, and their possible role in guiding therapeutic decisions. In our patient, we decided to continue anticoagulant treatment beyond 21 months with parallel anti-PF4 antibody monitoring.

BackgroundOlder age is a well-known risk factor for unfavorable outcome in traumatic brain injury (TBI). However, many older people with TBI respond well to aggressive treatments, suggesting that chronological age and TBI severity alone may be inadequate prognostic markers. Frailty is an age-related homeostatic imbalance of loss of physiologic and cognitive reserve resulting in both limitation in autonomy of activities of daily living and vulnerability to adverse events. We hypothesized that frailty would be associated with 6-month adverse functional outcome in older people affected by moderate or severe TBI.MethodsThis was a single-center prospective observational study. We enrolled consecutive patients aged ≥65 years after TBI with Glasgow Coma Scale ≤13 and admitted to our Neurosurgical Intensive Care Unit. Frailty was evaluated by Clinical Frailty Scale (CFS). Relationships between TBI severity, frailty and extended Glasgow Outcome Scale (GOSE) at 6-month were evaluated.ResultsSixty patients were studied, 65% were males, their age was 76 years (IQR 70–80) and their admission GCS was 8 (IQR 6–11) with a GCS motor score of 5 (IQR 4–5). Twenty eight were vulnerable-frail (defined as CFS ≥ 4). Vulnerable-frail patients showed greater 6-month mortality and unfavorable outcome compared to non-frail [87% vs. 30% OR and 95% CI: 15.7 (3.9–55.2), p

Este trabalho tem a finalidade de estudar a inserção dos transexuais no mercado de trabalho, bem como identificar se há ou não dificuldade no processo. Para melhor aprofundamento do tema, a metodologia utilizada foi a exploratória de caráter qualitativo. Para atingir o objetivo proposto, foi necessário estudar a escolaridade dos transexuais, os principais meios de atuação profissional desses e a preparação das empresas e seus colaboradores para recebê-los e os inserir de acordo com a legislação. Após a revisão de literatura, foi feito um estudo empírico de entrevistas por meio de com a população transexual e empresas para identificar se a prática condiz com a teoria estudada. Os resultados apontam que as empresas estudadas não possuem pleno conhecimento da legislação e de ferramentas para inclusão de transexuais. Os transexuais possuem maior inserção em determinadas áreas e a inserção acontece de forma muito incipiente no Brasil, carecendo de maiores leis afirmativas e popularização do tema.

This work has the learning to study the insertion of transsexuals in the job market, as well as to identify whether or not there is difficulty in the process. For a better understanding of the theme, a methodology used for exploratory faith of a qualitative character. To achieve the proposed objective, the necessary faith to study the education of transsexuals, their main means of professional activity and a preparation of companies and their collaborators to receive and insert them according to the legislation. After a review of the literature, it was conducted an empirical study of identification through a transsexual population and companies to identify whether a practice consistent with a theory studied. The results show that the companies studied do not have knowledge of the legislation and tools for the inclusion of transsexuals. Transsexuals have a greater insertion in certain areas and insertion happens very incipiently in Brazil, lacking the popularity.

Genetic deficiency of β-N-acetylhexosaminidase (Hex) functionality leads to accumulation of GM2 ganglioside in Tay-Sachs disease and Sandhoff disease (SD), which presently lack approved therapies. Current experimental gene therapy (GT) approaches with adeno-associated viral vectors (AAVs) still pose safety and efficacy issues, supporting the search for alternative therapeutic strategies. Here we leveraged the lentiviral vector (LV)-mediated intracerebral (IC) GT platform to deliver Hex genes to the CNS and combined this strategy with bone marrow transplantation (BMT) to provide a timely, pervasive, and long-lasting source of the Hex enzyme in the CNS and periphery of SD mice. Combined therapy outperformed individual treatments in terms of lifespan extension and normalization of the neuroinflammatory/neurodegenerative phenotypes of SD mice. These benefits correlated with a time-dependent increase in Hex activity and a remarkable reduction in GM2 storage in brain tissues that single treatments failed to achieve. Our results highlight the synergic mode of action of LV-mediated IC GT and BMT, clarify the contribution of treatments to the therapeutic outcome, and inform on the realistic threshold of corrective enzymatic activity. These results have important implications for interpretation of ongoing experimental therapies and for design of more effective treatment strategies for GM2 gangliosidosis.

Abstract Background Questions remain on the optimal management of subarachnoid hemorrhage (SAH) patients once they are admitted to the referring center, before and after the aneurysm treatment. To address these issues, we created a consensus of experts endorsed by the Italian Society of Anesthesia and Intensive Care (SIAARTI) to provide clinical guidance regarding this topic. Specifically, in this manuscript (part 2), we aim to provide a list of experts’ recommendations regarding the management of SAH patients in a center with neurosurgical/neuroendovascular facilities after aneurysm treatment. Methods A multidisciplinary consensus panel composed by 24 physicians selected for their established clinical and scientific expertise in the acute management of SAH patients with different specializations (anesthesia/intensive care, neurosurgery, and interventional neuroradiology) was created. A modified Delphi approach was adopted. Results A total of 33 statements were discussed, voted, and approved. Consensus was reached on 30 recommendations (28 strong and 2 weak). In 3 cases, where consensus could not be agreed upon, no recommendation was provided. Conclusions This consensus provides practical recommendations (and not mandatory standard of practice) to support clinician’s decision-making in the management of SAH patients in centers with neurosurgical/neuroendovascular facilities after aneurysm securing.

Abstract Background Alternative noninvasive methods capable of excluding intracranial hypertension through use of transcranial Doppler (ICPtcd) in situations where invasive methods cannot be used or are not available would be useful during the management of acutely brain-injured patients. The objective of this study was to determine whether ICPtcd can be considered a reliable screening test compared to the reference standard method, invasive ICP monitoring (ICPi), in excluding the presence of intracranial hypertension. Methods This was a prospective, international, multicenter, unblinded, diagnostic accuracy study comparing the index test (ICPtcd) with a reference standard (ICPi), defined as the best available method for establishing the presence or absence of the condition of interest (i.e., intracranial hypertension). Acute brain-injured patients pertaining to one of four categories: traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) or ischemic stroke (IS) requiring ICPi monitoring, were enrolled in 16 international intensive care units. ICPi measurements (reference test) were compared to simultaneous ICPtcd measurements (index test) at three different timepoints: before, immediately after and 2 to 3 h following ICPi catheter insertion. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated at three different ICPi thresholds (> 20, > 22 and > 25 mmHg) to assess ICPtcd as a bedside real-practice screening method. A receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC) was used to evaluate the discriminative accuracy and predictive capability of ICPtcd. Results Two hundred and sixty-two patients were recruited for final analysis. Intracranial hypertension (> 22 mmHg) occurred in 87 patients (33.2%). The total number of paired comparisons between ICPtcd and ICPi was 687. The NPV was elevated (ICP > 20 mmHg = 91.3%, > 22 mmHg = 95.6%, > 25 mmHg = 98.6%), indicating high discriminant accuracy of ICPtcd in excluding intracranial hypertension. Concordance correlation between ICPtcd and ICPi was 33.3% (95% CI 25.6–40.5%), and Bland–Altman showed a mean bias of -3.3 mmHg. The optimal ICPtcd threshold for ruling out intracranial hypertension was 20.5 mmHg, corresponding to a sensitivity of 70% (95% CI 40.7–92.6%) and a specificity of 72% (95% CI 51.9–94.0%) with an AUC of 76% (95% CI 65.6–85.5%). Conclusions and relevance ICPtcd has a high NPV in ruling out intracranial hypertension and may be useful to clinicians in situations where invasive methods cannot be used or not available. Trial registration: NCT02322970 .

Somitogenesis has been well characterized in model organisms, resulting in detailed description of the somite segmentation clock. Here they generate somitogenic organoids from human pluripotent stem cells that recapitulate somitogenesis, periodic segmentation, and proper polarity.

The aim of this study was to examine the impact of features of dysmetabolism on liver disease severity, evolution, and clinical outcomes in a real‐life cohort of patients treated with direct acting antivirals for chronic hepatitis C virus (HCV) infection. To this end, we considered 7,007 patients treated between 2014 and 2018, 65.3% with advanced fibrosis, of whom 97.7% achieved viral eradication (NAVIGATORE‐Lombardia registry). In a subset (n = 748), liver stiffness measurement (LSM) was available at baseline and follow‐up. Higher body mass index (BMI; odds ratio [OR] 1.06 per kg/m2, 1.03‐1.09) and diabetes (OR 2.01 [1.65‐2.46]) were independently associated with advanced fibrosis at baseline, whereas statin use was protective (OR 0.46 [0.35‐0.60]; P

Tegumentary leishmaniasis (TL) is endemic but neglected in southern Europe. Therefore, this study aimed to analyze the Leishmania strains causing TL cases in northeastern Italy, where an upsurge of TL cases has been observed in the last decade. Sections from 109 formalin-fixed and paraffin-embedded (FFPE) biopsies of skin and mucosal tissues were collected from TL cases in the selected area. Two DNA targets were amplified and sequenced: the ribosomal internal transcribed spacer 1 (ITS1) and the heat-shock protein 70 gene (hsp70). An in silico analysis was also performed on 149 genomes belonging to the Leishmania donovani complex. A total of 88 out of 109 (80.7%) samples from 83 TL cases were successfully typed by ITS1 and/or hsp70. ITS1 analysis identified L. infantum in 67 cases (91.8%), while L. major (n = 4, 5.5%) and L. tropica (n = 2, 2.7%) were detected in the remaining cases that were categorized as imported. Further, the hsp70 typing of 75 autochthonous cases showed the presence of eight distinct sequence variants belonging to the Leishmania donovani complex, with high genetic variability when compared to known L. infantum populations. In conclusion, our findings show that peculiar L. infantum variants are emerging in the novel focus on TL in northeastern Italy.

Abstract Background Issues remain on the optimal management of subarachnoid hemorrhage (SAH) patients once they are admitted to the referring center, before and after the aneurysm treatment. To address these issues, we created a consensus of experts endorsed by the Italian Society of Anesthesia and Intensive Care (SIAARTI). In this manuscript, we aim to provide a list of experts’ recommendations regarding the early management of SAH patients from hospital admission, in a center with neurosurgical/neuro-endovascular facilities, until securing of the bleeding aneurysm. Methods A multidisciplinary consensus panel composed of 24 physicians selected for their established clinical and scientific expertise in the acute management of SAH patients with different background (anesthesia/intensive care, neurosurgery, and interventional neuroradiology) was created. A modified Delphi approach was adopted. Results Among 19 statements discussed. The consensus was reached on 18 strong recommendations. In one case, consensus could not be agreed upon and no recommendation was provided. Conclusions This consensus provides practical recommendations for the management of SAH patients in hospitals with neurosurgical/neuroendovascular facilities until aneurysm securing. It is intended to support clinician’s decision-making and not to mandate a standard of practice.

Abstract Endometriosis is a chronic gynecological disorder involved in the pathogenesis of chronic pelvic pain, based on a probable up regulation of the inflammatory system. The objective of the study is to investigate the peritoneal and serum levels of ENA-78 with the severity of endometriosis symptoms (dysmenorrhea, chronic pelvic pain and dyspareunia) using the visual analogue scale (VAS). This is a prospective case–control study that included 53 symptomatic women with evidence of endometriosis and 53 age-matched controls who underwent elective laparoscopic surgery for benign diseases. The concentration of ENA-78 was assessed in blood and peritoneal fluid samples in the follicular phase. In peritoneal fluid and plasma, the concentration of ENA-78 was significantly higher in cases than in controls (p

Abstract Background Dravet Syndrome is a severe childhood pharmaco-resistant epileptic disorder mainly caused by mutations in the SCN1A gene, which encodes for the α1 subunit of the type I voltage-gated sodium channel (NaV1.1), that causes imbalance between excitation and inhibition in the brain. We recently found that eEF2K knock out mice displayed enhanced GABAergic transmission and tonic inhibition and were less susceptible to epileptic seizures. Thus, we investigated the effect of inhibition of eEF2K on the epileptic and behavioral phenotype of Scn1a ± mice, a murine model of Dravet Syndrome. Methods To elucidate the role of eEF2K pathway in the etiopathology of Dravet syndrome we generated a new mouse model deleting the eEF2K gene in Scn1a ± mice. By crossing Scn1a ± mice with eEF2K−/− mice we obtained the three main genotypes needed for our studies, Scn1a+/+ eEF2K+/+ (WT mice), Scn1a ± eEF2K+/+ mice (Scn1a ± mice) and Scn1a ± eEF2K−/− mice, that were fully characterized for EEG and behavioral phenotype. Furthermore, we tested the ability of a pharmacological inhibitor of eEF2K in rescuing EEG alterations of the Scn1a ± mice. Results We showed that the activity of eEF2K/eEF2 pathway was enhanced in Scn1a ± mice. Then, we demonstrated that both genetic deletion and pharmacological inhibition of eEF2K were sufficient to ameliorate the epileptic phenotype of Scn1a ± mice. Interestingly we also found that motor coordination defect, memory impairments, and stereotyped behavior of the Scn1a ± mice were reverted by eEF2K deletion. The analysis of spontaneous inhibitory postsynaptic currents (sIPSCs) suggested that the rescue of the pathological phenotype was driven by the potentiation of GABAergic synapses. Limitations Even if we found that eEF2K deletion was able to increase inhibitory synapses function, the molecular mechanism underlining the inhibition of eEF2K/eEF2 pathway in rescuing epileptic and behavioral alterations in the Scn1a ± needs further investigations. Conclusions Our data indicate that pharmacological inhibition of eEF2K could represent a novel therapeutic intervention for treating epilepsy and related comorbidities in the Dravet syndrome.

Electronic Health Records (EHRs) are electronically-stored health information in a digital format. EHRs are typically shared among healthcare stakeholders and face power failure, data misuse, lack of privacy, security, and audit trail. On the other hand, blockchain is the revolutionary invention of the twentieth century that offers a distributed and decentralized setting to communicate among nodes in a list of networks without a central authority. It can address the limitations of EHRs management and provide a safer, secured, and decentralized environment for exchanging EHRs data. Three categories of blockchain-based potential solutions have been proposed by researchers to handle EHRs: conceptual, prototype, and implemented. This study focused on a Systematic Literature Review (SLR) to find and analyze articles submitted either conceptual or implemented to manage EHRs using blockchain. The study examined 99 papers that were collected from various publication categories. The deep technical analysis focused on evaluating articles based on privacy, security, scalability, accessibility, cost, consensus algorithms, and the type of blockchain used. The SLR found that blockchain technology promises to provide decentralization, security, and privacy that traditional EHRs often lack. Moreover, results obtained from the detailed studies would provide potential researchers with the type of blockchain for future research. Finally, future research directions, in the end, would direct enthusiasm to combine new blockchain-based systems to manage EHRs properly.

Este artigo esboçauma proposta de interpretação da imigração genericamente definida como “russa” para o Rio Grande do Sul, estado do extremo sul do Brasil, transcorrida entre o final do século XIX e as primeiras décadas do século XX. A proposta se configura a partir da explicitação de alguns aspectos deste grupo migratório, entre os quais se destacam: a justaposição entre categorias de etnicidade e de nacionalidade, principalmente considerando a presença de judeus, poloneses e ucranianos egressos de território russo; a ocorrência de emigrações em diferentes momentos históricos do país de origem; o modo como foram vistos pelas autoridades locais e nacionais. Em diálogo com a literatura sobre o assunto, a pesquisa reúne dados de publicações, alguns depoimentos e vestígios dispersos, atentando para a manifestação de uma identidade étnica em condições complexas, ao mesmo tempo em que expõe a polissemia da identidade “russa”.

ObjectiveNarcissism may play a role in shaping body image concerns. Here we examined the relationships between narcissism (i.e., agentic extraversion, antagonism, narcissistic neuroticism, leadership/authority, exhibitionism/entitlement) and body image concerns and disturbances (i.e., drive for thinness, drive for muscularity, eating disorder symptoms, body mass index, current/desired fat, and current/desired muscularity).MethodsMechanical Turk workers from the USA (N = 430; 64% male) completed the Narcissistic Admiration and Rivalry Questionnaire, the Hypersensitive Narcissism Scale, the Narcissistic Personality Inventory, the Drive for Muscularity Scale, the Drive for Thinness Scale, the Eating Disorder Examination Questionnaire-Short, and the Sex-Specific Somatomorphic Matrixes.ResultsAll narcissistic factors were associated with a greater drive for thinness (except for leadership/authority) and for muscularity, more eating disorder symptoms, a greater desired body fat (except for leadership/authority), and a greater current muscularity. Greater agentic extraversion and exhibitionism/entitlement were associated with lower levels of current body fat, and greater antagonism was associated with a greater desired muscularity.DiscussionNotably, individual differences in narcissism appeared to be important in understanding body image concerns, broadly speaking. We found that narcissism may be associated with body image concerns among both sexes differently, and especially that drive for thinness was more related to narcissism in men. Our results emphasize the importance of narcissism in formulating and treating body image-related disorders for both men and women. Ultimately, narcissistic features of personality may be risk factors for developing and perpetuating body image concerns, and therefore should be considered in assessment, formulation, diagnosis, and treatment of eating disorders.

Abstract Background The immediate management of subarachnoid hemorrhage (SAH) patients in hospitals without neurosurgical/neurointerventional facilities and their transfer to a specialized center is challenging and not well covered in existing guidelines. To address these issues, we created a consensus of experts endorsed by the Italian Society of Anesthesia and Intensive Care (SIAARTI) to provide clinical guidance. Methods A multidisciplinary consensus panel composed by 19 physicians selected for their established clinical and scientific expertise in the acute management of SAH patients with different specializations (anesthesia/intensive care, neurosurgery and interventional neuroradiology) was created. A modified Delphi approach was adopted. Results A total of 14 statements have been discussed. Consensus was reached on 11 strong recommendations and 2 weak recommendations. In one case, where consensus could not be agreed upon, no recommendation could be provided. Conclusions Management of SAH in a non-specialized setting and early transfer are difficult and may have a critical impact on outcome. Clinical advice, based on multidisciplinary consensus, might be helpful. Our recommendations cover most, but not all, topics of clinical relevance.

O presente artigo tem a finalidade de relatar as experiências vivenciadas no mercado de trabalho da região Alto Tietê por homossexuais estereotipados, bem como se deparam com situações de discriminação ou não, a fim de ajudar a compreender essa diversidade dentro do mundo corporativo. Trata-se de um estudo de caso de caráter qualitativo, valendo-se de pesquisa on-line, devido à pandemia da COVID-19, cujos participantes são duas lésbicas masculinizadas, um gay afeminado e residentes nas cidades da região do Alto Tietê. Os resultados apontam que os participantes já passaram por atos de homofobia, vivenciados tanto no meio corporativo como fora. Evidencia-se também que as empresas em que esses profissionais atuaram demonstram dificuldades em lidar com o tema.

In this day and age, data are indispensable commodities and have become an integral part of our daily lives [...]

Background and Objectives: Postoperative non-invasive ventilation (NIV) has been proposed as an attractive strategy to reduce morbidity in obese subjects undergoing general anaesthesia. The increased body mass index (BMI) correlates with loss of perioperative functional residual capacity, expiratory reserve volume, and total lung capacity. The aim of the current study is to evaluate the efficacy of NIV in a post-anaesthesia care unit (PACU) in reducing post-extubation acute respiratory failure (ARF) after biliointestinal bypass (BIBP) in obese patients. Materials and Methods: A retrospective analysis was conducted from January 2019 to December 2020 to compare acute respiratory failure within the first 72 postoperative hours and oximetry values of obese patients who underwent BIBP after postoperative NIV adoption or conventional Venturi mask. Results: In total, 50 patients who received NIV postoperative protocol and 57 patients who received conventional Venturi mask ventilation were included in the study. After 120 min in PACU pH, pCO2, pO2, and SpO2 were better in the NIV group vs. control group (p < 0.001). Seventy-two hours postoperatively, one patient (2%) in the NIV group vs. seven patients (12.2%) in the control group developed acute respiratory failure. Therefore, conventional Venturi mask ventilation resulted in being significantly associated (p < 0.05) with postoperative ARF with an RR of 0.51 (IC 0.27–0.96). Conclusions: After bariatric surgery, short-term NIV during PACU observation promotes a more rapid recovery of postoperative lung function and oxygenation in obese patients, reducing the necessity for critical care in the days following surgery. Therefore, as day-case surgery becomes more advocated even for morbid obesity, it might be considered a necessary procedure.

Este artigo traz uma análise acerca da educação desenvolvida junto aos grupos de imigrantes poloneses que se estabeleceram na Colônia Erechim, criada em 1908, na zona norte do Rio Grande do Sul. Evidencia-se que a nacionalização do ensino no período do Estado Novo (1937-1945) facilita uma acentuação do preconceito linguístico em desfavor das culturas de origem estrangeira, característica excludente que perpassa a formação do projeto educativo brasileiro e, consequentemente, seu fazer pedagógico. Observa-se que a escola pública que vai sendo construída nesta área de imigração é tingida por estigmas, resistências e tensões diversas. Com a retrospectiva histórica deste processo, conclui-se que o planejamento educativo oficial requer a legitimação da escola necessária ao projeto hegemônico de desenvolvimento da sociedade.

This paper presents an unusual blue bunch of grapes-shaped ampulla from ancient Bergomum. The aim is the analysis of the types of glasses of bunch grapesshaped. According to the spread of these glasses and the find of a sample in Bergamo, this paper offers a possible case study of trade channels between the Levant, first area of production of these samples, and northern Italy.

Abstract Background Healthcare complaints are grievances that may be indicative of some system failures, individual failings, or a combination of both. Moreover, the experience of making a complaint, including its outcome, often falls short of patient expectations, particularly in relation to the interpersonal conduct of National Health Service (NHS) staff. Over half of unresolved (local) complaints are subsequently upheld by the ombudsman with others potentially resulting in costly litigation. Method A nuanced discourse analytical approach to analysing the language choices within complaint-responses could potentially provide greater insight into why many local complaints continue to remain unresolved. Over a period of 1 month we collated a data corpus of written complaints and their responses (n = 60) from an NHS healthcare area in Scotland, United Kingdom (UK) following anonymisation by NHS complaint handling staff. We took a qualitative approach to analysing the data drawing upon Discourse Analysis with this paper reporting on the complaint-responses only (n = 59). We had undertaken a similar review of the initial written complaints and this is reported elsewhere. In this paper we examine how, and to what extent, the complaint-responses fully addressed the complainants’ perceived grievances. Results The complaint-responses rarely acknowledged the amount of detail or ‘work’ involved in making the complaint. Complaint-responses constructed complainants’ accounts as subjective by using specific discourse strategies. Further, complaint responses used unintentionality or exceptionality to mitigate sub-standard experiences of care. We also observed the ‘fauxpology’ - a non-apology or false apology (e.g. I am sorry you feel) which imputes the cause of distress to the subjective (and possibly misguided) impressions of the complainant. The complaint-responses thereby evade blame or responsibility for the complainable action by implying that the complainants’ feelings do not align with the facts. Conclusions Complainants and complaint-responders work to different frames of reference. Complaint responders need to engage and align with complainants from the outset to ensure more appropriate complaint- responses. Complaint resolution as opposed to complaint handling could be enhanced by the approach of linguistic analysis and reference to the consumer literature’s justice-based approach to post-complaint behaviour.

Adrenal dysfunction (AD) and, in particular, adrenal crisis are uncommon events in pregnant women, but associated with significant maternal and fetal morbidity and mortality if untreated or undiagnosed. Adrenal crisis may be confused with the common symptoms of pregnancy: the obstetricians should be able to promptly diagnose and treat it in order to avoid the adverse outcomes regarding the mother and the fetus. For this reason, AD must be treated by an expert multidisciplinary team. We presented a case report of a young pregnant woman with adrenal crisis due to tuberculosis, cocaine abuse, and massive bilateral hemorrhage with symptoms of emesis, hypotension, sudden abdominal pain, and leukocytosis. The most common issues of diagnosis and treatment are discussed and analyzed. Finally, we performed a review of the literature regarding adrenal crisis and adrenal insufficiency (AI) in pregnancy in order to clarify the management of these diseases in obstetrics setting.

Starting from spring 2020, newspapers headlines and studies have suggested that the COVID-19 pandemics had a negative impact especially on the mental health of children and adolescents, so that terms like “lost generation” or “generation COVID-19” have been used to define youth in time of pandemic crisis. Similarly, international health agencies reported an increase in depression and anxiety among adolescents in COVID-19 time, but also a rise in bodily disorders, such as non-suicidal self-injury and eating disorders. However, scientific data on this matter are not as clear as they seem and theoretical-clinical proposals regarding the processes involved are lacking. Focusing specifically on bodily disorders in adolescents during COVID-19, the aim of this perspective paper is to review this issue and propose a novel viewpoint on it. Firstly, data regarding frequency and phenomenology of bodily disorders in adolescence before and during the pandemic will be presented to underline possible discrepancies, gaps, or hyperbolic descriptions in the literature published after the COVID-19 outbreak. Secondly, a specific theoretical-clinical perspective will be proposed, that is, a developmental psychopathology perspective which attempts to frame these phenomena in a more nuanced and complex way, taking into account the role of developmental processes in adolescence age and its difficulties in the specific, subjective life-context of the individual, when intertwining with vulnerability factors and stressful life events. As such, the function of the body for the adolescent as a primary mean for regulating the self-other relationship and developing a greater sense of self-agency will be highlighted. The final objective is to help the clinician in developing both a critical thinking about the data that are shared in public outlets and an intervention that takes into account the complexity of contemporary psychopathological phenomena.

Abstract Developmental patterning in Caenorhabditis elegans is known to proceed in a highly stereotypical manner, which raises the question of how developmental robustness is achieved despite the inevitable stochastic noise. We focus here on a population of epidermal cells, the seam cells, which show stem cell-like behaviour and divide symmetrically and asymmetrically over post-embryonic development to generate epidermal and neuronal tissues. We have conducted a mutagenesis screen to identify mutants that introduce phenotypic variability in the normally invariant seam cell population. We report here that a null mutation in the fusogen eff-1 increases seam cell number variability. Using time-lapse microscopy and single molecule fluorescence hybridisation, we find that seam cell division and differentiation patterns are mostly unperturbed in eff-1 mutants, indicating that cell fusion is uncoupled from the cell differentiation programme. Nevertheless, seam cell losses due to the inappropriate differentiation of both daughter cells following division, as well as seam cell gains through symmetric divisions towards the seam cell fate were observed at low frequency. We show that these stochastic errors likely arise through accumulation of defects interrupting the continuity of the seam and changing seam cell shape, highlighting the role of tissue homeostasis in suppressing phenotypic variability during development.

Abstract Background Several studies have shown that during COVID-19 pandemic outbreak, emotional symptoms increased in the general population. Less is known about youths. Methods We surveyed a sample of Italian adolescents during the strictest quarantine period and assessed the effects of socio-demographic and psychological factors on current emotional symptoms. A convenient sample of 326 adolescents (age range 14–19 years) participated in a web-based survey. We collected data on several socio-demographic and psychological variables (summarized into three indexes: environmental context, changes in lifestyle, and worries about infection) and psychopathological symptoms (previous psychopathological status, current anxiety and depressive symptoms). Results Descriptive analysis showed that adolescents have experienced quarantine under very different conditions; they reported 47.5 and 14.1% of anxiety and depressive symptoms, respectively. Regression analyses indicated that previous psychopathological status and worries about infection are linked to anxiety and that female gender, previous psychopathological status (moderated by change in lifestyle), worse environmental context are linked to depression. Conclusion This study indicates that, facing the COVID-19 pandemic and its related safety measures, adolescents show relevant emotional symptoms and therefore should be monitored, assessed and supported.

Abstract Background Acute severe asthma is a life-threatening medical emergency. Characteristics of asthma include increased airway resistance and dynamic pulmonary hyperinflation that can manifest in dangerous levels of hypercapnia and acidosis, with significant mortality and morbidity. Severe respiratory distress can lead to endotracheal intubation followed by mechanical ventilation, which can cause increased air trapping with dynamic hyperinflation, predisposing the lungs to barotraumas. Case presentation The present case report describes the use of the minimally invasive ECCO2R ProLUNG® (Estor) with protective low-tidal-volume ventilation, in a Caucasian patient with near-fatal asthma and with no response to conventional therapy. Conclusions Since hypercarbia rather than hypoxemia is the primary abnormality in status asthmaticus, a rescue therapeutic strategy combining the ECCO2R membrane ProLUNG® (Estor) with ultra-protective low-tidal-volume ventilation can be successfully applied to limit the risk of severe barotrauma during invasive mechanical ventilation. ECCO2R ProLUNG® is a partial respiratory support technique that, based on the use of an extracorporeal circuit with a gas-exchange membrane, achieves relevant CO2 clearance directly from the blood using double-lumen venous-venous vascular access, at blood flow in the range of 0.4–1.0 L/minute.

Over 40,000 patients in the United States are estimated to suffer from end-stage liver disease and acute hepatic failure, for which liver transplantation is the only available therapy. Human primary hepatocytes (HPH) have not been employed as a therapeutic tool due to the difficulty in growing and expanding them in vitro, their sensitivity to cold temperatures, and tendency to dedifferentiate following two-dimensional culture. The differentiation of human-induced pluripotent stem cells (hiPSCs) into liver organoids (LO) has emerged as a potential alternative to orthotropic liver transplantation (OLT). However, several factors limit the efficiency of liver differentiation from hiPSCs, including a low proportion of differentiated cells capable of reaching a mature phenotype, the poor reproducibility of existing differentiation protocols, and insufficient long-term viability in vitro and in vivo. This review will analyze various methodologies being developed to improve hepatic differentiation from hiPSCs into liver organoids, paying particular attention to the use of endothelial cells as supportive cells for their further maturation. Here, we demonstrate why differentiated liver organoids can be used as a research tool for drug testing and disease modeling, or employed as a bridge for liver transplantation following liver failure.

Parvoviruses are single-stranded DNA viruses, infecting many animals from insects to humans. Human parvovirus B19 (B19V) causes erythema infectiosum, arthropathy, anemia, and fetal death, and human bocavirus (HBoV) 1 causes respiratory tract infections, while HBoV2-4 are enteric. Parvoviral genomes can persist in diverse non-permissive tissues after acute infection, but the host-cell tropism and the impact of their tissue persistence are poorly studied. We searched for parvoviral DNA in a total of 427 intestinal biopsy specimens, as paired disease-affected and healthy mucosa, obtained from 130 patients with malignancy, ulcerative colitis (UC), or adenomas, and in similar intestinal segments from 55 healthy subjects. Only three (1.6%) individuals exhibited intestinal HBoV DNA (one each of HBoV1, 2, and 3). Conversely, B19V DNA persisted frequently in the intestine, with 50, 47, 31, and 27% detection rates in the patients with malignancy, UC, or adenomas, and in the healthy subjects, respectively. Intra-individually, B19V DNA persisted significantly more often in the healthy intestinal segments than in the inflamed colons of UC patients. The highest loads of B19V DNA were seen in the ileum and colon specimens of two healthy individuals. With dual-RNAscope in situ hybridization and immunohistochemistry assays, we located the B19V persistence sites of these intestines in mucosal B cells of lymphoid follicles and vascular endothelial cells. Viral messenger RNA transcription remained, however, undetected. RNA sequencing (RNA-seq) identified 272 differentially expressed cellular genes between B19V DNA-positive and -negative healthy ileum biopsy specimens. Pathway enrichment analysis revealed that B19V persistence activated the intestinal cell viability and inhibited apoptosis. Lifelong B19V DNA persistence thus modulates host gene expression, which may lead to clinical outcomes.

Pelvic organ prolapse (POP) affects many women and contributes significantly to a decrease in their quality of life causing urinary and/or fecal incontinence, sexual dysfunction and dyspareunia. To better understand POP pathophysiology, prevention and treatment, many researchers resorted to evaluating animal models. Regarding this example and because POP affects principally older women, our aim was to provide an overview of literature on the possible biomechanical changes that occur in the vaginas of animal models and their supportive structures as a consequence of aging. Papers published online from 2000 until May 2021 were considered and particular attention was given to articles reporting the effects of aging on the microscopic structure of the vagina and pelvic ligaments in animal models. Most research has been conducted on rodents because their vagina structure is well characterized and similar to those of humans; furthermore, they are cost effective. The main findings concern protein structures of the connective tissue, known as elastin and collagen. We have noticed a significant discordance regarding the quantitative changes in elastin and collagen related to aging, especially because it is difficult to detect them in animal specimens. However, it seems to be clear that aging affects the qualitative properties of elastin and collagen leading to aberrant forms which may affect the elasticity and the resilience of tissues leading to pelvic floor disease. The analysis of histological changes of pelvic floor tissues related to aging underlines how these topics appear to be not fully understood so far and that more research is necessary.

Metachromatic leukodystrophy (MLD) and globoid cell leukodystrophy (GLD or Krabbe disease) are severe neurodegenerative lysosomal storage diseases (LSD) caused by arylsulfatase A (ARSA) and galactosylceramidase (GALC) deficiency, respectively. Our previous studies established lentiviral gene therapy (GT) as a rapid and effective intervention to provide pervasive supply of therapeutic lysosomal enzymes in CNS tissues of MLD and GLD mice. Here, we investigated whether this strategy is similarly effective in juvenile non-human primates (NHP). To provide proof of principle for tolerability and biological efficacy of the strategy, we established a comprehensive study in normal NHP delivering a clinically relevant lentiviral vector encoding for the human ARSA transgene. Then, we injected a lentiviral vector coding for the human GALC transgene in Krabbe-affected rhesus macaques, evaluating for the first time the therapeutic potential of lentiviral GT in this unique LSD model. We showed favorable safety profile and consistent pattern of LV transduction and enzyme biodistribution in the two models, supporting the robustness of the proposed GT platform. We documented moderate inflammation at the injection sites, mild immune response to vector particles in few treated animals, no indication of immune response against transgenic products, and no molecular evidence of insertional genotoxicity. Efficient gene transfer in neurons, astrocytes, and oligodendrocytes close to the injection sites resulted in robust production and extensive spreading of transgenic enzymes in the whole CNS and in CSF, leading to supraphysiological ARSA activity in normal NHP and close to physiological GALC activity in the Krabbe NHP, in which biological efficacy was associated with preliminary indication of therapeutic benefit. These results support the rationale for the clinical translation of intracerebral lentiviral GT to address CNS pathology in MLD, GLD, and other neurodegenerative LSD.

Genetic mosaicism is frequently present in monogenic diseases of the central nervous system. Here the authors design a dual-colour reporter system that can be used to tune the degree of mosaicism in mouse models.

O presente artigo tem como objetivo analisar a audiodescrição (AD) de ilustrações presentes em dois textos literários direcionados ao público infantojuvenil: Simplesmente Diferente (2011), de autoria de Mônica Picavêa, e Cinderela (2014), adaptado por Anna Cláudia Ramos. Embora sejam propostas narrativas distintas, ambos os livros compõem as escassas produções de literatura acessível para cegos ou com baixa visão. Ao considerar a importância da ilustração na constituição deste gênero, analisar a produção das audiodescrições de tais materiais em um meio semiótico diferente do visual pode ser um caminho para traçar novas diretrizes para a produção de AD em materiais voltados para o público infantojuvenil, além dos já dispostos pela Audio Description Coalition (2010) e pela Norma Inglesa de Audiodescrição (2000). O aporte teórico deste trabalho está fundamentado em estudos de Turchi (2002), Piety (2004), Costa (2011), Coito (2015), Garbim (2017) e Praxedes Filho e Arraes (2017).