Determinants of HIV late presentation among men who have sex with men in Portugal (2014-2019): who's being left behind?

Introduction: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019. Methods: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP). Results: The median age was 31 years, 51% had a current income between 501-1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP. Conclusion: Our study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.

Natural proliferative phase frozen embryo transfer-a new approach which may facilitate scheduling without hindering pregnancy outcomes.

STUDY QUESTION: How does a natural proliferative phase (NPP) strategy for frozen embryo transfer (FET) compare with the conventional artificial (AC) and natural (NC) endometrial preparation protocols in terms of live birth rates (LBR)? SUMMARY ANSWER: This study supports the hypothesis that, just as for NC, NPP-FET may be a superior alternative to AC in terms of LBR. WHAT IS KNOWN ALREADY: Although FETs are increasing worldwide, the optimal FET protocol is still largely controversial. Despite recent evidence supporting a possibly higher efficacy and safety of NC FETs, their widespread use is limited by the difficulties encountered during cycle monitoring and scheduling. STUDY DESIGN, SIZE, DURATION: In this single center retrospective cohort study, we describe the NPP-FET protocol, in which vaginal progesterone is initiated during the proliferative phase as soon as an endometrium with a thickness of at least 7 mm is identified and ovulation is ruled out, regardless of mean diameter of the dominant follicle. PARTICIPANTS/MATERIALS, SETTING, METHODS: For comparison, we considered all blastocyst stage FET cycles preformed at a private infertility center between January 2010 and June 2022, subdivided according to the following subgroups of endometrial preparation: AC, NPP, and NC. We performed multivariable generalized estimating equations regression analysis to account for the following potential confounding variables: oocyte age at retrieval, oocyte source (autologous without preimplantation genetic testing for aneuploidies (PGT-A) versus autologous with PGT-A versus donated), number of oocytes retrieved/donated, embryo developmental stage (Day 5 versus Day 6), number of embryos transferred, quality of the best embryo transferred, and year of treatment. The main outcome measure was LBR. The secondary outcomes included hCG positive, clinical pregnancy and miscarriage rates, and the following perinatal outcomes: first trimester bleeding, second/third trimester bleeding, preterm rupture of membranes, gestational diabetes, gestational hypertensive disorders (GHD), and gestational age at delivery. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 5791 FET cycles were included in this analysis (2226 AC, 349 NPP, and 3216 NC). The LBR for FET was lower in the AC subgroup when compared to the NPP and NC (38.4%, 49.1%, and 45.2%, respectively; P < 0.01 AC versus NPP and AC versus NC). The rates of miscarriage were also lower in the NPP and NC subgroups when compared to AC (19.7%, 25.0%, and 34.9%, respectively; P < 0.01 NPP versus AC and NC versus AC). Considering perinatal outcomes, NPP-FET and NC were associated with a significantly lower first trimester bleeding compared to AC (17.3%, 14.7%, and 37.6%, respectively; P < 0.01 NPP versus AC and NC versus AC). Additionally, NC was associated with a lower rate of GHD when compared with AC (8.6% versus 14.5%, P < 0.01), while the rate following NPP-FET was 9.4%. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective design. Moreover, there was also a low number of patients in the NPP subgroup, which may have led the study to be underpowered to detect clinically relevant differences between the subgroups. WIDER IMPLICATIONS OF THE FINDINGS: Our study posits that the NPP-FET protocol may be an effective and safe alternative to both NC and AC, while still allowing for enhanced practicality in patient follow-up and FET scheduling. Further investigation on NPP-FET is warranted, with prospective studies including a larger and more homogeneous subsets of patients. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the IVI-RMA-Lisbon (2008-LIS-053-CG). The authors did not receive any funding for this study. The authors have no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

Cholesterol redistribution triggered by CYP46A1 gene therapy improves major hallmarks of Niemann-Pick type C disease but is not sufficient to halt neurodegeneration.

Cholesterol 24-hydroxylase (CYP46A1) is an exclusively neuronal cytochrome P450 enzyme responsible for converting cholesterol into 24S-hydroxycholesterol, which serves as the primary pathway for eliminating cholesterol in the brain. We and others have shown that increased activity of CYP46A1 leads to reduced levels of cholesterol and has a positive effect on cognition. Therefore, we hypothesized that CYP46A1 could be a potential therapeutic target in Niemann-Pick type C (NPC) disease, a rare and fatal neurodegenerative disorder, characterized by cholesterol accumulation in endolysosomal compartments. Herein, we show that CYP46A1 ectopic expression, in cellular models of NPC and in Npc1tm(I1061T) mice by adeno-associated virus-mediated gene therapy improved NPC disease phenotype. Amelioration in functional, biochemical, molecular and neuropathological hallmarks of NPC disease were characterized. In vivo, CYP46A1 expression partially prevented weight loss and hepatomegaly, corrected the expression levels of genes involved in cholesterol homeostasis, and promoted a redistribution of brain cholesterol accumulated in late endosomes/lysosomes. Moreover, concomitant with the amelioration of cholesterol metabolism dysregulation, CYP46A1 attenuated microgliosis and lysosomal dysfunction in mouse cerebellum, favoring a pro-resolving phenotype. In vivo CYP46A1 ectopic expression improves important features of NPC disease and may represent a valid therapeutic approach to be used concomitantly with other drugs. However, promoting cholesterol redistribution does not appear to be enough to prevent Purkinje neuronal death in the cerebellum. This indicates that cholesterol buildup in neurons might not be the main cause of neurodegeneration in this human lipidosis.

Nocardiosis: a single-center experience and literature review.

INTRODUCTION: Nocardiosis is a rare bacterial infection caused by Nocardia spp. However, an increasing incidence has been described whereby data about epidemiology and prognosis are essential. METHODS: A retrospective descriptive study was conducted among patients with positive Nocardia spp. culture, from January 2019 to January 2023, at a Terciary Hospital in Portugal. RESULTS: Nocardiosis was considered in 18 cases with a median age of 63.8-years-old. At least one immunosuppressive cause was identified in 70% of patients. Five patients had Disseminated Nocardiosis (DN). The lung was the most common site of clinical disease (77.8%) and Nocardia was most commonly identified in respiratory tract samples. The most frequently isolated species were Nocardia nova/africana (n = 7) followed by Nocardia cyriacigeorgica (n = 3) and Nocardia pseudobrasiliensis (n = 3). The majority of the patients (94.4%) received antibiotic therapy, of whom as many as 55.6% were treated with monotherapy. The most frequently prescribed antibiotic was trimethoprim-sulfamethoxazole. Selected antimicrobial agents were generally effective, with linezolid and cotrimoxazole (100% Susceptibility [S]) and amikacin (94% S) having the most activity against Nocardia species. The median (IQR) duration of treatment was 24.2 (1‒51.4) weeks for DN; The overall one-year case fatality was 33.3% (n = 6) and was higher in the DN (66.7%). No recurrence was observed. CONCLUSION: Nocardiosis is an emerging infectious disease with a poor prognosis, particularly in DN. This review offers essential epidemiological insights and underscores the importance of gaining a better understanding of the microbiology of nocardiosis. Such knowledge can lead to the optimization of antimicrobial therapy and, when necessary, guide appropriate surgical interventions to prevent unfavorable outcomes.

Peripheral Blood Serum NMR Metabolomics Is a Powerful Tool to Discriminate Benign and Malignant Ovarian Tumors.

Ovarian cancer is the major cause of death from gynecological cancer and the third most common gynecological malignancy worldwide. Despite a slight improvement in the overall survival of ovarian carcinoma patients in recent decades, the cure rate has not improved. This is mainly due to late diagnosis and resistance to therapy. It is therefore urgent to develop effective methods for early detection and prognosis. We hypothesized that, besides being able to distinguish serum samples of patients with ovarian cancer from those of patients with benign ovarian tumors, 1H-NMR metabolomics analysis might be able to predict the malignant potential of tumors. For this, serum 1H-NMR metabolomics analyses were performed, including patients with malignant, benign and borderline ovarian tumors. The serum metabolic profiles were analyzed by multivariate statistical analysis, including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) methods. A metabolic profile associated with ovarian malignant tumors was defined, in which lactate, 3-hydroxybutyrate and acetone were increased and acetate, histidine, valine and methanol were decreased. Our data support the use of 1H-NMR metabolomics analysis as a screening method for ovarian cancer detection and might be useful for predicting the malignant potential of borderline tumors.

Adverse Events of Latent Tuberculosis Treatment With Isoniazid in People Living With HIV: A Case-Control Study in a Resource-Rich Setting.

Introduction Multiple risk factors, such as human immunodeficiency virus (HIV) infection and immunosuppressive therapies, increase the odds of latent tuberculosis infection (LTBI) reactivation and progression to active tuberculosis. A six-to-nine-month preventive treatment with isoniazid (INH) decreases the risk of LTBI reactivation, but its effectiveness can be limited by its long duration and adverse events (AEs), including liver toxicity. Due to comorbidities and polypharmacy, people living with HIV (PLHIV) may be at increased risk of INH-associated AEs. Our study aimed to assess the prevalence of AEs among patients receiving INH treatment for LTBI, to identify risk factors for their occurrence, and to evaluate whether PLHIV have higher odds of developing INH-associated AEs. Methods We conducted a single-center retrospective case-control study, including 130 outpatients with LTBI treated with INH between July 2019 and March 2022. Participants who developed AE (cases) were compared to controls, and a subgroup of PLHIV was compared to HIV-negative participants. Demographics, socioeconomic variables, comorbidities, and clinical variables were compared between study groups. Patient data were obtained from institutional electronic medical records, and outcomes were measured at regularly scheduled appointments. Results We included 130 participants, of which 54 were PLHIV. The PLHIV subgroup was significantly younger (p = 0.01) and demonstrated significantly higher prevalences of chronic liver disease, previous viral hepatitis, daily alcohol consumption, and intravenous drug use (IDU). One-third of the participants had an AE (45 cases, 34.6%), with liver toxicity being the most common (22.3%). Participants who developed AEs were significantly older (p = 0.030) and had a higher prevalence of economic hardship (p = 0.037), as well as higher scores of the Charlson comorbidity index (p = 0.002) than the controls. INH withdrawal occurred in 17 participants (13.1%) and was mainly associated with liver toxicity (p < 0.01) and gastrointestinal symptoms (p = 0.022). In the adjusted effect model, an age ≥ 65 years, economic hardship, and excessive alcohol consumption were significantly associated with higher odds of AEs, while HIV infection decreased the odds by 68.4% (p = 0.033). Conclusions In our study, INH-associated AEs were common, with liver toxicity being the most frequent. Older age, economic hardship, and excessive alcohol consumption increased the odds of INH-associated AEs, while PLHIV had lower odds of developing INH-associated AEs, even when adjusting for other variables in the multivariate analysis. Further studies should be conducted to assess if these results are replicable in a larger population and in different settings.

Medulloblastoma Development in a Patient with a Constitutional Balanced t(5;22)(q35.1;q11.2) Involving the NF2 Gene.

Neurofibromatosis type 2 (NF2) is a brain tumor predisposing syndrome caused by inactivating alterations of the NF2 gene mapped at chromosome 22q. Currently, no genetic information exists on medulloblastomas occurring in NF2 patients. We herein report on the genetic alterations observed in a girl in which the NF2 gene was de novo altered due to a constitutional translocation: t(5;22)(q35.1;q11.2). This girl had a particularly aggressive disease course. At the age of 4, she had already been diagnosed with three lesions classified as schwannomas and a meningioma. At 10 years old, she developed a medulloblastoma. She died at the age of 14 due to a refractory acute myeloid leukemia (AML). From the genetic point of view, we observed that (1) the NF2 gene was rearranged in all patient samples: blood, tumor, and leukemic cells; (2) loss of 3' region of NF2 and the downstream regions of chromosome 22 were only detected in medulloblastoma cells; (3) the known cancer AML-related gene: NPM1 which is mapped at 5q35.1 was not the target of any alteration in our patient. Our data suggest that inactivation of the NF2 gene was relevant for the medulloblastoma pathogenesis. Furthermore, we know that malignant cancers are the result of a multi-epi-genetic sequence of events, and although, unquestionably limited to the genetic findings in one case. We may hypothesize, that as described for a fraction of medulloblastomas, the alteration of a gene mapped at 5q might also have been relevant for medulloblastoma development in our patient.

Eosinophilia in Amoxicillin-Induced Rash in Infectious Mononucleosis.

A link between amoxicillin-induced rash in infectious mononucleosis and allergy has been previously reported. However, the pathophysiological cause and aspects are unclear. Additionally, the complex immunological interaction between the host and Epstein-Barr virus needs to be studied. This article reports a case of amoxicillin-induced rash in infectious mononucleosis resulting in an exuberant rash, facial edema, and marked eosinophilia, which prompted additional workup. Both the eosinophilia and the rash brought to light a possible association with a persistent delayed-type hypersensitivity. Further scientific discussion and investigation can identify predictive indicators that can portend clinical outcome.

Nocardiosis: a single-center experience and literature review

ABSTRACT Introduction: Nocardiosis is a rare bacterial infection caused by Nocardia spp. However, an increasing incidence has been described whereby data about epidemiology and prognosis are essential. Methods: A retrospective descriptive study was conducted among patients with positive Nocardia spp. culture, from January 2019 to January 2023, at a Terciary Hospital in Portugal. Results: Nocardiosis was considered in 18 cases with a median age of 63.8-years-old. At least one immunosuppressive cause was identified in 70% of patients. Five patients had Disseminated Nocardiosis (DN). The lung was the most common site of clinical disease (77.8%) and Nocardia was most commonly identified in respiratory tract samples. The most frequently isolated species were Nocardia nova/africana (n = 7) followed by Nocardia cyriacigeorgica (n = 3) and Nocardia pseudobrasiliensis (n = 3). The majority of the patients (94.4%) received antibiotic therapy, of whom as many as 55.6% were treated with monotherapy. The most frequently prescribed antibiotic was trimethoprim-sulfamethoxazole. Selected antimicrobial agents were generally effective, with linezolid and cotrimoxazole (100% Susceptibility [S]) and amikacin (94% S) having the most activity against Nocardia species. The median (IQR) duration of treatment was 24.2 (1-51.4) weeks for DN; The overall one-year case fatality was 33.3% (n = 6) and was higher in the DN (66.7%). No recurrence was observed. Conclusion: Nocardiosis is an emerging infectious disease with a poor prognosis, particularly in DN. This review offers essential epidemiological insights and underscores the importance of gaining a better understanding of the microbiology of nocardiosis. Such knowledge can lead to the optimization of antimicrobial therapy and, when necessary, guide appropriate surgical interventions to prevent unfavorable outcomes.

Secondary Organising Pneumonia Among COVID-19 Patients: A Retrospective Case-Control Study.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Secondary organising pneumonia (OP) induced by SARS-CoV-2 infection is a recently recognised complication of COVID-19. We aimed to evaluate the prevalence of OP among hospitalised patients with COVID-19 pneumonia and to assess whether disease severity and other clinical factors and comorbidities are correlated with OP development. We conducted a retrospective case-control study including hospitalised patients due to COVID-19 who performed a chest CT scan during hospitalisation and compared patients with clinical and radiological evidence of OP to patients without evidence of OP. Demographics, comorbidities, disease severity, dexamethasone/remdesivir treatment, laboratory results, and outcomes were compared between groups. One hundred fifteen patients were included, of whom 48 (41.7%) fulfilled clinical and imaging criteria for OP. Among OP patients, the most common chest CT-scan findings were consolidations, arciform condensations, and subpleural bands. OP patients had longer hospitalisation (19.5 vs 10 days, p=0.002) and more frequent ICU admission, but no significant differences in readmittance or mortality rates within 180 days compared to controls. In the adjusted effects model, the need for supplementary oxygen on the 21st day after symptom onset, the presence of Ordinal Scale for Clinical Improvement (OSCI) = 4, when compared to OSCI ≤ 3, and higher C-reactive protein on admission, were significantly associated with higher odds for OP. No other differences were identified between OP and controls after adjusting for other factors. The use of remdesivir or dexamethasone did not impact the diagnosis of OP. Only 38% of OP patients required treatment with high-dose corticosteroids. In conclusion, SARS-CoV-2-induced OP may be more frequent than previously thought, especially among hospitalised patients and patients with a more severe disease, particularly those who fail to improve after the second week of disease or who present higher inflammatory markers on admission. It increases the length of stay, but not all patients require specific treatment and OP may improve despite the absence of high-dose corticosteroid treatment.

HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019.

Objective: To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks. Methods: Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses. Results: In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (p for-trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G. Conclusion: Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.

Perinatal outcomes in children born after fresh or frozen embryo transfer using donated oocytes.

STUDY QUESTION: Do children born after vitrified-thawed embryo transfers (ETs) using donated oocytes have worse perinatal outcomes when compared with fresh ET? SUMMARY ANSWER: No significant difference in birthweight and prematurity rates between fresh or frozen embryo transfers (FETs) in newborns after oocyte donation was found. WHAT IS KNOWN ALREADY: Autologous singletons born after fresh ET have been previously associated with higher rates of preterm birth and low birthweight, while FETs seem to confer a higher risk of hypertensive disorders during pregnancy and macrosomia. However, studies comparing these outcomes using autologous oocytes are unable to adequately disentangle the putative detrimental consequences of embryo vitrification from the possible effects that ovarian stimulation and endometrial preparation may have on endometrial receptivity prior to ET. The oocyte donation model is, for this reason, a more appropriate setting to study these hypotheses; however so far, the information available regarding neonatal outcomes in this patient population is limited to either small and/or heterogeneous studies. STUDY DESIGN, SIZE, DURATION: We performed a multicentre retrospective cohort study including 5848 singletons born between 2009 and February 2020 following oocyte donation and single blastocyst transfer, subdivided according to whether a fresh ET or FET was performed. We also performed two additional sensitivity analyses, subgrouping the sample according to the type of endometrial preparation (natural versus artificial) and whether the donated oocytes had previously been vitrified or not. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients with a first singleton livebirth after single blastocyst transfer were compared using multivariable regression analysis to account for potential confounding factors. The primary outcome was birthweight. Secondary outcomes were birthweight z-scores and percentiles, small/large for gestational age, gestational age at delivery, gender, prematurity (<37 weeks and <32 weeks), neonatal morbidity (Apgar scores and need for neonatal intensive care) and maternal morbidity (gestational hypertensive disorders, gestational diabetes and caesarean delivery). MAIN RESULTS AND THE ROLE OF CHANCE: There was no significant difference between the fresh ET and FET groups in terms of mean birthweight (3215 g versus 3200 g) and birthweight z-scores (0.03 versus 0.1), in both the unadjusted and confounder-adjusted models. However, artificial endometrial preparation was associated with a higher birthweight (3220 g versus 3105 g) and birthweight z-scores (0.06 versus -0.13) when compared with a transfer in a natural cycle. Although a 1-day statistically significant difference in gestational age at birth (275 versus 274 days) was detected, premature birth rates (<37 weeks) did not vary significantly between groups (9.9% and 11.2% for fresh ET and FET, respectively). No other statistically significant differences were found in the remaining neonatal and maternal outcomes studies between the fresh ET and FET groups. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective design and lack of information regarding congenital malformations. Moreover, the sample selection criteria that were used may limit the generalizability of our results. WIDER IMPLICATIONS OF THE FINDINGS: Perinatal outcomes did not seem to be affected significantly by the embryo vitrification process in an oocyte donation model. Hence, other factors may contribute to the hindered perinatal outcomes described in ART, particularly the potential effect that ovarian stimulation and endometrial preparation may have on endometrial receptivity. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was obtained for this study. All authors have no conflicts to declare. TRIAL REGISTRATION NUMBER: N/A.

Cysteine Boosts Fitness Under Hypoxia-Mimicked Conditions in Ovarian Cancer by Metabolic Reprogramming.

Among gynecologic malignancies, ovarian cancer is the third most prevalent and the most common cause of death, especially due to diagnosis at an advanced stage together with resistance to therapy. As a solid tumor grows, cancer cells in the microenvironment are exposed to regions of hypoxia, a selective pressure prompting tumor progression and chemoresistance. We have previously shown that cysteine contributes to the adaptation to this hypoxic microenvironment, but the mechanisms by which cysteine protects ovarian cancer cells from hypoxia-induced death are still to be unveiled. Herein, we hypothesized that cysteine contribution relies on cellular metabolism reprogramming and energy production, being cysteine itself a metabolic source. Our results strongly supported a role of xCT symporter in energy production that requires cysteine metabolism instead of hydrogen sulfide (H2S) per se. Cysteine degradation depends on the action of the H2S-synthesizing enzymes cystathionine ß-synthase (CBS), cystathionine γ-lyase (CSE), and/or 3-mercaptopyruvate sulfurtransferase (MpST; together with cysteine aminotransferase, CAT). In normoxia, CBS and CSE inhibition had a mild impact on cysteine-sustained ATP production, pointing out the relevance of CAT + MpST pathway. However, in hypoxia, the concomitant inhibition of CBS and CSE had a stronger impact on ATP synthesis, thus also supporting a role of their hydrogen sulfide and/or cysteine persulfide-synthesizing activity in this stressful condition. However, the relative contributions of each of these enzymes (CBS/CSE/MpST) on cysteine-derived ATP synthesis under hypoxia remains unclear, due to the lack of specific inhibitors. Strikingly, NMR analysis strongly supported a role of cysteine in the whole cellular metabolism rewiring under hypoxia. Additionally, the use of cysteine to supply biosynthesis and bioenergetics was reinforced, bringing cysteine to the plateau of a main carbon sources in cancer. Collectively, this work supports that sulfur and carbon metabolism reprogramming underlies the adaptation to hypoxic microenvironment promoted by cysteine in ovarian cancer.

The Impact of SARS-CoV-2 Viral Load on the Mortality of Hospitalized Patients: A Retrospective Analysis.

Introduction Coronavirus disease 2019 (COVID-19) has emerged worldwide since December 2019. The standard method for diagnosis is via nucleic acid amplification testing, usually with a reverse-transcription polymerase chain reaction (RT-PCR). Hospitalized infected individuals may require ventilation and may have higher mortality rates. We aim to evaluate the clinical impact of nasopharyngeal viral load on these outcomes. Materials and methods We conducted a retrospective cohort study of patients hospitalized with COVID-19 from 17 March 2020 to 1 June 2020 at a tertiary care hospital. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load was assessed using cycle threshold (Ct) values from an RT-PCR assay applied to nasopharyngeal swab samples. We compared the clinical characteristics of survivors vs. non-survivors and assessed whether the viral load was independently associated with in-hospital 30-day mortality. Results We evaluated 197 patients. Thirty-day mortality was verified in 71 (36%) subjects. In the adjusted effects model, only the E-gene Ct value [odd ratio (OR) .873; confidence interval (CI) 95% .769-.992; p .037], age, the number of days of symptoms before admission, lactate dehydrogenase (LDH), and the oxygen saturation (SatO2)-to-fraction of inspired oxygen (FiO2) ratio remained significantly associated with 30-day mortality. There was no identified association between the viral loads and disease severity, the need for ventilation, or length of stay. Discussion Our results are, in part, concordant with previous papers. One possible limitation to our study is the fact that possibly included disproportionately more patients with poorer outcomes since hospitalization was required. Therefore, further research is required. Conclusion SARS-CoV-2 viral load on admission may be an independent predictor of 30-day mortality among hospitalized patients with COVID-19. Providing this information to clinicians could potentially be used to guide risk stratification.

Decision making based on hybrid modeling approach applied to cellulose acetate based historical films conservation.

Preserving culture heritage cellulose acetate-based historical films is a challenge due to the long-term instability of these complex materials and a lack of prediction models that can guide conservation strategies for each particular film. In this work, a cellulose acetate degradation model is proposed as the basis for the selection of appropriate strategies for storage and conservation for each specimen, considering its specific information. Due to the formulation complexity and diversity of cellulose acetate-based films produced over the decades, we hereby propose a hybrid modeling approach to describe the films degradation process. The problem is addressed by a hybrid model that uses as a backbone a first-principles based model to describe the degradation kinetics of the pure cellulose diacetate polymer. The mechanistic model was successfully adapted to fit experimental data from accelerated aging of plasticized films. The hybrid model considers then the specificity of each historical film via the development of two chemometric models. These models resource on gas release data, namely acetic acid, and descriptors of the films (manufacturing date, AD-strip value and film type) to assess the current polymer degradation state and estimate the increase in the degradation rate. These estimations are then conjugated with storage conditions (e.g., temperature and relative humidity, presence of adsorbent in the film's box) and used to feed the mechanistic model to provide the required time degradation simulations. The developed chemometric models provided predictions with accuracy more than 87%. We have found that the storage archive as well as the manufacturing company are not determining factors for conservation but rather the manufacturing date, off gas data as well as the film type. In summary, this hybrid modeling was able to develop a practical tool for conservators to assess films conservation state and to design storage and conservation policies that are best suited for each cultural heritage film.

Remission of Pediatric Diffuse Intrinsic Pontine Glioma: Case Report and Review of the Literature.

BACKGROUND: Diffuse midline glioma (DMG) is one of the most aggressive pediatric tumors. Approximately 60% of pediatric DMG patients die within the first year of diagnosis. Complete clinical and radiological remission of DMG is extremely rare. The objective of this study was to describe a case of remission of pediatric DMG and to compare with similar cases published so far. RESULTS: DMG was diagnosed in a 2-year-old girl who presented with brainstem and increased intracranial pressure manifestations. Ventriculoperitoneal shunt and chemotherapy-based treatment were offered. From the diagnosis, in spite of progressive enlargement of the tumoral lesion, her clinical condition improved remarkably. After the end of chemotherapy, progressive and gradual imagiological improvements occurred. At the end of the 60th month of follow-up, she was asymptomatic with total remission. Six pediatric DMG cases, from birth to the age of 3, in whom remission occurred were found in the literature. Histology sample was available in two of them (fibrillary astrocytoma-WHO Grade II and anaplastic astrocytoma-WHO Grade III). None received chemotherapy or radiotherapy. CONCLUSION: Remission of pediatric DMG is extremely rare and reinforces the biological heterogeneity of the tumor. In the absence of reliable predictors of prognosis, offering the best supportive treatment, including neurosurgical interventions should be considered in similar cases.

First-Principles Model to Evaluate Quantitatively the Long-Life Behavior of Cellulose Acetate Polymers.

A deep understanding of the degradation of cellulose diacetate (CDA) polymer is crucial in finding the appropriate long-term stability solution. This work presents an investigation of the reaction mechanism of hydrolysis using electronic density functional theory calculations with the B3LYP/6-31++G** level of theory to determine the energetics of the degradation reactions. This information was coupled with the transition-state theory to establish the kinetics of degradation for both the acid-catalyzed and noncatalyzed degradation pathways. In this model, the dependence on water concentration of the polymer as a function of pH and the evaporation of acetic acid from the polymer is explicitly accounted for. For the latter, the dependence of the concentration of acetic acid inside the films with the partial pressure on the surrounding environment was measured by sorption isotherms, where Henry's law constant was measured as a function of temperature. The accuracy of this approach was validated through comparison with experimental results of CDA-accelerated aging experiments. This model provides a step forward for the estimation of CDA degradation dependence on environmental conditions. From a broader perspective, this method can be translated to establish degradation models to predict the aging of other types of polymeric materials from first-principles calculations.

Bilateral fracture of the shoulders following epileptic seizures: a case report / Fratura bilateral de ombros após convulsões epilépticas: relato de caso

Convulsive seizures caused by hyponatremia occur when this condition is severe and develops quickly, resulting in a brain's adaptive inability to contain brain swelling. Seizures are rarely the cause of shoulder fractures. This is a case report of bilateral humerus fracture following a single epileptic seizure caused by drug hyponatremia, an unconventional event in medical practice. A 69-year-old woman was admitted to the emergency room after a single tonic-clonic seizure with spontaneously ceased sphincter relaxation, showing Glasgow 6. No falls or restraint were reported by observers. When alert, the patient reported pain and difficulty moving both arms. During examination, the movement was li- mited to the right and left. Anteroposterior radiographs revealed bilateral fracture at the neck of humerus. To complement inves- tigation for further lesions, a computed tomography confirmed bilateral fracture-dislocation with impaction of the humeral head with the glenoid. Atraumatic bilateral fracture-dislocation of the humerus after epileptic seizure is a very rare event. It is believed that some of these diagnoses have been neglected due to the difficulty of characterizing the patient's pain in a postictal state. The importance of a detailed physical examination shall be emphasized in risk groups such as the polymedicated elderly.

Convulsive seizures caused by hyponatremia occur when this condition is severe and develops quickly, resulting in a brain's adaptive inability to contain brain swelling. Seizures are rarely the cause of shoulder fractures. This is a case report of bilateral humerus fracture following a single epileptic seizure caused by drug hyponatremia, an unconventional event in medical practice. A 69-year-old woman was admitted to the emergency room after a single tonic-clonic seizure with spontaneously ceased sphincter relaxation, showing Glasgow 6. No falls or restraint were reported by observers. When alert, the patient reported pain and difficulty moving both arms. During examination, the movement was li- mited to the right and left. Anteroposterior radiographs revealed bilateral fracture at the neck of humerus. To complement inves- tigation for further lesions, a computed tomography confirmed bilateral fracture-dislocation with impaction of the humeral head with the glenoid. Atraumatic bilateral fracture-dislocation of the humerus after epileptic seizure is a very rare event. It is believed that some of these diagnoses have been neglected due to the difficulty of characterizing the patient's pain in a postictal state. The importance of a detailed physical examination shall be emphasized in risk groups such as the polymedicated elderly.

Cysteine Aminotransferase (CAT): A Pivotal Sponsor in Metabolic Remodeling and an Ally of 3-Mercaptopyruvate Sulfurtransferase (MST) in Cancer.

Metabolic remodeling is a critical skill of malignant cells, allowing their survival and spread. The metabolic dynamics and adaptation capacity of cancer cells allow them to escape from damaging stimuli, including breakage or cross-links in DNA strands and increased reactive oxygen species (ROS) levels, promoting resistance to currently available therapies, such as alkylating or oxidative agents. Therefore, it is essential to understand how metabolic pathways and the corresponding enzymatic systems can impact on tumor behavior. Cysteine aminotransferase (CAT) per se, as well as a component of the CAT: 3-mercaptopyruvate sulfurtransferase (MST) axis, is pivotal for this metabolic rewiring, constituting a central mechanism in amino acid metabolism and fulfilling the metabolic needs of cancer cells, thereby supplying other different pathways. In this review, we explore the current state-of-art on CAT function and its role on cancer cell metabolic rewiring as MST partner, and its relevance in cancer cells' fitness.