Programmed death-ligand 1 (PD-L1) expression in cervical intraepithelial neoplasia and cervical squamous cell carcinoma of HIV-infected and non-infected patients.

Programmed death-ligand 1 (PD-L1) is overexpressed in cervical carcinoma, hindering tumor destruction. The aim of this study was to assess PD-L1 expression by immunohistochemistry in cervical squamous cell carcinoma (SCC) and squamous intraepithelial lesions (SILs) from human immunodeficiency virus-positive (HIV+) and human immunodeficiency virus-negative (HIV-) patients. A total of 166 SCC and SIL samples of HIV+ and HIV- patients were included and analyzed for PD-L1 expression through tumor proportion score (TPS), and results were stratified in five TPS groups using SP263 antibody and, combined positive score (CPS) using 22C3 antibody. In cohort 1 (SP263 clone), all HIV+ patients were negative for intraepithelial lesion or malignancy (NILM), and low-grade squamous intraepithelial lesions (LSILs) scored < 1; and 87.5% of high-grade squamous intraepithelial lesions (HSILs) adjacent to SCC, 19% of HSILs non-adjacent to SCC, and 69% of SCCs scored ≥ 1 (15.4% scored 5). In HIV- patients, all NILM, LSILs, HSILs adjacent to SCC, and two HSILs non-adjacent to SCC scored < 1. SCC: 88.2% scored ≥ 1 and 5.9% scored 5. In cohort 2 (SP263 and 22C3 clones), 16.7% of HIV+ patients with SCC were positive with both clones, CPS ≥ 1 (22C3) or score 5 (≥ 50%) (SP263), showing no significant differences in positivity between both clones. These results indicate that a relatively low percentage of SCCs (16.7%; both in HIV+ and in HIV- patients) express PD-L1 (TPS ≥ 50% and CPS > 1), which may be due to some samples being archival material, sample characteristics, or use of different methodologies, highlighting the need for standardization of PD-L1 assessment in SCC of the cervix. The fact that PD-L1 is overexpressed in SILs of HIV+ patients suggests potential additional applications for immunotherapy in this disease.

Asymptomatic chronic red eye: A surgical technique case report.

Introduction and importance: Ocular Surface Squamous-cell Neoplasia (OSSN) is an infrequent diagnosis whose clinical suspicion assumes great importance and should not be overlooked. The following case-report aims to describe the diagnosis and treatment of a patient with OSSN whose complaints were mild in comparison to the severity of the disease. The chosen surgical technique was paramount for a disease-free outcome while minimizing the scarring effects of surgical removal. CASE PRESENTATION: Patient presented mild discomfort right eye and painless persistent hyperaemia. Slit-lamp observation showed a clear diagnosis and lesion's extent evaluated through multimodal imaging. After surgical excision the patient underwent topical ocular treatment with mitomycin-C for a higher margin of safety even before the pathology results were available. DISCUSSION: Ancillary exam technology improvement has allowed a higher margin of safety while determining the extent of OSSN lesions. In the absence of clear diagnostic criteria and guidelines, clinical reasoning and OSSN awareness are critical for timely diagnosis and treatment, as several treatment options are available, allowing an increasing number of patients to be treated non-invasively. In this case-report, we highlight the importance of early-recognition and the reasoning for choosing a combined treatment option with a higher margin of safety. CONCLUSION: Early recognition and prompt treatment of OSSN lesions is of paramount importance to avoid ocular invasiveness and potentially preclude both ocular and systemic complication. The choice of a combined surgical and medical approach may provide a higher margin of safety for suitable cases. This patient is currently disease-free at 6-month follow-up.

Keratoconus tomographic indices in osteogenesis imperfecta.

PURPOSE: Osteogenesis imperfecta (OI) is a rare inherited disease affecting collagen-rich tissues. Ocular complications have been reported such as thin corneas, low ocular rigidity, keratoconus, among others. The purpose of this study is to characterize corneal tomographic features in OI patients compared to unaffected patients, with particular focus on commonly studied keratoconus indices. METHODS: Cross-sectional case-control study including 37 OI patients and 37 age-matched controls. Patients and controls underwent comprehensive ophthalmological examination including corneal Scheimpflug tomography with a Pentacam HR device (Oculus Optikgeräte GmbH, Wetzlar, Germany) to analyse and compare topometric, tomographic, pachymetric and Belin-Ambrósio Enhanced Ectasia Display III (BAD-D) data of both eyes of each patient. RESULTS: Most OI patients had type I disease (n = 24; 65%) but type III-VII patients were also included. Two patients had clinically overt bilateral keratoconus. OI patients had significantly higher maximum keratometry (45.2 ± 2.1 vs. 43.7 ± 1.2; p = 0.0416), front and back elevation (3.0 ± 3.3 vs. 2.1 ± 1.3, p = 0.0201; 11.1 ± 8.2 vs. 5.0 ± 3.7, p < 0.0001), index of surface variance (25.5 ± 13 vs. 17.4 ± 8.3; p = 0.0016), index of vertical asymmetry (0.21 ± 0.14 vs. 0.15 ± 0.06; p = 0.0215), index of height asymmetry (9.2 ± 14 vs. 6.0 ± 4.5; p = 0.0421), index of height decentration (0.02 ± 0.01 vs. 0.01 ± 0.01; p < 0.0001) and average pachymetric progression (1.01 ± 0.19 vs. 0.88 ± 0.14; p < 0.0001) readings. Thinnest corneal thickness and maximum Ambrósio relational thickness were significantly lower (477 ± 52 vs. 543 ± 26; 387 ± 95 vs. 509 ± 49; p < 0.0001). Two-thirds of OI patients had corneas with a minimum thickness < 500 µm. BAD-D value was significantly higher in OI patients (2.1 ± 1.4 vs. 0.9 ± 0.2; p < 0.0001). CONCLUSION: OI patients showed significant changes in corneal profiles compared with healthy subjects. A high proportion of patients had tomographically suspect corneas when using keratoconus diagnostic indices. Further studies are warranted to assess the true risk of corneal ectasia in OI patients.

Clonal hematopoiesis is not prevalent in Hutchinson-Gilford progeria syndrome.

Clonal hematopoiesis of indeterminate potential (CHIP), defined as the presence of somatic mutations in cancer-related genes in blood cells in the absence of hematological cancer, has recently emerged as an important risk factor for several age-related conditions, especially cardiovascular disease. CHIP is strongly associated with normal aging, but its role in premature aging syndromes is unknown. Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare genetic condition driven by the accumulation of a truncated form of the lamin A protein called progerin. HGPS patients exhibit several features of accelerated aging and typically die from cardiovascular complications in their early teens. Previous studies have shown normal hematological parameters in HGPS patients, except for elevated platelets, and low levels of lamin A expression in hematopoietic cells relative to other cell types in solid tissues, but the prevalence of CHIP in HGPS remains unexplored. To investigate the potential role of CHIP in HGPS, we performed high-sensitivity targeted sequencing of CHIP-related genes in blood DNA samples from a cohort of 47 HGPS patients. As a control, the same sequencing strategy was applied to blood DNA samples from middle-aged and elderly individuals, expected to exhibit a biological age and cardiovascular risk profile similar to HGPS patients. We found that CHIP is not prevalent in HGPS patients, in marked contrast to our observations in individuals who age normally. Thus, our study unveils a major difference between HGPS and normal aging and provides conclusive evidence that CHIP is not frequent in HGPS and, therefore, is unlikely to contribute to the pathophysiology of this accelerated aging syndrome.

Lymphocyte Subsets in Cervicovaginal Lavage Specimens of HIV-Infected Women: A Surrogate Risk Marker of HPV-Associated Cervical Lesions.

INTRODUCTION: To better understand the role of mucosa immunity in the development of cervical carcinoma in HIV infection, cervical lymphocyte subsets were characterized in HIV+ and HIV- women, as well as their relation to HPV-associated cervical lesions. METHODS: Eighty-three (52 HIV+, 31 HIV-) cell suspensions of cervicovaginal lavage (CVL) and 52 HIV+ peripheral blood (PB) samples were assessed by flow cytometry to evaluate lymphoid populations. High-risk (HR) HPV was assessed in liquid-based cytology and HIV mRNA in PB in the same patients. RESULTS: Cervical CD4+ T cells and CD4+/CD8+ ratio were decreased (p < 0.0001) and cervical CD8+ T cells were increased (p = 0.0080) in HIV+ women. These patients had lower CD4+ T-cell percentages in CVL compared to PB (p = 0.0257), and the opposite was true for CD8+ T cells (p = 0.0104). They also had a higher prevalence of high-grade squamous intraepithelial lesions (SILs) with an increased prevalence of HR HPV. Cervical CD8+ T cells were increased in HR HPV+ patients (p = 0.0300) and related to higher prevalence of SILs (p = 0.0001). DISCUSSION/CONCLUSION: Cervical lymphoid populations can be characterized by flow cytometry, showing a distinct cervical T-cell compartment in HIV+ women. This may represent a surrogate risk marker of HPV-associated cervical lesions in this population and prompt further research on this subject, contributing to improving patients' management.

In vivo expansion of a CD9+ decidual-like NK cell subset following autologous hematopoietic stem cell transplantation.

Autologous hematopoietic stem cell transplantation (autoHSCT) is a treatment option for hematological disorders and pediatric solid tumors. After an autoHSCT, natural killer (NK) cells are the first lymphocyte subset returning to normal levels. To uncover global changes during NK cell reconstitution after autoHSCT, we performed RNA-sequencing on NK cells before and after autoHSCT. Results showed profound changes in the gene expression profile of NK cells immediately after autoHSCT. Several biological processes including cell cycle, DNA replication and the mevalonate pathway were enriched. Significantly, we observed that following autoHSCT, NK cells acquired a decidual-like gene expression profile, including the expression of CD9. By using multiparametric flow cytometry, we confirmed the expansion of NK cells expressing CD9 immediately after autoHSCT, which exhibited higher granzyme B and perforin expression levels than CD9- NK cells. These results provide insights into the physiopathology of NK cells during their reconstitution after autoHSCT.

Pelvic Desmoid Tumor: A Rare Case with Difficult Diagnosis and Treatment.

Desmoid tumors are rare benign neoplasms, with locally aggressive characteristics. Ongoing or previous pregnancy, antecedent trauma, and familial adenomatous polyposis are known risk factors. Still, the majority of cases are sporadic and its etiology is still unknown. These tumors may occur in any body site, but retroperitoneal and pelvic desmoid tumors are extremely rare. Nonspecific clinical and radiological findings lead to erroneous diagnosis in 50% of patients before surgery. We present a case of a young multiparous female with a deep infiltrative lesion adherent to the right pelvic sidewall leading to severe right hydroureteronephrosis and ipsilateral loss of renal function. Although deep endometriosis was suspected, malignancy features could not be excluded by imaging studies. The patient underwent an exploratory laparotomy for definite diagnosis and treatment, which led to right nephrectomy, hysterectomy, and right oophorectomy because of deep infiltration and difficult dissection. Definite histologic diagnosis revealed the presence of a pelvic desmoid tumor. Positive margins were encountered but, until this moment, no disease relapse occurred.

Trained immunity induction by the inactivated mucosal vaccine MV130 protects against experimental viral respiratory infections.

MV130 is an inactivated polybacterial mucosal vaccine that confers protection to patients against recurrent respiratory infections, including those of viral etiology. However, its mechanism of action remains poorly understood. Here, we find that intranasal prophylaxis with MV130 modulates the lung immune landscape and provides long-term heterologous protection against viral respiratory infections in mice. Intranasal administration of MV130 provides protection against systemic candidiasis in wild-type and Rag1-deficient mice lacking functional lymphocytes, indicative of innate immune-mediated protection. Moreover, pharmacological inhibition of trained immunity with metformin abrogates the protection conferred by MV130 against influenza A virus respiratory infection. MV130 induces reprogramming of both mouse bone marrow progenitor cells and in vitro human monocytes, promoting an enhanced cytokine production that relies on a metabolic shift. Our results unveil that the mucosal administration of a fully inactivated bacterial vaccine provides protection against viral infections by a mechanism associated with the induction of trained immunity.

Topical corticosteroids with topical cyclosporine A versus topical corticosteroids alone for immunological corneal graft rejection.

PURPOSE: To assess the efficacy and safety of supplementing topical cyclosporine A (CsA) to topical corticosteroids (CS), in the prophylaxis and treatment of corneal graft rejection following penetrating keratoplasty (PK). METHODS: Meta-analysis. Search was performed in PubMed, CENTRAL, ClinicalTrials.gov, reference lists of articles and conference proceedings. Primary outcomes: 1-year rejection-free survival rate (prophylaxis); resolution rate of rejection episodes (treatment). Secondary outcomes: 6- and 24-month rejection-free graft survival rate, number of rejection episodes during follow-up, time-to-resolution of rejection episode, 12- and 24-months graft survival rate, adverse events. Subgroup analyses were planned for high-risk grafts; primary vs. secondary prophylaxis of graft rejection episodes; and CsA concentrations of 0.05%, 1%, and 2%. RESULTS: Five studies of moderate methodological quality were included (one retrospective, four RCT), assessing 459 eyes (CS + CsA 226, CS 233). In the prophylaxis setting, supplemental CsA was associated with a higher rejection-free survival rate at 12-months (RR 1.25, 95% CI: 1.00-1.56, p = 0.05) and 24-months post-PK (RR 1.56, 95% CI: 1.15-2.11, p < 0.01), though no differences were found at the 6-months timepoint (p = 0.93). This effect was mostly verified using CsA 2% in the high-risk subset of patients. In the treatment setting, no differences were found in the resolution rate of rejection episodes (p = 0.23). No differences existed on drug-related adverse events. CONCLUSION: In the prophylaxis of rejection episodes post-PK, the combined regimen of CS + CsA was associated with a higher 1- and 2-year rejection-free graft survival rate. Subgroup analysis mostly supported the use of CsA 2% for high-risk grafts. Further studies are needed to validate these results.

Estado, comunidades terapêuticas e neoliberalismo: um estudo sobre a política de drogas no Brasil / State, therapeutic communities and neoliberalism: a study on drug policy in Brazil

A partir das mudanças correntes na política de drogas brasileira, que incentivam a expansão de instituições denominadas Comunidades Terapêuticas (CTs) ­ unidades destinadas ao acolhimento de pessoas que fazem uso de drogas ­, tem-se feito cada vez mais necessários estudos sobre o tema. Diante do entendimento de que, para entender a inserção das CTs no Estado, é preciso expandir o olhar e complexificar a questão, identificamos a importância de uma discussão que aborde o modo de funcionamento do neoliberalismo em seus vieses de organização estatal e social. Por essa razão, este trabalho tem como objetivo ­ por meio de um estudo qualitativo e documental ­ identificar as afinidades entre o avanço da racionalidade neoliberal e a lógica de funcionamento das Comunidades Terapêuticas no Brasil. Para isso, trabalhamos com os fundamentos políticos do neoliberalismo, entendendo-o como uma racionalidade política que altera todos os aspectos da vida; identificamos os fundamentos das CTs e a relação dessas instituições com o Estado brasileiro por meio da análise de legislações; e discutimos, partindo da análise documental realizada nos jornais O Globo e Folha de São Paulo e em documentos oficiais, o cenário de alianças, disputas e discursos políticos que, ao se afinarem com os fundamentos neoliberais, possibilitaram a expansão das CTs. No que tange às afinidades encontradas, destacamos dois momentos políticos importantes: o primeiro, ainda sob o mandato de Dilma Rousseff (PT), entre 2011 e 2016, apresenta, principalmente, um discurso pluralista neoliberal aliado à ideia de liberdade negativa e à soberania compartilhada do Estado; o segundo ­ pós-impeachment, em 2016 ­ é de incremento aos fundamentos supracitados com a formação de uma plutocracia em defesa de uma moral conservadora aliada ao discurso de responsabilização individual e ao esvaziamento dos espaços públicos de discussão. Todos os fundamentos encontrados demonstram não só a afinidade entre a expansão neoliberal e as CTs como também o derretimento dos princípios da democracia. A partir desta análise, espera-se que este estudo possa qualificar e dar subsídios para a construção de políticas de saúde de caráter público destinadas a usuários de substâncias psicoativas que se sustentem a partir de uma lógica democrática.

Since the changes in the Brazilian drug policy are stimulating the growth of Therapeutic Communities (TCs) ­ residential units which offer care to drug users ­, studies on the subject prove to be needed. To understand the close relationship between the TCs and public policies, it is necessary to expand our debate, hence we will recognize the importance of a study that analyzes how neoliberalism works. That said, this thesis aims to identify ­ through qualitative study and documental analysis ­ the likeness between neoliberal rationality and TCs' operation. To achieve that, we have discussed the neoliberalism political foundations, understanding it as political rationality that changes the surroundings of life; we have identified the TCs foundations and their connection with the Brazilian legislation; through the documental analysis we have discussed, through the brazilian newspapers O Globo and Folha de São Paulo, as well as official documents, the alliances, disputes, and political discourses that, together with the neoliberal foundations, enabled the growth of TCs. In addition to that, we have highlighted two important political marks. The first ­ situated in Dilma Rousseff's (PT) presidential term (2011-2016) ­ presents a neoliberal pluralist discourse allied with the idea of negative liberty and the shared sovereignty of the State. The second ­ which took place after Dilma's impeachment, in 2016 ­ introduces, in addition to the above foundations, the formation of a plutocracy that defends a conservative morality allied with the discourse of individual accountability and the emptying of public spaces for discussion. All the foundations we found have shown not only the affinity between neoliberal and the TCs growth, but also the undoing of democracy. We expect this discussion to qualify and offer subsidies for the construction of public health policies for drug users that are sustained in democratic foundations.

Alterations in Circulating Monocytes Predict COVID-19 Severity and Include Chromatin Modifications Still Detectable Six Months after Recovery.

An early analysis of circulating monocytes may be critical for predicting COVID-19 course and its sequelae. In 131 untreated, acute COVID-19 patients at emergency room arrival, monocytes showed decreased surface molecule expression, including low HLA-DR, in association with an inflammatory cytokine status and limited anti-SARS-CoV-2-specific T cell response. Most of these alterations had normalized in post-COVID-19 patients 6 months after discharge. Acute COVID-19 monocytes transcriptome showed upregulation of anti-inflammatory tissue repair genes such as BCL6, AREG and IL-10 and increased accessibility of chromatin. Some of these transcriptomic and epigenetic features still remained in post-COVID-19 monocytes. Importantly, a poorer expression of surface molecules and low IRF1 gene transcription in circulating monocytes at admission defined a COVID-19 patient group with impaired SARS-CoV-2-specific T cell response and increased risk of requiring intensive care or dying. An early analysis of monocytes may be useful for COVID-19 patient stratification and for designing innate immunity-focused therapies.

Relative Age Effect in Physical Fitness of South Portugal Students between 10 and 18 Years Old.

Relative age is a phenomenon broadly studied in sport sciences. Youth sports participants born earlier in the selection year tend to present a maturational advantage over their peers. As it is also dependent on physical performance, older physical education students may also benefit from this effect in this school subject. The main goal of this manuscript was to determine whether the relative age effect is present within physical fitness outcomes of Portuguese children and adolescents. The physical-aerobic fitness, strength, flexibility and body composition of 885 students (490 females and 395 males) were collected and compared by quarters of birth, segmented by gender and age groups (10-12; 12-14; 14-16 and 16-18 years). The results reveal a moderate to small effect in physical fitness outcomes, with a trend for children and adolescents born in the early part of the year to present higher performance levels. These differences were more evident in ages closer to the physical maturational onset (12-14 y) and more apparent in male students. This physical fitness advantage may lead to a biased assessment and development of students born earlier in the year.

Detection of HIV mRNA in routine liquid-based cytology specimens of HIV-infected women.

OBJECTIVE: Human immunodeficiency virus-infected women have a high incidence of HPV infection, and HIV and HPV coinfection is associated with high incidence of cervical intraepithelial lesions and cervical cancer. This study investigated the ability to detect HIV mRNA in routine screening cervical liquid-based cytology (LBC) samples and its correlation with HPV coinfection and cervical intraepithelial lesions. METHODS: Liquid-based cytology samples from 80 HIV-infected women under combined antiretroviral therapy (cART) were studied for detection of HIV and HPV mRNA using Aptima® tests and for cytology diagnosis according to the 2014 Bethesda System for Reporting Cervical Cytology. Peripheral blood (PB) HIV mRNAs were assessed by real-time polymerase chain reaction (RT-PCR). Statistical analysis used Fisher's exact or Chi-square test to compare frequencies among groups and the Mann-Whitney U test to compare continuous variables. RESULTS: Human immunodeficiency virus mRNA was present in 21.3% of routine LBC samples in HIV-infected women, 12.5% of which had no detectable PB viral load. Among 10 patients diagnosed with high-grade squamous intraepithelial lesion (HSIL), 50% had detectable HIV viral load. The occurrence of HSIL vs low-grade intraepithelial lesion/negative intraepithelial lesion or malignancy in LBC samples was significantly higher in women with detectable HIV viral load (P = .029). CONCLUSIONS: Human immunodeficiency virus mRNA was present in routine LBC samples in HIV-positive women under cART. Detection of HIV viral load in LBC is significantly associated with cervical HSIL. This suggests the relevance of HIV mRNA viral load assessment in routine LBC, to evaluate patients' infectious potential and monitor efficacy of the cART scheme.

Clonal Hematopoiesis and Risk of Progression of Heart Failure With Reduced Left Ventricular Ejection Fraction.

BACKGROUND: Clonal hematopoiesis driven by somatic mutations in hematopoietic cells, frequently called clonal hematopoiesis of indeterminate potential (CHIP), has been associated with adverse cardiovascular outcomes in population-based studies and in patients with ischemic heart failure (HF) and reduced left ventricular ejection fraction (LVEF). Yet, the impact of CHIP on HF progression, including nonischemic etiology, is unknown. OBJECTIVES: The purpose of this study was to assess the clinical impact of clonal hematopoiesis on HF progression irrespective of its etiology. METHODS: The study cohort comprised 62 patients with HF and LVEF <45% (age 74 ± 7 years, 74% men, 52% nonischemic, and LVEF 30 ± 8%). Deep sequencing was used to detect CHIP mutations with a variant allelic fraction >2% in 54 genes. Patients were followed for at least 3.5 years for various adverse events including death, HF-related death, and HF hospitalization. RESULTS: CHIP mutations were detected in 24 (38.7%) patients, without significant differences in all-cause mortality (p = 0.151). After adjusting for risk factors, patients with mutations in either DNA methyltransferase 3 alpha (DNMT3A) or Tet methylcytosine dioxygenase 2 (TET2) exhibited accelerated HF progression in terms of death (hazard ratio [HR]: 2.79; 95% confidence interval [CI]: 1.31 to 5.92; p = 0.008), death or HF hospitalization (HR: 3.84; 95% CI: 1.84 to 8.04; p < 0.001) and HF-related death or HF hospitalization (HR: 4.41; 95% CI: 2.15 to 9.03; p < 0.001). In single gene-specific analyses, somatic mutations in DNMT3A or TET2 retained prognostic significance with regard to HF-related death or HF hospitalization (HR: 4.50; 95% CI: 2.07 to 9.74; p < 0.001, for DNMT3A mutations; HR: 3.18; 95% CI: 1.52 to 6.66; p = 0.002, for TET2 mutations). This association remained significant irrespective of ischemic/nonischemic etiology. CONCLUSIONS: Somatic mutations that drive clonal hematopoiesis are common among HF patients with reduced LVEF and are associated with accelerated HF progression regardless of etiology.

CD4+ and CD8+ cell populations in HIV-positive women with cervical squamous intra-epithelial lesions and squamous cell carcinoma.

INTRODUCTION: This study aimed to analyse cervical lymphocytic populations in HIV+ and HIV- patients and correlate different cervical lesions with HIV viral load and presence of high-risk HPV types. MATERIAL AND METHODS: A total of 132 histological specimens from 40 HIV+ and 72 HIV- patients were evaluated for CD4+ and CD8+ T cell distribution, presence of high-risk HPV types, peripheral blood HIV viral load and CD4+/CD8+ ratio. RESULTS: High-grade squamous intraepithelial lesions (HSIL) and squamous cell carcinoma (SCC) from HIV+ patients had lower CD4+ T cell scores compared with HIV- patients. In all lesion groups, HIV+ patients presented higher epithelial and stromal CD8+ T cell scores. HIV viral load was more often detectable in patients with SCC than in those with low-grade squamous intraepithelial lesion (LSIL) (p = 0.0409). HSIL HIV+ patients had lower circulating CD4+ T cell counts (p = 0.0434) and CD4+/CD8+ ratio (p = 0.0378) compared with LSIL HIV+ patients. High-risk HPV types other than 16 and 18/45 were more prevalent in the HIV+ group. DISCUSSION: These results support an imbalance between cervical CD4+ and CD8+ T lymphocytes of HIV+ patients with SIL and SCC, with increased CD8+ infiltrate density with lesion severity, even in patients with immune system recovery under cART.

Characterization of posterior corneal astigmatism in a population with keratoconus.

Background: The curvature of the anterior corneal surface is traditionally used as a surrogate to estimate corneal astigmatism. In recent years, increasing importance has been attributed to posterior corneal astigmatism as an indicator. Our aim is to characterize the posterior corneal surface in a population with keratoconus and investigate its predictive value to keratoconus progression. Methods: Retrospective study from a tertiary care centre (Hospital de Santa Maria, Lisbon, Portugal). Eighty-five patients (85 eyes) with keratoconus were included. All patients had two tomographical examinations ≥12 months apart (Pentacam HR). Vector analysis was used to calculate anterior (ACA), posterior (PCA), and total corneal astigmatism (TCA). Multivariate logistic regression was used to assess the predictive value of PCA to keratoconus progression, adjusting for ACA, TCA and several tomographical indices. Results: Study participants had a mean age of 32 (SD = 12.5) years. Mean tomographical keratoconus classification was 2.16 (SD = 0.95), with a mean Kmax of 55.8D (SD = 7.8). Mean power of PCA, ACA and TCA was, respectively, -0.88D (SD = 0.84), 3.74D (SD = 2.36), and 3.06D (SD = 2.01) and its centroids were 0.44D x 15º, 1.65D x 112º, and 1.61D x 106º, respectively. The power of PCA was ≥0.50, 1.00 and 2.00D in 75.3%, 32.9%, and 3.5% of patients, respectively, inducing against-the-rule astigmatism in 60.0% of patients. On average, ACA overestimated TCA in 0.35D x 151º (p < .01). ACA and TCA were highly correlated but showed a lack of agreement for clinical purposes. A predictive role for PCA was excluded. Conclusions: In this population with keratoconus, PCA contributed substantially to TCA. However, PCA was not a valuable predictor for disease progression.

Entre Caps AD e Comunidades Terapêuticas: o cuidado pela perspectiva dos usuários de um Caps AD / Between Caps AD and Therapeutic Communities: care from the perspective of users of Caps AD

RESUMO O debate em torno dos dispositivos e modelos de cuidado destinados aos usuários problemáticos de álcool e outras drogas tem ganhado cada vez mais espaço nas políticas públicas. A partir da discussão sobre os paradigmas da abstinência e da redução de danos, buscou-se investigar as relações e os sentidos que os usuários atribuem a esses paradigmas por meio da utilização das Comunidades Terapêuticas e dos Centros de Atenção Psicossocial Álcool e Drogas. Para isso, utilizou-se a metodologia da entrevista semiestruturada com usuários da rede de saúde mental que já haviam utilizado ou utilizavam os serviços supracitados. Além disso, investigaram-se os sentidos atribuídos ao conceito de redução de danos. Constatou-se que a utilização desses serviços possui pontos de convergência e divergência e que os momentos da busca por cada serviço não estão relacionados somente com uma demanda por tratamento. Observaram-se, também, a fragilidade na apreensão do conceito de redução de danos e a presença do ideal da abstinência na busca pelo tratamento. A partir da perspectiva dos usuários, espera-se contribuir para a ampliação das práticas de saúde mental no Sistema Único de Saúde.

ABSTRACT The debate regarding care models for problematic users of alcohol and other drugs has increased in Brazilian public policies. Based on the discussion on the abstinence and harm reduction paradigms, we sought to investigate the relationships and meanings that users attribute to such paradigms through the use of Therapeutic Communities and Psychosocial Care Centers for Alcohol and Drugs. For that, we used the semi-structured interview methodology with users of the mental health network who had already used the services mentioned above. In addition, the meanings attributed to the concept of harm reduction were investigated. It was found that the use of these services has points of convergence and divergence and that the moments of searching for each service are not related only to a demand for treatment. It was also observed a weak understanding of the concept of harm reduction and the presence of an abstinence ideal in the search for treatment. This research hopes to contribute to the expansion of mental health practices mainly, in the Brazilian Unified Health System.

A new oocyte-holding pipette for intracytoplasmic sperm injection without cytoplasmic aspiration: An experimental study in mouse oocytes.

We assessed the feasibility of using a new oocyte-holding pipette (pipette without aspiration, PiWA) for intracytoplasmic sperm injection (ICSI), which prevents cytoplasmic aspiration during microinjection. A pilot experimental study in eight mature mouse oocytes to assess the feasibility of the oocyte-holding PiWA for ICSI procedure. The absence of oocyte degeneration after microinjection and the viability of correct embryo development were also evaluated. The pipette comprises a suction conduit inside an elongated cylindrical body and a funnel-shaped working end, which is dimensioned to hold the oocyte in a tight-fitting manner. Upon aspirating via the suction conduit, the oocyte remains partially trapped inside the funnel and becomes deformed changing the spherical shape of its resting state to an oval shape that tensions the surface and increases the turgor. In all ICSI procedures using the new PiWA, the oocyte membrane presented some resistance but was easily broken when exerting some pressure or small aspiration. The eight oocytes developed, six of which reached the blastocyte stage. The results obtained in this study indicate that the increase in oocyte membrane turgidity caused by PiWA prevents vigorous aspiration of the cytoplasm during spermatozoa microinjection.

Double Cervix with Normal Uterus and Vagina - An Unclassified Müllerian Anomaly.

Müllerian anomalies are very common, and a frequent cause of infertility. The most used classification system until now, proposed by the American Society for Reproductive Medicine in 1988, categorizes comprehensively uterine anomalies but fails to classify defects of the cervix or vagina. This is based on a developmental theory that postulates that müllerian duct fusion is unidirectional, beginning caudally and extending cranially, which does not account for isolated cervical or vaginal defects. More recently, the European Society of Human Reproduction and Embryology has developed a consensus, which allows for independent cervical anomalies. We present a case of a 39-year-old woman with secondary infertility, found to have a cervical duplication in an anteroposterior disposition, which puts into question the principles of embryology formerly known, but supports the theory that development happens in a segmentary fashion.

DMEK versus DSAEK for Fuchs' endothelial dystrophy: A meta-analysis.

PURPOSE:: To compare the safety and efficacy profiles of Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) in adult patients with Fuchs' endothelial dystrophy. METHODS:: Electronic database search on MEDLINE and CENTRAL from inception to August 2017. We included all comparative studies of DMEK versus DSAEK in patients with diagnosed Fuchs' endothelial dystrophy. Studies assessing rescue procedures were excluded to minimize bias. Primary outcome: mean difference in best-corrected visual acuity (BCVA) at 3, 6, and 12 months postoperatively. Secondary outcomes: rates of graft primary failure, rejection, and rebubbling; other graft-related issues; mean difference in endothelial cell density; subjective visual outcomes; and patient satisfaction. RESULTS:: A total of 10 retrospective studies of moderate methodological quality were included (n = 947 eyes, 646 DMEK). BCVA was better with DMEK at all evaluated time points (0.16 logMAR at 12 months) comparing to DSAEK (0.30 logMAR; p < 0.001). DMEK had a 60% lower rate of rejection (risk ratio (RR) 0.4, 95% CI (0.24, 0.67), p = 0.0005), but required more rebubblings (RR = 2.48, 95% CI (1.32, 4.64), p = 0.005). DMEK had more primary graft failures and less endothelial cell density loss, but statistical difference was not reached. More patients were satisfied after DMEK (odds ratio = 10.29, 95% CI (3.55, 29.80), p < 0.0001). CONCLUSION:: DMEK showed better postoperative results regarding BCVA, patient satisfaction, and graft-related issues. However, the small number of studies with short follow-up times and other methodological issues prompt us to interpret these results carefully.