Non-obstetric Acute Abdomen in Pregnancy: a Review of Literature.

Background: Acute abdomen in pregnancy (AAP) is defined as intensive abdominal pain lasting less than 24 hours that may require urgent surgery. It is a challenging situation to diagnose and manage, as it is associated with pain due to the normal anatomical and physiological changes that occur during pregnancy. Objective: Therefore, understanding these changes and their effect on almost every system, will help us appreciate the upcoming causes of AAP, mainly the non-obstetric surgical emergencies (e.g., appendicitis, cholecystitis). Methods: This article highlights the importance of the well-rounded care that should be offered to every pregnant patient presenting to any center with a Non-obstetric Acute Abdomen. The causes are discussed separately (for surgical pearls), laparoscopic approach and radiologic modality decision-making in pregnancy, which is an academic and a practice-based helpful summary. Results and Discussion: This article highlights the importance of the well-rounded care that should be offered to every pregnant patient presenting to any center with a Non-obstetric Acute Abdomen. The causes are discussed separately (for surgical pearls), laparoscopic approach and radiologic modality decision-making in pregnancy, which is an academic and a practice-based helpful summary. Results and Discussion: In addition, the sequence of ideas and language used in the article was based to help the reader understand the topic, rather than inform them about it. In addition, the utility of laparoscopy in pregnancy remains a concern due to the possible risk of injury to the fetus and fetal acidosis. Although, trials showed that laparoscopy was associated with less blood loss and a shorter hospital stay. Moreover, in some cases radiographic imaging is necessary, posing a diagnostic dilemma. Conclusion: AAP is a major concern that requires early interventions to pinpoint the cause and manage the patient, properly.

The effect of protease inhibitor-based dual antiretroviral regimens on CD4/CD8 ratio during the first year of therapy in ART-naïve patients with HIV-infection.

OBJECTIVES: To assess the effect of protease inhibitor (PI)-based dual therapy on CD4/CD8 ratio during the first year of therapy in antiretroviral therapy (ART)-naïve patients using data from randomized controlled clinical trials. METHODS: We pooled data from the GARDEL and ANDES studies, both randomized controlled clinical trials that recruited ART-naïve people living with HIV and randomly assigned them to receive PI-based dual therapy (DT) or triple therapy (TT) aiming to compare viral efficacy. We compared median CD4/CD8 ratios and the proportion of patients with CD4/CD8 ratio > 1 at 48 weeks after ART initiation in both treatment arms using the Mann-Whitney U-test and the χ2 test. We performed subgroup analysis for patients > 50 years old, with baseline CD4 counts ≤ 200 cells/µL, viral load > 100 000 HIV RNA copies/mL, and ritonavir-boosted lopinavir-based therapy. RESULTS: We analysed data from 571 patients: 292 on DT and 279 on TT. No differences were observed in CD4/CD8 ratio (0.632 vs. 0.617, P = 0.729) or in the proportion of patients with CD4/CD8 ratio > 1 (17.9% vs. 19.3%, P = 0.678) 48 weeks after ART initiation. Subgroup analysis showed no further differences. CONCLUSION: The impact of PI-based DT regimens on the CD4/CD8 ratio during the first year of treatment for ART-naïve patients is similar to that of TT.

Social Network Organization, Structure, and Patterns of Influence Within a Community of Transgender Women in Lima, Peru: Implications for Biomedical HIV Prevention.

Understanding social network structures can contribute to the introduction of new HIV prevention strategies with socially marginalized populations like transgender women (TW). We conducted 20 semi-structured interviews and four focus groups (n = 32) with TW from selected social networks in Lima, Peru between May and July, 2015. Participants described layers of social influence from diverse actors in their social networks. The majority identified a close relative as their primary social support, with whom they confided secrets but avoided issues of transgender identity, sexuality, and sex work. Participants described close circles of TW friends with whom they shared information about gender identity, body modification, and sexual partners, but avoided issues like HIV. Community leadership included political leaders (who advocated for transgender rights) as well as social leaders (who introduced TW to hormone therapy, body modification, and commercial sex). Detailed analysis of TW social networks can contribute to implementation and acceptability of new HIV prevention technologies.

Adherence to international guidelines for the treatment of meningitis infections in Lebanon.

OBJECTIVES: To assess meningitis treatment in Lebanon's compatibility with the Infectious Diseases Society of America (IDSA) guidelines and the effect of non-compliance on mortality. Methods: This is a retrospective study, conducted in 5 Lebanese hospitals, and enrolling all patients diagnosed with meningitis who presented to the involved hospitals from January 2008 to December 2016.  Results: A total of 252 participants were enrolled in the study. Of these patients, 205 (82.7%) were diagnosed with viral meningitis and 47 (17.3%) with bacterial meningitis, which was confirmed using laboratory tests. For patients with viral meningitis, 128 (62.4%) remained on the initial prescribed antibiotics despite the negative cerebrospinal fluid (CSF) and blood culture results. For bacterial meningitis patients, 30.8% received treatment regimen incompatible with the IDSA guidelines. The most common reason for the treatment incompatibility was the definitive drug choice after the culture results (49.1%) and the least common reason was inappropriate hospital stay days (25.9%). The mortality rate was 13.5%. Having low proteins values in the CSF (odds ratio=0.095) was associated with lower mortality compared to patients with normal protein values. Conclusion: This study shows a high percentage of inappropriate treatment in Lebanese hospitals despite these hospitals having adopted international treatment guidelines. This inappropriate management was associated with an increasing rate of mortality and neurological complications.

Knowledge of tuberculosis and vaccine trial preparedness in Lima, Peru.

SETTING: A safe, effective vaccine would improve tuberculosis (TB) control worldwide. Extensive community engagement will be essential to ensure the interest and participation of populations at highest risk. OBJECTIVE/METHOD: To inform the potential implementation of efficacy studies, we assessed TB knowledge, attitudes towards licensed vaccines and willingness to participate in future TB vaccine efficacy trials among 262 household contacts of 79 recently diagnosed pulmonary TB cases in Lima, Peru. RESULTS: Overall knowledge of TB was low. Only 41.6% of household contacts perceived themselves as being at high risk of acquiring TB. Slightly above half (54.2%) indicated willingness to participate in a TB vaccine trial. After clustered analysis adjusting for homogeneity among families, willingness to enroll was associated with belief that receiving all recommended vaccinations is important (adjusted OR [aOR] 3.28, P = 0.016), desire to know more about TB risk factors and clinical trials (aOR 2.60, P = 0.004), older age (aOR 1.02, P = 0.027) and TB knowledge (aOR 0.05, P = 0.039). CONCLUSION: Barriers to participation in TB vaccine trials exist among individuals at high risk for TB. Targeted education about TB risk factors, TB transmission and education about the clinical trial process will be critical for laying the groundwork for future vaccine trials.

In men at risk of HIV infection, IgM, IgG1, IgG3, and IgA reach the human foreskin epidermis.

We profiled the humoral response in the penis, an area that has been minimally explored but may be relevant for protecting insertive men against HIV and other sexually acquired infections. Comparing paired tissue samples from 20 men at risk of HIV infection, foreskin contains less immunoglobulin A (IgA) and more IgG2 than colon. Using foreskin dermal and epidermal explants and paired plasma from 17 men, we examined Ig accumulation by normalizing Ig to human serum albumin (HSA) transudation. Dermal IgM, IgG2, IgA, and IgE ratios were greater than that in plasma, suggesting there is local antibody secretion at the dermis. Local Ig transcription was concentrated at the inner rather than the outer foreskin, and inner foreskin Ig ratios did not correlate with blood, indicating that localized production can contribute to the foreskin response. IgM, IgG1, IgG3, and IgA have preferential access to the foreskin epidermis, whereas IgG2, IgG4, and IgE are restricted to the dermis. Lastly, Ad5-specific IgA was selectively present in the colon, whereas foreskin Ad5 IgG was mainly derived from blood, and reached the inner epidermis at higher ratios than the outer (P<0.002). In summary, the foreskin antibody response combines local and systemic sources, and there is selective isotype accumulation in the epidermis.

Sampling methodologies for epidemiologic surveillance of men who have sex with men and transgender women in Latin America: an empiric comparison of convenience sampling, time space sampling, and respondent driven sampling.

Alternatives to convenience sampling (CS) are needed for HIV/STI surveillance of most-at-risk populations in Latin America. We compared CS, time space sampling (TSS), and respondent driven sampling (RDS) for recruitment of men who have sex with men (MSM) and transgender women (TW) in Lima, Peru. During concurrent 60-day periods from June-August, 2011, we recruited MSM/TW for epidemiologic surveillance using CS, TSS, and RDS. A total of 748 participants were recruited through CS, 233 through TSS, and 127 through RDS. The TSS sample included the largest proportion of TW (30.7 %) and the lowest percentage of subjects who had previously participated in HIV/STI research (14.9 %). The prevalence of newly diagnosed HIV infection, according to participants' self-reported previous HIV diagnosis, was highest among TSS recruits (17.9 %) compared with RDS (12.6 %) and CS (10.2 %). TSS identified diverse populations of MSM/TW with higher prevalences of HIV/STIs not accessed by other methods.

Dopamine selectively modulates lipopolysaccharide-induced TNF-alpha, IFN-gamma and IL-10 within mice tissues.

OBJECTIVES: Dopamine (DA) administration in sepsis is used to modulate the hypotensive condition and to normalize the blood vessels perfusion. However, whether this administration of DA has an effect on the release of cytokines in vivo deserves investigation. METHODS AND RESULTS: Pre-exposure of DA (1 µg/ml) to whole blood enhanced IL-10 (30%) production level following LPS stimulation. This IL-10 enhancement became statistically significant (p<0.001) upon the addition of D2-DA receptor (DAR) antagonists, Clozapine or Haloperidol. Furthermore, systemic administration of DA (0.5-50 mg/kg) in mice suppressed significantly LPS-induced TNF-α levels in blood, liver, spleen, brain, and lungs; IL-10 levels in blood, brain and liver; and IFN-γ levels in blood, liver, brain, and lungs. On the other hand, DA enhanced significantly LPS-induced IL-10 production in the lungs and spleen, and IFN-γ levels in the spleen. Administration of Clozapine (54 mg/kg) or Haloperidol (62 mg/kg) with LPS (1 µg) and DA (5 mg/kg) reversed DA suppressive effects on LPS-induced cytokines in blood, IFN-γ in brain and lungs, and enhanced significantly LPS-induced IL-10 production in blood, spleen, liver, and lungs. CONCLUSIONS: These results indicate that DA modulatory effect on LPS-induced blood cytokines-producing cells is mediated mainly by D2-DAR (D2/ D3/D4) through enhancing immune cells migration and extravasation into tissues. Furthermore, DA selectivity on cytokines modulation is tissue specific, mediated by the type of DAR expressed and on the immune cells lodged in each tissue.

[Pilot study for the inclusion of the portfolio of the family medicine specialist book in training]. / Estudio piloto para la incorporación del portafolio del libro del especialista en medicina de familia en formación.

BACKGROUND: The Spanish Family Medicine National Commission is proposing a new portfolio-type Specialist Training Book (STB). OBJECTIVE: To pilot its contents, structure, and implementation strategies. DESIGN: Cross-sectional, descriptive study. SETTING: A Provincial Family Medicine Teaching Unit. PARTICIPANTS: Twenty-eight tutors and 36 residents. METHODS: For 9 months the participants conducted a training assessment on diverse areas of competence by means of tasks at work. Tutors recorded information on the quality of reflection achieved by residents and the tasks they performed by means of the card model proposed in the STB. Residents filled in an ad hoc survey. A univariate analysis of quantitative data was conducted. RESULTS: Thirty-three surveys were received from residents; 21 tutors handed in 67 evaluation reports (average: 3 per tutor). They dealt with all the areas of competence, particularly those of communication, teaching, and ethics. Tasks most used were clinical sessions, critical incidents and video-recording. Both tutors and residents thought that the new method could be useful for reflecting on clinical practice, understanding their own areas of competence better and for strengthening the tutor-trainee relationship, especially if some suggestions to improve its practical use and reduce time and effort involved were taken into account. CONCLUSIONS: The new STB in its current version or with some modifications is a useful tool for residents' training assessment and is probably accepted well in our ambit.

Seroprevalence of and risk factors for HIV-1 infection among South American men who have sex with men.

OBJECTIVES: Sex among men constitutes an important route of transmission for HIV type 1 (HIV-1) in Latin America. Seeking better understanding of risk behaviours in this region, we determined the seroprevalence, potential risk factors, and geographic distribution of HIV-1 among groups of men who have sex with men (MSM). METHODS: Seroepidemiological, cross sectional studies of 13,847 MSM were conducted in seven countries of South America during the years 1999-2002. Volunteers were recruited in city venues and streets where anonymous questionnaires and blood samples were obtained. HIV-1 infection was determined by enzyme linked immunosorbent assay (ELISA) screening and western blot (WB) confirmatory tests. RESULTS: HIV-1 seroprevalence varied widely (overall 12.3%, range 11.0%-20.6%). The highest HIV-1 seroprevalence was noted in Bolivia (20.6%) and the lowest in Peru (11.0%). Predictors of HIV-1 infection varied among countries; however, a history of previous sexually transmitted disease (STD) was associated with a consistent increased risk (ORs=1.9-2.9, AORs=1.8-2.7). Multiple weekly sexual contacts was found to represent a secondary risk factor in Ecuador, Peru, and Argentina (ORs=1.6-2.9, AORs=1.6-3.1), whereas use of drugs such as cocaine was found to increase risk in Bolivia, Uruguay, and Paraguay (ORs=2.5-6.5, AORs=2.6-6.1). CONCLUSION: The results of this study illustrate an elevated HIV-1 seroprevalence among MSM participants from Andean countries. A previous STD history and multiple partners predicted HIV-1 infection in the seven countries of South America. In Southern Cone countries, HIV-1 infection was also associated with use of illegal drugs such as cocaine.

[Epidemiological study of risk behaviour in adolescents at school in two populations, semi-rural and urban]. / Estudio epidemiológico de comportamientos de riesgo en adolescentes escolarizados de dos poblaciones, semirrural y urbana.

OBJECTIVE: Describe the risk behavior relationships existing in school adolescents between themselves and with the place of residence. DESIGN: Cross-sectional descriptive study. PARTICIPANTS: School students from Cabra (semi-rural, 1319 students) and from one high school in Las Palmas de Gran Canaria (urban: 1,751 students). SAMPLE POPULATION: n=738 (368/370). Sampling unit classroom. MEASUREMENTS AND MAIN RESULTS. Anonymous, self-filled questionnaire, with several subjects: demographic data, traffic-related risk conducts, alcohol consumption, tobacco, other drugs, sexuality, physical exercise and dietetic habits. SELECTION CRITERIA: attendance at class on the day of the questionnaire and age 15-21. The relationship between variables was studied by logistical regression and multiple correspondence analysis (MCA); odds ratio (OR: logistical regression) with 95% confidence intervals (CI) were calculated. Median age: Cabra 17.6 (CI, 17.5-17.8), Las Palmas 16.4 (CI, 16.2-16.5). Those living in Las Palmas have a higher risk of heavy drinking on weekends (OR, 3.2; CI, 1.9-5.1), of being offered drugs (OR, 4.5; CI, 3.1-6.5) and of consuming them (OR, 4.1; CI, 2.1-8.3), as well as of having sexual intercourse (OR, 2.5; CI, 1.6-3.8). In the MCA tobacco, alcohol and other drug use, having sexual intercourse and not doing regular physical exercise were closely-located within themselves. CONCLUSIONS: Risk behaviours are interrelated and influenced by the habitat, and start to appear at the beginning of the adolescence.

Estudio epidemiológico de comportamientos de riesgo en adolescentes escolarizados de dos poblaciones, semirrural y urbana / Epidemiological study of risk behaviour in adolescents at school in two populations, semi-rural and urban

Objetivo. Describir la relación entre sí y con el lugar de residencia de comportamientos de riesgo de adolescentes escolarizados. Diseño. Estudio descriptivo, transversal. Participantes. Alumnos de enseñanza media de Cabra, en Córdoba (semirrural: 1.319 estudiantes) y de un instituto de Las Palmas de Gran Canaria (urbana: 1.751 estudiantes). Población muestral: n = 738 (368/370). Unidad de muestreo: el aula. Mediciones y resultados principales. Cuestionario anónimo, autocumplimentado, con los siguientes apartados: datos sociodemográficos, conductas de riesgo relacionadas con tráfico, consumo de alcohol, tabaco, otras drogas, sexualidad, ejercicio físico y hábitos dietéticos. Criterios de selección: asistencia a clase el día de la encuesta y edad 15-21 años. Se estudió la relación entre variables mediante regresión logística y análisis de correspondencias múltiples (ACM); se calcularon las odds ratio (OR: regresión logística) con intervalos de confianza (IC) del 95 per cent. Edad media: Cabra, 17,6 años (IC del 95 per cent, 17,5-17,8), Las Palmas 16,4 años (IC del 95 per cent, 16,216,5). En Las Palmas tienen un mayor riesgo de beber en exceso los fines de semana (OR, 3,2; IC del 95 per cent, 1,9-5,1), de que les ofrezcan drogas (OR, 4,5; IC del 95 per cent, 3,1-6,5) y de consumirlas (OR, 4,1; IC del 95 per cent, 2,1-8,3), así como de mantener relaciones sexuales (OR, 2,5; IC del 95 per cent, 1,6-3,8). En el ACM se agruparon entre sí el consumo de tabaco, alcohol y otras drogas, mantener relaciones sexuales completas y no practicar habitualmente ejercicio físico. Conclusiones. Los comportamientos de riesgo están interrelacionados e influidos por el hábitat, y se inician al comienzo de la adolescencia (AU)

Human immunodeficiency virus type 1 Nef mediates sustained membrane expression of tumor necrosis factor and the related cytokine LIGHT on activated T cells.

Human immunodeficiency virus (HIV) Nef downregulates the antigen recognition molecules major histocompatibility complex class I and CD4. Downregulation of surface CD4 by Nef relies on the ability of this viral protein to redirect the endocytic machinery to CD4. However, by redirecting the endocytic machinery, Nef may affect the internalization rates of other proteins. Here we show that Nef simultaneously enhances surface expression of the effector cytokines tumor necrosis factor (TNF) and LIGHT, leading to enhanced cytokine activity. A dileucine motif in Nef, which is essential for CD4 downregulation and is involved in the recruitment of adapter protein complexes by Nef, was required to increase surface levels of both cytokines. The physiological impact of the Nef-mediated interference with endocytosis was demonstrated by the fact that a TNF-responsive T-cell line chronically infected with HIV produced higher levels of p24 viral protein following expression of a Nef-green fluorescent protein (GFP) fusion protein. This enhancement was dependent on the levels of membrane-bound TNF, since it was abrogated by a recombinant soluble TNF receptor. Expression of Nef-GFP in human 293T cells reduced the endocytosis of LIGHT, whereas at the same time CD4 internalization was accelerated. Taken together, these results suggest that in infected cells Nef interferes with the internalization of these effector cytokines. By increasing TNF expression, Nef could accelerate disease progression in infected individuals. These findings may help explain the pleiotropic functions that Nef plays during infection and disease.

Discrete signaling regions in the lymphotoxin-beta receptor for tumor necrosis factor receptor-associated factor binding, subcellular localization, and activation of cell death and NF-kappaB pathways.

Lymphotoxin-beta receptor (LTbetaR), a member of the tumor necrosis factor receptor superfamily, is essential for the development and organization of secondary lymphoid tissue. Wild type and mutant LTbetaR containing successive truncations of the cytoplasmic domain were investigated by retrovirus-mediated gene transfer into HT29.14s and in 293T cells by transfection. Wild type receptors accumulated in perinuclear compartments and enhanced responsiveness to ligand-induced cell death and ligand-independent activation of NFkappaB p50 dimers. Coimmunoprecipitation and confocal microscopy mapped the TRAF3 binding site to amino acids PEEGDPG at position 389. However, LTbetaR truncated at position Pro(379) acted as a dominant positive mutant that down-modulated surface expression and recruited TRAF3 to endogenous LTbetaR. This mutant exhibited ligand-independent cell death and activated NF-kappaB p50 dimers. By contrast, truncation at Gly(359) created a dominant-negative mutant that inhibited ligand-induced cell death and activation of NF-kappaB p50/p65 heterodimers. This mutant also blocked accumulation of wild type receptor into perinuclear compartments, suggesting subcellular localization may be crucial for signal transduction. A cryptic TRAF-independent NF-kappaB activating region was identified. These mutants define discrete subregions of a novel proline-rich domain that is required for subcellular localization and signal transduction by the LTbetaR.

Cell-surface expression of CD4 reduces HIV-1 infectivity by blocking Env incorporation in a Nef- and Vpu-inhibitable manner.

BACKGROUND: Human immunodeficiency virus-1 (HIV-1) infection decreases the cell-surface expression of its cellular receptor, CD4, through the combined actions of Nef, Env and Vpu. Such functional convergence strongly suggests that CD4 downregulation is critical for optimal viral replication, yet the significance of this phenomenon has so far remained a puzzle. RESULTS: We show that high levels of CD4 on the surface of HIV-infected cells induce a dramatic reduction in the infectivity of released virions by the sequestering of the viral envelope by CD4. CD4 is able to accumulate in viral particles while at the same time blocking incorporation of Env into the virion. Nef and Vpu, through their ability to downregulate CD4, counteract this effect. CONCLUSIONS: The CD4-mediated 'envelope interference' described here probably explains the plurality of mechanisms developed by HIV to downregulate the cell-surface expression of its receptor.

The CD3 epsilon subunit of the TCR contains endocytosis signals.

Ligand binding to TCR induces its internalization and cell surface down-modulation. These phenomena contribute to the extinction of activation signals. Due to the multicomponent nature of the TCR-CD3 complex, its internalization may be mediated by one or several of its subunits. Although it has been reported that CD3 gamma and CD3 delta contain endocytosis motifs involved in the internalization of the TCR-CD3 complex, other subunits could also be involved in this process. For instance, CD3 epsilon and CD zeta display amino acid sequences reminiscent of internalization motifs. To investigate whether CD3 epsilon bears endocytosis signals, we have analyzed the internalization capacity of a panel of deletion and point mutants of CD3 epsilon that were expressed on the cell surface independently of other TCR-CD3 subunits. Here we report that CD3 epsilon displays endocytosis determinants. These data indicate that CD3 epsilon could contribute to the internalization and cell surface down-regulation of TCR-CD3 complexes. Moreover, the existence of endocytosis signals in this polypeptide could serve to retrieve unassembled CD3 epsilon subunits or partial CD3 complexes from the plasma membrane, thus restricting the expression on the cell surface to fully functional TCR-CD3 complexes.

Genetic analysis of poliovirus protein 3A: characterization of a non-cytopathic mutant virus defective in killing Vero cells.

A mutational and genetic analysis of the poliovirus protein 3A has led to the identification of a single amino acid mutant virus with a restrictive phenotype to form plaques in Vero cells. This mutant (I46T 3A) can be grown and amplified in HeLa cells, where virus replication takes place at wild-type levels. However, Vero cells infected with this virus cannot complete the growth cycle. I46T 3A virus has a defect in the ability to kill Vero cells, as estimated by FACS analysis of propidium iodide uptake by dead cells. Since these defects are observed under conditions where no abnormalities in the rate of synthesis and processing of the mutant polyprotein occur, the inability to induce the cytopathic effect in infected Vero cells denotes the existence of a defect in the activity of 3A, but not the level of expression of the viral genome. As a consequence of this impaired capability to generate the cytopathic effect, I46T 3A mutant viruses cannot be titrated by plaque assay in Vero cells. Only revertant viruses with the wild-type sequence arise and form lysis plaques in Vero cells. Our results suggest a role for the 3A protein (or a precursor thereof) in the virus-induced cytopathic effect. The mutant virus characterized in this work may be a useful tool to understand how poliovirus kills infected cells and carries out the final step of its life-cycle, the release of virus progeny.