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ObjectivesSome drugs that augment cell-intrinsic defenses or modulate cell death/survival pathways have been reported to selectively kill cells infected with HIV or Simian Immunodeficiency Virus (SIV), but comparative studies are lacking. We hypothesized that these drugs may differ in their ability to kill cells infected with intact and defective proviruses.DesignTo investigate this hypothesis, drugs were tested ex vivo on peripheral blood mononuclear cells (PBMC) from nine antiretroviral therapy (ART)-suppressed individuals.MethodsWe tested drugs currently in clinical use or human trials, including auranofin (p53 modulator), interferon alpha2A, interferon gamma, acitretin (RIG-I inducer), GS-9620/vesatolimod (TLR7 agonist), nivolumab (PD-1 blocker), obatoclax (Bcl-2 inhibitor), birinapant [inhibitor of apoptosis proteins (IAP) inhibitor], bortezomib (proteasome inhibitor), and INK128/sapanisertib [mammalian target of rapamycin mTOR] [c]1/2 inhibitor). After 6 days of treatment, we measured cell counts/viabilities and quantified levels of total, intact, and defective HIV DNA by droplet digital PCR (Intact Proviral DNA Assay).ResultsObatoclax reduced intact HIV DNA [median = 27-30% of dimethyl sulfoxide control (DMSO)] but not defective or total HIV DNA. Other drugs showed no statistically significant effects.ConclusionObatoclax and other Bcl-2 inhibitors deserve further study in combination therapies aimed at reducing the intact HIV reservoir in order to achieve a functional cure and/or reduce HIV-associated immune activation.

Background Aims Study design Results Conclusions Relevance to Clinical Practice Positive end‐expiratory pressure is a crucial mechanical breathing parameter. Intra‐abdominal hypertension is well defined as a sustained increase in the intra‐abdominal pressure ≥12 mmHg. There are still controversies about mechanical ventilation's effect and use of positive end‐expiratory pressure on intra‐abdominal pressure.We aimed to delineate the relationship between positive end‐expiratory pressure and intra‐abdominal pressure in mechanically ventilated patients admitted to the intensive care units of a large tertiary hospital in Upper Egypt.This study was a prospective observational study. The study was conducted at a university hospital from October 2023 to February 2024. The enrolled adult patients were allocated into two groups based on their positive end‐expiratory pressure: group I, low pressure (<8 cm H2O) and group II, high pressure (8–10 cm H2O).A total of 120 patients were enrolled, 60 patients in each group. The most commonly encountered diagnoses were pneumonia (32/120, 26.7%) and acute respiratory distress syndrome (ARDS) (31/120, 25.8%), respectively. There was a significant difference between the intra‐abdominal pressure mean values of the two patient groups, 18.9 ± 3.3 versus 24.4 ± 5.9 mmHg in the group of low versus high pressure (correlation value of .454, p < .001), respectively. There were highly significant correlations between intra‐abdominal pressure categories and the patient groups (correlation value of .495, p < .001). There were 24 (40%) versus 0 (0%) patients of high pressure versus low pressure within the category IV group of intra‐abdominal hypertension (>25 mmHg).We observed a significant relationship between positive end‐expiratory pressure and intra‐abdominal pressure in mechanically ventilated patients. The patient group with high pressure had higher mean values compared with the group with low pressure. The study highlights the importance of closely monitoring intra‐abdominal pressure in mechanically ventilated patients who receive positive end‐expiratory pressure. Further studies are warranted.The relationship between positive end‐expiratory pressure and intra‐abdominal pressure is an essential issue in daily critical care nursing clinical practice. Considering the occurrence of multiple organ dysfunction as a result of a non‐detected increase in intra‐abdominal pressure, critical care nurses should pay attention to measuring this pressure to maintain intra‐abdominal pressures that are safe for mechanically ventilated and critically ill intensive care unit patients, thereby preventing these undue effects. [ABSTRACT FROM AUTHOR]

This paper presents a multifaceted assessment of inhibitors of anti-apoptotic proteins (IAPs) in the context of head and neck squamous cell carcinoma (HNSCC). The article discusses the results of in vitro, in vivo, and clinical studies, highlighting the significance of IAPs in the resistance of cancer cells to apoptosis, which is a key factor hindering effective treatment. The main apoptosis pathways, including the intrinsic and extrinsic pathways, and the role of IAPs in their regulation, are presented. The study's findings suggest that targeting IAPs with novel therapies may offer clinical benefits in the treatment of advanced HNSCC, especially in cases resistant to conventional treatment methods. These conclusions underscore the need for further research to develop more effective and safer therapeutic strategies. [ABSTRACT FROM AUTHOR]

Measles, mumps, and rubella (MMR) are highly infectious viral diseases affecting young children and have high secondary attack rates. Present MMR vaccines show consistent seroconversion rates for anti-measles and anti-rubella antibodies with variable responses for anti-mumps antibodies. Most common strains for MMR vaccines, currently available in India, are the Edmonston-Zagreb measles strain, Leningrad Zagreb (L-Z) mumps strain, and the RA 27/3 rubella strain. L-Z strain of mumps virus has been found to be associated with aseptic meningitis by different studies from different parts of the world including India. Recently, a novel freeze-dried MMR vaccine developed by Zydus Lifesciences (Zyvac MMR) contains Edmonston Zagreb measles strain, Hoshino mumps strain, and RA 27/3 rubella strain. The Hoshino strain is WHO approved and was found to induce interferon gamma production. This review article aims to provide a comprehensive appraisal of the data available on the safety and immunogenicity of the novel MMR vaccine.

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Survivin holds significant importance as a member of the inhibitor of apoptosis protein (IAP) family due to its predominant expression in tumours rather than normal terminally differentiated adult tissues. The high expression level of survivin in tumours is closely linked to chemotherapy resistance, heightened tumour recurrence, and increased tumour aggressiveness and serves as a negative prognostic factor for cancer patients. Consequently, survivin has emerged as a promising therapeutic target for cancer treatment. In this review, we delve into the various biological characteristics of survivin in cancers and its pivotal role in maintaining immune system homeostasis. Additionally, we explore different therapeutic strategies aimed at targeting survivin. [ABSTRACT FROM AUTHOR]

Patients diagnosed with epithelial ovarian cancers (EOCs) often suffer from disease relapse associated with the emergence of resistance to standard platinum‑based chemotherapy. Treatment of patients with chemo‑resistant disease remains a clinical challenge. One mechanism of chemoresistance includes overexpression of pro‑survival proteins called inhibitors of apoptosis (IAP) which enable cancer cells to evade apoptosis. Due to their anti‑apoptotic activity, association with poor prognosis, and correlation with therapy resistance in multiple malignancies, IAP proteins have become an attractive target for development of anticancer therapeutics. Second mitochondrial activator of caspase (SMAC) mimetics are the most widely used IAP antagonists currently being tested in clinical trials as a monotherapy and in combination with different chemotherapeutic drugs to target different types of cancer. In the present study, the antitumor efficacy of combination therapy with birinapant, a bivalent SMAC mimetic compound, and carboplatin to target platinum‑resistant EOC cells was investigated. A 3D organoid bioassay was utilized to test the efficacy of the combination therapy in a panel of 7 EOC cell lines and 10 platinum‑resistant primary patient tumor samples. Findings from the in vitro studies demonstrated that the birinapant and carboplatin combination was effective in targeting a subset of ovarian cancer cell lines and platinum‑resistant primary patient tumor samples. This combination therapy was also effective in vitro and in vivo in targeting a platinum‑resistant patient‑derived xenograft (PDX) model established from one of the patient tumors tested. Overall, our study demonstrated that birinapant and carboplatin combination could target a subset of platinum‑resistant ovarian cancers and also highlights the potential of the 3D organoid bioassay as a preclinical tool to assess the response to chemotherapy or targeted therapies in ovarian cancer.

Abstract Objective To investigate intestinal injury, repair and vasculitis biomarkers that may illuminate the progression and/or pathogenesis of feline infectious peritonitis (FIP) or feline enteric coronavirus (FECV) infection. Materials and methods A total of 40 cats with effusive FIP (30 with abdominal effusion, AE group; 10 with thoracic effusion, TE group) and 10 asymptomatic but FECV positive cats (FECV group), all were confirmed by reverse transcription polymerase chain reaction either in faeces or effusion samples. Physical examinations and effusion tests were performed. Trefoil factor‐3 (TFF‐3), intestinal alkaline phosphatase (IAP), intestinal fatty acid binding protein (I‐FABP), myeloperoxidase‐anti‐neutrophilic cytoplasmic antibody (MPO‐ANCA) and proteinase 3‐ANCA (PR3‐ANCA) concentrations were measured both in serum and effusion samples. Results Rectal temperature and respiratory rate were highest in the TE group (p

Objective: To investigate the relationship between serum Presepsin, immunosuppressive acid protein (IAP), high mobility group B1 (HMGB1) and prognosis of percutaneous transhepatic cholangial drainage (PTCD) treatment in patients with acute obstructive suppurative cholangitis (AOSC). Methods: 220 patients with AOSC who received PTCD treatment in the Baoding Second Central Hospital from January 2021 to January 2023 were selected to be included in the AOSC group, and 88 healthy volunteers during the same period were selected to be included in the control group. The patients with AOSC were divided into survival group with 36 cases and death group with 184 cases according to whether they died during hospitalization after PTCD surgical. Serum Presepsin, IAP and HMGB1 levels were detected. Multivariate Logistic regression model was used to analyze the factors affecting the prognosis of PTCD surgical treatment in patients with AOSC, the predictive value of serum Presepsin, IAP and HMGB1 levels on postoperative death in patients with AOSC after PTCD surgical was analyzed by receiver operating characteristic (ROC) curve. Results: The serum Pressin, IAP, and HMGB1 levels in the AOSC group were higher than those in the control group (P＜0.05). The mortality rate during hospitalization after PTCD surgical in 220 patients with AOSC was 16.36% (36/220). Multivariate Logistic regression analysis showed that, time from onset to surgery ≥3 d, 24 h postoperative bile drainage ＜300 m L, elevated Presepsin, elevated IAP, and elevated HMGB1 were independent risk factors affecting the prognosis of PTCD treatment in patients with AOSC (P＜0.05). ROC curve analysis showed that, the area under the curve of serum Presepsin, IAP, and HMGB1 levels combined to predict postoperative death after PTCD surgical in patients with AOSC was 0.920, which was greater than the single indicator prediction. Conclusion: Elevated serum Presepsin, IAP, and HMGB1levels in patients with AOSC are independent risk factors for the prognosis of PTCD treatment. The combination of serum presepsin, IAP, and HMGB1 levels has high value in predicting the prognosis of PTCD treatment in patients with AOSC. [ABSTRACT FROM AUTHOR]

Copyright of Prospectiva is the property of Universidad del Valle and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

El presente artículo se base en la Tesis Educación parvulariaintercultural desde el enfoque pedagógico de Paulo Freire (Sánchez, 2019), investigación realizada para optar al grado de maestría, y querefleja el proceso reflexivo del equipo educativo de un Jardín Infantil intercultural, ubicado en la comuna de La Florida, quienes se cuestionaron la pertinencia del enfoque pedagógico tradicional con lo que planteaban en su misión, visión y sello. De este modo surgió la iniciativa de estudiar si el modelo pedagógico propuesto por Paulo Freire era pertinente a la educación intercultural, y si este enfoque metodológico se podía aplicar en Educación Parvularia.Para ello, se realizó una Investigación Acción Participativa (IAP), construyendo con la comunidad un plan de acción que buscaba relevar la diversidad cultural. Luego de aplicado, se utilizaron técnicas de investigación como análisis de documentos, entrevistas personales en profundidad y ungrupo focal, dando cuenta de lo que significó esta IAP, transformando su realidad, al democratizar y contextualizar el currículo. Finalmente se evidenció que, para que exista interculturalidad crítica es necesaria la participación comunitaria, democratizando la educación, la programación de los contenidos y la enseñanza, siendo completamente pertinente el modelo pedagógico de Paulo Freire para ello.

La condición de seropositividad implica un nuevo comienzo para las personas debido a que se presenta una escisión de su persona y requieren una reconstrucción de su vida. A nivel social, la deconstrucción vital puede estar caracterizada por la ausencia de poder y presencia de estigma social, lo que puede impactar en la afectividad y la participación comunitaria de las personas que viven con VIH (PVV). Este trabajo de sistematización tiene como objetivo reconstruir el proceso de una intervención llevada a cabo desde la Investigación Acción Participativa (IAP), para lo cual se retomó la Teoría de las Representaciones Sociales, con el fin de aproximarse a los componentes socioafectivos de un grupo de PVV y su relación con el estigma y la participación comunitaria. Se encontró que la afectividad representa un aspecto importante, siendo el diagnóstico un aspecto central en la modificación de sus significados y prácticas vitales, con tendencia hacia el aislamiento y baja participación social. Mediante la intervención, las personas participantes se fueron asumiendo como agentes de cambio, derivando un rompimiento con el estigma del VIH/SIDA, tanto intragrupal como con la comunidad. Se puede concluir que, construir procesos participativos desde la afectividad puede conducir al re-conocimiento y la potenciación de sus fortalezas.

ABSTRACT Latency reversal and subsequent elimination of the human immunodeficiency virus-1 (HIV-1) reservoir using a combination of compounds with different mechanisms of action are considered a promising tool for HIV-1 cure. Here, we analyzed HIV-1 reservoir reduction by targeting the two host factors; inhibitor of apoptosis proteins (IAPs) and DEAD-box polypeptide 3 (DDX3) using a SMAC mimetic (SMACm) and DDX3 inhibitor (DDX3i), respectively. We observed that SMACm efficiently reactivated HIV-1 in a latency Jurkat model, which was further enhanced by DDX3 inhibition. Strikingly, this compound combination strongly decreased the proportion of latently as well as transcriptionally active infected cells in a T cell line model with a dual-reporter virus. To determine the efficacy of compounds to eradicate the HIV-1 reservoir in people living with HIV (PWH), a novel ex vivo HIV-1 reservoir reduction assay (HIVRRA) was developed. DDX3i and SMACm alone reduced the HIV-1 reservoir in peripheral blood mononuclear cells (PBMCs) from the majority of PWH, whereas notably, the SMACm/DDX3i combination reduced the HIV-1 reservoir even further with 53%–90% in all PWH analyzed, while uninfected bystander cells were not affected. Our data highlight that IAPs as well as factors involved in HIV-1 replication like DDX3 are excellent targets for HIV-1 cure strategies. We show for the first time that the combination of SMACm and DDX3i reverses viral latency and specifically eliminates the HIV-1-infected cells in vitro and ex vivo. IMPORTANCE HIV-1 continues to be a major global health challenge. Current HIV-1 treatments are effective but need lifelong adherence. An HIV-1 cure should eliminate the latent viral reservoir that persists in people living with HIV-1. Different methods have been investigated that focus on reactivation and subsequent elimination of the HIV-1 reservoir, and it is becoming clear that a combination of compounds with different mechanisms of actions might be more effective. Here, we target two host factors, inhibitor of apoptosis proteins that control apoptosis and the DEAD-box helicase DDX3, facilitating HIV mRNA transport/translation. We show that targeting of these host factors with SMAC mimetics and DDX3 inhibitors induce reversal of viral latency and eliminate HIV-1-infected cells in vitro and ex vivo.

Childhood obesity represents a serious public health challenge today. Comparing childhood obesity in terms of national as well as international growth references helps in assessing the extent of agreement in classifying BMI status of children, allows for comparison on a global scale, and also aids in understanding the strengths and weaknesses of the different growth references. Thus, the objective of the study was to compare three growth references, one national (IAP, 2015) and two international (WHO (de Onis et al., 2007), Extended International IOTF (Cole and Lobstein, 2012)), with a focus on determining the prevalence of overweight and obesity and estimating the level of agreement between the growth references. In the cross-sectional study, 402 children aged 6-11 years, attending classes I to V, were the study participants. Height and weight of the participants were measured to calculate the BMI. BMI-for-age Z scores given by WHO (2007), IAP (2015) and IOTF (2012) were used to determine the BMI categories among the study participants. Kappa statistics was used to determine the level of agreement between the three growth references. The prevalence of overweight and obesity in the study participants was 18.2% and 12.2% by WHO (2007) reference, 16.2% and 19.4% by IAP (2015) reference and 18.9% and 7.2% by IOTF (2012) reference. The Kappa statistics showed that there was good agreement (k = 0.729) between WHO & IAP references to identify overweight/obesity while a moderate agreement was observed between WHO & IOTF (k = 0.625) references, and IOTF & IAP (k = 0.506) growth references. The study found that the IOTF reference classified the children in lower weight status categories compared to the WHO and IAP growth references. That is, compared to WHO and IAP references, the IOTF reference underestimated obesity. The IAP and WHO growth references were, in contrast, reasonably similar. [ABSTRACT FROM AUTHOR]

Objective: To investigate intestinal injury, repair and vasculitis biomarkers that may illuminate the progression and/or pathogenesis of feline infectious peritonitis (FIP) or feline enteric coronavirus (FECV) infection. Materials and methods: A total of 40 cats with effusive FIP (30 with abdominal effusion, AE group; 10 with thoracic effusion, TE group) and 10 asymptomatic but FECV positive cats (FECV group), all were confirmed by reverse transcription polymerase chain reaction either in faeces or effusion samples. Physical examinations and effusion tests were performed. Trefoil factor‐3 (TFF‐3), intestinal alkaline phosphatase (IAP), intestinal fatty acid binding protein (I‐FABP), myeloperoxidase‐anti‐neutrophilic cytoplasmic antibody (MPO‐ANCA) and proteinase 3‐ANCA (PR3‐ANCA) concentrations were measured both in serum and effusion samples. Results: Rectal temperature and respiratory rate were highest in the TE group (p < 0.000). Effusion white blood cell count was higher in the AE group than TE group (p < 0.042). Serum TFF‐3, IAP and I‐FABP concentrations were higher in cats with effusive FIP than the cats with FECV (p < 0.05). Compared with the AE group, TE group had lower effusion MPO‐ANCA (p < 0.036), higher IAP (p < 0.050) and higher TFF‐3 (p < 0.016) concentrations. Clinical significance: Markers of intestinal and epithelial surface injury were higher in cats with effusive FIP than those with FECV. Compared to cats with abdominal effusions, markers of apoptosis inhibition and immunostimulation to the injured epithelium were more potent in cats with thoracic effusion, suggesting the possibility of a poorer prognosis or more advanced disease in these patients. [ABSTRACT FROM AUTHOR]

Abstract Background The tick Amblyomma sculptum is the major vector of Rickettsia rickettsii, the causative agent of the highly lethal Brazilian spotted fever. It has been shown that R. rickettsii inhibits apoptosis in both human endothelial cells and tick cells. Apoptosis is regulated by different factors, among which inhibitors of apoptosis proteins (IAPs) play a central role. In the study reported here, we selected an IAP of A. sculptum that has not yet been characterized to assess its role in cell death and to determine the effects of its gene silencing on tick fitness and R. rickettsii infection. Methods An A. sculptum cell line (IBU/ASE-16) was treated with specific double-stranded RNA (dsRNA) for either IAP (dsIAP) or green fluorescent protein (dsGFP; as a control). The activity of caspase-3 and the exposure of phosphatidylserine were determined in both groups. In addition, unfed adult ticks, infected or not infected with R. rickettsii, were treated with either dsIAP or dsGFP and allowed to feed on noninfected rabbits. In parallel, noninfected ticks were allowed to feed on an R. rickettsii-infected rabbit. Ticks (infected or not with R. rickettsii) that remained unfed were used as a control. Results Caspase-3 activity and the externalization of phosphatidylserine were significantly higher in IBU/ASE-16 cells treated with dsIAP than in those treated with dsGFP. The mortality rates of ticks in the dsIAP group were much higher than those in the dsGFP group when they were allowed to feed on rabbits, independent of the presence of R. rickettsii. Conversely, lower mortality rates were recorded in unfed ticks. Conclusions Our results show that IAP negatively regulates apoptosis in A. sculptum cells. Moreover, IAP-silenced ticks experienced higher mortality rates following the acquisition of a blood meal, suggesting that feeding may trigger the activation of apoptosis in the absence of this physiological regulator. These findings indicate that IAP is a potential antigen for an anti-tick vaccine. Graphical Abstract

Proteolytic targeting chimaeras (PROTACs) have been developed as an effective technology for targeted protein degradation. PROTACs are heterobifunctional molecules that can trigger the polyubiquitination of proteins of interest (POIs) by recruiting the ubiquitin-proteasome system, thereby inhibiting the intracellular level of POIs. To date, a variety of small-molecule PROTACs (CRBN, VHL, IAP, and MDM2-based PROTACs) have been developed. IAP-based PROTACs, also known as specific and nongenetic IAP-dependent protein erasers (SNIPERs), are used to degrade the target proteins closely related to diseases. Their structures consist of three parts, including target protein ligand, E3 ligase ligand, and the linker between them. So far, many SNIPERs have been extensively studied worldwide and have performed well in multiple diseases, especially cancer. In this review, we will present the most relevant advances in the field of SNIPERs and provide our perspective on the opportunities and challenges for SNIPERs to become therapeutic agents.

Objective Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) represent a mainstay of treatment for peritoneal malignancies. There is evidence that HIPEC using high intra-abdominal pressure (IAP) results in increased tissue penetration, although its safety profile remains relatively unknown. We thus aim to evaluate differences in intra- and post-operative outcomes in patients undergoing CRS-HIPEC with different levels of IAP.Methods This pilot prospective cohort study was conducted from January 2020 to February 2021 with patients undergoing CRS-HIPEC. Low IAP during HIPEC was defined as

Objective: To account for the a backyard project, developed between a group of Mayan women from Canicab, Yucatán, Mexico and a team made up of non-Maya academic participants. Methodology: Within the framework of participatory-action-research and knowledge dialogue, we proposed a productive project that favored sustainability in this rural town, that has been identified as highly marginalized. Results the group made up of Mayan women opted for a backyard project that made it possible to have healthy food for their own and extended families by raising chickens. and egg production, a choice made based on their community ties and kinship. Limitations: Although we worked with women, the text lacks a gender perspective or feminist positions. Conclusions: we observed that the economy of these women, circulates in two logics, the Mayan cultural practices related to requesting, thanking and sharing, and the capitalist world that converts goods and well-being into money. Decisions made by these women have behind a history related to intercultural situations linked to government extension agents and bank extortionists, which led to Canicab the imposition of Western science, on the one hand, and deception and dispossession, on the other. [ABSTRACT FROM AUTHOR]

• The Inflatable Prone Support (IPS) effectively lowers Intra Abdominal Pressure (IAP). • The inflation of the IPS results in a significant decrease of IAP (p < 0.001). • Abdominal circumference could be as important as BMI in the prone position. • Body morphology is important in positioning for spine surgery. • Continuous IAP monitoring could be helpful during spine surgery. Both anaesthesiologists and spine surgeons consider the intra-abdominal pressure (IAP) as an important peri-operative factor affected by patient positioning. We assessed the change in IAP caused by using a thoraco pelvic support (inflatable prone support, IPS) with the subject under general anesthesia. The IAP was measured before, during and immediately after surgery. The Spine Intra-Abdominal Pressure study (SIAP trial) is a prospective, single-arm, monocenter, observational study looking at changes in IAP prior, during and after spine surgery. The objective is to assess the change in IAP, measured via an indwelling urinary catheter, using the inflatable prone support (IPS) device during prone positioning of patients in spinal surgery. Forty (40) subjects requiring elective lumbar spine surgery in prone position were enrolled after providing informed consent. The inflation of the IPS results in a significant decrease of IAP (from a median of 9.2 mmHg to 6.46 mmHg (p < 0.001)) in patients undergoing spine surgery in prone position. This decrease in IAP was maintained throughout the procedure despite the discontinuation of muscle relaxants. No serious adverse events or unexpected adverse events occurred. The use of the thoraco-pelvic support IPS device was able to significantly lower the IAP during spine surgery. [ABSTRACT FROM AUTHOR]

Copyright of Cuadernos Médico Sociales is the property of Colegio Medico de Chile (A.G.) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The tick Amblyomma sculptum is the major vector of Rickettsia rickettsii, the causative agent of the highly lethal Brazilian spotted fever. It has been shown that R. rickettsii inhibits apoptosis in both human endothelial cells and tick cells. Apoptosis is regulated by different factors, among which inhibitors of apoptosis proteins (IAPs) play a central role. In the study reported here, we selected an IAP of A. sculptum that has not yet been characterized to assess its role in cell death and to determine the effects of its gene silencing on tick fitness and R. rickettsii infection. Methods: An A. sculptum cell line (IBU/ASE-16) was treated with specific double-stranded RNA (dsRNA) for either IAP (dsIAP) or green fluorescent protein (dsGFP; as a control). The activity of caspase-3 and the exposure of phosphatidylserine were determined in both groups. In addition, unfed adult ticks, infected or not infected with R. rickettsii, were treated with either dsIAP or dsGFP and allowed to feed on noninfected rabbits. In parallel, noninfected ticks were allowed to feed on an R. rickettsii-infected rabbit. Ticks (infected or not with R. rickettsii) that remained unfed were used as a control. Results: Caspase-3 activity and the externalization of phosphatidylserine were significantly higher in IBU/ASE-16 cells treated with dsIAP than in those treated with dsGFP. The mortality rates of ticks in the dsIAP group were much higher than those in the dsGFP group when they were allowed to feed on rabbits, independent of the presence of R. rickettsii. Conversely, lower mortality rates were recorded in unfed ticks. Conclusions: Our results show that IAP negatively regulates apoptosis in A. sculptum cells. Moreover, IAP-silenced ticks experienced higher mortality rates following the acquisition of a blood meal, suggesting that feeding may trigger the activation of apoptosis in the absence of this physiological regulator. These findings indicate that IAP is a potential antigen for an anti-tick vaccine. [ABSTRACT FROM AUTHOR]

Abstract Background Pancreatic cancer is one of the most lethal cancers worldwide. The IAPs function as E3 ubiquitin ligases and contribute to pancreatic cancer initiation, progression, and metastasis. Although IAP-targeted therapies have been developed and shown anticancer efficacy in preclinical settings, none of them has been approved yet. Methods Transcriptome data from public datasets were used to analyze the correlation of IAPs and E2s, and the biological function of E2 UbcH5c in pancreatic cancer. A structure-based virtual screen was used to identify UbcH5c inhibitor, and surface plasmon resonance analysis and cellular thermal shift assays were employed to evaluate the binding affinity. The anticancer activities were demonstrated through in vitro and in vivo assays, while the related mechanisms were explored through transcriptomic and proteomic analyses and confirmed by western blot, immunofluorescence, and qRT-PCR. Results UbcH5c is positively correlated with the expression of IAPs in pancreatic cancer. We further found that UbcH5c is overexpressed and associated with a poor prognosis in pancreatic cancer. We identified a small-molecule UbcH5c inhibitor, termed DHPO, which directly bound to UbcH5c protein. DHPO inhibited cell viability and colony formation, induced apoptosis, and suppressed migration and invasion of pancreatic cancer cells in vitro. The compound inhibited UbcH5c-mediated IκBα degradation and NF-κB activation, which is critical for its anticancer activity. Furthermore, DHPO suppressed the tumor growth and metastasis in two orthotopic pancreatic tumor mouse models. Conclusions These results indicated that inhibiting UbcH5c is a novel and effective strategy for treating pancreatic cancer and DHPO represents a new class of UbcH5c inhibitor and may be further developed as an anti-pancreatic cancer therapeutic agent.

Copyright of Engineering Management & Technology Discussion is the property of Omniscient Pte. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Since the early days of foundational studies of nucleic acids, many chemical moieties have been discovered to decorate RNA and DNA in diverse organisms. In mammalian cells, one of these chemical modifications, N6-methyl adenosine (m6A), is unique in a way that it is highly abundant not only on RNA polymerase II (RNAPII) transcribed, protein-coding transcripts but also on non-coding RNAs, such as ribosomal RNAs and snRNAs, mediated by distinct, evolutionarily conserved enzymes. Here, we review RNA m6A modification in the light of the recent appreciation of nuclear roles for m6A in regulating chromatin states and gene expression, as well as the recent discoveries of the evolutionarily conserved methyltransferases, which catalyze methylation of adenosine on diverse sets of RNAs. Considering that the substrates of these enzymes are involved in many important biological processes, this modification warrants further research to understand the molecular mechanisms and functions of m6A in health and disease. [Display omitted] In this review, Sendinc and Shi discuss the recent appreciation of nuclear roles for m6A in regulating chromatin states and gene expression, as well as the recent discoveries of the evolutionarily conserved methyltransferases, which catalyze methylation of adenosine on diverse sets of RNAs. [ABSTRACT FROM AUTHOR]

Con base en la crítica etnográfica de procesos afrodescendientes compartidos, en este artículo abordo las diferencias dadas entre investigación-acción-participativa y etnografía colaborativa en contextos específicos de racialización. Para ello, profundizo primeramente en aquella configuración del campo etnográfico que es dada a partir de la participación radical y la performance-investigación, y posteriormente detallo los aportes de la radio universitaria en pos de la horizontalidad y el alcance político de la «antropología por demanda». Distingo esto último de aquella actividad que es llevada adelante por los intelectuales orgánicos.

In this study, 119 feta cheese samples taken from different vendors in Istanbul were examined for the presence of L. monocytogenes. Isolates were confirmed by PCR method using iap and hlyA primers, and the antibiotic susceptibility of the identified strains was performed by the Kirby-Bauer protocol. Seven Listeria spp. was isolated from three (% 2.52) of 119 cheese samples analyzed. The seven Listeria spp. obtained from these three samples were found to contain the iap gene region but not the hlyA gene region. As a result of the sequence analysis using the 16S rRNA gene region, it was determined that these isolates were L. seeligeri. As a result of antibiotic susceptibility tests, it was observed that L. seeligeri isolates were showed ciprofloxacin (% 85.71) and penicillin (% 42.85) resistance. All strains were susceptible to amikacin, amoxicillin/clavulanic acid, chloramphenicol, rifampin, gentamicin, cefaclor, ampicillin, trimethoprim-sulfamethoxazole, tetracycline, vancomycin, and clarithromycin antibiotics. The detection of Listeria bacteria in feta cheese samples made with pasteurized milk revealed that packaging, distribution, and storage practices following the pasteurization process should be followed more strictly. It is recommended to apply controls at each stage to prevent contamination.

The article examines the effect of cooking food in kitchens on the health of women, as women and children are at a greater risk to indoor air pollution (IAP). It is important to study the cooking practices and prevalent behaviours among African women to understand the magnitude of the danger they face. The study suggests that a decline in the combustion of solid fuels and the use of clean energy can improve health among women and children, as well as sustainability goals. Proverbs 17:22 says, ‘A joyful heart is the health of the body, but a depressed spirit dries up the bones’. Bible verse Numbers 35:33–34 indicates, ‘You shall not pollute the land in which you live’. The cooking fuel analysis framework among rural women in Africa will guide forward the governments’ sustainability policies for communities to ensure healthy lives and promote well-being of women and children. Contribution: The article conducts a comprehensive analysis of the literature on African cooking practices. A combined search string is made with keywords. Thematic content analysis is conducted with NVivo (produced by QSR International). The article covers two themes, namely improved well-being and suggesting policies to combat climate change and its impacts. Policies and schemes at grassroots levels and better economic conditions in African countries can help to overcome challenges and change health-damaging cooking behaviours. The new advanced sustainability analysis framework has the potential to influence modern kitchen fuels and increase the adoption of new technologies in African villages.

Anti-diabetic drug, metformin, has attracted attentions as an anti-cancer agent due to the suppression of mTORC1 as a master switch of cell growth in various cancers. Upon mTORC1 inhibition, translation of proteins possessing IRES elements in their mRNAs still occurs in order to maintain proper cell function. Thus, inhibitor of apoptosis proteins are expected to be upregulated by mTORC1 inhibition due to the possession of IRES elements. Surprisingly, however, inhibition of mTORC1 with metformin in breast cancer cell lines of MDA-MB-231 and MCF-7, caused the downregulation of IRES-element possessing proteins of cIAP1, XIAP and Bcl-2, 24 h post-treatment. Interestingly, a shorter treatment time of 8 h, however, was accompanied by increased expression of these proteins. Importantly, inclusion of the proteasome inhibitor, Bortezomib, caused the upregulation of the tested anti-apoptotic proteins in both cell lines. These observations suggest that mTORC1 inhibition has a bifold effect; first upregulation of IRES-dependent survival proteins to prevent untimely cell death followed by an opposite effect, which is the enhanced proteosomal degradation of these protein in order to maintain a balanced response. • Metformin mediated mTORC1 inhibition enhances IRES-dependent translation of antiapoptotic proteins. • This effect on ani-apoptotic proteins is countered by enhanced proteosomal degradation, also mediated by mTORC1 inhibition. • mTORC1 inhibition upregulated anti-apoptotic proteins to prevent untimely cell death. • Proteasome constantly degrades anti apoptosis proteins to keep a balanced response. [ABSTRACT FROM AUTHOR]

Although combination antiretroviral therapy (ART) has led to significant HIV‐1 suppression and improvement in immune function, persistent viral reservoirs remain that are refractory to intensified ART. ART poses many challenges such as adherence to drug regimens, the emergence of resistant virus, and cumulative toxicity resulting from long‐term therapy. Moreover, latent HIV‐1 reservoir cells can be stochastically activated to produce viral particles despite effective ART and contribute to the rapid viral rebound that typically occurs within 2 weeks of ART interruption; thus, lifelong ART is required for continued viral suppression. Several strategies have been proposed to address the HIV‐1 reservoir such as reactivation of HIV‐1 transcription using latency reactivating agents with a combination of ART, host immune clearance and HIV‐1‐cytotoxicity to purge the infected cells—a "shock and kill" strategy. However, these approaches do not take into account the multiple transcriptional and translational blocks that contribute to HIV‐1 latency or the complex heterogeneity of the HIV‐1 reservoir, and clinical trials have thus far failed to produce the desired results. Here, we describe alternative strategies being pursued that are designed to kill selectively HIV‐1‐infected cells while sparing uninfected cells in the absence of enhanced humoral or adaptive immune responses. [ABSTRACT FROM AUTHOR]

The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Most SARS-CoV-2 infections are mild or even asymptomatic. However, a small fraction of infected individuals develops severe, life-threatening disease, which is caused by an uncontrolled immune response resulting in hyperinflammation. However, the factors predisposing individuals to severe disease remain poorly understood. Here, we show that levels of CD47, which is known to mediate immune escape in cancer and virus-infected cells, are elevated in SARS-CoV-2-infected Caco-2 cells, Calu-3 cells, and air−liquid interface cultures of primary human bronchial epithelial cells. Moreover, SARS-CoV-2 infection increases SIRPalpha levels, the binding partner of CD47, on primary human monocytes. Systematic literature searches further indicated that known risk factors such as older age and diabetes are associated with increased CD47 levels. High CD47 levels contribute to vascular disease, vasoconstriction, and hypertension, conditions that may predispose SARS-CoV-2-infected individuals to COVID-19-related complications such as pulmonary hypertension, lung fibrosis, myocardial injury, stroke, and acute kidney injury. Hence, age-related and virus-induced CD47 expression is a candidate mechanism potentially contributing to severe COVID-19, as well as a therapeutic target, which may be addressed by antibodies and small molecules. Further research will be needed to investigate the potential involvement of CD47 and SIRPalpha in COVID-19 pathology. Our data should encourage other research groups to consider the potential relevance of the CD47/ SIRPalpha axis in their COVID-19 research.

P-element-induced wimpy-like (Piwil) proteins restrict the replication of mobile genetic elements in the germ line. They are also expressed in many transformed cell lines. In this study, we discovered that the human Piwil 2 (Hili) protein can also inhibit HIV replication, especially in activated CD4+ T cells that are the preferred target cells for this virus in the infected host. Although resting cells did not express Hili, its expression was rapidly induced following T cell activation. In these cells and transformed cell lines, depletion of Hili increased levels of viral proteins and new viral particles. Further studies revealed that Hili binds to tRNA. Some of the tRNAs represent rare tRNA species, whose codons are overrepresented in the viral genome. Targeting tRNAArg(UCU) with an antisense oligonucleotide replicated effects of Hili and also inhibited HIV replication. Finally, Hili also inhibited the retrotransposition of the endogenous intracysternal A particle (IAP) by a similar mechanism. Thus, Hili joins a list of host proteins that inhibit the replication of HIV and other mobile genetic elements.IMPORTANCE Piwil proteins inhibit the movement of mobile genetic elements in the germ line. In their absence, sperm does not form and male mice are sterile. This inhibition is thought to occur via small Piwi-interacting RNAs (piRNAs). However, in some species and in human somatic cells, Piwil proteins bind primarily to tRNA. In this report, we demonstrate that human Piwil proteins, especially Hili, not only bind to select tRNA species, including rare tRNAs, but also inhibit HIV replication. Importantly, T cell activation induces the expression of Hili in CD4+ T cells. Since Hili also inhibited the movement of an endogenous retrovirus (IAP), our finding shed new light on this intracellular resistance to exogenous and endogenous retroviruses as well as other mobile genetic elements.

Simple Summary: In spite of recent optimisation of surgical therapy and multimodal treatment options, late diagnosis and devastating overall prognosis continue to characterise pancreatic cancer. The inhibitor of apoptosis protein survivin has been established as a relevant if not unambiguously understood factor in the formation and progression of pancreatic ductal adenocarcinoma (PDAC) being upregulated already in the early stages of tumourigenesis. Therefore, we analysed the expression of survivin in primary PDAC and lymph node metastases in an ample collective of 236 patients and demonstrated that cytoplasmic as nuclear overexpression of the protein correlated significantly with clinicopathological indicators of disease progression and, accordingly, showed prognostic relevance. The findings support the use of survivin as a biomarker to further explore the aggressiveness of PDAC subtypes and encourage its therapeutic approach as a molecular target to expand current chances for disease survival and potential cure. Background: Survival after surgery for pancreatic ductal adenocarcinoma (PDAC) remains poor. Thus, novel therapeutic concepts focus on the development of targeted therapies. In this context, inhibitor of apoptosis protein (IAP) survivin is regarded as a promising oncotherapeutic target. However, its expression and prognostic value in different tumour compartments of PDAC have not been studied. Methods: Immunohistochemical analysis of survivin in different PDAC tumour compartments from 236 consecutive patients was correlated with clinicopathological variables and survival. Results: In comparison to healthy pancreatic tissue high nuclear (p < 0.001) and high cytoplasmic (p < 0.01) survivin expression became evident in the tumour centre, along the invasion front and in lymph node metastases. Cytoplasmic overexpression of survivin in tumour centres was related to the presence of distant metastasis (p = 0.016) and UICC III/IV stages (p = 0.009), while high cytoplasmic expression at the invasion front grouped with venous infiltration (p = 0.022). Increased nuclear survivin along the invasion front correlated with perineural invasion (p = 0.035). High nuclear survivin in tumour centres represented an independent prognostic factor for overall survival of pancreatic tail carcinomas (HR 13.5 95%CI (1.4–129.7)) and correlated with a limited disease-free survival in PDAC (HR 1.80 95%CI (1.04–3.12)). Conclusion: Survivin is associated with advanced disease stages and poor prognosis. Therefore, survivin will help to identify patients with aggressive tumour phenotypes that could benefit from the inclusion in clinical trials incorporating survivin inhibitors in PDAC. [ABSTRACT FROM AUTHOR]

The utilisation of biological organisms, especially lichens in the environmental biomonitoring approach, has been proven to be an effective and low-cost technique suitable for developing countries like Malaysia. Index of Atmospheric Purity (IAP) tracked compositional changes in lichen communities which correlate with changes in levels of atmospheric pollution. Gunung Jerai was formed during the Cambrian Period; thus, it is a biodiversity hotspot ideal for a diverse range of lichens. In the present work, a total of 44 corticolous lichen species were sampled and identified to evaluate the pollution status of Gunung Jerai using IAP, starting from 80 to 1200 m with 300 m intervals. The samples were collected within 10 × 50 cm sampling grids attached to 60 trees, bringing a total of 120 000 cm2 of the sampling area. The air quality of the sampling area was determined by IAP score, a low score indicated by high levels of pollution. Results showed that the lowest IAP score was recorded at 300 m; meanwhile, the highest IAP score was recorded at 900 m elevation. Elevational gradient and pollution have a significant effect on the IAP score of Gunung Jerai. On average, Gunung Jerai is indicated as having a low pollution status. However, several elevations of the rainforest showed high and moderate pollution status. The IAP method is best to assess environmental pollution and provide quicker results than chemical monitoring methods. Further research could be done to evaluate the other sampling sites adjacent to other areas of Gunung Jerai. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is one of the most lethal cancers worldwide. The IAPs function as E3 ubiquitin ligases and contribute to pancreatic cancer initiation, progression, and metastasis. Although IAP-targeted therapies have been developed and shown anticancer efficacy in preclinical settings, none of them has been approved yet. Methods: Transcriptome data from public datasets were used to analyze the correlation of IAPs and E2s, and the biological function of E2 UbcH5c in pancreatic cancer. A structure-based virtual screen was used to identify UbcH5c inhibitor, and surface plasmon resonance analysis and cellular thermal shift assays were employed to evaluate the binding affinity. The anticancer activities were demonstrated through in vitro and in vivo assays, while the related mechanisms were explored through transcriptomic and proteomic analyses and confirmed by western blot, immunofluorescence, and qRT-PCR. Results: UbcH5c is positively correlated with the expression of IAPs in pancreatic cancer. We further found that UbcH5c is overexpressed and associated with a poor prognosis in pancreatic cancer. We identified a small-molecule UbcH5c inhibitor, termed DHPO, which directly bound to UbcH5c protein. DHPO inhibited cell viability and colony formation, induced apoptosis, and suppressed migration and invasion of pancreatic cancer cells in vitro. The compound inhibited UbcH5c-mediated IκBα degradation and NF-κB activation, which is critical for its anticancer activity. Furthermore, DHPO suppressed the tumor growth and metastasis in two orthotopic pancreatic tumor mouse models. Conclusions: These results indicated that inhibiting UbcH5c is a novel and effective strategy for treating pancreatic cancer and DHPO represents a new class of UbcH5c inhibitor and may be further developed as an anti-pancreatic cancer therapeutic agent. [ABSTRACT FROM AUTHOR]

Rural communities experience problems derived from an undemocratic economic policy that puts the most disadvantaged social groups at a disadvantage, therefore, higher education institutions must develop in their students tools that are aimed at achieving social changes aimed at the search for quality of life and well-being of the population from Participatory Action Research (PAR). The purpose of the research is to analyze the problems of rural communities and seek solutions from the development of PAR in the daily training practice of educational interveners. 24 students, 15 community leaders and 50 families participated. It was based on the theory of community development. The survey, the research workshop and the interview were used, needs and problems organized in age groups were identified, an action plan was proposed that will be implemented with the support of government agencies and reflected on the influence of PAR on training as educational auditors. It was found that the theoretical-methodological training of university students to intervene in rural communities favors the development of critical social awareness of students and the praxis of research from the pedagogical reflection of teachers, a situation that impacts on transformation and innovation curricular. It is concluded that the training of education professionals oriented to social change demands a pedagogical reflective process from praxis and social and individual transformation as well as the change in the formal curriculum.

In recent years,the development wave of industrial Internet has attracted great attention from academia and industry.At present,there are still some problems in the development of industrial Internet,such as weak equipment commonality and poor software dynamic reconstruction ability.Based on the above problems,an IAP industrial Internet common platform was designed,which is based on data architecture driving engine technology (data engine) and can achieve data isomorphism and dynamic processing in heterogeneous platforms.At the same time,a test bed for IAP was designed.Through a series of experiments,the characteristic advantages of this platform were demonstrated,which provided a new technical scheme for industrial Internet interconnection.

E3 ligases constitute a large and diverse family of proteins that play a central role in regulating protein homeostasis by recruiting substrate proteins via recruitment domains to the proteasomal degradation machinery. Small molecules can either inhibit, modulate or hijack E3 function. The latter class of small molecules led to the development of selective protein degraders, such as PROTACs (PROteolysis TArgeting Chimeras), that recruit protein targets to the ubiquitin system leading to a new class of pharmacologically active drugs and to new therapeutic options. Recent efforts have focused on the E3 family of Baculovirus IAP Repeat (BIR) domains that comprise a structurally conserved but diverse 70 amino acid long protein interaction domain. In the human proteome, 16 BIR domains have been identified, among them promising drug targets such as the Inhibitors of Apoptosis (IAP) family, that typically contain three BIR domains (BIR1, BIR2, and BIR3). To date, this target area lacks assay tools that would allow comprehensive evaluation of inhibitor selectivity. As a consequence, the selectivity of current BIR domain targeting inhibitors is unknown. To this end, we developed assays that allow determination of inhibitor selectivity in vitro as well as in cellulo. Using this toolbox, we have characterized available BIR domain inhibitors. The characterized chemical starting points and selectivity data will be the basis for the generation of new chemical probes for IAP proteins with well-characterized mode of action and provide the basis for future drug discovery efforts and the development of PROTACs and molecular glues.

Mechanical stress is known to fuel several hallmarks of cancer, ranging from genome instability to uncontrolled proliferation or invasion. Cancer cells are constantly challenged by mechanical stresses not only in the primary tumour but also during metastasis. However, this latter has seldom been studied with regards to mechanobiology, in particular resistance to anoikis, a cell death programme triggered by loss of cell adhesion. Here, we show in vitro that migrating breast cancer cells develop resistance to anoikis following their passage through microporous membranes mimicking confined migration (CM), a mechanical constriction that cancer cells encounter during metastasis. This CM-induced resistance was mediated by Inhibitory of Apoptosis Proteins, and sensitivity to anoikis could be restored after their inhibition using second mitochondria-derived activator of caspase (SMAC) mimetics. Anoikis-resistant mechanically stressed cancer cells displayed enhanced cell motility and evasion from natural killer cell-mediated immune surveillance, as well as a marked advantage to form lung metastatic lesions in mice. Our findings reveal that CM increases the metastatic potential of breast cancer cells.

Group B streptococcus (Streptococcus agalactiae, GBS) is an important cause of life-threatening disease in newborns. Pregnant women colonized with GBS can transmit the bacteria to the developing fetus, as well as to their neonates during or after delivery where infection can lead to sepsis, meningitis, pneumonia, or/and death. While intrapartum antibiotic prophylaxis (IAP) is the standard of care for prevention of invasive GBS disease in some countries, even in such settings a substantial residual burden of disease remains. A GBS vaccine administered during pregnancy could potentially address this important unmet medical need and provide an adjunct or alternative to IAP for the prevention of invasive GBS disease in neonates. A hurdle for vaccine development has been relatively low disease rates making efficacy studies difficult. Given the well-accepted inverse relationship between anti-GBS capsular polysaccharide antibody titers at birth and risk of disease, licensure using serological criteria as a surrogate biomarker represents a promising approach to accelerate the availability of a GBS vaccine.

• Many PROTACs now in clinic but many opportunities for further improvements remain. • New degrading mechanisms needed to overcome limitations of existing TPD approaches. • New TPD mechanisms allow discovery of new degrading warheads with improved properties. • New TPD mechanisms will give increased scope and reduced potential for tumor resistance. The transformational mechanism of action underpinning targeted protein degradation strategies, including proteolysis-targeting chimeras (PROTACs), gives potential for potent in vivo pharmacology and has allowed projects to move rapidly to the clinic. Despite this remarkable progress, there remain many opportunities to improve current, first-generation approaches even further. Our expanding knowledge will allow discovery of new degrading mechanisms with potential to address several limitations of current approaches, including improving scope and efficiency of degradation, improving drug-like properties of degraders, and reducing potential for the emergence of acquired resistance. Here, we discuss potential routes to realize these advances to expand TPD utility even further. [ABSTRACT FROM AUTHOR]

Owing to increase in prevalence of obesity and metabolic syndrome in Indian children and adolescents, this study is conducted to assess the predictive value of IAP 2015 and WHO 2007 BMI for age cut-offs in identifying metabolic risk in Indian children. Cross-sectional multicentric school-based study on 9–18-year-old healthy children (n=1,418) randomly selected from three states of India. WHO 2007 and IAP 2015 charts classified 222 (15.7%) and 271 (19.1%) as overweight/obese, respectively. A total of 192 (13.5%) subjects had metabolic risk. Of these 47 (25%) and 36 (18.75%) were classified as having normal body mass index (BMI) by WHO and IAP, respectively. In identifying metabolic risk, IAP 2015 and WHO 2007 charts showed a sensitivity of 81.3 and 75%, negative predictive value 96.5% as against 94.8%, positive predictive value 57.5 and 64.8%, and specificity of 89.7 and 91.6%, respectively. Owing to obesity epidemic and high metabolic risk in Indians, IAP 2015 charts (as against the WHO 2007 references) which had a higher sensitivity in identifying metabolic risk may be more suitable in Indian children and adolescents. [ABSTRACT FROM AUTHOR]

Infants are born into a world filled with microbes and must adapt without undue immune response while exploiting the microbiota's ability to produce otherwise unavailable nutrients. The process by which humans and microbes establish this relationship has only recently begun to be studied with the aid of genomic methods. Nearly half of all pregnant women receive antibiotics during gestation to prevent maternal and neonatal infection. Though this has been largely successful in reducing early-onset sepsis, we have yet to understand the long-term consequences of antibiotic administration during gestation to developing infants. Studies involving antibiotic use in infants suggest that dysbiosis during this period is associated with increased obesity, allergy, autoimmunity, and chronic diseases in adulthood, however, research around the limited doses of intravenous antibiotics used for intrapartum prophylaxis is limited. In this mini review, we focused on the state of the science regarding the effects of intrapartum antibiotic prophylaxis on the newborn microbial colonization process. Although, the literature indicates that there is wide variety in the specific bacteria that colonize infants from birth, limited parenteral antibiotic administration prior to delivery consistently affects the microbiota of infants by decreasing bacteria in the phylum Bacteroidetes and increasing bacteria in the phylum Proteobacteria, thus altering the normal pattern of colonization that infants experience. Delivery by cesarean section and formula feeding magnify and prolong this effect. Our mini review shows that the impact of intravenous antibiotic administration during gestation has on early colonization, growth, or immune programming in the developing offspring has not been well studied in human or animal models.