HIV-1 Tat exacerbates lipopolysaccharide-induced cytokine release via TLR4 signaling in the enteric nervous system

The loss of gut epithelium integrity leads to translocation of microbes and microbial products resulting in immune activation and drives systemic inflammation in acquired immunodeficiency syndrome (AIDS) patients. Although viral loads in HIV patients are significantly reduced in the post-cART era, inflammation and immune activation persist and can lead to morbidity. Here, we determined the interactive effects of the viral protein HIV-1 Tat and lipopolysaccharide (LPS) on enteric neurons and glia. Bacterial translocation was significantly enhanced in Tat-expressing (Tat+) mice. Exposure to HIV-1 Tat in combination with LPS enhanced the expression and release of the pro-inflammatory cytokines IL-6, IL-1β and TNF-α in the ilea of Tat+ mice and by enteric glia. This coincided with enhanced NF-κB activation in enteric glia that was abrogated in glia from TLR4 knockout mice and by knockdown (siRNA) of MyD88 siRNA in wild type glia. The synergistic effects of Tat and LPS resulted in a reduced rate of colonic propulsion in Tat+ mice treated with LPS. These results show that HIV-1 Tat interacts with the TLR4 receptor to enhance the pro-inflammatory effects of LPS leading to gastrointestinal dysmotility and enhanced immune activation

A seemingly low risk patient develops urosepsis as a complication of transrectal prostate biopsy: A case study

Background: Prostate cancer (PCa) is the most common cancer in men, and the second most common cause of cancer deaths in the United States. Approximately 1 million Americans undergo prostate biopsies annually, with 97% undergoing the transrectal prostate biopsy (TRPB). While TRPB is reliable and relatively low risk, nearly 7% of patients develop infectious complications, with 3% requiring hospitalization due to sepsis. Risk factors for developing infection post-TRPB include antibiotic resistance, \u3e10 biopsy cores, diabetes mellitus, indwelling catheter, and African-American ethnicity. Identifying risk factors, considering a transperineal biopsy approach, and utilizing pre-procedural practices like rectal sterilization, screening urinalysis, prophylactic antibiotics, or rectal culture can significantly minimize infectious complications. Case Description: A healthy 66-year-old Asian male, with a family history of prostate cancer, complains of worsening nocturia. He denies fever, fatigue, weight change, back or abdominal pain, hematuria, dysuria, polydipsia, or history of recurring infections. Vitals including body mass index (BMI) are within normal range. The prostate is enlarged and non-tender on digital rectal exam. His prostate-specific antigen rose from 2.4 to 5.8 in a year, and a prostate MRI indicated high suspicion for cancer. Following rectal enema prep, urinalysis screen, and betadine sterilization, ultrasound-guided TRPB was performed. Antibiotic prophylaxis included intravenous ciprofloxacin and ceftriaxone followed by three days of oral cefdinir. Twelve biopsies were sampled, and the patient was discharged home in good condition. The following evening, he developed fever, chills, and malaise. He was disoriented in the Emergency Department, with a temperature of 101.2 Fahrenheit, blood pressure 150/82, heart rate 109, respiratory rate 24, and 94% oxygen saturation. Urinalysis revealed leukocytes, blood, glucose, and protein. HbA1c was 6.4%. His condition improved with IV fluid resuscitation, empiric vancomycin and aztreonam in the ED, and meropenem during the remainder of his hospitalization. Peripheral blood cultures confirmed pan-sensitive E. coli. He was discharged home on oral cefuroxime 500mg BID for thirteen more days, and experienced no further complications. Prostate pathology reports confirmed adenocarcinoma, for which he successfully completed radiation therapy. Discussion: Recognizing risk factors as well as following proper infection prevention protocols are essential in minimizing potential TRPB-related complications. While the number of biopsy cores may have contributed to our patient’s progression of urosepsis, he was otherwise seemingly low risk for post-procedural infection at first glance. However, a thorough retrospective review of the patient’s history brings into question whether his borderline diabetic HbA1c level played a role in his unfortunate outcome. This consideration stems from a study demonstrating a progression of altered inflammatory and immune responses in both prediabetic and diabetic patients, highlighting that biochemical changes responsible for diabetic-related complications are evident to a degree in prediabetics. Further studies are needed to explore prediabetes as a direct risk factor for post-procedural infectious complications. Depending on these results, infection-prevention strategies currently in place for diabetics (i.e. rectal cultures and broader antibiotic coverage) may prove helpful for certain prediabetic patients as well. Until then, these potential suggestions exist on speculation alone

Ventilator-associated Acinetobacter baumannii pneumonia

We report an outbreak of ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii in 6 infants with acute lower respiratory tract infection. Non-bronchoscopic bronchoalveolar lavage isolated A. baumannii in all these infants. Environmental microbiological survey of the Pediatric intensive care unit and pediatric wards identified oxygen humidifying chambers as the source of Acinetobacter. Practices of cleaning and changing of the humidifiers were reviewed and the outbreak was controlled with new recommendations

Antioxidant and Anti-Inflammatory Effects of Shungite against Ultraviolet B Irradiation-Induced Skin Damage in Hairless Mice

As fullerene-based compound applications have been rapidly increasing in the health industry, the need of biomedical research is urgently in demand. While shungite is regarded as a natural source of fullerene, it remains poorly documented. Here, we explored the in vivo effects of shungite against ultraviolet B- (UVB-) induced skin damage by investigating the physiological skin parameters, immune-redox profiling, and oxidative stress molecular signaling. Toward this, mice were UVB-irradiated with 0.75 mW/cm2 for two consecutive days. Consecutively, shungite was topically applied on the dorsal side of the mice for 7 days. First, we found significant improvements in the skin parameters of the shungite-treated groups revealed by the reduction in roughness, pigmentation, and wrinkle measurement. Second, the immunokine profiling in mouse serum and skin lysates showed a reduction in the proinflammatory response in the shungite-treated groups. Accordingly, the redox profile of shungite-treated groups showed counterbalance of ROS/RNS and superoxide levels in serum and skin lysates. Last, we have confirmed the involvement of Nrf2- and MAPK-mediated oxidative stress pathways in the antioxidant mechanism of shungite. Collectively, the results clearly show that shungite has an antioxidant and anti-inflammatory action against UVB-induced skin damage in hairless mice

“I Think Writing is…” A Multi-State Study of Teacher Candidates’ Changing Beliefs about Writing

While writing scholarship framed by sociocultural theory illuminates the complexity of writing, writing in schools is frequently presented in simplistic ways. For this to change, teacher educators must support future teachers to develop complex understandings of writing. The purpose of this multi-state study was to investigate teacher candidates’ changing beliefs about writing and to consider the implications for teacher preparation. Data sources were written responses from 113 teacher candidates to questions about good writing and the purposes of writing that were collected at the beginning and end of semester-long literacy courses in six institutions across the United States. The responses were examined using thematic and discourse analysis. Findings indicate that, almost all teacher candidates changed their beliefs related to writing as a social, personal, and/or school practice, although changes were minor. Responses centering writing as a school activity were pervasive, and certain key sociocultural understandings, such as the connections between writing, context, culture, and power, were absent. Implications highlight ways that teacher educators might work to disrupt and broaden teacher candidates’ beliefs about writing, so teacher candidates might expand how writing is taught in their future classrooms

Prandtl Number Dependent Natural Convection with Internal Heat Sources

Natural convection plays an important role in determining the thermal load from debris accumulated in the reactor vessel lower head during a severe accident. Recently, attention is being paid to the feasibility of external vessel flooding as a severe accident management strategy and to the phenomena affecting the success path for retaining the molten core material inside the vessel. The heat transfer inside the molten core material can be characterized by the strong buoyancy-induced flows resulting from internal heating due to decay of fission products. The thermo-fluid dynamic characteristics of such flow depend strongly on the thermal boundary conditions. The spatial and temporal variation of heat flux on the pool wall boundaries and the pool superheat are mainly characterized by the natural convection flow inside the molten pool. In general, the natural convection heat transfer phenomena involving the internal heat generation are represented by the modified Rayleigh number (Ra’), which quantifies the internal heat source and hence the strength of the buoyancy force. In this study, tests were conducted in a rectangular section 250 mm high, 500 mm long and 160 mm wide. Twenty-four T-type thermocouples were installed in the test section to measure temperatures. Four T-type thermocouples were used to measure the boundary temperatures. The thermocouples were placed in designated locations after calibration. A direct heating method was adopted in this test to simulate the uniform heat generation. The experiments covered a range of Ra' between 1.5x106 and 7.42x1015 and the Prandtl number (Pr) between 0.7 and 6.5. Tests were conducted with water and air as simulant. The upper and lower boundary conditions were maintained uniform. The results demonstrated feasibility of the direct heating method to simulate uniform volumetric heat generation. Particular attentions were paid to the effect of Pr on natural convection heat transfer within the rectangular pool

An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis

Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is a major cause of cancer-associated mortality. Secondary bone cancer (SBC) is a complex disease caused by metastasis of tumor cells from their primary site and is characterized by intricate interplay of molecular interactions. Identification of targets for multifactorial diseases such as SBC, the most frequent complication of breast and prostate cancers, is a challenge. Towards achieving our aim of identification of targets specific to SBC, we constructed a 'Cancer Genes Network', a representative protein interactome of cancer genes. Using graph theoretical methods, we obtained a set of key genes that are relevant for generic mechanisms of cancers and have a role in biological essentiality. We also compiled a curated dataset of 391 SBC genes from published literature which serves as a basis of ontological correlates of secondary bone cancer. Building on these results, we implement a strategy based on generic cancer genes, SBC genes and gene ontology enrichment method, to obtain a set of targets that are specific to bone metastasis. Through this study, we present an approach for probing one of the major complications in cancers, namely, metastasis. The results on genes that play generic roles in cancer phenotype, obtained by network analysis of 'Cancer Genes Network', have broader implications in understanding the role of molecular regulators in mechanisms of cancers. Specifically, our study provides a set of potential targets that are of ontological and regulatory relevance to secondary bone cancer.Comment: 54 pages (19 pages main text; 11 Figures; 26 pages of supplementary information). Revised after critical reviews. Accepted for Publication in PLoS ON

Metagenomic analysis reveals a marked divergence in the structure of belowground microbial communities at elevated CO2

Abstract Understanding the responses of biological communities to elevated CO 2 (eCO 2 ) is a central issue in ecology, but little is known about the influence of eCO 2 on the structure and functioning (and consequent feedbacks to plant productivity) of the belowground microbial community. Here, using metagenomic technologies, we showed that 10 years of field exposure of a grassland ecosystem to eCO 2 dramatically altered the structure and functional potential of soil microbial communities. Total microbial and bacterial biomass were significantly increased at eCO 2 , but fungal biomass was unaffected. The structure of microbial communities was markedly different between ambient CO 2 (aCO 2 ) and eCO 2 as indicated by detrended correspondence analysis (DCA) of gene-based pyrosequencing data and functional gene array data. While the abundance of genes involved in decomposing recalcitrant C remained unchanged, those involved in labile C degradation and C and N fixation were significantly increased under eCO 2. Changes in microbial structure were significantly correlated with soil C and N contents and plant productivity. This study provides insights into potential activity of microbial community and associated feedback responses of terrestrial ecosystems to eCO 2

Global assessment of sand and dust storms

The specific objectives of the assessment are to: 1) Synthesise and highlight the environmental and socio-economic causes and impacts of SDS, as well as available technical measures for their mitigation, at the local, regional and global levels; 2) Show how the mitigation of SDS can yield multiple sustainable development benefits; 3) Synthesize information on current policy responses for mitigating SDS and 4) Present options for an improved strategy for mitigating SDS at the local, regional and global levels, building on existing institutions and agreements