Interventions to prevent mother-to-child transmission in breastfeeding mothers with HIV: a systematic review and meta-analysis of randomized controlled trials.

This study aimed to systematically review interventions to prevent mother-to-child transmission of HIV during breastfeeding. We conducted a systematic review and meta-analysis using specific criteria to identify randomized controlled trials that focused on pregnant and breastfeeding women living with HIV and their children from birth to 2 years of age. We extensively searched electronic databases, including Web of Science, Scopus, PubMed, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Google Scholar up to October 24, 2023. After screening 3,110 titles and abstracts, we reviewed 306 full texts. Of these, we assessed the quality and risk of bias of fifty-five articles, ultimately identifying seven studies. Four of these studies, which focused on antiretroviral therapy (ART), were included in the meta-analysis. There was little heterogeneity in study methodology and pooled estimates. The postnatal HIV transmission rate was found to be 0.01 (95%CI: 0.00 - 0.02). Therefore, the risk of mother-to-child transmission among breastfeeding mothers with HIV was significantly lower in the intervention groups than in the placebo groups. Analysis of funnel plots and Egger's test (p = 0.589) showed no evidence of publication bias. In addition to the four articles, two studies compared different ART regimens and one study compared the administration of high-dose vitamin A to the mother or the child. The results suggest that the use of ART significantly reduces the risk of postnatal HIV transmission compared with placebo. However, the effectiveness of different ART regimens or other therapies, including high-dose vitamin A, is unclear.

Interventions to prevent mother-to-child transmission in breastfeeding mothers with HIV: a systematic review and meta-analysis of randomized controlled trials

ABSTRACT This study aimed to systematically review interventions to prevent mother-to-child transmission of HIV during breastfeeding. We conducted a systematic review and meta-analysis using specific criteria to identify randomized controlled trials that focused on pregnant and breastfeeding women living with HIV and their children from birth to 2 years of age. We extensively searched electronic databases, including Web of Science, Scopus, PubMed, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Google Scholar up to October 24, 2023. After screening 3,110 titles and abstracts, we reviewed 306 full texts. Of these, we assessed the quality and risk of bias of fifty-five articles, ultimately identifying seven studies. Four of these studies, which focused on antiretroviral therapy (ART), were included in the meta-analysis. There was little heterogeneity in study methodology and pooled estimates. The postnatal HIV transmission rate was found to be 0.01 (95%CI: 0.00 - 0.02). Therefore, the risk of mother-to-child transmission among breastfeeding mothers with HIV was significantly lower in the intervention groups than in the placebo groups. Analysis of funnel plots and Egger's test (p = 0.589) showed no evidence of publication bias. In addition to the four articles, two studies compared different ART regimens and one study compared the administration of high-dose vitamin A to the mother or the child. The results suggest that the use of ART significantly reduces the risk of postnatal HIV transmission compared with placebo. However, the effectiveness of different ART regimens or other therapies, including high-dose vitamin A, is unclear.

Deleted in lymphocytic leukemia 2 (DLEU2): a possible biomarker that holds promise for future diagnosis and treatment of cancer.

The mechanism of deleted in lymphocytic leukemia 2 (DLEU2)-long non-coding RNA in tumors has become a major point of interest in recent research related to the occurrence and development of a variety of tumors. Recent studies have shown that the long non-coding RNA DLEU2 (lncRNA-DLEU2) can cause abnormal gene or protein expression by acting on downstream targets in cancers. At present, most lncRNA-DLEU2 play the role of oncogenes in different tumors, which are mostly associated with tumor characteristics, such as proliferation, migration, invasion, and apoptosis. The data thus far show that because lncRNA-DLEU2 plays an important role in most tumors, targeting abnormal lncRNA-DLEU2 may be an effective treatment strategy for early diagnosis and improving the prognosis of patients. In this review, we integrated lncRNA-DLEU2 expression in tumors, its biological functions, molecular mechanisms, and the utility of DLEU2 as an effective diagnostic and prognostic marker of tumors. This study aimed to provide a potential direction for the diagnosis, prognosis, and treatment of tumors using lncRNA-DLEU2 as a biomarker and therapeutic target.

Insights into the genetic spatial structure of Nicaraguan weedy rice and control of its seed spread.

BACKGROUND: The genetic backgrounds and occurrence patterns of weedy rice (WR, Oryza sativa) are highly diverse, and so are the challenges facing its control among countries. WR control is difficult because it is similar to cultivated rice and manual removal is one of the few options for control. Understanding the ecology of WR will aid efforts to break its life cycle and establish long-term management strategies under both irrigated and rainfed systems. RESULTS: Nicaraguan WR (NWR) plants were genetically closer to the AUS and Indica pools in terms of to genetic distance. A map of admixture coefficients suggested a pattern of long-distance dispersal and spread of NWR across Nicaragua, which has likely been facilitated by commercial activities and sharing of harvesting equipment between border cities or important trading ports and inland regions. Moreover, the NWR plants from the soil seedbank in irrigated regions showed different habitats and lower grain number per panicle compared with plants spread by seed-mediated contamination. In addition, grain indexes showed that length-to-width ratio was a better indicator than awn length for distinguishing between NWR and Nicaraguan Indica cultivars. CONCLUSION: Analysis of the population structure and habitats of NWR revealed five clusters derived from seed-mediated contamination in rainfed upland regions, plants from the soil seedbank in irrigated double-cropping regions, and pollen-mediated contamination across both regions. Field weed management before harvesting and seed purification based on the length-to-width ratio can be conducted to improve the efficiency of long-term control of WR in Nicaragua. © 2022 Society of Chemical Industry.

Comparing the cycling behaviours of Australian, Chinese and Colombian cyclists using a behavioural questionnaire paradigm.

Cyclists are vulnerable road users and face disproportionately high rates of road trauma, especially in low- and middle-income countries. Behaviour of road users is a system outcome, and thus studying cyclist behaviours can identify problems in the whole road transport system and assist in generating long-lasting, cost-effective solutions to promote cyclist safety. This study aims to investigate the similarities and disparities of cycling behaviour among countries with different income levels and cycling prevalence, and the relationships among cyclist demographic characteristics, behaviours and crash involvement. It applies the Cycling Behaviour Questionnaire (CBQ) to measure the behaviour of cyclists in three countries: Australia (high-income, emerging cycling country), China (mid-income, traditional cycling country) and Colombia (low-income, emerging cycling country). A total of 1094 cyclists (Australia 347, China 368, and Colombia 379) with a mean age of 31.8 years completed the online questionnaire. Confirmatory Factor Analysis was used to examine the factorial structure of the CBQ. The results showed that the three-factor CBQ (i.e., Traffic Violations, Errors and Positive Behaviours) had a stable and uniform factorial structure across all three countries. Cyclists reported more frequent positive behaviours than risky behaviours across all three countries. The Australian cyclists reported more positive behaviours and fewer violations than cyclists from the other countries, which is likely to reflect the road environment, policy and enforcement differences. Male cyclists tended to engage in more risky riding than females and reported more crash involvement. Older cyclists reported less risky riding and less involvement in crashes than younger cyclists. Cyclists who rode more often reported more frequent risky riding. The study helps understand the prevalence of risky/positive cyclist behaviours among countries and provides insights for developing systematic countermeasures to improve cycling environment and cyclist safety.

Tropical Cyclone Exposures and Risks of Emergency Medicare Hospital Admission for Cardiorespiratory Diseases in 175 Urban United States Counties, 1999-2010.

BACKGROUND: Although injuries experienced during hurricanes and other tropical cyclones have been relatively well-characterized through traditional surveillance, less is known about tropical cyclones' impacts on noninjury morbidity, which can be triggered through pathways that include psychosocial stress or interruption in medical treatment. METHODS: We investigated daily emergency Medicare hospitalizations (1999-2010) in 180 US counties, drawing on an existing cohort of high-population counties. We classified counties as exposed to tropical cyclones when storm-associated peak sustained winds were ≥21 m/s at the county center; secondary analyses considered other wind thresholds and hazards. We matched storm-exposed days to unexposed days by county and seasonality. We estimated change in tropical cyclone-associated hospitalizations over a storm period from 2 days before to 7 days after the storm's closest approach, compared to unexposed days, using generalized linear mixed-effect models. RESULTS: For 1999-2010, 175 study counties had at least one tropical cyclone exposure. Cardiovascular hospitalizations decreased on the storm day, then increased following the storm, while respiratory hospitalizations were elevated throughout the storm period. Over the 10-day storm period, cardiovascular hospitalizations increased 3% (95% confidence interval = 2%, 5%) and respiratory hospitalizations increased 16% (95% confidence interval = 13%, 20%) compared to matched unexposed periods. Relative risks varied across tropical cyclone exposures, with strongest association for the most restrictive wind-based exposure metric. CONCLUSIONS: In this study, tropical cyclone exposures were associated with a short-term increase in cardiorespiratory hospitalization risk among the elderly, based on a multi-year/multi-site investigation of US Medicare beneficiaries ≥65 years.

Difference between CD25+Tregs and Helios+Tregs in a murine model of allergic rhinitis.

INTRODUCTION: Regulatory T or Treg cells, balance the peripheral immune response to allergens in allergic rhinitis. Traditionally, Treg (CD25+ Treg) is identified by the coexpression of Foxp3 and CD25, but this strategy does not represent the true inhibitory function of Treg cells. Helios has been thought of as novel marker of activated Tregs, with an important inhibitory function. Consequently, Helios was proposed as a marker of Treg. Recent articles have shown that Foxp3 and Helios co-expression (Helios+Tregs) is an important functional stage of Treg. OBJECTIVE: To compare the prevalence of CD25+Tregs and Helios+Tregs using a mouse model of allergic rhinitis. METHODS: Twenty mice were randomized into two groups. The test group comprised 10 allergic rhinitis model mice exposed to ovalbumin; the control group was exposed to saline. The fractions of CD25+Tregs, Helios+Tregs, Helios+CD25+, and Helios+Foxp3+CD25+Tregs present in the two groups were determined using flow cytometry. RESULTS: CD25+Tregs and Helios+Tregs were less abundant in the spleen and nasal mucosa cells of the allergic rhinitis model compared with the control. We also observed fewer Helios+Tregs than CD25+Tregs in nasal mucosa and splenic cells of both control and test groups. Moreover, we observed fewer Helios+Foxp3+, Helios+CD25+, and Helios+Foxp3+CD25+ Tregs in the nasal mucosa in the allergic rhinitis model. Helios was expressed the most in CD4+ CD25+Foxp3+ T-cells, followed by CD4+ CD25-Foxp3- T-cells. Approximately 75% of CD25+Tregs were Helios+ in spleens of allergic rhinitis and control mice. CONCLUSION: This is the first report of the proportions of Helios+Tregs in nasal mucosa and spleens of allergic rhinitis mice. Gating true inhibitory Tregs with the coexpression of Foxp3 and Helios might be more useful than relying on the expression of CD25. This study provides a new insight for Treg studies of allergic rhinitis, and the potential utility of the marker as a therapeutic target.

A metalloproteinase of the disintegrin and metalloproteinases and the ThromboSpondin Motifs 6 as a novel marker for colon cancer: functional experiments.

Herein, we aimed to investigate the functions of ADAMTS6 in colon cancer and its potential mechanism. Based on the data acquired from TCGA database, we revealed that ADAMTS6 was highly expressed in colon cancer tissues, and high expression of ADAMTS6 predicted worse prognosis in patients with colon cancer. Moreover, qRT-PCR demonstrated that the levels of ADAMTS6 were higher in colon cancer cell lines (NCI-H508, Caco-2, CW-2 and HCT 116) than that in normal control cell line CCD-18Co. Functional experiments displayed that depletion of ADAMTS6 repressed NCI-H508 cell growth, invasion and migration whilst overexpression of ADAMTS6 facilitated Caco-2 cell growth, invasion and migration. Moreover, ADAMTS6 silencing enhanced the protein expression of E-cadherin and reduced the levels of N-cadherin, Vimentin and Snail in NCI-H508 cells, whereas ADAMTS6 overexpression showed the counter effects in Caco-2 cells. The protein levels of p-AKT and p-p65 were decreased by depletion of ADAMTS6 in NCI-H508 cells, while their levels were enhanced by overexpression of ADAMTS6 in Caco-2 cells. These consequences indicated that the accelerating effect of ADAMTS6 on colon cancer cell growth, migration and invasion might be achieved by modulating EMT and AKT/NF-κB signaling pathway, offering important foundations for colon cancer treatment.

Chronic prostatitis alters the prostatic microenvironment and accelerates preneoplastic lesions in C57BL/6 mice.

BACKGROUND: Chronic prostatitis has been supposed to be associated with preneoplastic lesions and cancer development. The objective of this study was to examine how chronic inflammation results in a prostatic microenvironment and gene mutation in C57BL/6 mice. METHODS: Immune and bacterial prostatitis mouse models were created through abdominal subcutaneous injection of rat prostate extract protein immunization (EAP group) or transurethral instillation of uropathogenic E. coli 1677 (E. coli group). Prostate histology, serum cytokine level, and genome-wide exome (GWE) sequences were examined 1, 3, and 6 months after immunization or injection. RESULT: In the EAP and E. coli groups, immune cell infiltrations were observed in the first and last months of the entire experiment. After 3 months, obvious proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN) were observed accompanied with fibrosis hyperplasia in stroma. The decrease in basal cells (Cytokeratin (CK) 5+/p63+) and the accumulation of luminal epithelial cells (CK8+) in the PIA or PIN area indicated that the basal cells were damaged or transformed into different luminal cells. Hic1, Zfp148, and Mfge8 gene mutations were detected in chronic prostatitis somatic cells. CONCLUSION: Chronic prostatitis induced by prostate extract protein immunization or E. coli infection caused a reactive prostatic inflammation microenvironment and resulted in tissue damage, aberrant atrophy, hyperplasia, and somatic genome mutation.

Racial/Ethnic Disparities in Mortality Among Medicare Beneficiaries in the FL - PR CR eSD Study.

Background Racial/ethnic disparities in acute stroke care may impact stroke outcomes. We compared outcomes by race/ethnicity among elderly Medicare beneficiaries in hospitals participating in the FL-PR CReSD (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities) registry with those in hospitals not participating in any quality improvement programs (non- QI ) in Florida and Puerto Rico (PR). Methods and Results The population included fee-for-service Medicare beneficiaries age 65+ in Florida and PR , discharged with primary diagnosis of ischemic stroke ( International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM], codes 433, 434, 436) in 2010-2013. We used mixed logistic models to assess racial/ethnic differences in outcomes (in-hospital, 30-day, and 1-year mortality, and 30-day readmission) for CR e SD and non- QI hospitals, adjusted for demographic and clinical characteristics. The study included 62 CR e SD hospitals (N=44 013, 84% white, 9% black, 4% Florida Hispanic, 1% PR Hispanic) and 113 non- QI hospitals (N=14 422, 78% white, 7% black, 5% Florida Hispanic, 8% PR Hispanic). For patients treated at CR e SD hospitals, there were no differences in risk-adjusted in-hospital mortality by race/ethnicity; blacks had lower 30-day mortality versus whites (odds ratio, 0.86; 95% confidence interval, 0.77-0.97), but higher 30-day readmission (hazard ratio, 1.09; 1.00-1.18) and 1-year mortality (odds ratio, 1.13; 1.04-1.23); Florida Hispanics had lower 30-day readmission (hazard ratio, 0.87; 0.78-0.98). PR Hispanic and black stroke patients treated at non- QI hospitals had higher risk-adjusted in-hospital, 30-day and 1-year mortality, but similar 30-day readmission versus whites treated in non- QI hospitals. Conclusions Disparities in outcomes were less common in CR e SD than non- QI hospitals, suggesting the benefits of quality improvement programs, particularly those focusing on racial/ethnic disparities.

Chronic prostatitis alters the prostatic microenvironment and accelerates preneoplastic lesions in C57BL/6 mice

BACKGROUND: Chronic prostatitis has been supposed to be associated with preneoplastic lesions and cancer development. The objective of this study was to examine how chronic inflammation results in a prostatic microenvironment and gene mutation in C57BL/6 mice. METHODS: Immune and bacterial prostatitis mouse models were created through abdominal subcutaneous injection of rat prostate extract protein immunization (EAP group) or transurethral instillation of uropathogenic E. coli 1677 (E. coli group). Prostate histology, serum cytokine level, and genome-wide exome (GWE) sequences were examined 1, 3, and 6 months after immunization or injection. RESULT: In the EAP and E. coli groups, immune cell infiltrations were observed in the first and last months of the entire experiment. After 3 months, obvious proliferative inflammatory atrophy (PIA) and prostatic intraepithelial neoplasia (PIN) were observed accompanied with fibrosis hyperplasia in stroma. The decrease in basal cells (Cytokeratin (CK) 5+/p63+) and the accumulation of luminal epithelial cells (CK8+) in the PIA or PIN area indicated that the basal cells were damaged or transformed into different luminal cells. Hic1, Zfp148, and Mfge8 gene mutations were detected in chronic prostatitis somatic cells. CONCLUSION: Chronic prostatitis induced by prostate extract protein immunization or E. coli infection caused a reactive prostatic inflammation microenvironment and resulted in tissue damage, aberrant atrophy, hyperplasia, and somatic genome mutation.

Thiamine deficiency contributes to synapse and neural circuit defects.

BACKGROUND: The previous studies have demonstrated the reduction of thiamine diphosphate is specific to Alzheimer's disease (AD) and causal factor of brain glucose hypometabolism, which is considered as a neurodegenerative index of AD and closely correlates with the degree of cognitive impairment. The reduction of thiamine diphosphate may contribute to the dysfunction of synapses and neural circuits, finally leading to cognitive decline. RESULTS: To demonstrate this hypothesis, we established abnormalities in the glucose metabolism utilizing thiamine deficiency in vitro and in vivo, and we found dramatically reduced dendrite spine density. We further detected lowered excitatory neurotransmission and impaired hippocampal long-term potentiation, which are induced by TPK RNAi in vitro. Importantly, via treatment with benfotiamine, Aß induced spines density decrease was considerably ameliorated. CONCLUSIONS: These results revealed that thiamine deficiency contributed to synaptic dysfunction which strongly related to AD pathogenesis. Our results provide new insights into pathogenesis of synaptic and neuronal dysfunction in AD.

Variations in culturable bacterial communities and biochemical properties in the foreland of the retreating Tianshan No. 1 glacier

As a glacier retreats, barren areas are exposed, and these barren areas are ideal sites to study microbial succession. In this study, we characterized the soil culturable bacterial communities and biochemical parameters of early successional soils from a receding glacier in the Tianshan Mountains. The total number of culturable bacteria ranged from 2.19 × 105 to 1.30 × 106 CFU g-1 dw and from 9.33 × 105 to 2.53 × 106 CFU g-1 dw at 4 °C and 25 °C, respectively. The number of culturable bacteria in the soil increased at 25 °C but decreased at 4 °C along the chronosequence. The total organic carbon, total nitrogen content, and enzymatic activity were relatively low in the glacier foreland. The number of culturable bacteria isolated at 25 °C was significantly positively correlated with the TOC and TN as well as the soil urease, protease, polyphenoloxidase, sucrase, catalase, and dehydrogenase activities. We obtained 358 isolates from the glacier foreland soils that clustered into 35 groups using amplified ribosomal DNA restriction analysis. These groups are affiliated with 20 genera that belong to six taxa, namely, Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Actinobacteria, Bacteroides, and Deinococcus-Thermus, with a predominance of members of Actinobacteria and Proteobacteria in all of the samples. A redundancy analysis showed that the bacterial succession was divided into three periods, an early stage (10a), a middle stage (25-74a), and a late stage (100-130a), with the total number of culturable bacteria mainly being affected by the soil enzymatic activity, suggesting that the microbial succession correlated with the soil age along the foreland.(AU)

Variations in culturable bacterial communities and biochemical properties in the foreland of the retreating Tianshan No. 1 glacier

Abstract As a glacier retreats, barren areas are exposed, and these barren areas are ideal sites to study microbial succession. In this study, we characterized the soil culturable bacterial communities and biochemical parameters of early successional soils from a receding glacier in the Tianshan Mountains. The total number of culturable bacteria ranged from 2.19 × 105 to 1.30 × 106 CFU g-1 dw and from 9.33 × 105 to 2.53 × 106 CFU g-1 dw at 4 °C and 25 °C, respectively. The number of culturable bacteria in the soil increased at 25 °C but decreased at 4 °C along the chronosequence. The total organic carbon, total nitrogen content, and enzymatic activity were relatively low in the glacier foreland. The number of culturable bacteria isolated at 25 °C was significantly positively correlated with the TOC and TN as well as the soil urease, protease, polyphenoloxidase, sucrase, catalase, and dehydrogenase activities. We obtained 358 isolates from the glacier foreland soils that clustered into 35 groups using amplified ribosomal DNA restriction analysis. These groups are affiliated with 20 genera that belong to six taxa, namely, Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Actinobacteria, Bacteroides, and Deinococcus-Thermus, with a predominance of members of Actinobacteria and Proteobacteria in all of the samples. A redundancy analysis showed that the bacterial succession was divided into three periods, an early stage (10a), a middle stage (25-74a), and a late stage (100-130a), with the total number of culturable bacteria mainly being affected by the soil enzymatic activity, suggesting that the microbial succession correlated with the soil age along the foreland.

Variations in culturable bacterial communities and biochemical properties in the foreland of the retreating Tianshan No. 1 glacier.

As a glacier retreats, barren areas are exposed, and these barren areas are ideal sites to study microbial succession. In this study, we characterized the soil culturable bacterial communities and biochemical parameters of early successional soils from a receding glacier in the Tianshan Mountains. The total number of culturable bacteria ranged from 2.19×105 to 1.30×106CFUg-1dw and from 9.33×105 to 2.53×106CFUg-1dw at 4°C and 25°C, respectively. The number of culturable bacteria in the soil increased at 25°C but decreased at 4°C along the chronosequence. The total organic carbon, total nitrogen content, and enzymatic activity were relatively low in the glacier foreland. The number of culturable bacteria isolated at 25°C was significantly positively correlated with the TOC and TN as well as the soil urease, protease, polyphenoloxidase, sucrase, catalase, and dehydrogenase activities. We obtained 358 isolates from the glacier foreland soils that clustered into 35 groups using amplified ribosomal DNA restriction analysis. These groups are affiliated with 20 genera that belong to six taxa, namely, Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Actinobacteria, Bacteroides, and Deinococcus-Thermus, with a predominance of members of Actinobacteria and Proteobacteria in all of the samples. A redundancy analysis showed that the bacterial succession was divided into three periods, an early stage (10a), a middle stage (25-74a), and a late stage (100-130a), with the total number of culturable bacteria mainly being affected by the soil enzymatic activity, suggesting that the microbial succession correlated with the soil age along the foreland.

Down-regulated miR-448 relieves spinal cord ischemia/reperfusion injury by up-regulating SIRT1.

MicroRNAs play a crucial role in the progression of spinal cord ischemia/reperfusion injury (SCII). The role of miR-448 and SIRT1 in SCII was investigated in this study, to provide further insights into prevention and improvement of this disorder. In this study, expressions of miR-448 and SIRT1 protein were determined by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze cell apoptosis. The endogenous expression of genes was modulated by recombinant plasmids and cell transfection. Dual-luciferase reporter assay was performed to determine the interaction between miR-448 and SIRT1. The Basso, Beattie, and Bresnahan score was used to measure the hind-limb function of rat. The spinal cord ischemia reperfusion injury model of adult rats was developed by abdominal aorta clamping, and the nerve function evaluation was completed by motor deficit index score. In SCII tissues and cells treated with hypoxia, miR-448 was up-regulated while SIRT1 was down-regulated. Hypoxia treatment reduced the expression of SIRT1 through up-regulating miR-448 in nerve cells. Up-regulation of miR-448 induced by hypoxia promoted apoptosis of nerve cells through down-regulating SIRT1. Down-regulated miR-448 improved neurological function and hind-limb motor function of rats with SCII by up-regulating SIRT1. Down-regulated miR-448 inhibited apoptosis of nerve cells and improved neurological function by up-regulating SIRT1, which contributes to relieving SCII.

Thiamine deficiency contributes to synapse and neural circuit defects

BACKGROUND: The previous studies have demonstrated the reduction of thiamine diphosphate is specific to Alzheimer's disease (AD) and causal factor of brain glucose hypometabolism, which is considered as a neurodegenerative index of AD and closely correlates with the degree of cognitive impairment. The reduction of thiamine diphosphate may contribute to the dysfunction of synapses and neural circuits, finally leading to cognitive decline. RESULTS: To demonstrate this hypothesis, we established abnormalities in the glucose metabolism utilizing thiamine deficiency in vitro and in vivo, and we found dramatically reduced dendrite spine density. We further detected lowered excitatory neurotransmission and impaired hippocampal long-term potentiation, which are induced by TPK RNAi in vitro. Importantly, via treatment with benfotiamine, Aß induced spines density decrease was considerably ameliorated. CONCLUSIONS: These results revealed that thiamine deficiency contributed to synaptic dysfunction which strongly related to AD pathogenesis. Our results provide new insights into pathogenesis of synaptic and neuronal dysfunction in AD.

Down-regulated miR-448 relieves spinal cord ischemia/reperfusion injury by up-regulating SIRT1

MicroRNAs play a crucial role in the progression of spinal cord ischemia/reperfusion injury (SCII). The role of miR-448 and SIRT1 in SCII was investigated in this study, to provide further insights into prevention and improvement of this disorder. In this study, expressions of miR-448 and SIRT1 protein were determined by qRT-PCR and western blot, respectively. Flow cytometry was used to analyze cell apoptosis. The endogenous expression of genes was modulated by recombinant plasmids and cell transfection. Dual-luciferase reporter assay was performed to determine the interaction between miR-448 and SIRT1. The Basso, Beattie, and Bresnahan score was used to measure the hind-limb function of rat. The spinal cord ischemia reperfusion injury model of adult rats was developed by abdominal aorta clamping, and the nerve function evaluation was completed by motor deficit index score. In SCII tissues and cells treated with hypoxia, miR-448 was up-regulated while SIRT1 was down-regulated. Hypoxia treatment reduced the expression of SIRT1 through up-regulating miR-448 in nerve cells. Up-regulation of miR-448 induced by hypoxia promoted apoptosis of nerve cells through down-regulating SIRT1. Down-regulated miR-448 improved neurological function and hind-limb motor function of rats with SCII by up-regulating SIRT1. Down-regulated miR-448 inhibited apoptosis of nerve cells and improved neurological function by up-regulating SIRT1, which contributes to relieving SCII.

A double-blinded randomized trial on growth and feeding tolerance with Saccharomyces boulardii CNCM I-745 in formula-fed preterm infants / Ensaio duplo-cego randomizado sobre crescimento e tolerância de alimentação com a Saccharomyces boulardii CNCM I-745 em neonatos prematuros alimentados com fórmula

Abstract Objective: The use of probiotics is increasingly popular in preterm neonates, as they may prevent necrotizing enterocolitis sepsis and improve growth and feeding tolerance. There is only limited literature on Saccharomyces boulardii CNCM I-745 (S. boulardii) in preterm infants. Method: A prospective, randomized, case-controlled trial with the probiotic S. boulardii (50 mg/kg twice daily) was conducted in newborns with a gestational age of 30-37 weeks and a birth weight between 1500 and 2500 g. Results: 125 neonates were enrolled; 63 in the treatment and 62 in the control group. Weight gain (16.14 ± 1.96 vs. 10.73 ± 1.77 g/kg/day, p < 0.05) and formula intake at maximal enteral feeding (128.4 ± 6.7 vs. 112.3 ± 7.2 mL/kg/day, p < 0.05) were significantly higher in the intervention group. Once enteral feeding was started, the time needed to reach full enteral feeding was significantly shorter in the probiotic group (0.4 ± 0.1 vs. 1.7 ± 0.5 days, p < 0.05). There was no significant difference in sepsis. Necrotizing enterocolitis did not occur. No adverse effects related to S. boulardii were observed. Conclusion: Prophylactic supplementation of S. boulardii at a dose of 50 mg/kg twice a day improved weight gain, improved feeding tolerance, and had no adverse effects in preterm infants >30 weeks old.

Resumo Objetivo: O uso de probióticos está cada vez mais popular em neonatos prematuros, já que podem prevenir a enterocolite necrosante (ECN) e a sepse e aumentar o crescimento e a tolerância de alimentação. Há apenas uma literatura limitada sobre a Saccharomyces boulardii CNCM I-745 (S. boulardii) em neonatos prematuros. Método: Um ensaio de caso-controle prospectivo randomizado com o probiótico S. boulardii (50 mg/kg duas vezes por dia) foi feito com recém-nascidos com idade gestacional de 30 a 37 semanas e peso ao nascer entre 1.500 e 2.500 g. Resultados: Foram incluídos 125 neonatos, 63 no grupo de tratamento e 62 no de controle. O ganho de peso (16,14 ± 1,96 em comparação com 10,73 ± 1,77 g/kg/dia, p < 0,05) e a ingestão de fórmula com nutrição enteral máxima (128,4 ± 6,7 em comparação com 112,3 ± 7,2 mL/kg/dia, p < 0,05) foram significativamente maiores no grupo de intervenção. Assim que a nutrição enteral foi iniciada, o tempo necessário para atingir a nutrição enteral completa foi significativamente menor no grupo probiótico (0,4 ± 0,1 em comparação com 1,7 ± 0,5 dia, p < 0,05). Não houve diferença significativa em sepse. Não ocorreu ECN. Não foi observado efeito colateral relacionado à S. boulardii. Conclusão: A suplementação profilática de S. boulardii em uma dose de 50 mg/kg duas vezes por dia melhorou o ganho de peso, aumentou a tolerância de alimentação e não teve efeito colateral em neonatos prematuros > 30 semanas de idade.

A double-blinded randomized trial on growth and feeding tolerance with Saccharomyces boulardii CNCM I-745 in formula-fed preterm infants.

OBJECTIVE: The use of probiotics is increasingly popular in preterm neonates, as they may prevent necrotizing enterocolitis sepsis and improve growth and feeding tolerance. There is only limited literature on Saccharomyces boulardii CNCM I-745 (S. boulardii) in preterm infants. METHOD: A prospective, randomized, case-controlled trial with the probiotic S. boulardii (50mg/kg twice daily) was conducted in newborns with a gestational age of 30-37 weeks and a birth weight between 1500 and 2500g. RESULTS: 125 neonates were enrolled; 63 in the treatment and 62 in the control group. Weight gain (16.14±1.96 vs. 10.73±1.77g/kg/day, p<0.05) and formula intake at maximal enteral feeding (128.4±6.7 vs. 112.3±7.2mL/kg/day, p<0.05) were significantly higher in the intervention group. Once enteral feeding was started, the time needed to reach full enteral feeding was significantly shorter in the probiotic group (0.4±0.1 vs. 1.7±0.5 days, p<0.05). There was no significant difference in sepsis. Necrotizing enterocolitis did not occur. No adverse effects related to S. boulardii were observed. CONCLUSION: Prophylactic supplementation of S. boulardii at a dose of 50mg/kg twice a day improved weight gain, improved feeding tolerance, and had no adverse effects in preterm infants >30 weeks old.