Perineuronal Nets in the Rat Medial Prefrontal Cortex Alter Hippocampal-Prefrontal Oscillations and Reshape Cocaine Self-Administration Memories.

The medial prefrontal cortex (mPFC) is a major contributor to relapse to cocaine in humans and to reinstatement in rodent models of cocaine use disorder. The output from the mPFC is potently modulated by parvalbumin (PV)-containing fast-spiking interneurons, the majority of which are surrounded by perineuronal nets. We previously showed that treatment with chondroitinase ABC (ABC) reduced the consolidation and reconsolidation of a cocaine conditioned place preference memory. However, self-administration memories are more difficult to disrupt. Here we report in male rats that ABC treatment in the mPFC attenuated the consolidation and blocked the reconsolidation of a cocaine self-administration memory. However, reconsolidation was blocked when rats were given a novel, but not familiar, type of retrieval session. Furthermore, ABC treatment prior to, but not after, memory retrieval blocked reconsolidation. This same treatment did not alter a sucrose memory, indicating specificity for cocaine-induced memory. In naive rats, ABC treatment in the mPFC altered levels of PV intensity and cell firing properties. In vivo recordings from the mPFC and dorsal hippocampus (dHIP) during the novel retrieval session revealed that ABC prevented reward-associated increases in high-frequency oscillations and synchrony of these oscillations between the dHIP and mPFC. Together, this is the first study to show that ABC treatment disrupts reconsolidation of the original memory when combined with a novel retrieval session that elicits coupling between the dHIP and mPFC. This coupling after ABC treatment may serve as a fundamental signature for how to disrupt reconsolidation of cocaine memories and reduce relapse.

Analyzing RNA posttranscriptional modifications to decipher the epitranscriptomic code.

The discovery of RNA silencing has revealed that non-protein-coding sequences (ncRNAs) can cover essential roles in regulatory networks and their malfunction may result in severe consequences on human health. These findings have prompted a general reassessment of the significance of RNA as a key player in cellular processes. This reassessment, however, will not be complete without a greater understanding of the distribution and function of the over 170 variants of the canonical ribonucleotides, which contribute to the breathtaking structural diversity of natural RNA. This review surveys the analytical approaches employed for the identification, characterization, and detection of RNA posttranscriptional modifications (rPTMs). The merits of analyzing individual units after exhaustive hydrolysis of the initial biopolymer are outlined together with those of identifying their position in the sequence of parent strands. Approaches based on next generation sequencing and mass spectrometry technologies are covered in depth to provide a comprehensive view of their respective merits. Deciphering the epitranscriptomic code will require not only mapping the location of rPTMs in the various classes of RNAs, but also assessing the variations of expression levels under different experimental conditions. The fact that no individual platform is currently capable of meeting all such demands implies that it will be essential to capitalize on complementary approaches to obtain the desired information. For this reason, the review strived to cover the broadest possible range of techniques to provide readers with the fundamental elements necessary to make informed choices and design the most effective possible strategy to accomplish the task at hand.

Skeletal fluorosis: an uncommon cause, yet a rescue treatment?

PURPOSE: Skeletal fluorosis (SF) results from chronic exposure to fluoride (F-) causing excessive aberrantly mineralized brittle bone tissue, fractures, and exostoses. There is no established treatment other than avoiding the source of F-. Still, excess F- can persist in bone for decades after exposure ceases. CASE PRESENTATION: A 50-year-old woman presented with multiple, recurrent, low AQ2 trauma fractures yet high radiologic bone mineral density. Serum F- was elevated, and osteomalacia was documented by non-decalcified transiliac biopsy. She reported intermittently "huffing" a keyboard cleaner containing F- (difluoroethane) for years. Following cessation of her F- exposure, we evaluated the administration of the parathyroid hormone analog, abaloparatide, hoping to increase bone remodeling and diminish her skeletal F- burden. CONCLUSION: Due to the prolonged half-life of F- in bone, SF can cause fracturing long after F- exposure stops. Anabolic therapy approved for osteoporosis, such as abaloparatide, may induce mineralized bone turnover to replace the poorly mineralized osteomalacic bone characteristic of SF and thereby diminish fracture risk. Following abaloparatide treatment for our patient, there was a decrease in bone density as well as a reduction in F- levels.

Spatial variation of covid-19 morbidity status and identification of risk zone in Tamil Nadu (India) during first wave.

COVID-19 is a pandemic disease caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). The study area, Tamilnadu, is a southern state in India. The present study demonstrates the significance of mapping in identifying the risk zones of COVID-19 disease by taking a study of COVID-19 cases in Tamilnadu state. The main objective of the study was to identify the risk zone of COVID-19 disease in the first wave of Tamilnadu through geospatial mapping. Data on COVID-19 cases collected during March 2020 to March 2021 month wise in all 37 districts (unit area) of Tamilnadu in two-month interval wise was analysed. The study is based on secondary sources from respective office in Tamilnadu. Z-score techniques were used for standardizing data. Correlation analysis provided a measure of correlation between COVID-19 and working population. Location Quotient analysis aided the identification of COVID-19 risk zones in Tamilnadu. Present study indicates tertiary workers are more vulnerable to COVID-19 disease.

The utilization of social networking sites, their perceived benefits and their potential for improving the study habits of nursing students in five countries.

BACKGROUND: The abundance of easy and accessible information and the rapid development of social networking sites (SNSs) have proven that the world is small and within reach. The great implication of this interconnectivity is attributable to the change in the learning and sharing environment, which for the most part is something that classrooms are lacking. Considering the potential implications of SNSs in nursing education reveals the benefits of SNSs in allowing students to communicate and interact with a wider audience and beyond the classroom. The aim of this study is to identify the extent of SNS utilization, the perceived benefits of SNSs and the potential of SNSs for improving the study habits of nursing students in five countries (Israel, Iraq, Oman, the Philippines and Turkey). METHODS: This study is a quantitative cross-sectional study that determined the relationship between the utilization of SNSs, the perceived benefits of SNSs, and the potential of SNSs for improving the study habits of nursing students in the five participating countries (Israel, Iraq, Oman, the Philippines, and Turkey). This paper is based on carefully analysing the survey responses of a sample of 1137 students from an online hosting site. The online instrument focuses on the extent of the utilization and benefits of SNSs according to their accessibility, usability, efficiency and reliability. RESULTS: Based on the Pearson correlation coefficient (r) our findings, reveal a significant positive correlation between the extent of a possible improvement in study habits and the extent of SNS utilization in terms of the four domains, namely, accessibility (r = 0.246), usability (r = 0.377), reliability (r = 0.287) and efficiency (r = 0.387). CONCLUSION: It can be concluded that there is a significant positive correlation between students' study habits and the extent of SNS utilization, meaning that the more students devote themselves to their study habits, the higher the level of SNS utilization. The use of SNSs by nursing students has positive and negative implications, and there is greater potential for further improving approaches to nursing education through the adaptation of curricula based on the proper utilization of SNSs.

Artificial blastocyst collapse prior to vitrification significantly improves Na+/K+-ATPase-dependent post-warming blastocoel re-expansion kinetics without inducing endoplasmic reticulum stress gene expression in the mouse.

Blastocoel expansion during embryo development is known to be reliant on the Na+/K+-ATPase pump, but little is known about the relative contribution of active (Na+/K+-ATPase pump) and facilitated diffusion (aquaporins) water transport during blastocoel re-expansion after vitrification. The aims of this study were to examine potential effects of artificial blastocoel collapse (ABC) on markers of embryo stress and the contribution of active and facilitated diffusion water transport mechanisms to blastocoel re-expansion. Day 5 mouse embryos were vitrified using either a standard protocol, laser pulse ABC, a hyperosmotic sucrose ABC protocol or both laser pulse and sucrose. Using real-time polymerase chain reaction, no differences were found in the gene expression of the endoplasmic reticulum (ER) stress markers activating transcription factor 4 (Atf4) or heat shock protein 90-alpha (Hsp90α) 2h after warming. Similarly, expression of the Na+/K+-ATPase pump gene, ATPase, Na+/K+ transporting, beta 1 polypeptide (Atp1b1) and protein did not differ between groups. Aquaporin 8 (Aqp8) gene expression was significantly lower in the laser+sucrose ABC group than in fresh controls, and aquaporin 3 (Aqp3) expression significantly higher in standard vitrified embryos compared with all other groups. Ouabain, a potent and specific Na+/K+-ATPase pump inhibitor, inhibited blastocoel re-expansion in both standard protocol- and laser ABC-vitrified embryos, reducing both groups to the same rate of re-expansion 3h after warming. These results demonstrate that ABC before vitrification does not alter mRNA or protein expression of Na+/K+-ATPase, or mRNA levels of ER stress genes Atf4 and Hsp90α. Activity of the pump may be increased in ABC embryos, with potential compensation by AQP3 when it is compromised.

A Multicountry Study on Nursing Students' Self-Perceived Competence and Barriers to Evidence-Based Practice.

BACKGROUND: Nursing education and training are essential in the attainment of evidence-based practice (EBP) competence in nursing students. Although there is a growing literature on EBP among nursing students, most of these studies are confined to a single cultural group. Thus, cross-cultural studies may provide shared global perspectives and theoretical understandings for the advancement of knowledge in this critical area. AIMS: This study compared self-perceived EBP competence among nursing students in four selected countries (India, Saudi Arabia, Nigeria, and Oman) as well as perceived barriers to EBP adoption. METHODS: A descriptive, cross-sectional, and comparative survey of 1,383 nursing students from India, Saudi Arabia, Nigeria, and Oman participated in the study. The Evidence-Based Practice Questionnaire (EBP-COQ) and the BARRIERS scale were used to collect data during the months of January 2016 to August 2017. RESULTS: Cross-country comparisons revealed significant differences in EBP competence (F = 24.437, p < .001), knowledge (F = 3.621, p = .013), skills (F = 9.527, p < .001), and attitudes (F = 74.412, p < .001) among nursing students. Three variables including nursing students' gender (ß = .301, p < .001), type of institution, (ß = -0.339, p = .001), and type of nursing student (ß = .321, p < .001) were associated with EBP competence. Barriers to EBP adoption included having no authority to change patient care policies (M = 1.65, SD = 1.05), slow publication of evidence (M = 1.59, SD = 1.01), and paucity of time in the clinical area to implement the evidence (M = 1.59, SD = 1.05). LINKING EVIDENCE TO ACTION: Both academe and hospital administration can play a pivotal role in the successful acquisition of EBP competence in nursing students.

Recent and emerging reproductive biology research in Australia and New Zealand: highlights from the Society for Reproductive Biology Annual Meeting, 2017.

Research in reproductive science is essential to promote new developments in reproductive health and medicine, agriculture and conservation. The Society for Reproductive Biology (SRB) 2017 conference held in Perth (WA, Australia) provided a valuable update on current research programs in Australia and New Zealand. This conference review delivers a dedicated summary of significant questions, emerging concepts and innovative technologies presented in the symposia. This research demonstrates significant advances in the identification of precursors for a healthy pregnancy, birth and child, and discusses how these factors can influence disease risk. A key theme included preconception parental health and its effect on gametogenesis, embryo and fetal development and placental function. In addition, the perturbation of key developmental checkpoints was shown to contribute to a variety of pathological states that have the capacity to affect health and fertility. Importantly, the symposia discussed in this review emphasised the role of reproductive biology as a conduit for understanding the transmission of non-communicable diseases, such as metabolic disorders and cancers. The research presented at SRB 2017 has revealed key findings that have the prospect to change not only the fertility of the present generation, but also the health and reproductive capacity of future generations.

The impact of age and frailty on ventricular structure and function in C57BL/6J mice.

KEY POINTS: Heart size increases with age (called hypertrophy), and its ability to contract declines. However, these reflect average changes that may not be present, or present to the same extent, in all older individuals. That aging happens at different rates is well accepted clinically. People who are aging rapidly are frail and frailty is measured with a 'frailty index'. We quantified frailty with a validated mouse frailty index tool and evaluated the impacts of age and frailty on cardiac hypertrophy and contractile dysfunction. Hypertrophy increased with age, while contractions, calcium currents and calcium transients declined; these changes were graded by frailty scores. Overall health status, quantified as frailty, may promote maladaptive changes associated with cardiac aging and facilitate the development of diseases such as heart failure. To understand age-related changes in heart structure and function, it is essential to know both chronological age and the health status of the animal. ABSTRACT: On average, cardiac hypertrophy and contractile dysfunction increase with age. Still, individuals age at different rates and their health status varies from fit to frail. We investigated the influence of frailty on age-dependent ventricular remodelling. Frailty was quantified as deficit accumulation in adult (≈7 months) and aged (≈27 months) C57BL/6J mice by adapting a validated frailty index (FI) tool. Hypertrophy and contractile function were evaluated in Langendorff-perfused hearts; cellular correlates/mechanisms were investigated in ventricular myocytes. FI scores increased with age. Mean cardiac hypertrophy increased with age, but values in the adult and aged groups overlapped. When plotted as a function of frailty, hypertrophy was graded by FI score (r = 0.67-0.55, P < 0.0003). Myocyte area also correlated positively with FI (r = 0.34, P = 0.03). Left ventricular developed pressure (LVDP) plus rates of pressure development (+dP/dt) and decay (-dP/dt) declined with age and this was graded by frailty (r = -0.51, P = 0.0007; r = -0.48, P = 0.002; r = -0.56, P = 0.0002 for LVDP, +dP/dt and -dP/dt). Smaller, slower contractions graded by FI score were also seen in ventricular myocytes. Contractile dysfunction in cardiomyocytes isolated from frail mice was attributable to parallel changes in underlying Ca2+ transients. These changes were not due to reduced sarcoplasmic reticulum stores, but were graded by smaller Ca2+ currents (r = -0.40, P = 0.008), lower gain (r = -0.37, P = 0.02) and reduced expression of Cav1.2 protein (r = -0.68, P = 0.003). These results show that cardiac hypertrophy and contractile dysfunction in naturally aging mice are graded by overall health and suggest that frailty, in addition to chronological age, can help explain heterogeneity in cardiac aging.

Diversity of leisure-time sport activities in adolescence as a predictor of leisure-time physical activity in adulthood.

Because sustained physical activity is important for a healthy life, this paper examined whether a greater diversity of sport activities during adolescence predicts higher levels of leisure-time physical activity (LTPA) in adulthood. From sport activity participation reported by 17-year-old twins, we formed five groups: 1, 2, 3, 4, and 5+ different sport activities. At follow-up in their mid-thirties, twins were divided into four activity classes based on LTPA, including active commuting. Multinomial regression analyses, adjusted for several confounders, were conducted separately for male (N=1288) and female (N=1770) participants. Further, conditional logistic regression analysis included 23 twin pairs discordant for both diversity of sport activities in adolescence and LTPA in adulthood. The diversity of leisure-time sport activities in adolescence had a significant positive association with adulthood LTPA among females. Membership in the most active adult quartile, compared to the least active quartile, was predicted by participation in 2, 3, 4, and 5+ sport activities in adolescence with odds ratios: 1.52 (P=.11), 1.86 (P=.02), 1.29 (P=.39), and 3.12 (P=5.4e-05), respectively. Within-pair analyses, limited by the small sample of twins discordant for both adolescent activities and adult outcomes, did not replicate the association. A greater diversity of leisure-time sport activities in adolescence predicts higher levels of LTPA in adulthood in females, but the causal nature of this association remains unresolved.

The effects of parental education on exercise behavior in childhood and youth: a study in Dutch and Finnish twins.

Twin studies have estimated the relative contribution of genes and the environment to variance in exercise behavior and it is known that parental education positively affects exercise levels. This study investigates the role of parental education as a potential modifier of variance in exercise behavior from age 7 to 18 years. The study is based on large datasets from the Netherlands Twin Register (NTR: N = 24 874 twins; surveys around the ages of 7, 10, 12, 14, 16 and 18 years) and two Finnish twin cohorts (FinnTwin12: N = 4399; 12, 14 and 17 years; FinnTwin16: N = 4648; 16, 17 and 18 years). Regular participation in moderate-to-vigorous exercise activities during leisure time was assessed by survey. Parental education was dichotomized ("both parents with a low education" vs "at least one parent with a high education"). The mean in exercise behavior tended to be higher and the variance tended to be lower in children of high educated parents. Evidence for gene-by-environment interaction was weak. To develop successful interventions that specifically target children of low educated parents, the mechanisms causing the mean and variance differences between the two groups should be better understood.

Self-efficacy and self-care behaviours among adults with type 2 diabetes.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) has an impact on an individuals' health and is influenced by glycemic control. AIM: To examine the relationship between glycemic control, demographic and clinical factors on self-efficacy and self-care behaviours among adults with T2DM. DESIGN: A correlational, descriptive study was used. One hundred and forty Omani adults with T2DM were recruited from a public hospital. METHODS: Data on self-efficacy, self-care behaviours and glycemic control were collected between April and July 2016. The study was approved by the College Ethics Committee and Hospital Board. Bivariate and multivariate analyses were conducted. RESULTS: Most adults had a fasting blood glucose >7.2mmol/L (90.7%), with the majority demonstrating 'uncontrolled' or poor HbA1c of >8% (65%). Variance of self-care behaviour (20.6%) and 31.3% of the variance of the self-efficacy was explained by the age, duration of diabetes, medication, HbA1c and prevention of activities of living. CONCLUSIONS: Adults with T2DM with poor glycemic control were more probable to have poor self-efficacy and self-care behaviours. Glycemic control has an effect on improving diet, exercise, medication, foot care efficacy and behaviours. CLINICAL RELEVANCE: The study recommends using these findings to plan self-efficacy and self-care behaviour to improve glycemic control among adults with T2DM.

Neurolinguistic Studies of Reading in Chinese.

Using the Chinese writing system, which is unique with respect to the composition of each character in terms of its graphic shape, as an example, this chapter addresses the neurobiological underpinnings of reading and writing and how these brain circuits are used in different languages.

Downregulation of interleukin-18-mediated cell signaling and interferon gamma expression by the hepatitis B virus e antigen.

UNLABELLED: The mechanisms by which hepatitis B virus (HBV) establishes and maintains chronic hepatitis B infection (CHB) are poorly defined. Innate immune responses play an important role in reducing HBV replication and pathogenesis. HBV has developed numerous mechanisms to escape these responses, including the production of the secreted hepatitis B e antigen (HBeAg), which has been shown to regulate antiviral toll-like receptor (TLR) and interleukin-1 (IL-1) signaling. IL-18 is a related cytokine that inhibits HBV replication in hepatoma cell lines and in the liver through the induction of gamma interferon (IFN-γ) by NK cells and T cells. We hypothesized that HBV or HBV proteins inhibit IFN-γ expression by NK cells as an accessory immunomodulatory function. We show that HBeAg protein inhibits the NF-κB pathway and thereby downregulates NK cell IFN-γ expression. Additionally, IFN-γ expression was significantly inhibited by exposure to serum from individuals with HBeAg-positive but not HBeAg-negative chronic HBV infection. Further, we show that the HBeAg protein suppresses IL-18-mediated NF-κB signaling in NK and hepatoma cells via modulation of the NF-κB pathway. Together, these findings show that the HBeAg inhibits IL-18 signaling and IFN-γ expression, which may play an important role in the establishment and/or maintenance of persistent HBV infection. IMPORTANCE: It is becoming increasingly apparent that NK cells play a role in the establishment and/or maintenance of chronic hepatitis B infection. The secreted HBeAg is an important regulator of innate and adaptive immune responses. We now show that the HBeAg downregulates NK cell-mediated IFN-γ production and IL-18 signaling, which may contribute to the establishment of infection and/or viral persistence. Our findings build on previous studies showing that the HBeAg also suppresses the TLR and IL-1 signaling pathways, suggesting that this viral protein is a key regulator of antiviral innate immune responses.

An examination of the bidirectional relationship between functioning and symptom levels in patients with anxiety disorders in the CALM study.

BACKGROUND: Patients with anxiety disorders suffer marked functional impairment in their activities of daily living. Many studies have documented that improvements in anxiety symptom severity predict functioning improvements. However, no studies have investigated how improvements in functioning simultaneously predict symptom reduction. We hypothesized that symptom levels at a given time point will predict functioning at the subsequent time point, and simultaneously that functioning at a given time point will predict symptom levels at a subsequent time point. METHOD: Patients were recruited from primary-care centers for the Coordinated Anxiety Learning and Management (CALM) study and were randomized to receive either computer-assisted cognitive-behavioral therapy and/or medication management (ITV) or usual care (UC). A cross-lagged panel design examined the relationship between functional impairment and anxiety and depression symptom severity at baseline, 6-, 12-, and 18-month follow-up assessments. RESULTS: Prospective prediction of functioning from symptoms and symptoms from functioning were both important in modeling these associations. Anxiety and depression predicted functioning as strongly as functioning predicted anxiety and depression. There were some differences in these associations between UC and ITV. Where differences emerged, the UC group was best modeled with prospective paths predicting functioning from symptoms, whereas symptoms and functioning were both important predictors in the ITV group. CONCLUSIONS: Treatment outcome is best captured by measures of functional impairment as well as symptom severity. Implications for treatment are discussed, as well as future directions of research.

Denoising of Ultrasound Cervix Image Using Improved Anisotropic Diffusion Filter.

OBJECTIVE: The purpose of this study was to evaluate an improved oriented speckle reducing anisotropic diffusion (IADF) filter that suppress the speckle noise from ultrasound B-mode images and shows better result than previous filters such as anisotropic diffusion, wavelet denoising and local statistics. METHODS: The clinical ultrasound images of the cervix were obtained by ATL HDI 5000 ultrasound machine from the Regional Cancer Centre, Medical College campus, Thiruvananthapuram. The standardized ways of organizing and storing the image were in the format of bmp and the dimensions of 256 x 256 with the help of an improved oriented speckle reducing anisotropic diffusion filter. For analysis, 24 ultrasound cervix images were tested and the performance measured. RESULTS: This provides the quality metrics in case of maximum peak signal-to-noise ratio (PSNR) of 31 dB, structural similarity index map (SSIM) of 0.88 and edge preservation accuracy of 88%. CONCLUSIONS: The IADF filter is the optimal method and it is capable of strong speckle suppression with less computational complexity.

Fluoroscopy-guided Sacroiliac Joint Steroid Injection for Low Back Pain in a Patient with Osteogenesis Imperfecta.

BACKGROUND: Osteogenesis imperfecta, also known as 'brittle bone disease', is a genetic connective tissue disease. It is characterized by bone fragility and osteopenia (low bone density). In this case, a 57-year old female presented to the University Hospital of the West Indies (UHWI), Physical Medicine and Rehabilitation Clinic with left low back pain rated 6/10 on the numeric rating scale (NRS). Clinically, the patient had sacroiliac joint mediated pain although X-rays did not show the sacroiliac joint changes. Fluoroscopy-guided left sacroiliac joint steroid injection was done. METHODS: Numeric rating scale and Oswestry Disability Index (ODI) questionnaire were used to evaluate outcome. This was completed at baseline, one week follow-up and at eight weeks post fluoroscopy-guided sacroiliac joint steroid injection. RESULTS: Numeric rating scale improved from 6/10 before the procedure to 0/10 post procedure, and ODI questionnaire score improved from a moderate disability score of 40% to a minimal disability score of 13%. Up to eight weeks, the NRS was 0/10 and ODI remained at minimal disability of 15%. CONCLUSION: Fluoroscopy-guided sacroiliac joint injection is a known diagnostic and treatment method for sacroiliac joint mediated pain. To our knowledge, this is the first case published on the use of fluoroscopy-guided sacroiliac joint steroid injection in the treatment of sacroiliac joint mediated low back pain in a patient with osteogenesis imperfecta.

STAT1-independent control of a neurotropic measles virus challenge in primary neurons and infected mice.

Neurons are chiefly nonrenewable; thus, cytolytic immune strategies to clear or control neurotropic viral infections could have lasting neurologic consequences. IFN-γ is a potent antiviral cytokine that is critical for noncytolytic clearance of multiple neurotropic viral infections, including measles virus (MV); however, the downstream pathways through which IFN-γ functions in neurons have not been defined. Unlike most cell types studied to date in which IFN-γ affects gene expression via rapid and robust activation of STAT1, basal STAT1 levels in primary hippocampal neurons are constitutively low, resulting in attenuated STAT1 activation and consequently slower kinetics of IFN-γ-driven STAT1-dependent gene expression. Given this altered expression and activation of STAT1 in neurons, we sought to determine whether STAT1 was required for IFN-γ-mediated protection from infection in neurons. To do so, we evaluated the consequences of MV challenge of STAT1-deficient mice and primary hippocampal neurons explanted from these mice. Surprisingly, the absence of STAT1 did not restrict the ability of IFN-γ to control viral infection either in vivo or ex vivo. Moreover, the canonical IFN-γ-triggered STAT1 gene expression profile was not induced in STAT1-deficient neurons, suggesting that IFN-γ regulates neuronal STAT1-independent pathways to control viral replication.

Dietary sorbitol and mannitol: food content and distinct absorption patterns between healthy individuals and patients with irritable bowel syndrome.

BACKGROUND: Sorbitol and mannitol are naturally-occurring polyol isomers. Although poor absorption and induction of gastrointestinal symptoms by sorbitol are known, the properties of mannitol are poorly described. We aimed to expand data on food composition of these polyols, and to compare their absorptive capacities and symptom induction in patients with irritable bowel syndrome (IBS) and healthy individuals. METHODS: Food samples were analysed for sorbitol and mannitol content. The degree of absorption measured by breath hydrogen production and gastrointestinal symptoms (visual analogue scales) was evaluated in a randomised, double-blinded, placebo-controlled study in 21 healthy and 20 IBS subjects after challenges with 10 g of sorbitol, mannitol or glucose. RESULTS: Certain fruits and sugar-free gum contained sorbitol, whereas mannitol content was higher in certain vegetables. Similar proportions of patients with IBS (40%) and healthy subjects (33%) completely absorbed sorbitol, although more so with IBS absorbed mannitol (80% versus 43%; P = 0.02). Breath hydrogen production was similar in both groups after lactulose but was reduced in patients with IBS after both polyols. No difference in mean (SEM) hydrogen production was found in healthy controls after sorbitol [area-under-the-curve: 2766 (591) ppm 4 h(-1) ] or mannitol [2062 (468) ppm 4 h(-1) ] but, in patients with IBS, this was greater after sorbitol [1136 (204) ppm 4 h(-1) ] than mannitol [404 (154) ppm 4 h(-1) ; P = 0.002]. Overall gastrointestinal symptoms increased significantly after both polyols in patients with IBS only, although they were independent of malabsorption of either of the polyols. CONCLUSIONS: Increased and discordant absorption of mannitol and sorbitol occurs in patients with IBS compared to that in healthy controls. Polyols induced gastrointestinal symptoms in patients with IBS independently of their absorptive patterns, suggesting that the dietary restriction of polyols may be efficacious.