Effect of hormone replacement therapy on intervertebral disc height.

OBJECTIVE: Intervertebral discs act as shock absorbers, thereby helping to reduce the risk of vertebral body fractures. Previous studies have shown that estrogen loss following menopause is associated with disc height reduction whereas treatment with hormone replacement therapy (HRT) helps to maintain disc height. This study reports the effect of HRT on disc height from a post hoc analysis of a prospective randomized clinical trial of the effect of HRT on bone density. METHODS: A total of 355 healthy postmenopausal women aged (mean ± standard deviation) 55.4 ± 4.8 years were randomized to HRT with oral 1 mg or 2 mg estradiol plus dydrogesterone or placebo. Dual-energy X-ray absorptiometry measurements (Lunar DPX) were obtained at baseline and following 2 years of treatment. Intervertebral disc height was measured in discs between T12 and L3 using the bone densitometer ruler. RESULTS: Compared with baseline, treatment with HRT resulted in a significant increase in total disc height with 1 mg estradiol (0.16 ± 0.65 cm, p = 0.015) and with 2 mg estradiol (0.21 ± 0.86 cm, p = 0.006) whilst there was no significant increase with placebo (0.13 ± 0.65 cm, p = 0.096). Between-group differences were not statistically significant. CONCLUSIONS: These results are consistent with previous findings of a beneficial effect of estrogen on discs. This may be in part responsible for the anti-fracture efficacy of HRT on vertebral fractures.

Clinical impact of a community pharmacy-based health and wellness introductory pharmacy practice experience.

OBJECTIVE: To assess the clinical impact of an intensive community pharmacy-based Health and Wellness Introductory Pharmacy Practice Experience (IPPE) completed by second-year (P2) student pharmacists. DESIGN: The Health and Wellness IPPE was a 1-week rotation developed to provide P2 student pharmacists with opportunities to provide clinical services to patients within the community pharmacy setting. Student pharmacists administered immunizations, performed blood pressure screenings and blood glucose measurements, and provided education to patients under the guidance of licensed pharmacist preceptors. SETTING AND PARTICIPANTS: Second-year student pharmacists completing a required Health and Wellness IPPE rotation in the community pharmacy setting. OUTCOMES MEASURED: Student pharmacist interventions were assessed to determine the course's clinical impact, and preceptors were surveyed regarding the feasibility of student pharmacists performing clinical services at their training sites. RESULTS: A total of 147 student pharmacists completed the IPPE at 89 community pharmacy training sites and administered 9392 injections, 90% of which were influenza vaccinations. Student pharmacists performed 3458 patient health assessments, including measuring patients' blood pressure and blood glucose and reviewing patient education materials. Most preceptors indicated that core activities were feasible during the experience. CONCLUSION: This study found that implementing a concentrated IPPE focused on immunizations and health screenings allowed student pharmacists to enhance their clinical skills and fulfill a large public health need, improving patient outcomes. Future studies should explore utilizing student pharmacists in community pharmacy settings to expand clinical services offered beyond these 2 services, such as diabetes risk tests, influenza point-of-care testing, and smoking cessation counseling.

Photoperiod-induced changes in hypothalamic de novo DNA methyltransferase expression are independent of triiodothyronine in female Siberian hamsters (Phodopus sungorus).

Many temperate zone animals engage in seasonal reproductive physiology and behavior as a strategy to maximise the propagation of the species. The hypothalamus integrates environmental cues and hormonal signalling to optimize the timing of reproduction. Recent work has revealed that epigenetic modifications, such as DNA methylation, vary across seasonal reproductive states. Multiple hormones act in the hypothalamus to permit or inhibit reproductive physiology, and the increase in thyroid hormone triiodothyronine (T3) has been implicated in the initiation of breeding in many species. The objective of this study was to examine the effect of T3 on the photoperiod-dependent regulation of reproductive physiology and hypothalamic DNA methyltransferase enzyme expression in female Siberian hamsters (Phodopus sungorus). We tested the hypothesis that T3 in short days (SD) would stimulate hypothalamic Rfrp3 and de novo DNA methyltransferase (Dnmt) expression in female Siberian hamsters. 10 weeks of SD lengths induced a decrease in body and uterine mass. Hamsters maintained in SD were found to express lower levels of GnRH, Rfrp3, Dnmt3a and Dnmt3b. Two weeks of daily T3 injections did not affect body mass, uterine mass, Gnrh, Rfrp3, Dnmt3a or Dnmt3b expression in neuroendocrine tissues. SD significantly lowered Tshß mRNA expression and T3 reduced Tshß in LD hamsters. Our data indicate sex-dependent effects of T3 for the neuroendocrine regulation of seasonal reproduction in hamsters.

The use of gelatine in wound ballistics research.

Blocks of gelatine are used in both lethality and survivability studies for broadly the same reason, i.e. comparison of ammunition effects using a material that it is assumed represents (some part of) the human body. The gelatine is used to visualise the temporary and permanent wound profiles; elements of which are recognised as providing a reasonable approximation to wounding in humans. One set of researchers aim to improve the lethality of the projectile, and the other to understand the effects of the projectile on the body to improve survivability. Research areas that use gelatine blocks are diverse and include ammunition designers, the medical and forensics communities and designers of ballistic protective equipment (including body armour). This paper aims to provide an overarching review of the use of gelatine for wound ballistics studies; it is not intended to provide an extensive review of wound ballistics as that already exists, e.g. Legal Med 23:21-29, 2016. Key messages are that test variables, projectile type (bullet, fragmentation), impact site on the body and intermediate layers (e.g. clothing, personal protective equipment (PPE)) can affect the resulting wound profiles.

Disrupted seasonal biology impacts health, food security and ecosystems.

The rhythm of life on earth is shaped by seasonal changes in the environment. Plants and animals show profound annual cycles in physiology, health, morphology, behaviour and demography in response to environmental cues. Seasonal biology impacts ecosystems and agriculture, with consequences for humans and biodiversity. Human populations show robust annual rhythms in health and well-being, and the birth month can have lasting effects that persist throughout life. This review emphasizes the need for a better understanding of seasonal biology against the backdrop of its rapidly progressing disruption through climate change, human lifestyles and other anthropogenic impact. Climate change is modifying annual rhythms to which numerous organisms have adapted, with potential consequences for industries relating to health, ecosystems and food security. Disconcertingly, human lifestyles under artificial conditions of eternal summer provide the most extreme example for disconnect from natural seasons, making humans vulnerable to increased morbidity and mortality. In this review, we introduce scenarios of seasonal disruption, highlight key aspects of seasonal biology and summarize from biomedical, anthropological, veterinary, agricultural and environmental perspectives the recent evidence for seasonal desynchronization between environmental factors and internal rhythms. Because annual rhythms are pervasive across biological systems, they provide a common framework for trans-disciplinary research.

Association of blood pressure with sodium-related knowledge and behaviors in adults with hypertension.

OBJECTIVES To describe sodium-related knowledge and self-reported behaviors in adults with hypertension and assess the association between knowledge and behaviors and blood pressure levels in this population. METHODS Using convenience sampling of patients with hypertension, an oral cross-sectional survey was administered by student pharmacists in 45 community pharmacies in Alabama and Florida in May to July 2012. After survey questions were administered, patients' blood pressures were measured. Data were tested for significance at alpha < 0.05 using bivariate analyses of independent and dependent variables (systolic/diastolic blood pressure [SBP/DBP]) and parallel linear regression of significant independent variables. RESULTS The majority of the 664 patients surveyed were women (59.3%) and white (75.2%). Most resided in urban areas (81.5%). The mean SBP/DBP was 133.3 (SD = 15.7)/81.7 (SD = 9.1) mg Hg. Most participants recognized the relationship between salt intake and high blood pressure (91.1%) and stroke (78.0%). A small percentage of patients reported that they always look for sodium content on food products (15.0%) and always buy low-sodium products (10.6%). Patients with lower knowledge scores (B = -0.01, P < 0.001) and those who were advised to cut down on salt (B = 0.02, P = 0.037) had higher SBP levels when controlled for gender, race, and awareness of their blood pressure goals. In regression analysis, lower knowledge scores were associated with increased DBP levels (B = -0.52, P = 0.014) when controlled for gender and race. CONCLUSION Many patients were not aware of salt in processed food and did not always look for sodium content on nutritional labels. Pharmacists should address dietary salt when interacting with patients with hypertension.

Engaging early experiential learners to improve quality at a VA medical center - a cross-sectional analysis.

PURPOSE: An innovative population health-based introductory pharmacy practice experience (IPPE) leveraging a Veterans Affairs (VA) and college of pharmacy collaboration was implemented in fall 2019. All second-year pharmacy students from the college actively engage in the evaluation of the medical records of veterans identified using population health management tools as needing additional care or experiencing a gap in care. This study examines the clinical impact of the experience on the care of patients at the partnering VA medical center. METHODS: Course and patient records were reviewed to enumerate the number and types of interventions performed as part of the IPPE from fall 2019 to spring 2021. Descriptive statistics were used to report clinical impact. Where relevant, t test analysis was used to compare pre- and postintervention clinical values. RESULTS: A total of 1,794 medical records were reviewed. An average of 2.67 interventions were completed for each of the 615 veterans receiving an intervention. A total of 155 patients were identified as needing routine laboratory tests (eg, glycated hemoglobin), with 48.4% of patients receiving recommended laboratory tests within 3 months. Thirty-three veterans were eligible for prescription renewals, resulting in 43 medication orders. Thirty-six veterans were recommended to take a statin medication, and statin therapy was initiated in 11, resulting in a significant decrease in the mean (SD) low-density lipoprotein cholesterol concentration (-42.4 [30.3] mg/dL, P < 0.05). Eight hundred immunizations were recommended for 632 veterans, and 286 recommendations were verbally accepted. CONCLUSION: This study demonstrates that a population health-based IPPE can provide significant clinical support to the care of patients within the VA health system.

An Integrative Review of Micro-Credentials and Digital Badges for Pharmacy Educators.

Micro-credentials (MCs) and digital badges (DBs) have gained popularity in recent years as a means to supplement traditional degrees and certifications. MCs and DBs can play a significant role in supporting student-centered learning by offering personalized and flexible learning pathways, emphasizing real-world relevance and practical skills, and fostering a culture of continuous learning and growth. However, barriers currently exist within health professions education, including pharmacy education, that could limit the full adoption and implementation of MCs and DBs. Research on the use of MCs and DBs in Doctor of Pharmacy degree programs is sparse. In this integrative review, literature on the use of MCs and DBs in health professions education is reviewed, and perspectives on the benefits, issues, and potential future uses within Doctor of Pharmacy degree programs are presented.

Gonadotropin-releasing hormone plasticity: a comparative perspective.

Gonadotropin-releasing hormone 1 (GnRH1) is a key regulator of the reproductive neuroendocrine system in vertebrates. Recent developments have suggested that GnRH1 neurons exhibit far greater plasticity at the cellular and molecular levels than previously thought. Furthermore, there is growing evidence that sub-populations of GnRH1 neurons in the preoptic area are highly responsive to specific environmental and hormonal conditions. In this paper we discuss findings that reveal large variation in GnRH1 mRNA and protein expression that are regulated by social cues, photoperiod, and hormonal feedback. We draw upon studies using histochemistry and immediate early genes (e.g., c-FOS/ZENK) to illustrate that specific groups of GnRH1 neurons are topographically organized. Based on data from diverse vertebrate species, we suggest that GnRH1 expression within individuals is temporally dynamic and this plasticity may be evolutionarily conserved. We suggest that the plasticity observed in other neuropeptide systems (i.e. kisspeptin) may have evolved in a similar manner.

Impact of a health and wellness IPPE focused on immunizations and health assessments.

BACKGROUND AND PURPOSE: Health and wellness principles are included in pharmacy education outcomes and standards, supporting the importance of integrating these concepts within pharmacy curricula. The objective of this study was to describe the development, implementation, and assessment of an intensive community pharmacy-based health and wellness introductory pharmacy practice experience (IPPE) focused on immunizations and health assessments. EDUCATIONAL ACTIVITY AND SETTING: The health and wellness IPPE was a required, one-week rotation developed to provide second-year student pharmacists with direct patient care opportunities to reinforce knowledge, skills, and abilities related to health and wellness principles. Students administered immunizations, performed hypertension and diabetes assessments, and provided education to patients at community pharmacy training sites. Students completed pre- and post-rotation self-assessments. Preceptors completed individual summative student performance evaluations and were surveyed to obtain IPPE feedback. FINDINGS: One hundred forty-seven students completed the IPPE across 89 sites. The pre-post analysis of student self-assessment results found statistically significant improvement in student confidence across all survey items. The largest improvements were found within the immunization items, specifically for preparing and administering immunizations. Ninety-nine percent of students agreed or strongly agreed participation in IPPE activities improved their ability to contribute to patient care. Qualitative analysis revealed students gained confidence and skills after practicing in a real-world setting. SUMMARY: The integration of the health and wellness IPPE within the curriculum resulted in increased student confidence in providing preventative care services. This study provides a solution to integrating health and wellness principles into pharmacy curricula to meet accreditation standards.

Drivers of Infectious Disease Seasonality: Potential Implications for COVID-19.

Not 1 year has passed since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). Since its emergence, great uncertainty has surrounded the potential for COVID-19 to establish as a seasonally recurrent disease. Many infectious diseases, including endemic human coronaviruses, vary across the year. They show a wide range of seasonal waveforms, timing (phase), and amplitudes, which differ depending on the geographical region. Drivers of such patterns are predominantly studied from an epidemiological perspective with a focus on weather and behavior, but complementary insights emerge from physiological studies of seasonality in animals, including humans. Thus, we take a multidisciplinary approach to integrate knowledge from usually distinct fields. First, we review epidemiological evidence of environmental and behavioral drivers of infectious disease seasonality. Subsequently, we take a chronobiological perspective and discuss within-host changes that may affect susceptibility, morbidity, and mortality from infectious diseases. Based on photoperiodic, circannual, and comparative human data, we not only identify promising future avenues but also highlight the need for further studies in animal models. Our preliminary assessment is that host immune seasonality warrants evaluation alongside weather and human behavior as factors that may contribute to COVID-19 seasonality, and that the relative importance of these drivers requires further investigation. A major challenge to predicting seasonality of infectious diseases are rapid, human-induced changes in the hitherto predictable seasonality of our planet, whose influence we review in a final outlook section. We conclude that a proactive multidisciplinary approach is warranted to predict, mitigate, and prevent seasonal infectious diseases in our complex, changing human-earth system.

Managing the risk of heat illness on board type 23 frigates deploying to the Arabian Gulf.

Temperature extremes are commonplace in the Middle East, varying between 30 degrees C and 50 degrees C. During the summer months, temperatures reach 50 degrees C consistently, with high humidity and sea temperatures rarely dropping below 33 degrees C. Sailing from the temperate climate of the U.K., Ship's crews are deploying to these extremes and working in spaces within the Ship where temperatures climb as high as 520C for at least 4 out of 6 months. Type 23 frigates (T23) were designed for anti-submarine warfare (anecdotally assumed to be North Sea based), yet now deploy continuously to hotter climates which subjects personnel to increased heat stress putting them at risk of heat injury. These risks can be minimised with simple measures such as maintaining hydration, rest periods outside of hot workspaces and finally cooling techniques such as inserting the arms up to the elbows in cool water for 10 minutes. During the 4 months spent in the Arabian Gulf of a 6 month tour, during the summer of 2010, personnel on board the T23 frigate HMS SOMERSET suffered no cases of heat illness despite the risks, due to employing these simple strategies.

Deficits across multiple behavioral domains align with susceptibility to stress in 129S1/SvImJ mice.

Acute physical or psychological stress can elicit adaptive behaviors that allow an organism maintain homeostasis. However, intense and/or prolonged stressors often have the opposite effect, resulting in maladaptive behaviors and curbing goal-directed action; in the extreme, this may contribute to the development of psychiatric conditions like generalized anxiety disorder, major depressive disorder, or post-traumatic stress disorder. While treatment of these disorders generally focuses on reducing reactivity to potentially threatening stimuli, there are in fact impairments across multiple domains including valence, arousal, and cognition. Here, we use the genetically stress-susceptible 129S1 mouse strain to explore the effects of stress across multiple domains. We find that 129S1 mice exhibit a potentiated neuroendocrine response across many environments and paradigms, and that this is associated with reduced exploration, neophobia, decreased novelty- and reward-seeking, and spatial learning and memory impairments. Taken together, our results suggest that the 129S1 strain may provide a useful model for elucidating mechanisms underlying myriad aspects of stress-linked psychiatric disorders as well as potential treatments that may ameliorate symptoms.

Providing an Academic APPE Elective via Videoconference Between Off-campus Faculty and Students.

Objective. To describe students' experiences and learning outcomes of an academic advanced pharmacy practice experience (APPE) elective provided via videoconference. Faculty preceptor and experiential administration's perspectives also are described. Methods. This 5-week APPE was developed using backward design and delivered starting in 2015 via videoconferencing, with the faculty preceptor and students physically located in different locations throughout the state. After the APPE, students completed a retrospective survey comparing their perspectives and learning outcomes before and after the rotation. They also provided feedback on the experience. Students completed the standard APPE evaluation. Faculty preceptor's self-reflections and experiential administration's perspectives were documented. Results. Six students completed this unique APPE over three academic years. After the rotation, five students (83%) stated that their interest in a full-time academic career increased, while one student's (17%) interest stayed the same. All students stated there was "no hindrance" with this rotation being conducted via videoconference or with the geographical distance between the faculty preceptor and them. Student ratings of nine learning outcomes increased after completing the APPE, demonstrating their perception of their knowledge improved in all topic areas. Conclusion. Students, the faculty preceptor, and experiential administration deemed this videoconference academic APPE effective and successful. This experience affords students, without regard for physical location, the opportunity to pursue interests in academia, adds to the variety of APPEs offered by the school, and allows students to learn about careers in academic pharmacy, an area of growing need in the pharmacy profession.

Outcomes following limb salvage after combat hindfoot injury are inferior to delayed amputation at five years.

OBJECTIVES: The surgical challenge with severe hindfoot injuries is one of technical feasibility, and whether the limb can be salvaged. There is an additional question of whether these injuries should be managed with limb salvage, or whether patients would achieve a greater quality of life with a transtibial amputation. This study aims to measure functional outcomes in military patients sustaining hindfoot fractures, and identify injury features associated with poor function. METHODS: Follow-up was attempted in all United Kingdom military casualties sustaining hindfoot fractures. All respondents underwent short-form (SF)-12 scoring; those retaining their limb also completed the American Academy of Orthopaedic Surgeons Foot and Ankle (AAOS F&A) outcomes questionnaire. A multivariate regression analysis identified injury features associated with poor functional recovery. RESULTS: In 12 years of conflict, 114 patients sustained 134 fractures. Follow-up consisted of 90 fractures (90/134, 67%), at a median of five years (interquartile range (IQR) 52 to 80 months).The median Short-Form 12 physical component score (PCS) of 62 individuals retaining their limb was 45 (IQR 36 to 53), significantly lower than the median of 51 (IQR 46 to 54) in patients who underwent delayed amputation after attempted reconstruction (p = 0.0351).Regression analysis identified three variables associated with a poor F&A score: negative Bohler's angle on initial radiograph; coexisting talus and calcaneus fracture; and tibial plafond fracture in addition to a hindfoot fracture. The presence of two out of three variables was associated with a significantly lower PCS compared with amputees (medians 29, IQR 27 to 43 vs 51, IQR 46 to 54; p < 0.0001). CONCLUSIONS: At five years, patients with reconstructed hindfoot fractures have inferior outcomes to those who have delayed amputation. It is possible to identify injuries which will go on to have particularly poor outcomes.Cite this article: P. M. Bennett, T. Stevenson, I. D. Sargeant, A. Mountain, J. G. Penn-Barwell. Outcomes following limb salvage after combat hindfoot injury are inferior to delayed amputation at five years. Bone Joint Res 2018;7:131-138. DOI: 10.1302/2046-3758.72.BJR-2017-0217.R2.

Ambulatory care preceptors' perceptions on SOAP note writing in advanced pharmacy practice experiences (APPEs).

INTRODUCTION: Descriptions of SOAP note requirements and assessment methods used during advanced pharmacy practice experiences (APPEs) are limited in the literature. This study aimed to gather information from preceptors regarding SOAP note writing and assessment methods utilized during ambulatory care APPEs. METHODS: A survey was developed and distributed to ambulatory care preceptors with data collected via Qualtrics and analyzed using descriptive statistics, Fisher's exact test to assess the significance for associations between dependent and independent variables, and the Gamma test to assess dependent variables in grading habits and feedback types. RESULTS: The survey response rate was 62% with 75% of preceptors having students write SOAP notes during APPEs. A majority of preceptors (84%) do not formally grade SOAP notes with full-time faculty being more likely to grade and provide written feedback. Half of the preceptors perceived students as either prepared or very prepared to write SOAP notes but the majority felt that students struggle with the assessment portion of the note. There were significant differences between schools in the percentage of preceptors that formally grade SOAP notes, ranging from 2 to 45%. CONCLUSIONS: Preceptors' perception of student preparedness to write SOAP notes on ambulatory APPEs was similar, despite assessment methods varying widely.

The burden of gunshot wounding of UK military personnel in Iraq and Afghanistan from 2003-14.

INTRODUCTION: Gunshot wounding (GSW) is the second most common mechanism of injury in warfare after explosive injury. The aim of this study was to define the clinical burden of GSW placed on UK forces throughout the recent Iraq and Afghanistan conflicts. METHODS: This study was a retrospective review of data from the UK Military Joint Theatre Trauma Registry (JTTR). A JTTR search identified records within the 12 year period of conflict between 19 Mar 2003 and 27 Oct 2014 of all UK military GSW casualties sustained during the complete timelines of both conflicts. Included cases had their clinical timelines and treatment further examined from time of injury up until discharge from hospital or death. RESULTS: There were 723 casualties identified (177 fatalities, 546 survivors). Median age at the time of injury was 24 years (range 18-46 years), with 99.6% of casualties being male. Most common anatomical locations for injury were the extremities, with 52% of all casualties sustaining extremity GSW, followed by 16% GSW to the head, 15% to the thorax, and 7% to the abdomen. In survivors, the rate of extremity injury was higher at 69%, with head, thorax and abdomen injuries relatively lower at 5%, 11% and 6% respectively. All GSW casualties had a total of 2827 separate injuries catalogued. A total of 545 casualties (523 survivors, 22 fatalities) underwent 2357 recorded surgical procedures, which were carried out over 1455 surgical episodes between admission to a deployed medical facility and subsequent transfer to the Royal Centre for Defence Medicine (RCDM) in the UK. This gave a median of 3 (IQR 2-5) surgical procedures within a median of 2 (IQR 2-3) surgical episodes per casualty. Casualties had a combined length of stay (LoS) of 25 years within a medical facility, with a mean LoS in a deployed facility of 1.9 days and 14 days in RCDM. CONCLUSION: These findings define the massive burden of injury associated with battlefield GSW and underscore the need for further research to both reduce wound incidence and severity of these complex injuries.

A compliance assessment of midpoint formative assessments completed by APPE preceptors.

INTRODUCTION: Experiential pharmacy preceptors should provide formative and summative feedback during a learning experience. Preceptors are required to provide colleges and schools of pharmacy with assessments or evaluations of students' performance. Students and experiential programs value on-time completion of midpoint evaluations by preceptors. The objective of this study was to determine the number of on-time electronically documented formative midpoint evaluations completed by preceptors during advanced pharmacy practice experiences (APPEs). METHODS: Compliance rates of on-time electronically documented formative midpoint evaluations were reviewed by the Office of Experiential Education of a five-member consortium during the two-year study period prior to the adoption of Standards 2016. Pearson chi-square test and generalized linear models were used to determine if statistically significant differences were present. RESULTS: Average midpoint compliance rates for the two-year research period were 40.7% and 41% respectively. No statistical significance was noted comparing compliance rates for year one versus year two. However, statistical significance was present when comparing compliance rates between schools during year two. Feedback from students and preceptors pointed to the need for brief formal midpoint evaluations that require minimal time to complete, user friendly experiential management software, and methods for documenting verbal feedback through student self-reflection. CONCLUSIONS: Additional education and training to both affiliate and faculty preceptors on the importance of written formative feedback at midpoint is critical to remaining in compliance with Standards 2016.

Systematic review and meta-analysis: Efficacy of patented probiotic, VSL#3, in irritable bowel syndrome.

BACKGROUND: VSL#3 is a patented probiotic for which several clinical trials suggest benefits on motor function, bloating, and symptoms of irritable bowel syndrome (IBS). OBJECTIVES: To quantify effects of VSL#3 on abdominal pain, stool consistency, overall response, abdominal bloating, and quality of life (QOL) in IBS through meta-analysis. METHODS: MEDLINE (OvidSP and PubMed), EMBASE, Web of Science, and Scopus were searched up to May 2017. Using a fixed effects model, we pooled data from intention-to-treat analyses of randomized trials (RCTs) comparing VSL#3 to placebo in IBS. Data were reported as relative risk (RR), overall mean difference (MD), or standardized MD (SMD) with 95% confidence intervals (CI). Quality of evidence was rated using the GRADE approach. KEY RESULTS: Among 236 citations, 5 RCTs (243 patients) were included. No significant differences were observed for abdominal pain (SMD = -0.03; 95% CI -0.29 to 0.22), bloating (SMD = -0.15; 95% CI -0.40 to 0.11), proportion of bowel movements with normal consistency (overall MD = 0; 95% CI -0.09 to 0.08), or IBS-QOL (SMD = 0.08; 95% CI -0.22 to 0.39). VSL#3 was associated with a nearly statistically significant increase in overall response (RR = 1.39; 95% CI 0.99-1.98). CONCLUSIONS & INFERENCES: In this systematic review and meta-analysis, there was a trend toward improvement in overall response with VSL#3, but no clear evidence effectiveness for IBS. However, the number and sample sizes of the trials are small and the overall quality of evidence for 3 of the 5 outcomes was low. Larger trials evaluating validated endpoints in well-defined IBS patients are warranted.

Environmental and hormonal regulation of epigenetic enzymes in the hypothalamus.

Neuroendocrine structures integrate a vast range of external cues and internal signals that, in turn, result in adaptive physiological responses. Emerging data indicate that light, social cues, stress and energy balance stimulate relatively short- and long-term genomic modifications in discrete neuroendocrine structures, which are mediated by epigenetic mechanisms. Moreover, environmentally-induced fluctuations in the synthesis of local hypothalamic and circulating hormones provide an internal signal that contributes to the extensive neuroendocrine genomic plasticity. This review examines the impact of environmental stimuli and endogenous hormonal signals on the regulation of epigenetic enzymes in key neuroendocrine structures. The data discussed are predominantly derived from studies in the neuroendocrine control of seasonal reproduction and the impact of social stress in rodent models. The perspective presented considers the role of oestrogen and glucocorticoids as the primary catalysts for inducing epigenetic modifications (eg, DNA methylation) in specific neuroendocrine structures. Oestrogen and glucocorticoid actions suggest: (i) a preferential action for specific epigenetic enzymes and (ii) nucleus- and cell-specific modifications. Untangling the complex web of hormonal regulation of methylation and acetylation will enhance our understanding of short- and long-term changes in epigenetic enzymes that generate adaptive and pathological neuroendocrine responses.