High-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats.

Obesity, associated with the intake of a high-fat diet (HFD), and anxiety are common among those living in modern urban societies. Recent studies suggest a role of microbiome-gut-brain axis signaling, including a role for brain serotonergic systems in the relationship between HFD and anxiety. Evidence suggests the gut microbiome and the serotonergic brain system together may play an important role in this response. Here we conducted a nine-week HFD protocol in male rats, followed by an analysis of the gut microbiome diversity and community composition, brainstem serotonergic gene expression (tph2, htr1a, and slc6a4), and anxiety-related defensive behavioral responses. We show that HFD intake decreased alpha diversity and altered the community composition of the gut microbiome in association with obesity, increased brainstem tph2, htr1a and slc6a4 mRNA expression, including in the caudal part of the dorsomedial dorsal raphe nucleus (cDRD), a subregion previously associated with stress- and anxiety-related behavioral responses, and, finally, increased anxiety-related defensive behavioral responses. The HFD increased the Firmicutes/Bacteroidetes ratio relative to control diet, as well as higher relative abundances of Blautia, and decreases in Prevotella. We found that tph2, htr1a and slc6a4 mRNA expression were increased in subregions of the dorsal raphe nucleus in the HFD, relative to control diet. Specific bacterial taxa were associated with increased serotonergic gene expression in the cDRD. Thus, we propose that HFD-induced obesity is associated with altered microbiome-gut-serotonergic brain axis signaling, leading to increased anxiety-related defensive behavioral responses in rats.

High-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats

Obesity, associated with the intake of a high-fat diet (HFD), and anxiety are common among those living in modern urban societies. Recent studies suggest a role of microbiome-gut-brain axis signaling, including a role for brain serotonergic systems in the relationship between HFD and anxiety. Evidence suggests the gut microbiome and the serotonergic brain system together may play an important role in this response. Here we conducted a nine-week HFD protocol in male rats, followed by an analysis of the gut microbiome diversity and community composition, brainstem serotonergic gene expression (tph2, htr1a, and slc6a4), and anxiety-related defensive behavioral responses. We show that HFD intake decreased alpha diversity and altered the community composition of the gut microbiome in association with obesity, increased brainstem tph2, htr1a and slc6a4 mRNA expression, including in the caudal part of the dorsomedial dorsal raphe nucleus (cDRD), a subregion previously associated with stress- and anxiety-related behavioral responses, and, finally, increased anxiety-related defensive behavioral responses. The HFD increased the Firmicutes/Bacteroidetes ratio relative to control diet, as well as higher relative abundances of Blautia, and decreases in Prevotella. We found that tph2, htr1a and slc6a4 mRNA expression were increased in subregions of the dorsal raphe nucleus in the HFD, relative to control diet. Specific bacterial taxa were associated with increased serotonergic gene expression in the cDRD. Thus, we propose that HFD-induced obesity is associated with altered microbiome-gut-serotonergic brain axis signaling, leading to increased anxiety-related defensive behavioral responses in rats.

Initial Displacement of Humeral Shaft Fractures Is Associated With Failure of Nonoperative Management.

OBJECTIVES: To determine whether the initial radiographic displacement of humeral shaft fractures is associated with failure of nonoperative management. DESIGN: Retrospective cohort study. SETTING: Urban level 1 trauma center. PATIENTS/PARTICIPANTS: 106 patients with humeral shaft fractures (OTA/AO 12) initially managed nonoperatively. INTERVENTION: Functional bracing. MAIN OUTCOME MEASUREMENTS: Failure of nonoperative management, defined as conversion to surgery, malunion, and delayed union/nonunion. RESULTS: Nonoperative management failed in 33 (31%) of 106 included patients with 27 patients (25%) requiring surgery. On multivariate analysis, female sex [odds ratio (OR): 3.50, 95% confidence interval (CI): 1.09 to 11.21], American Society of Anesthesiologist classification >1 (OR: 7.16, CI: 1.95 to 26.29), initial fracture medial/lateral (ML) translation (OR: 1.09, CI: 1.01 to 1.17, per unit change), and initial fracture anterior-posterior (AP) angulation (OR: 1.09, CI: 1.02 to 1.15, per unit change) were independently associated with failure of nonoperative management. Initial fracture displacement values that maximized the sensitivity (SN) and specificity (SP) for failure included an AP angulation >11 degrees (SN 75%, SP 64%) and ML translation >12 mm (SN 55%, SP 75%). The failure rate in patients with none, 1, or both of these fracture parameters was 3.1% (1/32), 35.6% (20/56), and 66.6% (12/18), respectively. CONCLUSIONS: Nearly one-third of patients experienced failure of initial nonoperative management. Failure was found to be associated with greater initial fracture AP angulation and ML translation. Fracture displacement cut-off values were established that may be used by surgeons to counsel patients with these injuries. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Circumstances Involved in Unsupervised Solid Dose Medication Exposures among Young Children.

OBJECTIVE: To identify types of containers from which young children accessed solid dose medications (SDMs) during unsupervised medication exposures and the intended recipients of the medications to advance prevention. STUDY DESIGN: From February to September 2017, 5 US poison centers enrolled individuals calling about unsupervised solid dose medication exposures by children ≤5 years. Study participants answered contextually directed questions about exposure circumstances. RESULTS: Sixty-two percent of eligible callers participated. Among 4496 participants, 71.6% of SDM exposures involved children aged ≤2 years; 33.8% involved only prescription medications, 32.8% involved only over-the-counter (OTC) products that require child-resistant packaging, and 29.9% involved ≥1 OTC product that does not require child-resistant packaging. More than one-half of exposures (51.5%) involving prescription medications involved children accessing medications that had previously been removed from original packaging, compared with 20.8% of exposures involving OTC products (aOR, 3.39; 95% CI, 2.87-4.00). Attention deficit hyperactivity disorder medications (49.3%) and opioids (42.6%) were often not in any container when accessed; anticonvulsants (41.1%), hypoglycemic agents (33.8%), and cardiovascular/antithrombotic agents (30.8%) were often transferred to alternate containers. Grandparents' medications were involved in 30.7% of prescription medication exposures, but only 7.8% of OTC product exposures (aOR, 3.99; 95% CI, 3.26-4.87). CONCLUSIONS: Efforts to reduce pediatric SDM exposures should also address exposures in which adults, rather than children, remove medications from child-resistant packaging. Packaging/storage innovations designed to encourage adults to keep products within child-resistant packaging and specific educational messages could be targeted based on common exposure circumstances, medication classes, and medication intended recipients.

Survey of Blood Collection Centers and Implementation of Guidance for Prevention of Transfusion-Transmitted Zika Virus Infection--Puerto Rico, 2016.

Since November 2015, Puerto Rico has reported active mosquito-borne transmission of Zika virus. Because of the potential for Zika virus to be transmitted through transfusion of blood components, and because a high percentage of persons infected with Zika virus are asymptomatic, the Food and Drug Administration (FDA) recommended that blood collections cease in areas of the United States affected by active vector-borne transmission of Zika virus until laboratory screening of blood donations or pathogen reduction technology (PRT) for treatment of blood components can be implemented. To inform efforts to maintain the safety and availability of the blood supply in Puerto Rico, CDC, in collaboration with the Puerto Rico Department of Health, conducted a rapid assessment of blood collection and use on the island. A total of 139,369 allogeneic red blood cell (RBC) units, 45,243 platelet units, and 56,466 plasma units were collected in or imported to Puerto Rico during 2015, and 135,966 allogeneic RBC units, 13,526 therapeutic platelet units, and 25,775 plasma units were transfused. Because of the potential for local Zika virus transmission in areas with a competent mosquito vector, other areas of the United States should develop plans to ensure local blood safety and adequacy. Blood collection organizations and public health agencies should collaborate to maintain the safety and availability of local blood supplies in accordance with FDA guidance.

Transmission dynamics of pandemic influenza A(H1N1)pdm09 virus in humans and swine in backyard farms in Tumbes, Peru.

OBJECTIVES: We aimed to determine the frequency of pH1N1 transmission between humans and swine on backyard farms in Tumbes, Peru. DESIGN: Two-year serial cross-sectional study comprising four sampling periods: March 2009 (pre-pandemic), October 2009 (peak of the pandemic in Peru), April 2010 (1st post-pandemic period), and October 2011 (2nd post-pandemic period). SAMPLE: Backyard swine serum, tracheal swabs, and lung sample were collected during each sampling period. MAIN OUTCOME MEASURES: We assessed current and past pH1N1 infection in swine through serological testing, virus culture, and RT-PCR and compared the results with human incidence data from a population-based active surveillance cohort study in Peru. RESULTS: Among 1303 swine sampled, the antibody prevalence to pH1N1 was 0% pre-pandemic, 8% at the peak of the human pandemic (October 2009), and 24% in April 2010 and 1% in October 2011 (post-pandemic sampling periods). Trends in swine seropositivity paralleled those seen in humans in Tumbes. The pH1N1 virus was isolated from three pigs during the peak of the pandemic. Phylogenetic analysis revealed that these viruses likely represent two separate human-to-swine transmission events in backyard farm settings. CONCLUSIONS: Our findings suggest that human-to-swine pH1N1 transmission occurred during the pandemic among backyard farms in Peru, emphasizing the importance of interspecies transmission in backyard pig populations. Continued surveillance for influenza viruses in backyard farms is warranted.

Appropriate patient selection or health care rationing? Lessons from surgical aortic valve replacement in the Placement of Aortic Transcatheter Valves I trial.

OBJECTIVES: The study objectives were to (1) compare the safety of high-risk surgical aortic valve replacement in the Placement of Aortic Transcatheter Valves (PARTNER) I trial with Society of Thoracic Surgeons national benchmarks; (2) reference intermediate-term survival to that of the US population; and (3) identify subsets of patients for whom aortic valve replacement may be futile, with no survival benefit compared with therapy without aortic valve replacement. METHODS: From May 2007 to October 2009, 699 patients with high surgical risk, aged 84 ± 6.3 years, were randomized in PARTNER-IA; 313 patients underwent surgical aortic valve replacement. Median follow-up was 2.8 years. Survival for therapy without aortic valve replacement used 181 PARTNER-IB patients. RESULTS: Operative mortality was 10.5% (expected 9.3%), stroke 2.6% (expected 3.5%), renal failure 5.8% (expected 12%), sternal wound infection 0.64% (expected 0.33%), and prolonged length of stay 26% (expected 18%). However, calibration of observed events in this relatively small sample was poor. Survival at 1, 2, 3, and 4 years was 75%, 68%, 57%, and 44%, respectively, lower than 90%, 81%, 73%, and 65%, respectively, in the US population, but higher than 53%, 32%, 21%, and 14%, respectively, in patients without aortic valve replacement. Risk factors for death included smaller body mass index, lower albumin, history of cancer, and prosthesis-patient mismatch. Within this high-risk aortic valve replacement group, only the 8% of patients with the poorest risk profiles had estimated 1-year survival less than that of similar patients treated without aortic valve replacement. CONCLUSIONS: PARTNER selection criteria for surgical aortic valve replacement, with a few caveats, may be more appropriate, realistic indications for surgery than those of the past, reflecting contemporary surgical management of severe aortic stenosis in high-risk patients at experienced sites.

Can foot and ankle surgeons accurately estimate patient body mass index?

The body mass index (BMI) is an objective patient finding that has been established to have a negative effect on the development and outcomes of podiatric pathologic entities and interventions. The objective of the present investigation was to assess the ability of podiatric physicians to estimate the patient BMI from clinical and radiographic observation. For the clinical estimation of the patient BMI, podiatric specialists across 3 levels of experience (i.e., students, residents, and practicing clinicians) performed 294 estimations on 72 patients in 3 clinical situations (standing, sitting in a treatment chair, and lying in a hospital bed). It was more common to inaccurately estimate the patient BMI (77.9%) than it was to correctly estimate it (22.1%), with underestimations being the most common error (48.3%). The estimations were particularly inaccurate when the patients were in the common clinical situation of sitting in a treatment chair or lying in a hospital bed and with patients actually classified as obese. For the radiographic estimation of patient BMI, 150 consecutive lateral ankle radiographs were analyzed, with the ratio of the overlying soft tissue diameter to the underlying bone diameter calculated and compared. Positive, but weak, relationships were observed with these ratios. From these data, we have concluded that podiatric practitioners should perform an actual calculation of the patient BMI during the patient examination and medical decision-making process to fully appreciate the potential risks inherent to the treatment of obese patients.