Sex, pain, and the microbiome: The relationship between baseline gut microbiota composition, gender and somatic pain in healthy individuals.

BACKGROUND AND AIM: Relative to men, women present with pain conditions more commonly. Although consistent differences exist between men and women in terms of physiological pain sensitivity, the underlying mechanisms are incompletely understood and yet could inform the development of effective sex specific treatments for pain. The gut microbiota can modulate nervous system functioning, including pain signaling pathways. We hypothesized that the gut microbiota and critical components of the gut-brain axis might influence electrical pain thresholds. Further, we hypothesized that sex, menstrual cycle, and hormonal contraceptive use might account for inter-sex differences in pain perception. METHODS: Healthy, non-obese males (N = 15) and females (N = 16), (nine of whom were using hormonal contraceptives), were recruited. Male subjects were invited to undergo testing once, whereas females were invited three times across the menstrual cycle, based on self-reported early follicular (EF), late follicular (LF), or mid-luteal (ML) phase. On test days, electrical stimulation on the right ankle was performed; salivary cortisol levels were measured in the morning; levels of lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), pro-inflammatory cytokines were assessed in plasma, and microbiota composition and short-chain fatty acids (SCFAs) levels were determined in fecal samples. RESULTS: We observed that the pain tolerance threshold/pain sensation threshold (PTT/PST) ratio was significantly lesser in women than men, but not PST or PTT alone. Further, hormonal contraceptive use was associated with increased LBP levels (LF & ML phase), whilst sCD14 levels or inflammatory cytokines were not affected. Interestingly, in women, hormonal contraceptive use was associated with an increase in the relative abundance of Erysipelatoclostridium, and the relative abundances of certain bacterial genera correlated positively with pain sensation thresholds (Prevotella and Megasphera) during the LF phase and cortisol awakening response (Anaerofustis) during the ML phase. In comparison with men, women displayed overall stronger associations between i) SCFAs data, ii) cortisol data, iii) inflammatory cytokines and PTT and PST. DISCUSSION AND CONCLUSION: Our findings support the hypothesis that the gut microbiota may be one of the factors determining the physiological inter-sex differences in pain perception. Further research is needed to investigate the molecular mechanisms by which specific sex hormones and gut microbes modulate pain signaling pathways, but this study highlights the possibilities for innovative individual targeted therapies for pain management.

Posttraumatic stress disorder and breast cancer: Risk factors and the role of inflammation and endocrine function.

A breast cancer diagnosis can be a life-changing and stressful experience that can lead to chronic mental health conditions such as posttraumatic stress disorder (PTSD). Greater than one-third of patients initially diagnosed with PTSD after a diagnosis of breast cancer continue to have persistent or worsening PTSD symptoms after 4 years. An emerging body of literature has indicated several key environmental and biological risk factors for PTSD among survivors of breast cancer. Well-recognized risk factors include having a history of childhood trauma, being nonwhite, obesity, younger age at the time of diagnosis, diagnosis with a higher stage of breast cancer, and short time since treatment. Of the emerging risk factors related to fear circuitry in the brain, 2 pathways of particular importance are the stress-driven activation of inflammatory pathways and the long-term effect of antiendocrine therapies. These central and peripheral responses during and after stress exposure are important because increased fear and anxiety can lead to the maintenance of PTSD and worse patient outcomes. Given the poor outcomes associated with PTSD and the high prevalence of breast cancer in women, more research to identify those women at heightened risk of PTSD after breast cancer is warranted to reduce the number of diagnoses and lessen the negative impact of this chronic mental health condition.

Robotic Versus Laparoscopic Gastrectomy for Gastric Adenocarcinoma: Propensity-Matched Analysis.

Background. We compared the outcomes of laparoscopic-assisted (LA) and robotic-assisted (RA) gastrectomies performed for gastric adenocarcinoma in the National Cancer Database. Methods. The National Cancer Database was queried for patients 18 years old with stages I to III gastric adenocarcinoma who underwent LA or RA gastrectomy. Propensity matching was performed between the 2 groups with regard to clinical staging, adjuvant treatment, demographics, and the extent of surgery. Results. A cohort of 1893 (1262 = LA, 631 = RA) patients was identified in a 2:1 propensity matching. The groups were well matched. The rate of negative margin as well as 30- and 90-day mortality were similar between the 2 cohorts. Long-term survival was similar between the 2 groups (median survival 49.2 months in LA vs 56.2 months for RA, P = .405). However, the average number of lymph nodes (LNs) sampled was significantly higher in the RA group compared with the LA group (19.6 vs 17.4, P < .001). Similarly, the percentage of surgeries in which ≥15 LNs were sampled was also greater in the RA group compared with the LA group (63.9% vs 57.6%, P = .010). On multivariable analysis, having 15 LNs or more examined was associated with better survival (hazard ratio = 0.72, 95% confidence interval = 0.60-0.87, P < .001). Advanced age, nodal positivity, and advanced clinical stages were significantly associated with worse survival. Conclusions. RA gastrectomy may allow a greater harvest of LNs, and thus more accurate staging, without increasing short-term adverse outcomes compared with LA gastrectomy. Short-term and long-term outcomes in this well-matched cohort appear comparable for both approaches.

Trends and Outcomes of Synchronous Resection of Colorectal Metastasis in the Modern Era-Analysis of Targeted Hepatic NSQIP Database.

BACKGROUND: Previous studies using the NSQIP database to study hepatectomies lacked hepatic specific variables and outcomes. We used the targeted NSQIP hepatectomy database to examine the nationwide trend and the safety profile of synchronous liver and colorectal resection compared with hepatectomy alone for colorectal liver metastasis. METHODS: The targeted NSQIP hepatectomy database from 2014 was used to study patients who underwent hepatectomy for diagnosis of adenocarcinoma of the colon and rectum. RESULTS: Of the 3064 hepatic resections in the database, 1138 cases were performed for colorectal metastasis. Of these, 1040 were liver-alone surgery and 98 were synchronous liver and colorectal resection. Most (58.7%) patients received neoadjuvant therapy. The rate of neoadjuvant therapy, intraoperative ablation, biliary reconstruction, and the use of minimally invasive technique were similar between the two groups. The overall 30-d mortality in this cohort was low (1.1%). While the mortality rate in the synchronous group was similar to liver-only group (3.1% versus 0.9%, P = 0.077). The rate of liver failure (3.3% versus 4.1%, P = 0.722) and biliary leak (5.3% versus 9.6%, P = 0.084) were similar between the two groups. However, the rate of major complications was higher on multivariable analyses (25.5% versus 12.1%, OR 2.5, 95% CI 1.5-4.1, P < 0.001) for the synchronous group. CONCLUSIONS: Hepatic resection for colorectal metastasis in the modern era has low short-term mortality. While synchronous resection was associated with a higher incidence of major complications, liver-specific complications did not increase with synchronous resection.

Dietary Supplementation with a Magnesium-Rich Marine Mineral Blend Enhances the Diversity of Gastrointestinal Microbiota.

Accumulating evidence demonstrates that dietary supplementation with functional food ingredients play a role in systemic and brain health as well as in healthy ageing. Conversely, deficiencies in calcium and magnesium as a result of the increasing prevalence of a high fat/high sugar "Western diet" have been associated with health problems such as obesity, inflammatory bowel diseases, and cardiovascular diseases, as well as metabolic, immune, and psychiatric disorders. It is now recognized that modulating the diversity of gut microbiota, the population of intestinal bacteria, through dietary intervention can significantly impact upon gut health as well as systemic and brain health. In the current study, we show that supplementation with a seaweed and seawater-derived functional food ingredient rich in bioactive calcium and magnesium (0.1% supplementation) as well as 70 other trace elements, significantly enhanced the gut microbial diversity in adult male rats. Given the significant impact of gut microbiota on health, these results position this marine multi-mineral blend (MMB) as a promising digestive-health promoting functional food ingredient.

Prevalence, Diagnosis, and Treatment Rates of Mood Disorders among Opioid Users under Criminal Justice Supervision.

BACKGROUND: Individuals involved in the criminal justice system have disproportionately high rates of psychiatric disorders when compared to the general U.S. POPULATION: If left untreated, the likelihood of subsequent arrest increases and risk for adverse health consequences is great, particularly among opioid users. OBJECTIVES: To explore the prevalence, characteristics, and treatment of mood disorders among justice involved opioid-dependent populations. METHODS: The current study enrolled 258 treatment-seeking opioid-dependent individuals under community-based criminal justice supervision (e.g., probation, parole) screened from the larger parent study, Project STRIDE, a seek/test/treat randomized control trial (RCT) examining HIV and opioid use treatment. During baseline, individuals were screened for depression using the Patient Health Questionnaire-9 (PHQ-9) and screened for bipolar disorder using the Mood Disorder Questionnaire (MDQ) tool. RESULTS: Overall, 78 (30%) participants screened positive for moderate to severe depression and 54 (21%) screened positive for bipolar disorder. Participants self-reported mood disorders at higher rates than they screened positive for these conditions. Participants screening positive for these conditions experienced significantly greater family, legal, and medical problems on the Addiction Severity Index-Lite (ASI-Lite) than those who did not screen positive. Incidence of a lifetime suicide attempt was found to be associated with a positive screen for both mood disorders. Prescribed psychotropic treatment utilization was similar among those who screened positive for depression or bipolar disorder with approximately 38% reporting taking medication. IMPORTANCE: Findings suggest universal mood disorder screening to improve comprehensive psychiatric care and treatment of opioid-dependent justice-involved individuals.

On-Demand LoRa: Asynchronous TDMA for Energy Efficient and Low Latency Communication in IoT.

Energy efficiency is crucial in the design of battery-powered end devices, such as smart sensors for the Internet of Things applications. Wireless communication between these distributed smart devices consumes significant energy, and even more when data need to reach several kilometers in distance. Low-power and long-range communication technologies such as LoRaWAN are becoming popular in IoT applications. However, LoRaWAN has drawbacks in terms of (i) data latency; (ii) limited control over the end devices by the gateway; and (iii) high rate of packet collisions in a dense network. To overcome these drawbacks, we present an energy-efficient network architecture and a high-efficiency on-demand time-division multiple access (TDMA) communication protocol for IoT improving both the energy efficiency and the latency of standard LoRa networks. We combine the capabilities of short-range wake-up radios to achieve ultra-low power states and asynchronous communication together with the long-range connectivity of LoRa. The proposed approach still works with the standard LoRa protocol, but improves performance with an on-demand TDMA. Thanks to the proposed network and protocol, we achieve a packet delivery ratio of 100% by eliminating the possibility of packet collisions. The network also achieves a round-trip latency on the order of milliseconds with sensing devices dissipating less than 46 mJ when active and 1.83 µ W during periods of inactivity and can last up to three years on a 1200-mAh lithium polymer battery.

Development of a Global Respiratory Severity Score for Respiratory Syncytial Virus Infection in Infants.

Background: Respiratory syncytial virus (RSV) infection in infants has recognizable clinical signs and symptoms. However, quantification of disease severity is difficult, and published scores remain problematic. Thus, as part of a RSV pathogenesis study, we developed a global respiratory severity score (GRSS) as a research tool for evaluating infants with primary RSV infection. Methods: Previously healthy infants <10 months of age with RSV infections representing the spectrum of disease severity were prospectively evaluated. Clinical signs and symptoms were collected at 3 time points from hospitalized infants and those seen in ambulatory settings. Data were also extracted from office, emergency department, and hospital records. An unbiased data-driven approach using factor analysis was used to develop a GRSS. Results: A total of 139 infants (84 hospitalized and 55 nonhospitalized) were enrolled. Using hospitalization status as the output variable, 9 clinical variables were identified and weighted to produce a composite GRSS. The GRSS had an area under the receiver operator curve of 0.961. Construct validity was demonstrated via a significant correlation with length of stay (r = 0.586, P < .0001). Conclusions: Using routine clinical variables, we developed a severity score for infants with RSV infection that should be useful as an end point for investigation of disease pathogenesis and as an outcome measure for therapeutic interventions.

Preoperative Panel Testing for Hereditary Cancer Syndromes Does Not Significantly Impact Time to Surgery for Newly Diagnosed Breast Cancer Patients Compared with BRCA1/2 Testing.

BACKGROUND: This study seeks to determine whether there is a delay in time to surgery in breast cancer patients with panel tests compared with traditional BRCA testing. METHODS: This study was a retrospective review of women diagnosed with breast cancer who underwent genetic evaluation from our institution's Genetic Counselor Database from January 2013 to August 2015. Patients were excluded if they were male, clinical information was unavailable, the patient underwent neoadjuvant chemotherapy, had a diagnosis of recurrent breast cancer during time of study, or had postoperative genetics evaluation. RESULTS: Included in the study were 138 patients. The time from diagnosis to surgery for BRCA1/2 tested patients was 43.5 days compared with 51.0 days in the panel group (p = 0.186). Turnaround time for genetic testing decreased during the period studied and was approximately 6 days longer for panel testing than BRCA testing. It took 12.2 days for BRCA results and 18.9 days for the panel results (p < 0.01). Turnaround time for BRCA1/2 testing in 2014 and 2015 was 12.4 and 10.5 days respectively, whereas panel testing was 20.5 and 18.2 days (p ≤ 0.001). Of the variables included in multivariable linear regression, only mastectomy significantly contributed to time to surgery (p < 0.001). DISCUSSION: Panel genetic testing did not delay time to surgery compared with BRCA testing alone. The use of panel testing has increased over time, and lab turnaround time has decreased. Mastectomy was the only clinical variable contributing to longer time to surgery.

Revisiting Metchnikoff: Age-related alterations in microbiota-gut-brain axis in the mouse.

Over the last decade, there has been increased interest in the role of the gut microbiome in health including brain health. This is by no means a new theory; Elie Metchnikoff proposed over a century ago that targeting the gut by consuming lactic acid bacteria such as those in yogurt, could improve or delay the onset of cognitive decline associated with ageing. However, there is limited information characterising the relationship between the behavioural and physiological sequelae of ageing and alterations in the gut microbiome. To this end, we assessed the behavioural, physiological and caecal microbiota profile of aged male mice. Older mice (20-21months old) exhibited deficits in spatial memory and increases in anxiety-like behaviours compared to younger mice (2-3months old). They also exhibited increased gut permeability, which was directly correlated with elevations in peripheral pro-inflammatory cytokines. Furthermore, stress exacerbated the gut permeability of aged mice. Examination of the caecal microbiota revealed significant increases in phylum TM7, family Porphyromonadaceae and genus Odoribacter of aged mice. This represents a shift of aged microbiota towards a profile previously associated with inflammatory disease, particularly gastrointestinal and liver disorders. Furthermore, Porphyromonadaceae, which has also been associated with cognitive decline and affective disorders, was directly correlated with anxiety-like behaviour in aged mice. These changes suggest that changes in the gut microbiota and associated increases in gut permeability and peripheral inflammation may be important mediators of the impairments in behavioural, affective and cognitive functions seen in ageing.

Genomewide association between GLCCI1 and response to glucocorticoid therapy in asthma.

BACKGROUND: The response to treatment for asthma is characterized by wide interindividual variability, with a significant number of patients who have no response. We hypothesized that a genomewide association study would reveal novel pharmacogenetic determinants of the response to inhaled glucocorticoids. METHODS: We analyzed a small number of statistically powerful variants selected on the basis of a family-based screening algorithm from among 534,290 single-nucleotide polymorphisms (SNPs) to determine changes in lung function in response to inhaled glucocorticoids. A significant, replicated association was found, and we characterized its functional effects. RESULTS: We identified a significant pharmacogenetic association at SNP rs37972, replicated in four independent populations totaling 935 persons (P=0.0007), which maps to the glucocorticoid-induced transcript 1 gene (GLCCI1) and is in complete linkage disequilibrium (i.e., perfectly correlated) with rs37973. Both rs37972 and rs37973 are associated with decrements in GLCCI1 expression. In isolated cell systems, the rs37973 variant is associated with significantly decreased luciferase reporter activity. Pooled data from treatment trials indicate reduced lung function in response to inhaled glucocorticoids in subjects with the variant allele (P=0.0007 for pooled data). Overall, the mean (±SE) increase in forced expiratory volume in 1 second in the treated subjects who were homozygous for the mutant rs37973 allele was only about one third of that seen in similarly treated subjects who were homozygous for the wild-type allele (3.2±1.6% vs. 9.4±1.1%), and their risk of a poor response was significantly higher (odds ratio, 2.36; 95% confidence interval, 1.27 to 4.41), with genotype accounting for about 6.6% of overall inhaled glucocorticoid response variability. CONCLUSIONS: A functional GLCCI1 variant is associated with substantial decrements in the response to inhaled glucocorticoids in patients with asthma.

Genomic screening and replication using the same data set in family-based association testing.

The Human Genome Project and its spin-offs are making it increasingly feasible to determine the genetic basis of complex traits using genome-wide association studies. The statistical challenge of analyzing such studies stems from the severe multiple-comparison problem resulting from the analysis of thousands of SNPs. Our methodology for genome-wide family-based association studies, using single SNPs or haplotypes, can identify associations that achieve genome-wide significance. In relation to developing guidelines for our screening tools, we determined lower bounds for the estimated power to detect the gene underlying the disease-susceptibility locus, which hold regardless of the linkage disequilibrium structure present in the data. We also assessed the power of our approach in the presence of multiple disease-susceptibility loci. Our screening tools accommodate genomic control and use the concept of haplotype-tagging SNPs. Our methods use the entire sample and do not require separate screening and validation samples to establish genome-wide significance, as population-based designs do.

Endorsement of COVID-19 misinformation among criminal legal involved individuals in the United States: Prevalence and relationship with information sources.

Criminal legal system involvement (CLI) is a critical social determinant of health that lies at the intersection of multiple sources of health disparities. The COVID-19 pandemic exacerbates many of these disparities, and specific vulnerabilities faced by the CLI population. This study investigated the prevalence of COVID-19-related misinformation, as well as its relationship with COVID-19 information sources used among Americans experiencing CLI. A nationally representative sample of American adults aged 18+ (N = 1,161), including a subsample of CLI individuals (n = 168), were surveyed in February-March 2021. On a 10-item test, CLI participants endorsed a greater number of misinformation statements (M = 1.88 vs. 1.27) than non-CLI participants, p < .001. CLI participants reported less use of government and scientific sources (p = .017) and less use of personal sources (p = .003) for COVID-19 information than non-CLI participants. Poisson models showed that use of government and scientific sources was negatively associated with misinformation endorsement for non-CLI participants (IRR = .841, p < .001), but not for CLI participants (IRR = .957, p = .619). These findings suggest that building and leveraging trust in important information sources are critical to the containment and mitigation of COVID-19-related misinformation in the CLI population.

Efficacy of centhaquin as a small volume resuscitative agent in severely hemorrhaged rats.

Centhaquin has been reported to be an effective resuscitative agent. The present study was carried out to determine resuscitative effect of centhaquin when administered using a small volume of 3% hypertonic saline (HS) to hemorrhaged rats. Sprague-Dawley rats were anesthetized with urethane, and a pressure catheter SPR-320 was placed in the left femoral artery; another pressure-volume catheter SPR-869 was placed into the left ventricle. Hemorrhage was induced by withdrawing blood and mean arterial pressure (MAP) was maintained at 35 mm Hg for 30 minutes after which resuscitation was performed. Animals were divided in 2 groups: group A received HS and group B received centhaquin (0.05 mg/kg) dissolved in HS. The time by which MAP fell back to 35 mm Hg was observed at that time all animals were administered fresh blood. It was found that centhaquin significantly reduced blood lactate and improved cardiac output and MAP of hemorrhaged rats compared with HS. The time by which MAP fell back to 35 mm Hg in rats treated with HS was 55 ± 6 minutes, whereas it was 161 ± 14 minutes in centhaquin treated rats. Survival time following administration of fresh blood was 79 ± 7 minutes in vehicle-treated group, whereas it was 105 ± 9 minutes in centhaquin-treated rats. The total time of survival of rats treated with HS or centhaquin was 134 ± 12 minutes and 266 ± 16 minutes, respectively. Centhaquin, in small volume, maintained MAP of hemorrhaged rats for a considerable long time and improved the survival time.

An extremely rare case of multiple small bowel intussusceptions in a 20-year-old female.

Intussusception, which is characterized by the invagination of one portion of the gastrointestinal tract into an adjacent segment, is an uncommon cause of abdominal pain in adults. Given that it is typically associated with identifiable pathological abnormalities, intussusception can pose a diagnostic challenge in adults due to its rarity and nonspecific symptomatology. This report presents a unique case of multiple small bowel intussusceptions in a 20-year-old female, which emphasizes the importance of clinical suspicion and advanced imaging for an accurate diagnosis.

An extremely rare complication of intestinal stoma formation: parastomal evisceration 1-year post-loop ileostomy.

Intestinal stoma formation is an important and frequently performed procedure in emergency and elective general surgery. Parastomal evisceration is an extremely rare complication of stoma formation. The literature to date consists of a small number of case reports only. We report the case of a 54-year-old patient who presented 1-year post-loop ileostomy formation with a large parastomal evisceration. This was managed with emergency laparotomy. Our case highlights the high morbidity of this rare complication and the importance of emergent management and patient's education.

What Matters More in Explaining Drug Court Graduation and Rearrest: Program Features, Individual Characteristics, or Some Combination.

This study examines the program- and individual-level factors that impact the success of drug court clients in terms of: (1) graduation; and (2) not being arrested while participating in the court program. The data consist of 848 individuals in nine drug courts. This paper discusses how different individual- and program-level factors impact the success of drug court participants. The findings suggest that individual- and program-level factors are both important in predicting program graduation and arrest during drug court participation, while controlling for participant demographics. Clients' education, drug/alcohol usage, program staffing, and clinical standards impact program graduation while criminal history, drug/alcohol usage, number of program hours offered, program staffing, and use of rewards and sanctions predict in-program arrest. Models combining both program- and individual-level factors performed better than either alone, leading to recommendations that agencies should emphasize improving program quality while targeting clients' needs to achieve greater success.

A rare case of duodenal angiodysplasia-a case report.

Gastrointestinal bleeding can be manifested as a variety of symptoms and, often, it is difficult to classify as upper or lower gastrointestinal bleeding on mere symptomatology. This is a case report of a similar kind of patient who initially was diagnosed with fresh per rectum bleeding, subsequently diagnosed as bleeding angiodysplasia in duodenal diverticulum by a series of investigations and management including urgent oesophageal-gastroduodenoscopy (OGD), laparotomy, followed by computerized tomography-angiogram. As diagnosis was established after laparotomy, the patient was kept intubated and IR selective embolization was performed. Keeping this case report in view, it can be suggested that bleeding vascular malformation in any part duodenum should be considered as a cause of massive upper GI bleeding. Furthermore, if operative intervention is indicated, it should be preceded by OGD, not only for a therapeutic purpose but also as an adjunct for guidance for the operative plan.

Openness to change among COVID misinformation endorsers: Associations with social demographic characteristics and information source usage.

RATIONALE: Misinformation is a major concern for public health, with its presence and impact strongly felt in the COVID-19 pandemic. Misinformation correction has drawn strong research interest. In contrast, relatively little attention has been given to the likelihood of favorable behavioral change post correction (i.e., openness to change). OBJECTIVE: This study seeks to identify the characteristics of COVID misinformation endorsers who are open to adopt more self-protective behaviors after misinformation correction. METHODS: COVID misinformation endorsers (N = 1991) in a large, nationally representative survey (fielded in October and November 2021) were asked how likely they would adopt self-protective behaviors if a source they trusted debunked their prior misperceptions. Multiple linear regression estimated the relationships between openness to change and socio-demographics, health-related factors, and health information source usage patterns. RESULTS: Less than half of the misinformation endorsers in the sample (41.3%) indicated any openness to change. Openness to change was positively associated with minority status and negatively associated with leaning Republican in political affiliation, higher income, being currently unvaccinated or unsure about vaccination status, better health, and a greater number of misinformation items endorsed. Past-month use of government, community, and personal sources for health information positively predicted openness. The use of online media was negatively associated with openness. CONCLUSIONS: Openness to change is not guaranteed after misinformation correction. Targeted interventions based on openness to change are needed to enhance the public health impact of misinformation correction efforts.