Phase 1 dose expansion and biomarker study assessing first-in-class tumor microenvironment modulator VT1021 in patients with advanced solid tumors.

BACKGROUND: Preclinical studies have demonstrated that VT1021, a first-in-class therapeutic agent, inhibits tumor growth via stimulation of thrombospondin-1 (TSP-1) and reprograms the tumor microenvironment. We recently reported data from the dose escalation part of a phase I study of VT1021 in solid tumors. Here, we report findings from the dose expansion phase of the same study. METHODS: We analyzed the safety and tolerability, clinical response, and biomarker profile of VT1021 in the expansion portion of the phase I study (NCT03364400). Safety/tolerability is determined by adverse events related to the treatment. Clinical response is determined by RECIST v1.1 and iRECIST. Biomarkers are measured by multiplexed ion beam imaging and enzyme-linked immunoassay (ELISA). RESULTS: First, we report the safety and tolerability data as the primary outcome of this study. Adverse events (AE) suspected to be related to the study treatment (RTEAEs) are mostly grade 1-2. There are no grade 4 or 5 adverse events. VT1021 is safe and well tolerated in patients with solid tumors in this study. We report clinical responses as a secondary efficacy outcome. VT1021 demonstrates promising single-agent clinical activity in recurrent GBM (rGBM) in this study. Among 22 patients with rGBM, the overall disease control rate (DCR) is 45% (95% confidence interval, 0.24-0.67). Finally, we report the exploratory outcomes of this study. We show the clinical confirmation of TSP-1 induction and TME remodeling by VT1021. Our biomarker analysis identifies several plasmatic cytokines as potential biomarkers for future clinical studies. CONCLUSIONS: VT1021 is safe and well-tolerated in patients with solid tumors in a phase I expansion study. VT1021 has advanced to a phase II/III clinical study in glioblastoma (NCT03970447).

The network of cells that surround a tumor, the tumor microenvironment, can help cancers to grow. Therapies targeting the tumor microenvironment may help to stop tumor growth. One such therapy is VT1021. In animal models, VT1021 treatment stops tumor cells from growing by changing the tumor microenvironment. Here, we have tested VT1021 in a clinical trial and found that VT1021 treatment is safe and well tolerated in patients with cancer. We also see signs of efficacy in some patients and observe evidence that VT1021 modifies the tumor microenvironment, which may help to block tumor growth. Finally, we identified several markers from the blood that may help to predict which patients will best benefit from VT1021 treatment. With further testing in clinical trials, VT1021 may be a useful therapy for patients with cancer.

Prevalence of university non-continuation and mental health conditions, and effect of mental health conditions on non-continuation: a systematic review and meta-analysis.

BACKGROUND: University non-continuation, also termed as university dropout in literature, is a concern for institutions. Elevated stress levels, mental distress, and psychiatric issues affect academic performance and thus may contribute to non-continuation. There is a lack of systematic reviews exploring the link between mental health and university non-continuation. AIM: This systematic review aims to bridge this gap, by investigating the prevalence of non-continuation and mental health conditions among university students, and the impact of mental health on university non-continuation. METHODS: Following PRISMA guidelines this review synthesized data from 67 studies, utilising both narrative synthesis and meta-analytic techniques. RESULTS: The results revealed that the included studies reported a range of university non-continuation rates (5.9% to 43.6%) with a pooled prevalence of 17.9%, 95% CI [14.2%, 22.3%]. The prevalence of mental health concerns among students varied widely (2.2% to 83.6%), with a pooled prevalence of 26.3%, 95% CI [16.0%, 40.0%]. Depression, OR = 1.143 (95% CI [1.086, 1.203] p<.001), stress, OR = 1.413 (95% CI [1.106, 1.805], p=.006), and other mental health conditions, OR = 1.266 (95% CI [1.133, 1.414], p<.001), were associated with higher non-continuation. CONCLUSION: Some mental health conditions elevate non-continuation risks, and addressing mental health may enhance student retention in higher education.

A Study on the Efficacy of the Tabletop Roleplaying Game Dungeons & Dragons for Improving Mental Health and Self-Concepts in a Community Sample.

Purpose: Tabletop gaming has seen a rise in popularity over the past 10 years, with an influx of interest following the Coronavirus pandemic. Limited research has explored the impact of tabletop roleplaying games on mental health and self-concepts such as self-esteem and self-efficacy. This study used a repeated-measures design with four measurement points to quantitatively evaluate the effect of playing Dungeons & Dragons (D&D) on mental health and self-concepts in a community sample. Materials and Methods: Twenty-five community participants took part in 8 weeks of D&D gameplay (one 1 hour session per week), completing pre-, mid-, and postintervention surveys. Eighteen of these participants also completed a 1-month follow-up measure. Results: Participants demonstrated significant decreases in depression, stress, and anxiety and significant increases in self-esteem and self-efficacy over the study period. Conclusion: As such, D&D may have potential utility as a wellbeing intervention or prevention program.

The prevalence of incivility in hospitals and the effects of incivility on patient safety culture and outcomes: A systematic review and meta-analysis.

AIM: Workplace incivility is a barrier to safe and high-quality patient care in nursing workplaces and more broadly in tertiary hospitals. The present study aims to systematically review the existing evidence to provide a comprehensive understanding of the prevalence of co-worker incivility experienced and witnessed by nurses and other healthcare professionals, the effects of incivility on patient safety culture (PSC) and patient outcomes, and the factors which mediate the relationship between incivility and patient safety. METHODS: A systematic review with narrative synthesis and meta-analysis was undertaken to synthesize the data from 41 studies. DATA SOURCES: Databases searched included MEDLINE, PubMed, SCOPUS, CINAHL, PsycInfo, ProQuest, Emcare and Embase. Searches were conducted on 17 August 2021 and repeated on 15 March 2023. RESULTS: The pooled prevalence of experienced incivility was 25.0%. The pooled prevalence of witnessed incivility was 30.1%. Workplace incivility was negatively associated with the PSC domains of teamwork, reporting patient safety events, organization learning/improvement, management support for safety, leadership, communication openness and communication about error. The composite pooled effect size of incivility on these domains of PSC was OR = 0.590, 95% CI [0.515, 0.676]. Workplace incivility was associated with a range of patient safety outcomes (PSOs) including near misses, adverse events, reduced procedural and diagnostic performance, medical error and mortality. State depletion, profession, psychological responses to incivility, information sharing, help seeking, workload and satisfaction with organizational communication were found to mediate the relationship between incivility and patient safety. CONCLUSION: Experienced and witnessed incivility is prevalent in tertiary hospitals and has a deleterious effect on PSC and PSOs. A better understanding of the mechanisms of this relationship will support the development of interventions aimed at reducing both incivility and patient harm. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE IMPACT: This study quantifies the effect of incivility on PSC and outcomes. It provides support that interventions focusing on incivility are a valuable mechanism for improving patient care. It guides intervention design by highlighting which domains of PSC are most associated with incivility. It explores the profession-specific experiences of workplace incivility. REPORTING METHOD: This report adheres to PRISMA reporting guidelines. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. The focus of this study is the nursing and healthcare workforce, therefore, patient or public involvement not required.

Outcome comparison between primary and revisional bariatric surgery: A propensity-matched analysis.

BACKGROUND: Revisional bariatric procedures for weight recurrence are rising but are considered higher risk and less effective than primary bariatric procedures. This study aimed to compare clinical outcomes between primary and revisional bariatric surgery for weight recurrence. METHODS: Prospectively collected data from adult patients who underwent revisional or primary bariatric surgery from 2016 to 2020 in an academic institution were reviewed. Roux-en-Y gastric bypass and sleeve gastrectomy were performed primarily or as conversion procedures after laparoscopic adjustable gastric band, vertical banded gastroplasty, and sleeve gastrectomy. 1:1 propensity score matching was performed between revisional bariatric surgery and primary bariatric surgery, and logistic regression analysis was used to compare up to 2-year weight loss and comorbidity resolution outcomes. RESULTS: A total of172 cases (86 revisional bariatric surgery versus 86 primary bariatric surgery) were included. Groups were matched for age, sex, preoperative body mass index, bariatric procedure, diabetes, hypertension, and obstructive sleep apnea. Procedure duration (203 ± 78 vs 154 ± 69 minutes; P < .001) and length of stay (2.3 ± 2.1 vs 1.7 ± 1 days; P = .02) were longer for revisional bariatric surgery versus primary bariatric surgery, respectively. Total weight loss was less in revisional bariatric surgery compared with primary bariatric surgery at 1 year (23 ± 10% vs 32 ± 9%; P < .001) and 2 years (21 ± 12.% vs 32 ± 10%; P < .001) of follow-up; however, no differences were detected in postoperative occurrences, emergency department visits, readmissions, reintervention and reoperation rates, and comorbidity resolution. CONCLUSION: Although revisional bariatric surgery was associated with longer operation times, prolonged hospitalization, and lower weight loss than primary bariatric surgery, it was accomplished safely and led to substantial weight loss and comorbidity resolution. This information can guide patient counseling before revisional surgery for weight recurrence.

The Laparoscopy in Biliary Exploration Research and Training Initiative (LIBERTI) trial: simulator-based training for laparoscopic management of choledocholithiasis.

BACKGROUND: Laparoscopic cholecystectomy with common bile duct exploration (LCBDE) is equivalent in safety and efficacy to endoscopic retrograde cholangiopancreatography (ERCP) plus laparoscopic cholecystectomy (LC) while decreasing number of procedures and length of stay (LOS). Despite these advantages LCBDE is infrequently utilized. We hypothesized that formal, simulation-based training in LCBDE would result in increased utilization and improve patient outcomes across participating institutions. METHODS: Data was obtained from an on-going multi-center study in which simulator-based transcystic LCBDE training curricula were instituted for attending surgeons and residents. A 2-year retrospective review of LCBDE utilization prior to LCBDE training was compared to utilization up to 2 years after initiation of training. Patient outcomes were analyzed between LCBDE strategy and ERCP strategy groups using χ2, t tests, and Wilcoxon rank tests. RESULTS: A total of 50 attendings and 70 residents trained in LCBDE since November 2020. Initial LCBDE utilization rate ranged from 0.74 to 4.5%, and increased among all institutions after training, ranging from 9.3 to 41.4% of cases. There were 393 choledocholithiasis patients analyzed using LCBDE (N = 129) and ERCP (N = 264) strategies. The LCBDE group had shorter median LOS (3 days vs. 4 days, p < 0.0001). No significant differences in readmission rates between LCBDE and ERCP groups (4.7% vs. 7.2%, p = 0.33), or in post-procedure pancreatitis (0.8% v 0.8%, p > 0.98). In comparison to LCBDE, the ERCP group had higher rates of bile duct injury (0% v 3.8%, p = 0.034) and fluid collections requiring intervention (0.8% v 6.8%, p < 0.009) secondary to cholecystectomy complications. Laparoscopic antegrade balloon sphincteroplasty had the highest technical success rate (87%), followed by choledochoscopic techniques (64%). CONCLUSION: Simulator-based training in LCBDE results in higher utilization rates, shorter LOS, and comparable safety to ERCP plus cholecystectomy. Therefore, implementation of LCBDE training is strongly recommended to optimize healthcare utilization and management of patients with choledocholithiasis.

Resolution and recurrence of anemia following repair of paraesophageal hernias.

BACKGROUND: Iron deficiency anemia is a common paraesophageal hernia (PEH) symptom and may improve after repair. When present, anemia has also been proposed to be associated with an increase in length of hospital stay, morbidity, and mortality after PEH repair. This study aimed to determine anemia-related factors in patients with PEH, the rate of anemia resolution after PEH repair, and the risk of anemia recurrence when repair failed. METHODS: We included patients who received a PEH repair between June 2019 and June 2020 and had 24 months of postoperative follow-up. Demographics and comorbidities were recorded. Anemia was defined as pre-operative hemoglobin values < 12.0 for females and < 13.0 for males, or if patients were receiving iron supplementation. Anemia resolution was determined at 6 months post-op. Length of hospital stay, morbidity, and mortality was recorded. Logistic regression and ANCOVA were used for binary and continuous outcomes respectively. RESULTS: Of 394 patients who underwent PEH repair during the study period, 101 (25.6%) had anemia before surgery. Patients with pre-operative anemia had larger hernia sizes (6.55 cm ± 2.77 vs. 4.34 cm ± 2.50; p < 0.001). Of 68 patients with available data by 6 months after surgery, anemia resolved in 36 (52.9%). Hernia recurred in 6 patients (16.7%), 4 of whom also had anemia recurrence (66.7%). Preoperative anemia was associated with a higher length of hospital stay (3.31 days ± 0.54 vs 2.33 days ± 0.19 p = 0.046) and an increased risk of post-operative all-cause mortality (OR 2.7 CI 1.08-6.57 p = 0.05). Fundoplication type (p = 0.166), gastropexy, or mesh was not associated with an increased likelihood of resolution (OR 0.855 CI 0.326-2.243; p = 0.05) (OR 0.440 CI 0.150-1.287; p = 0.05). CONCLUSIONS: Anemia occurs in 1 out of 4 patients with PEH and is more frequent in patients with larger hernias. Anemia is associated with a longer hospital stay and all-cause mortality after surgery. Anemia recurrence coincided with hernia recurrence in roughly two-thirds of patients.

A systematic review and meta-analysis on adverse childhood experiences: Prevalence in youth offenders and their effects on youth recidivism.

BACKGROUND: Adverse childhood experiences (ACEs) have been found to be more prevalent among youth involved with the criminal justice system compared to their counterparts in the general population. The present study aims to systematically review the existing empirical studies to provide a comprehensive understanding of the prevalence of ACEs among youth offenders aged between 10 and 19 years, and the effects of both cumulative ACEs and individual ACE items on youth recidivism. METHOD: A systematic review approach was employed. Narrative synthesis and meta-analysis were performed to synthesise the data in 31 included studies. RESULTS: The pooled prevalence of cumulative ACEs was 39.4 %. The pooled prevalence of individual ACEs ranged between 13.7 % to 51.4 %. Cumulative ACEs and neglect were positively associated with youth recidivism, with OR = 1.966, 95%CI [1.582, 2.444] and OR = 1.328, 95%CI [1.078, 1.637], respectively. Physical and sexual abuse were not significantly associated with youth recidivism. Regarding the mechanisms underlying the relationship between ACEs and recidivism; moderators included gender, positive childhood experiences, strong social bonds, and empathy. Mediators included child welfare placement, emotional and behavioural problems, drug use, mental health problems, and negative emotionality. CONCLUSION: Developing programs to youth offenders aiming to address the impact of cumulative and individual ACE exposure, strengthen the protective factors and weaken the risk factors would be useful to reduce youth recidivism.

The effectiveness of mindfulness-based stress reduction (MBSR) on the mental health, HbA1C, and mindfulness of diabetes patients: A systematic review and meta-analysis of randomised controlled trials.

The clinically standardised mindfulness-based stress reduction (MBSR) has been utilised as an intervention for improving mental health among diabetes patients The present study aimed to assess the effectiveness of mindfulness-based stress reduction (MBSR) on the mental health, haemoglobin A1c (HbA1C), and mindfulness of diabetes patients. A systematic review and meta-analysis approach was employed to review randomised controlled trials published in the English language between the inception of eight databases to July 2022. Eleven articles from 10 studies, with a combined sample size of 718 participants, were included in the systematic review, and nine studies were included in the meta-analysis. In the meta-analysis, outcomes at post-intervention and follow-up were compared between the MBSR intervention and control groups with an adjustment of the baseline values. The results showed that MBSR demonstrated effects at post-intervention and follow-up (in a period between one to 12 months with a mean length of 4.3 months) in reducing anxiety and depressive symptoms, and enhancing mindfulness, with large effect sizes. However, the effect of MBSR on reducing stress was observed at follow-up, but not at post-intervention. Effects of MBSR on HbA1C were not detected at post-intervention and follow-up. The findings suggest that MBSR appears to be an effective treatment for improving mental health conditions and mindfulness in people with diabetes. The measurement of cortisol is recommended to be used as a biological measure to evaluate the effectiveness of MBSR in diabetes patients in future research.

Spontaneous Subperiosteal Orbital Hematoma Associated With Cocaine-Induced Midline Destructive Lesion.

The authors present a case of a non-traumatic, spontaneous subperiosteal orbital hematoma in a woman with a history of chronic pansinusitis and absence of midline nasal cavity structures due to chronic inhalational cocaine use. The patient underwent left orbitotomy and drainage of the lesion, showing mostly blood with a small amount of purulence that grew methicillin-resistant Staphylococcus aureus when cultured. The patient received 4 weeks of intravenous antibiotics in addition to functional endoscopic sinus surgery. At 1 month after surgery, her vision had returned to baseline, and proptosis was resolved. Fewer than 20 cases of subperiosteal orbital hematomas associated with chronic sinusitis have been reported. To the authors' knowledge, this is the first reported case of a subperiosteal orbital hematoma associated with cocaine-induced midline destructive lesions. Patient consent to obtain photographs was obtained and archived. All collection and evaluation of patient health information were compliant with the Health Insurance Portability and Accountability Act, and this report adheres to the Declaration of Helsinki.

Alcohol and Smoking Cessation as Potential Modulators for Smoking-Associated Psoriasis Risk in Postmenopausal Women: The Women's Health Initiative.

BACKGROUND: The association of alcohol with psoriasis has been inconsistent among studies. OBJECTIVES: We aimed (1) to determine whether alcohol consumption (by status, frequency, and subtype of alcohol) modulates smoking-related psoriasis risk in postmenopausal women while stratifying for smoking status and pack-years and (2) to evaluate the effect of smoking cessation on psoriasis risk in postmenopausal women. METHODS: This prospective cohort study included 106,844 postmenopausal women enrolled in the Women's Health Initiative between 1993 and 1998. Patients diagnosed with psoriasis were identified using fee-for-service Medicare International Classification of Diseases, Ninth Revision, Clinical Modification codes assigned by dermatologists or rheumatologists. Self-administered questionnaires were used to obtain information on demographics, medical history, and smoking and alcohol habits. Hazard ratios from Cox regression models were adjusted for ethnicity, income, body mass index, and history of non-melanoma skin cancer and were stratified on age and on randomization status in the Women's Health Initiative study components. RESULTS: In the initial statistical model, past and current alcohol drinkers had higher risks of psoriasis compared with never-drinkers (P-trend < 0.001). This association was not observed after adjusting for cigarette smoking (P-trend: 0.478). The effect of alcohol (by status, frequency, and alcohol subtype) isolated by stratifying the analysis by smoking status (i.e., among never smokers) showed no association with psoriasis. Smoking showed an increasing risk for psoriasis with greater pack-years compared with those who have never smoked (P-trend: < 0.001). Compared to smokers at baseline, past smokers had a lower risk of psoriasis across women who smoked 5-14 cigarettes per day (hazard ratio 0.67, 95% confidence interval 0.51-0.88) and across women who smoked for 5-24 years (hazard ratio 0.65, 95% confidence interval 0.46-0.90). CONCLUSIONS: These findings indicate that alcohol consumption does not modulate smoking-related psoriasis risk. Cigarette smoking, but not alcohol consumption, is an independent risk factor for psoriasis in postmenopausal women. As greater pack-years was associated with a higher risk of psoriasis and smoking cessation was conversely associated with a lower risk of psoriasis for moderate smokers, a greater emphasis on smoking abstinence and cessation counseling may benefit patients who already have other risk factors for psoriasis.

The Upper Respiratory Tract Microbiome Network Impacted by SARS-CoV-2.

The microbiome of upper respiratory tract (URT) acts as a gatekeeper to respiratory health of the host. However, little is still known about the impacts of SARS-CoV-2 infection on the microbial species composition and co-occurrence correlations of the URT microbiome, especially the relationships between SARS-CoV-2 and other microbes. Here, we characterized the URT microbiome based on RNA metagenomic-sequencing datasets from 1737 nasopharyngeal samples collected from COVID-19 patients. The URT-microbiome network consisting of bacteria, archaea, and RNA viruses was built and analyzed from aspects of core/periphery species, cluster composition, and balance between positive and negative interactions. It is discovered that the URT microbiome in the COVID-19 patients is enriched with Enterobacteriaceae, a gut associated family containing many pathogens. These pathogens formed a dense cooperative guild that seemed to suppress beneficial microbes collectively. Besides bacteria and archaea, 72 eukaryotic RNA viruses were identified in the URT microbiome of COVID-19 patients. Only five of these viruses were present in more than 10% of all samples, including SARS-CoV-2 and a bat coronavirus (i.e., BatCoV BM48-31) not detected in humans by routine means. SARS-CoV-2 was inhibited by a cooperative alliance of 89 species, but seems to cooperate with BatCoV BM48-31 given their statistically significant, positive correlations. The presence of cooperative bat-coronavirus partner of SARS-CoV-2 (BatCoV BM48-31), which was previously discovered in bat but not in humans to the best of our knowledge, is puzzling and deserves further investigation given their obvious implications. Possible microbial translocation mechanism from gut to URT also deserves future studies.

Kawasaki Disease with Hepatobiliary Manifestations.

Background and Objectives: Kawasaki Disease (KD) incidence has been on the rise globally throughout the years, particularly in the Asia Pacific region. KD can be diagnosed based on several clinical criteria. Due to its systemic inflammatory nature, multi-organ involvement has been observed, making the diagnosis of KD more challenging. Notably, several studies have reported KD patients presenting with hepatobiliary abnormalities. Nonetheless, comprehensive data regarding the hepatobiliary manifestations of KD are limited in Malaysia, justifying a more in-depth study of the disease in this country. Thus, in this article, we aim to discuss KD patients in Malaysia with hepatobiliary manifestations. Materials and Methods: A total of six KD patients with hepatobiliary findings who presented at Hospital Canselor Tuanku Muhriz (HCTM) from 2004 to 2021 were selected and included. Variables including the initial presenting signs and symptoms, clinical progress, laboratory investigations such as liver function test (LFT), and ultrasound findings of hepatobiliary system were reviewed and analyzed. Results: Out of these six KD patients, there were two patients complicated with hepatitis and one patient with gallbladder hydrops. Different clinical features including jaundice (n = 3) and hepatomegaly (n = 4) were also observed. All patients received both aspirin and intravenous immunoglobulin (IVIG) as their first-line treatment and all of them responded well to IVIG. The majority of them (n = 5) had a complete recovery and did not have any cardiovascular and hepatobiliary sequelae. Conclusions: Despite KD mostly being diagnosed with the classical clinical criteria, patients with atypical presentations should always alert physicians of KD as one of the possible differential diagnoses. This study discovered that hepatobiliary manifestations in KD patients were not uncommon. More awareness on the epidemiology, diagnosis, and management of KD patients with hepatobiliary manifestations are required to allow for the initiation of prompt treatment, thus preventing further complications.

The impact of oil industry-related social exclusion on community wellbeing and health in African countries.

Background: Oil is the mainstay revenue for a number of African countries. However, extraction can result in multiple impacts on the health and wellbeing of communities living in oil-rich areas. This review explored evidence of oil industry-related social exclusion on community health and wellbeing on the African continent. Methods: We used a systematic approach guided by PRISMA to search six databases for empirical and descriptive sources focused on oil industry impacts, in any African country, between 1960 to 2021. Findings were grouped according to four dimensions of the Social Exclusion Knowledge Network (SEKN) framework: political, social, economic, and cultural. Results: Fifteen articles were identified, of which 13 articles focused on Nigeria; while one focused on Sudan, and one on Côte d'Ivoire and South Africa. Evidence relating to political aspects of social exclusion encompassed marginalization of indigenous communities through land grabs and unequal representation in political decision making. Limited compensation for environmental damage and livelihood displacement caused by oil-extraction, and high rates of unemployment and poverty were key themes of the economic dimension. Evidence of social impacts included lack of government, or oil-industry investment in social infrastructure; poor health and wellbeing linked to land, air, and water pollution; homelessness and lack of social cohesion. The cultural dimension of social exclusion was comparatively underexplored and only six sources included data collection with indigenous residents, and comparatively more sources were written by non-citizens or non-residents of oil-industry affected areas. Major themes included impacts on collective identity, ways of life and values, particularly where loss of ownership or access to land was experienced. Conclusion: Oil industry activities in African countries are clearly associated with multiple exclusionary impacts. However, the narrow body of empirical research limits understanding of the lived experiences and management of social exclusion by residents of oil-rich areas themselves and is an area deserving of further attention.

Diversity-scaling analysis of human breast milk microbiomes from population perspective.

Quantitative measuring the population-level diversity-scaling of human microbiomes is different from conventional approach to traditional individual-level diversity analysis, and it is of obvious significance. For example, it is well known that individuals are of significant heterogeneity with their microbiome diversities, and the population-level analysis can effectively capture such kind of individual differences. Here we reanalyze a dozen datasets of 2,115 human breast milk microbiome (BMM) samples with diversity-area relationship (DAR) to tackle the previous questions. Our focus on BMM is aimed to offer insights for supplementing the gut microbiome research from nutritional perspective. DAR is an extension to classic species-area relationship, which was discovered in the 19th century and established as one of a handful fundamental laws in community ecology. Our DAR modeling revealed the following numbers, all approximately: (i) The population-level potential diversity of BMM is 1,108 in terms of species richness (number of total species), and 67 in terms of typical species. (ii) On average, an individual carry 17% of population-level diversity in terms of species richness, and 61% in terms of typical species. (iii) The similarity (overlap) between individuals according to pair-wise diversity overlap (PDO) should be approximately 76% in terms of total species, and 92% in terms of typical species, which symbolizes the inter-individual heterogeneity. (iv) The average individual (alpha-) diversity of BMM is approximately 188 (total-species) and 37 (typical-species). (v) To deal with the potential difference among 12 BMM datasets, we conducted DAR modeling separately for each dataset, and then performed permutation tests for DAR parameters. It was found that the DAR scaling parameter that measures inter-individual heterogeneity in diversity is invariant (constant), but the population potential diversity is different among 30% of the pair-wise comparison between 12 BMM datasets. These results offer comprehensive biodiversity analyses of the BMM from host individual, inter-individual, and population level perspectives.

Microbiome-host-phylogeny relationships in animal gastrointestinal tract microbiomes.

Among the factors influencing the animal gastrointestinal tract microbiome (AGM) diversity, diet and phylogeny have been extensively studied. However, what made the studies particularly challenging is that diet characteristics per se are product of evolution, and hence totally disentangling both effects is unrealistic, likely explaining the lack of consensus in existing literatures. To further explore microbial diversity and host-phylogeny-diet relationships, we performed a big-data meta-analysis with 4903 16S rRNA AGM samples from 318 animal species covering all six vertebrate and four major invertebrate classes. We discovered that the relationship between AGM-diversity and phylogenetic timeline (PT) follows a power-law or log-linear model, including diet specific power-law relationships. The log-linear nature predicts a generally rising trend of AGM diversity along the evolutionary tree starting from the root, which explains the observation why Mammalia exhibited the highest AGM-diversity. The power-law property suggests that a handful of taxa carry disproportionally large weights to the evolution of diversity patterns than the majority of taxa, which explains why the species richness of Insecta was significant different than those from the other nine classes. Finally, we hypothesize that the diversity-PT power-law relationship explains why species-abundance distributions generally follow highly skewed probability distributions.

Kidney-specific KO of the circadian clock protein PER1 alters renal Na+ handling, aldosterone levels, and kidney/adrenal gene expression.

PERIOD 1 (PER1) is a circadian clock transcription factor that is regulated by aldosterone, a hormone that increases blood volume and Na+ retention to increase blood pressure. Male global Per1 knockout (KO) mice develop reduced night/day differences in Na+ excretion in response to a high-salt diet plus desoxycorticosterone pivalate treatment (HS + DOCP), a model of salt-sensitive hypertension. In addition, global Per1 KO mice exhibit higher aldosterone levels on a normal-salt diet. To determine the role of Per1 in the kidney, male kidney-specific Per1 KO (KS-Per1 KO) mice were generated using Ksp-cadherin Cre recombinase to remove exons 2-8 of Per1 in the distal nephron and collecting duct. Male KS-Per1 KO mice have increased Na+ retention but have normal diurnal differences in Na+ excretion in response to HS + DOCP. The increased Na+ retention is associated with altered expression of glucocorticoid and mineralocorticoid receptors, increased serum aldosterone, and increased medullary endothelin-1 compared with control mice. Adrenal gland gene expression analysis revealed that circadian clock and aldosterone synthesis genes have altered expression in KS-Per1 KO mice compared with control mice. These results emphasize the importance of the circadian clock not only in maintaining rhythms of physiological functions but also for adaptability in response to environmental cues, such as HS + DOCP, to maintain overall homeostasis. Given the prevalence of salt-sensitive hypertension in the general population, these findings have important implications for our understanding of how circadian clock proteins regulate homeostasis.NEW & NOTEWORTHY For the first time, we show that knockout of the circadian clock transcription factor PERIOD 1 using kidney-specific cadherin Cre results in increased renal Na+ reabsorption, increased aldosterone levels, and changes in gene expression in both the kidney and adrenal gland. Diurnal changes in renal Na+ excretion were not observed, demonstrating that the clock protein PER1 in the kidney is important for maintaining homeostasis and that this effect may be independent of time of day.

Predictive Factors for Depression and Anxiety in Men During the Perinatal Period: A Mixed Methods Study.

The purpose of this study was to identify the risk factors associated with paternal perinatal mental distress in a sample of Australian men. A mixed-methods design was used. The qualitative component (N = 13) using thematic analysis identified maternal depression, marital distress, masculine gender role stress, unplanned pregnancy, work-family conflict, and sleep disturbance as risk factors for paternal perinatal mental distress. The quantitative component (N = 525) expanded on the qualitative findings and examined the associations between the identified risk factors and mental distress of fathers in the perinatal period measured by Edinburgh postnatal depression scale. Hierarchical multiple regression analysis revealed six significant predictors of paternal perinatal mental distress with masculine gender role stress being the most significant risk factor for paternal perinatal mental distress. The results from this study provide an insight into how masculine gender role may affect the expression and experience of mental distress in fathers within the perinatal period. Implications of research findings are discussed.