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.

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.

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.

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.

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.

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.

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.

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.

Using Case Costing to Evaluate the Potential Impact of a Reintegration Unit on an Acute-Care Hospital's Capacity and Resources.

The Ontario Ministry of Health funded a reintegration unit to transition hospitalized patients who no longer required acute care to alternate level of care (ALC), such as long-term care. In its first year, 102 (3.5%) patients of the hospital's waiting-for-ALC population were transferred, with 37.3% transferred on the day of ALC readiness. The reintegration unit reduced direct hospital costs by $861,000. Using case costing, we modelled optimized scenarios including all transfers on the day of ALC readiness and increased transfers to the reintegration unit; this helped reduce avoided direct costs by $2.3-$5.4 million. Acute-care bed capacity could have increased by 11%. We outline strategies to optimize future performance of the reintegration unit.

LRP1 regulates food intake and energy balance in GABAergic neurons independently of leptin action.

Low-density lipoprotein receptor-related protein 1 (LRP1) is a member of LDL receptor family that plays a key role in systemic glucose and lipid homeostasis. LRP1 also regulates energy balance in the hypothalamus by mediating leptin's anorexigenic action, although the underlying neurocircuitry involved is still unclear. Because GABAergic neurons are a major mediator of hypothalamic leptin action, we studied the role of GABAergic LRP1 in energy balance and leptin action using mice lacking LRP1 in Vgat- or AgRP-expressing neurons (Vgat-Cre; LRP1loxP/loxP or AgRP-Cre; LRP1loxP/loxP). Here, we show that LRP1 deficiency in GABAergic neurons results in severe obesity in male and female mice fed a normal-chow diet. This effect is most likely due to increased food intake and decreased energy expenditure and locomotor activity. Increased adiposity in GABAergic neuron-specific LRP1-deficient mice is accompanied by hyperleptinemia and hyperinsulinemia. Insulin resistance and glucose intolerance in these mice are occurred without change in body weight. Importantly, LRP1 in GABAergic neurons is not required for leptin action, as evidenced by normal leptin's anorexigenic action and leptin-induced hypothalamic Stat3 phosphorylation. In contrast, LRP1 deficiency in AgRP neurons has no effect on adiposity and caloric intake. In conclusion, our data identify GABAergic neurons as a key neurocircuitry that underpins LRP1-dependent regulation of systemic energy balance and body-weight homeostasis. We further find that the GABAergic LRP1 signaling pathway modulates food intake and energy expenditure independently of leptin signaling and AgRP neurons.

Ecological and network analyses identify four microbial species with potential significance for the diagnosis/treatment of ulcerative colitis (UC).

BACKGROUND: Ulcerative colitis (UC) is one of the primary types of inflammatory bowel disease (IBD), the occurrence of which has been increasing worldwide. Although IBD is an intensively studied human microbiome-associated disease, research on Chinese populations remains relatively limited, particularly on the mucosal microbiome. The present study aimed to analyze the changes in the mucosal microbiome associated with UC from the perspectives of medical ecology and complex network analysis. RESULTS: In total, 56 mucosal microbiome samples were collected from 28 Chinese UC patients and their healthy family partners, followed by amplicon sequencing. Based on sequencing data, we analyzed species diversity, shared species, and inter-species interactions at the whole community, main phyla, and core/periphery species levels. We identified four opportunistic "pathogens" (i.e., Clostridium tertium, Odoribacter splanchnicus, Ruminococcus gnavus, and Flavonifractor plautii) with potential significance for the diagnosis and treatment of UC, which were inhibited in healthy individuals, but unrestricted in the UC patients. In addition, we also discovered in this study: (i) The positive-to-negative links (P/N) ratio, which measures the balance of species interactions or inhibition effects in microbiome networks, was significantly higher in UC patients, indicating loss of inhibition against potentially opportunistic "pathogens" associated with dysbiosis. (ii) Previous studies have reported conflicting evidence regarding species diversity and composition between UC patients and healthy controls. Here, significant differences were found at the major phylum and core/periphery scales, but not at the whole community level. Thus, we argue that the paradoxical results found in existing studies are due to the scale effect. CONCLUSIONS: Our results reveal changes in the ecology and network structure of the gut mucosal microbiome that might be associated with UC, and these changes might provide potential therapeutic mechanisms of UC. The four opportunistic pathogens that were identified in the present study deserve further investigation in future studies.

Professional quality of life as potential mediators of the association between anxiety and depression among Chinese health-care clinicians.

OBJECTIVE: Building upon the tripartite model of anxiety and depression, the current study aims to examine mechanisms of comorbidity between anxiety and depression using the ProQOL (Professional Quality of Life; including the constructs of burnout, secondary traumatic stress, and compassion satisfaction) in a sample of Chinese health-care clinicians. METHOD: A randomized cross-sectional survey was distributed to 1620 participants who were recruited from eight state-owned hospitals in a city in southern China between January and May 2017. A total of 1562 questionnaires were returned (a response rate of 96.4%). After the cases with more than 10% missing variables and multivariate outliers being removed, 1423 valid cases remained. Multiple mediator models were used for mediation analysis that was conducted using the PROCESS v3.1 macro for SPSS. RESULTS: The indirect effects of anxiety upon depression through burnout (a1 = . 601 (95% confidence interval (CI): .552, .650), p < .001; b1 = .137 (95% CI: .101, .174), p < .001) and compassion satisfaction (a3= -.297 (95% CI: -.352, -.241), p < .001; b3 = -.069 (95% CI: -.100, -.039), p < .001) were significant, while there was no evidence that anxiety influenced depression by changing secondary traumatic stress. The indirect effects of depression upon anxiety through secondary traumatic stress (a2 = . 535 (95% CI: .483, .588), p < .001); b2 = .154 (95% CI: .120, .188), p < .001) were both positive and significant, while there was no evidence that depression influenced anxiety by changing burnout and compassion satisfaction. CONCLUSIONS: In the current sample, burnout and compassion satisfaction mediated the effect of anxiety upon depression and secondary traumatic stress mediated the effect of depression upon anxiety. The findings of the current study offer support to the tripartite model.

Convergence: Lactosylceramide-Centric Signaling Pathways Induce Inflammation, Oxidative Stress, and Other Phenotypic Outcomes.

Lactosylceramide (LacCer), also known as CD17/CDw17, is a member of a large family of small molecular weight compounds known as glycosphingolipids. It plays a pivotal role in the biosynthesis of glycosphingolipids, primarily by way of serving as a precursor to the majority of its higher homolog sub-families such as gangliosides, sulfatides, fucosylated-glycosphingolipids and complex neutral glycosphingolipids-some of which confer "second-messenger" and receptor functions. LacCer is an integral component of the "lipid rafts," serving as a conduit to transduce external stimuli into multiple phenotypes, which may contribute to mortality and morbidity in man and in mouse models of human disease. LacCer is synthesized by the action of LacCer synthase (ß-1,4 galactosyltransferase), which transfers galactose from uridine diphosphate galactose (UDP-galactose) to glucosylceramide (GlcCer). The convergence of multiple physiologically relevant external stimuli/agonists-platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), stress, cigarette smoke/nicotine, tumor necrosis factor-α (TNF-α), and in particular, oxidized low-density lipoprotein (ox-LDL)-on ß-1,4 galactosyltransferase results in its phosphorylation or activation, via a "turn-key" reaction, generating LacCer. This newly synthesized LacCer activates NADPH (nicotinamide adenine dihydrogen phosphate) oxidase to generate reactive oxygen species (ROS) and a highly "oxidative stress" environment, which trigger a cascade of signaling molecules and pathways and initiate diverse phenotypes like inflammation and atherosclerosis. For instance, LacCer activates an enzyme, cytosolic phospholipase A2 (cPLA2), which cleaves arachidonic acid from phosphatidylcholine. In turn, arachidonic acid serves as a precursor to eicosanoids and prostaglandin, which transduce a cascade of reactions leading to inflammation-a major phenotype underscoring the initiation and progression of several debilitating diseases such as atherosclerosis and cancer. Our aim here is to present an updated account of studies made in the field of LacCer metabolism and signaling using multiple animal models of human disease, human tissue, and cell-based studies. These advancements have led us to propose that previously unrelated phenotypes converge in a LacCer-centric manner. This LacCer synthase/LacCer-induced "oxidative stress" environment contributes to inflammation, atherosclerosis, skin conditions, hair greying, cardiovascular disease, and diabetes due to mitochondrial dysfunction. Thus, targeting LacCer synthase may well be the answer to remedy these pathologies.

The reflective risk assessment model of professional quality of life in Chinese nurses.

AIM: To apply the reflective risk assessment model in a Chinese health care setting to investigate the relationships between professional quality of life and mental health risk profiles. BACKGROUND: Few studies have connected the quality of work life with contributing and coexisting factors such as depression, anxiety and stress, but none to date in a Chinese health care setting. METHOD: A cross-sectional survey of 950 registered Chinese nurses was employed. RESULTS: 299 of 861 participants (34.7%) were categorized into four of five professional quality of life risk profiles, consistent with the reflective risk assessment model. Significant differences were seen with large-sized effects in the mean scores of stress, anxiety and depression among the participants, with participants of the very distressed profile having significantly higher mean scores in stress, anxiety and depression, followed by the at-risk profile group. CONCLUSION: The reflective risk assessment model and professional quality of life five risk profiles are supported by this study. IMPLICATIONS FOR NURSING MANAGEMENT: The reflective risk assessment model can be used to detect risk factors for mental health in nurses and for the design of interventions that promote nurses' mental health.

Risankizumab for the Treatment of Moderate to Severe Plaque Psoriasis.

Objective: Risankizumab (Skyrizi), an interleukin-23 (IL-23) antagonist, was approved by the Food and Drug Administration (FDA) for the treatment of moderate to severe plaque psoriasis in April 2019. This article will review phase II and III clinical trials to assess the efficacy, safety, and clinical application of this drug. Data Sources: A systematic literature review was performed using the terms "psoriasis AND risankizumab" in the OVID MEDLINE, PubMed, Cochrane Library, EMBASE, and Web of Science databases. ClinicalTrials.gov was searched to identify ongoing or nonpublished studies. Study Selection and Data Extraction: Articles written in English between January 2000 and October 2019 discussing phase II and phase III clinical trials were evaluated. Data Synthesis: By the primary end point at week 16 in phase III trials, more patients achieved Psoriasis Area and Severity Index 90 receiving 150 mg risankizumab (72%-75%) compared with placebo (2.0%-4.9%, P < 0.001), 45 or 90 mg ustekinumab (42.0%-48%, P < 0.0001), and 40 mg adalimumab (47%, P < 0.0001). More patients achieved a static Physician's Global Assessment score of 0 or 1 receiving 150 mg risankizumab (84%-88%) compared with placebo (5.1%-7.8%, P < 0.001), 45 or 90 mg ustekinumab (62%-63%, P < 0.0001), and 40 mg adalimumab (60%, P < 0.0001). Risankizumab was well tolerated across all studies. Conclusion: Risankizumab is a newly FDA-approved IL-23 inhibitor that shows particular promise in the treatment of plaque psoriasis. Based on this review, it is an effective and safe addition to the armamentarium of biologics that are currently available.

Knockout of the circadian clock protein PER1 results in sex-dependent alterations of ET-1 production in mice in response to a high-salt diet plus mineralocorticoid treatment.

Previously, we showed that global knockout (KO) of the circadian clock transcription factor PER1 in male, but not female, mice fed a high-salt diet plus mineralocorticoid treatment (HS/DOCP) resulted in nondipping hypertension and decreased night/day ratio of sodium (Na) excretion. Additionally, we have shown that the endothelin-1 (ET-1) gene is targeted by both PER1 and aldosterone. We hypothesized that ET-1 would exhibit a sex-specific response to HS/DOCP treatment in PER1 KO. Here we show that male, but not female, global PER1 KO mice exhibit a decreased night/day ratio of urinary ET-1. Gene expression analysis revealed significant genotype differences in ET-1 and endothelin A receptor (ETA) expression in male, but not female, mice in response to HS/DOCP. Additionally, both wild-type and global PER1 KO male mice significantly increase endothelin B receptor (ETB) expression in response to HS/DOCP, but female mice do not. Finally, siRNA-mediated knockdown of PER1 in mouse cortical collecting duct cells (mpkCCDc14) resulted in increased ET-1 mRNA expression and peptide secretion in response to aldosterone treatment. These data suggest that PER1 is a negative regulator of ET-1 expression in response to HS/DOCP, revealing a novel mechanism for the regulation of renal Na handling in response to HS/DOCP treatment.

Bathing suit ichthyosis: Two Burmese siblings and a review of the literature.

Bathing suit ichthyosis (BSI) is a subtype of autosomal recessive congenital ichthyosis (ARCI) characterized by the development of large platelike scales mainly limited to the trunk. It is caused by temperature sensitive variants in transglutaminase 1, encoded by the gene TGM1. We describe a rare case of intrafamilial variation in phenotypic expressivity in two Burmese siblings with BSI that demonstrates the heterogeneity of the disorder within the same family and even in the same individual across time. We also present a concise review of the genotypic spectrum of BSI from 54 cases reported in the literature as evidence that both environmental and additional genetic factors can significantly alter the clinical phenotype.

Dying and relational aftermath concerns among terminal cancer patients in China.

The need to make sense of one's mortality is of central concern for death studies. We aimed to explore the meaning of aftermath concerns in the process of preparing for death. Using a qualitative approach, we explored aftermath concerns among 25 participants with terminal cancer in China. Three aftermath concern themes were developed from the participants' narratives: mental concerns about parents, material concerns about children, and spiritual concerns about the self. Aftermath concerns are relational because they are not about what happens within an individual, but between individuals which are manifested within the broader cultural, social, economic, and political contexts.

Pneumocephalus and Sixth Nerve Palsy after Epidural Steroid Injection: Case Report and Review of the Literature.

BACKGROUND: Pneumocephalus has been described as an unintended outcome after epidural injections. However, oculomotor palsy from pneumocephalus after epidural injection is very rare. CASE REPORT: We report a case of pneumocephalus-induced sixth nerve palsies and diplopia in an 87-year-old woman after epidural steroid injection. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Pneumocephalus-induced oculomotor palsy is a rare complication after epidural injection, a commonly performed medical procedure. Knowledge of this presentation will help emergency physicians distinguish between this entity and other causes of neurologic deficits.