Prospective Placebo-Controlled Assessment of Spore-Based Probiotic Supplementation on Sebum Production, Skin Barrier Function, and Acne.

Probiotic supplementation has been shown to modulate the gut-skin axis. The goal of this study was to investigate whether oral spore-based probiotic ingestion modulates the gut microbiome, plasma short-chain fatty acids (SCFAs), and skin biophysical properties. This was a single-blinded, 8-week study (NCT03605108) in which 25 participants, 7 with noncystic acne, were assigned to take placebo capsules for the first 4 weeks, followed by 4 weeks of probiotic supplementation. Blood and stool collection, facial photography, sebum production, transepidermal water loss (TEWL), skin hydration measurements, and acne assessments were performed at baseline, 4, and 8 weeks. Probiotic supplementation resulted in a decreasing trend for the facial sebum excretion rate and increased TEWL overall. Subanalysis of the participants with acne showed improvement in total, noninflammatory, and inflammatory lesion counts, along with improvements in markers of gut permeability. The gut microbiome of the nonacne population had an increase in the relative abundance of Akkermansia, while the subpopulation of those with acne had an increase in the relative abundance of Lachnospiraceae and Ruminococcus gnavus. Probiotic supplementation augmented the circulating acetate/propionate ratio. There is preliminary evidence for the use of spore-based probiotic supplementation to shift the gut microbiome and augment short-chain fatty acids in those with and without acne. Further spore-based supplementation studies in those with noncystic acne are warranted.

Medicinal Plant Extracts and Natural Compounds for the Treatment of Cutaneous Lupus Erythematosus: A Systematic Review.

Cutaneous lupus erythematosus (CLE) is a group of autoimmune connective tissue disorders that significantly impact quality of life. Current treatment approaches typically use antimalarial medications, though patients may become recalcitrant. Other treatment options include general immunosuppressants, highlighting the need for more and more targeted treatment options. The purpose of this systematic review was to identify potential compounds that could be repurposed for CLE from natural products since many rheumatologic drugs are derived from natural products, including antimalarials. This study was registered with PROSPERO, the international prospective register of systematic reviews (registration number CRD42021251048). We comprehensively searched Ovid Medline, Cochrane Library, and Scopus databases from inception to April 27th, 2021. These terms included cutaneous lupus erythematosus; general plant, fungus, bacteria terminology; selected plants and plant-derived products; selected antimalarials; and JAK inhibitors. Our search yielded 13,970 studies, of which 1,362 were duplicates. We screened 12,608 abstracts, found 12,043 to be irrelevant, and assessed 565 full-text studies for eligibility. Of these, 506 were excluded, and 59 studies were included in the data extraction. The ROBINS-I risk of bias assessment tool was used to assess studies that met our inclusion criteria. According to our findings, several natural compounds do reduce inflammation in lupus and other autoimmune skin diseases in studies using in vitro methods, mouse models, and clinical observational studies, along with a few randomized clinical trials. Our study has cataloged evidence in support of potential natural compounds and plant extracts that could serve as novel sources of active ingredients for the treatment of CLE. It is imperative that further studies in mice and humans are conducted to validate these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=251048.

A Diagnostic Quagmire: PFIC5 Presenting as a Rare Cause of Neonatal Cholestasis.

Progressive familial intrahepatic cholestasis is a heterogeneous group of autosomal recessive disorders defined by defects in bile excretion and transport. We describe a 6-week-old boy from Micronesia presenting with failure to thrive and jaundice. His diagnostic workup was remarkable for direct hyperbilirubinemia, hepatitis, and hepatic ultrasound with possible portosystemic shunting. The presence of toxoplasma IgG initially raised concern for congenital toxoplasmosis. Ultimately, the absence of bile salt export pump staining on liver histology and subsequent genetic studies confirmed a diagnosis of progressive familial intrahepatic cholestasis type 5, an exceedingly rare cause of neonatal cholestasis.

Short-Term Western Diet Intake Promotes IL-23‒Mediated Skin and Joint Inflammation Accompanied by Changes to the Gut Microbiota in Mice.

We previously showed that exposure to a high-sugar and moderate-fat diet (i.e., Western diet [WD]) in mice induces appreciable skin inflammation and enhances the susceptibility to imiquimod-induced psoriasiform dermatitis, suggesting that dietary components may render the skin susceptible to psoriatic inflammation. In this study, utilizing an IL-23 minicircle-based model with features of both psoriasiform dermatitis and psoriatic arthritis, we showed that intake of WD for 10 weeks predisposed mice not only to skin but also to joint inflammation. Both WD-induced skin and joint injuries were associated with an expansion of IL-17A‒producing γδ T cells and increased expression of T helper type 17 cytokines. After IL-23 minicircle delivery, WD-fed mice had reduced microbial diversity and pronounced dysbiosis. Treatment with broad-spectrum antibiotics suppressed IL-23‒mediated skin and joint inflammation in the WD-fed mice. Strikingly, reduced skin and joint inflammation with a partial reversion of the gut microbiota were noted when mice switched from a WD to a standard diet after IL-23 minicircle delivery. These findings reveal that a short-term WD intake‒induced dysbiosis is accompanied by enhanced psoriasis-like skin and joint inflammation. Modifications toward a healthier dietary pattern should be considered in patients with psoriatic skin and/or joint disease.

Randomized double-blind vehicle controlled study of the effects of topical acetyl zingerone on photoaging.

OBJECTIVE: Acetyl zingerone (AZ), a derivative of the phytochemical zingerone from Zingiber officinale (ginger), is a novel compound that is purported to have antiaging properties. The objective of this clinical study was to assess the role of acetyl zingerone in its ability to improve the appearance of facial skin wrinkles, redness, pigmentation, and photoaging was assessed. METHODS: Thirty-one healthy participants (age 44 ± 7 years) were randomized in blinded fashion to apply either 1% AZ or placebo, consisting of the vehicle base cream, to the full face twice daily for 8 weeks with a total of 3 visits. Signs of photoaging, including wrinkles, dyspigmentation, and redness were assessed with facial image analysis photography and software. RESULTS: There was a significant decrease in average wrinkle severity (P = .019; Mean=-25.7% change), total wrinkle volume (P = .003; Mean=-30.1% change), pigment intensity (P = .021; Mean=-25.6% change), and redness intensity (P = .035; Mean=-20.7% change) in the AZ group by 8 weeks compared with the placebo. No significant itching, burning, or stinging was noted by study participants. There was also no significant difference between both groups in the clinical assessment of scaling, erythema, hypopigmentation, or hyperpigmentation. CONCLUSIONS AND RELEVANCE: Topical AZ improves photodamage and decreases the appearance of wrinkles, dyspigmentation, and redness intensity when compared to placebo (vehicle) formulation. Acetyl zingerone is well tolerated with daily use.

Total gastrectomy with delayed Hunt-Lawrence pouch reconstruction for neonatal gastric perforation presenting with hematemesis.

The differential for neonatal hematoma sis ranges from benign etiologies to life-threatening emergencies. Neonatal gastric perforation is a rare cause of neonatal hematoma sis but is a deadly condition, requiring prompt diagnosis and treatment. The etiology is usually related to conditions predisposing to over distension of the stomach, such as positive pressure ventilation or distal obstruction, but in some cases cannot be determined. Patients generally present with abdominal distension and respiratory distress. We present a case of a 1-day old term baby girl who developed sudden onset hematoma sis and clinical deterioration, who was found to have a large proximal gastric perforation requiring emergent total gastrectomy with delayed reconstruction.

Esophageal pH Capsule Retention.

The wireless pH capsule is widely used to evaluate gastroesophageal reflux disease in patients. Common complications include premature capsule detachment, dysphagia, chest pain, and technical malfunctions. We present a 6-year-old boy who presented to our institution with a 2-day history of coffee-ground emesis. A pH capsule was found to be lodged in his distal esophagus 45 days after initial placement. We explore the possible reasons for capsule retention and briefly discuss the safety implications of this finding because we believe that this complication may be underreported.

Reclassification of the Clostridium clostridioforme and Clostridium sphenoides clades as Enterocloster gen. nov. and Lacrimispora gen. nov., including reclassification of 15 taxa.

The genus Clostridium belongs to the family Clostridiaceae. However, many species with the genus name Clostridium are found in different families and even crossing into a different phylum. Motivated by recently completed genome sequences, we propose the reclassification of two separate clades that include misclassified Clostridium species which phylogenetically lie within the family Lachnospiraceae, known for being benign members of gut microbiomes and for their plant-degrading capabilities. We use several phylogenetic and phylogenomic perspectives as well as phenotypic comparisons to gain insight into the evolutionary history of these taxa. One clade, which includes Clostridium clostridioforme, Clostridium aldenense, Clostridium asparagiforme, Clostridium bolteae, Clostridium citroniae and Clostridium lavalense, we propose to reclassify as Enterocloster gen. nov., and reclassify the species as Enterocloster clostridioformis comb. nov., Enterocloster aldensis comb. nov., Enterocloster asparagiformis comb. nov., Enterocloster bolteae comb. nov., Enterocloster citroniae comb. nov. and Enterocloster lavalensis comb. nov. The other clade comprises Clostridium sphenoides, Clostridium aerotolerans, Clostridium algidixylanolyticum, Clostridium amygdalinum, Clostridium celerecrescens, Clostridium indolis, Clostridium saccharolyticum, Clostridium xylanolyticum and Desulfotomaculum guttoideum, and we propose to reclassify it as Lacrimispora gen. nov., including reclassification of the members as Lacrimispora sphenoides comb. nov., Lacrimispora aerotolerans comb. nov., Lacrimispora algidixylanolytica comb. nov., Lacrimispora amygdalina comb. nov., Lacrimispora celerecrescens comb. nov., Lacrimispora indolis comb. nov., Lacrimispora saccharolytica comb. nov. and Lacrimispora xylanolytica comb. nov. We emend the description of D. guttoideum to reflect that it is a later heterotypic synonym of Clostridiums phenoides, which we have reclassified as Lacrimispora sphenoides.

Potential Role of Curcumin Against Biofilm-Producing Organisms on the Skin: A Review.

Turmeric root (Curcuma longa) is predominantly used as a spice, but has also long been known to possess antimicrobial, analgesic, antiinflammatory, and anticancer properties. One predominant group of active compounds in turmeric are curcuminoids, namely bright yellow-pigmented curcumin. While modern science has yet to fully investigate the therapeutic claims of turmeric and its derivatives, results have proven promising in decreasing pain and inflammation in arthritis, improving insulin sensitivity in diabetes, and even curing a variety of infections. The purpose of this review is to discuss the potential for curcumin as an agent against microbial infections, with a special focus on the skin and in the development of bacterial biofilms. Curcumin has demonstrated bactericidal efficacy against a variety of infections when administered with antibiotics in several clinical studies, with consistent antimicrobial activity demonstrated in vitro, as well as in urinary tract infections, gingival infections, and chronic wound infections. Hypothesized mechanisms of action include curcumin's ability to perturb bacterial membranes, disturb protofillament assembly, and even impair bacterial virulence factors. Further investigation is needed to fully understand which organisms are most susceptible to the effects of curcumin and how curcumin can be implemented in dermatology to treat skin conditions such as chronic wounds and acne vulgaris. Copyright © 2017 John Wiley & Sons, Ltd.

Edible Plants and Their Influence on the Gut Microbiome and Acne.

Acne vulgaris affects most people at some point in their lives. Due to unclear etiology, likely with multiple factors, targeted and low-risk treatments have yet to be developed. In this review, we explore the multiple causes of acne and how plant-based foods and supplements can control these. The proposed causative factors include insulin resistance, sex hormone imbalances, inflammation and microbial dysbiosis. There is an emerging body of work on the human gut microbiome and how it mediates feedback between the foods we eat and our bodies. The gut microbiome is also an important mediator of inflammation in the gut and systemically. A low-glycemic load diet, one rich in plant fibers and low in processed foods, has been linked to an improvement in acne, possibly through gut changes or attenuation of insulin levels. Though there is much interest in the human microbiome, there is much more unknown, especially along the gut-skin axis. Collectively, the evidence suggests that approaches such as plant-based foods and supplements may be a viable alternative to the current first line standard of care for moderate acne, which typically includes antibiotics. Though patient compliance with major dietary changes is likely much lower than with medications, it is a treatment avenue that warrants further study and development.

Kineothrix alysoides, gen. nov., sp. nov., a saccharolytic butyrate-producer within the family Lachnospiraceae.

An anaerobic, saccharolytic, spore-forming, butyrate-producing bacterium, strain KNHs209T, was isolated from a switchgrass microcosm seeded with forest soil. Cells were highly motile rods, often forming long filamentous chains which were easily observed moving under the microscope. Its closest phylogenetic relative was Eisenbergiella tayi (16S rRNA gene sequence identity 94.2 %), although it was easily distinguishable based on its morphology and physiology. Whole-genome sequencing enabled development of a minimal medium, and also suggested that the organism is capable of fixing nitrogen. Its wide variety of growth substrates was mirrored by a high number of encoded chemotaxis receptors (45, the highest in the family Lachnospiraceae). Strain KNHs209T utilized a wide variety of carbohydrates, but not cellulose or xylan. Fermentation products included formate, acetate and butyrate; sulfur compounds and nitrate were not reduced. Strain KNHs209T grew optimally at 35-40 °C and pH 7. The genomic DNA G+C content was 42.74 mol%; the major membrane fatty acids were C14 : 0 and C16 : 0. Based on phenotypic, genomic, phylogenetic and chemotaxonomic analyses, this organism represents a novel genus and species within the family Lachnospiraceae for which the name Kineothrix alysoides, gen. nov., sp. nov. is proposed. The type strain is KNHs209T (=ATCC TSD-26T=DSM 100556T).

Text Message Intervention (TEACH) Improves Quality of Life and Patient Activation in Celiac Disease: A Randomized Clinical Trial.

OBJECTIVE: To determine the impact of the Text Message Educational Automated Compliance Help (TEACH) text message intervention as a pragmatic approach for patient engagement among adolescents with celiac disease (CD) as measured by gluten-free diet (GFD) adherence, patient activation, and quality of life (QOL). STUDY DESIGN: Randomized controlled trial with patient recruitment at a pediatric, university-based hospital and through social media; 61 participants ages 12-24 years with CD diagnosed at least 1 year were enrolled. The TEACH intervention cohort received 45 unique text messages over a 3-month study period while the control group received standard of care treatment. Primary outcome measures included objective markers of GFD adherence included serum tissue transglutaminase IgA and deamidated gliadin peptide IgA levels. Secondary patient-reported outcomes collected via online survey included the Celiac Dietary Adherence Test, National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS) Global Short Form measure of QOL, Celiac Symptom Index, and Patient Activation Measure. All measures were assessed at enrollment and after the 3-month study period. Statistical analysis performed using the 2-tailed paired Student t test. RESULTS: Among the TEACH intervention group, there was significant improvement comparing enrollment scores with 3-month follow-up scores in patient activation (Patient Activation Measure score 63.1 vs 72.5, P?=?.01) and QOL (NIH PROMIS Global Mental Health 50.8 vs 53.3, P?=?.01 and NIH PROMIS Global Physical Health 50.8 vs 57.7, P?=?.03). There was no statistically significant difference in patient-reported or objectively measured GFD adherence. CONCLUSIONS: TEACH is an effective intervention among patients with CD to improve patient activation and QOL, even among a cohort with GFD adherence at baseline. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02458898.

Mass cytometry reveals a distinct immunoprofile of operational tolerance in pediatric liver transplantation.

Long-term IS in transplant patients has significant morbidity, poorer quality of life, and substantial economic costs. TOL, defined as graft acceptance without functional impairment in the absence of IS, has been achieved in some pediatric LT recipients. Using mass cytometry, peripheral blood immunotyping was performed to characterize differences between tolerant patients and patients who are stable on single-agent IS. Single-cell mass cytometry was performed using blood samples from a single-center pediatric LT population of operationally tolerant patients to comprehensively characterize the immune cell populations in the tolerant state compared with patients on chronic low-dose IS. Specific T-cell populations of interest were confirmed by flow cytometry. This high-dimensional phenotypic analysis revealed distinct immunoprofiles between transplant populations as well as a CD4+ TOT (CD4+ CD5+ CD25+ CD38-/lo CD45RA) that correlates with tolerance in pediatric LT recipients. In TOL patients, the TOT was significantly increased as compared to patients stable on low levels of IS. This TOT cell was confirmed by flow cytometry and is distinct from classic Treg cells. These results demonstrate the power of mass cytometry to discover significant immune cell signatures that have diagnostic potential.

Role of imaging in the evaluation of inflammatory bowel disease: How much is too much?

Inflammatory bowel disease (IBD) is a lifelong condition with waxing and waning disease course that requires reassessment of disease status as well as screening for complications throughout a patient's lifetime. Laboratory testing, endoscopic assessment, and fecal biomarkers are often used in the initial diagnosis and ongoing monitoring of a patient with IBD. Imaging plays an integral role in the diagnosis and evaluation of IBD. Different imaging modalities can be used over the course of a patient's lifetime, from the initial screening and diagnosis of IBD, to determining the extent of intestinal involvement, monitoring for disease activity, and evaluating for complications of uncontrolled IBD. The various imaging modalities available to the provider each have a unique set of risks and benefits when considering cost, radiation exposure, need for anesthesia, and image quality. In this article we review the imaging techniques available for the evaluation of IBD including fluoroscopic small bowel follow-through, computed tomography enterography, magnetic resonance enterography, and transabdominal ultrasound with particular focus on the judicious use of imaging and the risks and benefits of each option. We also review the risks of ionizing radiation, strategies to reduce exposure to ionizing radiation, and current imaging guidelines among pediatric and adult patient with IBD.

Video capsule endoscopy impacts decision making in pediatric IBD: a single tertiary care center experience.

BACKGROUND: Little is known about the impact of video capsule endoscopy (VCE) on decision making in pediatric patients with IBD. Moreover, few studies have reported on the outcomes of treatment changes made based on VCE findings. Our aim was to identify the added value of VCE in pediatric patients in a tertiary IBD center with established or suspected IBD, by assessing changes in treatments and outcomes before and after VCE. METHODS: A retrospective chart review was performed in children with established (n = 66) or suspected (n = 17) IBD who underwent VCE. Diagnostic classifications, treatments, and clinical outcomes before and 1 year after VCE were compared. RESULTS: Primary indications for VCE included patients treated for Crohn's disease (CD) with poor growth or active symptoms (60%), patients with ulcerative colitis/IBD-unclassified (19%), and suspected IBD (20%). Abnormal VCE was seen in 86% of patients with CD, of whom 75% underwent treatment escalation. One year after VCE, patients with CD improved in growth (mean z-scores at baseline and 12 months, -0.5 and 0.2, respectively; P < 0.0001), mean body mass index (18.3 and 19.8, respectively; P = 0.004), mean erythrocyte sedimentation rate (25 versus 16, respectively; P = 0.012), and median Harvey-Bradshaw Index (2 and 0, respectively; P = 0.003). VCE revealed more extensive disease than concurrent imaging modalities in 43% of the patients with CD. VCE "ruled out" IBD in 94% who had suspected IBD, whereas 50% with presumed ulcerative colitis/IBD-unclassified had a diagnosis changed to CD. CONCLUSIONS: VCE provides additional clinical information that impacted management of pediatric patients with IBD in a tertiary IBD center and was associated with improved outcomes.

Involvement of a bacterial microcompartment in the metabolism of fucose and rhamnose by Clostridium phytofermentans.

BACKGROUND: Clostridium phytofermentans, an anaerobic soil bacterium, can directly convert plant biomass into biofuels. The genome of C. phytofermentans contains three loci with genes encoding shell proteins of bacterial microcompartments (BMC), organelles composed entirely of proteins. METHODOLOGY AND PRINCIPAL FINDINGS: One of the BMC loci has homology to a BMC-encoding locus implicated in the conversion of fucose to propanol and propionate in a human gut commensal, Roseburia inulinivorans. We hypothesized that it had a similar role in C. phytofermentans. When C. phytofermentans was grown on fucose, the major products identified were ethanol, propanol and propionate. Transmission electron microscopy of fucose- and rhamnose-grown cultures revealed polyhedral structures, presumably BMCs. Microarray analysis indicated that during growth on fucose, operons coding for the BMC locus, fucose dissimilatory enzymes, and an ATP-binding cassette transporter became the dominant transcripts. These data are consistent with fucose fermentation producing a 1,2-propanediol intermediate that is further metabolized in the microcompartment encoded in the BMC locus. Growth on another deoxyhexose sugar, rhamnose, resulted in the expression of the same BMC locus and similar fermentation products. However, a different set of dissimilatory enzymes and transport system genes were induced. Quite surprisingly, growth on fucose or rhamnose also led to the expression of a diverse array of complex plant polysaccharide-degrading enzymes. CONCLUSIONS/SIGNIFICANCE: Based on physiological, genomic, and microarray analyses, we propose a model for the fermentation of fucose and rhamnose in C. phytofermentans that includes enzymes encoded in the same BMC locus. Comparative genomic analysis suggests that this BMC may be present in other clostridial species.

Relationship between resting blood pressure and laboratory-induced pain among healthy children.

BACKGROUND: Adult studies have demonstrated that increased resting blood pressure (BP) levels correlate with decreased pain sensitivity. However, few studies have examined the relationship between BP and experimental pain sensitivity among children. OBJECTIVES: This study investigated the association between resting BP levels and experimental pain tolerance, intensity, and unpleasantness in healthy children. We also explored whether these BP-pain relationships were age and gender dependent. METHODS: Participants underwent separate 4-trial blocks of cutaneous pressure and thermal pain stimuli, and 1 trial of a cold pain stimulus in counterbalanced order. RESULTS: A total of 235 healthy children (49.6% female; mean age 12.7 [2.9] years; age range 8-18 years) participated. The study revealed specific gender-based BP-pain relationships. Girls with higher resting systolic BP levels were found to have lower thermal intensity ratings than girls with lower resting systolic BP levels; this relationship was stronger among adolescent girls than among younger girls. Among young girls (8-11 years), those with higher resting diastolic BP (DBP) levels were found to have lower cold intensity and unpleasantness as well as lower thermal intensity ratings than did young girls with lower resting DBP levels; these DBP-pain response relationships were not seen among adolescent girls. CONCLUSIONS: Age, rather than resting BP, was predictive of laboratory pain ratings in boys. The findings suggest that the relationship between BP and experimental pain is age and gender dependent. These aspects of cardiovascular relationships to pain in males and females need further attention to understand their clinical importance.

Children's early approaches to learning and academic trajectories through fifth grade.

Children's early approaches to learning (ATL) enhance their adaptation to the demands they experience with the start of formal schooling. The current study uses individual growth modeling to investigate whether children's early ATL, which includes persistence, emotion regulation, and attentiveness, explain individual differences in their academic trajectories during elementary school. Using data from the Early Childhood Longitudinal Study - Kindergarten Cohort (ECLS-K), the present investigation examined the association between ATL at kindergarten entry and trajectories of reading and math achievement across 6 waves of data from kindergarten, 1st, 3rd, and 5th grade (n = 10,666). The current study found a positive link between early ATL and individual trajectories of reading and math performance. Overall, children's early ATL was equally beneficial for children regardless of their race/ethnicity and dimensions of their socioeconomic background. However, links between early ATL and academic trajectories differed by their gender and initial levels of math and reading achievement.