Gram-positive anaerobe <i>cocci </i>(GPAC) are underrepresented in the microbiome of filaggrin-deficient human skin

Contains fulltext : 174203.pdf (publisher's version ) (Closed access

Guided internet-based transdiagnostic individually tailored Cognitive Behavioral Therapy for symptoms of depression and/or anxiety in college students: A randomized controlled trial

Common mental disorders, such as depression and anxiety, often emerge in college students during the transition into early adulthood. Mental health problems can seriously impact students' functioning, interpersonal relationships, and academic achievement. Actively reaching out to college students with mental health problems and offering them internet-based interventions may be a promising way of providing low-threshold access to evidence-based treatment in colleges. This randomized controlled trial aimed to assess the effectiveness of a guided web-based transdiagnostic individually tailored Cognitive Behavioral Therapy (iCBT) in treating college students with depression and/or anxiety symptoms. Through an online survey that screened college students' mental health, we recruited 100 college students aged ≥18 years who reported mild to moderate depression and/or anxiety symptoms and were attending colleges in the Netherlands. Participants were randomly allocated to guided iCBT (n = 48) or treatment as usual (TAU) control (n = 52). Primary outcomes were symptoms of depression and anxiety measured at post-treatment (7 weeks post-randomization). We also measured all outcomes at 6- and 12-months post-randomization. All analyses were based on the intention-to-treat principle and were repeated using the complete-case sample. We found no evidence of a difference between the effects of guided iCBT and TAU in any of the examined outcomes (i.e., symptoms of depression and anxiety, quality of life, educational achievement, and college dropout) across all time points (p > .05). There was no evidence that effects of iCBT were associated with treatment satisfaction and adherence. More research into transdiagnostic individually tailored iCBT is necessary. Further, future studies should recruit larger samples to investigate possible smaller but clinically relevant effects of internet-based interventions for college students with depression and/or anxiety

Proteomics of human liver membrane transporters: a focus on fetuses and newborn infants

Background: Hepatic membrane transporters are involved in the transport of many endogenous and exogenous compounds, including drugs. We aimed to study the relation of age with absolute transporter protein expression in a cohort of 62 mainly fetus and newborn samples. Methods: Protein expressions of BCRP, BSEP, GLUT1, MCT1, MDR1, MRP1, MRP2, MRP3, NTCP, OCT1, OATP1B1, OATP1B3, OATP2B1 and ATP1A1 were quantified with LC-MS/MS in isolated crude membrane fractions of snap-frozen post-mortem fetal and pediatric, and surgical adult liver samples. mRNA expression was quantified using RNA sequencing, and genetic variants with TaqMan assays. We explored relationships between protein expression and age (gestational age [GA], postnatal age [PNA], and postmenstrual age); between protein and mRNA expression; and between protein expression and genotype. Results: We analyzed 36 fetal (median GA 23.4 weeks [range 15.3–41.3]), 12 premature newborn (GA 30.2 weeks [24.9–36.7], PNA 1.0 weeks [0.14–11.4]), 10 term newborn (GA 40.0 weeks [39.7–41.3], PNA 3.9 weeks [0.3–18.1]), 4 pediatric (PNA 4.1 years [1.1–7.4]) and 8 adult liver samples. A relationship with age was found for BCRP, BSEP, GLUT1, MDR1, MRP1, MRP2, MRP3, NTCP, OATP1B1 and OCT1, with the strongest relationship for postmenstrual age. For most transporters mRNA and protein expression were not correlated. No genotype-protein expression relationship was detected. Discussion and conclusion: Various developmental patterns of protein expression of hepatic transporters emerged in fetuses and newborns up to four months of age. Postmenstrual age was the most robust factor predicting transporter expression in this cohort. Our data fill an important gap in current pediatric transporter ontogeny knowledge

Pattern recognition receptors in immune disorders affecting the skin.

Contains fulltext : 109004.pdf (publisher's version ) (Open Access)Pattern recognition receptors (PRRs) evolved to protect organisms against pathogens, but excessive signaling can induce immune responses that are harmful to the host. Putative PRR dysfunction is associated with numerous immune disorders that affect the skin, such as systemic lupus erythematosus, cryopyrin-associated periodic syndrome, and primary inflammatory skin diseases including psoriasis and atopic dermatitis. As yet, the evidence is often confined to genetic association studies without additional proof of a causal relationship. However, insight into the role of PRRs in the pathophysiology of some disorders has already resulted in new therapeutic approaches based on immunomodulation of PRRs

Percutaneous radiofrequency lesions adjacent to the dorsal root ganglion alleviate spasticity and pain in children with cerebral palsy: pilot study in 17 patients

BACKGROUND: Cerebral palsy (CP) may cause severe spasticity, requiring neurosurgical procedures. The most common neurosurgical procedures are continuous infusion of intrathecal baclofen and selective dorsal rhizotomy. Both are invasive and complex procedures. We hypothesized that a percutaneous radiofrequency lesion of the dorsal root ganglion (RF-DRG) could be a simple and safe alternative treatment. We undertook a pilot study to test this hypothesis. METHODS: We performed an RF-DRG procedure in 17 consecutive CP patients with severe hip flexor/adductor spasms accompanied by pain or care-giving difficulties. Six children were systematically evaluated at baseline, and 1 month and 6 months after treatment by means of the Modified Ashworth Scale (MAS), Gross Motor Function Measure (GMFM) and a self-made caregiver's questionnaire. Eleven subsequent children were evaluated using a Visual Analogue Scale (VAS) for spasticity, pain and ease of care. RESULTS: A total of 19 RF-DRG treatments were performed in 17 patients. We found a small improvement in muscle tone measured by MAS, but no effect on the GMFM scale. Despite this, the caregivers of these six treated children unanimously stated that the quality of life of their children had indeed improved after the RF-DRG. In the subsequent 11 children we found improvements in all VAS scores, in a range comparable to the conventional treatment options. CONCLUSION: RF-DRG is a promising new treatment option for severe spasticity in CP patients, and its definitive effectiveness remains to be defined in a randomised controlled trial

Dysregulation of proinflammatory versus anti-inflammatory human TH_H17 cell functionalities in the autoinflammatory Schnitzler syndrome

Background: T$_H$17 cells have so far been considered to be crucial mediators of autoimmune inflammation. Two distinct types of T$_H$17 cells have been described recently, which differed in their polarization requirement for IL-1b and in their cytokine repertoire. Whether these distinct T$_H$17 phenotypes translate into distinct T$_H$17 cell functions with implications for human health or disease has not been addressed yet. Objective: We hypothesized the existence of proinflammatory and anti-inflammatory human T$_H$17 cell functions based on the differential expression of IL-10, which is regulated by IL-1 beta. Considering the crucial role of IL-1 beta in the pathogenesis of autoinflammatory syndromes, we hypothesized that IL-1 beta mediates the loss of anti-inflammatory T$_H$17 cell functionalities in patients with Schnitzler syndrome, an autoinflammatory disease. Methods: To assess proinflammatory versus anti-inflammatory T$_H$17 cell functions, we performed suppression assays and tested the effects of IL-1 beta dependent and independent T$_H$17 subsets on modulating proinflammatory cytokine secretion by monocytes. Patients with Schnitzler syndrome were analyzed for changes in T$_H$17 cell functions before and during therapy with IL-1 beta-blocking drugs. Results: Both T$_H$17 cell subsets differ in their ability to suppress T-cell proliferation and their ability to modulate proinflammatory cytokine production by antigen-presenting cells because of their differential IL-10 expression properties. In patients with Schnitzler syndrome, systemic overproduction of IL-1 beta translates into a profound loss of anti-inflammatory T$_H$17 cell functionalities, which can be reversed by anti-IL-1b treatment. Conclusion: IL-1 beta signaling determines the differential expression pattern of IL-10, which is necessary and sufficient to induce proinflammatory versus anti-inflammatory T$_H$17 cell functions. Our data introduce T$_H$17 cell subsets as novel players in autoinflammation and thus novel therapeutic targets in autoinflammatory syndromes including other IL-1 beta mediated diseases. This demonstrates for the first time alterations in the adaptive immune system in patients with autoinflammatory syndromes

Endovascular abdominal aortic aneurysm repair complicated by spondylodiscitis and iliaco-enteral fistula.

Contains fulltext : 70358.pdf (publisher's version ) (Closed access)Infections of abdominal aortic endografts are rare. There are no reports on the association with spondylodiscitis. We report a case of a 74-year-old man who underwent endovascular aneurysm repair (EVAR) and subsequently femorofemoral bypass placement due to occlusion of the right limb of the endograft. Six months later, he presented with rectal bleeding, weight loss, back pain, and low abdominal pain. Computed tomography revealed extensive abscess formation with air in and around the endograft and psoas muscles, in continuity with destructive spondylodiscitis L3-4. There was a small bowel loop in close proximity to the occluded right leg of the endograft, which was filled with air bubbles. An axillofemoral bypass was created followed by a laparotomy. Intra-operatively, an iliaco-enteral fistula was found. The small bowel defect was sutured, the endograft completely removed, and the infrarenal aorta and both common iliac arteries were closed. Necrotic fragments of the former L3-4 disk were removed. The postoperative course was uneventful. Seven months postoperatively, the patient had recovered well. Iliaco-enteric fistula and spondylodiscitis are rare complications of aortic aneurysm repair. This is the first report of spondylodiscitis after EVAR