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Compatibly, cytotoxic T-cells isolated from these tumors demonstrated increased production of IFN-γ. In colon cancer tumors, T-cells infiltration was significantly increased following long treatment duration with TTFields plus anti-PD-1. Collectively, our results suggest that TTFields therapy can induce anticancer immune response. Furthermore, we demonstrate robust efficacy of concomitant application of TTFields and anti-PD-1 therapy. These data suggest that integrating TTFields with anti-PD-1 therapy may further enhance antitumor immunity, hence achieve better tumor control.PURPOSE Despite the fact that open reduction and internal fixation with a plate, either non-locked or locked, is the standard of care for managing lateral malleolus fractures, intramedullary (IM) fixation of the fibula has been recently introduced as an alternative, mainly for some potential complicated situations. We hypothesized that almost all patterns of distal fibula fracture can be safely fixed with an IM device, with the potential benefit of providing biomechanical efficiency, but using a soft-tissue friendly implant. Here, we present a multicenter case series based on a proposed algorithm. PATIENTS AND METHODS Sixty-nine consecutive patients were managed with fibular IM fixation for closed malleolar fractures. Twenty patients were managed by IM screw fixation and 49 by fibular nailing. Outcome was measured both according to the American Orthopaedic Foot and Ankle Society (AOFAS) score for ankle and hindfoot, and the time to bone union. RESULTS The mean AOFAS for Group I was 99.35 ± 1.95 points and that for Group II was 89.30 ± 16.98 points. There were no significant differences between the fracture pattern, according to the Lauge-Hansen classification, and post-operative levels of pain and functional activity among patients in both groups (p > 0.05). All fractures healed uneventfully in both groups. The mean time to union for Group I was 8.15 weeks and for Group II was 8.25 weeks (p > 0.05). CONCLUSION In this multicenter case series, intramedullary fixation for the lateral malleolus fracture presented itself as a viable and safe option for the treatment of almost all patterns of fibula fracture in adults. Overall, we were able to demonstrate the potential indications of the proposed algorithm for the choice of IM implant for the lateral malleolus fracture in terms of the Lauge-Hansen staged classification.OBJECTIVE The currently available anti-inflammatory drugs often cause diverse side effects with long-term use. Exploring anti-inflammatory drugs with better efficacy and lower toxicity presents an ongoing challenge. Aloperine is an alkaloid extracted from the leaves and seeds of Sophora alopecuroides L. However, the anti-inflammatory effects of Aloperine have not been fully elucidated. This study aimed to investigate whether Aloperine suppresses lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 macrophages. METHODS RAW264.7 macrophages were stimulated with LPS (1 μg/mL) in the presence or absence of Aloperine (50 and 100 μM). mRNA expression was measured by real-time PCR, and protein expression was assessed by western blot analysis. The secretion of pro-inflammatory cytokines was measured by ELISA. The levels of nitric oxide (NO) and reactive oxygen species (ROS) were measured by staining. The transcriptional activity of NF-κB was assayed by a luciferase activity assay. RESULTS The results proved that Aloperine inhibited the expression of LPS-induced pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-17A (IL-17A)] in macrophages. Treatment with Aloperine inhibited NO production through suppressing inducible nitric oxide synthase (iNOS) expression and the secretion of prostaglandin E2 (PGE2) by inhibiting cyclooxygenase 2 (COX-2) expression. Aloperine prevented LPS-induced oxidative stress by reducing the generation of ROS. Furthermore, aloperine significantly reduced Toll-like receptor 4 (TLR4) and myeloid differentiation factor (Myd-88) levels and prevented the nuclear translocation of nuclear factor-κB (NF-κB) in LPS-treated macrophages. CONCLUSION Taken together, our findings show that Aloperine could suppress LPS-induced macrophage activation by inhibiting the TLR4/Myd-88/NF-κB pathway.OBJECTIVE AND DESIGN Gallic acid (GA) a naturally occurring phenolic compound, known to possess antioxidant/anti-inflammatory activities. The aim of the present work was to investigate the beneficial effects of GA against COPD-linked lung inflammation/emphysema by utilizing elastase (ET) and cigarette smoke (CS)-induced mice model. MATERIALS Male BALB/c mice were treated with ET (1U/mouse) or exposed to CS (9 cigarettes/day for 4 days). GA administration was started 7 days (daily) prior to ET/CS exposure. Broncho-alveolar lavage was analyzed for inflammatory cells and pro-inflammatory cytokines. Lung homogenate was assessed for MPO activity/GSH/MDA/protein carbonyls. Further, Lung tissue was subjected to semi-quantitative RT-PCR, immunoblotting, and histological analysis. RESULTS GA suppressed the ET-induced neutrophil infiltration, elevated MPO activity and production of pro-inflammatory cytokines (IL-6/TNF-α/IL-1β) at 24 h. Reduced inflammation was accompanied with normalization of redox balance as reflected by ROS/GSH/MDA/protein carbonyl levels. Further, GA suppressed phosphorylation of p65NF-κB and IκBα along with down-regulation of IL-1β/TNF-α/KC/MIP-2/GCSF genes. Furthermore, GA offered protection against ET-induced airspace enlargement and ameliorated MMP-2/MMP-9. Finally, GA suppressed the CS-induced influx of neutrophils and macrophages and blunted gene expression of TNF-α/MIP-2/KC. CONCLUSION Overall, our data show that GA effectively modulates pulmonary inflammation and emphysema associated with COPD pathogenesis in mice.Intertriginous psoriasis is a variant of psoriasis that is associated with inflammatory lesions in skin folds. Patients often feel ashamed, are subjected to stigmatization, social isolation, or experience mental health issues. There is no general consensus on the definition of intertriginous psoriasis. Depending on the definition used, the prevalence varies substantially. Due to the particular location of skin lesions, therapeutic management is very challenging. Mild symptoms can be treated with topical corticosteroids or topical immunomodulators. There are encouraging data demonstrating the efficacy of ixekizumab, possibly charting the way for it to become a systemic treatment option.BACKGROUND According to the current scabies guideline, topical treatment with permethrin 5% cream is the first-line therapy of common scabies in Germany. However, in the course of growing incidence of scabies in recent years there have been increasing numbers of reports of reduced efficacy in standard therapy. OBJECTIVE To establish a better understanding for the efficacy of scabies therapy under practice conditions, a survey focusing on the first-line therapy with permethrin was conducted in dermatological hospitals, outpatient clinics and dermatology practices. METHODS The postal survey addressed all dermatologically active physicians in Germany and queried diagnostic methods, the individual initial treatment, the estimated efficacy of permethrin therapy, the frequency and reasons for therapy failures under permethrin and the therapeutic approach in case of failure of the initial therapy. EGFR inhibitor drugs RESULTS The efficacy of permethrin was rated with 73% by 187 physicians. About 74% reported to treat initially with 5% permethrin cream. The most common reasons identified for treatment failure were application errors, lack of compliance and inadequate hygiene measures. Suspected diminished efficacy or development of resistance against permethrin and re-infestations were also mentioned. In the case of ineffectiveness of initial therapy, most clinicians opt for oral ivermectin, a repetition of permethrin therapy or a combination of both. CONCLUSION Although there are localized reports of decreased effectiveness of permethrin therapy, results of this survey point towards a persisting high efficacy of first-line standard treatment of scabies with permethrin 5% cream in Germany.RATIONALE Is it possible to have a psychedelic experience from a placebo alone? Most psychedelic studies find few effects in the placebo control group, yet these effects may have been obscured by the study design, setting, or analysis decisions. OBJECTIVE We examined individual variation in placebo effects in a naturalistic environment resembling a typical psychedelic party. METHODS Thirty-three students completed a single-arm study ostensibly examining how a psychedelic drug affects creativity. The 4-h study took place in a group setting with music, paintings, coloured lights, and visual projections. Participants consumed a placebo that we described as a drug resembling psilocybin, which is found in psychedelic mushrooms. To boost expectations, confederates subtly acted out the stated effects of the drug and participants were led to believe that there was no placebo control group. The participants later completed the 5-Dimensional Altered States of Consciousness Rating Scale, which measures changes in conscious experience. RESULTS There was considerable individual variation in the placebo effects; many participants reported no changes while others showed effects with magnitudes typically associated with moderate or high doses of psilocybin. In addition, the majority (61%) of participants verbally reported some effect of the drug. Several stated that they saw the paintings on the walls "move" or "reshape" themselves, others felt "heavy… as if gravity [had] a stronger hold", and one had a "come down" before another "wave" hit her. CONCLUSION Understanding how context and expectations promote psychedelic-like effects, even without the drug, will help researchers to isolate drug effects and clinicians to maximise their therapeutic potential.PURPOSE To investigate whether testis-epididymis dissociation encountered in boys with cryptorchidism/hydrocele is related with an abnormal persistence of the fetal mesentery of testis and associated ducts. METHODS We examined the morphology of peritoneal folds of the testis, epididymis, and vas deferens in 25 boys operated for unilateral cryptorchidism [inguinal (n = 20), intrabdominal (n = 5)] and 20 boys operated for unilateral communicating hydrocele. Findings were compared with the normally persisting genital mesentery of rats (n = 30, both sides), a known animal model of the genital mesentery of human fetuses, as well as with the normal mature pattern of genital peritoneal folds in adult male cadavers (n = 12, both sides). Rats before testis descent [aged 18 days (n = 15)] served for comparison with boys with cryptorchidism, while rats after testis descent [aged 50 (n = 15)] known to retain patent processi vaginales for comparison with boys with hydrocele. RESULTS A well-developed genital mesentery, identical to the fetal-type genital mesentery in the rat, was documented in cryptorchidism and hydrocele. The peritoneum enveloped the testis, epididymis, and vas deferens, and formed wide ligaments between testis-epididymis, epididymis-vas deferens, and vas-posterior wall; processus vaginalis was patent in all cases. The testis-epididymis ligament was related with testis-epididymis distancing, the so-called testis-epididymis dissociation. On the contrary, genital mesentery had involuted in the adult male cadavers, except for a small portion of testis-epididymis ligament corresponding to the so-called sinus epididymis. CONCLUSION The testis-epididymis dissociation encountered in cryptorchidism/hydrocele is part of an anomalously persisting fetal-type genital mesentery.
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