Laryngeal Candidiasis Mimicking Supraglottic Carcinoma by Prolonged Inhaled Steroid Therapy: A Case Report and Review of the Literature

Candidiasis is a rare entity reported as an isolated and primary laryngeal disease. In this condition, inhaled steroids were the single most common predisposing factor. Also mycotic infections of larynx are frequently seen in patients with immune insufficiency, although they have also been reported in individual with normal immune status. We report a case of isolated laryngeal Candidiasis in an immunocompetent individual, with an unusual presentation with exophytic lesion, edema, ulceration, white plaque, and pseudomembranous formation mimicking supraglottic carcinoma, to highlight the clinical of this condition and provide a review of the literature

SIRT3 Modulates Endothelial Mitochondrial Redox State during Insulin Resistance

Emerging evidence indicates that defects in sirtuin signaling contribute to impaired glucose and lipid metabolism, resulting in insulin resistance (IR) and endothelial dysfunction. Here, we examined the effects of palmitic acid (PA) treatment on mitochondrial sirtuins (SIRT2, SIRT3, SIRT4, and SIRT5) and oxidative homeostasis in human endothelial cells (TeloHAEC). Results showed that treatment for 48 h with PA (0.5 mM) impaired cell viability, induced loss of insulin signaling, imbalanced the oxidative status (p < 0.001), and caused negative modulation of sirtuin protein and mRNA expression, with a predominant effect on SIRT3 (p < 0.001). Restoration of SIRT3 levels by mimic transfection (SIRT3+) suppressed the PA-induced autophagy (mimic NC+PA) (p < 0.01), inflammation, and pyroptosis (p < 0.01) mediated by the NLRP3/caspase-1 axis. Moreover, the unbalanced endothelial redox state induced by PA was counteracted by the antioxidant δ-valerobetaine (δVB), which was able to upregulate protein and mRNA expression of sirtuins, reduce reactive oxygen species (ROS) accumulation, and decrease cell death. Overall, results support the central role of SIRT3 in maintaining the endothelial redox homeostasis under IR and unveil the potential of the antioxidant δVB in enhancing the defense against IR-related injuries

Early versus delayed endoscopic treatment of acute pilonidal abscess: a propensity score-matched analysis

Background: According to the Italian Society of Colorectal Surgery guidelines, the most effective approach to the pilonidal abscess is adequate surgical drainage, concerning incision and drainage of the pilonidal cavity. Few recent studies have demonstrated that endoscopic approach could be a valid treatment option even in the case of acute pilonidal abscess. The aim of our study is to assess if video-assisted ablation of pilonidal sinus (VAAPS) could be an alternative to treat an acute pilonidal abscess and to evaluate if an immediate endoscopic approach to the pilonidal abscess is preferable to a delayed procedure after incision and drainage. Methods: All consecutive patients with an acute pilonidal abscess since 1 January 2014 to 31 December 2018 were enrolled in our propensity score-matched analysis and divided into two groups: the early VAAPS group and the delayed VAAPS group. Primary outcomes were recurrence rate at 1-year, 3-year, and 5-year follow-up. Secondary outcomes were time off, time to wound healing, incomplete wound healing, perioperative infection, patients’ satisfaction 1 month after the complete wound healing, and their health status before surgery and 6 months after complete wound healing. Results: After the propensity score matching, 82 patients were included in the final analysis (41 in each group). No differences were found in terms of recurrence in the two groups. Early endoscopic approach was associated with a better patients’ satisfaction (8.17 ± 1.2 vs 6.06 ± 1.48, p = 0.001) and a better postoperative health status (86.27 ± 6.54 vs 77.32 ± 5.85, p = 0.001). Conclusions: Our results encouraged to perform an immediate endoscopic approach to an acute pilonidal abscess

Towards the Formalization of Fractional Calculus in Higher-Order Logic

Fractional calculus is a generalization of classical theories of integration and differentiation to arbitrary order (i.e., real or complex numbers). In the last two decades, this new mathematical modeling approach has been widely used to analyze a wide class of physical systems in various fields of science and engineering. In this paper, we describe an ongoing project which aims at formalizing the basic theories of fractional calculus in the HOL Light theorem prover. Mainly, we present the motivation and application of such formalization efforts, a roadmap to achieve our goals, current status of the project and future milestones.Comment: 9 page

Long-Term Functional Results of a Modified Caudal-to-Cranial Approach in Laparoscopic Segmental Left Colectomy for Diverticular Disease

A modified caudal-to-cranial approach to perform laparoscopic left colectomy for benign diseases has been recently designed to facilitate the low-tie mesenteric dissection. A chart review has been performed including all consecutive patients with uncomplicated diverticulitis who have been treated by segmental left colectomy with a caudal-to-cranial approach. A total of 34 patients were included in the study. 21 patients were male, mean age was 54.1±11.3, and mean BMI was 26±5.5. Patients with ASA Score I were 7, with ASA II were 9, and with ASA Score III were 5. Incontinence Score (IS) resulted in an average of 5±2,2 grade of incontinence and the CS score showed an average of 10±3,2 grade of constipation. Health status, evaluated by Short Form-36 questionnaire, was demonstrated in these patients' great physical function, role, general health, and social function. The anorectal manometry performed 6 months after surgery showed a normal value in terms of the anal resting pressure (47±13 mmHg) and an increased volume to stimulate desire to defecate (197±25 ml). The length of the anal sphincter was normal compared to the reference value (37±5.4 mm). Although further studies are required to obtain definitive conclusions, our results are encouraging to propose low-tie segmental colectomy as the standard procedure for the treatment of uncomplicated diverticulitis, and our modified surgical approach could be considered useful to facilitate the surgical approach

A new estimation of the recent tropospheric molecular hydrogen budget using atmospheric observations and variational inversion

This paper presents an analysis of the recent tropospheric molecular hydrogen (H2) budget with a particular focus on soil uptake and European surface emissions. A variational inversion scheme is combined with observations from the RAMCES and EUROHYDROS atmospheric networks, which include continuous measurements performed between mid-2006 and mid-2009. Net H2 surface flux, then deposition velocity and surface emissions and finally, deposition velocity, biomass burning, anthropogenic and N2 fixation-related emissions were simultaneously inverted in several scenarios. These scenarios have focused on the sensibility of the soil uptake value to different spatio-temporal distributions. The range of variations of these diverse inversion sets generate an estimate of the uncertainty for each term of the H2 budget. The net H2 flux per region (High Northern Hemisphere, Tropics and High Southern Hemisphere) varies between −8 and +8 Tg yr−1. The best inversion in terms of fit to the observations combines updated prior surface emissions and a soil deposition velocity map that is based on bottom-up and top-down estimations. Our estimate of global H2 soil uptake is −59±9 Tg yr−1. Forty per cent of this uptake is located in the High Northern Hemisphere and 55% is located in the Tropics. In terms of surface emissions, seasonality is mainly driven by biomass burning emissions. The inferred European anthropogenic emissions are consistent with independent H2 emissions estimated using a H2/CO mass ratio of 0.034 and CO emissions within the range of their respective uncertainties. Additional constraints, such as isotopic measurements would be needed to infer a more robust partition of H2 sources and sinks

Vitamin d deficiency induces chronic pain and microglial phenotypic changes in mice

The bioactive form of vitamin .D, 1,25‐dihydroxyvitamin D (1,25D3), exerts immunomodulatory actions resulting in neuroprotective effects potentially useful against neurodegenerative and autoimmune diseases. In fact, vitamin D deficiency status has been correlated with painful manifestations associated with different pathological conditions. In this study, we have investigated the effects of vitamin D deficiency on microglia cells, as they represent the main immune cells responsible for early defense at central nervous system (CNS), including chronic pain states. For this purpose, we have employed a model of low vitamin D intake during gestation to evaluate possible changes in primary microglia cells obtained from postnatal day(P)2‐ 3 pups. Afterwards, pain measurement and microglia morphological analysis in the spinal cord level and in brain regions involved in the integration of pain perception were performed in the parents subjected to vitamin D restriction. In cultured microglia, we detected a reactive—activated and proliferative—phenotype associated with intracellular reactive oxygen species (ROS) generation. Oxidative stress was closely correlated with the extent of DNA damage and increased β‐galactosidase (B‐gal) activity. Interestingly, the incubation with 25D3 or 1,25D3 or palmitoylethanolamide, an endogenous ligand of peroxisome proliferator‐activated‐receptor‐alpha (PPAR‐α), reduced most of these effects. Morphological analysis of ex‐vivo microglia obtained from vitamin‐D‐deficient adult mice revealed an increased number of activated microglia in the spinal cord, while in the brain microglia appeared in a dystrophic phenotype. Remarkably, activated (spinal) or dystrophic (brain) microglia were detected in a prominent manner in females. Our data indicate that vitamin D deficiency produces profound modifications in microglia, suggesting a possible role of these cells in the sensorial dysfunctions associated with hypovitaminosis D

Endoscopic Treatment of Pilonidal Sinus Disease: State of Art and Review of the Literature

Background: Pilonidal sinus disease (PSD) is a chronic troublesome pathology of the natal cleft of the sacrococcygeal region, with an estimated incidence of 26 cases in every 100,000 inhabitants. The aim of this review is to give a snapshot of the current literature on the endoscopic approach to PSD. Methods: A search on endoscopic treatment of pilonidal disease was performed according to PRISMA guidelines, adopting the following search terms: (pilonidal OR sacrococcygeal) and (endoscopic OR VAAPS OR EPSiT OR minimally invasive OR video-assisted OR video assisted). Results: Thirty-four articles were included in the final analysis, among which 23 were on adults and 11 were on pediatric population. The endoscopic approach is associated with painless postoperative pain, good aesthetic results, short time off work, and high patient satisfaction. Despite these advantages in short-term outcomes, results on recurrence rate in a long-term follow up are needed to definitively confirm the importance of this technique. Conclusions: The endoscopic approach is associated with significant postoperative advantages over other standard surgical approaches, and it should be included in the surgical portfolio for the treatment of PSD. According to the Italian guidelines, this technique could be considered as the gold standard for limited PSD. However, the favorable short-term-outcomes and lack of reliable data on long-term follow-up must be a stimulus to perform further high-quality studies to give definitive conclusions on this technique

CAR T cells targeting tumor endothelial marker CLEC14A inhibit tumor growth

Engineering T cells to express chimeric antigen receptors (CARs) specific for antigens on hematological cancers has yielded remarkable clinical responses, but with solid tumors, benefit has been more limited. This may reflect lack of suitable target antigens, immune evasion mechanisms in malignant cells, and/or lack of T cell infiltration into tumors. An alternative approach, to circumvent these problems, is targeting the tumor vasculature rather than the malignant cells directly. CLEC14A is a glycoprotein selectively overexpressed on the vasculature of many solid human cancers and is, therefore, of considerable interest as a target antigen. Here, we generated CARs from 2 CLEC14A-specific antibodies and expressed them in T cells. In vitro studies demonstrated that, when exposed to their target antigen, these engineered T cells proliferate, release IFN-γ, and mediate cytotoxicity. Infusing CAR engineered T cells into healthy mice showed no signs of toxicity, yet these T cells targeted tumor tissue and significantly inhibited tumor growth in 3 mouse models of cancer (Rip-Tag2, mPDAC, and Lewis lung carcinoma). Reduced tumor burden also correlated with significant loss of CLEC14A expression and reduced vascular density within malignant tissues. These data suggest the tumor vasculature can be safely and effectively targeted with CLEC14A-specific CAR T cells, offering a potent and widely applicable therapy for cancer

The blockade of the transient receptor potential vanilloid type 1 and fatty acid amide hydrolase decreases symptoms and central sequelae in the medial prefrontal cortex of neuropathic rats

<p>Abstract</p> <p>Background</p> <p>Neuropathic pain is a chronic disease resulting from dysfunction within the "pain matrix". The basolateral amygdala (BLA) can modulate cortical functions and interactions between this structure and the medial prefrontal cortex (mPFC) are important for integrating emotionally salient information. In this study, we have investigated the involvement of the transient receptor potential vanilloid type 1 (TRPV1) and the catabolic enzyme fatty acid amide hydrolase (FAAH) in the morphofunctional changes occurring in the pre-limbic/infra-limbic (PL/IL) cortex in neuropathic rats.</p> <p>Results</p> <p>The effect of <it>N</it>-arachidonoyl-serotonin (AA-5-HT), a hybrid FAAH inhibitor and TPRV1 channel antagonist, was tested on nociceptive behaviour associated with neuropathic pain as well as on some phenotypic changes occurring on PL/IL cortex pyramidal neurons. Those neurons were identified as belonging to the BLA-mPFC pathway by electrical stimulation of the BLA followed by hind-paw pressoceptive stimulus application. Changes in their spontaneous and evoked activity were studied in sham or spared nerve injury (SNI) rats before or after repeated treatment with AA-5-HT. Consistently with the SNI-induced changes in PL/IL cortex neurons which underwent profound phenotypic reorganization, suggesting a profound imbalance between excitatory and inhibitory responses in the mPFC neurons, we found an increase in extracellular glutamate levels, as well as the up-regulation of FAAH and TRPV1 in the PL/IL cortex of SNI rats. Daily treatment with AA-5-HT restored cortical neuronal activity, normalizing the electrophysiological changes associated with the peripheral injury of the sciatic nerve. Finally, a single acute intra-PL/IL cortex microinjection of AA-5-HT transiently decreased allodynia more effectively than URB597 or I-RTX, a selective FAAH inhibitor or a TRPV1 blocker, respectively.</p> <p>Conclusion</p> <p>These data suggest a possible involvement of endovanilloids in the cortical plastic changes associated with peripheral nerve injury and indicate that therapies able to normalize endovanilloid transmission may prove useful in ameliorating the symptoms and central sequelae associated with neuropathic pain.</p