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Previous evidence showed abnormal parietal sources of resting-state electroencephalographic (EEG) delta (< 4 Hz) and alpha (8–12 Hz) rhythms in treatment-Naïve HIV (Naïve HIV) subjects, as cortical neural synchronization markers in quiet wakefulness. Here, we tested the hypothesis that these local abnormalities may be related to functional cortical dysconnectivity as an oscillatory brain network disorder.The present EEG database regarded 128 Naïve HIV and 60 Healthy subjects. The eLORETA freeware estimated lagged linear EEG source connectivity (LLC). The area under receiver operating characteristic (AUROC) curve indexed the accuracy in the classification between Healthy and HIV individuals.Parietal intrahemispheric LLC solutions in alpha sources were abnormally lower in the Naïve HIV than in the control group. Furthermore, those abnormalities were greater in the Naïve HIV subgroup with executive and visuospatial deficits than the Naïve HIV subgroup with normal cognition. AUROC curves of those LLC solutions exhibited moderate/good accuracies (0.75–0.88) in the discrimination between the Naïve HIV individuals with executive and visuospatial deficits vs. Naïve HIV individuals with normal cognition and control individuals.In quiet wakefulness, Naïve HIV subjects showed clinically relevant abnormalities in parietal alpha source connectivity. HIV may alter a parietal “hub” oscillating at the alpha frequency in quiet wakefulness as a brain network disorder.

Abstract The coronavirus disease (COVID‐19), during its course, may involve several organs, including the skin with a petechial skin rash, urticaria and erythematous rash, or varicella‐like eruption, representing an additional effect of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, as commonly observed in other viral diseases. Considering that symptomatic patients with COVID‐19 generally undergo multidrug treatments, the occurrence of a possible adverse drug reaction presenting with cutaneous manifestations should be contemplated. Pleomorphic skin eruptions occurred in a 59‐year‐old Caucasian woman, affected by a stable form of chronic lymphocytic leukemia, and symptomatic SARS‐CoV‐2 infection, treated with a combination of hydroxychloroquine sulfate, darunavir, ritonavir, sarilumb, omeprazole, ceftriaxone, high‐flow oxygen therapy devices, filgrastim (Zarzio®) as a single injection, and enoxaparin. The patient stopped all treatment but oxygen and enoxaparin were continued and the patient received a high‐dose Desametasone with complete remission of dermatological impairment in 10 days. It is very important to differentially diagnose COVID‐19 disease‐related cutaneous manifestations, where is justified to continue the multidrug antiviral treatment, from those caused by an adverse drug reaction, where it would be necessary to identify the possible culprit drug and to start appropriate antiallergic treatment.

Massimo Mammucari,1 Teresa Paolucci,2 Domenico Russo,3 Enrica Maggiori,1 Raffaele Di Marzo,4 Alberto Migliore,5 Umberto Massafra,5 Gianpaolo Ronconi,6 Paola Emilia Ferrara,6 Fabio Gori,7 Barbara Bifarini,7 Stefano Brauneis,8 Renato Vellucci,9 Rocco Domenico Mediati,9 Bartolomeo Violo,10 Silvia Natoli,11 Carmen Pediliggieri,12 Cristiana Di Campli,12 Maria Chiara Collina12 1Primary Care Unit, ASL RM 1, Rome, Italy; 2Unit of Physical Medicine and Rehabilitation, G. D’ Annunzio University of Chieti-Pescara, Department of Oral Medical Science and Biotechnology (DSMOB), Chieti, Italy; 3“San Marco” Hospice and Palliative Care, Latina, Italy; 4Member of the Italian Society of Mesotherapy, Rome, Italy; 5Unit of Rheumatology, San Pietro Fatebenefratelli Hospital, Rome, Italy; 6Physical Medicine and Rehabilitation Unit, IRCCS, Catholic University of Sacred Heart, Rome, Italy; 7Section of Anaesthesia, Intensive Care, and Pain Medicine, University Hospital Santa Maria Della Misericordia, Perugia, Italy; 8Pain Centre “Enzo BorzomatI”, University Hospital of Rome “Policlinico Umberto I”, Rome, Italy; 9Anaesthesiology Department, University Hospital Careggi, Florence, Italy; 10Pain Therapy Unit, S. Spirito Nuovo Regina Margherita Hospital, Rome, Italy; 11Department of Clinical Science and Translational Medicine, Tor Vergata University, Rome, Italy; 12Department of Vascular Surgery, Limb Salvage and Diabetic Foot, IDI-IRCCS, Rome, ItalyCorrespondence: Massimo MammucariPrimary Care Unit, Local Health, ASL RM 1, Rome, 00165, ItalyTel +39-06-61560695 Email massimo.mammucari@libero.itAbstract: Mesotherapy (local intradermal therapy, LIT) is a technique used to slowly spread drugs in tissues underlying the site of injection to prolong the pharmacological effect with respect to intramuscular injection. Recommendations for proper medical use of this technique have been made for pain medicine and rehabilitation, chronic venous disease, sport medicine, musculoskeletal disorders, several dermatological conditions, skin ageing, and immune-prophylaxis. Although mesotherapy is considered a valid technique, unresolved questions remain, which should be answered to standardize methodology and dosing regimen as well as to define the right indications in clinical practice. New randomized controlled trials are needed to test single products (dose, frequency of administration, efficacy and safety). Even infiltration of substances for dermo-cosmetic purposes must be guided by safety and efficacy tests before being proposed by mesotherapy. In this article, we put forth a preclinical and clinical research plan and a health technology assessment as a call to action by doctors, researchers and scientific societies to aid national health authorities in considering mesotherapy for prevention, treatment and rehabilitation paths.Keywords: mesotherapy, intradermal therapy, research plan

Cutaneous chronic wounds are a major global health burden in continuous growth, because of population aging and the higher incidence of chronic diseases, such as diabetes. Different treatments have been proposed: biological, surgical, and physical. However, most of these treatments are palliative and none of them can be considered fully satisfactory. During a spontaneous wound healing, endogenous regeneration mechanisms and resident cell activity are triggered by the released platelet content. Activated stem and progenitor cells are key factors for ulcer healing, and they can be either recruited to the wound site from the tissue itself (resident cells) or from elsewhere. Transplant of skin substitutes, and of stem cells derived from tissues such as bone marrow or adipose tissue, together with platelet-rich plasma (PRP) treatments have been proposed as therapeutic options, and they represent the today most promising tools to promote ulcer healing in diabetes. Although stem cells can directly participate to skin repair, they primarily contribute to the tissue remodeling by releasing biomolecules and microvesicles able to stimulate the endogenous regeneration mechanisms. Stem cells and PRP can be obtained from patients as autologous preparations. However, in the diabetic condition, poor cell number, reduced cell activity or impaired PRP efficacy may limit their use. Administration of allogeneic preparations from healthy and/or younger donors is regarded with increasing interest to overcome such limitation. This review summarizes the results obtained when these innovative treatments were adopted in preclinical animal models of diabetes and in diabetic patients, with a focus on allogeneic preparations.

Helicobacter pylori colonizes human gastric mucosa, overcoming stressful conditions and entering in a dormant state. This study evaluated: (i) H. pylori’s physiological changes from active to viable-but-non-culturable (VBNC) and persister (AP) states, establishing times/conditions; (ii) the ability of vitamin C to interfere with dormancy generation/resuscitation. A dormant state was induced in clinical MDR H. pylori 10A/13 by: nutrient starvation (for VBNC generation), incubating in an unenriched medium (Brucella broth) or saline solution (SS), and (for AP generation) treatment with 10xMIC amoxicillin (AMX). The samples were monitored after 24, 48, and 72 h, 8–14 days by OD600, CFUs/mL, Live/Dead staining, and an MTT viability test. Afterwards, vitamin C was added to the H. pylori suspension before/after the generation of dormant states, and monitoring took place at 24, 48, and 72 h. The VBNC state was generated after 8 days in SS, and the AP state in AMX for 48 h. Vitamin C reduced its entry into a VBNC state. In AP cells, Vitamin C delayed entry, decreasing viable coccal cells and increasing bacillary/U-shaped bacteria. Vitamin C increased resuscitation (60%) in the VBNC state and reduced the aggregates of the AP state. Vitamin C reduced the incidence of dormant states, promoting the resuscitation rate. Pretreatment with Vitamin C could favor the selection of microbial vegetative forms that are more susceptible to H. pylori therapeutical schemes.

Background: There is no consensus on which molar incisor hypomineralization (MIH) indices are more suitable for epidemiological surveys. Aim: To compare the operational aspects and diagnostic ability of the MIH index (simplified/MIH_s and extended/MIH_e) with the MIH‐Severity Scoring System (MIH‐SSS) in classifying and diagnosing MIH. Design: This cross‐sectional study assessed the indices in a homogeneous group of 680 6‐ to 10‐year‐old schoolchildren in Bauru, Brazil, who had at least one first permanent molar, ensuring consistent conditions. Followed by toothbrushing, the children seated on school chairs were examined by the two calibrated researchers under artificial lighting, using mouth mirror and WHO probe, and chronometer recording the duration of examinations. Results: The prevalence of MIH was 24.7%. The most common characteristic of MIH was demarcated opacity, with a prevalence of 81.7% and 85.45% according to the MIH_s and the MIH‐SSS, respectively. A positive association was observed among the MIH_s, the MIH_e, and the MIH‐SSS (chi‐squared test; p <.01). The MIH‐SSS demonstrated a shorter average application time than both versions of the MIH index (ANOVA/Tukey; p <.05). Additionally, fluorosis was found to be the most prevalent among other developmental defects of enamel, with a prevalence of 38.38%. Conclusion: All systems effectively diagnosed MIH and its characteristics. [ABSTRACT FROM AUTHOR]

BackgroundThe sensitivity of teeth with molar incisor hypomineralization (MIH) can affect children’s quality of life and is a challenging problem for dentists. Remineralizing agents such as sodium fluoride varnish seem to reduce the sensitivity of teeth with MIH, but long-term clinical trials with large samples are still needed for more evidence about its effectiveness as a desensitizing agent before its clinical recommendation. ObjectiveThis randomized clinical trial aims to compare three treatment interventions for teeth with MIH and hypersensitivity. MethodsA total of 60 children aged 6-10 years presenting with at least one first permanent molar with sensitivity and no loss of enamel will be randomly assigned to three groups: the control group (sodium fluoride varnish; Duraphat, Colgate); experimental group I (4% titanium tetrafluoride varnish); and experimental group II (a coating resin containing surface prereacted glass-ionomer filler; PRG Barrier Coat, Shofu). The sodium fluoride varnish and 4% titanium tetrafluoride varnish will be applied once per week for 4 consecutive weeks and the PRG Barrier Coat resin will be applied in the first session and the application will be simulated the following 3 weeks to guarantee the blinding of the study. The primary outcome will be sensitivity level measured at different moments (before each material application, immediately after application or simulation, and 1, 2, 4, and 6 months after the last application/simulation) by one examiner using the Wong-Baker FACES Pain Rating Scale, the Schiff Cold Air Sensitivity Scale, and the FLACC (Face, Legs, Activity, Cry, Consolability) scale. As secondary outcomes, parental satisfaction and child self-reported discomfort after the treatment will be measured with a questionnaire prepared by the researcher. The data will undergo statistical analysis and the significance level will be set at 5%. ResultsThe project was funded in 2018, and enrollment was completed in November 2019. The recruitment of participants is currently underway and the first results are expected to be submitted for publication in 2022. ConclusionsIf found effective in reducing the patient’s sensitivity long term, these agents can be considered as a treatment choice, and the findings will contribute to the development of a treatment protocol for teeth with sensitivity due to MIH. Trial RegistrationBrazilian Registry of Clinical Trials Universal Trial Number U1111-1237-6720; https://tinyurl.com/mr4x82k9 International Registered Report Identifier (IRRID)DERR1-10.2196/27843

Background: The use of low-molecular-weight heparin (LMWH) for long-term therapy of venous thromboembolism (VTE) in patients without cancer has not been consistently evaluated. Methods: We used the data in the RIETE registry to compare the 3-month outcomes (VTE recurrences, major bleeding or death) in non-cancer patients with VTE, according to long-term therapy with LMWH or vitamin K antagonists (VKAs). Results: As of March 2018, 14,582 non-cancer patients with VTE had received initial therapy with LMWH and then switched to VKAs, while 9151 were prescribed LMWH for initial and long-term therapy. Overall, 11,494 had initially presented with pulmonary embolism (PE) and 12,239 with isolated deep vein thrombosis (DVT). Among 11,494 patients initially presenting with PE, 84 had VTE recurrences, 204 major bleeding and 406 died. Among 12,239 patients with isolated DVT, 133 developed VTE recurrences, 137 bled and 289 died. On propensity score analysis, PE patients on long-term LMWH therapy were at increased risk for PE recurrences (OR: 3.30; 95%CI: 1.67–6.48), major bleeding (OR: 1.68; 95%CI: 1.21–2.32) or death (OR: 3.16; 95%CI: 2.43–4.09) compared with those receiving VKAs. In patients with DVT, those on long-term LMWH also were at increased risk for PE recurrences (OR: 2.31; 95%CI: 1.13–4.73), major bleeding (OR 2.28; 95%CI: 1.51–3.44) or death (OR: 2.32; 95%CI: 1.54–3.51). Conclusions: In the RIETE non-cancer patients with VTE, long-term therapy with VKAs was associated with a lower risk for recurrences, major bleeding or death.

The hypothesis supported by this paper is, in regional studies, that the common characterization of Amazonia as a frontier should be deeply revised. This territory has been part of the capitalist world system form more than five centuries and may be better be conceived and interpreted as a composition of enclave environments, economies and ecologies, whose relationships to external political and socio-economic powers is deep-rooted and far less fragile than the frontier usage implies. Methodologically, the analysis focuses on socio-territorial literature about Amazonia and about Amazonian territorial constructions highlighting those many factors that seem to contribute to the continued plausibility of the frontier notion. Principal results are related to the construction of a critique to the sense and fertility of the concept of ‘frontier’ in territorial planning and administration practices in contemporary Amazonian territories. Keywords: frontier; Amazonia; coexistence; socio-spatial processes; coloniality

Marinesco–Sjogren syndrome (MSS) is a rare multisystem pediatric disorder, caused by loss-of-function mutations in the gene encoding the endoplasmic reticulum cochaperone SIL1. SIL1 acts as a nucleotide exchange factor for BiP, which plays a central role in secretory protein folding. SIL1 mutant cells have reduced BiP-assisted protein folding, cannot fulfil their protein needs, and experience chronic activation of the unfolded protein response (UPR). Maladaptive UPR may explain the cerebellar and skeletal muscle degeneration responsible for the ataxia and muscle weakness typical of MSS. However, the cause of other more variable, clinical manifestations, such as mild to severe mental retardation, hypogonadism, short stature, and skeletal deformities, is less clear. To gain insights into the pathogenic mechanisms and/or adaptive responses to SIL1 loss, we carried out cell biological and proteomic investigations in skin fibroblasts derived from a young patient carrying the SIL1 R111X mutation. Despite fibroblasts not being overtly affected in MSS, we found morphological and biochemical changes indicative of UPR activation and altered cell metabolism. All the cell machineries involved in RNA splicing and translation were strongly downregulated, while protein degradation via lysosome-based structures was boosted, consistent with an attempt of the cell to reduce the workload of the endoplasmic reticulum and dispose of misfolded proteins. Cell metabolism was extensively affected as we observed a reduction in lipid synthesis, an increase in beta oxidation, and an enhancement of the tricarboxylic acid cycle, with upregulation of eight of its enzymes. Finally, the catabolic pathways of various amino acids, including valine, leucine, isoleucine, tryptophan, lysine, aspartate, and phenylalanine, were enhanced, while the biosynthetic pathways of arginine, serine, glycine, and cysteine were reduced. These results indicate that, in addition to UPR activation and increased protein degradation, MSS fibroblasts have profound metabolic alterations, which may help them cope with the absence of SIL1.