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Dois casos de neuropatia sensitiva e autonômica hereditária do tipo 2 são descritos. Este tipo de neuropatia faz parte de um grupo constituído por cinco entidades diferentes. A sistematização destas neuropatias depende de múltiplos critérios como idade de início, aspectos genéticos, manifestações clínicas, aspectos eletroneuromiográficos e patológicos. Neste relato descrevemos dois irmãos com 27 e 35 anos de idade que foram acompanhados em nosso Serviço, com quadro de insensibilidade à dor e conseqüentes deformidades de membros e distúrbios sensitivo-tróficos. Para estes pacientes foi definido o diagnóstico de neuropatia sensitiva e autonômica hereditária do tipo 2, com modalidade de transmissão hereditária autossômica recessiva. A idade de início do quadro, os aspectos hereditários, as manifestações clínicas e os aspectos eletroneuromiográficos são analisados. O diagnóstico diferencial com outras neuropatias sensitivas hereditárias e adquiridas é considerado.

Background: Sodium-glucose co-transporters (SGLT) inhibitors (SGLT2i) showed many beneficial effects at the cardiovascular level. Several mechanisms of action have been identified. However, no data on their capability to act via epigenetic mechanisms were reported. Therefore, this study aimed to investigate the ability of SGLT2 inhibitors (SGLT2i) to induce protective effects at the cardiovascular level by acting on DNA methylation., Methods: To better clarify this issue, the effects of empagliflozin (EMPA) on hyperglycemia-induced epigenetic modifications were evaluated in human ventricular cardiac myoblasts AC16 exposed to hyperglycemia for 7 days. Therefore, the effects of EMPA on DNA methylation of NF-κB, SOD2, and IL-6 genes in AC16 exposed to high glucose were analyzed by pyrosequencing-based methylation analysis. Modifications of gene expression and DNA methylation of NF-κB and SOD2 were confirmed in response to a transient SGLT2 gene silencing in the same cellular model. Moreover, chromatin immunoprecipitation followed by quantitative PCR was performed to evaluate the occupancy of TET2 across the investigated regions of NF-κB and SOD2 promoters., Results: Seven days of high glucose treatment induced significant demethylation in the promoter regions of NF-kB and SOD2 with a consequent high level in mRNA expression of both genes. The observed DNA demethylation was mediated by increased TET2 expression and binding to the CpGs island in the promoter regions of analyzed genes. Indeed, EMPA prevented the HG-induced demethylation changes by reducing TET2 binding to the investigated promoter region and counteracted the altered gene expression. The transient SGLT2 gene silencing prevented the DNA demethylation observed in promoter regions, thus suggesting a role of SGLT2 as a potential target of the anti-inflammatory and antioxidant effect of EMPA in cardiomyocytes., Conclusions: In conclusion, our results demonstrated that EMPA, mainly acting on SGLT2, prevented DNA methylation changes induced by high glucose and provided evidence of a new mechanism by which SGLT2i can exert cardio-beneficial effects., (© 2023. The Author(s).)

In the body of research on the relationship between gesture and speech, some models propose they form an integrated system while others attribute gestures a compensatory role in communication. This study addresses the gesture-speech relationship by taking disfluency phenomena as a case study. Since it is part of a project aimed at designing virtual agents to be employed in museums, an analysis was performed on the communicative behavior of tourist guides. Results reveal that gesturing is more frequent during speech than pauses. Moreover, when comparing the types of gestures and types of pauses they co-occur with, non-communicative gestures (idles and manipulators) turn out to be more frequent than communicatively-meaningful gestures, which instead more often co-occur with speech. We discuss these findings as relevant for a theoretical model viewing speech and gesture as an integrated system., (© 2022. The Author(s), under exclusive licence to Marta Olivetti Belardinelli.)

Atherosclerosis is a progressive inflammatory disease leading to mortality and morbidity in the civilized world. Atherosclerosis manifests as an accumulation of plaques in the intimal layer of the arterial wall that, by its subsequent erosion or rupture, triggers cardiovascular diseases. Diabetes mellitus is a well-known risk factor for atherosclerosis. Indeed, Type 2 diabetes mellitus patients have an increased risk of atherosclerosis and its associated-cardiovascular complications than non-diabetic patients. Sodium-glucose co-transport 2 inhibitors (SGLT2i), a novel anti-diabetic drugs, have a surprising advantage in cardiovascular effects, such as reducing cardiovascular death in a patient with or without diabetes. Numerous studies have shown that atherosclerosis is due to a significant inflammatory burden and that SGLT2i may play a role in inflammation. In fact, several experiment results have demonstrated that SGLT2i, with suppression of inflammatory mechanism, slows the progression of atherosclerosis. Therefore, SGLT2i may have a double benefit in terms of glycemic control and control of the atherosclerotic process at a myocardial and vascular level. This review elaborates on the anti-inflammatory effects of sodium-glucose co-transporter 2 inhibitors on atherosclerosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Scisciola, Cataldo, Taktaz, Fontanella, Pesapane, Ghosh, Franzese, Puocci, De Angelis, Sportiello, Marfella and Barbieri.)

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We report two cases of endometriosis of the round ligament in a 37 and 26 - years old women, with a lump in their right groin and catamenial pain referred to plastic surgery department. MRI showed in both cases nodular lesion in the right inguinal region. The patological examination of the surgical specimen revealed endometriosis of the round ligament. The presence of a groin mass with pain increasing during the menstrual period must raise the suspicion of inguinal endometriosis and a gynecological evaluation is essential to provide a correct management of this rare condition.

Purpose: The current gold standard for chronic endometritis (CE) diagnosis is immunohistochemistry (IHC) for CD-138. However, IHC for CD-138 is not exempt from diagnostic limitations. The aim of our study was to evaluate the reliability and accuracy of MUM-1 IHC, as compared with CD-138., Methods: This is a multi-centre, retrospective, observational study, which included three tertiary hysteroscopic centres in university teaching hospitals. One hundred ninety-three consecutive women of reproductive age were referred to our hysteroscopy services due to infertility, recurrent miscarriage, abnormal uterine bleeding, endometrial polyps or myomas. All women underwent hysteroscopy plus endometrial biopsy. Endometrial samples were analysed through histology, CD138 and MUM-1 IHC. The primary outcome was to evaluate the diagnostic accuracy of MUM-1 IHC for CE, as compared with CD-138 IHC., Results: Sensitivity and specificity of CD-138 and MUM-1 IHC were respectively 89.13%, 79.59% versus 93.48% and 85.03%. The overall diagnostic accuracy of MUM-1 and CD-138 IHC were similar (AUC = 0.893 vs AUC = 0.844). The intercorrelation coefficient for single measurements was high between the two techniques (ICC = 0.831, 0.761-0.881 95%CI). However, among CE positive women, MUM-1 allowed the identification of higher number of plasma cells/hpf than CD-138 (6.50 [SD 4.80] vs 5.05 [SD 3.37]; p = 0.017). Additionally, MUM-1 showed a higher inter-observer agreement as compared to CD-138., Conclusion: IHC for MUM-1 and CD-138 showed a similar accuracy for detecting endometrial stromal plasma cells. Notably, MUM-1 showed higher reliability in the paired comparison of the individual samples than CD-138. Thus, MUM-1 may represent a novel, promising add-on technique for the diagnosis of CE., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ultrasound-guided sampling methods are usually minimally invasive techniques applied to obtain cytological specimens or tissue samples, mainly used for the diagnosis of different types of tumors. The main benefits of ultrasound guidance is its availability. It offers high flexibility in the choice of sampling approach (transabdominal, transvaginal, and transrectal) and short duration of procedure. Ultrasound guided sampling of pelvic masses represents the diagnostic method of choice in selected patients. We carried out a narrative review of literatures regarding the ultrasound-guided methods of cytological and histological evaluation of pelvic masses as well as the positive and negative predictors for the achievement of an adequate sample.

Conflicting data are reported on the relationship between hyperglycaemia, diabetes and SIRT6 expression. To elucidate hyperglycaemia-induced molecular mechanisms regulating SIRT6 expression, the effect of hyperglycaemia on DNA methylation and SIRT6 expression has been evaluated in human aortic endothelial cells exposed to high glucose. DNA methylation of SIRT6 and any potential clinical implication was also evaluated in type 2 diabetic patients and compared with healthy controls. Endothelial cells exposed to high glucose showed lower methylation levels in SIRT6 promoter and increased SIRT6 and TET2 expression. The high glucose-induced epigenetic changes persisted after 48 h of glucose normalization. Diabetic patients showed lower levels of SIRT6 DNA methylation compared with nondiabetic patients. SIRT6 DNA methylation levels inversely correlated with plasma glucose. Our results firstly demonstrate the involvement of epigenetic mechanisms in regulating SIRT6 expression. Further experiments are necessary to clarify metabolic memory mechanisms driving to diabetic complications and how SIRT6 is potentially involved., (© 2020 Wiley Periodicals LLC.)

Cervical cancer (CC) is the fourth most frequent cancer in women worldwide. HPV infection is associated with the majority of CC cases, but a small proportion of CCs actually test negative for HPV. The prevalence of HPV among CC histotypes is very different. It has been suggested that HPV-negative CC may represent a biologically distinct subset of tumors, relying on a distinct pathogenetic pathway and carrying a poorer prognosis, than HPV-positive CCs. Although, the discordance in terms of sensitivity and specificity between different HPV tests as well as the potential errors in sampling and storing tissues may be considered as causes of false-negative results. The identification of HPV-negative CCs is essential for their correct management. The aim of this narrative review is to summarize the clinical and pathological features of this variant. We also discuss the pitfalls of different HPV tests possibly leading to classification errors.

Sarcopenia is a geriatric syndrome characterized by the progressive degeneration of muscle mass and function, and it is associated with severe complications, which are falls, functional decline, frailty, and mortality. Sarcopenia is associated with cognitive impairment, defined as a decline in one or more cognitive domains as language, memory, reasoning, social cognition, planning, making decisions, and solving problems. Although the exact mechanism relating to sarcopenia and cognitive function has not yet been defined, several studies have shown that skeletal muscle produces and secrete molecules, called myokines, that regulate brain functions, including mood, learning, locomotor activity, and neuronal injury protection, showing the existence of muscle-brain cross-talk. Moreover, studies conducted on physical exercise supported the existence of muscle-brain cross-talk, showing how physical activity, changing myokines' circulating levels, exerts beneficial effects on the brain. The review mainly focuses on describing the role of myokines on brain function and their involvement in cognitive impairment in sarcopenia.

The effect of GLP-1R agonists on DNA methylation levels of NF-κB and SOD2 genes in human aortic endothelial cells exposed to high glucose and in diabetic patients treated and not with incretin-based drugs, was evaluated. Methylation levels, mRNA and protein expression of NF-κB and SOD2 genes were measured in human endothelial cells exposed to high glucose for 7 days and treated with GLP-1R agonists. Methylation status of NF-κB and SOD2 promoter was also analyzed in 128 diabetics and 116 nondiabetics and correlated with intima media thickness (ITM), an early marker of atherosclerotic process. Cells exposed to high glucose showed lower NF-κB and SOD2 methylation levels, increased NF-κB and reduced SOD2 expression compared to normal glucose cells. Co-treatment with GLP-1 agonists prevented methylation and genes expression changes induced by high glucose. Both high glucose and incretins exposure increased DNA methyltransferases and demethylases levels. In diabetics, incretin treatment resulted a significant predictor of NF-κB DNA methylation, independently of age, sex, body mass index (BMI), glucose and plasma lipid levels. NF-κB DNA methylation inversely correlated with IMT after adjusting for multiple covariates. Our results firstly provide new evidences of an additional mechanism by which incretin drugs could prevent vascular diabetic complications., (© 2020 Federation of American Societies for Experimental Biology.)

The Athabasca Valles flood lava is among the most recent (<50 Ma) and best preserved effusive lava flows on Mars and was probably emplaced turbulently. The Williams et al. [2005] model of thermal erosion by lava has been applied to what we term "proximal Athabasca," the 75 km long upstream portion of Athabasca Valles. For emplacement volumes of 5000 and 7500 km 3 and average flow thicknesses of 20 and 30 m, the duration of the eruption varies between ~11 and ~37 days. The erosion of the lava flow substrate is investigated for three eruption temperatures (1270°C, 1260°C, and 1250°C), and volatile contents equivalent to 0-65 vol% bubbles. The largest erosion depths of ~3.8-7.5 m are at the lava source, for 20 m thick and bubble-free flows that erupted at their liquidus temperature (1270°C). A substrate containing 25 vol% ice leads to maximum erosion. A lava temperature 20°C below liquidus reduces erosion depths by a factor of ~2.2. If flow viscosity increases with increasing bubble content in the lava, the presence of 30-50 vol % bubbles leads to erosion depths lower than those relative to bubble-free lava by a factor of ~2.4. The presence of 25 vol % ice in the substrate increases erosion depths by a factor of 1.3. Nevertheless, modeled erosion depths, consistent with the emplacement volume and flow duration constraints, are far less than the depth of the channel (~35-100 m). We conclude that thermal erosion does not appear to have had a major role in excavating Athabasca Valles.

Acute HIV infection rarely presents as venous thromboembolism as evidenced by a paucity of medical literature. HIV predisposes to hypercoagulability by a number of pathways.

The risk of mortality is high in burn patients and correlates with age, burn area extent, and sepsis. Immunosuppression has been reported to occur after severe burn. Cytotoxic cells possess specialized granules containing perforin and a group of serine proteases (granzymes). Granzyme A is a serine protease constitutively expressed by gammadelta and NK cells, in agreement with their functional cytolytic potential. In vitro studies have shown that GrA may be released extracellularly during cytotoxic cell degranulation, indicating the activation of cytotoxic cells. The aim of our study was to determine plasma GrA activity in burned patients and to verify if decreased GrA levels were associated with poor prognosis. Specific GrA activity was tested in the plasma of burned and healthy subjects by esterase assay. Plasma GrA was significantly decreased in septic rather than in nonseptic burn patients and in healthy subjects (p < 0.05 and p < 0.001, respectively). At day 3 plasma GrA was significantly lower in nonsurvivor than in survivor septic patients (p < 0.05). The value of 91 mOD showed a sensitivity of 100% and a specificity of 84% in differentiating survivor from nonsurvivor septic patients. Because this is a retrospective study, Granzyme A is not a confirmed predictor of septic outcome after burn, but its determination could give useful information about the development and severity of sepsis., (2010. Published by Elsevier Ltd.)

Therapy with imatinib mesylate is a standard of care for most patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML). However, resistance or intolerance to imatinib develops in a considerable number of patients leading to relapse or discontinuation of treatment. Nilotinib is a rationally designed second-generation tyrosine kinase inhibitor (TKI) with improved affinity and specificity against the BCR-ABL kinase, when compared with imatinib. Considerable efficacy after imatinib failure has been demonstrated in clinical trials leading to nilotinib's current approval as second-line therapy for CML in chronic and accelerated phase (AP). The role of nilotinib as first-line treatment for CML, in combinatorial strategies and in the context of specific BCR-ABL mutations, requires future studies.

Burns are associated with immune suppression and subsequent development of sepsis. Dendritic cells (DCs) are potent antigen-presenting cells that serve as a critical link between the innate and acquired immune systems, and are essential in coordinating the host response to pathogens. Using multicolour flow cytometry, the percentages of LIN(-) DR(+) CD11c(+) myeloid (mDC) and LIN(-) DR(+) CD123(+) plasmacytoid (pDC) subsets were determined in peripheral blood from 32 people (15 septic and 5 non-septic burn victims and 12 age- and gender-matched healthy controls, up to 20 days from injury). Analysis revealed significant reductions in circulating mDCs and pDCs in survivor as well as non-survivor septic cases compared with non-septic cases and controls (p<0.001). These findings suggest that deficiencies in mDCs and pDC subsets are related to sepsis following severe burn, and may contribute to immunosuppression among burn victims.

Burn injury induces a suppression of the Th1 response, which is associated with an increased susceptibility to conditions of infection, morbidity, and mortality. It is well established that cytokines modulate the pathogenesis of burn injury. In this study, plasma levels of interleukin-6 (IL-6) and interleukin-10 (IL-10) were determined in burn patients and correlated with the severity of sepsis. Sixty adult burn patients (total body surface area burned, 8-80%) were included in the study, of whom 34 developed sepsis and 14 died. The nonseptic group consisted of 26 patients. Thirty-one healthy blood donors served as controls. Patients were not treated with antibiotics until sepsis occurred. Plasma samples were collected immediately post-burn and after several days, and cytokine concentrations were determined by ELISA. Within three days, all the patients presented high levels of circulating IL-6, which were significantly higher in septic patients than in nonseptic patients (349 ± 278 vs 63 ± 56 pg/ml, p < 0.001).IL-10 levels were higher in septic patients than in nonseptic patients at all times in our study. The value of 60 pg/ml shows a sensitivity of 92% and a specificity of 93% in the differentiation of survivor from nonsurvivor septic patients. In this study the high value of circulating IL-10 on day 3 suggests that cytokine may discriminate between nonsurvivor septic and survivor septic patients.

Amperometric immunosensor configurations featuring covalently bound anti-biotin antibodies (Ab) embedded into a polylysine (PLL)-single walled carbon nanotube (SWCNT) composite layer were evaluated. Assemblies were made by first oxidizing pyrolytic graphite (PG) electrodes to form surface carboxylic acid groups, to which PLL, SWCNTs and anti-biotin were covalently linked. Incorporating SWCNT into PLL-antibody assemblies improved the amperometric detection limit for biotin (Ag) labeled with horseradish peroxidase to 10 fmol mL(-1). Anti-biotin embedded into the PLL matrix had improved thermal stability and retained its binding ability for biotin after exposure to temperatures of 42 degrees C for up to 3 hours, while the noncrosslinked antibody was inactivated at this temperature in several minutes.

Burn injury is associated with immune suppression and the subsequent development of sepsis. Severe burn injury is associated with depressed immune response, including a functional impairment of Th1 lymphocytes and natural killer cells and a decrease in interferon-a production. Dendritic cells (DCs) are potent antigen-presenting cells and play a key role in T cell activation; they are essential in coordinating the host response to pathogens. Using three-colour flow cytometry, we determined the percentage of lineage-negative LIN-DR+ DCs in burn patients and healthy subjects. The percentages of DCs were lower in the circulation of septic than in nonseptic patients and healthy subjects at all times examined (14 days) after burn injury. In contrast, the DC percentage in nonseptic patients was low at day 1, increased from day 3 to day 10, and reverted to normal levels at day 14. The data from the present study suggest that the DC percentage decreased early after burn injury. In addition, in the presence of severe sepsis, the DC percentage remained lower until day 14. This DC reduction may contribute to the immunosuppression observed after burn injury.

Multiple myeloma is a malignant proliferation of plasma cells that typically occurs in older individuals and is characterized by anemia, renal failure, bone pain, lytic lesions, and a monoclonal gammopathy. This disease is associated with significant morbidity and mortality.

The catalytic alpha and glycoprotein beta subunits of the gastric H/K ATPase are major molecular targets in human and mouse autoimmune gastritis. We have previously shown that the H/K ATPase beta subunit is required for the initiation of mouse gastritis and identified a gastritogenic H/K ATPase beta subunit peptide (H/Kbeta253-277). Here we report the generation of MHC class II-restricted TCR transgenic mice using V(alpha)9 and V(beta)8.3 TCR chains with specificity for the gastritogenic H/Kbeta253-277 peptide. We found an 8-fold reduction in CD4(+) T cells in the thymus of the transgenic mice. Despite the reduction in intrathymic CD4(+) T cells, V(beta)8. 3-expressing T cells comprised the majority (>90%) of peripheral spleen and lymph node T cells. These peripheral T cells retained their capacity to proliferate in vitro to the H/Kbeta253-277 peptide. Using the responsive T cells, we have restricted the gastritogenic T cell epitope to H/Kbeta261-274. Despite the capacity of the peripheral T cells to proliferate in vitro to the peptide, the majority ( approximately 80%, 13 of 16) of transgenic mice remained free of gastritis while a minority (20%, three of 16) spontaneously developed an invasive and destructive gastritis. Our results confirm that H/Kbeta261-274 is a gastritogenic peptide. The data also suggest that CD4 T cell tolerance to the gastritogenic peptide in the transgenic mice is maintained by a combination of intrathymic and peripheral tolerance mechanisms.