The emergence of circulating activated autoreactive Dsg3-specific Tfr cells is associated with long-term efficacy of RTX in PV patients.

BACKGROUND: Pemphigus vulgaris (PV) is characterized by autoantibodies targeting keratinocytes adhesion proteins desmoglein (Dsg) 1 and 3, and by the HLA-DRB1-0402 predisposition allele. Treatment using rituximab (RTX) combined with short-term corticosteroids (CS) allows disease control and long-lasting remission. OBJECTIVE: The principal aim of this study is to evaluate the impact of RTX on the circulating subpopulations of Dsg-3-specific T lymphocytes that specifically regulate B cell responses: follicular helper (Tfh) and follicular regulatory T (Tfr) lymphocytes. METHODS: Using the HLA-DRB1-0402 tetramer loaded with the Dsg-3 immunodominant peptide, we analysed by flow cytometry the frequency, the polarisation and the activation status of blood Dsg-3-specific follicular T cell populations at baseline, Month 6 and long-term follow-up (Month 60-90) from PV patients. RESULTS: At baseline, we observed a predominance of Tfh1* and Tfh17 subsets and an underrepresentation of the Tfh2 subset among autoreactive Dsg-3-specific Tfh cells as compared with non-autoreactive Tfh cells. RTX treatment induced a decrease of autoreactive Tfh cells with no effect on their polarisation during patients' follow-up. In parallel, we observed the emergence of a Dsg-3-specific Tfr subpopulation with a significant overexpression of the surface activation markers PD1, ICOS, and CD25 that was not observed at the surface of autoreactive Tfh and non-autoreactive Tfr cells of the same PV patients. In contrast, a very few Dsg-3 specific Tfr cells were observed in PV patients treated with CS alone. CONCLUSION: Here we show that the emergence of circulating autoreactive Dsg-3-specific Tfr cells is associated with the long-term efficacy of RTX in PV patients.

An in vitro evaluation of endodontic sealers and an antibiotic to assess their antimicrobial effect against Enterococcus faecalis.

Objective: This study aimed to compare the antimicrobial effect of three endodontic sealers (AH Plus, Mineral trioxide aggregate [MTA] Fillapex, and BioRoot RCS) with and without amoxicillin against E. faecalis. Methodology: Amoxicillin, equivalent to 10% of the sealers' total weight, was mixed with the sealers. Another batch was prepared without amoxicillin. The direct contact test (DCT) and the agar diffusion test were used to assess the antibacterial effect. Results were analysed using one-way analysis of variance (ANOVA), the F-test, and the Kruskal-Wallis test. Results: AH Plus significantly suppressed E. faecalis without the addition of amoxicillin in the DCT (p = 0.011), while in the agar diffusion test, BioRoot RCS had a larger inhibition zone than the control (p < 0.001). When amoxicillin was added to the sealers, AH Plus (p = 0.003) and MTA Fillapex (p = 0.042) reduced E. faecalis growth. In contrast, all three sealers showed larger inhibition zones than the control (p = 0.001), with AH Plus displaying a larger inhibition zone than MTA Fillapex (p = 0.042) and BioRoot RCS (p = 0.032). Conclusions: It was thus concluded that the addition of amoxicillin to endodontic sealers enhances their antimicrobial activity against E. faecalis.

An evaluation of 'ChatGPT' Compared to Dermatological Surgeons' Choice of Reconstruction of Mohs Surgical Defects.

BACKGROUND: ChatGPT® (OpenAI; California, USA) is an open-access chatbot developed using artificial intelligence (AI) that generates human-like responses. OBJECTIVE: To evaluate the ChatGPT-4's concordance with three dermatologic surgeons on reconstructions for dermatological surgical defects. METHODS: A total of 70 cases of non-melanoma skin cancer treated with surgery were obtained from clinical records for analysis. A list of 30 reconstruction options was designed by the main authors which included primary closure, secondary skin closure, skin flaps and skin grafts. Three blinded dermatologic surgeons, along with ChatGPT-4, were asked to select two reconstruction options from the list. RESULTS: Seventy responses were analyzed using Cohen's kappa looking for concordance between each dermatologist and ChatGPT. The level of agreement among dermatologic surgeons was higher compared to that between dermatologic surgeons and ChatGPT, highlighting differences in decision-making. In the best reconstruction technique, the results indicated a fair level of agreement among the dermatologists ranging between κ 0.268 and 0.331. However, the concordance with ChatGPT-4 and the dermatologists was slight with κ values from 0.107 to 0.121. In the analysis of the second-choice options, the dermatologists showed slight agreement. In contrast, the level of concordance between ChatGPT-4 and the dermatologists was below chance. CONCLUSIONS: As anticipated, this study reveals variability in medical decisions between dermatologic surgeons and ChatGPT. Although these tools offer exciting possibilities for the future, it's vital to acknowledge the risk of inadvertently rely on non-certified AI for medical advice.

A Persistent Dark Macule on the Hand of a Hispanic Patient.

A 38-year-old Hispanic man without comorbidities presented to our dermatology clinic for the evaluation of an asymptomatic dark macule on his left hand, which had gradually grown since he was a child. The hyperpigmentation involved the dorsum and palm (Figure 1). The patient was right-handed and denied previous trauma, inflammation, occupational exposure to chemicals, or using any medications. During physical examination, no other similar pigmentation was found on the rest of his body. An incisional biopsy of the left palm was performed (Figure 2). The histopathology revealed the presence of spindle-shaped cells with melanin granules in the superficial and middle dermis, surrounding the blood vessels, and between collagen bundles, which are findings compatible with acquired dermal melanocytosis (1,2). On dermoscopy, we found a pattern of regular pigment with a gray-brown tone and whitish spots within. We discussed the benignity of this rare entity with the patient, and he decided not to pursue treatment. Acquired dermal melanocytosis (ADM) is a rare condition, with isolated presentation on the hand and with less than 10 cases reported (1). Dermal melanocytosis includes several benign pigmented lesions histologically characterized by the presence of melanocytes in the dermis, which are spindle-shaped dendritic cells containing brown melanin pigment. Melanocytes can also be identified with immunoperoxidase staining for S100 and Fontana-Masson melanin stain (2). The physiopathology of ADM remains unclear, but it has been proposed that it involves reactivation of latent dermal melanocytes due to external factors such as trauma, inflammation, chemical exposure, sunlight, drugs, and hormonal treatment with estrogen and/or progesterone (3). ADM with hand involvement usually appears in the Asian population without sex predilection. The lesions develop in adolescence or young adulthood and tend to affect both hands and other body areas such as the face or the legs; there have also been two reported cases in the Hispanic population (both by Fitzpatrick III) (3,4). ADM must be differentiated from ectopic Mongolian spots, plaque-type blue nevi, tinea nigra, or other pigmented neoplasms. A biopsy is mandatory to establish a proper diagnosis. Ectopic Mongolian spots and plaque-type blue nevi are both congenital dermal melanocytoses that may present as bluish macules on the hand. However, these lesions show deep and more widely scattered distribution of melanocytes (1). There have also been some reports of malignant melanoma and acquired dermal melanocytosis that appeared on congenital nevus spilus (5). ADM is a benign condition, and reassurance should be offered to these patients.

Antimicrobial effectiveness of root canal sealers against Enterococcus faecalis.

We evaluated four root canal sealers to determine their antimicrobial effectiveness against E. faecalis. The direct contact test was used to measure the effectiveness of the study materials and close contact between bacteria on the kinetics of bacterial growth. The agar diffusion test (ADT) was also performed for comparison. Using one-way ANOVA and the F-test, significant differences between the sealers were confirmed. Whereas BioRoot endodontic sealer had an antimicrobial effect statistically similar to the zinc oxide-eugenol control (p=.99), EndoSequence sealer and AH Plus sealer both had a significantly lower antimicrobial effect than the control (p=.0000266 and p=.0000068, respectively).

Ageing of T-dependent B cell responses.

The human immune system is in continuous interaction with environmental factors (pathogens, exercise, stress, pollutants, diet, vaccines, and therapeutics) that condition its efficiency by promoting or moderating multiple immune mechanisms. While the deleterious impact of external factors can be avoided or limited, the immune system itself grows weaker with age. Immune cells persist in the elderly, and the observed decline of cellular immunity is related to cellular senescence. Immunosenescence, which affects both T and B cells, erodes lymphocyte-dependent responses to vaccines and pathogens. Germinal centers (GCs), the organized lymphoid structures where B cells engage in affinity maturation, are regulated by follicular helper (Tfh) and follicular regulatory (Tfr) T cells, the major T cell components of GCs. This review discusses how age-related changes affect Tfh and Tfr cells as key components of B cell immunity, and how they ultimately shape the response of the ageing immune system to vaccines and infectious challenges.

A high glucose diet induces autophagy in a HLH-30/TFEB-dependent manner and impairs the normal lifespan of C. elegans.

A high-glucose diet (HGD) is associated with the development of metabolic diseases that decrease life expectancy, including obesity and type-2 diabetes (T2D); however, the mechanism through which a HGD does so is still unclear. Autophagy, an evolutionarily conserved mechanism, has been shown to promote both cell and organismal survival. The goal of this study was to determine whether exposure of Caenorhabditis elegans to a HGD affects autophagy and thus contributes to the observed lifespan reduction under a HGD. Unexpectedly, nematodes exposed to a HGD showed increased autophagic flux via an HLH-30/TFEB-dependent mechanism because animals with loss of HLH-30/TFEB, even those with high glucose exposure, had an extended lifespan, suggesting that HLH-30/TFEB might have detrimental effects on longevity through autophagy under this stress condition. Interestingly, pharmacological treatment with okadaic acid, an inhibitor of the PP2A and PP1 protein phosphatases, blocked HLH-30 nuclear translocation, but not TAX-6/calcineurin suppression by RNAi, during glucose exposure. Together, our data support the suggested dual role of HLH-30/TFEB and autophagy, which, depending on the cellular context, may promote either organismal survival or death.

The MXL-3/SBP-1 Axis Is Responsible for Glucose-Dependent Fat Accumulation in C. elegans.

Chronic exposure to elevated glucose levels leads to fatty acid accumulation, which promotes the development of metabolic diseases such as obesity and type 2 diabetes. MXL-3 is a conserved transcriptional factor that modulates the inhibition of lipolysis in Caenorhabditis elegans. However, the role of MXL-3 in lipid metabolism during nutrient excess remains unknown. We hypothesized that inhibition of MXL-3 prevents glucose-dependent fat accumulation. Nematodes from wild-type N2, MXL-3::GFP and sbp-1 or mxl-3 null strains were grown on standard, high glucose or high glucose plus metformin plates for 24 h. Using laser-scanning confocal microscopy, we monitored the glucose-induced activation of MXL-3 labeled with GFP (MXL-3::GFP). Lipid levels were determined by Oil Red O (ORO) staining and gas chromatography/mass spectrometry, and gene expression was assessed by qRT-PCR. We found that high glucose activated MXL-3 by increasing its rate of nuclear entry, which in turn increased lipid levels via sterol regulatory element-binding protein (SBP-1). This activated critical genes that synthesize long chain unsaturated fatty acids (MUFAs and PUFAs) and repress lipolytic genes. Interestingly, the anti-diabetic drug metformin inhibited MXL-3 activation and subsequently prevented glucose-dependent fat accumulation. These findings highlight the importance of the MXL-3/SBP-1 axis in the regulation of lipid metabolism during nutritional excess and provide new insight into the mechanism by which metformin prevents lipid accumulation. This study also suggests that inhibition of MXL-3 may serve as a potential target for the treatment of chronic metabolic diseases, including obesity, type 2 diabetes, and cardiovascular disease.

Implants failures related to endodontic treatment. An observational retrospective study.

OBJECTIVE: The aim of the study was to analyze potential etiological risk factors that constitute a complex problem in the clinical management of peri-implantitis. MATERIALS AND METHODS: An observational retrospective study was conducted to describe the possible effect of lesions of origin pulpar and/or periapical success or failure of the implant. The sample consisted of review of 800 implants, of which 500 were conducted at the Faculty of Dentistry of the UANL and 300 private clinics of Maxillofacial surgeons experienced in the placement of those who reside in Monterrey, Mexico. Five hundred and eighty cases correspond to female patients while that 220 patients of the male gender. The age of patients at the time of placing the implant ranged from 28 to 81 years. RESULTS: Of 800 study subjects who underwent dental implant treatments, 200 cases (25%) were detected which presented endodontic failure prior and/or adjacent to the placement of the implant. The 50.41% had peri-implantitis, recording 62 cases in the Faculty and 18 cases (23.38%) in private clinics, finding that there was a statistically significant difference between the presence and absence of peri-implantitis in terms of failed endodontic prior and/or adjacent to the placement of the implant. CONCLUSIONS: Within the limitations of this observational retrospective study, it could be concluded that the development of inflammatory changes mediated by the presence of remnant bacteria surrounding hard tissues adjacent to implants might induce late failures of implants, and potentially trigger pathological features of apical peri-implantitis.

Melatonin: bone metabolism in oral cavity.

Throughout life, bone tissue undergoes a continuous process of resorption and formation. Melatonin, with its antioxidant properties and its ability to detoxify free radicals, as suggested by Conconi et al. (2000) may interfere in the osteoclast function and thereby inhibit bone resorption, as suggested by Schroeder et al. (1981). Inhibition of bone resorption may be enhanced by a reaction of indoleamine in osteoclastogenesis. That it has been observed melatonin, at pharmacological doses, decrease bone mass resorption by suppressing through down regulation of the RANK-L, as suggested by Penarrocha Diago et al. (2005) and Steflik et al. (1994). These data point an osteogenic effect towards that may be of melatonin of clinical importance, as it could be used as a therapeutic agent in situations in which would be advantageous bone formation, such as in the treatment of fractures or osteoporosis or their use as, a bioactive surface on implant as suggested by Lissoni et al. (1991).

Imagery of errors in typing.

Using a typing task we investigated whether insufficient imagination of errors and error corrections is related to duration differences between execution and imagination. In Experiment 1 spontaneous error imagination was investigated, whereas in Experiment 2 participants were specifically instructed to imagine errors. Further, in Experiment 2 we manipulated correction instructions (whether or not to correct errors) and controlled for visual feedback in executed typing (letters appearing on the screen or not). Participants executed and imagined typing proverbs of different lengths. Errors and error corrections explained a significant amount of variance of execution minus imagination differences in Experiment 1, and in Experiment 2 when participants were instructed to correct errors, but not when participants were instructed not to correct errors. In Experiment 2 participants corrected and reported more errors with than without visual feedback. However, the relation between execution-imagination duration differences and errors and error corrections was unaffected by visual feedback. The types of errors reported less often in imagination than in execution were related to processes in typing execution. We conclude that errors and error corrections are not spontaneously imagined during motor imagery, and that even when attention is drawn to their occurrence only some are imagined. This may be due to forward models not predicting all aspects of an action, imprecise forward models, or a neglect of monitoring error signals during motor imagery.

Klebsiella pneumoniae y K. oxytoca aisladas de niños con diarrea: adherencia y citotoxicidad en líneas celulares / Klebsiella pneumoniae and K. oxytoca isolates from children diarrhea: adherence and cytotoxicity in cellular lines

La capacidad de adherencia y citotoxicidad de cepas de Klebsiella pneumoniae y Klebsiella oxytoca sobre líneas celulares intestinales HT-29 y CaCo-2, fue medida a partir de cepas aisladas de heces de niños de 0 a 5 años cuyas principales características son la pobreza y desnutrición, los cuales son factores importantes en problemas de salud publica en Venezuela. Cinco de las seis cepas estudiadas son adherentes y citotóxicas para ambas líneas celulares. Estos resultados confirman que las cepas de K. pneumoniae y K. oxytoca presentan dos mecanismos de enteropatogenicidad: uno de adherencia específico y otro de citotoxicidad en líneas celulares intestinales HT-29 y CaCo-2.

¿Cuáles son los conocimientos del personal de enfermería sobre la atención y el manejo de pacientes con VIH/SIDA en la sala de Internados del Instituto de Medicina Tropical?

Estudio descriptivo de una muestra que representa el 79 por ciento del personal de enfermería del área Internado Adulto del Instituto de Medicina Tropical. Presenta a la enfermedad con sus características, diagnóstico y tratamiento. Describe las estrategias laborales de las profesionales y auxiliares de enfermería para la atención del enfermo