Toll-like receptor 9 polymorphisms in brazilian patients with systemic lupus erythematosus: a pilot study

Toll-like receptor 9 (TLR9) is an important component of the innate immune system and have been associated with several autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). The aim of this study was to investigate polymorphisms in TLR9 gene in a Brazilian SLE patients group and their association with clinical manifestation, particularly Jaccoud’s arthropathy (JA). We analyzed DNA samples from 204 SLE patients, having a subgroup of them presenting JA (n=24). A control group (n=133) from the same city was also included. TLR9 single nucleotide polymorphisms (SNPs) (−1237 C>T and +2848 G>A) were identified by sequencing analysis. The TLR9 gene genotype frequency was similar both in SLE patients and the control group. In the whole SLE population, an association between the homozygosis of allele C at position −1237 with psychosis and anemia (p < 0.01) was found. Likewise, the homozygosis of allele G at position +2848 was associated with a discoid rash (p < 0.05). There was no association between JA and TLR9 polymorphisms. These data show that TLR9 polymorphisms do not seem to be a predisposing factor for SLE in the Brazilian population, and that SNPs are not associated with JA.

Changes in symptoms of dry eyes in health professionals with increased duration of wearing the mask

: In normal population and patient, the significant increase in dry eyes manifestations have been observed. Similarly, aggravated symptoms and complaints of dryness have also been observed in clinical and hospital staff by using a face mask for an extended time period. The purpose of the study was to observe the association between symptoms of dry eyes and the duration of using masks in health professionals.: An unspecified questionnaire was distributed using Google Forms through different social media platforms, asking each respondent to contribute to the survey. Data were collected from December 2021 to January 2021. Statistical analysis was performed using SPSS software. Statistical significance was considered if p-value was less than 0.05. A total of 39 responses was included for analysis in the study. There was a positive correlation between the frequency of the symptoms of dryness and the duration of using the mask. Similarly, the severity of the symptoms for dry eyes was strongly correlated with an increase in the frequency of symptoms for dry eyes.The finding reflects that the frequency of the dryness along with the severity will increase with the increase in the duration of wearing a mask. Moreover, it also suggests that cloth mask is the probable predisposing factor for the increase in the dry eye symptoms in this study.

Dipeptidyl-peptidase IV inhibitor (DPP4i) confers increased odds of bullous pemphigoid even years after drug initiation

The timing pattern in which dipeptidyl-peptidase IV inhibitors (DPP4i) confer the risk of bullous pemphigoid (BP) is unknown. To investigate the odds of BP following exposure to DPP4i and to perform a duration-response analysis evaluating the risk of BP in relation to the duration of exposure to the culprit drug. A population-based nested case–control study was performed comparing diabetic patients with BP (n = 1458) with age-, sex- and ethnicity-matched diabetic control subjects (n = 6051) with respect to the prevalence of exposure to DPP4i. Adjusted odds ratios (ORs) were estimated by logistic regression. Overall exposure to DPP4i was associated with an 80% increase in the odds of subsequent BP (OR, 1.81; 95% CI, 1.46–2.08; P < 0.001). In an intraclass analysis, the odds of BP were increased in association with vildagliptin (OR, 3.40; 95% CI, 2.69–4.29; P < 0.001) and sitagliptin (OR, 1.56; 95% CI, 1.33–1.84; P < 0.001). In a duration-response analysis, the highest likelihood of BP was found 1–2 years after commencing the drug (OR, 2.66; 95% CI, 1.97–3.59; P < 0.001). The odds of BP were increased across all time periods and retained its statistical significance even ≥ 6 years after the drug initiation (OR, 1.44; 95% CI, 1.09–1.91; P = 0.011). Relative to other diabetic patients with BP, patients with DPP4i-associated BP were more likely to be admitted to inpatient dermatologic wards (OR, 1.66; 95% CI, 1.30–2.13; P < 0.001) and had higher mean(SD) numbers of outpatient dermatologist visits (14.7[14.8] vs. 12.3[13.2], respectively; P = 0.006). DPP4i should be suspected as a predisposing factor for BP even numerous years after the drug initiation.

Improved Outcomes with Concurrent Instrumentation and Fusion of the Sacroiliac Joint in Patients with Long Lumbosacral Constructs

Study Design Retrospective Cohort Study Objective Spinal fusion, specifically constructs connected to pelvic bones, has been consistently reported as a predisposing factor to sacroiliac joint (SIJ) pain. The aim of this study is to compare SIJ outcomes in patients with constructs to the pelvis following instrumentation vs instrumentation plus fusion of the SIJ. Methods Data of study subjects was extracted from a prospectively maintained database as well as retrospectively collected from records at a tertiary academic medical center in the United States between 2018 and 2020. Results A cohort of 103 patients was divided into 2 groups: 65 in Group 1 [S2AI screw without fusion device] and 38 in Group 2 [S2AI screw with fusion device]. None of the patients in Group 2 developed postoperative SIJ pain compared to 44.6% in Group 1. Sacroiliac joint fusion occurred in all Group 2 but none of Group 1 patients. The postoperative Visual Analogue Scale (VAS) for lower extremity (LE) pain (.8 vs .5; P = .03) and postoperative Oswestry Disability Index (ODI) (18.7 vs 14.2; P < .01) were significantly higher in Group 1. The rate of distal junctional break, failure, and/or kyphosis (DJBFK) and time to DJBFK were not significantly different between the two groups, and the rate of DJBFK did not change in the presence of multiple covariates. Conclusion The SIJs carry the heavy load of long lumbosacral fusion constructs extending to the pelvis. Simultaneous SIJ instrumentation and fusion decreases the risk of disability, prevents the development of postoperative SIJ pain, and may also protect the S2AI screw from loosening and failure.

Global Adversities, the Media, and Mental Health

Global communities are currently confronted with a number of complex problems and threats, the reality of which is amplified by the media. These environmental and socio-political stressors have been accompanied by the spread of problematic psychological and behavioural tendencies, such as the growing polarisation of opinions and values, online radicalisation and extremism, deepening xenophobia and nationalism, the proliferation of irrational beliefs and conspiracy theories, and resistance to rational public policy measures. Here we argue that although they fall outside the scope of psychopathology, they nevertheless currently constitute a major challenge for psychiatry as a research domain and a clinical practise. To substantiate this claim, we outline the mechanisms by which media-transmitted stressors impact mental well-being and possibly psychopathology. The common denominator of these global problems and the media's construction of reality is the increase in uncertainty, unpredictability, and uncontrollability, which prompts defensive responding and, in predisposed individuals, functions as a potent source of chronic stress. These contribute to cognitive inflexibility, a strong predisposing factor for the development of rigid beliefs and attitudes, which to varying degrees underlie the adverse psychological and behavioural tendencies mentioned above. We suggest that the tightening of beliefs and ideas that is the result of cognitive rigidity may correspond to the clinical characteristics of induced delusional disorder. This can be seen as a (ultimately maladaptive) defensive strategy for coping with a high degree of uncertainty and unpredictability. We conclude by briefly outlining the possible ways in which psychiatry can face this challenge.

Machine Learning and In Vitro Chemical Screening of Potential α-Amylase and α-Glucosidase Inhibitors from Thai Indigenous Plants

Diabetes mellitus is a major predisposing factor for cardiovascular disease and mortality. α-Amylase and α-glucosidase enzymes are the rate-limiting steps for carbohydrate digestion. The inhibition of these two enzymes is clinically used for the treatment of diabetes mellitus. Here, in vitro study and machine learning models were employed for the chemical screening of inhibiting the activity of 31 plant samples on α-amylase and α-glucosidase enzymes. The results showed that the ethanolic twig extract of Pinus kesiya had the highest inhibitory activity against the α-amylase enzyme. The respective ethanolic extract of Croton oblongifolius stem, Parinari anamense twig, and Polyalthia evecta leaf showed high inhibitory activity against the α-glucosidase enzyme. The classification analysis revealed that the α-glucosidase inhibitory activity of Thai indigenous plants was more predictive based on phytochemical constituents, compared with the α-amylase inhibitory activity (1.00 versus 0.97 accuracy score). The correlation loading plot revealed that flavonoids and alkaloids contributed to the α-amylase inhibitory activity, while flavonoids, tannins, and reducing sugars contributed to the α-glucosidase inhibitory activity. In conclusion, the ethanolic extracts of P. kesiya, C. oblongifolius, P. anamense, and P. evecta have the potential for further chemical characterization and the development of anti-diabetic recipes.

Compare the management of granular myringitis: carbon dioxide laser and caustic agent cauterization

Background and Objectives Granular myringitis is troublesome for otologist because uncertain etiology and often been overlooked due to vague clinical symptoms and signs. The ideal treatment is elusive. Our study was to investigate the clinical characteristics of granular myringitis and analyzing the effect of the two different strategies, including carbon dioxide laser (CO2 laser) and caustic agent cauterization to manage granular myringitis. Study Design: Retrospective review Subjects and Methods One hundred and thirty patients with granular myringitis receiving treatment at a single medical center from July 2009 to January 2018 were enrolled. We retrospectively reviewed the charts and surgical records. The main two different strategies to manage focal refractory granular myringitis were analyzed, including carbon dioxide laser and caustic solution. We also recorded the clinical course and determine which strategy is better. Results One hundred and thirty patients with granular myringitis were enrolled. 47/130 (36.1%) had previous otologic procedures. Frequent ototrrhea is the most common symptom (66.1%). Posterior-inferior quadrant is the most common site of involvement (58%). The successful rate of CO2 laser, caustic agent were 94.9% and 79.2%. The recurrence rate was comparable between CO2 laser and caustic agent. No major complication was found in either individual group. Conclusion: Otologic procedure may be a predisposing factor of focal chronic myringitis. Ear drops had poor efficacy compared to other treatments. It can be apply only on minor and fresh symptom cases. In this study, we suggest CO2 laser can be the first line treatment, especially for the troublesome or refractory GM cases, which had the higher successful rate and less complication comparing to caustic agent cauterization.

Dual fates of exogenous tau seeds: lysosomal clearance vs. cytoplasmic amplification

Tau assembly propagation from the extracellular to intracellular space of a cell may underlie neurodegenerative tauopathies. The first step involves tau binding to heparan sulfate proteoglycans on the cell surface, followed by macropinocytosis. Pathological tau assemblies are thought to exit the vesicular compartment as seeds for replication in the cytoplasm. Tau uptake is highly efficient, but only ~1-10% of cells that take up aggregates exhibit seeding. To investigate the basis for this observation, we used fluorescently tagged full-length (FL) tau fibrils added to native U2OS cells, and biosensor cells expressing FL tau or repeat domain fused to mClover (Clo). FL tau-Clo bound tubulin, but seeds triggered its aggregation in multiple locations simultaneously in the cytoplasm, generally independent of visible exogenous aggregates. Most exogenous tau trafficked to the lysosome, but imaging revealed a small percentage that slowly and steadily accumulated in the cytosol. Intracellular expression of Gal3-mRuby, which binds intravesicular galactosides and forms puncta upon vesicle rupture, revealed no evidence of vesicle damage following tau exposure. In fact, most seeded cells had no evidence of lysosome rupture. However, live cell imaging indicated that cells with pre-existing Gal3-positive puncta exhibited seeding at a slightly higher rate than the general population, indicating a potential role for vesicle instability as a predisposing factor. Clearance of tau seeds occurred rapidly in both vesicular and cytosolic fractions. Bafilomycin inhibited vesicular clearance, whereas MG132 inhibited cytosolic clearance. Tau seeds that enter the cell thus have at least two fates: lysosomal clearance that degrades most tau, and entry into the cytosol, where seeds replicate, and are cleared by the proteasome.

Oral Health Status of Children Living with Type 1 Diabetes Mellitus

Background: Diabetes is a well-known predisposing factor for oral diseases, so prevention in an early age is mandatory. Objective: To provide oral screening for children living with type 1 diabetes. We aimed to investigate the oral and general health indexes of T1DM children and compare these data to healthy siblings and controls. Methods: In this cross-sectional study, 120 DM patients and 78 siblings, thereafter 80 DM children and 95 controls, took part. A detailed questionnaire, panoramic radiographs, and lateral cephalograms were obtained in every orthodontic consultation. We used Pearson’s chi-square test for statistical analysis and compared the data of the study and control groups. Results: The oral health values of DM children were significantly better (DMF-T 0.83–1.3) than the national average (3.8–4.5). A total of 75% (n = 60) of the children needed orthodontic treatment for orthodontic or skeletal anomalies. The prevalence of skeletal anomalies was significantly (p < 0.05) higher among patients with diabetes mellitus (DM) than in the control group. The frequency of coeliac disease was significantly elevated compared to any literature data (1–3.5%) in the study (15%) and in the control sibling group (13%). Conclusions: Co-morbidities such as CD should get more attention as a prognostic factor for a future higher incidence of diabetes. T1DM children can be motivated and health-conscious patients with excellent oral hygiene and dental status. Orthodontic treatment can help eliminate the oral complications of DM. Special diabetes ambulances may help provide oral care for patients with DM.

Therapeutic Exercise and Conservative Injection Treatment for Early Knee Osteoarthritis in Athletes: A Scoping Review

Background and Objectives: Recent evidence highlighted a higher prevalence of knee osteoarthritis (kOA) among young and former ex-professional athletes. Although the practice of a highly demanding sport is considered a predisposing factor for the knee joint cartilage degeneration, articular cartilage seems to positively respond to a moderate load increase. We aim to investigate recent evidence on the conservative management of early kOA in athletes, with a particular emphasis on therapeutic exercise and injection treatment, in order to highlight whether there are any indications that can influence clinical and rehabilitation practice. Materials and Methods: A scoping review was conducted, screening MEDLINE and PEDro databases for studies published over the past twenty years on the topic. Studies in English, with accessible abstracts, were included in the review. The PICO framework was used (P—patient: athletes, I—Intervention: conservative treatment with therapeutic exercise or injection therapies, C—Comparison: not needed, O—Outcomes: clinical outcomes). Clinical trials, randomized controlled trials, and longitudinal studies were considered. Results: Four studies were finally included in the review. Therapeutic exercise seems to have beneficial effects on prevention of cartilage degeneration, on pain reduction, and on physical function enhancement. On the other hand, in mild to moderate stages of kOA the intra-articular viscosupplementation with Hyaluronic Acid showed a medium to long-term improvement in joint pain and function. The Platelet Rich Plasma treatment also showed a significant improvement in pain and function up to 12 months. Conclusions: Despite the heterogeneity of the studies considered, a multimodal treatment combining therapeutic exercise and moderate aerobic activity (such as running) should be indicated to prevent kOA development. In cases of symptomatic kOA it may be indicated to add minimally invasive injection therapy that seems to contribute to the improvement of motor function and symptomatology.