BACKGROUND: The safety profile of venom immunotherapy (VIT) is a relevant issue, and considerable differences have been reported in the safety and efficacy of this treatment modality. The primary aim of this study was to evaluate the safety of angiotensin-converting enzyme inhibitors and ß-blockers during VIT. In a second analysis, we evaluated data on premedication and venom preparations and their association with systemic adverse events (AEs) during the up-dosing phase and the first year of the maintenance phase, as well as the outcome of field stings and sting challenges. METHODS: Ours was an open, prospective, observational, multicenter study that recruited 1425 patients, of whom 1342 underwent VIT. RESULTS: Premedication with oral antihistamines was taken by 52.1% of patients during up-dosing and 19.7% of patients during the maintenance phase. Antihistamines had no effect on the frequency of systemic AEs (P=.11), although large local reactions (LLRs) were less frequent (OR, 0.74; 95%CI, 0.58-0.96; P=.02). Aqueous preparations were preferred for up-dosing (73.0%), and depot preparations were used for the maintenance phase (64.5%). The type of venom preparation had no influence on the frequency of systemic AEs or on the effectiveness of VIT (P=.26 and P=.80, respectively), while LLRs were less frequent with depot preparations (P<.001). CONCLUSIONS: Pretreatment with oral antihistamines during VIT significantly reduces the frequency of LLRs but not systemic AEs. All venom preparations were equally effective and did not differ in terms of the frequency of systemic AEs.
- MeSH
- Allergens immunology administration & dosage MeSH
- Histamine Antagonists therapeutic use MeSH
- Adrenergic beta-Antagonists therapeutic use MeSH
- Desensitization, Immunologic * methods adverse effects MeSH
- Child MeSH
- Adult MeSH
- Angiotensin-Converting Enzyme Inhibitors therapeutic use adverse effects MeSH
- Insect Bites and Stings immunology MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Prospective Studies MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Venoms immunology adverse effects therapeutic use MeSH
- Animals MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Observational Study MeSH
Despite the availability of new drugs on the clinics in recent years, drug-resistant epilepsy remains an unresolved challenge for healthcare, and one-third of epilepsy patients remain refractory to anti-seizure medications. Gene therapy in experimental models has emerged as effective treatment targeting specific neuronal populations in the epileptogenic focus. When combined with an external chemical activator using chemogenetics, it also becomes an "on-demand" treatment. Here, we evaluate a targeted and specific chemogenetic therapy, the PSAM/PSEM system, which holds promise as a potential candidate for clinical application in treating drug-resistant epilepsy. We show that the inert ligand uPSEM817, which selectively activates the chloride-permeable channel PSAM4-GlyR, effectively reduces the number of depolarization-induced action potentials in vitro. This effect is likely due to the shunting of depolarizing currents, as evidenced by decreased membrane resistance in these cells. In organotypic slices, uPSEM817 decreased the number of bursts and peak amplitude of events of spontaneous epileptiform activity. Although administration of uPSEM817 in vivo did not significantly alter electrographic seizures in a male mouse model of temporal lobe epilepsy, it did demonstrate a strong trend toward reducing the frequency of interictal epileptiform discharges. These findings indicate that PSAM4-GlyR-based chemogenetics holds potential as an anti-seizure strategy, although further refinement is necessary to enhance its efficacy.
- MeSH
- Action Potentials drug effects MeSH
- Epilepsy physiopathology genetics drug therapy therapy metabolism MeSH
- Genetic Therapy methods MeSH
- Hippocampus * metabolism MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The clinical assessment of microvascular pathologies (in diabetes and in inflammatory skin diseases, for example) requires the visualization of superficial vascular anatomy. Photoacoustic tomography (PAT) scanners based on an all-optical Fabry-Perot ultrasound sensor can provide highly detailed 3D microvascular images, but minutes-long acquisition times have precluded their clinical use. Here we show that scan times can be reduced to a few seconds and even hundreds of milliseconds by parallelizing the optical architecture of the sensor readout, by using excitation lasers with high pulse-repetition frequencies and by exploiting compressed sensing. A PAT scanner with such fast acquisition minimizes motion-related artefacts and allows for the volumetric visualization of individual arterioles, venules, venous valves and millimetre-scale arteries and veins to depths approaching 15 mm, as well as for dynamic 3D images of time-varying tissue perfusion and other haemodynamic events. In exploratory case studies, we used the scanner to visualize and quantify microvascular changes associated with peripheral vascular disease, skin inflammation and rheumatoid arthritis. Fast all-optical PAT may prove useful in cardiovascular medicine, oncology, dermatology and rheumatology.
BACKGROUND: Mucosal visualization during upper gastrointestinal (UGI) endoscopy can be impaired by the presence of foam, bubbles, and mucus. Some UGI endoscopy visibility scales have been proposed but have not undergone multicenter validation. This study aimed to develop and validate the Gastroscopy RAte of Cleanliness Evaluation (GRACE) scale. METHODS: A multicenter, international, cross-sectional study was conducted. The GRACE scale is based on a score from 0 (worst) to 3 (excellent) for esophagus, stomach, and duodenum, for a total ranging from 0 to 9. In phase 1, four expert endoscopists evaluated 60 images twice, with a 2-week interval between rounds; in phase 2, the same 60 images were scored twice by one expert and one nonexpert endoscopist from 27 endoscopy departments worldwide. For reproducibility assessment and real-time validation, the scale was applied to consecutive patients undergoing gastroscopy at each center. RESULTS: On internal validation, interobserver agreement was 0.81 (95 %CI 0.73-0.87) and 0.80 (95 %CI 0.72-0.86), with reliability of 0.73 (95 %CI 0.63-0.82) and 0.72 (95 %CI 0.63-0.81), in the two rounds, respectively. On external validation, overall interobserver agreement was 0.85 (95 %CI 0.82-0.88) and reliability was 0.79 (95 %CI 0.73-0.84). In real-time evaluation, the overall proportion of correct classifications was 0.80 (95 %CI 0.77-0.82). CONCLUSIONS: The GRACE scale showed good interobserver agreement, reliability, and validity. The widespread use of this scale could enhance quality and standardize the assessment of mucosal cleanliness during UGI endoscopy, pushing endoscopists to strive for excellent visibility and reducing the risk of missed lesions.
- MeSH
- Adult MeSH
- Duodenum MeSH
- Gastroscopy * methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Observer Variation * MeSH
- Cross-Sectional Studies MeSH
- Reproducibility of Results MeSH
- Aged MeSH
- Gastric Mucosa MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Validation Study MeSH
BACKGROUND: Adolescents' movement behaviours (MB) vary between schooldays and weekends, potentially impacting health-related quality of life (HRQoL) and well-being. This study aimed to identify transitions between 24-h MB profiles on schooldays and weekends and examine their associations with HRQoL and well-being. METHODS: This is a cross-sectional study of 1070 Czech adolescents (average age: 13.8 years and standard deviation: 2.2 years; 56% girls). Participants wore accelerometers for 7 consecutive days to assess physical activity (PA) of different intensities, sedentary behaviour (SB) and sleep. A subsample of 451 participants provided data on HRQoL, which was measured using the Paediatric Quality of Life Inventory, and 484 provided valid well-being data measured with the 5-item World Health Organisation Well-Being Index. Latent transition analysis was used on the MB variables to identify transitions across MB profiles, and linear regression was used to examine associations between transitions and HRQoL or well-being. RESULTS: Four MB profiles were identified: Excellent (high PA, low SB and high sleep duration), Good (average MB values), Fair (below-average PA and sleep, above-average SB) and Poor (low PA and sleep, high SB). Most adolescents transitioned to less favourable profiles on weekends. Those remaining in the Excellent profile had higher HRQoL than those transitioning to less favourable profiles. Transitions to the Poor profile were associated with the lowest HRQoL and well-being scores. CONCLUSION: This study underscores the dynamic nature of adolescents' MB and the importance of consistent, healthy routines. Interventions optimizing 24-h MB throughout the week and especially on weekends may enhance adolescent HRQoL and well-being, but further evidence from longitudinal and intervention studies is needed. SUMMARY: We observed a contrast in 24-h MB between schooldays and weekends: 29.7% of adolescents were in the Excellent on schooldays, but only 5.8% did so on weekends, while the prevalence of the Poor profile rose from 1.6% on schooldays to 27.7% on weekends. Adolescents who maintained the Excellent profile across the whole week recorded the highest scores for HRQoL and well-being. Moving into the Poor profile on weekend was associated with about 9 points poorer HRQoL and 14 points lower well-being, compared with peers who remained in the Excellent profile. Behaviour change strategies should target the entire week to preserve PA, reduce SB and protect sleep.
- MeSH
- Accelerometry MeSH
- Time Factors MeSH
- Adolescent Behavior * psychology physiology MeSH
- Exercise * psychology physiology MeSH
- Quality of Life * psychology MeSH
- Humans MeSH
- Adolescent MeSH
- Cross-Sectional Studies MeSH
- Sedentary Behavior MeSH
- Sleep physiology MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Although chronic inflammation is implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL), the mechanisms responsible are unknown. We demonstrate that the overexpression of the collagen receptor, DDR1, correlates with reduced expression of spindle checkpoint genes, with three transcriptional signatures of aneuploidy and with a higher frequency of copy number alterations, pointing to a potential role for DDR1 in the acquisition of aneuploidy in DLBCL. In support of this, we found that collagen treatment of primary germinal centre B cells transduced with DDR1, not only partially recapitulated the aberrant transcriptional programme of DLBCL but also downregulated the expression of CENPE, a mitotic spindle that has a crucial role in preventing chromosome mis-segregation. CENPE expression was also downregulated following DDR1 activation in two B-cell lymphoma lines and was lost in most DDR1-expressing primary tumours. Crucially, the inhibition of CENPE and the overexpression of a constitutively activated DDR1 were able to induce aneuploidy in vitro. Our findings identify a novel mechanistic link between DDR1 signalling and chromosome instability in B cells and provide novel insights into factors driving aneuploidy in DLBCL.
- MeSH
- Aneuploidy * MeSH
- B-Lymphocytes metabolism MeSH
- Chromosomal Instability * genetics MeSH
- Lymphoma, Large B-Cell, Diffuse * genetics pathology metabolism MeSH
- Collagen pharmacology MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Discoidin Domain Receptor 1 * genetics metabolism MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Signal Transduction MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
S recidivujícími infekcemi močových cest se v klinickém praxi setkáváme velmi často. Intravezikální aplikace kyseliny hyaluronové napomáhá k obnovení ochranné glykosaminoglykanové vrstvy na povrchu urotelu a přispívá ke snížení počtu recidiv. Tato léčba představuje účinnou možnost zejména u pacientek, u kterých režimová opatření v kombinaci s non-antimikrobiální či antimikrobiální profylaxí nemají dostatečný efekt.
Recurrent urinary tract infections are very common in clinical practice. Endovesical installation of hyaluronic acid helps to restore the protective glycosaminoglycan layer on the surface of bladder urothelium and reduces the frequency of recidives. This treatment represents an effective option especially for patients in whom regime measures in combination with non-antimicrobial or antimicrobial prophylaxis has been unsuccessful.
BACKGROUND: Peptic ulcer perforation (PUP) is a surgical emergency and life-threatening complication affecting 2-10% of peptic ulcer disease (PUD) patients. Delayed diagnosis and surgical management are associated with significant morbidity and mortality. This study assessed the magnitude and outcome of PUP among patients operated on at two public hospitals in Jigjig town, Ethiopia. METHODS: A 3-year hospital-based retrospective cross-sectional study was conducted on 130 patients operated for PUP at the study hospitals in Jigjig from April 1st, 2018, to July 30th, 2021. Data were collected from medical records. Bivariate analysis identified key factors impacting outcomes in PUP patients. RESULTS: The cohort had a male-to-female ratio of 8.7:1, and a mean age of 38 ± 13.3 years, with 48.8% smokers and 56.6% chat chewers. Duodenal perforations accounted for 93.7% of cases, with post-operative complications in 29.1% and an in-hospital mortality rate of 5.5%. Significant predictors of morbidity and mortality included advanced age (AOR 23.88), comorbidities (AOR 26.80), pre-operative hypotension (AOR 32.33), and delayed hospital presentation (AOR 30.10). CONCLUSIONS: Male predominance, younger age, high smoking and chat chewing rates, and primarily duodenal perforations are common in perforated peptic ulcer cases. Advanced age, comorbidities, pre-operative hypotension, and delayed hospital presentation significantly increase postoperative complications and mortality, emphasizing the need for timely intervention and targeted public health measures to improve patient outcomes. Early intervention and careful management of comorbidities are crucial to improve survival and reduce complications in patients with PUP.
- MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Hospital Mortality trends MeSH
- Peptic Ulcer Perforation * mortality surgery epidemiology MeSH
- Cross-Sectional Studies MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Ethiopia MeSH
Compounds in sand fly saliva elicit specific immune responses that may play a role in the establishment of canine Leishmania infection. Although canine antibodies to anti-sand fly saliva antigens have been extensively studied, little is known about cellular immune responses against Phlebotomus perniciosus salivary proteins. This study aimed to explore humoral and T-cell-mediated immunity against P. perniciosus salivary proteins in dogs (n = 85) from Mallorca (Spain), a leishmaniosis-endemic area, and find correlations with demographic (age, sex, and breed) and parasite-specific immunological parameters. Anti-sand fly saliva IgG was examined using a P. perniciosus whole salivary gland homogenate (SGH) ELISA and recombinant salivary protein rSP03B ELISA. Interferon gamma (IFN-γ) release whole blood assays with L. infantum soluble antigen (LSA), SGH, and rSP03B were also performed. Positive correlations were found between IgG levels in the SGH and rSP03B tests and between concentrations of SGH IFN-γ and rSP03B IFN-γ. While concentrations of SGH IFN-γ and rSP03B IFN-γ were low and produced only by a minority of dogs (less than 20%), high levels and frequencies of LSA IFN-γ as well as anti-saliva IgG for SGH and rSP03B were detected in a majority of dogs (61% and 75%, respectively). LSA IFN-γ levels were positively correlated with age and Leishmania-specific antibodies. In conclusion, dogs from a leishmaniosis-endemic area presented high humoral immunity against P. perniciosus salivary proteins, but their cellular immunity to these proteins was low and less frequent.
- MeSH
- Immunity, Cellular * MeSH
- Endemic Diseases MeSH
- Insect Proteins * immunology MeSH
- Immunity, Humoral * MeSH
- Immunoglobulin G blood immunology MeSH
- Interferon-gamma MeSH
- Leishmaniasis * immunology veterinary epidemiology MeSH
- Dog Diseases * immunology parasitology epidemiology MeSH
- Phlebotomus * immunology MeSH
- Dogs MeSH
- Salivary Proteins and Peptides * immunology MeSH
- T-Lymphocytes * immunology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Dogs MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Spain MeSH
Heart rate variability (HRV) analysis is a noninvasive tool that allows cardiac autonomic control to be assessed. Numerous studies have reported HRV measurements, related changes, and clinical implications for heart failure patients. This review evaluates HRV characteristics in congestive heart failure (CHF), focusing on different recording durations and the diagnostic and prognostic values using HRV measurements. The recording durations are classified as (a) ultra short-term (substantially shorter than 5 minutes), (b) short-term (5 minutes), and (c) long-term (nominal 24 hours). This review of HRV diagnostic and prognostic significance in CHF focuses on time- and frequency-domain HRV measures that have previously been extensively studied. Reported studies document that HRV is lowered in CHF patients, whereas HRV increases may indicate disease improvement, e.g., in CHF patients undergoing cardiac resynchronization therapy. Reduced HRV has consistently been found to be associated with all-cause mortality in CHF patients. However, different thresholds of long-term HRV indices have been proposed as mortality predictors; meanwhile, findings related to the prediction of other cardiac events, including sudden cardiac death, remain inconsistent. HRV is reduced in CHF patients, but the use of HRV as a risk factor remains controversial, with no established cut-off values. HRV does not provide a clinically useful prediction of sudden cardiac death or other cardiac events in CHF patients. Thus, we advocate standardization of investigative protocols based on the existing time- and frequency-domain HRV indices rather than further developing more complex methods. Short-term recordings are preferable for clinical application and measurement reproducibility; thus, future investigations should focus on the following key questions: 1. How to design standardized short HRV tests suitable for outpatient settings? 2. Which HRV indices should be preferred, and what are their optimal prognostic thresholds? 3. How to standardize HRV assessment conditions to minimize external influences?
- Publication type
- Journal Article MeSH
- Review MeSH
