OBJECTIVES: This study of 331 primary brain abscess (PBA) patients aimed to understand infecting agents, predisposing factors, and outcomes, with a focus on factors affecting mortality. METHODS: Data were collected from 39 centers across 16 countries between January 2010 and December 2022, and clinical, radiological, and microbiological findings, along with their impact on mortality, were analyzed. RESULTS: The patients had a mean ± SD age of 46.8 ± 16.3 years, with a male predominance of 71.6%. Common symptoms included headache (77.9%), fever (54.4%), and focal neurological deficits (53.5%). Gram-positive cocci were the predominant pathogens, with Viridans group streptococci identified as the most frequently isolated organisms. All patients received antimicrobial therapy and 71.6% underwent interventional therapies. The 42-day and 180-day survival rates were 91.9% and 86.1%, respectively. Significant predictors of 42-day mortality included intravenous drug addiction (HR: 6.02, 95% CI: 1.38-26.26), malignancy (HR: 3.61, 95% CI: 1.23-10.58), confusion (HR: 2.65, 95% CI: 1.19-5.88), and unidentified bacteria (HR: 4.68, 95% CI: 1.76-12.43). Significant predictors of 180-day mortality included malignancy (HR: 2.70, 95% CI: 1.07-6.81), confusion (HR: 2.14, 95% CI: 1.11-4.15), temporal lobe involvement (HR: 2.10, 95% CI: 1.08-4.08), and unidentified bacteria (HR: 3.02, 95% CI: 1.49-6.15). CONCLUSION: The risk of death in PBA extends beyond the infection phase, with different factors influencing the 42-day and 180-day mortality rates. Intravenous drug addiction was associated with early mortality, while temporal lobe involvement was associated with late mortality.
- MeSH
- Brain Abscess * microbiology mortality MeSH
- Anti-Bacterial Agents therapeutic use MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Survival Rate MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
Cognitive decline represents a severe non-motor symptom of Parkinson's disease (PD) that can significantly reduce the benefits of subthalamic deep brain stimulation (STN DBS). Here, we aimed to describe post-surgery cognitive decline and identify pre-surgery cognitive profile associated with faster decline in STN DBS-treated PD patients. A retrospective observational study of 126 PD patients treated by STN DBS combined with oral dopaminergic therapy followed for 3.54 years on average (SD = 2.32) with repeated assessments of cognition was conducted. Pre-surgery cognitive profile was obtained via a comprehensive neuropsychological examination and data analysed using exploratory factor analysis and Bayesian generalized linear mixed models. On the whole, we observed a mild annual cognitive decline of 0.90 points from a total of 144 points in the Mattis Dementia Rating Scale (95% posterior probability interval [-1.19, -0.62]) with high inter-individual variability. However, true score changes did not reach previously reported reliable change cut-offs. Executive deficit was the only pre-surgery cognitive variable to reliably predict the rate of post-surgery cognitive decline. On the other hand, exploratory analysis of electrode localization did not yield any statistically clear results. Overall, our data and models imply mild gradual average annual post-surgery cognitive decline with high inter-individual variability in STN DBS-treated PD patients. Nonetheless, patients with worse long-term cognitive prognosis can be reliably identified via pre-surgery examination of executive functions. To further increase the utility of our results, we demonstrate how our models can help with disentangling true score changes from measurement error in future studies of post-surgery cognitive changes.
- MeSH
- Deep Brain Stimulation * methods MeSH
- Cognition physiology MeSH
- Cognitive Dysfunction * etiology therapy physiopathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Neuropsychological Tests MeSH
- Subthalamic Nucleus * MeSH
- Parkinson Disease * therapy physiopathology MeSH
- Retrospective Studies MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
Over the last decade, research on the most studied parasite, Plasmodium falciparum, has disclosed significant findings in protease research. Detailed descriptions of the individual roles of protease isoenzymes from various protease classes encoded by the parasite genome have been elucidated, along with their functional and biochemical characterizations. These insights have enabled the development of innovative chemotherapy using low molecular weight inhibitors targeting specific molecular sites. Progress has been made in understanding the proteolytic cascade associated with the apical complex, particularly the roles of aspartyl proteases plasmepsins IX and X as master regulators. Additionally, advancements in direct and alternative methods of proteasome inhibition and expression regulation have been achieved. Research on digestive/food vacuole-associated proteases, with a focus on essential metalloproteases, has also seen significant developments. The rise of extensive genomic datasets and functional genomic tools for other parasitic organisms now allows these approaches to be applied to the study and treatment of other, less known parasitic diseases, aiming to uncover specific biological mechanisms and develop innovative, less toxic chemotherapies.
- MeSH
- Antimalarials * pharmacology therapeutic use MeSH
- Protease Inhibitors * therapeutic use MeSH
- Humans MeSH
- Malaria drug therapy MeSH
- Plasmodium falciparum * enzymology drug effects genetics MeSH
- Peptide Hydrolases metabolism genetics MeSH
- Malaria, Falciparum drug therapy parasitology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: The arteriovenous access stage (AVAS) classification provides evaluation of upper extremity vessels for vascular access (VA) suitability. It divides patients into classes within three main groups: suitable for native fistula (AVAS1) or prosthetic graft (AVAS2), and patients not suitable for conventional native or prosthetic VA (AVAS3). We validated this system on a prospective dataset. METHODS: A prospective, international observational study (NCT04796558) involved 11 centres from 8 countries. Patient recruitment was from March 2021 to January 2024. Demographic data, risk factors, vessels parameters, VA types, AVAS class and early VA failure were collected. Percentage agreement was used to assess predictive ability of AVAS (comparison of AVAS and created VA) and consistency of AVAS assessment between evaluators. Pearson's Chi-squared test was used for comparison of early failure rate of conventional (predicted by AVAS) and unconventional (not predicted by AVAS) VA. RESULTS: From 1034 enrolled patients, 935 had arteriovenous fistula or graft, 99 patients did not undergo VA creation due opting for alternative renal replacement therapies, experiencing health complications, death or non-compliance. AVAS1 had 91.2%, AVAS2 7.2% and AVAS3 1.6% of patients. Agreement between evaluators was 89%. The most frequently created VAs were radial-cephalic (46%) and brachial-cephalic (27%) fistulae. The accuracy of AVAS versus created access was 79%. In comparison, VA predicted by clinicians versus created access was 62.1%. Inaccuracy of AVAS prediction was more common with higher AVAS classes, and the most common reason for inaccuracy was creation of distal VA despite less favourable anatomy (17%). Patients with unconventional VA had higher early failure rate than patients with conventional VA (20% vs 9.3%, respectively, P = .002). CONCLUSION: AVAS is effective in predicting VA creation, but overall accuracy is reduced at higher AVAS classes when the complexity of decision-making increases and proximal vessels require preservation. When AVAS was followed by clinicians, early failure was significantly decreased.
- Publication type
- Journal Article MeSH
Inherited thrombocytopenias (ITs) encompass a group of rare disorders characterized by diminished platelet count. Recent advancements have unveiled various forms of IT, with inherited thrombocytopenia 2 (THC2) emerging as a prevalent subtype associated with germline variants in the critical 5' untranslated region of the ANKRD26 gene. This region is crucial in regulating the gene expression of ANKRD26, particularly in megakaryocytes. THC2 is an autosomal dominant disorder presenting as mild-to-moderate thrombocytopenia with minimal symptoms, with an increased risk of myeloproliferative malignancies. In our study of a family with suspected IT, three affected individuals harbored the c.-118C>T ANKRD26 variant, while four healthy members carried the c.-140C>G ANKRD26 variant. We performed a functional analysis by studying platelet-specific ANKRD26 gene expression levels using quantitative real-time polymerase-chain reaction. Functional analysis of the c.-118C>T variant showed a significant increase in ANKRD26 expression in affected individuals, supporting its pathogenicity. On the contrary, carriers of the c.-140C>G variant exhibited normal platelet counts and no significant elevation in the ANKRD26 expression, indicating the likely benign nature of this variant. Our findings provide evidence confirming the pathogenicity of the c.-118C>T ANKRD26 variant in THC2 and suggest the likely benign nature of the c.-140C>G variant.
- MeSH
- 5' Untranslated Regions * MeSH
- Adult MeSH
- Genetic Predisposition to Disease MeSH
- Middle Aged MeSH
- Humans MeSH
- Intercellular Signaling Peptides and Proteins MeSH
- Pedigree * MeSH
- Thrombocytopenia * genetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The Achilles tendon (AT) is the strongest tendon of the human body. The knowledge of AT anatomy is a basic prerequisite for the successful treatment of acute and chronic lesions. The structure of the AT results from a complicated fusion of three parts: the tendons of the medial and lateral gastrocnemius and the soleus muscles. From proximal to distal, the tendon fibers twist in a long spiral into a roughly 90° internal rotation. The tendon is narrowest approximately 5-7 cm above its calcaneal insertion and from there it expands again. The topography of the footprints of the individual AT components reflects the tendon origins. The anterior (deep) AT fibers insert into the middle third of the posterior aspect of the calcaneal tuberosity, the posterior (superficial) fibers pass over the calcaneal tuberosity and fuse with the plantar aponeurosis. A deep calcaneal bursa is interposed between the calcaneal tuberosity and the AT anterior surface. The AT has no synovial sheath but is covered along its entire length with a sliding connective tissue, the paratenon which is, however, absent on its anterior surface. The AT is supplied by the posterior tibial artery (PTA) and the peroneal artery (PA). Motor innervation of the triceps surae muscle is provided by fibers of the tibial nerve which also gives off sensitive fibers for the AT. Sensitive innervation is also provided via the sural nerve. The sural nerve crosses the AT approximately 11 cm proximal to the calcaneal tuberosity. The forces acting on the AT during exercise may be up to 12 times the body weight. Physiological stretching of AT collagen fibers ranges between 2% and 4% of its length. Stretching of the tendon over 4% results in microscopic failure and stretching beyond 8% in macroscopic failure.
- MeSH
- Achilles Tendon * anatomy & histology MeSH
- Muscle, Skeletal anatomy & histology innervation MeSH
- Humans MeSH
- Models, Anatomic MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
OBJECTIVES: To determine how social factors influence career decisions of dental service providers, particularly focusing on examining the impact of dentists' origins. METHODS: Online survey of Hessian panel dentists, with pairwise comparisons to a set of factors impacting their decision-making process. An Analytic Hierarchy Process examined the weighting of influencing drivers in career choice. RESULTS: Dentists from rural backgrounds were more likely to establish practices in rural areas than those from urban origins. Origin correlated with entrepreneurial intentions and a strong association of rural origin. Dentists who grew up in rural areas were 4.19 times more likely to start a business. CONCLUSION: These findings may support efficient resource allocation and support for rural dental businesses.
- MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Small Business MeSH
- Professional Practice Location MeSH
- Surveys and Questionnaires MeSH
- Rural Population MeSH
- Career Choice * MeSH
- Rural Health Services MeSH
- Dentists statistics & numerical data psychology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Germany MeSH
During vertical jump evaluations in which jump height is estimated from flight time (FT), the jumper must maintain the same body posture between vertical takeoff and landing. As maintaining identical posture is rare during takeoff and landing between different jump attempts and in different individuals, we simulated the effect of changes in ankle position from takeoff to landing in vertical jumping to determine the range of errors that might occur in real-life scenarios. Our simulations account for changes in center of mass position during takeoff and landing, changes in ankle position, different subject statures (1.44-1.98 m), and poor to above-average jump heights. Our results show that using FT to estimate jump height without controlling for ankle position (allowing dorsiflexion) during the landing phase of the vertical jump can overestimate jump height by 18% in individuals of average stature and performing an average 30 cm jump or may overestimate by ≤60% for tall individuals performing a poor 10 cm jump, which is common for individuals jumping with added load. Nevertheless, as assessing jump heights based on FT is common practice, we offer a correction equation that can be used to reduce error, improving jump height measurement validity using the FT method allowing between-subject fair comparisons.
- MeSH
- Biomechanical Phenomena physiology MeSH
- Adult MeSH
- Ankle Joint physiology MeSH
- Ankle physiology MeSH
- Humans MeSH
- Young Adult MeSH
- Computer Simulation MeSH
- Movement physiology MeSH
- Posture * physiology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Stathmin, a cytosolic microtubule-destabilizing phosphoprotein involved in the regulation of mitosis, is widely expressed in various malignancies and acts as an adverse prognostic factor. Our research analyzed its immunohistochemical expression on a large cohort of ovarian sex cord-stromal tumors, evaluating its potential utility in differential diagnosis, prognosis, and therapeutic application. METHODS: We examined 390 cases of ovarian sex cord-stromal tumors including 281 adult granulosa cell tumors (AGCT), 5 juvenile granulosa cell tumors (JGCT), 33 Sertoli-Leydig cell tumors (SLCT), 50 fibromas/thecomas (F/T), 11 Leydig cell tumors/steroid cell tumors (LCT/SterCT), 5 sex-cord stromal tumors NOS (SCST-NOS), 3 Sertoli cell tumors (SCT), and 2 sclerosing stromal tumors (ScST). Immunohistochemical analysis was performed using TMAs. RESULTS: Strong expression (> 50%) was observed in all cases of AGCT, JGCT, SLCT, SCST-NOS, SCT and 1 ScST. The other case of ScST exhibited mild expression (5-10%). The negative cases included exclusively F/T and LCT/SterCT, with F/T showing 24% of negative cases and LCT/SterCT comprising 64% of negative cases. CONCLUSION: The results of our study indicate that stathmin is neither a prognostic marker nor suitable for the differential diagnosis of challenging cases of ovarian sex cord-stromal tumors. However, its predictive value may be theoretically significant, as a decrease in stathmin expression potentialy influences response to chemotherapy treatment.
- MeSH
- Diagnosis, Differential MeSH
- Adult MeSH
- Sex Cord-Gonadal Stromal Tumors * pathology diagnosis metabolism therapy MeSH
- Immunohistochemistry * MeSH
- Middle Aged MeSH
- Humans MeSH
- Biomarkers, Tumor * analysis MeSH
- Ovarian Neoplasms * pathology diagnosis metabolism therapy MeSH
- Prognosis MeSH
- Stathmin * analysis metabolism MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
