Machine Learning-Based Prediction Models for Cognitive Decline Progression: A Comparative Study in Multilingual Settings Using Speech Analysis.

Background: Mild cognitive impairment (MCI) is a condition commonly associated with dementia. Therefore, early prediction of progression from MCI to dementia is essential for preventing or alleviating cognitive decline. Given that dementia affects cognitive functions like language and speech, detecting disease progression through speech analysis can provide a cost-effective solution for patients and caregivers. Design-Participants: In our study, we examined spontaneous speech (SS) and written Mini Mental Status Examination (MMSE) scores from a 60-patient dataset obtained from the Mugla University Dementia Outpatient Clinic (MUDC) and a 153-patient dataset from the Alzheimer's Dementia Recognition through Spontaneous Speech (ADRess) challenge. Our study, for the first time, analyzed the impact of audio features extracted from SS in distinguishing between different degrees of cognitive impairment using both an Indo-European language and a Turkic language, which exhibit distinct word order, agglutination, noun cases, and grammatical markers. Results: When each machine learning model was tested on its respective trained language, we attained a 95% accuracy using the random forest classifier on the ADRess dataset and a 94% accuracy on the MUDC dataset employing the multilayer perceptron (MLP) neural network algorithm. In our second experiment, we evaluated the effectiveness of each language-specific machine learning model on the dataset of the other language. We achieved accuracies of 72% for English and 76% for Turkish, respectively. Conclusion: These findings underscore the cross-language potential of audio features for automated tracking of cognitive impairment progression in MCI patients, offering a convenient and cost-effective option for clinicians or patients.

Systematic review and meta-analysis: pharmacogenetics of anti-TNF treatment response in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects ~1% of the Caucasian population. Over the last decades, the availability of biological drugs targeting the proinflammatory cytokine tumour necrosis factor α, anti-TNF drugs, has improved the treatment of patients with RA. However, one-third of the patients do not respond to the treatment. We wanted to evaluate the status of pharmacogenomics of anti-TNF treatment. We performed a PubMed literature search and all studies reporting original data on associations between genetic variants and anti-TNF treatment response in RA patients were included and results evaluated by meta-analysis. In total, 25 single nucleotide polymorphisms were found to be associated with anti-TNF treatment response in RA (19 from genome-wide association studies and 6 from the meta-analyses), and these map to genes involved in T cell function, NFκB and TNF signalling pathways (including CTCN5, TEC, PTPRC, FCGR2A, NFKBIB, FCGR2A, IRAK3). Explorative prediction analyses found that biomarkers for clinical treatment selection are not yet available.

Systematic review: genetic biomarkers associated with anti-TNF treatment response in inflammatory bowel diseases.

BACKGROUND: Personalised medicine, including biomarkers for treatment selection, may provide new algorithms for more effective treatment of patients. Genetic variation may impact drug response and genetic markers could help selecting the best treatment strategy for the individual patient. AIM: To identify polymorphisms and candidate genes from the literature that are associated with anti-tumour necrosis factor (TNF) treatment response in patients with inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis. METHODS: We performed a PubMed literature search and retrieved studies reporting original data on association between polymorphisms and anti-TNF treatment response and conducted a meta-analysis. RESULTS: A functional polymorphism in FCGR3A was significantly associated with anti-TNF treatment response among CD patients using biological response criterion (decrease in C-reactive protein, levels). Meta-analyses showed that polymorphisms in TLR2 (rs3804099, OR (95% CI) = 2.17 (1.35-3.47)], rs11938228 [OR = 0.64 (0.43-0.96)], TLR4 (rs5030728) [OR = 3.18 (1.63-6.21)], TLR9 (rs352139) [OR = 0.43 (0.21-0.88)], TNFRSF1A (rs4149570) [OR = 2.06 (1.02-4.17)], IFNG (rs2430561) [OR = 1.66 (1.05-2.63)], IL6 (rs10499563) [OR = 1.65 (1.04-2.63)] and IL1B (rs4848306) [OR = 1.88 (1.05-3.35)] were significantly associated with response among IBD patients using clinical response criteria. A positive predictive value of 0.96 was achieved by combining five genetic markers in an explorative analysis. CONCLUSIONS: There are no genetic markers currently available which are adequately predictive of anti-TNF response for use in the clinic. Genetic markers bear the advantage that they do not change over time. Therefore, hypothesis-free approaches, testing a large number of polymorphisms in large, well-characterised cohorts, are required in order to identify genetic profiles with larger effect sizes, which could be employed as biomarkers for treatment selection in clinical settings.

Cytochrome P4501A1 genotypes and smoking- and hypertension-related ischemic stroke risk.

This study aimed to determine whether the coding (A4889G) and noncoding region (T6235C) polymorphisms of the gene coding for cytochrome P4501A1 (CYP1A1), a xenobiotic-metabolizing enzyme responsible for the metabolism of carcinogenic polycyclic aromatic hydrocarbons, are involved in the pathogenesis of ischemic stroke in Turkish population. Study group consisted of 226 ischemic stroke patients and 113 controls. Genotypes were attained by allele-specific polymerase chain reaction (PCR) for A4889G and PCR/restriction fragment length polymorphism analysis for T6235C. Frequency of 6235C allele was significantly lower in patients (0.151) compared with controls (0.226, P = 0.015). Prevalence of hypertension and hypertension-associated ischemic stroke risk was lower for 6235C allele carriers. This allele decreased ischemic stroke risk twofold (adjusted odds ratio = 0.48, P = 0.005). There was almost no difference in 4889G allele frequencies in patients (0.445) and controls (0.425). However, prevalence of hypertension was lower in 4889G allele carriers when compared with the wild-type genotypes. In addition, risk of ischemic stroke for smoker and hypertensive individuals was lower when they have at least one 4889G allele. The present study demonstrated that CYP1A1 genetic variants contribute to interindividual variability in smoking- and hypertension-induced ischemic stroke risk.

Diffuse villous hyperplasia of choroid plexus.

Diffuse villous hyperplasia of choroid plexus (DVHCP) is a rare condition which is characterized by the presence of diffuse enlargement of the entire choroid plexus throughout the length of the choroidal fissure and overproduction of CSF. The diagnosis of diffuse villous hyperplasia of choroid plexus can be established by the MR demonstration of diffusely large, contrast enhanced choroid plexus in the cases of overproduction hydrocephalus. Although some authors recommend choroid plexus excision or coagulation, ventriculo-atrial shunt insertion is a simple and effective treatment modality in cases of diffuse villous hyperplasia of the choroid plexus. In this report we present a case of diffuse villous hyperplasia of the choroid plexus and a short review of the literature. To our knowledge, in the CT and MRI era only 5 cases of DVHCP cases have been reported.

Non-traumatic intradiploic arachnoid cyst.

In this report, we present a case of non-traumatic intradiploic arachnoid cyst in a 65 year-old woman with a slow growing swelling in the right frontotemporal region without a history of head trauma, which was diagnosed intra-operatively. Extradural intracranial location of non-traumatic arachnoid cyst is a rare clinical entity with a few reported cases in the literature. Characteristic features of non-traumatic intradiploic arachnoid cysts are also described in this mini-review article.

A retrospective drug utilization evaluation of vancomycin usage in paediatric patients.

OBJECTIVE: To evaluate the appropriateness of use of vancomycin in paediatric patients at KK Women's and Children's Hospital, the major paediatric hospital in Singapore to identify potential problems in prescribing practices that may necessitate intervention to optimize vancomycin usage. METHODS: A retrospective drug utilization evaluation was performed for paediatric patients who received intravenous vancomycin from 1 June 1998 to 31 June 1999. The outcome measures were consistency of vancomycin indication with recommended guidelines, dosing regimens, microbiological data, monitoring of serum drug levels, renal function, clinical outcomes and adverse drug reactions (ADRs). RESULTS: A total of 96 cases was available for evaluation. Sixty-two (64.6%) courses of vancomycin were consistent with guidelines for indication of therapy. Eighty-six (89.6%) of the dosing regimen were consistent. All infusion times that were recorded (56.3%) were consistent with criteria. Of the patients treated with vancomycin for more than 1 day, peak and/or trough serum vancomycin levels were ordered for 70 cases. Of the 56 cases with paired levels ordered, 46 cases had at least one level that fell outside the therapeutic range. Nineteen (19.8%) cases of ADRs were documented. Fifty-eight (60.4%) cases received concurrent nephrotoxic drugs. However, a substantial portion of vancomycin courses were apparently not prescribed for appropriate indications, and there was poor recording of vancomycin administration information and sampling time. CONCLUSION: The majority of dosing regimens of vancomycin was consistent with guideline criteria. The most evident problem was the sub-optimal use of the monitoring of vancomycin serum levels. The information derived from this study may be used as a for further study and for the development of strategies for optimize vancomycin usage.

Aspergillus pituitary abscess.

BACKGROUND: Pituitary abscess is rare and most of the cases are of bacterial origin. True fungal pituitary abscess is extremely rare only five cases have been reported. In this report, we present a case of aspergillus pituitary abscess. Mortality rate in intracranial aspergillosis is close to 100% especially in immunsuppressed patients when undiagnosed and untreated. In focal CNS aspergillosis total cure can be achieved in approximately 30% of the cases by surgical drainage and intensive antifungal therapy. Although this is the first reported case with magnetic resonance imaging examination the definitive diagnosis was established only by histopathological examination. CLINICAL PRESENTATION: A 42 year-old man was referred to our hospital with the diagnosis of sellar suprasellar mass accompanied by frontal headache and decreased visual acuity. His medical history was insignificant. Physical examination was normal and the patient was afebrile. The neurological examination revealed bilateral papilledema and bitemporal hemianopsia but no stiff neck and motor or sensory deficit. In the light of MRI examination, the preoperative diagnosis was pituitary abscess secondary to paranasal sinus infection or hemorrhagic pituitary adenoma. INTERVENTION: The patient was successfully treated by transsphenoidal surgery. Histopathological examination of sphenoid sinus mucosa revealed normal mucosal appearance with inflammation and histopathological examination of the intrasellar mass resulted in the diagnosis of aspergillosis. All cultures obtained from sphenoid sinus were reported as having no growth. However in the second week after the operation fungal culture of the intrasellar mass grew aspergillus. After 8 weeks of amphothericine-B treatment, the patient was discharged. At the last follow up examination two years after the operation, the patient was symptom free with normal pituitary function. CONCLUSION: Aspergillus pituitary abscess should be considered in the differential diagnosis of a pituitary mass. The correct diagnosis of pituitary aspergillosis can only be achieved by histopathological examination because clinical and radiological findings including MRI are not specific and culture results are obtained later. Immediately after the diagnosis, intensive antifungal therapy should be started for a successful treatment.

Phenytoin penetration into chronic subdural haematomas.

The pathophysiology of chronic subdural haematomas (CSH) is still unclear. In the light of recent ultrastructural examination, exudation from the macrocapillaries in the outer membrane of CSH may play an important role in the enlargement of CSH. In this study, exudation from the macrocapillaries was assessed by the measurement of phenytoin, a protein-bound antiepileptic agent used in cases of CSH. In 22 patients, 1 h after the administration of 250 mg of phenytoin intravenously, blood and subdural haematoma samples were taken and phenytoin levels were measured. The ratio of subdural haematoma level to the blood phenytoin level was determined and defined as the phenytoin penetration ratio (PPR). The correlation between the phenytoin penetration ratio and clinical neurological grades (Markwalder and Glasgow Coma Scale), age of the patients and the CT appearance of CSH were investigated. The mean phenytoin penetration ratio was 19.5%. As the neurological grades of patients increased, average PPR also increased. The average PPR values were 17.64 and 20.84% in the patients younger than 60 years (nine patients) and older patients (13 patients), respectively. Mean PPRs in the groups according to the CT appearance were as follows: low density 11.21% (seven patients), isodensity in 15.88% (10 patients), high density in 38.5% (five patients). A subdural reaccumulation was detected in nine patients with a mean PPR of 27.72%, while mean PPR was 14.56% in the others. Exudation from macrocapillaries in the outer membrane of chronic subdural haematomas probably plays an important role in the enlargement of chronic subdural haematoma, and measuring phenytoin levels in the chronic subdural haematoma is a simple method for the quantitative estimation of the exudation in CSH.

Brownian dynamics study of a multiply-occupied cation channel: application to understanding permeation in potassium channels.

The behavior of a multiply-occupied cation-selective channel has been computed by Brownian dynamics. The length, cross-section, ion-ion repulsion force, and ionic mobility within the channel are all estimated from data and physical reasoning. The only free parameter is a partition energy at the mouth of the channel, defining the free energy of an ion in the channel compared to the bath. It is presumed that this partition energy is associated with the energetics of exchanging a bulk hydration environment for a channel hydration environment. Varying the partition energy alone, keeping all other parameters fixed, gives approximately the full range of magnitudes of single channel conductances seen experimentally for K channels. Setting the partition energy at -11 kT makes the computed channel look similar to a squid axon K channel with respect to magnitude of conductance, shape of the I-V curve, non-unity of Ussing flux ratio exponents, decrease of current and increase of conductance with extracellular ion accumulation, and saturation at high ion concentration in the bathing solution. The model includes no preferred binding sites (local free energy minima) for ions in the channel. Therefore it follows that none of the above-mentioned properties of K channels are strong evidence for the existence of such sites. The model does not show supersaturation of current at very high bathing concentrations nor any pronounced voltage-dependence of the Ussing flux ratio exponent, suggesting that these features would require additional details not included in the model presented herein.