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Brain MRI is almost always abnormal, typically with T2 subcortical hyperintensities, and sometimes brain atrophy or calcifications. In addition to the classic antiepileptic drugs, immunosuppressive drugs should be considered as potential epilepsy treatment. CONCLUSION To the best of our knowledge, this is the first review dedicated to the characteristics of paediatric patients with PRS and epilepsy. Seizures are usually focal, became refractory in 40 %, and have a significant impact on the quality of life and neurodevelopment of patients. PURPOSE Our aim was to study the microstructural architecture of the contralateral hippocampus to the affected side in patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and its relation with surgical outcome. METHOD We included 33 consecutive patients evaluated in our epilepsy surgery program during a five-year period. They underwent a presurgical MRI with volumetric T1 and diffusion weighted sequences. 22 patients with TLE-HS (13 women, 12 right TLE-HS) were finally selected. Median follow-up after surgery was 6.25 years (4.5-8.83 years). We segmented the hippocampal subfields of the contralateral hippocampus using FreeSurfer and calculated the fractional anisotropy (FA) and the mean diffusivity (MD) of each subfield. We also scanned 18 healthy age-matched controls. RESULTS After surgery, 50 % of the patients (n = 11) remained seizure-free (SF) following surgery. Comparing non-SF to SF patients, the MD showed increased values of the CA1 (p = 0.035), the molecular layer (p = 0.010) and the dentate gyrus (p = 0.041) in the healthy hippocampus. Using a cut-off point for a survival analysis, we found that patients with lower values of MD of the molecular layer and the CA1 remained SF during long-term post-operative follow-up (p less then 0.0001). CONCLUSIONS The contralateral hippocampal internal microstructure may have be implicated in post-surgery seizure freedom in patients with TLE-HS. BACKGROUND Continuous ambulatory peritoneal dialysis (CAPD) is the first option for patients with end-stage renal disease under the benefit package of Thailand. Nevertheless, automated peritoneal dialysis (APD) may benefit these patients in terms of both medical and quality-of-life aspects, but it is more expensive. The economic evidence for the comparison between CAPD and APD is not inconclusive. Thus, this study aims to evaluate the cost-effectiveness of CAPD compared with APD in PD patients. OBJECTIVES To assess the health-related quality of life and costs between patients treated with CAPD and APD. METHODS A Markov model was developed to evaluate the cost-effectiveness of CAPD and APD from the societal perspective. Costs and outcomes were calculated over a lifetime horizon and discounted at an annual rate of 3%. The outcomes were presented as quality-adjusted life-years (QALYs) of CAPD and APD. Utility scores were calculated from the utility values of the 5-level EuroQol questionnaire. A probabilistic sensitivity analysis using 5000 Monte Carlo simulations was performed to evaluate the stability of the results. RESULTS The costs of APD and CAPD were 12 868 080 and 11 144 786 Thai baht, respectively, whereas the QALYs were 24.28 and 24.72 QALYs, respectively. APD was more costly but less effective than CAPD. The most sensitive parameter was direct medical cost of outpatient visits. When the willingness-to-pay threshold was 160 000 Thai baht per QALY, the probability of APD providing a cost-effective alternative to CAPD was 19%. CONCLUSION APD was not a cost-effective strategy as compared with CAPD at the current Thai threshold. These findings should encourage clinicians and policy makers to encompass the use of CAPD as a good value for money for PD treatment. OBJECTIVES Countries have constrained healthcare budgets and must prioritize new interventions depending on health goals and time frame. This situation is relevant in the sphere of national immunization programs, for which many different vaccines are proposed, budgets are limited, and efficient choices must be made in the order of vaccine introduction. METHODS A constrained optimization (CO) model for infectious diseases was developed in which different intervention types (prophylaxis and treatment) were combined for consideration in Malaysia. Local experts defined their priority public health issues pneumococcal disease, dengue, hepatitis B and C, rotavirus, neonatal pertussis, and cholera. Epidemiological, cost, and effectiveness data were informed from local or regionally published literature. The model aimed to maximize quality-adjusted life-year (QALY) gain through the reduction of events in each of the different diseases, under budget and intervention coverage constraints. The QALY impact of the interventions was assessed over 2 periods lifetime and 20 years. The period of investment was limited to 15 years. RESULTS The assessment time horizon influenced the prioritization of interventions maximizing QALY gain. The incremental health gains compared with a uninformed prioritization were large for the first 8 years and declined thereafter. Rotaviral and pneumococcal vaccines were identified as key priorities irrespective of time horizon, hepatitis B immune prophylaxis and hepatitis C treatment were priorities with the lifetime horizon, and dengue vaccination replaced these with the 20-year horizon. CONCLUSIONS CO modeling is a useful tool for making economically efficient decisions within public health programs for the control of infectious diseases by helping prioritize the selection of interventions to maximize health gain under annual budget constraints. When Stanley Falkow introduced Molecular Koch's Postulates (Falkow, 1988) as a conceptual framework to identify microbial factors that contributed to disease, he reaffirmed the prominent role that the basic principles of genetic analysis should play in defining genotype-phenotype associations in microbial pathogens. In classical bacterial genetics the nature of mutations is inferred through cis-trans complementation and by indirectly mapping their relative position and physical distance through recombination frequencies - all of which were made possible by the genetic tools of the day natural transformations, conjugation and transduction. Unfortunately, many of these genetic tools are not always available to study pathogenic bacteria. The recombinant DNA revolution in the 1980s launched the field of molecular pathogenesis as genes could be treated as physical units that could be cut, spliced and transplanted from one microbe to another and thus not only 'prove' that an individual gene complemented a virulence defect in a mutant strain but also could impart pathogenic properties to otherwise benign microbes. The recombinant DNA revolution also enabled the generation of newer versions of genetic tools to generate mutations and engineer microbial genomes. The last decade has ushered in next generation sequencing technologies as a new powerful tool for bacterial genetics. selleckchem The routine and inexpensive sequencing of microbial genomes has increased the number and phylogenetic scope of microbes that are amenable to functional characterization and experimentation. In this review, we highlight some salient advances in this rapidly evolving area. Intravacuolar bacterial pathogens establish intracellular niches by constructing membrane-encompassed compartments. The vacuoles surrounding the bacteria are remarkably stable, facilitating microbial replication and preventing exposure to host cytoplasmically localized innate immune sensing mechanisms. To maintain integrity of the membrane compartment, the pathogen is armed with defensive weapons that prevent loss of vacuole integrity and potential exposure to host innate signaling. In some cases, the microbial components that maintain vacuolar integrity have been identified, but the basis for why the compartment degrades in their absence is unclear. In this review, we point out that lessons from the microbial-programmed degradation of the vacuole by the cytoplasmically localized Shigella flexneri provide crucial insights into how degradation of pathogen vacuoles occurs. We propose that in the absence of bacterial-encoded guard proteins, aberrant trafficking of host membrane-associated components results in a dysfunctional pathogen compartment. As a consequence, the vacuole is poisoned and replication is terminated. Though there was initial interest in the use of psychedelic drugs for psychiatric treatment, bad outcomes and subsequent passage of the Substance Act of 1970, which placed psychedelic drugs in the Schedule I category, significantly limited potential progress. More recently, however, there has been renewal in interest and promise of psychedelic research. The purpose of this review is to highlight contemporary human studies on the use of select psychedelic drugs, such as psilocybin, LSD, MDMA and ayahuasca, in the treatment of various psychiatric illnesses, including but not limited to treatment-resistant depression, post-traumatic stress disorder, end-of-life anxiety, and substance use disorders. The safety and efficacy as reported from human and animal studies will also be discussed. Accumulated research to date has suggested the potential for psychedelics to emerge as breakthrough therapies for psychiatric conditions refractory to conventional treatments. However, given the unique history and high potential for misuse with popular distribution, special care and considerations must be undertaken to safeguard their use as viable medical treatments rather than drugs of abuse. Prolactinomas are tumors of the pituitary gland, which overproduces prolactin leading to dramatic fluctuations of endogenous hormone levels throughout the body. While it is not fully understood how endogenous hormone disorders affect a patient's brain, it is well known that fluctuating hormone levels can have negative neuropsychological effects. Using resting-state functional magnetic resonance imaging (rs-fMRI), we investigated whole-brain functional connectivity (FC) and its relationship with hormone levels in prolactinomas. By performing seed-based FC analyses, we compared FC metrics between 33 prolactinoma patients and 31 healthy controls matched for age, sex, and hand dominance. We then carried out a partial correlation analysis to examine the relationship between FC metrics and hormone levels. Compared to healthy controls, prolactinoma patients showed significantly increased thalamocortical and cerebellar-cerebral FC. Endogenous hormone levels were also positively correlated with increased FC metrics, and these hormone-FC relationships exhibited sex differences in prolactinoma patients. Our study is the first to reveal altered FC patterns in prolactinomas and to quantify the hormone-FC relationships. These results indicate the importance of endogenous hormones on functional compensation of the brain in patients with prolactinomas. The role of cannabis in medicine is rapidly evolving. Medical cannabis is now legal in a majority of states, and THC and CBD, the prominent cannabinoids found in cannabis, have both been utilized in the development of FDA-approved drugs. Due to the complicated legal status of cannabis and cannabinoids, as well as regulations that vary from state to state, the appropriate use of these substances for both patients as well as clinicians is often unclear. Advancements in the understanding of the pharmacology of cannabis have led to numerous proposed uses of these drugs, including as antidepressant or analgesic agents. However, clinical trial data for these substances suggests that many purported indications of cannabis and cannabinoids are not supported by good clinical data. Furthermore, cannabis and several cannabinoid-based medications have potentially concerning side effect profiles that may limit their use in certain patient populations. As the legal status and clinical database of these medications continue to evolve, physicians will need to continue to balance the real potential of these compounds with their limitations and adverse effects.
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