Unlocking Therapeutic Potential: The Role of Theta Burst Stimulation in Multiple Sclerosis Management.

Objective: Current therapies for multiple sclerosis (MS) often have limited efficacy and side effects, necessitating alternative approaches. Noninvasive brain stimulation (NIBS), such as transcranial direct current stimulation and transcranial magnetic stimulation (TMS), offers potential solutions. Among NIBS techniques, theta burst stimulation (TBS) is notable for its ability to modulate cortical activity. The objective of this systematic review is to assess the impact of TBS on MS symptoms.Data Sources: The study conducted rigorous systematic searches in PubMed, Google Scholar, and Scopus databases up to June 2023, using specific Medical Subject Headings terms related to NIBS and MS, such as TMS and TBS, in conjunction with terms like MS or demyelinating disease. Additionally, the bibliographic references of included studies, book chapters, and original articles were manually reviewed.Study Selection: The study selection process involved a 2-tiered screening mechanism, beginning with an evaluation of titles and abstracts, followed by a full-text review of selected articles. Inclusion criteria incorporated randomized controlled trials (RCTs) focusing on TBS with MS patients. Exclusion criteria included non-qualitative, non-MS, and non-TBS studies. Risk of bias assessment was conducted using the 2008 Cochrane Risk of Bias 2 Scale for RCTs.Data Extraction: Data extraction was conducted by thoroughly reviewing each research article and systematically recording the relevant information using a standardized data extraction form, ensuring consistency and accuracy throughout the process.Results: In a systematic review encompassing 5 randomized controlled trials involving 117 individuals with relapsing-remitting or secondary progressive MS across Italy, France, and Russia, various forms of TBS were applied. These interventions ranged from intermittent TBS (iTBS) to continuous intermittent TBS (c-iTBS) that demonstrated favorable outcomes. Notably, TBS interventions led to significant reductions in spasticity, fatigue, and pain, with c-iTBS combined with vestibular rehabilitation showing additional improvements in vestibular-ocular reflexes, gait, and balance. While specific protocols varied among the studies, collectively, the results suggest promise for TBS approaches in alleviating MS-related symptoms.Conclusions: The findings of this review suggest that TBS may hold promise in addressing specific MS symptoms, notably fatigue and spasticity. Future research should include a more diverse participant pool to explore TBS effects across different MS subtypes and aim for larger sample sizes to enhance statistical power and result reliability.Prim Care Companion CNS Disord 2024;26(2):23r03645. Author affiliations are listed at the end of this article.

Synergistic interactions between anammox and dissimilatory nitrate reducing bacteria sustains reactor performance across variable nitrogen loading ratios.

Anaerobic ammonium oxidizing (anammox) bacteria are utilized for high efficiency nitrogen removal from nitrogen-laden sidestreams in wastewater treatment plants. The anammox bacteria form a variety of competitive and mutualistic interactions with heterotrophic bacteria that often employ denitrification or dissimilatory nitrate reduction to ammonium (DNRA) for energy generation. These interactions can be heavily influenced by the influent ratio of ammonium to nitrite, NH4+:NO2-, where deviations from the widely acknowledged stoichiometric ratio (1:1.32) have been demonstrated to have deleterious effects on anammox efficiency. Thus, it is important to understand how variable NH4+:NO2- ratios impact the microbial ecology of anammox reactors. We observed the response of the microbial community in a lab scale anammox membrane bioreactor (MBR) to changes in the influent NH4+:NO2- ratio using both 16S rRNA gene and shotgun metagenomic sequencing. Ammonium removal efficiency decreased from 99.77 ± 0.04% when the ratio was 1:1.32 (prior to day 89) to 90.85 ± 0.29% when the ratio was decreased to 1:1.1 (day 89-202) and 90.14 ± 0.09% when the ratio was changed to 1:1.13 (day 169-200). Over this same timespan, the overall nitrogen removal efficiency (NRE) remained relatively unchanged (85.26 ± 0.01% from day 0-89, compared to 85.49 ± 0.01% from day 89-169, and 83.04 ± 0.01% from day 169-200). When the ratio was slightly increased to 1:1.17-1:1.2 (day 202-253), the ammonium removal efficiency increased to 97.28 ± 0.45% and the NRE increased to 88.21 ± 0.01%. Analysis of 16 S rRNA gene sequences demonstrated increased relative abundance of taxa belonging to Bacteroidetes, Chloroflexi, and Ignavibacteriae over the course of the experiment. The relative abundance of Planctomycetes, the phylum to which anammox bacteria belong, decreased from 77.19% at the beginning of the experiment to 12.24% by the end of the experiment. Analysis of metagenome assembled genomes (MAGs) indicated increased abundance of bacteria with nrfAH genes used for DNRA after the introduction of lower influent NH4+:NO2- ratios. The high relative abundance of DNRA bacteria coinciding with sustained bioreactor performance indicates a mutualistic relationship between the anammox and DNRA bacteria. Understanding these interactions could support more robust bioreactor operation at variable nitrogen loading ratios.

A Five-Year Clinical Course of Potential Phenocopy Syndrome of Behavioral Variant Frontotemporal Dementia: A Case Report and Literature Review.

Frontotemporal dementia is a neurocognitive disorder that affects language, behavior, or executive functioning. This disease includes a spectrum of presentations that includes multiple variants. The phenocopy syndrome of the behavioral variant of frontotemporal dementia mimics the behavioral variant of frontotemporal dementia. Patients with this condition show a decline in personality, social conduct, and cognitive ability but often display no signs of neurological imaging and exhibit slow progression. This case focuses on a now 70-year-old male who has shown signs of behavioral changes with a slowly progressive clinical course and minimal findings on positron emission tomography (PET) scan, but moderate changes seen on MRI. This report details a clinical presentation of an individual potentially with phenocopy syndrome of behavioral variant frontotemporal dementia and provides context to how symptoms can be managed to better help assist patients and their caregivers.

Empathy and the Medical Student House Call: The Effect of Clinical Settings on Empathy in Third Year Medical Students.

Objective: This study measured the effect the experience of house calls might have on third-year medical students. Methods: Students were surveyed via an anonymous online survey at the start of their geriatrics clerkship, again at the end of their clerkship, and once more three months later. Empathy was measured using the Jefferson Scale of Empathy - Student version (JSE) and student attitudes towards the geriatrics population was measured using the UCLA Geriatrics Attitudes Scale (GAS). Data were analyzed using SPSS version 27.0. Results: No changes in empathy were found when comparing students who completed house calls versus those who did not. However, students who trained in office settings were noted to have higher JSE scores at the three-month follow-up survey, students who worked in hospital settings had higher JSE scores at the completion of the clerkship, and student who worked in assisted living facilities had higher GAS scores at the completion of the clerkship. Conclusions: Teaching students ways to improve empathy can be challenging. The setting in which a student trains may be an area of focus for improving empathy among trainees and should be researched further.

Cohesin SA2 is a sequence-independent DNA-binding protein that recognizes DNA replication and repair intermediates.

Proper chromosome alignment and segregation during mitosis depend on cohesion between sister chromatids, mediated by the cohesin protein complex, which also plays crucial roles in diverse genome maintenance pathways. Current models attribute DNA binding by cohesin to entrapment of dsDNA by the cohesin ring subunits (SMC1, SMC3, and RAD21 in humans). However, the biophysical properties and activities of the fourth core cohesin subunit SA2 (STAG2) are largely unknown. Here, using single-molecule atomic force and fluorescence microscopy imaging as well as fluorescence anisotropy measurements, we established that SA2 binds to both dsDNA and ssDNA, albeit with a higher binding affinity for ssDNA. We observed that SA2 can switch between the 1D diffusing (search) mode on dsDNA and stable binding (recognition) mode at ssDNA gaps. Although SA2 does not specifically bind to centromeric or telomeric sequences, it does recognize DNA structures often associated with DNA replication and double-strand break repair, such as a double-stranded end, single-stranded overhang, flap, fork, and ssDNA gap. SA2 loss leads to a defect in homologous recombination-mediated DNA double-strand break repair. These results suggest that SA2 functions at intermediate DNA structures during DNA transactions in genome maintenance pathways. These findings have important implications for understanding the function of cohesin in these pathways.

Detection of brown adipose tissue and thermogenic activity in mice by hyperpolarized xenon MRI.

The study of brown adipose tissue (BAT) in human weight regulation has been constrained by the lack of a noninvasive tool for measuring this tissue and its function in vivo. Existing imaging modalities are nonspecific and intrinsically insensitive to the less active, lipid-rich BAT of obese subjects, the target population for BAT studies. We demonstrate noninvasive imaging of BAT in mice by hyperpolarized xenon gas MRI. We detect a greater than 15-fold increase in xenon uptake by BAT during stimulation of BAT thermogenesis, which enables us to acquire background-free maps of the tissue in both lean and obese mouse phenotypes. We also demonstrate in vivo MR thermometry of BAT by hyperpolarized xenon gas. Finally, we use the linear temperature dependence of the chemical shift of xenon dissolved in adipose tissue to directly measure BAT temperature and to track thermogenic activity in vivo.

Simplified ultrasonically- and microwave-assisted solvent extractions for the determination of ginsenosides in powdered Panax ginseng rhizomes using liquid chromatography with UV absorbance or electrospray mass spectrometric detection.

New approaches for the recovery of ginsenosides are presented that greatly simplify the liquid chromatographic (LC) determination of the total content of eight ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, Rg1 and Rg2) in powdered Panax ginseng rhizomes. The extraction protocols not only recover the neutral ginsenosides, but also simultaneously incorporate base-catalyzed hydrolysis of the malonyl-ginsenosides using dilute potassium hydroxide added to the methanol-water extractant. This eliminates the need for an independent extraction step followed by acid- or base-catalyzed hydrolysis. Both ultrasonically-assisted and microwave-assisted extraction methods are developed. The optimization of these simplified methods to remove pendant malonate esters, while retaining the glycosidic linkages, was determined by LC through variation of the extraction/hydrolysis time, order of hydrolysis reagent addition, and evaluation of multiple extractions. A comparison of the ginsenoside profiles obtained with and without addition of base to the extractant solution was made using LCMS with positive-mode electrospray ionization (ESI(+)) detection. A number of malonyl-ginsenosides were tentatively identified by their mass spectral fragmentation spectra and indicating that they were converted to the free ginsenosides by the new extraction/hydrolysis procedure.

Application of capillary electrophoresis to predict crossover frequency of polystyrene particles in dielectrophoresis.

CE is used to calculate the zeta potential of polystyrene particles in order to estimate the surface conductivity of the particles. These values are used to predict the dielectrophoretic behavior, including the crossover frequency of particles under the influence of an AC electric field. Predictions for fluorescent polystyrene particles that are unmodified, carboxylate-modified, or streptavidin-modified are tested using miniaturized dielectrophoresis cells containing patterned gold quadrupole electrodes. The particle surface conductivities derived from CE separations differ from those derived from dielectrophoresis experiments by < or =0.003 S/m and serve as a guide to effectively select the suspending medium to generate a crossover frequency approximately 0.5 MHz. Prediction of dielectrophoresis crossover frequency is limited by several factors, especially the accuracy and precision of the conductivity measurements for the particle and suspending medium. A rapid analysis of particles by CE is a viable alternative to determine zeta potential.

Electrophoretic screening of ligands under suppressed EOF with an inert phospholipid coating.

The applicability of dual injection CE for affinity selection of biopolymers that contain multiple binding sites is demonstrated. The efficient analysis of biomolecules such as carbohydrates and proteins, as well as pharmaceuticals by CE requires the reduction or elimination of nonspecific interactions with the capillary surface. Phospholipids are integral components of cell membranes and aqueous phospholipid liquid crystals adopt a bilayer structure on fused-silica. This phospholipid surface does not interact significantly with the following biomolecules: serum albumin, the 96-110 heparin binding domain of amyloid precursor protein (APP), polydisperse glycosaminoglycans, and variable chain-length oligosaccharides. Pharmaceuticals including five anionic nonsteroidal anti-inflammatory drugs, three cationic analgesics, and two cationic beta-blockers, also show minimal interaction with the surface. In addition, the use of a phospholipid coating suppresses EOF, which enables reversed-polarity separations, dual opposite injection CE, affinity screening via CE by dual opposite injection, and serial target-ligand injections.