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Background: Residency program applicants use a variety of resources during the application cycle. Program websites can vary substantially, and it is unclear how the website information is used by applicants. We aimed to determine the most popular information source used by applicants. We also sought to identify specific online content that was deemed important in the decision-making process. Methods: A survey was distributed to fourth-year medical students at an academic institution. Demographic information was collected, and the importance of various online resources was gauged using a Likert scale. Subgroup analysis was performed for procedural versus non-procedural specialty applicants. Results: 91 of the 169 fourth-year medical students (54%) completed the survey. The most utilized sources for the students were residency program websites (41%), the Fellowship and Residency Electronic Interactive Database (FREIDA) website (36%), and the Doximity website (14%). The most valued (Likert scale of 4 and 5) website content for the students included information on resident wellness (86%), resident fellowship acquisition (85%), faculty data (84%), residency location and resident lifestyle (81%), and application point of contact (79%). There were significant differences between what procedural specialty applicants deemed important versus what those applying to non-procedural specialties deemed important. Conclusion: Residency program websites are commonly used among applicants during the residency match process. Content on resident wellness was highly valued irrespective of specialty choice; however, this information was often not present on residency websites. These findings may help guide website content development initiatives for residency programs to reflect applicant needs more adequately.

Glioblastoma, the most common and aggressive primary brain tumor, is highly invasive and neurologically destructive. The mean survival for glioblastoma patients is approximately 15 months and there is no effective therapy to significantly increase survival times to date. The development of effective therapy including mechanism-based therapies is urgently needed. At a molecular biology level, N6-methyladenine (m6A) mRNA modification is the most abundant posttranscriptional RNA modification in mammals. Recent studies have shown that m6A mRNA modifications affect cell survival, cell proliferation, invasion, and immune evasion of glioblastoma. In addition, m6A mRNA modifications are critical for glioblastoma stem cells, which could initiate the tumor and lead to therapy resistance. These findings implicate the function of m6A mRNA modification in tumorigenesis and progression, implicating its value in prognosis and therapies of human glioblastoma. This review focuses on the potential clinical significance of m6A mRNA modifications in prognostic and therapeutics of glioblastoma. With the identification of small-molecule compounds that activate or inhibit components of m6A mRNA modifications, a promising novel approach for glioblastoma therapy is emerging.

Aberrant phosphorylation and subsequent aggregation of the trans-activation response (TAR) element DNA binding protein 43 (TDP-43) is a common feature of multiple neurodegenerative disorders and contributes to disease severity. Here, we investigated whether pathologic phosphorylation of TDP-43 (pTDP-43) is a hallmark of human immunodeficiency virus (HIV)- infected brains. We evaluated pTDP-43 immunoreactivity and TDP-43 kinases in HIV-infected (HIV + ) and seronegative post-mortem brain samples. We then used an inducible transgenic mouse model of the HIV-1 protein Tat and primary neuronal cultures, to decipher the underlying mechanism of the proteinopathy. Since opioid use disorder (OUD) can exaggerate HIV neuropathology, we explored interactions between HIV-1 Tat and morphine, a prototypical opioid, for all outcome measures. Cytoplasmic pTDP-43 and TDP-43 immunoreactivities were increased in neurons of the basal ganglia of post-mortem, HIV+ human tissues compared to seronegative controls. An evaluation of TDP-43 kinases revealed an increase in the levels of cytoplasmic casein kinase 2 (CK2) in HIV-positive human tissues but not CK1δ. There was a significant positive correlation between pTDP-43 and CK2 levels. Eight weeks of Tat induction and 2-week subcutaneous morphine exposure (10–40 mg/kg, increasing by 10 mg/kg/b.i.d.) independently produced similar outcomes for cytoplasmic pTDP-43 and CK2 levels in the mouse striatum. In primary, mouse striatal neuronal cultures, co-exposure to Tat and morphine for 24 h increased pTDP-43 levels and CK2 activity. Co-treatment with the CK2 antagonist CX-4945 prevented the Tat- and morphine-induced increases in pTDP-43 levels. Our results demonstrate that CK2 may be a viable therapeutic target for treating pTDP-43 proteinopathy in neuroHIV and OUD. Summary Statement HIV/HIV-1 Tat and morphine independently increase pathologic phosphorylation of TAR DNA binding protein 43 in the striatum. HIV- and opioid-induced pathologic phosphorylation of TAR DNA binding protein 43 may involve enhanced CK2 activity and protein levels.

Introduction Langerhans cell histiocytosis (LCH) is a rare disease that encompasses a spectrum of clinical syndromes. It is characterized by the proliferation and infiltration of white blood cells into organs or organ systems. Reports of management of these lesions have included biopsy, resection, curettage, radiation and/or chemotherapy. Case Presentation A 40-year-old man presented with a history of right proptosis and retro-orbital pain and was found to have a lytic mass involving the greater wing of the sphenoid extending into the right orbit. A stereotactic needle biopsy using neuronavigation demonstrated this to be LCH. After no further treatment, the mass spontaneously resolved, with virtual normalization of the orbital MRI at 10 months following the needle biopsy. The bony defect of the temporal bone caused by the mass also re-ossified following the needle biopsy. Discussion This report highlights the potential for an isolated LCH lesion to regress after simple needle biopsy, an outcome only rarely reported previously. Thus, expectant management of such lesions following biopsy or initial debridement should be considered prior to proceeding with additional treatment.

Glioblastoma is the most common and most lethal primary malignant brain tumor. N6-methyladenosine (m6A) is a widespread and abundant internal messenger RNA (mRNA) modification found in eukaryotes. Accumulated evidence demonstrates that m6A modification is aberrantly activated in human cancers and is critical for tumorigenesis and metastasis. m6A modification is also strongly involved in key signaling pathways and is associated with prognosis in glioblastoma. Here, we briefly outline the functions of m6A and its regulatory proteins, including m6A writers, erasers, and readers of the fate of RNA. We also summarize the latest breakthroughs in this field, describe the underlying molecular mechanisms that contribute to the tumorigenesis and progression, and highlight the inhibitors targeting the factors in m6A modification in glioblastoma. Further studies focusing on the specific pathways of m6A modification could help identify biomarkers and therapeutic targets that might prevent and treat glioblastoma.

During the last decade, the advent of multi-drug resistant pathogens responsible for skin infections tends to make conventional treatments obsolete. Even though many studies have reported the antimicrobial properties of essential oils (EOs), the inconsistent use of various susceptibility testing methods has made information on antimicrobial potential of many EO varieties fragmentary. Using a single method approach, the objective of this work was to assess and to compare the antibacterial and antifungal properties, against skin pathogens, of EOs extracted from West African aromatic plants.Twenty-three plant samples collected in Benin and Burkina Faso were screened against 20 bacterial and fungal isolates obtained from skin lesions. Activity was evaluated by the determination of minimal inhibitory concentrations (MICs), with readings facilitated by the use of resazurin, a blue dye metabolized into pink resorufin by viable cells.Following this screening, nine EOs were found particularly active with MICs lower than 0.35% v/v. Gas Chromatography-Mass Spectrometry (GC/MS) analysis was used to determine the phytochemical profile of these active EOs which were found exceptionally rich in oxygenated monoterpenes, especially aldehydes, alcohols or phenols and their derivatives.Through this study, we demonstrated that several West African EOs have a significant antimicrobial potential which could, however, be considerably impacted by plant growing or harvesting place due to phytochemical composition variation. These EOs, even if their antimicrobial effects appeared lower than those of conventional antibiotics, constitute easily available mixtures of active compounds and could nevertheless be considered, in the context of increasing multidrug resistance, as complementary or alternative therapies in common skin infections management.

Background: Exposure of cells to very short (

Cell swelling and blebbing has been commonly observed following nanosecond pulsed electric field (nsPEF) exposure. The hypothesized origin of these effects is nanoporation of the plasma membrane (PM) followed by transmembrane diffusion of extracellular fluid and disassembly of cortical actin structures. This investigation will provide evidence that shows passive movement of fluid into the cell through nanopores and increase of intracellular osmotic pressure are not solely responsible for this observed phenomena. We demonstrate that phosphatidylinositol-4,5-bisphosphate (PIP2) depletion and hydrolysis are critical steps in the chain reaction leading to cellular blebbing and swelling. PIP2 is heavily involved in osmoregulation by modulation of ion channels and also serves as an intracellular membrane anchor to cortical actin and phospholipase C (PLC). Given the rather critical role that PIP2 depletion appears to play in the response of cells to nsPEF exposure, it remains unclear how its downstream effects and, specifically, ion channel regulation may contribute to cellular swelling, blebbing, and unknown mechanisms of the lasting “permeabilization” of the PM.

Optoacoustic (OA) microscopy using an all-optical system based on the probe beam deflection technique (PBDT) for detection of laser-induced acoustic signals was investigated as an alternative to conventional piezoelectric transducers. PBDT provides a number of advantages for OA microscopy including (i) efficient coupling of laser excitation energy to the samples being imaged through the probing laser beam, (ii) undistorted coupling of acoustic waves to the detector without the need for separation of the optical and acoustic paths, (iii) high sensitivity and (iv) ultrawide bandwidth. Because of the unimpeded optical path in PBDT, diffraction-limited lateral resolution can be readily achieved. The sensitivity of the current PBDT sensor of 22 μV/Pa and its noise equivalent pressure (NEP) of 11.4 Pa are comparable with these parameters of the optical micro-ring resonator and commercial piezoelectric ultrasonic transducers. Benefits of the present prototype OA microscope were demonstrated by successfully resolving micron-size details in histological sections of cardiac muscle.

Above a threshold electric field strength, 600 ns-duration pulsed electric field (nsPEF) exposure substantially porates and permeabilizes cellular plasma membranes in aqueous solution to many small ions. Repetitive exposures increase permeabilization to calcium ions (Ca2+) in a dosage-dependent manner. Such exposure conditions can create relatively long-lived pores that reseal after passive lateral diffusion of lipids should have closed the pores. One explanation for eventual pore resealing is active membrane repair, and an ubiquitous repair mechanism in mammalian cells is lysosome exocytosis. A previous study shows that intracellular lysosome movement halts upon a 16.2 kV/cm, 600-ns PEF exposure of a single train of 20 pulses at 5 Hz. In that study, lysosome stagnation qualitatively correlates with the presence of Ca2+ in the extracellular solution and with microtubule collapse. The present study tests the hypothesis that limitation of nsPEF-induced Ca2+ influx and colloid osmotic cell swelling permits unabated lysosome translocation in exposed cells. The results indicate that the efforts used herein to preclude Ca2+ influx and colloid osmotic swelling following nsPEF exposure did not prevent attenuation of lysosome translocation. Intracellular lysosome movement is inhibited by nsPEF exposure(s) in the presence of PEG 300-containing solution or by 20 pulses of nsPEF in the presence of extracellular calcium. The only cases with no significant decreases in lysosome movement are the sham and exposure to a single nsPEF in Ca2+-free solution.

We report here the crystal structure of a ten-coordinate lanthanum(III) metal coordinated by five bidentate ethylenediamine ligands, [La(C2H8N2)5]Cl3·C2H8N2·CH2Cl2. One free ethylenediamine molecule and three Cl− anions are also located in the asymmetric unit. The overall structure is held together by an extensive hydrogen-bonding network between the Cl− anions and the NH groups on the metal-bound ethylenediamine ligands. The free ethylenediamine molecule is held in an ordered position by additional hydrogen bonds involving both the chlorides and –NH groups on the metal-bound ligands. One highly disordered molecule of dichloromethane is located on an inversion center; however, all attempts to model this disorder were unsuccessful. The electron density in this space was removed using the BYPASS procedure [van der Sluis & Spek (1990). Acta Cryst. A46, 194–201].

Nanosecond electrical pulse (nsEP) exposure activates signaling pathways, produces oxidative stress, stimulates hormone secretion, causes cell swelling and induces apoptotic and necrotic death. The underlying biophysical connection(s) between these diverse cellular reactions and nsEP has yet to be elucidated. Using global genetic analysis, we evaluated how two commonly studied cell types, U937 and Jurkat, respond to nsEP exposure. We hypothesized that by studying the genetic response of the cells following exposure, we would gain direct insight into the stresses experienced by the cell and in turn better understand the biophysical interaction taking place during the exposure. Using Ingenuity Systems software, we found genes associated with cell growth, movement and development to be significantly up-regulated in both cell types 4 h post exposure to nsEP. In agreement with our hypothesis, we also found that both cell lines exhibit significant biological changes consistent with mechanical stress induction. These results advance nsEP research by providing strong evidence that the interaction of nsEPs with cells involves mechanical stress.

The function of the appendix is largely unknown, but its microbiota likely contributes to function. Alterations in microbiota may contribute to appendicitis, but conventional culture studies have not yielded conclusive information. We conducted a pilot, culture-independent 16S rRNA-based microbiota study of paired appendix and rectal samples.We collected appendix and rectal swabs from 21 children undergoing appendectomy, six with normal appendices and fifteen with appendicitis (nine perforated). After DNA extraction, we amplified and sequenced 16S rRNA genes and analyzed sequences using CLoVR. We identified organisms differing in relative abundance using ANOVA (p

Nontraumatic symptomatic hypotension in all patients requires prompt diagnosis and appropriate treatment for optimum outcome. The female population specifically has an expanded differential diagnosis that should be considered when these patients present with hemodynamic collapse. While the most common causes of hypotension in pregnant patients are dehydration, ruptured ectopic pregnancy, and placental and uterine abnormalities, less common nonobstetrical etiologies such as hepatic rupture and ruptured abdominal and visceral artery aneurysms should also be considered. Splenic artery aneurysms are associated with high rates of mortality and in cases of pregnancy, maternal and fetal mortality. These high rates can be attributed to the asymptomatic nature of the aneurysm, rapid deterioration after rupture, and frequent misdiagnosis. In patients with hemodynamic collapse, the role of traditional imaging is limited mainly due to the critical condition of the patient. Bedside ultrasound has emerged as a diagnostic imaging resource in patients with undifferentiated hypotension and in patients with traumatic injuries. However, its use has not been studied specifically in the female population. We present two patients with ruptured splenic artery aneurysms, discuss the role of bedside ultrasound in their management, and introduce a new ultrasound protocol for use in reproductive age female patients with hemodynamic collapse.

The study of living cells may require advanced imaging techniques to track weak and rapidly changing signals. Fundamental to this need is the recent advancement in camera technology. Two camera types, specifically sCMOS and EM-CCD, promise both high signal-to-noise and high speed (>100 fps), leaving researchers with a critical decision when determining the best technology for their application. In this article, we compare two cameras using a live-cell imaging test case in which small changes in cellular fluorescence must be rapidly detected with high spatial resolution. The EM-CCD maintained an advantage of being able to acquire discernible images with a lower number of photons due to its EM-enhancement. However, if high-resolution images at speeds approaching or exceeding 1000 fps are desired, the flexibility of the full-frame imaging capabilities of sCMOS is superior.

Gastroesophageal reflux (GER) is common in the pediatric population. Most cases represent physiologic GER and as the lower esophageal sphincter (LES) matures and a solid diet is introduced, many of these patients (>65%) experience spontaneous resolution of symptoms by two years of age. Those who continue to have symptoms and develop complications such as failure to thrive, secondary respiratory disease, and others are classified as having gastroesophageal reflux disease (GERD). Goals of GERD treatment include the resolution of symptoms and prevention of complications. Treatment options to achieve these goals include dietary or behavioral modifications, pharmacologic intervention, and surgical therapy. This paper will review the clinical presentation of GERD and discuss options for surgical management and outcomes in these patients.

High-amplitude, MV/m, nanosecond pulsed electric fields (nsPEF) have been hypothesized to cause nanoporation of the plasma membrane. Phosphatidylserine (PS) externalization has been observed on the outer leaflet of the membrane shortly after nsPEF exposure, suggesting local structural changes in the membrane. In this study, we utilized fluorescently-tagged Annexin V to observe the externalization of PS on the plasma membrane of isolated Chinese Hamster Ovary (CHO) cells following exposure to nsPEF. A series of experiments were performed to determine the dosimetric trends of PS expression caused by nsPEF as a function of pulse duration, τ, delivered field strength, ED, and pulse number, n. To accurately estimate dose thresholds for cellular response, data were reduced to a set of binary responses and ED50s were estimated using Probit analysis. Probit analysis results revealed that PS externalization followed the non-linear trend of (τ*ED (2))(-1) for high amplitudes, but failed to predict low amplitude responses. A second set of experiments was performed to determine the nsPEF parameters necessary to cause observable calcium uptake, using cells preloaded with calcium green (CaGr), and membrane permeability, using FM1-43 dye. Calcium influx and FM1-43 uptake were found to always be observed at lower nsPEF exposure parameters compared to PS externalization. These findings suggest that multiple, higher amplitude and longer pulse exposures may generate pores of larger diameter enabling lateral diffusion of PS; whereas, smaller pores induced by fewer, lower amplitude and short pulse width exposures may only allow extracellular calcium and FM1-43 uptake.

Currently, traumatic brain injury (TBI) is detected by medical imaging; however, medical imaging requires expensive capital equipment, is time- and resource-intensive, and is poor at predicting patient prognosis. To date, direct measurement of elevated protease activity has yet to be utilized to detect TBI. In this work, we engineered an activity-based nanosensor for TBI (TBI-ABN) that responds to increased protease activity initiated after brain injury. We establish that a calcium-sensitive protease, calpain-1, is active in the injured brain hours within injury. We then optimize the molecular weight of a nanoscale polymeric carrier to infiltrate into the injured brain tissue with minimal renal filtration. A calpain-1 substrate that generates a fluorescent signal upon cleavage was attached to this nanoscale polymeric carrier to generate an engineered TBI-ABN. When applied intravenously to a mouse model of TBI, our engineered sensor is observed to locally activate in the injured brain tissue. This TBI-ABN is the first demonstration of a sensor that responds to protease activity to detect TBI.

Ferumoxytol is a promising non-gadolinium-based contrast agent with numerous varied magnetic resonance imaging applications. Previous reviews of vascular applications have focused primarily on cardiac and aortic applications. After considering safety concerns and technical issues, the objective of this paper is to explore peripheral applications for ferumoxytol-enhanced magnetic resonance angiography (MRA) and venography (MRV) in the upper and lower extremities. Separate searches for each of the following keywords were performed in pubmed: "ferumoxytol," "ultrasmall superparamagnetic iron oxide," and "USPIO." All studies pertaining to MRA or MRV in humans are included in this review. Case-based examples of various peripheral applications are used to supplement a relatively scant literature in this space. Ferumoxytol's unique properties including high T1 relaxivity and prolonged intravascular half-life make it the optimal vascular imaging contrast agent on the market and one whose vast potential has only begun to be tapped.

This study examined the efficacy of project LePWaR, a game-based reading instructional tool, in enhancing the reading performance of key stage 2 learners at Labu-ay Elementary School during the first quarter of the 2023-2024 academic year. Employing a quasi-experimental research design, the study focuses on the influence of project LePWaR on the reading fluency and vocabulary levels of a selected group of 30 learners. Furthermore, the research explores the association between the game-based reading instructional tool and the fluency and vocabulary levels of key stage 2 learners. The investigation employs pre-and post-assessment measures, incorporating the Phil-IRI assessment tool for English oral reading. Additionally, qualitative data are gathered through adapted and modified survey questionnaires and open-ended interviews to evaluate the project's impact comprehensively. Based on the findings, the intervention produced significant improvements in vocabulary (M = 56.79) and fluency (M = 27.56) post-test scores, along with a noticeable rise in standard deviation. These results suggest that learners have improved a wider range of skills, highlighting the effectiveness of the intervention in promoting fluency and vocabulary acquisition. The implications of the study's findings for practice, educational policies, and future research are significant. For practice, educators can consider integrating game-based instructional tools like project LePWaR into their teaching methods, particularly for enhancing reading fluency and vocabulary among key stage 2 learners. This approach can provide engaging and effective learning experiences, catering to diverse learning styles and preferences. Moreover, educational policies could be informed by these results, potentially advocating for the integration of similar game-based interventions into curriculum frameworks or funding initiatives to support innovative teaching practices. Future research could build upon this study by delving deeper into the specific mechanisms through which gamebased learning impacts reading proficiency. Investigating factors such as learner engagement, motivation, and cognitive processes during gameplay could offer valuable insights for optimizing instructional design. Additionally, exploring the long-term effects of such interventions and their sustainability over extended periods would contribute to a more comprehensive understanding of their efficacy and practical implications. Integrating these implications into the abstract would enrich its relevance and inform readers about the broader significance of the study's findings. [ABSTRACT FROM AUTHOR]

This study aimed to determine the level of knowledge on transitional devices in written compositions and writing difficulties of Grade 10 students in Aleosan Secondary Schools. In employing the descriptive-correlational design, the study determined and described the respondents' demographic profiles, such as sex, age, level of the knowledge of the usage of transitional devices in written compositions, and their writing difficulties. Also, the study determined the significant difference in the level of knowledge on transitional devices in written compositions between male and female Grade 10 students and the significant difference in their writing difficulties. The paragraph test and writing test were the main instruments of this study. Findings revealed no significant difference in the level of knowledge of transitional devices in written composition between male and female respondents. However, there is a significant difference in their writing difficulties. Moreover, there is a significant relationship between the level of knowledge of transitional devices and the writing difficulties encountered by the respondents. [ABSTRACT FROM AUTHOR]