Femoral neck stress fracture and medial tibial stress syndrome following high intensity interval training: A case report and review of literature.

BACKGROUND: Femoral and tibial stress injuries are commonly found in long distance running athletes. Stress fractures have rarely been reported in athletes performing high intensity interval training (HIIT) exercise. The objective of this study was to report a case of a patient who presented with medial tibial stress syndrome and femoral neck stress fracture after performing HIIT exercises. CASE SUMMARY: A 26 year old female presented with bilateral medial tibial pain. She had been performing HIIT exercise for 45 min, five times weekly, for a seven month period. Her tibial pain was gradual in onset, and was now severe and worse on exercise, despite six weeks of rest. Magnetic resonance imaging (MRI) revealed bilateral medial tibial stress syndrome. As she was taking norethisterone for birth control, a dual energy X-ray absorbitometry scan was performed which demonstrated normal bone mineral density of her lumbar spine and femoral neck. She was managed conservatively with analgesia and physiotherapy, but continued to exercise against medical advice. She presented again six months later with severe right hip pain. MRI of her right hip demonstrated an incomplete stress fracture of her subtrochanteric region. Her symptoms resolved with strict rest and physiotherapy. CONCLUSION: HIIT may cause stress injury of the tibia and femur in young individuals.

Implementation of a multidisciplinary inpatient opioid overdose education and naloxone distribution program at a large academic medical center.

PURPOSE: Opioid overdose-related deaths continue to rise. Despite public health efforts, there is still variability in obtainment of naloxone, a lifesaving antidote. We share our experience in the implementation of a novel opioid overdose education and naloxone distribution (OEND) program at a large academic medical center. METHODS: Collaborative efforts made by pharmacists, pharmacy students, physicians, nurses, and recovery coaches were employed in the design of the program. The service was available Monday through Friday, 9 am to 6 pm, and primarily carried out by pharmacy students on a rotating basis. Services offered included bedside delivery of naloxone and education prior to the day of discharge. In preparation for their role, the pharmacy students were required to complete a series of trainings and competency assessments. RESULTS: A total of 40 patients were included in the program evaluation. Of the completed consults 96.7% (n = 30) of patients received both counseling and naloxone delivery. Eighty percent of patients had a history of nonfatal opioid overdose, but only 37.5% had naloxone listed as a home medication. OEND services were provided to 66% of individuals with patient-directed discharges. CONCLUSION: Implementation of an inpatient OEND program by mobilizing trained student pharmacists is feasible and expands naloxone access to patients during transitions of care. A similar model could be considered in the future for the delivery of harm reduction supplies to this patient population.

Ketamine in Refractory Cyclic Vomiting Syndrome: A Case Report and Review of Literature.

PURPOSE: To describe the use of ketamine in an adult patient in aborting a cyclic vomiting syndrome (CVS) episode. SUMMARY: A 40-year-old man with a history of CVS was admitted after several days of nausea and vomiting. He was given parenteral doses of lorazepam and ondansetron but was unable to remain emesis-free. Ketamine was recommended by Gastroenterology as a therapeutic option after exhausting all first- and second-line agents. Ketamine is a noncompetitive N-methyl-D-aspartate receptor antagonist that is widely used for its analgesic and sedative effects. While there is some data to support its use in CVS, most of the published literature has been limited to the Emergency Department setting and no specific therapeutic dose has been established. We will review our institution's experience with low dose ketamine in an adult patient with a CVS episode that is refractory to first-line agents. CONCLUSION: In the case described, ketamine at a low sub-anesthetic dose successfully aborted a CVS episode with no appreciable side effects. As much of ketamine's full effects remain relatively unknown, additional studies are needed to determine optimal strategies for ketamine use in patients with a CVS episode.

Novel Seizure Biomarkers in Continuous Electrocardiograms from Pediatric Epilepsy Patients.

There is growing evidence that seizures are accompanied by multi-system changes, not only in the brain but also in organs and systems under its control. Non-EEG measurements from these systems could be leveraged to improve seizure prediction, which is difficult but critical to the success of next-generation epilepsy therapies. Clinical electrophysiology studies during presurgical patient evaluations routinely collect continuous EEG but also ECG data that span multiple days. Prior work has reported electrocardiographic changes but has primarily focused on ventricular activity and brief peri-ictal intervals. Using novel data-driven classification and separation of the ECG high-dimensional signal space, this study investigated seizure-related changes in both ventricular and atrial activity. Measures of complexity as well as heart rate and R-R interval length were analyzed over time in continuous ECGs from 22 pediatric patients with pharmacoresistant seizures and no diagnosed cardiovascular anomalies. Fifteen patients (>68%) had significant changes in atrial or ventricular activity (or both) in intervals containing seizures. Thus, for a substantial number of patients, cardiac markers may be specifically modulated by seizures and could be leveraged to improve and personalize seizure prediction.

Risk Factors for Mortality in an Older Veteran Population With infective Endocarditis.

OBJECTIVE: To determine 30-day and 1-year mortality in patients treated for infective endocarditis (IE) in a VA population. The secondary objective was to identify risk factors for increased risk of mortality in veterans diagnosed with IE. DESIGN: A retrospective cohort study. SETTING: Veterans Affairs Western New York Healthcare System PARTICIPANTS: Patients who had a diagnosis of IE between the years 2005 and 2016. Patients were identified via International Classification of Diseases (ICD) codes. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Factors for death and survival were compared using a bivariate analysis. Significant factors were built into a multivariate logistic regression analysis to determine risk factors for death at 30 days and 1 year. RESULTS: Between 2005 and 2016, there were 153 patients with IE. All-cause mortality at 30 days was 14% versus 39% at 1 year. Patients were more likely to die at 1 year with higher Pitt Bacteremia Scores, older age, and lower number of minor criteria according to Duke Criteria. Comorbidities were similar between groups. CONCLUSIONS: Older patients with higher Pitt Bacteremia Scores and lower numbers of minor criteria are more likely to experience mortality at one year. Given the high rates of death at one year, close monitoring, even after completion of therapy may be necessary in older patients. Senior care pharmacists are in a unique position to monitor these patients.

Identification of regulatory elements required for Stra8 expression in fetal ovarian germ cells of the mouse.

In mice, the entry of germ cells into meiosis crucially depends on the expression of stimulated by retinoic acid gene 8 (Stra8). Stra8 is expressed specifically in pre-meiotic germ cells of females and males, at fetal and postnatal stages, respectively, but the mechanistic details of its spatiotemporal regulation are yet to be defined. In particular, there has been considerable debate regarding whether retinoic acid is required, in vivo, to initiate Stra8 expression in the mouse fetal ovary. We show that the distinctive anterior-to-posterior pattern of Stra8 initiation, characteristic of germ cells in the fetal ovary, is faithfully recapitulated when 2.9 kb of the Stra8 promoter is used to drive eGFP expression. Using in vitro transfection assays of cutdown and mutant constructs, we identified two functional retinoic acid responsive elements (RAREs) within this 2.9 kb regulatory element. We also show that the transcription factor DMRT1 enhances Stra8 expression, but only in the presence of RA and the most proximal RARE. Finally, we used CRISPR/Cas9-mediated targeted mutation studies to demonstrate that both RAREs are required for optimal Stra8 expression levels in vivo.

Micro-RNA Clusters Integrate Evolutionary Constraints on Expression and Target Affinities: The miR-6/5/4/286/3/309 Cluster in Drosophila.

A striking feature of micro-RNAs is that they are often clustered in the genomes of animals. The functional and evolutionary consequences of this clustering remain obscure. Here, we investigated a micro-RNA cluster miR-6/5/4/286/3/309 that is conserved across drosophilid lineages. Small RNA sequencing revealed expression of this micro-RNA cluster in Drosophila melanogaster leg discs, and conditional overexpression of the whole cluster resulted in leg appendage shortening. Transgenic overexpression lines expressing different combinations of micro-RNA cluster members were also constructed. Expression of individual micro-RNAs from the cluster resulted in a normal wild-type phenotype, but either the expression of several ancient micro-RNAs together (miR-5/4/286/3/309) or more recently evolved clustered micro-RNAs (miR-6-1/2/3) can recapitulate the phenotypes generated by the whole-cluster overexpression. Screening of transgenic fly lines revealed downregulation of leg-patterning gene cassettes in generation of the leg-shortening phenotype. Furthermore, cell transfection with different combinations of micro-RNA cluster members revealed a suite of downstream genes targeted by all cluster members, as well as complements of targets that are unique for distinct micro-RNAs. Considered together, the micro-RNA targets and the evolutionary ages of each micro-RNA in the cluster demonstrate the importance of micro-RNA clustering, where new members can reinforce and modify the selection forces on both the cluster regulation and the gene regulatory network of existing micro-RNAs. Key words: micro-RNA, cluster, evolution.

Plasma extracellular vesicle microRNAs for pulmonary ground-glass nodules.

In this study, we evaluated the diagnostic value and molecular characteristics of plasma extracellular vesicles (EVs)-derived miRNAs for patients with solitary pulmonary nodules (SPNs), particularly ground-glass nodules (GGNs). This study was registered at www.clinicaltrials.gov under registration number NCT03230019. Small RNA sequencing was performed to assess plasma EVs miRNAs in 59 patients, including 12 patients with benign nodules (2017, training set). MiRNA profiles of 40 an additional individuals were sequenced (2018, validation set). Overall, 16 pure GGNs, 21 mixed GGNs, and 42 solid nodules were included, with paired post-operative plasma samples available for 20 patients. The target miRNA/reference miRNA ratio was used to construct a support vector machine (SVM) model. The SVM model with the best specificity showed 100% specificity in both the training and validation sets independently. The model with the best sensitivity showed 100% and 96.9% sensitivity in the training and validation sets, respectively. Principal component analysis revealed that pure GGN distributions were distinct from those of solid nodules, and mixed GGNs had a diffuse distribution. Among differentially expressed miRNAs, miR-500a-3p, miR-501-3p, and miR-502-3p were upregulated in tumor tissues and enhanced overall survival. The SVM classifier accurately distinguished malignant GGNs and benign nodules. The distinct profile characteristics of miRNAs provided insights into the feasibility of EVs miRNAs as prognostic factors in lung cancer.

Adaptation to deep-sea chemosynthetic environments as revealed by mussel genomes.

Hydrothermal vents and methane seeps are extreme deep-sea ecosystems that support dense populations of specialized macro-benthos such as mussels. But the lack of genome information hinders the understanding of the adaptation of these animals to such inhospitable environments. Here we report the genomes of a deep-sea vent/seep mussel (Bathymodiolus platifrons) and a shallow-water mussel (Modiolus philippinarum). Phylogenetic analysis shows that these mussel species diverged approximately 110.4 million years ago. Many gene families, especially those for stabilizing protein structures and removing toxic substances from cells, are highly expanded in B. platifrons, indicating adaptation to extreme environmental conditions. The innate immune system of B. platifrons is considerably more complex than that of other lophotrochozoan species, including M. philippinarum, with substantial expansion and high expression levels of gene families that are related to immune recognition, endocytosis and caspase-mediated apoptosis in the gill, revealing presumed genetic adaptation of the deep-sea mussel to the presence of its chemoautotrophic endosymbionts. A follow-up metaproteomic analysis of the gill of B. platifrons shows methanotrophy, assimilatory sulfate reduction and ammonia metabolic pathways in the symbionts, providing energy and nutrients, which allow the host to thrive. Our study of the genomic composition allowing symbiosis in extremophile molluscs gives wider insights into the mechanisms of symbiosis in other organisms such as deep-sea tubeworms and giant clams.

The effect of attention on the release of anticipatory timing actions.

A loud auditory stimulus (LAS) presented during movement preparation can result in an earlier than normal movement onset. This effect had initially been assumed to be independent of the sensorial modality people attended to trigger their responses. In 2 experiments, we tested whether this assumption was warranted. In Experiment 1, we employed a timed response paradigm in which participants were cued in relation to the precise moment of movement onset of their motor responses. In the visual task, participants were cued about movement onset via visual cues on a monitor screen. In the auditory task, participants were cued about movement onset through tones delivered via headphones. During both tasks, we delivered an unexpected LAS 200 ms prior to movement onset. We found that the responses were initiated earlier by the LAS in the auditory task in relation to the visual task. In Experiment 2, we presented participants with a sequence of tones and flashes interleaved. The participants' task was to ignore either the tones or the flashes and make a movement in sync with the last tone or flash. The results showed that when participants had to ignore the task-irrelevant tones in the background, the early responses were much reduced. In contrast, when participants had to pay attention to the tones and ignore the flashes, the early release of anticipatory actions was robust. Our results indicate that attention to a specific sensorial modality can affect the early release of motor responses by LAS.