Clock gene homologs lin-42 and kin-20 regulate circadian rhythms in C. elegans.

Circadian rhythms are endogenous oscillations in nearly all organisms, from prokaryotes to humans, allowing them to adapt to cyclical environments for close to 24 h. Circadian rhythms are regulated by a central clock, based on a transcription-translation feedback loop. One important protein in the central loop in metazoan clocks is PERIOD, which is regulated in part by Casein kinase 1ε/δ (CK1ε/δ) phosphorylation. In the nematode Caenorhabditis elegans, period and casein kinase 1ε/δ are conserved as lin-42 and kin-20, respectively. Here, we studied the involvement of lin-42 and kin-20 in the circadian rhythms of the adult nematode using a bioluminescence-based circadian transcriptional reporter. We show that mutations of lin-42 and kin-20 generate a significantly longer endogenous period, suggesting a role for both genes in the nematode circadian clock, as in other organisms. These phenotypes can be partially rescued by overexpression of either gene under their native promoter. Both proteins are expressed in neurons and epidermal seam cells, as well as in other cells. Depletion of LIN-42 and KIN-20, specifically in neuronal cells after development, was sufficient to lengthen the period of oscillating sur-5 expression. Therefore, we conclude that LIN-42 and KIN-20 are critical regulators of the adult nematode circadian clock through neuronal cells.

Clostridioides difficile Infection in Hospitalized Pediatric Patients: Comparisons of Epidemiology, Testing, and Treatment from 2013 to 2019.

OBJECTIVES: To compare the incidence, epidemiology, testing patterns, treatment, and outcomes of Clostridioides difficile infection (CDI) among hospitalized pediatric patients from 2013 to 2019. STUDY DESIGN: The Pediatric Health Information System database was queried for patient admissions (age 0-17 years) with International Classification of Diseases, 9th and 10th edition, codes for diagnoses of CDI with a billing code for a CDI-related antibiotic treatment. RESULTS: We identified 17 142 pediatric patients, representing 23 052 admissions, with CDI. The adjusted annual CDI incidence decreased over the study period from 7.09 cases per 10 000 patient-days (95% CI, 6.15-8.18) in 2013 to 4.89 cases per 10 000 patient-days (95% CI, 4.03-5.93) in 2019 (P < .001). C difficile-specific testing also decreased during the study period (P < .001). Chronic gastrointestinal conditions (36%) and malignancy (32%) were the most common comorbidities in CDI encounters. Oral metronidazole use decreased during the study period (P < .01) and oral vancomycin use increased (P < .001). CONCLUSIONS: Our study demonstrates a decrease in CDI incidence in hospitalized pediatric patients, a notable change from prior studies, although this may have been influenced by altered testing patterns. We found a high incidence of CDI in patients with cancer and gastrointestinal conditions: groups that warrant targeted evaluation of CDI prevention and treatment.

Observational descriptive study of ultrasound use and its impact on clinical decisions in the accident and emergency department at Georgetown public hospital corporation.

INTRODUCTION: Point-of-care ultrasound (POCUS) is physician-performed at the bedside, and it is a powerful diagnostic tool, especially in resource-limited emergency medicine healthcare settings. This study aims to quantify both the use of ultrasound and its impact on patient care at the Accident and Emergency Department at the Georgetown Public Hospital Corporation (GPHC). METHODS: This is a cross-sectional observational descriptive analysis of data collected for quality assessment in the GPHC Accident and Emergency Department. Over the course of two months, physicians were asked to record each ultrasound exam performed and record whether the ultrasound results changed patient disposition or the medication used in management. RESULTS: During the study period, there were 173 ultrasound data sheets collected representing 426 ultrasound studies. 196 studies were positive with pathologic findings (46.0%). The use of ultrasound in patient care either changed the patient's final disposition or medication 78.6% of the time. CONCLUSION: Ultrasound is used frequently at the Georgetown Public Hospital Corporation for a wide variety of applications. When utilized, POCUS frequently influenced patient care.

Repeat-Dose Toxicity Study Using the AFPL1-Conjugate Nicotine Vaccine in Male Sprague Dawley Rats.

Tobacco smoking is the cause of 20% of Canadian deaths per year. Nicotine vaccines present a promising alternative to traditional smoking cessation products, but to date, no vaccine has been able to move through all phases of clinical trials. We have previously demonstrated that the AFPL1-conjugate nicotine vaccine does not induce systemic or immunotoxicity in a mouse model and that a heterologous vaccination approach is more advantageous than the homologous routes to inducing mucosal and systemic anti-nicotine antibodies. The purpose of this study was to confirm the safety profile of the vaccine in a repeat-dose toxicity study. The heterologous vaccination strategy was again used, and Sprague Dawley rats were administered a dose five times greater than in our previous studies. Physiological conditions, food and water consumption, body temperature, injection site inflammation, relative weights of organs, histopathology, and blood chemistry and hematology were evaluated during the course of the vaccination period to determine the safety of the vaccine. The AFPL1-conjugate nicotine vaccine did not induce clinically relevant changes or induce symptoms that would be associated with toxicity, making it a promising candidate for future investigations.

Case Reports of Situs Inversus Totalis and Dextrocardia in Sprague Dawley Rats.

Situs inversus totalis is a condition where there is a transposition of all internal organs from their normal anatomical location. This infrequent and rare congenital condition has been described in several species of mammals. Dextorcardia is a series of conditions associated with an abnormal congenital positioning of the heart, and is often associated with situs inversus totalis. Here we report a case of situs inversus totalis and two cases of dextrocardia identified in Sprague Dawley rats during gross necropsy evaluations at both the Health Sciences North Research Institute (HSNRI) in Canada and Finlay Institute of Vaccine Research and Production in Cuba. The intent of this report is to share our findings and aid in the accumulation of data on these rare conditions.

Emergency Ultrasound Training Program in Guyana: Systematic Credentialing Process in a Resource-limited Setting.

Ultrasound has become an important skill for emergency physicians. Ultrasound is more crucial in resource-limited settings where diagnostic testing may not be as timely or available at all. In 2015, an emergency medicine ultrasound curriculum was implemented at Georgetown Public Hospital Corporation in Georgetown, Guyana. Implementing an ultrasound-training curriculum in Guyana had four main challenges: limited ultrasound equipment, lack of informational technology infrastructure to record and review ultrasound examinations, availability of local emergency ultrasound expertise, and competing educational needs within the curriculum. These challenges were met with creative solutions and the formation of a formalized curriculum and credentialing process. The experience of creating the program is described along with the curriculum, credentialing process, and plan for sustainability. Since implementation, every graduating resident has displayed competency on final assessment.

Hospital Readmissions in Children with Pulmonary Hypertension: A Multi-Institutional Analysis.

OBJECTIVE: To assess the rate of and risk factors for 30-day hospital readmission in children with pulmonary hypertension. STUDY DESIGN: The Pediatric Health Information System database was analyzed for patients ≤18 years old with pulmonary hypertension (International Classification of Diseases, Ninth Revision, diagnosis codes of 416.0, 416.1, 416.8, or 416.9) admitted from 2005 through 2014. A generalized hierarchical regression model was used to determine significant ORs and 95% CIs associated with 30-day readmission. RESULTS: A total of 13580 patients met inclusion criteria (median age 1.7 years [IQR 0.3-8.7], 45.3% with congenital heart disease). Admissions increased 4-fold throughout the study period. Associated hospital charges increased from $119 million in 2004 to $929 million in 2014. During initial admission, 57.4% of patients required admission to the intensive care unit, and 48.2% required mechanical ventilation. The 30-day readmission rate was 26.3%. Mortality during readmission was 4.2%. Factors increasing odds of readmission included a lower hospital volume of pulmonary hypertension admissions (1.41 [1.23-1.57], P < .001) and having public insurance (1.26 [1.16-1.38], P < .001). Decreased odds of readmission were associated with older age and the presence of congenital heart disease (0.86 [0.79-0.93], P < .001). CONCLUSIONS: The pediatric pulmonary hypertension population carries significant morbidity, as reflected by a high use of intensive care unit resources and a high 30-day readmission rate. Younger patients and those with public insurance represent particularly at-risk groups.

Rehabilitación de columna lumbar / Rehabilitation of lumbar spine

EI síndrome de dolor lumbar crónico esta asociado a una serie de disfunciones neuromusculares, neuromecánicas y trastornos emocionales, siendo de consenso mundial que el abordaje terapéutico debe basarse en el modelo biopsicosocial, donde el factor emocional es el más relevante. Desde el punto de vista neuromecánico, estudios biomecánicos de correlación y electrofisiológicos de elevada confiabilidad, señalan que la columna vertebral es inherentemente inestable y que su estabilidad depende tanto de la integridad del sistema sensorio motriz como de la indemnidad de los tres subsistemas de control espinal, siendo los mecanismos de respuesta aferentes (feedback) y eferentes (feedforward) indispensables para el control motor articular. Desde el punto de vista neuromuscular, toda activación muscular asociada a un movimiento de un segmento corporal se acompaña de un patrón motor y de movimiento especifico para dicha acción, donde cada patrón de movimiento posee un patrón secuencial de activación muscular tipo, el cual puede variar en presencia de disfunción. Se postula que la co-contracción de la musculatura abdominal y paravertebral es fundamental para lograr la estabilidad espinal al aumentar la rigidez vertebral. Esta actividad muscular debe ser coordinada en intensidad, tiempo y frecuencia para desencadenar los mecanismos protectores de la estabilidad espinal. La disfunción del sistema muscular estabilizador local y global está asociada al síndrome de dolor lumbar crónico, donde la reeducación de la contracción muscular a través de respuestas motoras voluntarias, reflejas e involuntarias del sistema muscular estabilizador es fundamental para evitar recidivas y reagudizaciones. Es decir, el objetivo final y esencial en un proceso de rehabilitación espinal es convertir el control consciente del movimiento correcto a un nivel inconciente. El objetivo de esta revisión es entregar conceptos neurofisiológicos y neuromecánicos de avanzada según medicina en...

The chronic lumbar pain syndrome is associated to a series of neuromuscular neuro-mechanic dysfunctions and emotional disorders, being world-wide known that the therapeutic approach must be based in the bio-psychosocial model, where the emotional factor is the most relevant. From the neuro-mechanic point of view, bio-mechanic studies of correlation and highly reliable electro-physiologic studies indicating that the vertebral column is inherently instable and that its stability depends both of the sensor motor system integrity as well as of the three spinal control subsystemsindemnity, being the feedback response and feed-forward mechanism essential for the articular motor control. From the neuromuscular point of view, all muscular activation associated to a corporal segment movement is accompanied of a motor pattern and of specific movement for said action; where each movement pattern has a sequence of muscular type activation, which may vary when there is a dysfunction. It is assumed that the abdominal muscular and para-vertebralco-contraction is fundamental to achieve the spinal stability when increasing the vertebral rigidity. This muscular activity must be coordinated in intensity, time and frequency to generate the protective mechanism for the spinal stability. The muscular system dysfunction of the local and global muscular stabilizer is associated to chronic lumbar pain, where the reeducation of the muscular contraction by means of voluntary, reflex and involuntary motor responses of the muscular stabilizer system is fundamental to avoid relapsing and acute exacerbation. Likewise, the final and essential objective in a spine rehabilitation process is to convert the conscious control of the correct movement to an unconscious level The objective of this review is to deliver advance neurophysiologic and neuro-mechanical concepts according to evidence based medicine (EBM), fundamental for the development of essential therapeutical strategies in the...

Brazilian hydroxyapatite implant.

PURPOSE: To evaluate a synthetic hydroxyapatite (HA) (manufactured in Brazil) in a rabbit model. METHODS: Nine New Zealand white rabbits underwent enucleation of one eye followed by implantation of either a 12-mm Brazilian synthetic HA implant or a 12-mm BioEye, wrapped in polyglactin 910 mesh. Magnetic resonance imaging was performed to assess fibrovascular ingrowth 4, 8, and 12 weeks after implantation. Three animals were killed at each of the times for histopathologic examination. The Brazilian implant was also examined chemically and by scanning electron microscopy. RESULTS: The Brazilian HA was found to be heavier than either the BioEye or synthetic FCI3 HA implants. It did not have a visible, regularly arranged interconnected porous architecture. Rather, it had randomly appearing channels apparent on its external and internal surface in addition to large cystic areas within the body of the implant. Scanning electron microscopy revealed the implant to have a microporous architecture in addition to the large channels and cystic cavities. Histopathologically, central vascularization occurred by 4 weeks and was also present at 8 and 12 weeks. In three Brazilian implants an unrecognizable, nonbirefringent material was identified. The cause of it was unclear. Chemical analysis confirmed the implant to consist of pure HA. CONCLUSION: The Brazilian implant is pure HA that appears solid but has randomly arranged channels as well as a microporous architecture that allows vascularization to its center. It is heavier than other available HA implants and has the presence of an unidentified foreign material within it. Although this implant is less expensive and does not require a costly manufacturing process, the structural characteristics of the material do not offer any theoretical or clinical advantages. The implant is only available in Brazil at this time.

Paediatric cardiac anaesthesia in a developing country. Guatemala Heart Team.

During the week of October 15-24, 1995 a team of 65 medical, anaesthesiology, surgical, nursing and paramedical personnel travelled to Guatemala City, Guatemala to perform cardiac surgery on children with complex congenital and acquired valvular heart disease. During this mission 42 patients had their lesions surgically repaired. Cardiopulmonary bypass was required in 36 cases. There were no anaesthetic or surgical deaths. All six patients who did not require cardiopulmonary bypass were extubated in the operating room. Of the patients who required cardiopulmonary bypass, 23 were extubated in the operating room (64%). There was no intraoperative anaesthetic morbidity nor postoperative respiratory complications. No patients was reintubated after planned extubation. Cardiac surgery in paediatric age patients can safely be performed in developing countries if close attention is paid to proper patient selection and one maintains the standards of care practised in developed countries.

Aspectos neurofisiológicos mecánicos y clínicos del tratamiento del dolor con neuromoduladores transcutáneos, tipo tens / Mechanic neurophysiological and clinical aspects of pain treatment with transcutaneal neuromodulators, tens type

Gracias al consenso mayoritario, pero no absoluto, en relación a los mecanismos neuro-fisiológicos que regulan la información dolorosa, presentados en la teoría de control de entrada, se puede enfrentar mejor la terapéutica analgésica por parte del kinesiológo. Dentro de la gama de corrientes de baja frecuencia, está la estimulación eléctrica transcutánea, transcutaneal electric nerve stimulation (TENS), que utilizando estímulos eléctricos de alta frecuencia y de amplitud baja (80-100 Hz, TENS convencionales) o estímulos eléctricos de baja frecuencia y amplitud alta (2-10 Hz, TENS tipo acupuntura) realizan la neuromodulación del dolor a nivel periférico o central respectivamente. La electroanalgesia transcutánea presenta una mínima cantidad de contraindicaciones y su efecto terapéutico no produce consecuencias secundarias. A continuación se presentan condiciones físicas y se entregan antecedentes neurofisiológicos que favorecerán la aplicación del TENS por parte del kinesiológo

SUBCOMMISSURAL IMPLANTATION OF AORTIC PROSTHESES WITH THE USE OF THE NONCORONARY SINUS AND THE FIBROUS TRIGONES.

The technique described here permits insertion of a large prosthesis into a small aortic annulus and avoids the necessity of additional procedures for enlarging the aortic ring. Inspection of the fibrous skeleton of the heart reveals that the large intervalvular trigone and the noncoronary sinus of Valsalva are remarkably elastic. Full advantage of this natural elasticity is achieved by suturing the prosthesis to the base of these structures from outside the aorta. Sutures are placed in the sinuses of the right and left cusps in the usual manner. Judicious application of this procedure allows the implantation of a No. 23 or No. 24 prosthesis in cases that would require a No. 19 or No. 21 with the use of conventional methods.