Novel FREM1 mutations expand the phenotypic spectrum associated with manitoba‐oculo‐tricho‐anal (MOTA) syndrome and bifid nose renal agenesis anorectal malformations (BNAR) syndrome

Loss of function mutations in FREM1 have been demonstrated in Manitoba‐oculo‐tricho‐anal (MOTA) syndrome and Bifid Nose Renal Agenesis and Anorectal malformations (BNAR) syndrome, but the wider phenotypic spectrum that is associated with FREM1 mutations remains to be defined. We screened three probands with phenotypic features of MOTA syndrome. In one severely affected infant who was diagnosed with MOTA syndrome because of bilateral eyelid colobomas, a bifid nasal tip, hydrometrocolpos and vaginal atresia, we found two nonsense mutations that likely result in complete loss of FREM1 function. This infant also had renal dysplasia, a finding more consistent with BNAR syndrome. Another male who was homozygous for a novel stop mutation had an extensive eyelid colobomas, corneopalpebral synechiae, and unilateral renal agenesis. A third male child diagnosed with MOTA syndrome because of corneopalpebral synechiae and eyelid colobomas had a homozygous splice site mutation in FREM1. These cases illustrate that disruption of the FREM1 gene can produce a spectrum of clinical manifestations encompassing the previously described MOTA and BNAR syndromes, and that features of both syndromes may be seen in the same individual. The phenotype of FREM1‐related disorders is thus more pleiotropic than for MOTA and BNAR syndrome alone and more closely resembles the widespread clinical involvement seen with Fraser syndrome. Moreover, our first case demonstrates that vaginal atresia may be a feature of FREM1‐related disorders. © 2013 Wiley Periodicals, Inc.     

Genetic analysis of structural proteins in the adsorption apparatus of bacteriophage epsilon 15

AIM: To probe the organizational structure of the adsorption apparatus of bacteriophage epsilon 15 (E15) using genetic and biochemical methodologyMETHODS: Hydroxylamine was used to create nonsense mutants of bacteriophage E15. The mutants were then screened for defects in their adsorption apparatus proteins, initially by measuring the concentrations of free tail spike proteins in lysates of cells that had been infected by the phage mutants under non-permissive growth conditions. Phage strains whose infected cell lysates contained above-average levels of free tail spike protein under non-permissive growth conditions were assumed to contain nonsense mutations in genes coding for adsorption apparatus proteins. These mutants were characterized by classical genetic mapping methods as well as automated sequencing of several of their genes. Finally, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography were used to examine the protein compositions of the radioactive particles produced when the various mutants were grown on a non-permissive host cell in the presence of ³⁵S-methionine and co-purified along with E15wt phage on CsCl block gradients.RESULTS: Our results are consistent with gp4 forming the portal ring structure of E15. In addition, they show that proteins gp15 and gp17 likely comprise the central tube portion of the E15 adsorption apparatus, with gp17 being more distally positioned than gp15 and dependent upon both gp15 and gp16 for its attachment. Finally, our data indicates that tail spike proteins comprised of gp20 can assemble onto nascent virions that contain gp7, gp10, gp4 and packaged DNA, but which lack both gp15 and gp17, thereby forming particles that are of sufficient stability to survive CsCl buoyant density centrifugation.CONCLUSION: The portal ring (gp4) of E15 is bound to tail spikes (gp20) and the tail tube (gp15 and gp17); gp17’s attachment requires both gp15 and gp16.     

Adverse drug and device reactions in the oral cavity: Surveillance and reporting

BackgroundAccording to the U.S. Centers for Disease Control and Prevention, 48 percent of Americans (roughly 144 million people) used at least one prescribed medication in the preceding month; 11 percent used five or more. The authors describe the U.S. Food and Drug Administration's (FDA's) MedWatch program, the safety surveillance system for drugs and devices in the United States, and the dentist's role with regard to voluntary reporting of adverse effects (AEs). They also identify the most frequent AEs in the oral cavity as reported in the FDA Adverse Event Reporting System (FAERS).MethodsThe authors reviewed the literature regarding MedWatch, and they mined data in the FAERS public database for the 100 most commonly prescribed medications and their associated AEs.ResultsPharyngitis was the most common AE. Cough, dysgeusia and dysphagia also were common.ConclusionThe MedWatch program and its related databases contain useful information about AEs of pharmaceuticals and devices manifested in the oral cavity. Increased participation in the reporting of suspected adverse reactions will improve the national surveillance system and ultimately will protect patients' safety.Practical ImplicationsAs pharmaceutical consumption increases exponentially for a growing segment of the population, and as innovation in dental technology and devices flourishes, dentists have a distinct role in safeguarding patients' well-being. Promptly reporting AEs in the oral cavity improves quality of care and protects patients' well-being.     

Effects of training in short-term psychodynamic psychotherapy: changes in graduate clinician technique

Abstract

This study investigates the effects of graduate clinician training in short-term psychodynamic psychotherapy (STPP; Book, 1998; Luborsky, 1984; Strupp & Binder, 1984; Wachtel, 1993) on the acquisition of techniques within and across two training cases. Sessions 3 and 9 from the first and second treatment cases of 15 graduate clinicians receiving structured training in STPP were examined for the frequency of psychodynamic–interpersonal (PI) therapeutic techniques. Results demonstrated that structured training in STPP led to a significantly increased use of PI therapeutic techniques both within and across cases. The authors also examined the frequency of cognitive–behavioral (CB) therapeutic techniques used by the graduate clinicians. No changes in the number of CB interventions were observed over the same set of sessions. Practical implications for the use of structured clinical training and issues pertinent to supervision in graduate education are reviewed. Finally, the impact of structured training on graduate clinicians’ ability to form positive collaborative relationships with their patients is also discussed.

Zusammenfassung

Die Effekte von Training in psychodynamischer Kurzzeittherapie: Veränderungen in der Technik bei graduierten klinischen Studenten

Diese Studie untersucht die Effekte von Training auf das Aneignen von Techniken in psychodynamischer Kurzzeittherapie innerhalb und über 2 Trainingsfälle hinweg bei graduierten klinischen Studenten. Die dritte und 9. Sitzung des ersten und 2. Trainingsfalls von 15 graduierten Klinikern, die ein strukturiertes Training für psychodynamische Kurzzeittherapie durchliefen, wurden auf die Häufigkeit psychodynamischer individueller therapeutisccher Techniken hin untersucht. Die Ergebnisse zeigten, dass eine strukturiertes Training in psychodynamischer Kurzzeittherapie zu einem signifikant häufigeren Einsatz von psychodynamisch interpersonellen therapeutischen Techniken, sowohl innerhalb eines Trainingsfalles als auch über beide Fälle hinweg, führt. Die Autoren haben auch die Häufigkeit von kognitiv-verhaltensmässigen Techniken der Auszubildenden untersucht. Hierbei gab es für die untersuchten Sitzungen keine Veränderung in den Häufigkeiten. Praktische Implikationen zur Verwendung des strukturierten klinischen Trainings und Themen, die für die Supervision der Ausbildung in der zweiten Phase relevant sind, werden durchgenommen. Schließlich wird auch der Einfluß des strukturierten Trainings auf die Fähigkeit der Auszubildenden, positive Beziehungen in der Zusammenarbeit mit ihren Patienten zu bilden, diskutiert.

Résumé

Les effets de la formation dans la psychothérapie psychodynamique brève?: changements dans la technique chez le clinicien postgradué

Cette étude investigue les effets de la formation des cliniciens postgradués en psychothérapie psychodynamique brève?(STPP?; Book, 1998?; Luborsky, 1984?; Strupp & Binder, 1984?; Wachtel, 1993) sur l'acquisition de techniques dans et entre deux cas de formation. Les séances 3 et 9 du premier et deuxième cas de formation de 15 cliniciens postgradués recevant de la formation structurée en STPP étaient examinés en fonction de la fréquence des techniques thérapeutiques psychodynamiques – interpersonnelles (PI). Les résultats ont démontré que la formation structurée en STPP a entraîné un emploi augmenté de façon significative de techniques thérapeutiques PI aussi bien dans qu'entre les cas. Les auteurs ont examiné également la fréquence de techniques thérapeutiques cognitives-comportementales (CB) utilisées par les cliniciens postgradués. Aucun changement du nombre d'interventions CB n'a été observé dans le même ensemble de séances. Des implications pratiques pour l'application d'une formation clinique structurée et des sujets en lien avec la supervision dans l’éducation postgraduée sont revues. Finalement, l'impact d'une formation structurée sur la capacité du clinicien postgradué à former des relations de collaboration positive avec leurs patients est également discuté.

Resumen

Efectos de la supervisión en psicoterapia psicodinámica breve: cambios en la técnica clínica del graduado

Este estudio investiga los efectos de la supervisión clínica del graduado en psicoterapia psicodinámica breve (STPP; Libro, 1998, Luborsky, 1984, Strupp /& Binder, 1984, Wachtel, 1993) sobre la adquisición de técnicas dentro y a través de dos casos de supervisión. Se estudiaron las 3ra. y 9na. sesiones del primero y segundo casos de supervisión de quince clínicos graduados que recibieron supervisión en STPP, para ver la frecuencia de las técnicas terapéuticas psicodinámicas-interpersonales (PI). Los resultados demostraron que la supervisión estructurada en STPP condujo a un aumento significativo del uso de técnicas terapéuticas PI tanto dentro como a través de los casos. Los autores también estudiaron la frecuencia de técnicas terapéuticas cognitivo-comportamentales (CB) usadas por los clínicos graduados. No se observaron cambios en el número de intervenciones CB en el mismo conjunto de sesiones. Se pasó revista a las implicaciones prácticas del uso de la supervisión clínica estructurada y a cuestiones pertinentes a la supervisión en la educación de los graduados. Finalmente, también se debate sobre el impacto que puede tener la supervisión estructurada sobre la capacidad de los clínicos graduados para formar relaciones colaboradoras positivas con sus pacientes.

Resumo

Efeitos do treino em psicotetrapia psicodinâmica breve: Mudanças nas técnicas de estudantes

Este estudo examina os efeitos do treino clínico de estudantes graduados em psicoterapia psicodinâmica breve (PPB; Book, 1998; Luborsky, 1984; Strupp & Binder, 1984; Wachtel, 1993) em termos de aquisições das técnicas durante e entre dois casos de treino. Foi analisada a frequência de técnicas terapêuticas de psicoterapia interpessoal (PI), nas sessões 3 e 9 do primeiro e do segundo caso de treino de 15 estudantes graduados que estavam recebendo formação estruturada em PPB. Os resultados demonstraram que o treino estruturado em PPB conduzia a um aumento significativo no uso de técnicas terapêuticas de PI durante e entre os casos. Os autores analisaram também a frequência das técnicas terapêuticas cognitivo-comportamentais (CC) utilizadas pelos estudantes. Não se verificaram mudanças no número de intervenções CC durante o mesmo conjunto de sessões. São revistas as implicações práticas para a utilização de treino clínico estruturado e aspectos pertinentes para a supervisão de estudantes graduados. Finalmente, será também discutido o impacto do treino estruturado sobre as capacidades dos estudantes para estabelecerem relações terapêuticas positivas com os seus pacientes.

     

Injury Characteristics and Outcomes in Elderly Trauma Patients in Sub-Saharan Africa

Background

Traumatic injury in the elderly is an emerging global problem with an associated increase in morbidity and mortality. This study sought to describe the epidemiology of elderly injury and outcomes in sub-Saharan Africa.

Methods

We conducted a retrospective analysis of adult patients (≥ 18 years) with traumatic injuries presenting to the Kamuzu Central Hospital (KCH) in Lilongwe, Malawi, over 5 years (2009–2013). Elderly patients were defined as adults aged ≥65 years and compared to adults aged 18–44 and 45–64 years. We used propensity score matching and logistic regression to compare the odds of mortality between age groups using the youngest age group as the reference.

Results

42,816 Adult patients with traumatic injuries presented to KCH during the study period. 1253 patients (2.9 %) were aged ≥65 years with a male preponderance (77.4 %). Injuries occurred more often at home as age increased (25.3, 29.5, 41.1 %, p < 0.001) and falls were more common (14.1, 23.8, 36.3 %, p < 0.001) for elderly patients. Elderly age was associated with a higher proportion of hospital admissions (10.6, 21.3, 35.2 %, p < 0.001). Upon propensity score matching and logistic regression analysis, the odds ratio of mortality for patients aged ≥65 was 3.15 (95 % CI 1.45, 6.82, p = 0.0037) compared to the youngest age group (18–44 years).

Conclusions

Elderly trauma in a resource-poor area in sub-Saharan Africa is associated with a significant increase in hospital admissions and mortality. Significant improvements in trauma systems, pre-hospital care, and hospital capacity for older, critically ill patients are imperative.

     

A systematic review of low‐level light therapy for treatment of diabetic foot ulcer

Diabetes mellitus (DM) is a significant international health concern affecting more than 387 million individuals. A diabetic person has a 25% lifetime risk of developing a diabetic foot ulcer (DFU), leading to limb amputation in up to one in six DFU patients. Low‐level light therapy (LLLT) uses low‐power lasers or light‐emitting diodes to alter cellular function and molecular pathways, and may be a promising treatment for DFU. The goal of this systematic review is to examine whether the clinical use of LLLT is effective in the healing of DFU at 12 and 20 weeks in comparison with the standard of care, and to provide evidence‐based recommendation and future clinical guidelines for the treatment of DFU using LLLT. On September 30, 2015, we searched PubMed, EMBASE, CINAHL, and Web of Science databases using the following terms: “diabetic foot” AND “low level light therapy,” OR “light emitting diode,” OR “phototherapy,” OR “laser.” The relevant articles that met the following criteria were selected for inclusion: randomized control trials (RCTs) that investigated the use of LLLT for treatment of DFU. Four RCTs involving 131 participants were suitable for inclusion based upon our criteria. The clinical trials used sham irriadiation, low dose, or nontherapeutic LLLT as placebo or control in comparison to LLLT. The endpoints included ulcer size and time to complete healing with follow‐up ranging from 2 to 16 weeks. Each article was assigned a level of evidence (LOE) and graded according to the Oxford Center for Evidence‐based Medicine Levels of Evidence Grades of Recommendation criteria. Limitations of reviewed RCTs include a small sample size (N < 100), unclear allocation concealment, lack of screening phase to exclude rapid healers, unclear inclusion/exclusion criteria, short (<30 days) follow‐up period, and unclear treatment settings (wavelength and treatment time). However, all reviewed RCTs demonstrated therapeutic outcomes with no adverse events using LLLT for treatment of DFU. This systematic review reports that LLLT has significant potential to become a portable, minimally invasive, easy‐to‐use, and cost effective modality for treatment of DFU. To enthusiastically recommend LLLT for treatment of DFU, additional studies with comparable laser parameters, screening period to exclude rapid healers, larger sample sizes and longer follow‐up periods are required. We envision future stringent RCTs may validate LLLT for treatment of DFU. Systematic review registration number: PROSPERO CRD42015029825.     

Schizophrenia and phenotypic plasticity: schizophrenia may represent a predictive, adaptive response to severe environmental adversity that allows both bioenergetic thrift and a defensive behavioral strategy

It is well recognized that investigation into the relationship between early life programming and subsequent neurological disorders may have powerful implications for understanding the human vulnerability to psychopathology. The present article will propose that schizophrenia may be adaptively programmed by early environmental adversity permitting physiological and behavioral characteristics that would have created a fitness advantage in the ancestral environment under conditions of nutritional scarcity and severe environmental stress. This proposition will be analyzed in terms of phenotypic plasticity theory which explains how and why specific environmental stressors can alter normal gene expression resulting in an alternative phenotype that is better suited for an adverse environment. The primary neurophysiological symptoms of schizophrenia can be induced in animals through exposure to prenatal and postnatal stressors, and that schizophrenia itself is known to be associated with exposure to stress during development, supports the view that the "disorder" may represent a predictive, adaptive response to adversity. In fact, maternal malnutrition, maternal stress, multiparity, short birth interval and stress provoking postnatal events are well recognized epidemiological risk factors for schizophrenia that may represent cues for the initiation of epigenetic programming. Behavioral and physiological characteristics of schizophrenia will be analyzed and interpreted as protective in the context of environmental hardship. For instance, the hypometabolic areas of the schizophrenic brain--the hippocampus and the frontal lobes--are the same areas that are known to become adaptively hypometabolic in response to starvation, stress and variations in ecological rigor in birds and mammals. Individuals with schizophrenia are also highly genetically inclined to develop the metabolic syndrome, which is widely thought to allow developmentally deprived mammals to conserve energy under poor circumstances. It is well known that schizophrenia features an up-regulated hypothalamic-pituitary-adrenal axis and an exaggerated stress response--both alterations thought to represent predictive, adaptive responses to stress in mammals--which may have increased attentiveness to the environment and created a defensive, vigilance-based behavioral strategy. The habituation deficits characteristic of schizophrenia--which can be induced in other mammals through stress--may represent a cognitive strategy that alerts the organism to salient, potentially informative stimuli and that permits it to be more impulsive and vigilant. Inability to calm instinctual drives, ignore arousing stimuli, and inhibit transient desires are all core characteristics of the disorder, which predict social and vocational disabilities in modern times, but may have amounted to a robust, selfish strategy in prehistoric times.     

BV/ODV-E26: a palmitoylated, multifunctional structural protein of Autographa californica nucleopolyhedrovirus

Autographa californica nucleopolyhedrovirus Ac16 is 1 of 17 genes conserved within Type 1 nucleopolyhedroviruses. This report demonstrates that multiple isoforms of the protein encoded by Ac16, BV/ODV-E26 (E26), are present in the infected cell. One form of E26 associates with viral DNA or DNA-binding proteins, while a second form associates with intracellular membranes and this is likely due to palmitoylation. The different forms of E26 present unique epitopes that can be discriminated by antiserum produced to bacterially or virally produced antigen. A summation of the data now available on E26 suggests that it is a multifunctional protein and the functional states assume unique conformations that can be discriminated by differing antisera.