Surgical treatment of long-standing overt ventriculomegaly in adults (LOVA)

Background Longstanding overt ventriculomegaly in adults (LOVA) is characterised by chronic hydrocephalus presumed to begin during infancy, but arresting before becoming clinically detectable. Later in life clinical features of hydrocephalus ensue, typically in the 5th or 6th decades. Only a relatively small number of LOVA case series have been published, and ambiguity remains regarding optimal management. This case series describes a series of patients with LOVA treated successfully at a single neurosurgical institution using endoscopic third ventriculostomy (ETV). Methods A series of 14 patients were diagnosed with LOVA using established clinical and radiological criteria. All patients underwent an ETVand their clinical conditions were followed up for up to 5 years post-operatively. Results Fourteen patients (100 %) reported either improvement or halt of progression in their presenting symptoms 3 months after ETV; 93 % of patients (n = 13) did not require any further surgical intervention. One patient (7 %) reported deterioration in symptoms beyond 3 months post-operatively, which necessitated further surgery (ventriculoperitoneal shunt). These promising outcomes after ETV are mirrored in numerous other LOVA case series. Other works have analysed the value of CSF shunting procedures in LOVA, with mixed results. A direct, prospective comparison of outcomes after shunt procedures and ETV, with a specific focus on LOVA patients, is yet to be completed. A minority of patients fail to respond, or develop recurrence of symptoms, months or years after initial surgical interventio

The Impact of a Brief Intervention on Medical Students\u27 Readiness to Screen for DV - Changes in Decisional Balance and Self-Efficacy

Introduction: Domestic violence (DV) affects millions of Americans each year. Yet, there is a dearth of theory-based DV curricula, resulting in physicians unprepared to screen for DV. This study utilized a survey based on constructs from the Transtheoretical Model to assess the readiness of first- and second-year medical students to screen for DV. Information from this survey will be used to help institutionalize DV education into the medical curriculum. [See PDF for complete abstract

Slow and steady wins the race: learning and the innovation process

How should incumbent firms innovate in IT-based services in the long term? Past empirical research and conventional wisdom suggest that firms should be fast during the radical and incremental phase. We challenge this view in the context of the knowledge economy. We contend that incumbent firms can either be fast during the radical phase or during the subsequent incremental phase of the innovation process. We draw on the innovation and organizational learning literature to argue that sequential combination of modes of learning during the innovation process explains this phenomenon. We show that incumbent firms that learn through the path of internal knowledge creation during the radical phase followed by external knowledge transfer during the incremental phase will be slow at initial radical innovation but fast at subsequent incremental innovations. In contrast, incumbent firms that learn through any other path will be faster at radical innovation but slower at incremental innovations. We study the innovation in IT-based service of online retail banking over nine years (from 1995 to 2003) using archival data. Analysis of a longitudinal data set of 89 incumbent U.S. banks provides evidence for the thesis

Learning curve for robotic-assisted laparoscopic colorectal surgery.

BACKGROUND: Robotic-assisted laparoscopic surgery (RALS) is evolving as an important surgical approach in the field of colorectal surgery. We aimed to evaluate the learning curve for RALS procedures involving resections of the rectum and rectosigmoid. METHODS: A series of 50 consecutive RALS procedures were performed between August 2008 and September 2009. Data were entered into a retrospective database and later abstracted for analysis. The surgical procedures included abdominoperineal resection (APR), anterior rectosigmoidectomy (AR), low anterior resection (LAR), and rectopexy (RP). Demographic data and intraoperative parameters including docking time (DT), surgeon console time (SCT), and total operative time (OT) were analyzed. The learning curve was evaluated using the cumulative sum (CUSUM) method. RESULTS: The procedures performed for 50 patients (54% male) included 25 AR (50%), 15 LAR (30%), 6 APR (12%), and 4 RP (8%). The mean age of the patients was 54.4 years, the mean BMI was 27.8 kg/m(2), and the median American Society of Anesthesiologists (ASA) classification was 2. The series had a mean DT of 14 min, a mean SCT of 115.1 min, and a mean OT of 246.1 min. The DT and SCT accounted for 6.3% and 46.8% of the OT, respectively. The SCT learning curve was analyzed. The CUSUM(SCT) learning curve was best modeled as a parabola, with equation CUSUM(SCT) in minutes equal to 0.73 × case number(2) - 31.54 × case number - 107.72 (R = 0.93). The learning curve consisted of three unique phases: phase 1 (the initial 15 cases), phase 2 (the middle 10 cases), and phase 3 (the subsequent cases). Phase 1 represented the initial learning curve, which spanned 15 cases. The phase 2 plateau represented increased competence with the robotic technology. Phase 3 was achieved after 25 cases and represented the mastery phase in which more challenging cases were managed. CONCLUSIONS: The three phases identified with CUSUM analysis of surgeon console time represented characteristic stages of the learning curve for robotic colorectal procedures. The data suggest that the learning phase was achieved after 15 to 25 cases

Design and Development of Surfactants Based Elastic Vesicular Drug Carrier System containing Antifungal Drug for Ophthalmic Disorder.

The work depicts utility of a novel; surfactants based elastic vesicular drug carrier system (SEVs), for targeting topically applied drug(s) to the posterior segment of the eye. The system comprised span 20 and an edge activator (tween 80). Terbinafine hydrochloride is a synthetic allylamine antifungal with a low molecular weight (327.89 Da.). It is hydrophilic in nature and has high protein binding and a limiting solubilityis expected to show a poor transport across the cornea; hence no ocular formulations are available. It is used to treat ocular mycoses, the second most usual drive of blindness in developing countries. However, its administered poor patient compliance and limited use due to its variable half-life. Therefore, Terbinafine hydrochloride was comprised into a novel sorbitan (spans) based elastic (SEVs) vesicular system with intent to achieve a prolonged and better effect. It was found to be safe in terms of dermal and eye irritation/corrosion tests according to OECD guidelines. Safety was a crucial issue considering that the system is novel (Indian Patent Application 2390/DEL/2008; 1447/DEL/2010) and is completely surfactant based (spans plus edge activators) formulation

Local Application of Sodium Salicylate Enhances Auditory Responses in the Rat’s Dorsal Cortex of the Inferior Colliculus

Sodium salicylate (SS) is a widely used medication with side effects on hearing. In order to understand these side effects, we recorded sound-driven local-field potentials in a neural structure, the dorsal cortex of the inferior colliculus (ICd). Using a microiontophoretic technique, we applied SS at sites of recording and studied how auditory responses were affected by the drug. Furthermore, we studied how the responses were affected by combined local application of SS and an agonists/antagonist of the type-A or type-B γ-aminobutyric acid receptor (GABAA or GABAB receptor). Results revealed that SS applied alone enhanced auditory responses in the ICd, indicating that the drug had local targets in the structure. Simultaneous application of the drug and a GABAergic receptor antagonist synergistically enhanced amplitudes of responses. The synergistic interaction between SS and a GABAA receptor antagonist had a relatively early start in reference to the onset of acoustic stimulation and the duration of this interaction was independent of sound intensity. The interaction between SS and a GABAB receptor antagonist had a relatively late start, and the duration of this interaction was dependent on sound intensity. Simultaneous application of the drug and a GABAergic receptor agonist produced an effect different from the sum of effects produced by the two drugs released individually. These differences between simultaneous and individual drug applications suggest that SS modified GABAergic inhibition in the ICd. Our results indicate that SS can affect sound-driven activity in the ICd by modulating local GABAergic inhibition

Anti-Cancer Mechanisms of Action of Therapeutic Alternating Electric Fields (Tumor Treating Fields [TTFields])

Despite improved survival outcomes across many cancer types, the prognosis remains grim for certain solid organ cancers including glioblastoma and pancreatic cancer. Invariably in these cancers, the control achieved by time-limited interventions such as traditional surgical resection, radiation therapy, and chemotherapy is short-lived. A new form of anti-cancer therapy called therapeutic alternating electric fields (AEFs) or tumor treating fields (TTFields) has been shown, either by itself or in combination with chemotherapy, to have anti-cancer effects that translate to improved survival outcomes in patients. Although the pre-clinical and clinical data are promising, the mechanisms of TTFields are not fully elucidated. Many investigations are underway to better understand how and why TTFields is able to selectively kill cancer cells and impede their proliferation. The purpose of this review is to summarize and discuss the reported mechanisms of action of TTFields from pre-clinical studies (both in vitro and in vivo). An improved understanding of how TTFields works will guide strategies focused on the timing and combination of TTFields with other therapies, to further improve survival outcomes in patients with solid organ cancers

Hinderin, a five-domains protein including coiled-coil motifs that binds to SMC3

BACKGROUND: The structural maintenance of chromosome proteins SMC1 and SMC3 play an important role in the maintenance of chromosomal integrity by preventing the premature separation of the sister chromatids at the onset of anaphase. The two proteins are constitutive components of the multimeric complex cohesin and form dimers by interacting at their central globular regions. RESULTS: In order to identify proteins that by binding to SMC3 may interfere with the protein dimerization process, a human cDNA library was screened by the yeast two-hybrid system by using the hinge region of SMC3 as bait. This has lead to the identification of Hinderin, a novel five domains protein including two coiled-coil motifs and sharing a strikingly structural similarity to the SMC family of proteins. Hinderin is ubiquitously expressed in human tissues. Orthologue forms of the protein are present in other vertebrates but not in lower organisms. A mapping of the interaction sites revealed that the N- and C-terminal globular domains mediate the binding of Hinderin to SMC3. Hinderin/SMC3 complexes could be recovered by immunoprecipitation from cell lysates using an anti-SMC3 antibody, thus demonstrating that the two proteins interact in vivo. On the contrary, Hinderin did not interact with SMC1. In vivo the rate of SMC1/SMC3 interaction was decreased by the ectopic expression of Hinderin. CONCLUSIONS: Hinderin is a novel binding partner of SMC3. Based on its ability to modulate SMC1/SMC3 interaction we postulate that Hinderin affects the availability of SMC3 to engage in the formation of multimeric protein complexes

La asociación : revista de primera enseñanza: Año XI Número 541 - (07/07/23)

There have been few new therapies for patients with chronic kidney disease in the last decade. However, the management of patients affected by genetic kidney disease is rapidly evolving. Inherited or genetic kidney disease affects around 10% of adults with end-stage kidney disease and up to 70% of children with early onset kidney disease. Advances in next-generation sequencing have enabled rapid and cost-effective sequencing of large amounts of DNA. Next-generation sequencing-based diagnostic tests now enable identification of a monogenic cause in around 20% of patients with early-onset chronic kidney disease. A definitive diagnosis through genomic testing may negate the need for prolonged diagnostic investigations and surveillance, facilitate reproductive planning and provide accurate counselling for at-risk relatives. Genomics has allowed the better understanding of disease pathogenesis, providing prognostic information and facilitating development of targeted treatments for patients with inherited or genetic kidney disease. Although genomic testing is becoming more readily available, there are many challenges to implementation in clinical practice. Multidisciplinary renal genetics clinics serve as a model of how some of these challenges may be overcome. Such clinics are already well established in most parts of Australia, with more to follow in future. With the rapid pace of new technology and gene discovery, collaboration between expert clinicians, laboratory and research scientists is of increasing importance to maximize benefits to patients and health-care systems