Cover slip external cavity diode laser

The design of a 671 nm diode laser with a mode-hop-free tuning range of 40 GHz is described. This long tuning range is achieved by simultaneously ramping the external cavity length with the laser injection current. The external cavity consists of a microscope cover slip mounted on piezoelectric actuators. In such a configuration the laser output pointing remains fixed, independent of its frequency. Using a diode with an output power of 5-7 mW, the laser linewidth was found to be smaller than 30 MHz. This cover slip cavity and feedforward laser current control system is simple, economical, robust, and easy to use for spectroscopy, as we demonstrate with lithium vapor and lithium atom beam experiments.Comment: 7 pages, 6 figures, submitted to Review of Scientific Instruments 7/29/0

The Use of Bovine Pericardial Buttress on Linear Stapler Fails to Reduce Pancreatic Fistula Incidence in a Porcine Pancreatic Transection Model

We investigate the effectiveness of buttressing the surgical stapler to reduce postoperative pancreatic fistulae in a porcine model. As a pilot study, pigs (n = 6) underwent laparoscopic distal pancreatectomy using a standard stapler. Daily drain output and lipase were measured postoperative day 5 and 14. In a second study, pancreatic transection was performed to occlude the proximal and distal duct at the pancreatic neck using a standard stapler (n = 6), or stapler with bovine pericardial strip buttress (n = 6). Results. In pilot study, 3/6 animals had drain lipase greater than 3x serum on day 14. In the second series, drain volumes were not significantly different between buttressed and control groups on day 5 (55.3 ± 31.6 and 29.3 ± 14.2 cc, resp.), nor on day 14 (9.5 ± 4.2 cc and 2.5 ± 0.8 cc, resp., P = 0.13). Drain lipase was not statistically significant on day 5 (3,166 ± 1,433 and 6,063 ± 1,872 U/L, resp., P = 0.25) or day 14 (924 ± 541 and 360 ± 250 U/L). By definition, 3/6 developed pancreatic fistula; only one (control) demonstrating a contained collection arising from the staple line. Conclusion. Buttressed stapler failed to protect against pancreatic fistula in this rigorous surgical model

Adverse Health Outcomes among U.S. Testicular Cancer Survivors after Cisplatin-Based Chemotherapy vs. Surgical Management

We evaluated for the first time adverse health outcomes (AHOs) among U.S. testicular cancer survivors (TCS) given chemotherapy (n = 381) vs. surgery-only patients (n = 98) managed at a single institution, accounting for non-treatment-related risk factors to delineate chemotherapy’s impact. Chemotherapy consisted largely of bleomycin-etoposide-cisplatin (BEP) administered in 3 or 4 cycles (BEPX3, n = 235; BEPX4, n = 82). Incidence of ≥ 3 AHOs was lowest in surgery-only TCS and increased with BEPX3, BEPX4 and other cisplatin-based regimens (12.2%, 40.8%, 52.5%, 54.8%; P<0.0001). Multivariate modeling assessed associations of risk factors and treatment with hearing impairment, tinnitus, peripheral neuropathy, and Raynaud phenomenon. Risk for each AHO significantly increased with both increasing chemotherapy burden (P < 0.0001) and selected modifiable risk factors (P < 0.05): hypertension (OR = 2.40) and noise exposure (OR ≥ 2.3) for hearing impairment; noise exposure for tinnitus (OR ≥ 1.69); peripheral vascular disease for neuropathy (OR = 8.72), and current smoking for Raynaud phenomenon (OR = 2.41). Clinicians should manage modifiable risk factors for AHOs among TCS

Exploring hypotheses of the actions of TGF-beta 1 in epidermal wound healing using a 3D computational multiscale model of the human epidermis

In vivo and in vitro studies give a paradoxical picture of the actions of the key regulatory factor TGF-beta 1 in epidermal wound healing with it stimulating migration of keratinocytes but also inhibiting their proliferation. To try to reconcile these into an easily visualized 3D model of wound healing amenable for experimentation by cell biologists, a multiscale model of the formation of a 3D skin epithelium was established with TGF-beta 1 literature-derived rule sets and equations embedded within it. At the cellular level, an agent-based bottom-up model that focuses on individual interacting units ( keratinocytes) was used. This was based on literature-derived rules governing keratinocyte behavior and keratinocyte/ECM interactions. The selection of these rule sets is described in detail in this paper. The agent-based model was then linked with a subcellular model of TGF-beta 1 production and its action on keratinocytes simulated with a complex pathway simulator. This multiscale model can be run at a cellular level only or at a combined cellular/subcellular level. It was then initially challenged ( by wounding) to investigate the behavior of keratinocytes in wound healing at the cellular level. To investigate the possible actions of TGF-beta 1, several hypotheses were then explored by deliberately manipulating some of these rule sets at subcellular levels. This exercise readily eliminated some hypotheses and identified a sequence of spatial-temporal actions of TGF-beta 1 for normal successful wound healing in an easy-to-follow 3D model. We suggest this multiscale model offers a valuable, easy-to-visualize aid to our understanding of the actions of this key regulator in wound healing, and provides a model that can now be used to explore pathologies of wound healing

Platelet-rich plasma versus corticosteroid injections in the management of patients with rotator cuff disease: A systematic review and meta-analysis.

Platelet-rich plasma (PRP) is an alternative to corticosteroid (CS) injections in managing rotator cuff disease. This meta-analysis investigated differences between PRP and CS for function and pain scores in significance and minimal clinical important difference (MCID). A literature search of Ovid Cochrane Library, Medline, Embase, Epub, and Scopus was conducted from inception to October 28, 2021. Eligible studies reported patients older than 18 years with a diagnosis of rotator cuff disease. This review was registered in PROSPERO (ID: CRD42021278740). Twelve studies met eligibility criteria (n = 639) of patients receiving either PRP or CS. At short-term follow-up, a difference favored CS compared to PRP in baseline change for disability of arm, shoulder, and hand (DASH) score (MD = -5.08, 95% CI: -8.00, -2.15; p = 0.0007; I2  = 0%) and simple shoulder test (SST) (MD = 1.25, 95% CI: 0.33, 2.18; p = 0.008; I2  = 0%). At intermediate follow-up, a difference favored PRP to CS baseline change of the DASH score (MD = 3.41, 95% CI: 0.67, 6.15; p = 0.01; I2  = 0%). At medium-term, a difference favored PRP to CS baseline change of the American Shoulder and Elbow Surgeons Shoulder (ASES) score (MD = -4.42, 95% CI: -8.16, -0.67; p = 0.02; I2  = 0%). Both treatments achieved individual MCID for each score. Despite favoring CS at short-term follow-up and PRP at intermediate- and medium-term follow-up, functional and pain scores did not demonstrate any clinical difference between the two treatment modalities in management of rotator cuff disease at all follow-up periods

Vertebral rotation measurement: a summary and comparison of common radiographic and CT methods

Current research has provided a more comprehensive understanding of Adolescent Idiopathic Scoliosis (AIS) as a three-dimensional spinal deformity, encompassing both lateral and rotational components. Apart from quantifying curve severity using the Cobb angle, vertebral rotation has become increasingly prominent in the study of scoliosis. It demonstrates significance in both preoperative and postoperative assessment, providing better appreciation of the impact of bracing or surgical interventions. In the past, the need for computer resources, digitizers and custom software limited studies of rotation to research performed after a patient left the scoliosis clinic. With advanced technology, however, rotation measurements are now more feasible. While numerous vertebral rotation measurement methods have been developed and tested, thorough comparisons of these are still relatively unexplored. This review discusses the advantages and disadvantages of six common measurement techniques based on technology most pertinent in clinical settings: radiography (Cobb, Nash-Moe, Perdriolle and Stokes' method) and computer tomography (CT) imaging (Aaro-Dahlborn and Ho's method). Better insight into the clinical suitability of rotation measurement methods currently available is presented, along with a discussion of critical concerns that should be addressed in future studies and development of new methods

AAV5-miHTT gene therapy demonstrates suppression of mutant huntingtin aggregation and neuronal dysfunction in a rat model of Huntington's disease.

Huntington's disease (HD) is a fatal progressive neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene. To date, there is no treatment to halt or reverse the course of HD. Lowering of either total or only the mutant HTT expression is expected to have therapeutic benefit. This can be achieved by engineered micro (mi)RNAs targeting HTT transcripts and delivered by an adeno-associated viral (AAV) vector. We have previously showed a miHTT construct to induce total HTT knock-down in Hu128/21 HD mice, while miSNP50T and miSNP67T constructs induced allele-selective HTT knock-down in vitro. In the current preclinical study, the mechanistic efficacy and gene specificity of these selected constructs delivered by an AAV serotype 5 (AAV5) vector was addressed using an acute HD rat model. Our data demonstrated suppression of mutant HTT messenger RNA, which almost completely prevented mutant HTT aggregate formation, and ultimately resulted in suppression of DARPP-32-associated neuronal dysfunction. The AAV5-miHTT construct was found to be the most efficient, although AAV5-miSNP50T demonstrated the anticipated mutant HTT allele selectivity and no passenger strand expression. Ultimately, AAV5-delivered-miRNA-mediated HTT lowering did not cause activation of microglia or astrocytes suggesting no immune response to the AAV5 vector or therapeutic precursor sequences. These preclinical results suggest that using gene therapy to knock-down HTT may provide important therapeutic benefit for HD patients and raised no safety concerns, which supports our ongoing efforts for the development of an RNA interference-based gene therapy product for HD

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021:a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed.FundingBill &amp; Melinda Gates Foundation.<br/