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Performance of nonfullerene‐based organic solar cells is largely dependent on the donor:acceptor blend morphology, which is initially tuned by composition. However, morphological design rules are difficult to identify due to the complex relationship between composition‐dependent phase behavior and performance properties. In this study, the authors are able to establish a direct link between PM6:Y6 film morphology and device properties by combining grazing‐incidence wide‐angle X‐ray scattering with highly sensitive Fourier transform photocurrent spectroscopy. By analyzing properties across the full composition range, interfacial microstructure and the corresponding charge transfer (CT) states are identified and direct structure–property relationships are established. The results indicate that open‐circuit voltage is controlled by the CT state at amorphous‐PM6:crystalline‐Y6 interfaces. Crystalline Y6 is found to increase both transport and non‐radiative recombination, suggesting that morphological tradeoffs may be necessary for overall device optimization. [ABSTRACT FROM AUTHOR]

Blastomycoses dermatitidis is a dimorphic fungus that can cause disseminated blastomycosis with varying clinical manifestations and multiorgan involvement. While blastomycosis commonly causes pulmonary disease, extrapulmonary spread can result in skin, bone, and central nervous system involvement. Cutaneous blastomycosis can present as pustular lesions that evolve into ulcerative or verrucous plaques. We present a case of disseminated blastomycosis in an immunocompetent patient with both pulmonary and cutaneous features. The patient developed hypoxic respiratory failure and was subsequently diagnosed with disseminated blastomycosis after undergoing bronchoscopy with bronchial washing. He was found to have ulcerative nasal lesions as part of his disseminated disease. He was successfully treated with amphotericin B and ultimately discharged from the hospital. [ABSTRACT FROM AUTHOR]

Background: Cross-cultural research with patient-reported outcomes measures (PROMs) assumes that the PROM in the target language will measure the same construct in the same way as the PROM in the source language. Yet translation methods are rarely used to qualitatively maximise construct equivalence or to describe the intents of each item to support common understanding within translation teams. This study aimed to systematically investigate the utility of the Translation Integrity Procedure (TIP), in particular the use of item intent descriptions, to maximise construct equivalence during the translation process, and to demonstrate how documented data from the TIP contributes evidence to a validity argument for construct equivalence between translated and source language PROMs.Methods: Analysis of secondary data was conducted on routinely collected data in TIP Management Grids of translations (n = 9) of the Health Literacy Questionnaire (HLQ) that took place between August 2014 and August 2015: Arabic, Czech, French (Canada), French (France), Hindi, Indonesian, Slovak, Somali and Spanish (Argentina). Two researchers initially independently deductively coded the data to nine common types of translation errors. Round two of coding included an identified 10th code. Coded data were compared for discrepancies, and checked when needed with a third researcher for final code allocation.Results: Across the nine translations, 259 changes were made to provisional forward translations and were coded into 10 types of errors. Most frequently coded errors were Complex word or phrase (n = 99), Semantic (n = 54) and Grammar (n = 27). Errors coded least frequently were Cultural errors (n = 7) and Printed errors (n = 5).Conclusions: To advance PROM validation practice, this study investigated a documented translation method that includes the careful specification of descriptions of item intents. Assumptions that translated PROMs have construct equivalence between linguistic contexts can be incorrect due to errors in translation. Of particular concern was the use of high level complex words by translators, which, if undetected, could cause flawed interpretation of data from people with low literacy. Item intent descriptions can support translations to maximise construct equivalence, and documented translation data can contribute evidence to justify score interpretation and use of translated PROMS in new linguistic contexts. [ABSTRACT FROM AUTHOR]

Background: Surgical site infection (SSI) following spine surgery is associated with increased morbidity, reoperation rates, hospital readmissions, and cost. The incidence of SSI following posterior cervical spine surgery is higher than anterior cervical spine surgery, with rates from 4.5% to 18%. It is well documented that higher body mass index (BMI) is associated with increased risk of SSI after spine surgery. There are only a few studies that examine the correlation of BMI and SSI after posterior cervical instrumented fusion (PCIF) using national databases, however, none that compare trauma and nontraumatic patients.Purpose: The purpose of this study is to determine the odds of developing SSI with increasing BMI after PCIF, and to determine the risk of SSI in both trauma and nontraumatic adult patients.Study Design: This is a retrospective cohort study of a prospective surgical database collected at one academic institution.Patient Sample: The patient sample is from a prospectively collected surgical registry from one institution, which includes patients who underwent PCIF from April 2011 to October 2017.Outcome Measures: A SSI that required return to the operating room for surgical debridement.Methods: This is a retrospective cohort study using a prospectively collected database of all spine surgeries performed at our institution from April 2011 to October 2017. We identified 1,406 patients, who underwent PCIF for both traumatic injuries and nontraumatic pathologies using International Classification of Diseases 9 and 10 procedural codes. Thirty-day readmission data were obtained. Patient's demographics, BMI, presence of diabetes, preoperative diagnosis, and surgical procedures performed were identified. Using logistic regression analysis, the risk of SSI associated with every one-unit increase in BMI was determined. This study received no funding. All the authors in this study report no conflict of interests relevant to this study.Results: Of the 1,406 patients identified, 1,143 met our inclusion criteria. Of those patients, 688 had PCIF for traumatic injuries and 454 for nontraumatic pathologies. The incidence of SSI for all patients, who underwent PCIF was 3.9%. There was no significant difference in the rate of SSI between our trauma group and nontraumatic group. There was a higher rate of infection in patients, who were diabetic and with BMI≥30 kg/m2. The presence of both diabetes and BMI≥30 kg/m2 had an added effect on the risk of developing SSI in all patients, who underwent PCIF. Additionally, logistic regression analysis showed that there was a positive difference measure between BMI and SSI. Our results demonstrate that for one-unit increase in BMI, the odds of having a SSI is 1.048 (95% CI: 1.007-1.092, p=.023).Conclusions: Our study demonstrates that our rate of SSI after PCIF is within the range of what is cited in the literature. Interestingly, we did not see a statistically significant difference in the rate of infection between our trauma and nontrauma group. Overall, diabetes and elevated BMI are associated with increased risk of SSI in all patients, who underwent PCIF with even a higher risk in patient, who are both diabetic and obese. Obese patients should be counseled on elevated SSI risk after PCIF, and those with diabetes should be medically optimized before and after surgery when possible to minimize SSI. [ABSTRACT FROM AUTHOR]

Introduction Increasing smartphones access has allowed for increasing development and use of smart phone applications (apps). Mobile health interventions have previously relied on voice or text-based short message services (SMS), however, the increasing availability and ease of use of apps has allowed for significant growth of smartphone apps that can be used for health behaviour change. This review considers the current body of knowledge relating to the evaluation of apps for health behaviour change. The aim of this review is to investigate approaches to the evaluation of health apps to identify any current best practice approaches. Method A systematic review was conducted. Data were collected and analysed in September 2016. Thirty-eight articles were identified and have been included in this review. Results Articles were published between 2011- 2016, and 36 were reviews or evaluations of apps related to one or more health conditions, the remaining two reported on an investigation of the usability of health apps. Studies investigated apps relating to the following areas: alcohol, asthma, breastfeeding, cancer, depression, diabetes, general health and fitness, headaches, heart disease, HIV, hypertension, iron deficiency/anaemia, low vision, mindfulness, obesity, pain, physical activity, smoking, weight management and women's health. Conclusion In order to harness the potential of mobile health apps for behaviour change and health, we need better ways to assess the quality and effectiveness of apps. This review is unable to suggest a single best practice approach to evaluate mobile health apps. Few measures identified in this review included sufficient information or evaluation, leading to potentially incomplete and inaccurate information for consumers seeking the best app for their situation. This is further complicated by a lack of regulation in health promotion generally. [ABSTRACT FROM AUTHOR]

Issue addressed More than 87% of Australians own a mobile phone with Internet access and 82% of phone owners use their smartphones to search for health information, indicating that mobile phones may be a powerful tool for building health literacy. Yet, online health information has been found to be above the reading ability of the general population. As reading on a smaller screen may further complicate the readability of information, this study aimed to examine how health information is displayed on mobile phones and its implications for readability. Methods Using a cross-sectional design with convenience sampling, a sample of 270 mobile webpages with information on 12 common health conditions was generated for analysis, they were categorised based on design and position of information display. Results The results showed that 71.48% of webpages were mobile-friendly but only 15.93% were mobile-friendly webpages designed in a way to optimise readability, with a paging format and queried information displayed for immediate viewing. Conclusion With inadequate evidence and lack of consensus on how webpage design can best promote reading and comprehension, it is difficult to draw a conclusion on the effect of current mobile health information presentation on readability. So what? Building mobile-responsive websites should be a priority for health information providers and policy-makers. Research efforts are urgently required to identify how best to enhance readability of mobile health information and fully capture the capabilities of mobile phones as a useful device to increase health literacy. [ABSTRACT FROM AUTHOR]

Kidney formation involves patterning events that induce renal progenitors to form nephrons with an intricate composition of multiple segments. Here, we performed a chemical genetic screen using zebrafish and discovered that prostaglandins, lipid mediators involved in many physiological functions, influenced pronephros segmentation. Modulating levels of prostaglandin E2 (PGE2) or PGB2 restricted distal segment formation and expanded a proximal segment lineage. Perturbation of prostaglandin synthesis by manipulating Cox1 or Cox2 activity altered distal segment formation and was rescued by exogenous PGE2. Disruption of the PGE2 receptors Ptger2a and Ptger4a similarly affected the distal segments. Further, changes in Cox activity or PGE2 levels affected expression of the transcription factors irx3b and sim1a that mitigate pronephros segment patterning. These findings show for the first time that PGE2 is a regulator of nephron formation in the zebrafish embryonic kidney, thus revealing that prostaglandin signaling may have implications for renal birth defects and other diseases. [ABSTRACT FROM AUTHOR]

Cytogenetics provides a unique platform to study in situ structural, functional, and evolutionary aspects of the genome. As such it holds powerful promise in decoding mechanisms and processes of genome architectural changes and their role in organism's diversification and evolution. Since the early 80s, such an approach has been applied to the study of the Antarctic notothenioid fishes. In almost three decades, the cytogenetic information has expanded to cover half of the known species inhabiting the high Antarctic waters. Although started 10 years later, cytogenetic studies of species from the Ross sea region have provided valuable contributions to this bulk of knowledge. Here, we synthesize the currently available cytogenetic information on Antarctic notothenioid fishes from the Ross Sea Region, inclusive of both conventional karyotyping and gene mapping. In addition, new karyotypic data on four species ( Lepidonotothen squamifrons, Trematomus scotti, T. loennbergii, and T. lepidorhinus) are provided. In discussing these data, specific focus is made on the patterns and subtleties of cytogenetic diversity at inter- and intra-specific levels aiming at contributing to the refinement of the knowledge of fish diversity in a region, the Ross Sea area, whose primary ecological value is widely recognized. [ABSTRACT FROM AUTHOR]

The kidney is comprised of working units known as nephrons, which are epithelial tubules that contain a series of specialized cell types organized into a precise pattern of functionally distinct segment domains. There is a limited understanding of the genetic mechanisms that establish these discrete nephron cell types during renal development. The zebrafish embryonic kidney serves as a simplified yet conserved vertebrate model to delineate how nephron segments are patterned from renal progenitors. Here, we provide a concise review of recent advances in this emerging field, and discuss how continued research using zebrafish genetics can be applied to gain insights about nephrogenesis. [ABSTRACT FROM AUTHOR]

The mechanisms that establish nephron segments are poorly understood. The zebrafish embryonic kidney, or pronephros, is a simplified yet conserved genetic model to study this renal development process because its nephrons contain segments akin to other vertebrates, including the proximal convoluted and straight tubules (PCT, PST). The zebrafish pronephros is also associated with the corpuscles of Stannius (CS), endocrine glands that regulate calcium and phosphate homeostasis, but whose ontogeny from renal progenitors is largely mysterious. Initial patterning of zebrafish renal progenitors in the intermediate mesoderm (IM) involves the formation of rostral and caudal domains, the former being reliant on retinoic acid (RA) signaling, and the latter being repressed by elevated RA levels. Here, using expression profiling to gain new insights into nephrogenesis, we discovered that the gene si ngle m inded family bHLH transcription factor 1a ( sim1a ) is dynamically expressed in the renal progenitors—first marking the caudal domain, then becoming restricted to the proximal segments, and finally exhibiting specific CS expression. In loss of function studies, sim1a knockdown expanded the PCT and abrogated both the PST and CS populations. Conversely, overexpression of sim1a modestly expanded the PST and CS, while it reduced the PCT. These results show that sim1a activity is necessary and partially sufficient to induce PST and CS fates, and suggest that sim1a may inhibit PCT fate and/or negotiate the PCT/PST boundary. Interestingly, the sim1a expression domain in renal progenitors is responsive to altered levels of RA, suggesting that RA regulates sim1a , directly or indirectly, during nephrogenesis. sim1a deficient embryos treated with exogenous RA formed nephrons that were predominantly composed of PCT segments, but lacked the enlarged PST observed in RA treated wild-types, indicating that RA is not sufficient to rescue the PST in the absence of sim1a expression. Alternately, when sim1a knockdowns were exposed to the RA inhibitor diethylaminobenzaldehyde (DEAB), the CS was abrogated rather than expanded as seen in DEAB treated wild-types, revealing that CS formation in the absence of sim1a cannot be rescued by RA biosynthesis abrogation. Taken together, these data reveal previously unappreciated roles for sim1a in zebrafish pronephric proximal tubule and CS patterning, and are consistent with the model that sim1a acts downstream of RA to mitigate the formation of these lineages. These findings provide new insights into the genetic pathways that direct nephron development, and may have implications for understanding renal birth defects and kidney reprogramming. [ABSTRACT FROM AUTHOR]

Abstract: The reconstruction of musculoskeletal defects is a constant challenge for orthopaedic surgeons. Musculoskeletal injuries such as fractures, chondral lesions, infections and tumor debulking can often lead to large tissue voids requiring reconstruction with tissue grafts. Autografts are currently the gold standard in orthopaedic tissue reconstruction; however, there is a limit to the amount of tissue that can be harvested before compromising the donor site. Tissue engineering strategies using allogeneic or xenogeneic decellularized bone, cartilage, skeletal muscle, tendon and ligament have emerged as promising potential alternative treatment. The extracellular matrix provides a natural scaffold for cell attachment, proliferation and differentiation. Decellularization of in vitro cell-derived matrices can also enable the generation of autologous constructs from tissue specific cells or progenitor cells. Although decellularized bone tissue is widely used clinically in orthopaedic applications, the exciting potential of decellularized cartilage, skeletal muscle, tendon and ligament cell-derived matrices has only recently begun to be explored for ultimate translation to the orthopaedic clinic. [Copyright &y& Elsevier]

Abstract: The zebrafish pronephros provides a conserved model to study kidney development, in particular to delineate the poorly understood processes of how nephron segment pattern and cell type choice are established. Zebrafish nephrons are divided into distinct epithelial regions that include a series of proximal and distal tubule segments, which are comprised of intercalated transporting epithelial cells and multiciliated cells (MCC). Previous studies have shown that retinoic acid (RA) regionalizes the renal progenitor field into proximal and distal domains and that Notch signaling later represses MCC differentiation, but further understanding of these pathways has remained unknown. The transcription factor mecom ( mds1/evi1 complex) is broadly expressed in renal progenitors, and then subsequently marks the distal tubule. Here, we show that mecom is necessary to form the distal tubule and to restrict both proximal tubule formation and MCC fate choice. We found that mecom and RA have opposing roles in patterning discrete proximal and distal segments. Further, we discovered that RA is required for MCC formation, and that one mechanism by which RA promotes MCC fate choice is to inhibit mecom. Next, we determined the epistatic relationship between mecom and Notch signaling, which limits MCC fate choice by lateral inhibition. Abrogation of Notch signaling with the γ-secretase inhibitor DAPT revealed that Notch and mecom did not have additive effects in blocking MCC formation, suggesting that they function in the same pathway. Ectopic expression of the Notch signaling effector, Notch intracellular domain (NICD), rescued the expansion of MCCs in mecom morphants, indicating that mecom acts upstream to induce Notch signaling. These findings suggest a model in which mecom and RA arbitrate proximodistal segment domains, while MCC fate is modulated by a complex interplay in which RA inhibition of mecom, and mecom promotion of Notch, titrates MCC number. Taken together, our studies have revealed several essential and novel mechanisms that control pronephros development in the zebrafish. [Copyright &y& Elsevier]

Abstract: Despite the knowledge that superficial zone chondrocytes (SZC, located within 100 μm of the articular surface) and deep zone chondrocytes (DZC, located near the calcified zone) have distinct phenotypes, previous studies on bone morphogenetic proteins (BMPs) have not differentiated its effects on SZC versus DZC. Using a pellet culture model we have compared phenotype, morphology and matrix accumulation in SZC and DZC with or without adenovirus-mediated overexpression of BMP2 or -7 or the BMP antagonist Noggin. Greater accumulation of proteoglycan (PG)-rich matrix in the untreated DZC was associated with a hypertrophic phenotype with large cell diameters and high gene expression levels of runt-related transcription factor-2 (Runx2) as well as higher endogenous BMP activity. Noggin overexpression decreased matrix accumulation and cell diameters in SZC and DZC, confirming a role for endogenous BMP in both processes. In DZC, overexpression of either BMP2 or -7 increased cell diameter without increasing PG-rich matrix accumulation. In contrast, in SZC, BMP overexpression increased matrix accumulation and type II collagen gene expression without increasing cell diameter. These data indicate that differences in endogenous BMP activity level and responsiveness to BMPs define, in part, the differences between the SZC and DZC phenotype. They also suggest that SZC may be a more appropriate target for BMP therapy than DZC. [Copyright &y& Elsevier]

Abstract: Metalworking fluids (MWFs) are widely used for cooling and lubricating during the machining process. The worldwide annual usage is estimated to exceed 2×109 l and the waste could be more than ten times the usage, as the MWFs have to be diluted prior to use. For UK industry the disposal cost is estimated to be up to £16 million per year. Used MWFs cause high levels of contamination and rancid odours due to the presence of complex chemicals, biocides, etc., so that their treatment and final disposal must be handled carefully. Conventionally this has been done by combined physical and chemical methods but, with tightened legislation, these routes are no longer acceptable. Now, biological treatment is being increasingly adopted as it seems to offer an alternative with the potential for significant cost saving. However, there are significant difficulties in operating bioreactors, such as maintenance of the stability of the microbial communities present in activated sludge plants (ASP). In order to resolve these problems, four major areas need to be considered: (1) the composition of the spent MWF and its inherent biodegradability, (2) the recalcitrant compounds existing in waste MWFs and their impact on microbes, (3) the nature of the microbial consortia and means of optimising it, e.g, temperature and the practical design of the bioreactor and (4) the requirements for nutrient supplements and optimal control conditions. The potential importance of understanding the microbial community has been studied by the use of molecular biological techniques such as polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE), fatty acid methyl ester (FAME) and fluorescent in situ hybridization (FISH). The application of attached biofilm bioreactors and thermophilic aerobic technology (TAT) has also been studied. This review describes recent advances in each of these areas. [Copyright &y& Elsevier]

Objective: The objective of this study is to evaluate factors associated with discharge to subacute care after surgery for degenerative cervical myelopathy. Design: This is a retrospective chart review of adults who underwent cervical spine surgery for degenerative cervical myelopathy between 2014 and 2020 (N = 135). Results: Patients discharged to a subacute setting were older (68.1 ± 8.6 vs. 64.1 yrs ± 8.8, P = 0.01), more likely to be unmarried (55.8% vs. 33.7% married, P = 0.01), and more likely to have Medicare or Medicaid (83.7% vs. 65.9% private insurance, P = 0.03) than patients discharged home. A posterior surgical approach was associated with discharge to a subacute setting (62.8% vs. 43.5% anterior approach, P = 0.04). A total of 87.8% of patients discharged to a subacute setting required moderate or maximum assistance for bed mobility versus 26.6% of patients discharged home (P < 0.0001). Compared with patients discharged home, patients discharged to a subacute setting ambulated a shorter distance in their first physical therapy evaluation after surgery (8.9 ± 35.8 vs. 53.7 ± 61.78 m in the home discharge group, P < 0.0001). Conclusions: Analysis of these factors may guide discussions about patient expectations for postoperative discharge placement. [ABSTRACT FROM AUTHOR]

Spinal epidural abscess (SEA) is a rare and life-threatening infection within the epidural space with significant functional impairment and morbidity. Active debate remains over whether to operate for SEAs, with limited existing data comparing the long-term survivability after surgical versus nonsurgical management. This study aims to determine the long-term survival of patients who underwent surgical and nonsurgical management for SEA. Retrospective cohort study. A total of 250 consecutive SEA patients. Survival and mortality rates, complications. All patients treated at a tertiary medical center for a primary SEA from January 2000 to June 2020 are identified. Data collection is by retrospective chart review. Cox proportional hazards regression models are used for all survival analyses while controlling for potential confounding variables and with multiple testing corrections. A total of 35 out of 250 patients died with an overall all-cause mortality of 14%. More than half of all deaths occurred within 90 days after treatment. The 90-day, 3-year, and 5-year survival rates are 92.8%, 89.2%, and 86.4%, respectively. Among surgery patients, the all-cause mortality was 13.07%, compared to 16.22% for medically-managed patients. Surgical treatment (decompression, fusion, debridement) significantly reduced the risk of death by 62.4% compared to medical therapy (p=.03), but surgery patients experienced a significantly longer mean length of stay (p=.01). Risk factors of short-term mortality included hypoalbuminemia (<3.5 g/dL), American Society of Anesthesiologists (ASA) 4+, and cardiac arrest. Risk factors of long-term mortality were immunocompromised state, elevated WBC count >12,000, sepsis, septic shock, ASA 4+, and cardiac arrest (p<.05). In terms of complications, surgically-managed patients experienced a higher proportion of deep vein thrombosis (p<.05). The overall long-term survivability of SEA treatment is relatively high at (86% at 5-year) in this study. The following SEA mortality risk factors were identified: hypoalbuminemia (short-term), immunocompromised state (long-term), leukocytosis (long-term), sepsis and septic shock (long-term), ASA 4+ and cardiac arrest (overall). For primary SEA patients, surgical management may reduce mortality risk compared to nonsurgical management. [ABSTRACT FROM AUTHOR]

Between 2014 and 2019, unexpected mortalities were observed in a colony of Dryococelus australis, an endangered stick-insect kept at the Melbourne Zoo for a breeding and conservation program. Pure cultures of Serratia spp. were obtained from the haemolymph of moribund and recently deceased individuals. The combined bacteriological and histopathological observations suggested an infectious cause of these mortalities. Genotyping of Serratia sp. isolated from the insects and their environment revealed a predominant strain profile. A representative isolate, AM923, was entirely sequenced and compared to 616 publicly available Serratia spp. genomes, including 37 associated with insects. The genomes were distributed into 3 distinct groups, with 63% of the insect-associated isolates within a single clade (clade A) containing AM923, separated from most environmental/plant-associated strains (clade B) and human isolates (clade C). Average nucleotide identity and phylogenetic analyses identified AM923 as S. ureilytica and revealed similarities with putatively entomopathogenic strains. An experimental infection model in honey bees (Apis mellifera) confirmed the pathogenic potential of AM923. A urease operon was found in most insect isolates and a PCR assay, based on the ureB gene sequence, was used to confirm the presence of AM923 in experimentally infected bees. This species-specific PCR could be applied to detect entomopathogenic Serratia spp. in infected insects or their environment. [ABSTRACT FROM AUTHOR]

Issue Addressed: With an ageing population and growing complexity and fragmentation of health care systems, health literacy is increasingly important in managing health. This study investigated health literacy strengths and challenges reported by older Australians (people aged 65 or over) and identified how socio‐demographic and health factors related to their health literacy profiles. Methods: The sample comprised 1578 individuals responding to the Australian Government's 2018 Health Literacy Survey, conducted between January and August. Regression modelling was used to estimate the association between each of nine domains of the Health Literacy Questionnaire (HLQ) and individual socio‐demographic and health characteristics. The model allowed for correlation between HLQ scores that was linked to unobserved characteristics of individuals. Results: Across the health literacy domains, few individuals received mean scores in the lowest score range. Key individual characteristics associated with higher health literacy were increasing age, English proficiency, higher education levels, better self‐assessed health and having certain chronic conditions (cancer, hypertension and arthritis). Conclusions: Our findings suggest that, among those aged 65 or over, being older or living with chronic illnesses were associated with greater confidence in engaging with providers, accessing information and navigating health services compared to individuals aged 65–69 and those older individuals without chronic illness. Lower health literacy was associated with psychological distress and low English proficiency. So What?: Interventions to improve individual health literacy and organisation health literacy responsiveness to minimise complexity of the Australian health system are required. This may enhance uptake and use of health information and services for the underserviced members of the community. [ABSTRACT FROM AUTHOR]

Each cone photoreceptor in the retina responds to light in a limited range of wavelengths, giving it a spectral phenotype. This phenotype is determined by the most prevalent of the photoreceptor's visual-pigment proteins (opsins) and is assumed to remain unchanged during an animal's lifetime. Here we show that in the Pacific pink salmon, Oncorhynchus gorbuscha, single cones can switch their spectral phenotype from ultraviolet to blue by regulating the production of the appropriate opsins as the fish grow older. This photoreceptor plasticity may operate to modulate colour vision as the salmon's lifestyle changes. [ABSTRACT FROM AUTHOR]

Background Context: Tandem spinal stenosis (TSS) refers to a narrowing of the spinal canal in distinct, noncontiguous regions. TSS most commonly occurs in the cervical and lumbar regions. Decompressive surgery is indicated for those with cervical myelopathy or persistent symptoms from lumbar stenosis despite conservative management. Surgical management typically involves staged procedures, with cervical decompression taking precedence in most cases, followed by lumbar decompression at a later time. However, several studies have shown favorable outcomes in simultaneous decompression.Purpose: The aim of this study is to provide a literature review and compare surgical outcomes in patients undergoing staged vs simultaneous surgery for TSS.Study Design/setting: Systematic literature review.Methods: A systematic review using PRISMA guidelines to identify original research articles for tandem spinal stenosis. PubMed, Cochrane, Ovid, Scopus, and Web of Science were used for electronic literature search. Original articles from 2005 to 2021 with more than eight adult patients treated surgically for cervical and lumbar TSS in staged or simultaneous procedures were included. Articles including pediatric patients, primarily thoracic stenosis, stenosis secondary to neoplasm or infectious disease, minimally invasive surgery, and non-English language were excluded. Demographic, perioperative, complications, functional outcome, and neurologic outcome data including mJOA (modified Japanese Orthopaedic Association), Nurick grade (NG), and ODI (Oswestry disability index), were extracted and summarized.Results: A total of 667 articles were initially identified. After preliminary screening, 21 articles underwent full-text screening. Ten articles met our inclusion criteria. A total of 831 patients were included, 571 (68%) of them underwent staged procedures, and 260 (32%) underwent simultaneous procedures for TSS. Mean follow-ups ranged from 12 to 85 months. There was no difference in estimated blood loss (EBL) between staged and simultaneous groups (p=.639). Simultaneous surgeries had shorter surgical time than staged surgeries (p<.001). Mean changes in mJOA, NG, and ODI was comparable between staged and simultaneous groups. Complications were similar between the groups. There were more major complications reported in simultaneous operations, although this was not statistically significant (p=.301).Conclusion: Staged and simultaneous surgery for TSS have comparable perioperative, functional, and neurologic outcomes, as well as complication rates. Careful selection of candidates for simultaneous surgery may reduce the length of stay and consolidate rehabilitation, thereby reducing hospital-associated costs. [ABSTRACT FROM AUTHOR]

Novel Deep Neural Network (DNN) accelerators based on crossbar arrays of non-volatile memories (NVMs)—such as Phase-Change Memory or Resistive Memory—can implement multiply-accumulate operations in a highly parallelized fashion. In such systems, computation occurs in the analog domain at the location of weight data encoded into the conductances of the NVM devices. This allows DNN training of fully-connected layers to be performed faster and with less energy. Using a mixed-hardware-software experiment, we recently showed that by encoding each weight into four distinct physical devices—a "Most Significant Conductance" pair (MSP) and a "Least Significant Conductance" pair (LSP)—we can train DNNs to software-equivalent accuracy despite the imperfections of real analog memory devices. We surmised that, by dividing the task of updating and maintaining weight values between the two conductance pairs, this approach should significantly relax the otherwise quite stringent device requirements. In this paper, we quantify these relaxed requirements for analog memory devices exhibiting a saturating conductance response, assuming either an immediate or a delayed steep initial slope in conductance change. We discuss requirements on the LSP imposed by the "Open Loop Tuning" performed after each training example and on the MSP due to the "Closed Loop Tuning" performed periodically for weight transfer between the conductance pairs. Using simulations to evaluate the final generalization accuracy of a trained four-neuron-layer fully-connected network, we quantify the required dynamic range (as controlled by the size of the steep initial jump), the tolerable device-to-device variability in both maximum conductance and maximum conductance change, the tolerable pulse-to-pulse variability in conductance change, and the tolerable device yield, for both the LSP and MSP devices. We also investigate various Closed Loop Tuning strategies and describe the impact of the MSP/LSP approach on device endurance. [ABSTRACT FROM AUTHOR]

INTRODUCTIONAcute cartilage injury and subsequent osteoarthritis are a debilitating and common syndrome in the aging population. Transplantation of MSCs to joints has been successfully used in small animal models. However, in extensive defects the application of MSCs improved defect filling with only fibrous tissue. Enhancing chondrogenesis of the MSCs by TGF-β1 gene transduction before transplantation may provide the impetus for better quality cartilaginous repair.MATERIALS AND METHODSAadenovirus vector encoding equine TGF-β1 (AdTGF-β1) was used to transfect MSCs. Monolayer cultures were transduced with AdTGF-β1, AdGFP, or no virus. Monolayers were pelleted after 24 hours, and 15 pellets harvested at 2, 7, 14, and 21 days. Chondrogenesis was determined by qPCR assessment of TGF-β1, aggrecan, coll IIA, and coll IIB gene expression. Medium was assayed for PG and TGF-β1. Confirmation of pellet chondrogenesis was made by HandE architecture, collagen II elaboration on immunohistochemistry, and toluidine blue PG staining.RESULTSPCR indicated AdTGFβ1 transfected MSCs expressed TGF-β1 RNA (Fig 1), which induced markers of chondrogenic differentiationincluding aggrecan, and collagen types IIA and IIB (Fig 2). Aggrecan expression was significantly enhanced on day 2. Immuno analysis detected collagen type II as early as 2 days after beginning aggregate cultures. This phenomenon continued through day 21, with intense collagen type II as the predominant collagen on day 21 (Fig 2). Collagen type I immuno analysis showed collagen type I deposition throughout all time periods, with increases under the influence of TGF-β1.DISCUSSIONSignificant increases in TGF-β1 expression were induced in AdTGF-β1 transduced MSC cells. Chondrogenic response was reflected in collagen type IIA and IIB expression which were significantly increased on day 7, 14 and 21. Longer term cultures showed a preponderance of collagen type IIB expression. Combined with morphologic evidence of strong chondrogenic condensation, these data provide molecular, histological and immunohistochemical evidence for substantial in vitro chondrogenic differentiation of equinebone-marrow derived MSCs. Based on these results AdTGF-β1 treated MSCs may be a robust source of chondrocytes for use in cartilage repair.Molecular Therapy (2006) 13, S353–S353; doi: 10.1016/j.ymthe.2006.08.1006 [ABSTRACT FROM AUTHOR]

Acute postoperative surgical site infections (SSI) following instrumented lumbar spine fusions are a relatively infrequent occurrence. Treatment of an SSI with prompt surgical debridement and prolonged, parenteral antibiotics is generally effective and most often results in eradication of the infection and maintenance of the instrumentation. However, it is not clear what the long-term effect of an SSI may be on clinical outcome and more specifically the potential for development of a symptomatic nonunion or instrumentation failure. To evaluate the long-term clinical and radiographic outcomes of patients who underwent an instrumented lumbar fusion complicated by an acute postoperative SSI that necessitated surgical debridement and prolonged parenteral antibiotics. A retrospective review of consecutively patients. A total of 1,602 patients were included. Multiple perioperative clinical and radiographic factors of patients who developed an SSI were compared with a cohort of patients who underwent a similar procedure during the same time period but did not develop an infection. Analysis of variants analysis was employed to assess significance of these factors. Multiple perioperative clinical and radiographic factors of patients who developed an SSI were compared with a cohort of patients who underwent a similar procedure during the same time period but did not develop an infection. Analysis of variants analysis was employed to assess significance of these factors. An acute surgical site infection occurred in 39 patients (2.8%). Significant risk factors for the development of an early SSI included age greater than 80, BMI > 30, diabetes, osteoporosis and prior decompressive surgery. Notable nonsignificant factors included length of surgery, preoperative deformity diagnosis (degenerative spondylolisthesis or degenerative scoliosis), use of iliac crest autograft or allograft, duration of postoperative suction drain, or occurrence of an incidental durotomy requiring repair. Mean length of hospital stay was significantly longer in patients with an SSI, 3.2 days versus 7.2 days (p=.02). Long-term follow-up revealed revision surgery to address symptomatic nonunion was slightly greater in the SSI cohort, 6 patients (15%) versus 15 patients (12%) in the non-infected cohort, but this did not reach significance. Radiographic evidence of a nonunion or loose instrumentation was not significantly different between the 2 cohorts at latest follow-up. At 6-month follow-up, clinical outcomes were consistently better in the non-infected cohort: VAS back (p=.04), VAS leg (p=.03) and ODI (p=.04), as were patient reported satisfaction (p=.04) and willingness to repeat the index procedure (p=.04). However, by one-year postoperatively and thereafter to the latest follow-up, no significant difference was noted in clinical outcome, patient reported satisfaction or willingness to repeat the index surgery. In this study of 1,602 patients undergoing an instrumented lumbar fusion, there was a 2.8% incidence of an acute postoperative infection requiring surgical debridement. Older, obese, diabetic patients were more at higher and the initial 6-month clinical outcomes were inferior to patients without an SSI. However, long-term follow-up showed no significant difference clinically or radiographically between those with and without an infection. Late revision surgeries were not more common with a history of an SSI. Recognition of a postoperative infection, especially in high risk patients, followed by prompt surgical intervention and appropriate parenteral antibiotics allows for maintenance of instrumentation and favorable clinical outcomes. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

Patients with a spinal epidural abscess (SEA) and associated sepsis and neurologic deterioration require immediate evaluation and prompt surgical intervention. The goals of surgery are life preservation, eradication of the infectious nidus, and restoration of neurologic function. The focus of treatment in these critically ill patients is to achieve these immediate goals. There has been limited attention given to the long-term status of patients who have survived this life threatening condition. To identify the survivability and long-term outcome of patients who underwent emergent surgical management for a SEA with associated sepsis and neurologic decline. A retrospective review of all consecutive patients with a SEA, sepsis and neurologic decline treated at a single, tertiary referral medical center from 2000-2010. Fifty-four patients. Survival/mortality, neurologic improvement (ASIA Grade), need for further spine surgery. All patients were clinically septic and had documented neurologic deterioration directly related to a spinal epidural abscess. Surgery was performed emergently from the time of notification of the spine service. Surgical approach was determined by the location of the abscess in relation to the thecal sac; 8 occurred in the cervical spine (all anterior), 20 in the thoracic spine (7 anterior, 13 posterior) and 26 in the lumbar spine (9 anterior, 17 posterior). All cervical SEA underwent an anterior decompression and fusion with structural grafting and plating, while anterior SEA within the thoracic or lumbar spines underwent anterior decompression and fusion with structural grafting followed by a staged, posterior instrumented fusion. Posterior SEA in the thoracic or lumbar spine underwent decompression and abscess evacuation only. Preoperative neurologic status was ASIA B in 20 patients, C in 20, and D in 10. The mean time of neurologic deterioration documented in the medical record was 24 hours (range: 6 hours-5 days). Stepwise multiple regression analysis was performed to identify risk factors for survival and neurologic improvement. Long-term survival was assessed using the institution's electronic medical record and subsequently confirmed by direct patient contact. All patients survived the surgery, although 6 (11%) died within one month. Significant risk factors for early mortality included age >70 (p=.01), hospitalization >5 days prior to surgery (p=.02), ASIA D (p=.02), diabetes (p=.02), end stage renal disease (p=.02), and MRSA sepsis (p=.02). Of the surviving patients, the mean neurologic improvement was 2.4 ASIA grades. Of surviving patients, 92% (44/48) regained the ability to ambulate. Significant factors for neurologic improvement included age <70 (p=.01), documented neurologic decline <24 hours (p=.01), non-diabetic (p=.02), a cervical abscess (p=.01), a thoracic or lumbar abscess not requiring fusion (p=.02), and preoperative ASIA D (p=.01). At the 10-year follow-up, 88% (42/48) of the patients who survived their perioperative course were still alive. The six non-surviving patients had died of causes unrelated to their spine infections. At the 10-year follow-up, all 42 patients were noted to have maintained their level of neurologic recovery, with none having evidence of recurrent neurologic deficits or loss of ambulatory ability. Ten percent (4/42) of the long-term surviving patients had undergone additional spine surgery, 2 for removal of painful segmental instrumentation and 2 for extension of fusions for symptomatic adjacent level disease. None of the long-term survivors required additional surgery for a recurrent spine infection. Advanced imaging (MRI or CT scan) was available for 30 of the surviving patients. Aside from the 2 patients requiring surgery for adjacent level stenosis, there were no instances of residual infectious spinal column involvement, segmental instability or sagittal plane deformity in any patient. Spinal epidural abscesses in patients with sepsis and neurologic deterioration can be effectively managed when diagnosed promptly and treated with emergent surgery. In this series, the majority of patients survived, had neurologic recovery and regained independent ambulation. However, there was a notable early mortality rate (11%), with older, diabetic patients with prolonged neurologic deficits most susceptible. Long-term survival occurred in 88% of patients, with evidence of sustained neurologic improvement, permanent eradication of the spine infection, and relatively uncommon need for additional surgery. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

Incidental durotomies (ID) are a known occurrence in lumbar spine surgery. In most cases, an ID can be effectively managed with direct repair that is often supplemented by fibrin glue or a synthetic or biologic patch. Generally, there is minimal adverse effect to the patient other than a longer than expected postoperative hospitalization accounting for a period of recumbence following the dural repair. However, on occasion, a recurrent CSF leak occurs postoperatively which can cause troubling symptoms and may require additional surgery to repair. To identify the frequency of recurrent CSF leaks in patients who underwent surgery for lumbar spinal stenosis that was complicated by a dural tear and subsequently to both define risk factors for the occurrence of a recurrent leak and to assess the effect upon the ultimate clinical outcome. A retrospective analysis of a prospectively-treated cohort of patients. A total of 1,480 consecutive patients who underwent elective, primary surgery for lumbar spinal stenosis over a 5-year period by one of four surgeons at a single academic, tertiary care medical center. Clinical follow-up was a minimum of 2 years (range: 2-8 years). VAS Score (1-10) for back and leg pain, Oswestry Disability Index, Patient Satisfaction Assessment, and Retrospective Willingness to Repeat Surgery. A dural tear (DT) occurred in 103 of 1,481 patients (7%). Fourteen of 103 patients (14%) developed a symptomatic, postoperative CSF leak requiring additional surgery. Overall, a recurrent CSF leak occurred in 14 of the 1,481 patients (0.9%) who underwent a primary lumbar decompression for spinal stenosis who were evaluated in the study. All dural tears were identified at the time of the index surgery. Dural repairs were directly repaired with either a 4-0 silk or 6-0 polypropylene suture in a water tight fashion and assessed with a Valsalva maneuver prior to closure. Repairs were augmented with fibrin glue in 70% of cases, a collagen patch in 32%, and both in 20%. Patients were kept on bedrest following surgery for 1-3 days. A subfascial drain was employed in 82% of patients. Choice of suture, augmentation of repair, use of drain and duration of bedrest were based on surgeon discretion. Multi-variate regression analysis was employed to identify significant risk factors for a postoperative CSF leak. Of the 14 patients with a recurrent CSF leak, symptoms arose during the postoperative hospitalization in 11 patients (79%) and after discharge in 3 (21%). Each patient had a palpable subcutaneous mass and 4 patients (29%) had a percutaneous CSF leak. Each patient was symptomatic with postural headache and 10(71%) experienced photophobia. Significant risk factors for development of a CSF leak included age > 70, body mass index > 30 (obese), history of diabetes and chronic use of corticosteroids. Notable factors not significant included duration of surgery, the additional diagnosis of degenerative spondylolisthesis or degenerative scoliosis, presence of a fusion, numbers of levels decompressed or fused, use of BMP or particular bone graft choice, nor preoperative use of pharmacologic anticoagulation. The likelihood of a recurrent leak was not significantly affected by a particular type of surgical dural repair, the suture material employed, nor the use of a synthetic patch or fibrin glue. As well, the use of a postoperative, subfascial drain nor the duration of recumbancy after the initial surgery did not significantly affect the development of a recurrent CSF leak. At 3-month follow-up, two patient reported outcomes (ODI, patient satisfaction) were slightly less in patients who had a recurrent CSF leak, compared with both durotomy patients with no recurrent leak and those with no durotomy, although this did not reach statistical significance. At 6 month, 12 month, and final follow-up, there were no statistical differences in patient-reported outcomes between the recurrent CSF leak, durotomy without recurrent leak, and no durotomy cohorts. Length of hospitalization was an average of 4.2 days longer in patients with a recurrent CSF leak compared with patients with no durotomy and 2.2 days longer than patients with a durotomy but no recurrent leak. Cost of hospitalization was $65,000 greater in patients with a recurrent leak compared to those with no durotomy and $35,000 greater than those with a durotomy but no recurrent leak. Incidental durotomy is a relatively uncommon occurrence in primary surgery to treat lumbar spinal stenosis. Recurrent CSF leak following repair of a durotomy is also uncommon, with an incidence of 14% of patients with a durotomy in this large single center study. Prompt recognition of a recurrent CSF leak and subsequent surgical repair effectively treats this problem and adverse sequelae did not occur and ultimate clinical outcomes were not altered compared to those without a durotomy or a recurrent CSF leak. Hospital length of stay and cost were greater in those with this uncommon complication. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

In organic mixed ionic–electronic conductors (OMIECs), it is critical to understand the motion of ions in the electrolyte and OMIEC. Generally, the focus is on the movement of net charge during gating, and the motion of neutral anion–cation pairs is seldom considered. Uptake of mobile ion pairs by the semiconductor before electrochemical gating (passive uptake) can be advantageous as this can improve device speed, and both ions can participate in charge compensation during gating. Here, such passive ion pair uptake in high‐speed solid‐state devices is demonstrated using an ion gel electrolyte. This is compared to a polymerized ionic liquid (PIL) electrolyte to understand how ion pair uptake affects device characteristics. Using X‐ray photoelectron spectroscopy, the passive uptake of ion pairs from the ion gel into the OMIEC is detected, whereas no uptake is observed with a PIL electrolyte. This is corroborated by X‐ray scattering, which reveals morphological changes to the OMIEC from the uptake of ion pairs. With in situ Raman, a reorganization of both anions and cations is then observed during gating. Finally, the speed and retention of OMIEC‐based neuromorphic devices are tuned by controlling the freedom of charge motion in the electrolyte. [ABSTRACT FROM AUTHOR]

The article focuses on a prospective cross-sectional study to establish a normative database of peripapillary retinal nerve fiber layer (RNFL) thickness, macular thickness, and retinal layer thickness in healthy North American children, using spectral-domain optical coherence tomography (SD OCT). The results of this study indicated that SD OCT can be used to assess peripapillary RNFL thickness, macular thickness, and retinal layer thickness in children as young as 5 years.

Introduction and Purpose: A number of studies have evaluated visual acuity (VA) of special needs children, but no analyses of the parents' perception of VA testing or the utilization of VA test results by pediatric ophthalmologists have been reported. Patients and Methods: Special needs children referred for an initial VA test (Teller Acuity Cards) during a 2-year period were enrolled (n = 309). Within the overall cohort, twenty consecutive parents whose child attended during a 6-week period completed a Parent Questionnaire before and after VA testing. Also, 58 parents of infants with cortical visual impairment (CVI) completed the Parental Stress Index-Short Form (PSI-SF) before VA testing and 3 months later. Referring pediatric ophthalmologists (n = 12) completed a Physician Questionnaire. Results: VA testing was associated with parents reporting increased knowledge scores and decreased concerns about their children's vision on the Parent Questionnaire. VA testing was also associated with reduced Total and Parental Distress subscale scores on the PSI-SF by parents of infants with CVI. Ophthalmologists reported that VA results were useful in diagnosis and clinical management and provided new information to parents, Early Childhood Intervention programs, schools, and social agencies. Conclusion: VA testing is of benefit in children with special needs to both their parents and ophthalmologists, providing quantitative information about visual impairment and reducing stress experienced by parents. [ABSTRACT FROM AUTHOR]

Abstract: Bone morphogenic proteins (BMPs) are growth factors important for skeletal development and bone growth. Noggin, one of the soluble BMP antagonists, regulates the action of BMPs on mesenchymal precursor cells, partially through a feedback type of inhibition. In this study, we constructed a novel BMP2/7 ‘fusion gene’ that encodes both BMP2 and BMP7 genes in tandem by a linker. Polymerase chain reaction (PCR) and Western blotting showed that the BMP2/7 fusion gene construct led to the production of BMP2/7 heterodimers in A549 ‘producer’ cells. When applied to C2C12 myoblastic cells, BMP2/7 heterodimers increased alkaline phosphatase (ALP) activity and osteocalcin (OCN) expression (markers of osteoblastic differentiation) more effectively than either BMP2 or BMP7 homodimers. Moreover, this heterodimer induced significantly lower levels of Noggin expression in C2C12 cells than respective homodimers at similar doses. The addition of Noggin did not affect the heterodimer''s activities in increasing osteoblastic differentiation in C2C12 cells. In contrast, BMP2 and BMP7 homodimers were largely inhibited by Noggin. Our finding suggests that the ‘fusion gene’ construct led to the production of bioactive BMP2/7 heterodimers, which were not antagonized by Noggin as effectively as it to BMP homodimers. The weaker Noggin antagonism on BMP heterodimers compared to homodimers may contribute to increased osteogenic potency of heterodimers in vitro and in vivo. [Copyright &y& Elsevier]

The polyacrylamide SDS electrophoretic pattern of protein extracted from the stratum corneum obtained by scraping the surface of involved skin of patients with psoriasis was different from that of uninvolved skin and normal controls. The pattern from superficial scales was similar to that of whole stratum corneum in the case of involved psoriatic epidermis but different in uninvolved and normal epidermis. These data indicate that the changes which are observed in the structural proteins during normal keratinization are not seen in involved psoriatic epidermis. In addition, the relative proportion of keratin polypeptides was different in involved psoriatic epidermis compared to normal skin. That these changes are not specific for psoriasis was shown by finding similar electrophoretic patterns with stratum corneum proteins from patients with other keratinizing disorders. [ABSTRACT FROM AUTHOR]

The introduction of the techniques of molecular biology as tools to study skin carcinogenesis has provided more precise localization of biochemical pathways that regulate the tumor phenotype. This approach has identified genetic changes that are characteristic of each of the specific stages of squamous cancer pathogenesis: initiation, exogenous promotion, premalignant progression, and malignant conversion. Initiation can result from mutations in a single gene, and the Harvey allele of the ras gene family has been identified as a frequent site for initiating mutations. Heterozygous activating mutations in c-rasHa are dominant, and affected keratinocytes hyperproliferate and are resistant to signals for terminal differentiation. An important pathway impacted by c-rasHa activation is the protein kinase C (PKC) pathway, a major regulator of keratinocyte differentiation. Increased activity of PKCα and suppression of PKCδ by tyrosine phosphorylation contribute to the phenotypic consequences of rasHa gene activation in keratinocytes. Tumor promoters disturb epidermal homeostasis and cause selective clonal expansion of initiated cells to produce multiple benign squamous papillomas. Resistance to differentiation and enhanced growth rate of initiated cells impart a growth advantage when the epidermis is exposed to promoters. The frequency of premalignant progression varies among papillomas, and subpopulations at high risk for progression have been identified. These high-risk papillomas overexpress the α6β4 integrin and are deficient in transforming growth factor β1 and β2 peptides, two changes associated with a very high proliferation rate in this subset of tumors. The introduction of an oncogenic rasHa gene into epidermal cells derived from transgenic mice with a null mutation in the TGFβ1 gene have an accelerated rate of malignant progression when examined in vivo. Thus members of the TGFβ gene family contribute a tumor-suppressor function in carcinogenesis. Accelerated malignant progression is also found with v-rasHa transduced keratinocytes from skin of mice with a null mutation in the p53 gene. The similarities in risk for malignant conversion by initiated keratinocytes from TGFβ and p53 null geneotypes suggest that a common, growth-related pathway may underly the tumor-suppressive functions of these proteins in the skin carcinogenesis model. [ABSTRACT FROM AUTHOR]

Proteins from mouse epidermis cytosol extracts react on immunoblots with a polyclonal rabbit antiserum raised against rat skin calcium-binding protein (SCaBP), a parvalbumin of the panniculus carnosus. Three mouse epidermal proteins with molecular weights between 10-12K, which are distinct from SCaBP, are recognized by the antiserum. The synthesis of these proteins in keratinocyte culture is modulated by Ca++, as is the differentiation of the keratinocytes. Proliferating mouse keratinocytes in medium containing 0.07 mM Ca++ (low CaCa++) undergo terminal differentiation when the Ca++ concentration is elevated to 1.8 mM (high Ca++). Synthesis of the 3 antigens can be demonstrated when soluble extracts of keratinocytes labeled with [35S]methionine in low Ca++ medium are immunoprecipitated with anti-SCaBP serum. These antigens are not synthesized in cultures of dermal fibroblasts. When keratinocytes are switched to high Ca++ medium, synthesis of these antigens is greatly diminished over the course of 48-72 h. However, the antigens persist in differentiating cells. When proliferating keratinocytes in low Ca++ medium are exposed to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), differentiation is induced in a subpopulation of cells, and specific antigen synthesis is transiently inhibited. The inhibition correlates with the time when many cells are differentiating in response to TPA. When proliferating keratinocytes are pulse-labeled with 32PO4, the 11 K antigen is phosphorylated and the phosphorylation is not enhanced by TPA exposure. All 3 antigens are synthesized in a reticulocyte lysate preparation with added newborn mouse epidermis messenger RNA or mRNA from keratinocytes cultured in low Ca++ medium. Thus, these antigens are likely to represent unique proteins rather than processed or degraded ones. The coordinately regulated expression of these antigens associated with the differentiation state of the keratinocyte proliferation and differentiation. [ABSTRACT FROM AUTHOR]

Complementary DNA (cDNA) clones constructed to the 55, 59 and 67 kilodalton (K) keratins, the major keratins synthesized in newborn mouse epidermis, were used as molecular hybridization probes to examine the expression of these genes in newborn epidermis and normal and malignantly transformed epidermal cells in culture. Transcripts of these three keratin genes are abundant in newborn epidermis. However, primary cultures of epidermal cells contain very low levels of these RNAs, The decreased expression of these keratin genes in primary cells appears to be due to factors within the culture system. Unlike primary-cell cultures, the malignantly transformed cell line Pam 212 synthesizes keratin proteins and mRNAs similar to newborn epidermis, including the 67 K keratin, However, synthesis of the 67 K keratin in Pam 212 cells is modulated by culture factors. Keratin gene expression in another Pam line, 321, differs from that of Pam 212 cells in that decreased expression of these three keratin genes occurs. These results indicate that keratin genes that are normally expressed in vivo in epidermis may be expressed in malignant epidermal cells under conditions that do not permit expression of these genes in nonmalignant primary epidermal cells. [ABSTRACT FROM AUTHOR]

The development of a postoperative epidural hematoma following lumbar spinal stenosis surgery is an uncommon but potentially devastating complication. It is unclear of the long-term clinical and economic impact related to the additional surgical care needed to treat these adverse events. To define the incidence of acute postoperative epidural hematomas requiring subsequent surgical evacuation following primary decompressive laminectomy surgery, as well as the perioperative risk factors, effect on short and long-term outcomes, and the economic impact due to the need for the additional care required. A retrospective analysis of prospectively collected patients. A total of 610 consecutive patients. Patient recorded outcomes including visual analog pain scores, Oswestry Disability Index, patient satisfaction, willingness to repeat surgery, hospital length of stay and estimated cost. Patients who developed a symptomatic epidural hematoma within the acute postoperative period (4 weeks from the index procedure) were evaluated. Perioperative risk factors were assessed for significance with a multivariate regression analysis. The clinical and economic impact of the need for a second surgery was compared to the cohort of patients who underwent surgery during the same time period but did not develop a hematoma. An acute postoperative epidural hematoma occurred in 21 patients (3.7%). The presence of a symptomatic hematoma occurred at an average of 6.5 days (range 3-21 days) postoperatively. The most common symptoms associated with a hematoma were worsening back pain (100% of patients), increased leg pain (90%), new onset leg weakness (52%) and urinary retention (29%). An MRI confirmed the clinical diagnosis in 11 of 21 patients (52%). Clinical risk factors significant (p<.05) for the development of a hematoma included age greater than 80 years old, body mass index greater than 30, history of diabetes, rheumatoid arthritis, a connective tissue disorder requiring preoperative steroid and osteoporosis. Notable factors not significant included duration of surgery, the need for a spine fusion, number of surgical levels fused or decompressed, a diagnosis of degenerative scoliosis or degenerative spondylolisthesis, the preoperative use of pharmacologic anticoagulation and the use of BMP or other bone graft substitutes. No significant correlation could be found between the development of an epidural hematoma and the use of a postoperative subfascial drain, the amount of postoperative drainage, nor the duration the drain was kept in place. At 3-month followup, all patient reported outcome measures were significantly less favorable in those patients who had an epidural hematoma. However, by 6 months following surgery and at the time of latest followup (minimum 10 years), there was no significant difference in any patient reported outcome measure. Length of stay was increased an average of 4.3 days and cost of hospitalization was greater by an average of $140,000. A postoperative epidural hematoma following lumbar spinal stenosis surgery occurred in 3.7% of 610 consecutive patients. Older, unhealthier patients were more prone to the development of a hematoma. With the need for surgical evacuation, the initial patient reported outcome measures and patient satisfaction rates were significantly lower, but ultimately no long-term difference was noted when compared with a cohort of patients without a hematoma. Prompt identification and surgical evacuation appears to be effective in lowering any long-term morbidity associated with the development of a postoperative epidural hematoma. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

Degenerative cervical myelopathy (DCM) represents a collection of age-related degenerative processes of the cervical spine that can result in motor, sensory and autonomic dysfunction, leading to significant reductions in quality of life. Older individuals, and in particular octogenarians, with advanced myelopathy pose unique clinical challenges, as they may be severely compromised and while they may benefit from surgery, the extent of neurologic improvement may be unpredictable and the risk of adverse events may be higher than younger patients. The aim of this study was to better characterize outcomes following cervical spine surgery in octogenarians with advanced myelopathy. A retrospective analysis of a consecutively treated patients older than age 80 with degenerative cervical myelopathy who underwent cervical decompression surgery at a single institution over a 10-year period (2010-2019). A total of 57 patients. Nurick grade, mJOA scores, patient-reported satisfaction. All patients experienced myelopathic features and exhibited multi-level spinal cord compression on preoperative MRI. Surgical techniques employed were based on location of the compressive neural pathology, spinal alignment and the presence of segmental instability. The average followup duration was 3.50 ± 1.56 years. Paired t-tests and Wilcoxon-signed rank tests were used to compare Nurick and mJOA scores before and after surgery. Multiple preoperative clinical and radiographic variables were evaluated to assess their effect on postoperative outcome. A multivariate analysis of variants was employed to assess the significance of these variables. Fifty of 57 (88%) patients noted improvement in both Nurick grade and mJOA score postoperatively. The mean Nurick grade improved from 4.15 ± 0.21 to 2.02 ± 0.72 (p < 0.001, paired t-test; 95% CI -2.08 to -1.71). The mean mJOA score improved from 9.48 ± 1.31 to 14.50 ± 1.37 (p < 0.001, paired t-test; 95% CI 2.59 to 3.45). Eleven of 14 patients (78%) who were nonambulatory prior to surgery regained the ability to ambulate. Significant risk factors for the 12% of patients who did not improve included preoperative symptoms greater than 1 year, diabetes, residing in an assisted living environment, preoperative nonambulation. Notable factors not significantly affecting outcome included type of surgical procedure, number of levels of preoperative cord compression, or presence of myelomalacia. Adverse events requiring additional surgery occurred in 4 patients (8%), including anterior plate displacement in 1 patient, persistent dysphagia requiring temporary gastrostomy tube in 1 patient, and additional posterior surgery for instrumentation failure and development of kyphotic deformity. In comparison with a cohort of nonoctogenarians undergoing myelopathy surgery, adverse events and need for further surgery were not significantly different. Our study demonstrated that elderly patients with severe forms of DCM experienced significant improvement in neurological function following cervical decompression surgery. These improvements indicate that cervical decompression surgery is effective in this patient population and while consideration of the effect of age in elderly patients must always be given consideration, it is not a contraindication for surgery. This abstract does not discuss or include any applicable devices or drugs. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD) clinically predisposes to columnar Barrett's metaplasia (BM) in the distal esophagus. We demonstrate evidence supporting the cellular origin of BM from reprograming or transcommitment of resident normal esophageal squamous (NES) epithelial cells in response to acid and bile (A + B) exposure using an in vitro cell culture model. The hTERT-immortalized NES cell line NES-B10T was exposed 5 min/day to an A + B mixture for 30 wk. Morphological changes, mRNA, and protein expression levels for the inflammatory marker cyclooxygenase-2; the lineage-determining transcription factors TAp63 (squamous), CDX2, and SOX9 (both columnar); and the columnar lineage markers Villin, Muc-2, CK8, and mAb Das-1 (incomplete phenotype of intestinal metaplasia) were assessed every 10 wk. Markers of columnar lineage and inflammation increased progressively, while squamous lineage-determining transcriptional factors were significantly decreased both at the mRNA and/or protein level in the NES-B10T cells at/after A + B treatment for 30 wk. Distinct modifications in morphological features were only observed at/after 30 wk of A + B exposure. These changes acquired by the NES-B10T 30-wk cells were retained even after cessation of A + B exposure for at least 3 wk. This study provides evidence that chronic exposure to the physiological components of gastric refluxate leads to repression of the discernable squamous transcriptional factors and activation of latent columnar transcriptional factors. This reflects the alteration in lineage commitment of the precursor-like biphenotypic, NES-B10T cells in response to A + B exposure as the possible origin of BM from the resident NES cells. [ABSTRACT FROM AUTHOR]

The simplified and genetically conserved zebrafish pronephros is an excellent model to examine the cryptic processes of cell fate decisions during the development of nephron segments as well as the origins of associated endocrine cells that comprise the corpuscles of Stannius (CS). Using whole mount in situ hybridization, we found that transcripts of the zebrafish genes t-box 2a ( tbx2a ) and t-box 2b ( tbx2b ), which belong to the T-box family of transcription factors, were expressed in the caudal intermediate mesoderm progenitors that give rise to the distal pronephros and CS. Deficiency of tbx2a , tbx2b or both tbx2a/b reduced the size of the distal late (DL) segment, which was accompanied by a proximal convoluted segment (PCT) expansion. Further, tbx2a/b deficiency led to significantly larger CS clusters. These phenotypes were also observed in embryos with the from beyond (fby) c144 mutation, which encodes a premature stop codon in the tbx2b T-box sequence. Conversely, overexpression of tbx2a and tbx2b in wild-type embryos expanded the DL segment where cells were comingled with the adjacent DE, and also decreased CS cell number, but notably did not alter PCT development—providing independent evidence that tbx2a and tbx2b are each necessary and sufficient to promote DL fate and suppress CS genesis. Epistasis studies indicated that tbx2a acts upstream of tbx2b to regulate the DL and CS fates, and likely has other targets as well. Retinoic acid (RA) addition and inhibition studies revealed that tbx2a and tbx2b are negatively regulated by RA signaling. Interestingly, the CS cell expansion that typifies tbx2a/b deficiency also occurred when blocking Notch signaling with the chemical DAPT (N-[N-(3,5-difluorophenacetyl)- L -alanyl]-S-phenylglycine t-butyl ester). Ectopic activation of Notch in Tg ( hsp70::Gal4; UAS::NICD )(NICD) embryos led to a reduced CS post heat-shock induction. To further examine the link between the tbx2a/b genes and Notch during CS formation, DAPT treatment was used to block Notch activity in tbx2a/b deficient embryos, and tbx2a/b knockdown was performed in NICD transgenic embryos. Both manipulations caused similar CS expansions, indicating that Notch functions upstream of the tbx2a/b genes to suppress CS ontogeny. Taken together, these data reveal for the first time that tbx2a/b mitigate pronephros segmentation downstream of RA, and that interplay between Notch signaling and tbx2a/b regulate CS formation, thus providing several novel insights into the genetic regulatory networks that influence these lineages. [ABSTRACT FROM AUTHOR]

An abstract of the article "Comparison of CT vs CT-MRI Fusion Imaging in Assessment of Mastoid Cavity Involvement by Cholesteatoma: Implications for Endoscopic Ear Surgery" by Alexander Saxby and others is presented.

The kidney is comprised of nephrons – epithelial tubes with specialized segments that reabsorb and secrete solutes, perform osmoregulation, and produce urine. Different nephron segments exhibit unique combinations of ion channels, transporter proteins, and cell junction proteins that govern permeability between neighboring cells. The zebrafish pronephros is a valuable model to study the mechanisms of vertebrate nephrogenesis, but many basic features of segment gene expression in renal progenitors and mature nephrons have not been characterized. Here, we analyzed the temporal and spatial expression pattern of tight junction components during zebrafish kidney ontogeny. During nephrogenesis, renal progenitors show discrete expression domains of claudin (cldn) 15a, cldn8, occludin (ocln) a, oclnb, tight junction protein (tjp) 2a, tjp2b , and tjp3 . Interestingly, transcripts encoding these genes exhibit dynamic spatiotemporal domains during the time when pronephros segment domains are established. These data provide a useful gene expression map of cell junction components during zebrafish nephrogenesis. As such, this information complements the existing molecular map of nephron segment characteristics, and can be used to characterize kidney development mutants as well as various disease models, in addition to aiding in the elucidation of mechanisms governing epithelial regeneration after acute nephron injury. [ABSTRACT FROM AUTHOR]

CLIC4/mtCLIC, a chloride intracellular channel protein, localizes to the mitochondria and cytoplasm of keratinocytes and participates in the apoptotic response to stress. We now show that multiple stress inducers cause the translocation of cytoplasmic CLIC4 to the nucleus. Immunogold electron microscopy and confocal analyses indicate that nuclear CLIC4 is detected prior to the apoptotic phenotype. CLIC4 associates with the Ran, NTF2, and Importin-α nuclear import complexes in immunoprecipitates of lysates from cells treated with apoptotic/stress-inducing agents. Deletion or mutation of the nuclear localization signal in the C terminus of CLIC4 eliminates nuclear translocation, whereas N terminus deletion enhances nuclear localization. Targeting CLIC4 to the nucleus via adenoviral transduction accelerates apoptosis when compared with cytoplasmic CLIC4, and only nuclear-targeted CLIC4 causes apoptosis in Apaf null mouse fibroblasts or in Bcl-2-overexpressing keratinocytes. These results indicate that CLIC4 nuclear translocation is an integral part of the cellular response to stress and may contribute to the initiation of nuclear alterations that are associated with apoptosis. [ABSTRACT FROM AUTHOR]

Staurosporine (stsp) induces assembly of cornified envelopes in mouse keratinocyte cultures. To clarify whether this effect is the consequence of a coordinated differentiation program similar to that observed in epidermis, we assessed the expression of multiple differentiation-specific markers in stsp-treated keratinocytes. In medium containing 0.05 mM Ca&sup2+; in which the basal cell phenotype is normally maintained, stsp induced dose-dependent increases in keratin 1, epidermal and keratinocyte transglutaminases, SPR-1, loricrin, and profilaggrin mRNA. Based on nuclear run-on analysis, stsp-mediated marker expression was found to be due at least in part to increased transcription. Since protein kinase C (PKC) activation is required for keratinocyte differentiation, we tested whether stsp influenced this signaling pathway. Stsp induced the translocation of multiple PKC isoforms from the cytosol to membrane and/or cytoskeletal fractions, inducing isozyme downregulation within 24 h. Moreover, AP-1 DNA binding activity was elevated in stsp-treated keratinocytes, consistent with the notion that this agent influences keratinocyte-specific gene expression via the PKC pathway. Stsp-mediated marker expression was inhibited by the PKC inhibitor GF 109203X. In cells pre-treated with bryostatin 1 to selectively down-modulate specific PKC isoforms, stsp-induced loricrin, filaggrin, and SPR-1 expression was suppressed when PKC α, &epsiv;, and/or δ were downregulated, suggesting that these isozymes may be necessary for marker expression in response to this agent. Thus, in addition to its effects on cornified envelope assembly, stsp induces a coordinate program of differentiation-specific keratinocyte gene expression that is mediated at least in part by the PKC signaling pathway. [ABSTRACT FROM AUTHOR]

Keratinocyte differentiation requires integrating signaling among intracellular ionic changes, kinase cascades, sequential gene expression, cell cycle arrest, and programmed cell death. We now show that Cl¯ intracellular channel 4 (CLIC4) expression is increased in both mouse and human keratinocytes undergoing differentiation induced by Ca2+, serum and the protein kinase C (PKC)-activator, 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Elevation of CLIC4 is associated with signaling by PKCδ, and knockdown of CLIC4 protein by antisense or shRNA prevents Ca2+-induced keratin 1, keratin 10 and filaggrin expression and cell cycle arrest in differentiating keratinocytes. CLIC4 is cytoplasmic in actively proliferating keratinocytes in vitro, but the cytoplasmic CLIC4 translocates to the nucleus in keratinocytes undergoing growth arrest by differentiation, senescence or transforming growth factor β (TGFβ) treatment. Targeting CLIC4 to the nucleus of keratinocytes via adenoviral transduction increases nuclear Cl¯ content and enhances expression of differentiation markers in the absence of elevated Ca2+. In vivo, CLIC4 is localized to the epidermis in mouse and human skin, where it is predominantly nuclear in quiescent cells. These results suggest that CLIC4 participates in epidermal homeostasis through both alterations in the level of expression and subcellular localization. Nuclear CLIC4, possibly by altering the Cl¯and pH of the nucleus, contributes to cell cycle arrest and the specific gene expression program associated with keratinocyte terminal differentiation. [ABSTRACT FROM AUTHOR]