Electrical conductivity and the red shift of absorption in olivine and spinel at high pressure.
Above 100 kilobars the apparent absorption edges (approximately 3 electron volts) of single-crystal and polycrystalline samples of the metastable olivine and stable spinel forms of Fe(2)SiO(4) shift rapidly with pressure from the near-ultraviolet into the lower-energy infrared region. Simultaneously, an exponential increase in electrical conductivity occurs. These effects are reversible as pressure is reduced or reapplied and are not accompanied by a first-order phase change in olivine or spinel. These observations relate to fundamental concepts of electrical conductivity and photon absorption in complex transition-metal silicates in that they cannot be readily interpreted in terms of an intrinsic band-gap model. The intensity and energy changes are too great and the effect occurs at too low a pressure to be explained by processes such as spin-pairing and other crystal-field effects. The results suggest that a new mechanism of conduction, perhaps symbiotic and employing an efficient charge-transfer process, is induced at high pressure.


[Sonographic detection of fasciculations].
Fasciculations are an important neurological sign of spinal muscular atrophies. 26 patients able to walk suffering from adult onset spinal muscular atrophies were examined by real time sonography. On an average 18 limb and extremity muscles on both sides were examined. In 21 cases fasciculations became sonographically apparent as muscular twitchings lasting for 0.2 to 0.5 seconds. Detection of fasciculations in profound muscular layers and in obese patients was easier by sonography than by clinical examination.


Target Occupancy and Functional Inhibition of JAK3 and TEC Family Kinases by Ritlecitinib in Healthy Adults: An Open-Label, Phase 1 Study.
Ritlecitinib is a small molecule in clinical development that covalently and irreversibly inhibits Janus kinase 3 (JAK3) and the TEC family of kinases (BTK, BMX, ITK, TXK, and TEC). This phase 1, open-label, parallel-group study assessed target occupancy and functional effects of ritlecitinib on JAK3 and TEC family kinases in healthy participants aged 18-60 years who received 50 or 200 mg single doses of ritlecitinib on day 1. Blood samples to assess ritlecitinib pharmacokinetics, target occupancy, and pharmacodynamics were collected over 48 hours. Target occupancy was assessed using mass spectroscopy. Functional inhibition of JAK3-dependent signaling was measured by the inhibition of the phosphorylation of its downstream target signal transducer and activator of transcription 5 (pSTAT5), following activation by interleukin 15 (IL-15). The functional inhibition of Bruton's tyrosine kinase (BTK)-dependent signaling was measured by the reduction in the upregulation of cluster of differentiation 69 (CD69), an early marker of B-cell activation, following treatment with anti-immunoglobulin D. Eight participants received one 50 mg ritlecitinib dose and 8 participants received one 200 mg dose. Ritlecitinib plasma exposure increased in an approximately dose-proportional manner from 50 to 200 mg. The maximal median JAK3 target occupancy was 72% for 50 mg and 64% for 200 mg. Ritlecitinib 50 mg had >94% maximal target occupancy of all TEC kinases, except BMX (87%), and 200 mg had >97% for all TEC kinases. For BTK and TEC, ritlecitinib maintained high target occupancy throughout a period of 48 hours. Ritlecitinib reduced pSTAT5 levels following IL-15- and BTK-dependent signaling in a dose-dependent manner. These target occupancy and functional assays demonstrate the dual inhibition of the JAK3- and BTK-dependent pathways by ritlecitinib. Further studies are needed to understand the contribution to clinical effects of inhibiting these pathways.


Accuracy of prenatal ultrasound in detecting jejunal and ileal atresia: systematic review and meta-analysis.
The accuracy of prenatal ultrasound examination in detecting jejunal and ileal atresia has been reported in the literature to be highly variable, at 25-90%. The aim of this systematic review was to evaluate the accuracy of prenatal ultrasound in detecting non-duodenal small bowel atresia (ND-SBA). MEDLINE, EMBASE and The Cochrane Library, including The Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and The Cochrane Central Register of Controlled Trials (CENTRAL), were searched electronically. The overall detection rate of jejunal or ileal atresia using ultrasound was reported. The accuracy of using polyhydramnios and dilated loops of bowel as diagnostic signs was also explored. Sixteen studies involving 640 fetuses were included in this review. The detection rate of ND-SBA by prenatal ultrasound was highly variable, with values ranging from 10 to 100%, with an overall prediction of 50.6% (95% CI, 38.0-63.2%). When analyzed separately, the detection rates of jejunal and ileal atresia were 66.3%, (95% CI, 33.9-91.8%) and 25.9% (95% CI, 4.0-58.0%), respectively. Both dilated loops of bowel and polyhydramnios as diagnostic signs for ND-SBA provided a low overall detection rate. The diagnostic performance of prenatal ultrasound in identifying ND-SBA is extremely variable. Large studies are needed in order to identify objective and combined criteria for the diagnosis of these anomalies.


Dopamine D1 receptor involvement in latent inhibition and overshadowing.
Latent inhibition (LI) manifests as poorer conditioning to a stimulus that has previously been experienced without consequence. There is good evidence of dopaminergic modulation of LI, as the effect is reliably disrupted by the indirect dopamine (DA) agonist amphetamine. The disruptive effects of amphetamine on LI are reversed by both typical and atypical antipsychotics, which on their own are able to facilitate LI. However, the contribution of different DA receptors to these effects is poorly understood. Amphetamine effects on another stimulus selection procedure, overshadowing, have been suggested to be D1-mediated. Thus, in the current experiments, we systematically investigated the role of D1 receptors in LI. First, we tested the ability of the full D1 agonist SKF 81297 to abolish LI and compared the effects of this drug on LI and overshadowing. Subsequently, we examined whether the D1 antagonist SCH 23390 can lead to the emergence of LI under conditions that do not produce the effect in normal animals (weak pre-exposure). Finally, we tested the ability of SCH 23390 to block amphetamine-induced disruption of LI. We found little evidence that direct stimulation of D1 receptors abolishes LI (although there was some attenuation of LI at 0.4 mg/kg SKF 81297). Similarly, SCH 23390 failed to enhance LI. However, SCH 23390 did block amphetamine-induced disruption of LI. These data indicate that, while LI may be unaffected by selective manipulation of activity at D1 receptors, the effects of amphetamine on LI are to some extent dependent on actions at D1 receptors.


Hydroxyapatite-coated collars reduce radiolucent line progression in cemented distal femoral bone tumor implants.
Aseptic loosening of massive bone tumor implants is a major cause of prosthesis failure. Evidence suggests that an osteointegrated hydroxyapatite (HA)-coated collar would reduce the incidence of aseptic loosening around the cemented intramedullary stem in distal femoral bone tumor prostheses. Because these implants often are used in young patients with a tumor, such treatment might extend the longevity of tumor implants. Questions/purposes We asked whether (1) HA-coated collars were more likely to osteointegrate; (2) HA collars were associated with fewer progressive radiolucent lines around the stem-cement interface; and (3) HA-coated collars were associated with less bone loss at the bone-shoulder implant junction? Twenty-two patients were pair-matched to one of two groups--either (1) implants with a HA-coated ingrowth collar (HA Collar Group); or (2) implants without an ingrowth collar (Noncollar Group). Age, sex, and length of followup were similar in both groups. HA-coated collars were developed and used at our institution from 1992 to address the high failure rate attributable to aseptic loosening in patients with massive bone tumor implants. Before this, smooth titanium shafts were used routinely adjacent to bone at the transection site. The minimum followup was 2 years (mean, 7 years; range, 2-12 years). Radiographs obtained throughout the followup period were analyzed and osteointegration at the shaft of the implant quantified. Radiolucent line progression around the cemented stem was semi-quantitatively assessed and cortical bone loss at the bone-shoulder implant junction was measured during the followup period. Comparison of the most recent radiographs showed nine of 11 patients had osteointegrated HA collars, whereas only one patient in the Noncollar Group had osteointegration (p > 0.001). The radiolucent line score quantified around the cemented stem was lower in the HA Collar Group when compared with the Noncollar Group (p = 0.001). Results showed an increase in cortical bone loss at the bone-shoulder implant junction in the Noncollar Group when compared with the HA Collar Group (p < 0.001). Osteointegration at the implant collar resulted in fewer radiolucent lines adjacent to the intramedullary cemented stem and decreased cortical bone loss immediately adjacent to the transection site. These results suggest that the HA collar may help reduce the risk of aseptic loosening in patients with this type of implant, but longer followup and a larger prospective comparison series are necessary to prove this more definitively.


Sequestration of cardenolides inOncopeltus fasciatus: Morphological and physiological adaptations.
The morphological and physiological adaptations associated with sequestration of cardenolides by the lygaeidOncopeltus fasciatus are summarized and discussed. Cardenolides are efficiently accumulated inO. fasciatus; however, the insect does not appear to suffer any physiological cost as a result of handling large amounts of these plant toxins. Morphological adaptations of the insect include a modified integument composed of a double layered epidermis with an inner layer (the dorsolateral space) specialized for cardenolide storage. Special weak areas of the cuticle are found on both the thorax and abdomen, which rupture when the insect is squeezed, resulting in the cardenolide-rich contents of the inner epidermal layer being released onto the body surface in the form of discrete spherical droplets. Physiological adaptations include selective sequestration of food plant cardenolides, concentration of cardenolides in the dorsolateral space, passive uptake of cardenolides at the gut and dorsolateral space requiring little energy output, reabsorption of secreted cardenolides by the Malpighian tubules, high in vivo tolerance to cardenolides, and the presence of cardenolide-resistant Na,K-ATPases.


Novel tumour suppressor roles for GZMA and RASGRP1 in Theileria annulata-transformed macrophages and human B lymphoma cells.
Theileria annulata is a tick-transmitted apicomplexan parasite that infects and transforms bovine leukocytes into disseminating tumours that cause a disease called tropical theileriosis. Using comparative transcriptomics we identified genes transcriptionally perturbed during Theileria-induced leukocyte transformation. Dataset comparisons highlighted a small set of genes associated with Theileria-transformed leukocyte dissemination. The roles of Granzyme A (GZMA) and RAS guanyl-releasing protein 1 (RASGRP1) were verified by CRISPR/Cas9-mediated knockdown. Knocking down expression of GZMA and RASGRP1 in attenuated macrophages led to a regain in their dissemination in Rag2/γC mice confirming their role as dissemination suppressors in vivo. We further evaluated the roles of GZMA and RASGRP1 in human B lymphomas by comparing the transcriptome of 934 human cancer cell lines to that of Theileria-transformed bovine host cells. We confirmed dampened dissemination potential of human B lymphomas that overexpress GZMA and RASGRP1. Our results provide evidence that GZMA and RASGRP1 have a novel tumour suppressor function in both T. annulata-infected bovine host leukocytes and in human B lymphomas.


[Disease models and change in attitude of involuntarily admitted schizophrenic patients].
The attitude to illness and therapy of 28 involuntary and 31 voluntary patients admitted to a state psychiatric hospital was investigated by means of a questionnaire at the time of admission and prior to discharge. Involuntary patients have less illness consciousness, and only 17.9% of them but 67.7% of the voluntary patients show insight into their illness; they favour a medical-somatic model of illness and express less positive therapy expectations. Their whole attitude proves to be dysfunctional concerning compliance with medical treatment. Attitudes of involuntary patients changed during the hospital stay and became similar to those of voluntary patients, which hardly changed. This attitudinal change extended to illness consciousness, insight into illness and therapy expectations, whereas models of illness were found to be very stable. One third of the involuntary patients stayed in hospital voluntarily for further treatment. It is discussed that patients attitudes to illness and therapy should be taken more often into consideration and integrated into the planning of therapy.


Bone marrow cells ameliorate liver fibrosis and express albumin after transplantation in CCl₄-induced fibrotic liver.
We investigated the effect of bone marrow-derived stem cell (BMSC) transplantation on carbon tetrachloride (CCl 4 )-induced liver fibrosis. BMSCs of green fluorescent protein (GFP) mice were transplanted into 4-week CCl 4 -treated C57BL/6 mice directly to the liver, and the mice were treated for 4 more weeks with CCl 4 (total, 8 weeks). After sacrificing the animals, quantitative data of percentage fibrosis area and the number of cells expressing albumin was obtained. One-way analysis of variance was applied to calculate the significance of the data. GFP expressing cells clearly indicated migrated BMSCs with strong expression of albumin after 28 days post-transplantation shown by anti-albumin antibody. Double fluorescent immunohistochemistry showed reduced expression of αSMA on GFP-positive cells. Four weeks after BMSC transplantation, mice had significantly reduced liver fibrosis as compared with that of mice treated with CCl 4 assessed by Sirius red staining. Mice with BMSC transplantation with continuous CCl 4 injection had reduced liver fibrosis and a significantly improved expression of albumin compared with mice treated with CCl 4 alone. These findings strengthen the concept of cellular therapy in liver fibrosis.


Persistent extreme ultraviolet irradiance in Antarctica despite the ozone recovery onset.
Attributable to the Montreal Protocol, the most successful environmental treaty ever, human-made ozone-depleting substances are declining and the stratospheric Antarctic ozone layer is recovering. However, the Antarctic ozone hole continues to occur every year, with the severity of ozone loss strongly modulated by meteorological conditions. In late November and early December 2020, we measured at the northern tip of the Antarctic Peninsula the highest ultraviolet (UV) irradiances recorded in the Antarctic continent in more than two decades. On Dec. 2nd, the noon-time UV index on King George Island peaked at 14.3, very close to the largest UV index ever recorded in the continent. On Dec. 3rd, the erythemal daily dose at the same site was among the highest on Earth, only comparable to those recorded at high altitude sites in the Atacama Desert, near the Tropic of Capricorn. Here we show that, despite the Antarctic ozone recovery observed in early spring, the conditions that favor these extreme surface UV events persist in late spring, when the biologically effective UV radiation is more consequential. These conditions include long-lasting ozone holes (attributable to the polar vortex dynamics) that often bring ozone-depleted air over the Antarctic Peninsula in late spring. The fact that these conditions have been occurring at about the same frequency during the last two decades explains the persistence of extreme surface UV events in Antarctica.


Developmental patterns of change in the influence of safe and risky peer choices on risky decision-making.
Adolescents take more risks when peers monitor their behavior. However, it is largely unknown how different types of peer influence affect adolescent decision-making. In this study, we investigate how information about previous choices of peers differentially influences decision-making in adolescence and young adulthood. Participants (N = 99, age range 12-22) completed an economic choice task in which choice options were systematically varied on levels of risk and ambiguity. On each trial, participants selected between a safer choice (low variability in outcome) and a riskier choice (high variability in outcome). Participants made choices in three conditions: a solo condition in which they made choices with no additional information, a social condition in which they saw choices of supposed peers, and a computer condition in which they saw choices of a computer. Results showed that participants' choices conform to the choices made by the peers, but not a computer. Furthermore, when peers chose the safe option, late adolescents were especially likely to make a safe choice. Conversely, when the peer made a risky choice, late adolescents were least likely to follow choices made by the peer. We did not find evidence for differential influence of social information on decisions depending on their level of risk and ambiguity. These results show that information about previous decisions of peers are a powerful modifier for behavior and that the effect of peers on adolescents' decisions is less ubiquitous and more specific than previously assumed.


Drug-induced nodular regenerative hyperplasia.
Drug-induced nodular regenerative hyperplasia is an uncommon injury with unique pathophysiology, clinical, and diagnostic considerations. This injury is characteristically asymptomatic in its early phases with only mild elevations in transaminases (< 3× upper limit of normal [ULN]). The latency period is typically more than 6 months. Once clinically apparent, it is marked by complications of portal hypertension, including hypersplenism, ascites, and variceal bleeding, with little or no hepatic dysfunction. Hence, it is an important cause of noncirrhotic portal hypertension. The most commonly associated drugs include thiopurines, chemotherapeutic agents, and antiretroviral agents. Diagnosis is aided by the recognition of noncirrhotic portal hypertension, a detailed history of prior drug exposure, and exclusion of the other causes of nodular regenerative hyperplasia. Clinical history, abdominal imaging, and hepatic hemodynamic studies provide important diagnostic clues, but histologic examination remains the diagnostic gold standard. Therapeutic intervention is aimed at earliest discontinuation of the offending agent and of portal hypertension complications. The natural history varies widely, and portal hypertension can progresses despite drug discontinuation.


Genomic profile of roundup treatment of yeast using DNA microarray analysis.
The herbicide Roundup, which contains glyphosate as the active ingredient, was first introduced in 1974 and has enjoyed widespread use in Japan and elsewhere in the world. Roundup-induced reactions occurring in the yeast Saccharomyces cerevisiae may have a predictive value for understanding responses in higher eukaryotes, and we applied yeast DNA microarray analysis for this purpose. Functional characterization of up-regulated open reading frames (ORFs) following Roundup treatment suggests that Roundup affects membrane structures and cellular organelles. Expression profiles induced by treatments with detergents, oils and hydrostatic pressure were similar to those following Roundup treatment based on cluster analysis. Glyphosate alone was not found to inhibit yeast growth at the concentration contained in the Roundup treatment used for microarray analysis. The toxicity of Roundup appeared to be due to detergent in the product.


Microsatellite Instability in Glioblastoma: Is It Really Relevant in Tumor Prognosis?
To evaluate the frequency and prognostic significance of microsatellite instability (MSI) in patients with glioblastoma (GBM), an immunohistochemical analysis of mismatch repair (MMR) proteins was performed. A total of 71 patients with GBM who underwent surgery between 2011 and 2019, were included in the study. MMR protein expression was examined using immunohistochemistical analysis of tumor tissue samples; the association between the MMR status and clinicopathological findings was evaluated. Immunohistochemical analysis revealed expressions of MLH1, MSH2, MSH6, and PMS2 proteins in 67 (94.4%), 65 (91.5%), 67 (94.4%), and 64 (90.1%) patients, respectively. Among the 71 patients, 64 (90.1%) expressing all MMR proteins were considered microsatellite stable (MSS), and 7 (9.9%) patients showing loss of at least one of the MMR proteins were considered to show MSI. Tumor recurrence was noted in 25 (39.1%) patients in the MSS GBM group, and 4 (57.1%) patients in the MSI GBM group (p=0.433). The overall median survival was 30.65 ± 5.1 and 10.71 ± 5.2 months in the MSS GBM and MSI GBM groups, respectively (p=0.059). The results of this study showed no significant relationships between MMR protein expression and recurrence rates or overall survival in patients with GBM.


Perceptual learning in speech.
This study demonstrates that listeners use lexical knowledge in perceptual learning of speech sounds. Dutch listeners first made lexical decisions on Dutch words and nonwords. The final fricative of 20 critical words had been replaced by an ambiguous sound, between [f] and [s]. One group of listeners heard ambiguous [f]-final words (e.g., [WItlo?], from witlof, chicory) and unambiguous [s]-final words (e.g., naaldbos, pine forest). Another group heard the reverse (e.g., ambiguous [na:ldbo?], unambiguous witlof). Listeners who had heard [?] in [f]-final words were subsequently more likely to categorize ambiguous sounds on an [f]-[s] continuum as [f] than those who heard [?] in [s]-final words. Control conditions ruled out alternative explanations based on selective adaptation and contrast. Lexical information can thus be used to train categorization of speech. This use of lexical information differs from the on-line lexical feedback embodied in interactive models of speech perception. In contrast to on-line feedback, lexical feedback for learning is of benefit to spoken word recognition (e.g., in adapting to a newly encountered dialect).


"Should I Say Something?": A Simulation Curriculum on Addressing Lapses in Professionalism to Improve Patient Safety.
Medical students may witness lapses in professionalism but lack tools to effectively address such episodes. Current professionalism curricula lack opportunities to practice communication skills in addressing professionalism lapses. We designed a simulation curriculum to introduce professionalism expectations, provide communication tools using elements of the Agency for Healthcare Research and Quality TeamSTEPPS program, and address observed professionalism lapses involving patient safety in hierarchical patient care teams. Students were surveyed on knowledge, skills, and attitude regarding professionalism before, immediately after, and 6 months after participation. Of 253 students, 70 (28%) completed baseline and immediate postsurveys, and 39 (15%) completed all surveys. In immediate postsurveys, knowledge of communication tools (82% to 94%, p = .003) and empowerment to address residents (19% to 44%, p = .001) and attendings (15% to 39%, p < .001) increased. At 6 months, 96% of students reported witnessing a professionalism lapse. The curriculum was successful in reported gains in knowledge of communication tools and empowerment to address professionalism lapses, but few students reported using the techniques to address witnessed lapses in real life.


Vision Recovery and Connectivity by Fetal Retinal Sheet Transplantation in an Immunodeficient Retinal Degenerate Rat Model.
To characterize a recently developed model, the retinal degenerate immunodeficient S334ter line-3 rat (SD-Foxn1 Tg(S334ter)3Lav) (RD nude rat), and to test whether transplanted rat fetal retinal sheets can elicit lost responses to light. National Institutes of Health nude rats (SD-Foxn1 Tg) with normal retina were compared to RD nude rats with and without transplant for morphology and visual function. Retinal sheets from transgenic rats expressing human placental alkaline phosphatase (hPAP) were transplanted into the subretinal space of RD nude rats between postnatal day (P) 26 and P38. Transplant morphology was examined in vivo using optical coherence tomography (OCT). Visual function was assessed by optokinetic (OKN) testing, electroretinogram (ERG), and superior colliculus (SC) electrophysiology. Cryostat sections were analyzed for various retinal/synaptic markers and for the expression of donor hPAP. Optical coherence tomography scans showed the placement and laminar development of retinal sheet transplants in the subretinal space. Optokinetic testing demonstrated a deficit in visual acuity in RD nude rats that was improved after retinal sheet transplantation. No ERG responses were detected in the RD nude rats with or without transplantation. Superior colliculus responses were absent in age-matched control and sham surgery RD nude rats; however, robust light-evoked responses were observed in a specific location in the SC of transplanted RD nude rats. Responsive regions corresponded to the area of transplant placement in the eye. The quality of visual responses correlated with transplant organization and placement. The data suggest that retinal sheet transplants integrate into the host retina of RD nude rats and recover significant visual function.


In the Era of Direct-Acting Antivirals, Liver Transplant Delisting Due to Clinical Improvement for Hepatitis C Remains Infrequent.
Studies have suggested marked increases in transplant delisting due to clinical improvement for patients with hepatitis C virus (HCV) associated cirrhosis in the era of direct acting antivirals (DAAs). This study provides a 'real world' assessment of waitlist dynamics for HCV transplant candidates in the current era. This was a retrospective cohort study of adults waitlisted for liver transplant (LT) alone between 1/1/2005-12/31/2018 using national US data. The post-DAA era included all listings occurring after 1/1/2013. Temporal trends in waitlisting, patient characteristics and outcomes with decompensated cirrhosis were evaluated. Adjusted competing risks models assessed the interaction of DAA-era and HCV history on (i) waitlist mortality, and (ii) delisting due to clinical improvement. Overall listing rates for HCV patients have decreased in the DAA era and particularly with Model for End-stage Liver Disease score ≥15 and ≥30. Rates of refractory ascites and severe encephalopathy at listing have increased. Delisting due to clinical improvement remains low (6.1% for 2013-2017 versus 5.2% for 2009-2012 versus 4% for 2005-2008; p < .001) and, for many, ascites (46.5%) and encephalopathy (30.5%) persist at delisting. Waitlist recovery is more frequent for HCV patients post-DAA (adjusted SHR 1.78 vs pre-DAA, 95% CI: 1.58-2.02; p < .001), while improvements in waitlist mortality by era are similar to non-HCV candidates (adjusted SHR 0.74 [95% CI: 0.7-0.78; p < .001] and 0.77 [95% CI: 0.74-0.8; p < .001], respectively). Listing rates for decompensated HCV cirrhosis have decreased in the DAA era. Delisting of HCV patients for clinical improvement has increased, but remains infrequent and many continue to experience considerable morbidity.


Disclosures Undisclosed.
The Centers for Medicare & Medicaid Services (CMS) Open Payments public database, resulting from the Physician Payments Sunshine Act of 2010, was designed to increase transparency of physicians' financial relationships with pharmaceutical manufacturers. We compared physician-reported conflict-of-interest (COI) disclosures in journal articles with this database to determine any discrepancies in physician-reported disclosures. COIs reported by authors from 2014 through 2016 were analyzed in 3 journals: Foot & Ankle International (FAI), The Journal of Bone & Joint Surgery (JBJS), and The Journal of Arthroplasty (JOA). Payment information in the CMS Open Payments database was cross-referenced with each author's disclosure statement to determine if a disclosure discrepancy was present. We reviewed 3,465 authorship positions (1,932 unique authors) in 1,770 articles. Within this sample, 7.1% of authorships had a recorded undisclosed COI (disclosure discrepancy), and 13.2% of articles had first and/or last authors with a disclosure discrepancy. Additionally, we saw a great variation in the percentage of authorships with disclosure discrepancies among the journals (JBJS, 2.3%; JOA, 3.6%; and FAI, 23.7%). Discrepancies exist between payment disclosures made by authors and those published in the CMS Open Payments database. Although the percentage of articles with these discrepancies varies widely among the journals that were analyzed in this study, no trend was found when analyzing the number of discrepancies over the 3-year period. COI disclosures are important for the interpretation of study results and need to be accurately reported. However, COI disclosure criteria vary among orthopaedic journals, causing uncertainty regarding which conflicts should be disclosed.


Effects of nonsteroidal anti-inflammatory drugs on osseointegration: a review.
The purpose of this study was to review the effects of nonsteroidal anti-inflammatory drugs on osseointegration and determine whether they cause failures in dental implants and whether patients who use them chronically can receive dental implants safely. A bibliographic electronic search was performed using the Cochrane Library, PubMed, and Medline databases, selecting articles published between January 1982 and December 2012. The search included the following keywords, either alone or combined: "nonsteroidal anti-inflammatory drugs," "dental implants," "bone healing," and "osteoprogenitor cells." The inclusion criteria were the following: randomized, double-blind, placebo-controlled clinical studies, in vivo animal model studies of osseointegration, and in vitro studies of the effects of these agents on osteoprogenitor cells. The literature search revealed 360 references. A total of 31 articles met the inclusion criteria, including 2 clinical trials, 20 animal studies, and 9 osteoprogenitor cell studies. The clinical trials revealed that cyclooxygenase-1 (COX-1) inhibitors did not impair osseointegration. The animal studies showed that any drug that is capable of inhibiting COX-2 may impair the osseointegration process. The in vitro studies showed that COX-2 inhibitors are the most potent depressors of osseointegration at the cellular level. Caution must be taken when selecting COX-2 nonsteroidal anti-inflammatory drugs during the postoperative period.


Multivariable Prediction Model for Biochemical Response to First-Generation Somatostatin Receptor Ligands in Acromegaly.
First-generation somatostatin receptor ligands (fg-SRLs) represent the mainstay of medical therapy for acromegaly, but they provide biochemical control of disease in only a subset of patients. Various pretreatment biomarkers might affect biochemical response to fg-SRLs. To identify clinical predictors of the biochemical response to fg-SRLs monotherapy defined as biochemical response (insulin-like growth factor (IGF)-1 ≤ 1.3 × ULN (upper limit of normal)), partial response (>20% relative IGF-1 reduction without normalization), and nonresponse (≤20% relative IGF-1 reduction), and IGF-1 reduction. Retrospective multicenter study. Eight participating European centers. We performed a meta-analysis of participant data from 2 cohorts (Rotterdam and Liège acromegaly survey, 622 out of 3520 patients). Multivariable regression models were used to identify predictors of biochemical response to fg-SRL monotherapy. Lower IGF-1 concentration at baseline (odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.72-0.95 IGF-1 ULN, P = .0073) and lower bodyweight (OR = 0.99, 95% CI 0.98-0.99 kg, P = .038) were associated with biochemical response. Higher IGF-1 concentration at baseline (OR = 1.40, (1.19-1.65) IGF-1 ULN, P ≤ .0001), the presence of type 2 diabetes (oral medication OR = 2.48, (1.43-4.29), P = .0013; insulin therapy OR = 2.65, (1.02-6.70), P = .045), and higher bodyweight (OR = 1.02, (1.01-1.04) kg, P = .0023) were associated with achieving partial response. Younger patients at diagnosis are more likely to achieve nonresponse (OR = 0.96, (0.94-0.99) year, P = .0070). Baseline IGF-1 and growth hormone concentration at diagnosis were associated with absolute IGF-1 reduction (β = 0.90, standard error (SE) = 0.02, P ≤ .0001 and β = 0.002, SE = 0.001, P = .014, respectively). Baseline IGF-1 concentration was the best predictor of biochemical response to fg-SRL, followed by bodyweight, while younger patients were more likely to achieve nonresponse.


Two-stage removal of giant fibrovascular polyp of the oesophagus.
A patient presented with several months' history of dysphagia, chest pain, symptoms of regurgitation and weight loss. He underwent an upper gastrointestinal endoscopy, which revealed a giant polyp of the oesophagus. After confirming the diagnosis of giant fibrovascular polyp of the oesophagus, the patient underwent a two-stage division of the stalk and retrieval of the polyp. The postoperative period was uneventful and the patient was asymptomatic at the time of discharge. He is being followed up with a plan for surveillance endoscopy in a year.


Effects of ultraviolet light in vascular cells in vitro and in intact atherosclerotic explants: potential role of apoptosis in vascular biology.
Complex cell-to-cell interactions are known to participate during vascular injury and remodeling, resulting in smooth muscle cell proliferation. Mechanical interventions have yielded little benefit in limiting this process and several site-specific genetic therapies are not yet clinically available. The aim of this study was to delineate the effect of very short wavelength ultraviolet (UVC) light therapy on the viability of macrophage and smooth muscle cells. Vascular cells were both treated in vitro and in intact explanted atherosclerotic aortic segments ex vivo with UVC light. Brief exposure to short wavelength UVC light in the absence of photosensitizers elicited a differential temporal and functional response among treated cells. However, dramatic reduction in both cellular viability and proliferative capacity with eventual cell demise was observed in all UVC-treated cells. Flow cytometry and immunohistochemical analyses revealed the presence of extensive DNA fragmentation, suggestive of apoptosis as a predominant pathway of cell death in these cells exposed to UVC light. We hypothesize that selective induction of apoptosis, in contrast to necrosis, with UVC light may represent a beneficial approach to interdict the complex biologic cascade of messengers that participate in the restenotic response to vascular injury.


Sequential and quantitative analysis of a murine model of elastase-induced emphysema.
Emphysema, one of chronic obstructive pulmonary disease (COPD), is characterized as destruction of airway wall and small airway inflammation. To assess the kinetics of disease progression in murine model of elastase-induced emphysema, we used micro-computed tomography (CT) compared with morphological changes. Two week after elastase administration, a significant increase in the volume of low-density areas, recognized as -800--600 Hounsfield units by micro-CT, was observed. Coefficient of correlation between mean linear intercept (Lm) and low-density area examined by CT, was 0.79 (p<0.01). Micro-CT can quantitatively and sequentially detect murine emphysematous changes, offering a practical method to sequentially analyze the therapeutic effects of treatments in a murine model of emphysema.


E-Health Interventions for Adult and Aging Population With Intellectual Disability: A Review.
To answer the question about which e-health and e-therapy applications are being used with people with intellectual disabilities, we searched the PsycINFO, Medline, PubMed, ERIC, CINAHL, Scopus, Web of Science, and Cochrane databases. This is an extensive search. Inclusion criteria were academic journals and any design type that addressed the topic of interest. Studies that do not include adults or elderly, and studies that do not focus on people with disabilities but on third parties, were excluded. After an initial selection of 515 articles, 32 full-text articles were subjected to in-depth analysis leading to the final selection of 18 articles. We used the AAID framework definition of intellectual disability to analyze the dimensions explored by the selected studies and found that the majority of studies focused on the use of technology as supports to instrumental activities of daily life. The ISO classification of assistive products allowed us to identify that many e-health products are aimed at providing psychological or medical treatment. In summary, this review suggests that there is a very small number of studies focusing on the use of technology by older persons with intellectual disabilities. The studies present substantial limitations regarding generalization and replication and pay little attention to the maintenance of cognitive abilities in this population. These aspects, together with premature aging generally associated with many conditions that lead to intellectual disability, underscore the need to pay more attention to and develop e-health interventions for cognitive stimulation for this group.


[Hygienic aspects of cellular communication in school age].
In the article there are presented the materials of research on the spread and usage of mobile phones among children and adolescents of different age groups in the Russian regions, the data of the performed tests of cellular communication devices, as well as the established effects of electromagnetic radiation (EMR) on biological objects. Risk groups of schoolchildren for adverse effect of EMR on health have been determined.


Adeno-associated virus type 2-mediated gene transfer: correlation of tyrosine phosphorylation of the cellular single-stranded D sequence-binding protein with transgene expression in human cells in vitro and murine tissues in vivo.
Although the adeno-associated virus type 2 (AAV)-based vector system has gained attention as a potentially useful alternative to the more commonly used retroviral and adenoviral vectors for human gene therapy, the single-stranded nature of the viral genome, and consequently the rate-limiting second-strand viral DNA synthesis, significantly affect its transduction efficiency. We have identified a cellular tyrosine phosphoprotein, designated the single-stranded D sequence-binding protein (ssD-BP), which interacts specifically with the D sequence at the 3' end of the AAV genome and may prevent viral second-strand DNA synthesis in HeLa cells (K. Y. Qing et al., Proc. Natl. Acad. Sci. USA 94:10879-10884, 1997). In the present studies, we examined whether the phosphorylation state of the ssD-BP correlates with the ability of AAV to transduce various established and primary cells in vitro and murine tissues in vivo. The efficiencies of transduction of established human cells by a recombinant AAV vector containing the beta-galactosidase reporter gene were 293 > KB > HeLa, which did not correlate with the levels of AAV infectivity. However, the amounts of dephosphorylated ssD-BP which interacted with the minus-strand D probe were also as follows: 293 > KB > HeLa. Predominantly the phosphorylated form of the ssD-BP was detected in cells of the K562 line, a human erythroleukemia cell line, and in CD34+ primary human hematopoietic progenitor cells; consequently, the efficiencies of AAV-mediated transgene expression were significantly lower in these cells. Murine Sca-1+ lin- primary hematopoietic stem/progenitor cells contained predominantly the dephosphorylated form of the ssD-BP, and these cells could be efficiently transduced by AAV vectors. Dephosphorylation of the ssD-BP also correlated with expression of the adenovirus E4orf6 protein, known to induce AAV gene expression. A deletion mutation in the E4orf6 gene resulted in a failure to catalyze dephosphorylation of the ssD-BP. Extracts prepared from mouse brain, heart, liver, lung, and skeletal-muscle tissues, all of which are known to be highly permissive for AAV-mediated transgene expression, contained predominantly the dephosphorylated form of the ssD-BP. Thus, the efficiency of transduction by AAV vectors correlates well with the extent of the dephosphorylation state of the ssD-BP in vitro as well as in vivo. These data suggest that further studies on the cellular gene that encodes the ssD-BP may promote the successful use of AAV vectors in human gene therapy.


Common practices in botulinum toxin injection for spasmodic dysphonia treatment: A national survey.
Although no clear guidelines exist, protocols in the treatment of spasmodic dysphonia (SD) vary among physicians. Previously published work comes from relatively few centers. A descriptive survey among experts (laryngologists who practice Botulinum toxin injections for SD). An online 58-item survey was sent to all otolaryngologists who self-identify as laryngologists on the American Academy of Otolaryngology-Head and Neck Surgery website. Items surveyed included botulinum toxin injection technique, laterality, and dosage. An 80% response rate was achieved (70 completed the survey). Participants collectively reported treating >4,000 SD patients in the past year (mean, 71 ± 68 patients/laryngologist). Eighty-seven percent perform injections exclusively in the office; the remainder both in the office and operating room. For adductor SD injections, 88% use electromyographic (EMG) guidance alone via cricothyroid approach. The remainder use anatomical landmarks alone (9%) or EMG with endoscopic guidance (3%). Sitting is the preferred patient position (70%; supine, 30%). A substantial majority (87%) begin with bilateral injections (starting dosage mode, 1.25 units/side). For abductor SD injections, 67% use EMG guidance alone and 31% use endoscopic guidance with or without EMG. Sitting is the preferred patient position (84%; supine, 16%). The preferred approach is anterior-translaryngeal (51%), followed by lateral-retrolaryngeal with rotation (34%). A considerable majority (79%) begin with unilateral injections (starting dosage mode, 5 units). When deciding on initial dosage, the most influential factor was balancing patients' desire/needs, followed by patients' frailty and risk of aspiration. The typical planned interval between injections is 3 to 4 months. Laryngologists follow fairly uniform protocols in the treatment of SD with some important and previously unpublished differences. This study documents areas of agreement and discordance among laryngologists in the United States for the treatment of SD. 4 Laryngoscope, 129:1650-1656, 2019.


The association between cardiovascular health and depression: Results from the 2007-2020 NHANES.
Limited research has been conducted on the correlation between Life's Essential 8 (LE8), the recently updated algorithm for evaluating cardiovascular health (CVH), and depression. A total of 21,942 individuals were chosen from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2020. The depression was determined using the Patient Health Questionnaire (PHQ-9), with a score of 10 or higher indicating diagnosis. The LE8 score consists of 8 metrics: sleep health, diet, physical activity, nicotine exposure, body mass index, blood lipids, blood glucose, and blood pressure. Each LE8 metric was scored from 0 to 100 points. The summation of all metrics divided by 8 generated the total LE8 score and was categorized into low (0-49), moderate (50-79), and high (80-100) CVH. Weighted logistic regression and restricted cubic splines (RCS) were used to assess the association between LE8 score and depression. A significant inversely nonlinear relationship was observed between LE8 score and depression. When compared to participants with high CVH, those with moderate CVH had multivariable adjusted odds ratios (ORs) for depression of 2.36 (95 % CI, 1.79-3.10), while those with low CVH had ORs of 4.71 (95 % CI, 3.44-6.47). Moreover, the effect size of the LE8 score on depression remained stable in all pre-specified subgroups, with all P-values for interaction being more than 0.05. The results indicate a significant inversely nonlinear relationship between LE8 score and depression, particularly among males. These findings emphasize the importance of maintaining higher CVH as a preventive measure against depression.


Genotypic analysis of Tropheryma whipplei from patients with Whipple disease in the Americas.
Tropheryma whipplei, the agent of Whipple disease, causes a rare bacterial disease that may be fatal if not treated. The classical form of the disease includes diarrhoea, weight loss, arthritis, endocarditis and neurological manifestations. Genotyping studies done in Europe, Africa and Asia showed high genetic diversity with no correlation between genotypes and clinical features, but contributed to a better understanding of the epidemiology of the disease. More than 70 genotypes have been described. No similar assessment of T. whipplei in the USA and the Caribbean has been performed. In this study, we describe genetic analysis of DNA from histopathological samples obtained from 30 patients from the Americas with Whipple disease and compare the genotypes with those previously identified. Complete genotypes were obtained from 18 patients (60%). Only 4 genotypes were previously described, and 14 were newly reported, confirming the diversity of T. whipplei strains.


Nonstructural carbohydrate dynamics' relationship to leaf development under varying environments.
Leaf-out in temperate forests is a critical transition point each spring and advancing with global change. The mechanism linking phenological variation to external cues is poorly understood. Nonstructural carbohydrate (NSC) availability may be key. Here, we use branch cuttings from northern red oak (Quercus rubra) and measure NSCs throughout bud development in branch tissue. Given genes and environment influence phenology, we placed branches in an arrayed factorial experiment (three temperatures × two photoperiods, eight genotypes) to examine their impact on variation in leaf-out timing and corresponding NSCs. Despite significant differences in leaf-out timing between treatments, NSC patterns were much more consistent, with all treatments and genotypes displaying similar NSC concentrations across phenophases. Notably, the moderate and hot temperature treatments reached the same NSC concentrations and phenophases at the same growing degree days (GDD), but 20 calendar days apart, while the cold treatment achieved only half the GDD of the other two. Our results suggest that NSCs are coordinated with leaf-out and could act as a molecular clock, signaling to cells the passage of time and triggering leaf development to begin. This link between NSCs and budburst is critical for improving predictions of phenological timing.


An overview of currently available anti-insulin-like growth factor I receptor antibodies.
A number of studies during the last two decades revealed that the insulin-like growth factor I receptor (IGFIR) is an attractive target for cancer molecular therapy. Different molecular strategies have been developed and evaluated in experimental systems, and one such strategy involves anti-IGFIR antibodies, which have been rigorously tested for their therapeutic potential over the last 5-6 years. This mini-review thus introduces currently available IGFIR antibodies with a particular emphasis on epitope mapping and anti-IGFIR antibody-induced cancer growth inhibition.


Tobacco smoke cooperates with interleukin-1beta to alter beta-catenin trafficking in vascular endothelium resulting in increased permeability and induction of cyclooxygenase-2 expression in vitro and in vivo.
Cigarette smoking affects all phases of atherosclerosis from endothelial dysfunction to acute occlusive clinical events. We explored activation by exposure to tobacco smoke of two genes, beta-catenin and COX-2, that play key roles in inflammation and vascular remodeling events. Using both in vivo and in vitro smoke exposure, we determined that tobacco smoke (TS) induced nuclear beta-catenin accumulation and COX-2 expression and activity and moreover interacted with IL-1beta to enhance these effects. Exposure of cardiac endothelial cells to tobacco smoke plus IL-1beta (TS/IL-1beta) enhanced permeability of endothelial monolayers and disrupted membrane VE-cadherin/beta-catenin complexes, decreased beta-catenin phosphorylation, and increased phosphorylation of GSK-3beta, Akt, and EGFR. Transfection of endothelial cells with beta-catenin-directed small interfering RNA (siRNA) suppressed TS/IL-1beta-mediated effects on COX-2 modulation. Inhibitors of EGFR and phosphatidylinositol-3-kinase also abolished both the TS/IL-1beta-mediated modulation of the Akt/GSK-3beta/beta-catenin pathway and enhancement of COX-2 expression. Moreover, increased levels of Akt and GSK-3beta phosphorylation, nuclear beta-catenin accumulation, COX-2 expression, and IL-1beta were observed in cardiovascular tissue of ApoE-/- mice exposed to cigarette smoke daily for 2 wk. Our results suggest a novel mechanism by which cigarette smoking can induce proinflammatory and proatherosclerotic effects in vascular tissue.


Laser-polarization effects on coherent vibronic excitation of molecules with quasi-degenerate electronic states.
The laser-polarization effects on nonadiabatically coupled π-electron rotation (ring current) and molecular vibration have been theoretically analyzed for aromatic molecules with quasi-degenerate excited states irradiated by an ultrashort laser pulse of arbitrary polarization. We first derived general formulations of the coherent electronic wave packet and expectation value of electronic angular momentum within a frozen-nuclei model. The relative quantum phase of the superposed quasi-degenerate states, which determines the oscillating behavior of angular momentum, can be manipulated by the ellipticity and orientation of the incident laser. Nuclear wave packet simulations with a model molecule confirmed the controllability of π-electron rotation, although the angular momentum is gradually reduced by nonadiabatic couplings. The amplitude of molecular vibration depends prominently on the orientation of linear polarization vectors rather than the helicity of circular polarization. The characteristic feature in vibrational amplitudes is attributed to the interference in nonadiabatic transition governed by the relative quantum phase between nuclear wave packets. This offers a new strategy for laser control of molecular vibrations through the wave packet interference in nonadiabatic transition.


A threshold concept for cancer therapy.
Oxygen free radicals have been implicated in many disease processes, including aging and carcinogenesis, and have been associated with a variety of complications resulting from the treatment of cancer. As a result, the treatment of free radical-induced disease with antioxidants or free radical scavengers has become an important therapeutic modality. Ironically, these same oxygen free radicals also play a critical role in anti-cancer therapies. The use of antioxidants such as superoxide dismutase (SOD), in this setting, has been found to decrease the efficacy of anti-tumor therapies, which depend on free radical generation for their action. In addition, increased antioxidant activity can often be utilized by the tumor cell to favor increased growth. Therefore, the appropriate application of oxygen free radicals and antioxidants seems to be critically important in designing proper strategies for both prevention and treatment of malignant disorders. This review will summarize free radical and antioxidant regimens that have been employed to date, examine some of the problems associated with these regimens, introduce the 'threshold concept' explaining the dual effects of oxygen free radicals and antioxidants, and discuss a novel hypothesis regarding therapy that could potentially improve outcome in cancer patients.


[Diagnosis and therapy of patients with adrenocortical insufficiency].
Most symptoms and signs of adrenocortical insufficiency are aspecific. For a definitive diagnosis a stimulation test is often needed. In case of secondary adrenocortical insufficiency glucocorticoid substitution nearly always suffices. Patients with primary adrenocortical insufficiency need substitution not only with glucocorticoids but also with mineralocorticoids. A standard daily dose of 30 mg hydrocortisone as glucocorticoid substitution is too high for many patients, while for some a standard daily dose of 0.1 mg fludrocortisone as mineralocorticoid substitution is too low. Patients with adrenocortical insufficiency need adequate instructions about what to do in case of stress, such as a (febrile) illness or trauma. Duration and severity of the suppression of the pituitary-adrenal axis by the use of pharmacological amounts of glucocorticoids are highly variable. When pharmacological amounts of glucocorticoids (> 7.5 mg prednisone daily) are used for 3 weeks or longer, a clinically relevant suppression of the pituitary-adrenal axis is possible, and this may persist for one year after discontinuing the use of glucocorticoids.


Sox2 modulates reprogramming of gene expression in two-cell mouse embryos.
Sox2 is a key gene that controls transcriptional networks required for pluripotency. The role of Sox2 in the developmental transition of a highly differentiated oocyte to totipotent blastomeres of the early preimplantation embryo, however, is not known. We report that Sox2, which is localized in the nucleus, is first zygotically expressed during the 2-cell stage and that its expression dramatically increases between the morula and blastocyst stages. Injecting a cRNA encoding Sox2 into 1-cell embryos resulted in overexpression of SOX2 by approximately 70% and developmental arrest at the 2-cell stage, whereas injecting cRNAs encoding Pou5f1, Myc (also known as c-Myc), or Klf4 has little effect on the ability of 2-cell embryos to cleave to the 4-cell stage. Global transcription assessed by bromo uridine triphosphate incorporation is reduced by approximately 15%, and transcript profiling revealed that approximately 15% of zygotically expressed genes are dramatically repressed in 2-cell embryos overexpressing SOX2. Furthermore, overexpressing a dominant-negative SOX2 perturbs reprogramming of gene expression in 2-cell embryos, though to a much lesser extent than that observed following overexpression of SOX2, and leads to developmental failure after the 2-cell stage but before the 8-cell stage. Results of these experiments implicate Sox2 as a critical transcriptional regulator in the oocyte-to-embryo transition that entails formation of totipotent blastomeres and indicate that the amount of Sox2 is critical for successful execution of this transition.


[Use of the Grade of Membership method to identify consumption patterns and eating behaviors among adolescents in Rio de Janeiro, Brazil].
To identify food patterns and eating behaviors among adolescents and to describe the prevalence rates, this study applied the Grade of Membership method to data from a survey on health risk factors among adolescent students in Rio de Janeiro, Brazil (N = 1,632). The four profiles generated were: "A" (12.1%) more frequent consumption of all foods labeled as healthy, less frequent consumption of unhealthy foods, and healthy eating behaviors; "B" (45.8%) breakfast and three meals a day as a habit, less frequent consumption of fruits and vegetables and of five markers of unhealthy diet; "C" (22.8%) lack of healthy eating behaviors, less frequent consumption of vegetables, fruit, milk, cold cuts, cookies, and soft drinks; and "D" (19.3%) more frequent consumption of all unhealthy foods and less frequent consumption of fruits and vegetables. The results indicate the need for interventions to promote healthy eating in this age group.


Protease-associated import systems are widespread in Gram-negative bacteria.
Bacteria have evolved sophisticated uptake machineries in order to obtain the nutrients required for growth. Gram-negative plant pathogens of the genus Pectobacterium obtain iron from the protein ferredoxin, which is produced by their plant hosts. This iron-piracy is mediated by the ferredoxin uptake system (Fus), a gene cluster encoding proteins that transport ferredoxin into the bacterial cell and process it proteolytically. In this work we show that gene clusters related to the Fus are widespread in bacterial species. Through structural and biochemical characterisation of the distantly related Fus homologues YddB and PqqL from Escherichia coli, we show that these proteins are analogous to components of the Fus from Pectobacterium. The membrane protein YddB shares common structural features with the outer membrane ferredoxin transporter FusA, including a large extracellular substrate binding site. PqqL is an active protease with an analogous periplasmic localisation and iron-dependent expression to the ferredoxin processing protease FusC. Structural analysis demonstrates that PqqL and FusC share specific features that distinguish them from other members of the M16 protease family. Taken together, these data provide evidence that protease associated import systems analogous to the Fus are widespread in Gram-negative bacteria.


A novel technique for stabilization of high-grade spondylolisthesis with transvertebral fusion without reduction.
Surgical treatment of high-grade spondylolisthesis and spondyloptosis is recommended in symptomatic patients, yet there exists much debate regarding the optimal surgical approach and the need for reduction. Similar to the Bohlman technique in that fixation is achieved across two vertebral endplates, we discuss a novel technique with the advantage of using bilateral threaded pedicle screws of large diameter and length instead of a single fibula allograft. Patients underwent posterior instrumented fusion without spondylolisthesis reduction using a novel technique placing pedicle screws with a transvertebral trajectory through the two end plates involved in the spondylolisthesis. Following screw placement, patients underwent decompression ± discectomy. Screws were connected to adjacent pedicle screws either in the upper adjacent vertebrae (i.e. L5) or the more rostral adjacent vertebrae (i.e. L4) if spinal alignment or instability necessitate including additional levels of fixation. Three patients were reviewed with ages of 67, 62, 58 years, operative times of 377-790 min, estimated blood loss 400-1050 cc, and follow-up times of 478-1082 days. There were no CSF leaks, intragenic neurologic deficits post-operatively, implant failures, revisions, or other systemic events. Two patients achieve radiographic fusion assessed by CT. At the time of final follow up, all patients were satisfied and essentially pain free. This one-stage technique offers the ability to manage local malalignment with a technique that inherently minimizes risk. The minimal complications and favorable outcomes make this technique an effective, efficient and safe procedure. Additional studies will focus on long term outcomes and should include larger patient samples.


Where do spontaneous first impressions of faces come from?
Humans spontaneously attribute a wide range of traits to strangers based solely on their facial features. These first impressions are known to exert striking effects on our choices and behaviours. In this paper, we provide a theoretical account of the origins of these spontaneous trait inferences. We describe a novel framework ('Trait Inference Mapping') in which trait inferences are products of mappings between locations in 'face space' and 'trait space'. These mappings are acquired during ontogeny and allow excitation of face representations to propagate automatically to associated trait representations. This conceptualization provides a framework within which the relative contribution of ontogenetic experience and genetic inheritance can be considered. Contrary to many existing ideas about the origins of trait inferences, we propose only a limited role for innate mechanisms and natural selection. Instead, our model explains inter-observer consistency by appealing to cultural learning and physiological responses that facilitate or 'canalise' particular face-trait mappings. Our TIM framework has both theoretical and substantive implications, and can be extended to trait inferences from non-facial cues to provide a unified account of first impressions.


Delivering preference for place of death in a specialist palliative care setting.
Over the last 10 years, one of the key themes of public policy in palliative care has been achievement of choice in place of death. In Marie Curie Hospice Edinburgh a baseline audit conducted in 2006 showed that only a small proportion (18%) of patients referred to hospice services died at home. The audit also revealed that only 31% of those who expressed a preference to die at home were able to do so, whereas 91% of those who chose a setting other than home achieved their preference. Overall achievement of preferred place of death was 56%. However a significant number of patients (29%) did not have a recorded preference. A programme of quality improvement has continued over the last 7 years to improve identification, communication and achievement of preferred place of death for all patients. The mechanisms to change practice have been: changes to documentation; changes to clinical systems to support use of documentation; support for clinical staff to recognise the value of discussing preferences; and support for clinical staff to develop new skills. In addition the programme has been incorporated into local clinical strategy and this has enabled gaps in service to be addressed with a new service to support early discharge of those patients who wish to die at home. A recent audit showed that all patients had a recorded preference or a documented reason why their preference was unclarified. One third of patients died at home - nearly double the proportion that died at home in the baseline audit. Seventy one per cent of patients who wished to die at home actually died at home - a substantial increase from 31% at baseline. Achievement of preferred place of death for patients wishing to die in the hospice remained high at 88%. The focus on assessment of preference for place of death has led to substantial improvements in the identification and achievement of preference for patients dying under the care of the hospice. Furthermore, it has been associated with an increase in the overall proportion of patients who die at home.


Novel isoforms of the sodium channels Nav1.8 and Nav1.5 are produced by a conserved mechanism in mouse and rat.
The voltage-gated sodium channel Na(v)1.8 is only expressed in subsets of neurons in dorsal root ganglia (DRG) and trigeminal and nodose ganglia. We have isolated mouse partial length Na(v)1.8 cDNA clones spanning the exon 17 sequence, which have 17 nucleotide substitutions and 12 predicted amino acid differences from the published sequence. The absence of a mutually exclusive alternative exon 17 was confirmed by sequencing 4.1 kilobases of genomic DNA spanning exons 16-18 of Scn10a. A novel cDNA isoform was identified, designated Na(v)1.8c, which results from alternative 3'-splice site selection at a CAG/CAG motif to exclude the codon for glutamine 1031 within the interdomain cytoplasmic loop IDII/III. The ratio of Na(v)1.8c (CAG-skipped) to Na(v)1.8 (CAG-inclusive) mRNA in mouse is approximately 2:1 in adult DRG, trigeminal ganglion, and neonatal DRG. A Na(v)1.8c isoform also occurs in rat DRG, but is less common. Of the two other tetrodotoxin-resistant channels, no analogous alternative splicing of mouse Na(v)1.9 was detected, whereas rare alternative splicing of Na(v)1.5 at a CAG/CAG motif resulted in the introduction of a CAG trinucleotide. This isoform, designated Na(v)1.5c, is conserved in rat and encodes an additional glutamine residue that disrupts a putative CK2 phosphorylation site. In summary, novel isoforms of Na(v)1.8 and Na(v)1.5 are each generated by alternative splicing at CAG/CAG motifs, which result in the absence or presence of predicted glutamine residues within the interdomain cytoplasmic loop IDII/III. Mutations of sodium channels within this cytoplasmic loop have previously been demonstrated to alter electrophysiological properties and cause cardiac arrhythmias and epilepsy.


Comparison of platelet transfusion as fresh whole blood versus apheresis platelets for massively transfused combat trauma patients (CME).
At major combat hospitals, the military is able to provide blood products to include apheresis platelets (aPLT), but also has extensive experience using fresh whole blood (FWB). In massively transfused trauma patients, we compared outcomes of patients receiving FWB to those receiving aPLT. This study was a retrospective review of casualties at the military hospital in Baghdad, Iraq, between January 2004 and December 2006. Patients requiring massive transfusion (≥10 units in 24 hr) were divided into two groups: those receiving FWB (n = 85) or aPLT (n = 284) during their resuscitation. Admission characteristics, resuscitation, and survival were compared between groups. Multivariate regression analyses were performed comparing survival of patients at 24 hours and at 30 days. Secondary outcomes including adverse events and causes of death were analyzed. Unadjusted survival between groups receiving aPLT and FWB was similar at 24 hours (84% vs. 81%, respectively; p = 0.52) and at 30 days (60% versus 57%, respectively; p = 0.72). Multivariate regression failed to identify differences in survival between patients receiving PLT transfusions either as FWB or as aPLT at 24 hours or at 30 days. Survival for massively transfused trauma patients receiving FWB appears to be similar to patients resuscitated with aPLT. Prospective trials will be necessary before consideration of FWB in the routine management of civilian trauma. However, in austere environments where standard blood products are unavailable, FWB is a feasible alternative.


Mechanisms of adaptation to proteinuria in adriamycin nephrosis.
To evaluate the impact of urinary protein losses on whole body protein turnover (WBPT) independent of acidosis or uremia, we utilized a model of unilateral adriamycin nephrosis. Control rats were matched by weight to nephrotic rats and pair fed 22% protein chow for 14-18 days; urinary urea nitrogen (UUN) was measured on day 12, and leucine turnover measurement was performed on the final day. Growth rates of nephrotic and pair-fed control rats did not differ during the first 2 wk of pair feeding; thereafter, a small difference in growth could be detected. Despite an identical intake of dietary protein, UUN excretion was 29% less in the nephrotic rats (P < or = 0.02). Fasting whole body protein synthesis and degradation did not differ between nephrotic and control rats; in contrast, leucine oxidation decreased by 21% in nephrosis (P < 0.05). On the basis of near normal growth and normal rates of WBPT, we conclude that nephrotic rats fed ad libitum can adapt to the stress of continuous protein losses. A reduction in amino acid oxidation and UUN excretion were the primary mechanisms responsible for protein conservation in experimental nephrosis.


Diagnosis of occult fractures and dislocations.
The principles to be followed in the identification of occult injuries include: a good history and physical examination to arouse a high index of suspicion; high quality radiographs; radiographs of the whole bone and associated joints above and below, particularly in the lower cervical spine and hip; special views to delineate fractures, particularly oblique films, tangenital and axial views and stress films. Tomograms may also be helpful; follow-up and re-check films, especially with fractures and epiphyseal injuries. With early identification of fractures that are commonly missed, these injuries eventually cease to be occult and appropriate management can be instituted.


Statistical Considerations in the Design of Biosimilar Cancer Clinical Trials.
When the patent of an innovative (brand-name) small-molecule drug expires, generic copies of the innovative drug may be marketed if their therapeutic equivalence to the innovative drug has been shown. The small-molecule drugs are considered therapeutically equivalent and can be used interchangeably if two drugs are shown to be pharmaceutically equivalent with identical active substance and bioequivalent with comparable pharmacokinetics in a crossover clinical trial. However, the therapeutic equivalence paradigm cannot be applied to biosimilars since the active ingredients of biosimilars are huge molecules with complex and heterogeneous structures, and these molecules are difficult to replicate in every detail. The European Medicine Agency (EMEA) has introduced a regulatory biosimilar pathway which mandates clinical trials to show therapeutic equivalence. In this paper, we discuss statistical considerations in the design and analysis of biosimilar cancer clinical trials.


[Effect of the natriuretic hormone on ion transport through erythrocyte membrane].
A study of the mechanism of the natriuretic hormone action on ion transport across cellular membranes was carried out in normal donor blood erythrocytes and their shadows. The natriuretic hormone obtained from canine arterial blood changed sodium and potassium ion transport, when acting on external membrane surface. Its effect can be compared to that of strophanthin which produces a similar change in sodium and potassium transport and is only active on the outer side of closed erythrocyte shadows.


Arc Interacts with the Integral Endoplasmic Reticulum Protein, Calnexin.
Activity-regulated cytoskeleton-associated protein, Arc, is a major regulator of long-term synaptic plasticity and memory formation. Here we reveal a novel interaction partner of Arc, a resident endoplasmic reticulum transmembrane protein, calnexin. We show an interaction between recombinantly-expressed GST-tagged Arc and endogenous calnexin in HEK293, SH-SY5Y neuroblastoma and PC12 cells. The interaction was dependent on the central linker region of the Arc protein that is also required for endocytosis of AMPA-type glutamate receptors. High-resolution proximity-ligation assays (PLAs) demonstrate molecular proximity of endogenous Arc with the cytosolic C-terminus, but not the lumenal N-terminus of calnexin. In hippocampal neuronal cultures treated with brain-derived neurotrophic factor (BDNF), Arc interacted with calnexin in the perinuclear cytoplasm and dendritic shaft. Arc also interacted with C-terminal calnexin in the adult rat dentate gyrus (DG). After induction of long-term potentiation (LTP) in the perforant path projection to the DG of adult anesthetized rats, enhanced interaction between Arc and calnexin was obtained in the dentate granule cell layer (GCL). Although Arc and calnexin are both implicated in the regulation of receptor endocytosis, no modulation of endocytosis was detected in transferrin uptake assays. Previous work showed that Arc interacts with multiple protein partners to regulate synaptic transmission and nuclear signaling. The identification of calnexin as a binding partner further supports the role of Arc as a hub protein and extends the range of Arc function to the endoplasmic reticulum, though the function of the Arc/calnexin interaction remains to be defined.


Proposal for international guidelines for reproductive and developmental toxicity testing for pharmaceuticals.
1. A Workshop was organized by the Centre for Medicines Research in London, 13th-15th May 1991 to discuss the current situation concerning tests for reproductive and developmental toxicity required for new drug development, and whether a unified series of guidelines could be developed which would satisfy Regulatory Authorities and Scientists worldwide. 2. The international group of experts invited to participate in this meeting reached a consensus regarding the desirability of developing new and flexible guidelines. An approach was proposed based on the state of the art of scientific knowledge in the field of reproductive and developmental toxicology coupled with the minimum use of experimental animals, and taking into consideration the European proposal for a new guideline which has been open for discussion since 1989. 3. Although time did not permit detailed discussion of all study designs, several which are considered to provide acceptable tests for reproductive and developmental toxicity of new therapeutic candidates have been proposed for further discussion. These include the possibility of considerable reduction in duration and size of studies, and numbers of animals used where there is an indication that a low hazard potential exists. 4. Whichever of the combinations are ultimately used in the premarketing assessment, it is most important that the investigators justify in detail the rationale underlying the choice of studies undertaken. This should take into account the specific properties of the drug molecule and its proposed clinical use. 5. This paper reflects the discussions which took place at the Workshop and its publication has been agreed to by the participants. It is intended that it could be used as the basis for discussions of a harmonized approach to reproductive and developmental toxicity testing of pharmaceuticals. As such, it will be made available to regulatory agencies, trade associations and other appropriate groups for their consideration and acceptance, modification or scientific augmentation.


Propranolol inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats.
Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for β-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (0.5 g/L propranolol given in the drinking water) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.


Phospholipophilicity of CxHyN(+) amines: chromatographic descriptors and molecular simulations for understanding partitioning into membranes.
Using immobilized artificial membrane high-performance liquid chromatography (IAM-HPLC) the sorption affinity of 70 charged amine structures to phospholipids was determined. The amines contained only 1 charged moiety and no other polar groups, the rest of the molecule being aliphatic and/or aromatic hydrocarbon groups. We systematically evaluated the influence of the amine type (1°, 2°, 3° amines and quaternary ammonium), alkyl chain branching, phenyl ring positioning, charge positioning (terminal vs. central in the molecule) on the phospholipid-water partitioning coefficient (KPLIPW). These experimental results were compared with quantum-chemistry based three-dimensional (3D) molecular simulations of the partitioning of charged amines, including the most likely solute conformers, using a hydrated phospholipid bilayer in the COSMOmic module of COSMOtherm software. Both IAM-HPLC retention data and the simulations suggest that the molecular orientation of charged amines at the location in the bilayer with the lowest calculated Gibbs free energy exerts a strong influence over the partitioning within the membrane. The most favourable position of charged amines coincides with the region where the phosphate anions in the phospholipid bilayer are most abundant. Hydrocarbon units oriented in this layer are located more towards the aqueous phase and contribute less to the overall membrane affinity than hydrocarbon units extending into the more hydrophobic core of the bilayer. COSMOmic simulations explain most of the trends between the structural differences observed in IAM-HPLC based KPLIPW. For this set of cationic structures, the mean absolute difference between COSMOmic simulations and IAM-HPLC data, accounting only for amine type corrective increments, is 0.31 log units.


Validation and reliability of the Turkish Utian Quality-of-Life Scale in postmenopausal women.
There are a limited number of menopause-specific quality-of-life scales for the Turkish population. This study was conducted to evaluate the validity and reliability of the Turkish Utian Quality-of-Life Scale in postmenopausal women. The study group was comprised of 250 postmenopausal women who applied to a training and research hospital's menopause clinic in Turkey. A survey form and the Turkish Utian quality-of-Life Scale were used to collect data, and the Turkish version of Short Form-36 was used to evaluate reliability with an equivalent form. Language-validity, content-validity, and construct-validity methods were used to assess the validity of the scale, and Cronbach's α coefficient calculation and the equivalent-form reliability methods were used to assess the reliability of the scale. The Turkish Utian Quality-of-Life Scale was determined to be a valid and reliable instrument for measuring the quality of life of postmenopausal women. Confirmatory factor analysis demonstrates that the instrument fits well with 23 items and a four-factor model. The Cronbach's α coefficient for the quality-of-life domains were as follows: 0.88 overall, 0.79 health, 0.78 emotional, 0.76 sexual, and 0.75 occupational. Reliability of the instrument was confirmed through significant correlations between scores on the Turkish version of the Utian Quality-of-Life Scale and the Turkish version of the Short Form-36 (r = 0.745, P < 0.001). This research emphasizes that the Turkish Utian Quality-of-Life Scale is reliable and valid in postmenopausal women-it is a useful instrument for measuring quality of life during menopause.


Overview on desonide 0.05%: a clinical safety profile.
Desonide (as a cream, ointment, or lotion formulation) is widely used for the treatment of steroid-responsive dermatoses. This paper provides information on its safety record, as determined from adverse event reports and published trial results. A pharmacovigilance program, initiated in 1992 for all countries where desonide is available, collected reports of adverse events associated with topical desonide over nine years. Published accounts of randomized, controlled trials of desonide in comparison with hydrocortisone were reviewed. Sixty-two reports have been collected; most were from consumers and were not medically substantiated. There were no serious reactions directly attributable to desonide treatment and the majority of events reported were classified as expected local reactions, generally mild in nature. This level of reporting is against a background of extensive prescribing of desonide; almost one million packs are dispensed per annum in the US alone. The excellent safety profile of desonide revealed by this pharmacovigilance program is supported by a review of published clinical trial results.


Lack of Prenylated Proteins, Autophagy Impairment and Apoptosis in SH-SY5Y Neuronal Cell Model of Mevalonate Kinase Deficiency.
Mevalonate Kinase Deficiency (MKD), is a hereditary disease due to mutations in mevalonate kinase gene (MVK). MKD has heterogeneous clinical phenotypes: the correlation between MVK mutations and MKD clinical phenotype is still to be fully elucidated. Deficiency of prenylated proteins has been hypothesized as possible MKD pathogenic mechanism. Based on this hypothesis and considering that neurologic impairment characterizes Mevalonic Aciduria (MA), the most severe form of MKD, we studied the effects of I268T and N301T MVK mutations on protein prenylation, autophagy and programmed cell death in SH-SY5Y neuroblastoma cell lines. SH-SY5Y cells were transiently transfected, with the pCMV-6 plasmid containing MVK wild type and the two mutated sequences. Protein prenylation levels were evaluated using GFP-RhoA-F to assess farnesylation, and GFP-RhoA to evaluate geranylgeranylation; autophagy was measured by evaluating LC3 and p62 protein levels, while Annexin V-FITC and Propidium Iodide staining allowed apoptosis detection. MVK mutants' over-expression causes decreased levels of farnesylation and geranylgeranylation, and also increased LC3 lipidation in SH-SY5Y, with concomitant p62 accumulation. Treatment with bafilomycin A1 (an inhibitor of vacuolar H+-ATPase, a late autophagy inhibitor) further increase LC3-II and p62 levels, suggesting that degradation of autophagolysosome could be impaired. SH-SY5Y, with both MVK mutants, showed apoptosis increase; the presence of N301T associated with augmented cell death. We hypothesize that mevalonate pathway impairment causes alteration of farnesylation and geranylgeranylation proteins and alteration of the autophagic flux; these changes can induce apoptosis, possibly more relevant in the presence of N301T mutation.


Intracoronary thermography.
Arteriosclerosis is an inflammatory disease. Inflammatory processes play a role in the initiation of plaque development and the early stages of the disease as well as in complex plaques and complications such as intraarterial thrombosis. A method to detect inflammation in coronary arteries has the potential to characterize both local and systemic activation of arteriosclerotic plaque disease. It could help to define in more detail what constitutes a vulnerable plaque or vulnerable vessel and thus improve the prediction of acute coronary syndromes. Intracoronary thermography records a cardinal sign of inflammation. Heat is probably produced by (activated) macrophages. Experimental work has suggested that thermal heterogeneity is present in arteriosclerotic plaques and that increased temperature is found at the site of inflammatory cellular-macrophage-infiltration. Preliminary experience in patients undergoing coronary angiography has demonstrated that it is safe and feasible to perform intracoronary thermography using various systems. A graded relationship between thermal heterogeneity and clinical symptoms has been reported, with the greatest temperature elevation in acute myocardial infarction. Increases in thermal heterogeneity appeared to be associated with a comparably unfavorable long-term prognosis. Intracoronary thermography has the potential to provide insights into location and extent of inflammation as well as the prognostic consequences. Currently, this novel method and the underlying concepts are extensively evaluated.


Dopamine content and metabolism in mesencephalic and diencephalic cell cultures: sex differences and effects of sex steroids.
Sexual differentiation of dopaminergic neurons was studied in gender-specific cultures. Dissociated cell cultures were prepared from di- or mesencephalon of gestational day 14 rat embryos and raised in the absence or presence of 17 beta-estradiol or testosterone for up to 13 days in vitro (DIV). Developmental profiles of levels of dopamine (DA) and metabolites as well as capacity for vesicular storage of the transmitter were determined by HPLC. Tyrosine hydroxylase-immunoreactive (TH-IR) neurons were counted. Higher levels of DA were measured in female than in male cultures of both brain regions. In mesencephalic cultures, the differences in DA levels were fully accounted for by sex differences in numbers of TH-IR cells, whereas no sex differences in cell numbers were found in diencephalic cultures. Dihydroxyphenylacetic acid (DOPAC) levels and vesicular storage capacity matured faster in mesencephalic than in diencephalic cultures, but no sex differences were observed. Homovanillic acid (HVA) could not be detected except in 13-DIV mesencephalic cultures. Hormonal treatment did not erase sexual differentiation of dopaminergic neurons. Irrespective of the gender, however, both steroids decreased DA and DOPAC contents in diencephalic cultures but not in mesencephalic cultures. It is proposed that sexual differentiation of dopaminergic systems proceeds in a region-specific fashion and that neurogenesis and development of various parameters of dopaminergic activity may be differentially affected. Sexual differentiation of dopaminergic neurons may be initiated independently of the action of gonadal steroid hormones and may subsequently be modified by differences in hormonal environment.


HIV counseling, testing, and prevention in primary care.
Human immunodeficiency virus (HIV) continues to be the second leading cause of death for persons ages 25 to 44 years in the United States, whereas new HIV infection rates remain steady. Coupled with the advent of new antiviral therapies that have significantly decreased mortality and morbidity rates, the importance of the primary care clinician in HIV prevention, early detection, and treatment is paramount. This article presents HIV risk analysis and prevention strategies for the primary care clinician practice. New HIV testing methods are reviewed as well as the Centers for Disease Control (CDC) pretest and posttest counseling guidelines.


Structure and Control of Healthy Worker Effects in Studies of Pregnancy Outcomes.
Much of the literature on the healthy worker effect focuses on studies of chronic disease and mortality; however, when studying pregnancy outcomes, these effects might differ because of the short, defined risk periods of most pregnancy outcomes. Three pregnancy-specific healthy worker effects have also been described, but the structure of these effects has not yet been investigated when occupational exposure, and not employment status, is the exposure of interest. We used directed acyclic graphs to examine healthy worker effects in studies of occupational exposures and pregnancy outcomes: the healthy hire effect, the healthy worker survivor effect, the desperation/privilege effect (differential workforce reentry after pregnancy), the reproductively unhealthy worker effect (women with live births leave the workforce, while women with nonlive births do not), and the insecure pregnancy effect (women with adverse pregnancy outcomes reduce their exposures in subsequent pregnancies). Given our assumptions, we conclude that the healthy hire effect, the desperation/privilege effect, the reproductively unhealthy worker effect, and the insecure pregnancy effect result from confounding that can be addressed if data on measured confounders, such as employment status, are available. The presence of the healthy worker survivor effect, however, varies by study design. Different types of healthy worker effects can be present in studies of occupational exposure and pregnancy outcomes, and many of them are easily addressed analytically.


Chapter 2: Nasal obstruction.
Nasal obstruction is one of the most common presenting symptoms requiring medical attention at both the primary care physician and the otorhinolaryngologists' level. Nasal obstruction may be caused by anatomic, physiological, or neurologic factors. Complexity is added to this situation because, often, the causation may be multifactorial. Nasal obstruction is the primary symptom of persistent allergic rhinitis (AR) and affects up to 40% of the population. AR must be treated throughout the year; thus, treatment choices and patient compliance must be considered. It is interesting to note that AR directly affects an individual's quality of life, quality of sleep, and workplace efficiency. Therefore, the magnitude of costs to both the individual and the society must be recognized. Various medical therapies and surgical techniques will be described for the treatment of nasal obstruction.


The composition of triglycerides from liver, egg yolk and adipose tissue of the laying hen.
The composition of the triglycerides of liver, egg yolk and adipose tissue of laying hens fed on a standard diet were investigated by using argentation thin-layer chromatography to separate the triglycerides according to their degree of unsaturation. About 40% of liver triglycerides consisted of one saturated and two monoenoic fatty acids. Triglycerides containing linoleate were more abundant in adipose tissue than in either yolk or liver. Hydrolysis by pancreatic lipase of the tissue triglycerides and fractions obtained from these triglycerides showed that the triglycerides of adipose tissue had a less ordered arrangement of fatty acids at the 2-position than did either yolk or liver triglycerides. The labelling patterns of triglycerides formed in liver slices incubated in the presence of [1-(3)(14)C]glycerol indicated that triglycerides containing four or more double bonds are formed to a greater extent than are other triglyceride fractions. This is evidence for the concept that the type of triglyceride formed depends on the availability of fatty acids to the liver cells.


Effect of tunicamycin on the biogenesis of hepatitis C virus glycoproteins.
Hepatitis C virus (HCV) infects humans, with a prevalence around 3% of population, causing acute and chronic hepatitis and hepatocellular carcinoma. We studied the effect of inhibition of glycosylation on the assembly of the HCV particle. HCV possesses two envelope glycoproteins E1 and E2 that are highly modified by N-glycans. These glycan residues are crucial for viral entry and maturation of the progeny. Here, we examined the influence of inhibition of N-glycosylation on expression of E1 and E2. Since the propagation of HCV in cell culture is limited, we used a recombinant baculovirus producing viral-like particles in insect cells. Our data showed that blocking of N-glycan transfer to the nascent polypeptide chain with the antibiotic tunicamycin resulted in the loss of E1 and E2. We also found that a dose of tunicamycin that did not influence the cell viability significantly reduced the E2 level in infected cells. The results indicate that blocking of glycosylation at an early step efficiently reduces the assembly of HCV virions. Thus, we suggest that derivatives of tunicamycin that preferentially block glycosylation of viral proteins may become potential therapeutic agents against HCV.


Health-related quality of life of Korean older adults according to age, sex, and living arrangements: a cross-sectional study.
The number and proportion of older adults living alone is a significant issue. While the number of the oldest old people is also expected to increase, their health characteristics are poorly understood. This study aims to evaluate the health-related quality of life (HRQoL) of the oldest old people according to age, sex, and living arrangements. This study is based on the Korea Community Health Survey 2021. Among the survey's 229,242 observations, 73,617 observations aged 65 or higher were used for the analysis. The study participants were divided into 5-year age intervals (from 65-69 to 90+), sex, and living arrangements. The outcome variables are the EuroQol 5 Dimensions (EQ-5D) index score and the problem reporting rates of the five dimensions of EQ-5D. The mean EQ-5D index scores were 0.896 at 65-69 and 0.741 at 90+. The mean EQ-5D index score decreased more rapidly as age increased. Women showed consistently lower mean EQ-5D index scores than men in all age intervals. The proportion of older adults living alone increased from 18.1% at 65-69 to 43.6% at 90+. The odds of reporting problems with anxiety/depression among older men living alone were estimated to be significantly higher than older men living with someone (aOR 1.22 95% CI 1.05-1.43). The odds of reporting problems in self-care and usual activity among older women living alone were estimated to be significantly lower than older women living with someone (aOR 0.88 95% CI 0.70-0.83 and aOR 0.88 95% CI 0.82-0.94). This study showed that older adults' HRQoL deteriorates as their age increases. Moreover, living alone may lead to different effects on older adults' HRQoL according to sex. More comprehensive studies and collaborative attention are needed to identify and provide customized care for older adults.


Coupling desalination and energy storage with redox flow electrodes.
Both freshwater shortage and energy crisis are global issues. Herein, we present a double-function system of faradaic desalination and a redox flow battery consisting of VCl3|NaI redox flow electrodes and a feed stream. The system has a nominal cell potential (E0 = +0.79 V). During the discharge process, the salt ions in the feed are extracted by the redox reaction of the flow electrodes, which is indicated by salt removal. Stable and reversible salt removal capacity and electricity can be achieved up to 30 cycles. The energy consumption is as low as 10.27 kJ mol-1 salt. The energy efficiency is as high as 50% in the current aqueous redox flow battery. With energy recovery, the desalination energy consumption decreases greatly to 5.38 kJ mol-1; this is the lowest reported value to date. This "redox flow battery desalination generator" can be operated in a voltage range of 0.3-1.1 V. Our research provides a novel method for obtaining energy-saving desalination and redox flow batteries.


Anterior cingulate cortex and the Stroop task: neuropsychological evidence for topographic specificity.
Neuroimaging studies have implicated the anterior cingulate cortex (ACC) in many aspects of attention and cognition. Major theories of ACC function have proposed a role in conflict monitoring, executive control, response selection, and general arousal. Although the ACC is often treated as a unitary structure, extensive evidence suggests it exhibits anatomical and functional specificity. ACC activity during the Stroop color word interference task has been of particular interest. The purpose of the present study was to determine whether two different ACC subregions are necessary for intact color naming performance in the Stroop task. One experiment utilized blocked trial and mixed trial designs to emulate neuroimaging studies and to compare interference and facilitation effects, respectively. A third variant manipulated the probabilities of congruent and incongruent trials to alter levels of interference and cognitive control, or engagement of strategic processes, on a block by block basis. Two patients with focal lesions in either right mid-caudal (patient D.L.) or left rostral to mid-dorsal ACC (patient R.N.) exhibited distinctive performance profiles in these three versions of the Stroop task, providing further support for topographic specificity of function within the human ACC. Contrary to predictions from some neuroimaging experiments, damage to right mid-caudal ACC was associated with normal levels of interference and accurate performance on incongruent trials. Instead, D.L. showed reduced levels of facilitation relative to controls. Further, interference was not modulated by the probability manipulation in D.L., suggesting equivalently high levels of cognitive control in both conditions. Conversely, damage to left mid-dorsal ACC resulted in consistently lower accuracy on incongruent trials, indicating deficits in maintaining task set and inhibiting the automatic response. These results can help to constrain interpretations of ACC activations in functional imaging experiments of the Stroop task.