Diabetes distress instruments in adults with Type 1 diabetes: A systematic review using the COSMIN (COnsensus-based Standards for the selection of health status Measurement INstruments) checklist.
To identify all extant instruments used to measure diabetes distress in adults with Type 1 diabetes and to evaluate the evidence for the measurement properties of these instruments. Medline, Embase, CINAHL plus and PsycINFO were systematically searched from inception up until 12 March 2020 for all publications which evaluated the psychometric properties of diabetes distress measurement instruments. The quality of the methodology and the measurement properties in the identified studies were evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines. Seven out of the 7656 articles retrieved in the search were included in the final review. Four diabetes distress measurement instruments were identified, none of which displayed evidence for all measurement properties specified in the COSMIN guidelines. The Problem Areas in Diabetes-11 (PAID-11) demonstrated the best psychometric properties, displaying strong evidence for structural validity, internal consistency, hypothesis testing, responsiveness and criterion validity. The Problem Areas in Diabetes scale (PAID) was the most frequently investigated instrument, demonstrating good relevance and hypothesis testing across four studies; however, concerns remain over its factor structure. The PAID-11 appears to be the most psychometrically sound instrument for measuring diabetes distress in adults with Type 1 diabetes, displaying strong evidence for a range of measurement properties. However, as only one study evaluated this instrument and its content validity has yet to be assessed, further validation is warranted. Additional qualitative work is needed to assess the content validity of these instruments among individuals with Type 1 diabetes.


Pembrolizumab versus chemotherapy in recurrent, advanced urothelial cancer in Japanese patients: a subgroup analysis of the phase 3 KEYNOTE-045 trial.
The open-label, randomized, active-controlled KEYNOTE-045 study (NCT02256436) showed that second-line pembrolizumab significantly improved overall survival (OS) of patients with advanced/metastatic urothelial cancer (UC) that progressed after first-line platinum-containing chemotherapy, compared with standard chemotherapy (paclitaxel, docetaxel, or vinflunine). Pembrolizumab is approved for patients with bladder cancer in Japan. Analysis was performed in the subgroup of Japanese patients enrolled in the KEYNOTE-045 study. Coprimary end points were OS and progression-free survival (PFS). Objective response rate (ORR) and safety were secondary end points. Fifty-two Japanese patients (pembrolizumab, n = 30; chemotherapy, n = 22) were followed up for a median of 26.1 months. Patients who received pembrolizumab compared with chemotherapy had a 19% lower risk for death (hazard ratio [HR] 0.81, 95% CI 0.44-1.50); after adjusting for baseline covariates, the HR for OS was 0.61 (95% CI 0.32-1.15). The 24-month OS rate was higher with pembrolizumab (26.9% vs 14.3%). PFS was 2.0 and 4.9 months for pembrolizumab and chemotherapy, respectively (HR 1.71, 95% CI 0.95-3.08). ORR was similar for pembrolizumab and chemotherapy (20.0% vs 18.2%); durability of response was higher with pembrolizumab: 67% and 33% of patients, respectively, maintained a response for > 12 months. Treatment-related adverse events, including grade 3-5 events, occurred less frequently with pembrolizumab. Pembrolizumab provided durable antitumor activity in patients with locally advanced/metastatic UC that progressed after platinum-containing chemotherapy in the overall population and in the Japanese subgroup; safety profile was consistent with that previously observed for pembrolizumab.


Life history variation in the black swallowtail butterfly.
The growth, development, and reproduction of black swallowtail butterflies (Papilio polyxenes) from Turrialba, Costa Rica and Brooktondale, New York are compared. When New York larvae are reared under a short photoperiod, they produce pupae that diapause and are smaller than those produced under long photoperiods. As a consequence, reproduction in the field is limited to two broods per summer and the adults of Brood I are smaller. Costa Rican larvae exhibit no response to photoperiod and breeding occurs throughout the year. Dispersal of adults in Costa Rica is thought to serve a function analogous to that of diapause in New York: to bridge temporal or spatial gaps between favorable habitats. Under favorable conditions, females from both locations grow rapidly, lay several hundred eggs soon after adult eclosion, and are short-lived, as expected for a colonizing species. However, differences occur in three specific life history traits: adult females from Brood I in New York are similar in size to Costa Rican females, but lay fewer eggs and at a slower rate; adult females from Brood II in New York are larger than Costa Rican females, but have a similar rate of egg production and total fecundity; the eggs of New York females are larger than those of Costa Rican females. It is unclear whether or not these differences reflect divergent adaptation of the life history to different environments. An adaptive hypothesis that emphasizes selection for early age at first reproduction in Costa Rica and for high fecundity in New York, and predicts disrupted latitudinal clines in size, is proposed to account in part for the observations reported here.


Yohimbine hydrochloride reversal of ketamine hydrochloride and xylazine hydrochloride immobilization of Bengal tigers and effects on hematology and serum chemistries.
Six bengal tigers (Panthera tigris tigris) were immobilized five times at 2-wk intervals with ketamine hydrochloride (ketamine) and xylazine hydrochloride (xylazine) mixtures at different dose levels. Hematology and serum chemistry analyses on blood samples collected at each immobilization remained normal during the study. There were acute changes in hematocrit, chloride, potassium, glucose, and bilirubin as a function of xylazine dose level. The effect of yohimbine hydrochloride (yohimbine) on the depth and duration of immobilization was evaluated in a crossover design with every animal serving as its own control at each dose. Administration of yohimbine resulted in recovery of the animals within 4-8 min in contrast to greater than 60 min with no yohimbine treatment. There were no adverse effects noted with the yohimbine treatment and the tigers did not exhibit a relapse over the next 24 hr. Yohimbine at a dose of 5-15 mg per adult tiger provided effective reversal of 50-150 mg of xylazine per tiger.


Compliance status of product labels to the international code on marketing of breast milk substitutes.
The aim of this study was to determine the compliance status of product labels regarding Article 9 of the International Code on Marketing of Breast-milk Substitutes (the Code) in Denizli province, Turkey. A cross-sectional study design was employed to determine the compliance status. The product labels were obtained from a convenience sample of five supermarkets, one store and 5 pharmacies in the City centre and district of Honaz. Using a data collection form prepared by previously published studies, data were collected between July 26, 2010 and August 06, 2010. Data collection form included 13 criteria. In addition, we checked the boxes for the availability of a Turkish written label. Forty product labels of 7 companies were reached and evaluated. These products consisted of 83.0% of the products marketed by these companies in Turkey. Thirty seven (92.5%) of the labels violated Article 9 of the Code in terms of one or more criteria. Thirty four (85.0%) of the labels had photos or pictures idealizing the use of infant formula. Nine (22.5%) had a photo, a picture or any representation of an infant, and five (12.5%) had text which idealize the use of infant formula or discouraging breastfeeding. Eight (20%) did not state that breastfeeding is the best. Four (10%) had a term such as 'similar to breast milk or human milk'. In conclusion, the majority of the product labels of breast milk substitutes marketed in our country violate the Code. It is appropriate that the Turkish Ministry of Health, medical organizations, companies, and NGOs work more actively to increase awareness of this issue.


Advances in Food Allergy.
Food allergy has been increasing in prevalence for the last few decades, and numerous studies have evaluated ways of improving the allergy practitioner's ability to accurately diagnose patients who are truly food allergic, rather than sensitive but able to tolerate food. Once diagnosed, the current standard treatment is food elimination and avoidance, but other potential treatment options like oral immunotherapy, sublingual immunotherapy, and epicutaneous immunotherapy are becoming promising alternatives. Due the health care costs and potential for life-threatening adverse reactions, much attention has been given to the prevention of food allergies, resulting a shift in recent guideline recommendations.


Amelioration of Chromium VI Toxicity in Sorghum (Sorghum bicolor L.) using Glycine Betaine.
The main objective of the present research work was to study the effect of Cr toxicity and its amelioration by glycine betaine (GB) in sorghum (HJ 541 and SSG 59-3). Chromium (Cr VI), 2 and 4 ppm led to a significant reduction in plant height, root length, chlorophyll content, antioxidant enzymes viz. catalase, peroxidase, ascorbate peroxidase, glutathione reductase, polyphenol oxidase, and superoxide dismutase; and metabolites viz. ascorbate, proline, and glutathione. The results of the present study supported the findings that the application of GB can minimize or reduce the toxic effects caused by Cr VI which reaches the plants via soil, water, and air pollution. It is concluded that GB at both 50, as well as 100 mM concentrations, successfully ameliorated Cr VI (up to 4 ppm) toxicity and its application may be recommended for crops affected by Cr VI toxicity to get better growth and yield.


Changes of the brain synapses during aging. New aspects.
The process of brain aging is an interaction of age-related losses and compensatory mechanisms. This review is focused on the changes of the synaptic number and structure, their functional implications, regarding neurotransmission, as well as the electrical activity of neuronal circuits. Moreover, the importance of calcium homeostasis is strongly emphasized. It is also suggested that many neuronal properties are preserved, as a result of adaptive mechanisms, and that a series of interdependent factors regulate brain aging. The "new frontier" in research is the challenge of understanding the effects of aging, both to prevent degenerative diseases and reduce their consequences. New aspects are considered a) the role of nitric oxide, b) free radicals and apoptosis, c) impaired cerebral microcirculation, d) metabolic features of aging brain, e) the possible neuroprotective role of insulin-like growth factor-1 (IGF-1) and ovarian steroids and e) stress and aging. These numerous multifactorial approaches are essential to understand the process of aging. The more we learn about it, the more we realize how to achieve "successful" aging.


Fibroblasts from FAD-linked presenilin 1 mutations display a normal unfolded protein response but overproduce Abeta42 in response to tunicamycin.
Many patients affected by early onset familial Alzheimer's disease (FAD), carry mutations in the presenilin 1 (PS1) gene. Since it has been suggested that FAD-linked PS1 mutations impair the unfolded protein response (UPR) due to endoplasmic reticulum (ER) stress, we analyzed the UPR and amyloid beta-protein processing in fibroblasts bearing various PS1 mutations. Neither in normal conditions nor after induction of ER stress with DTT or tunicamycin were the mRNA levels of UPR-responsive genes (BiP and PDI) significantly different in control and FAD fibroblasts. DTT, which blocked APP transport to the Golgi, caused a 30% decrease of secreted Abeta42 in wild type and PS1 mutant fibroblasts. In contrast, tunicamycin, which allowed exit of APP from the ER, increased secreted Abeta42 only in PS1 mutant fibroblasts. Our findings suggest that, although the UPR is active in fibroblasts from FAD patients, mutant PS1 may selectively increase Abeta42 secretion when N-glycosylation is impaired.


[Nasolacrimal stent: modifications to Ho-Young Song's technique].
To introduce modifications to Song's technique in the treatment of nasolacrimal occlusion by means of a polyuretane stent. Thirty five polyuretane stents were placed under fluoroscopic guidance in 32 patients diagnosed with total and partial nasolacrimal occlusion. Technical success rate was 90%. Sixteen right and nineteen left nasolacrimal systems were probed. The introduction of a guidewire through the lower punctum, the use of a Ritleng guide, a Crawford hook and ocular protectors are modifications of Song's procedure that may help in successfully performing this technique in a fast and easy way.


Adverse effects of high dose carnitine supplementation of total parenteral nutrition on protein and fat oxidation in the critically ill.
The aim of the present study was to investigate the effects of continuous and acute L-carnitine supplementation of total parenteral nutrition (TPN) on protein and fat oxidation in severe catabolism. A critically ill and severely malnourished male patient received TPN (non protein energy = 41 kcal/kg/day, provided equally as fat and glucose) over 38 days, without L-carnitine for 23 days and with carnitine supplements (15 mg/kg/day) for the following 15 days. Subsequently, he was given carnitine-free enteral nutrition for 60 more days. A four-hour infusion of 100 mg L-carnitine was given on day 11 of each TPN period. Indirect calorimetry was carried out after 11 days of either carnitine-free or supplemented TPN and at the initiation of enteral nutrition. Additional measurements were performed 4 hours and 24 hours after the acute infusions of carnitine. The rate of protein oxidation and the respiratory quotient were found to be higher, and the rate of fat oxidation to be lower, with carnitine-supplemented TPN, than with either carnitine-free TPN or enteral nutrition. Acute infusion of carnitine resulted in an increased rate of protein oxidation and a reduced rate of fat oxidation on both TPN-regimens. These unfavourable effects on protein metabolism may be due to an impairment of fat oxidation by excess amounts of carnitine.


Anterior cervical arachnoid cyst presenting with traumatic quadriplegia.
Intraduralspinal arachnoid cysts are rare. Rarer still are cysts located anteriorto the cervical spinal cord. To date,only 10 such cases have been re-ported in the English-language liter-ature. Two cases ofanterior cervical arachnoid cysts thatpresented as traumatic quadriplegiaare reported.


Yeast communities from host plants and associated Drosophila in southern arizona: new isolations and analysis of the relative importance of hosts and vectors on comunity composition.
The yeast communities from slime fluxes of three deciduous trees (Prosopis juliflora, Populus fremontii and Quercus emoryi) and the necroses of two cacti (Opuntia phaeacantha and Carnegiea gigantea) were surveyed in the region of Tucson, Arizona. In addition, the yeasts carried by dipterans associated with the fluxes or necroses (Drosophila carbonaria, D. brooksae, D. nigrospiracula, D. mettleri, and Aulacigaster leucopeza) were sampled. The results indicate that each host sampled had a distinct community of yeasts associated with it. The dipterans, which can act as vectors of the yeasts, deposited yeasts from other sources in addition to those found on their associated hosts. It is argued that host plant physiology is relatively more important than the activity of the vector in determining yeast community composition. Furthermore, the average number of yeast species per flux or necrosis is not different from the average number of yeast species per fly. It is hypothesized that the vector may affect the number of species per individual flux or not, and that the number is lower than the rot or necrosis could potentially support.


The anterolateral thigh flap; variations in its vascular pedicle.
The anterolateral thigh flap is based on the septocutaneous perforators of the lateral circumflex femoral artery. Little has been written about anomalies of its vascular pedicle. We report two variants of the pedicle vessel in eight patients in whom this flap was used, and absence of the perforators in five other cases in whom it was attempted. The anterolateral thigh flap has the advantages of thin and pliable skin, long and large pedicle, inconspicuous donor scar and the technical possibility of combination with fascia, sensory nerve and iliac bone. If the perforators are absent, a tensor fasciae latae musculocutaneous flap or anteromedial thigh flap is available with only minor changes of the flap outline.


Metabolic engineering for the high-yield production of polydatin in Yarrowia lipolytica.
Polydatin, a glycosylated derivative of resveratrol, has better structural stability and biological activity than resveratrol. Polydatin is the extract of Polygonum cuspidatum, which has various pharmacological effects. Owing to its Crabtree-negative characteristics and high supply of malonyl-CoA, Yarrowia lipolytica was selected to produce polydatin. Initially, the resveratrol synthetic pathway was established in Y. lipolytica. By enhancing the shikimate pathway flow, redirecting carbon metabolism, and increasing the copies of key genes, a resveratrol yield of 487.77 mg/L was obtained. In addition, by blocking the degradation of polydatin, its accumulation was successfully achieved. Finally, by optimizing the glucose concentration and supplementing with two nutritional marker genes, a high polydatin yield of 6.88 g/L was obtained in Y. lipolytica, which is the highest titer of polydatin produced in a microbial host to date. Overall, this study demonstrates that Y. lipolytica has great potential for glycoside synthesis.


Human immunodeficiency virus (HIV) infection in children.
HIV infection in pediatric patients is a multisystem chronic disease that manifests as a clinical spectrum from asymptomatic infection through symptomatic infection with opportunistic infections and malignancies. The hematopoietic system is involved early in the systemic manifestations of this disease. The hematologic abnormalities seen are most probably a reflection of persistent viral infection, inflammation, and immune dysregulation, and may be complicated by secondary infections, chronic disease, drug toxicities, and nutritional deficiencies. Anemia and lymphopenia are commonly found in adult AIDS patients. Although both are also seen in pediatric patients, lymphopenia is much less common. Atypical lymphocytes with plasmacytoid characteristics have been identified in both adults and children. Pediatric bone marrow evaluation has shown an increase in plasma cells and plasmacytoid lymphocytes. Besides these findings, adult marrow findings include an increase in reticulum and lymphocytes appearing in a diffuse or aggregate pattern.


Pay-it-forward incentives for hepatitis virus testing in men who have sex with men: a cluster randomized trial.
Pay-it-forward incentives involve having a person receive a free test with community-generated messages and then asking if those who received a free test would like to donate money to support others to receive free testing. Here we undertook a two-arm cluster-randomized trial to evaluate pay-it-forward incentives with active community participation to promote hepatitis B virus (HBV) and hepatitis C virus (HCV) testing among men who have sex with men in China. Men randomized to the pay-it-forward arm received free HBV and HCV testing and were offered a chance to pay-it-forward by donating money to support the testing of another anonymous person. Each participant paid for their HCV and HBV test at 7.7 USD per test in the standard-of-care arm. The primary outcome was the proportion of men who tested for HBV and HCV. Between 28 March and 6 November 2021, 32 groups (10 men per group) of men were randomized to the pay-it-forward (n = 160, 16 clusters) and standard-of-care (n = 162, 16 clusters) arms, respectively. HBV and HCV rapid testing were higher in the pay-it-forward arm (59.4%) than in the standard-of-care arm (25.3%) (proportion difference 35.2%, 95% confidence interval 24.1-46.3%). No adverse events were reported. The community-led pay-it-forward incentives improved HBV and HCV testing among men who have sex with men. Clinical Trial registration: ChiCTR 2100046140.


Fasting and daylong triglycerides in obesity with and without type 2 diabetes.
Postprandial hypertriglyceridemia associated with insulin resistance is one of the cardiovascular risk factors in obesity and type 2 diabetes. It is not known whether diabetics have a more pronounced postprandial hypertriglyceridemia than obese subjects. Daylong triglyceridemia, representing postprandial lipemia, was determined in obese subjects with and without type 2 diabetes and in lean subjects. Nineteen type 2 diabetics (F/M: 7/12, body mass index [BMI]: 30.6 +/- 5.4 kg/m(2)), 45 obese nondiabetics (F/M: 16/29, BMI: 29.5 +/- 2.6 kg/m(2)) and 78 lean subjects (F/M: 28/50, BMI: 23.7 +/- 2.2 kg/m(2)) measured capillary triglycerides (TGc) during 3 days on 6 fixed time-points each day in an out-of-hospital situation. Daylong TGc profiles were calculated as mean integrated area under the TGc-curve (TGc-AUC). Fasting plasma TG were higher in diabetics and obese nondiabetics (1.81 +/- 0.79 and 1.77 +/- 0.80 mmol/L) compared with lean subjects (1.23 +/- 0.67 mmol/L, P <.001). TGc-AUC was similarly increased in both diabetics and obese nondiabetics (35.0 +/- 12.1 and 35.2 +/- 10.6 mmol.1 h/L) compared with lean controls (25.5 +/- 12.0 mmol.1 h/L, P <.001). Self-reported energy intake was not significantly different between the groups. Fasting TGc (r =.87, P <.001) and waist circumference (r =.51, P <.001) were the parameters best associated with TGc-AUC. Using stepwise multiple regression analysis, fasting TGc, BMI, total cholesterol, and high-density lipoprotein (HDL) cholesterol were the best predictors of TGc-AUC, explaining 77% of the variation. The cut-off level for "normal" TGc-AUC, calculated as the 75th percentile of TGc-AUC in lean subjects, was 30.7 mmol.1 h/L and corresponded with a fasting TGc of 1.8 mmol/L (eg, 1.6 mmol/L in plasma), calculated using univariate regression analysis. In conclusion, daylong triglyceridemia is similarly increased in diabetics and obese nondiabetics compared with lean subjects. Fasting TG and central obesity largely determine daylong triglyceridemia, independent of the presence of type 2 diabetes. Decreasing fasting plasma TG below 1.6 mmol/L could lead to a normalization of postprandial lipemia in obese subjects with and without diabetes.


Cockroaches in relation to bronchial asthma in the Durban area.
Thirty patients from the White and Coloured asthma clinics were subjected to skin prick tests with various antigens. Although the house-dust mite was found to be the main offender, 9 of the 30 patients showed a significant reaction to cockroach antigen. It is felt that cockroaches play a role in the pathogenesis of asthma in the Durban area and that this fact should be considered in desensitization programmes.


The role of transmembrane cationic gradients in immune complex stimulation of human polymorphonuclear leukocytes.
The role of monovalent cationic gradients in human polymorphonuclear leukocyte (PMNL) stimulation was investigated by monitoring immune complex-stimulated transmembrane depolarization and superoxide production, events which accompany--and have been used as indicators of --PMNL activation. Abolishing only the Na+ gradient by substitution of choline for extracellular Na+ did not affect the resting membrane potential but reduced the rate of stimulus-induced transmembrane depolarization to 50% of control. In contrast, collapsing both Na+ and K+ gradients by suspension in K+ buffer (high K-PRK) depolarized the cells and reduced the stimulus-induced rate of depolarization to 11% of control. Pretreatment of cells suspended in Na+ buffers with 5-(N,N-dimethyl)amiloride hydrochloride (DMA) or with valinomycin reduced by one-half the rate of immune complex induced membrane depolarization. Conversely, in the absence of either or of both Na+ or K+ gradients, or in the presence of valinomycin, immune complex elicited an enhanced rate of superoxide production. However, PMNL prepared via NH4Cl (NH4Cl-PMNL) instead of H2O (H2O-PMNL) lysis of residual red blood cells exhibited an absolute requirement for an intact Na+ gradient in cell stimulation. The present results thus demonstrate that: 1) both Na+ and K+ gradients participate equally in the membrane depolarization elicited by immune complex; 2) neither a Na+ or a K+ gradient is required for immune complex activation, or for activity of the respiratory burst; and 3) an artifactual requirement for an intact Na+ gradient occurs in neutrophils prepared by the NH4Cl lysis technique.


[Effect of diethylnitrosamine on the protein-synthesizing cell system of the rat liver].
Diethylnitrosoamine is found to alter the course of the regenerative processes induced by partial hepatectomy, which is manifested in essentially other, than in the control, changes of polyribosomes and mRNA. In early terms following DENA injection one may observe a reduced content of total polyribosomes, a sharp decrease in the amount of membrane-bound polyribosomes, the inhibited incorporation of newly produced mRNA in both classes of polyribosomes. In later terms, a proportion of the membrane-bound polyribosomes is again diminished, while the ratio of the specific radioactivity of free and membrane-bound polyribosomes is raised.


Energy metabolism: A critical target of cardiovascular injury.
Cardiovascular diseases are the main killers threatening human health. Many studies have shown that abnormal energy metabolism plays a key role in the occurrence and development of acute and chronic cardiovascular diseases. Regulating cardiac energy metabolism is a frontier topic in the treatment of cardiovascular diseases. However, we are not very clear about the choice of different substrates, the specific mechanism of energy metabolism participating in the course of cardiovascular disease, and how to develop appropriate drugs to regulate energy metabolism to treat cardiovascular disease. Therefore, this paper reviews how energy metabolism participates in cardiovascular pathophysiological processes and potential drugs aimed at interfering energy metabolism.It is expected to provide good suggestions for promoting the clinical prevention and treatment of cardiovascular diseases from the perspective of energy metabolism.


[Surgical strategy in the treatment of infantile ureterocele].
The authors describe their experience on the surgical treatment of ureterocele in the pediatric age. The anatomic and clinical features which condition the choice between various therapeutic solutions are presented. All problems concerning any kind of different surgical approach are discussed, stressing the importance of the endovesical radical treatment.


Topographical anatomy of the ciliary sulcus.
The topography of the ciliary sulcus area in humans was examined by slitlamp biomicroscopy and scanning electron microscopy. Characteristics of this area included the following: the sulcus was angulated anteriorly; the ciliary processes were of unequal length; the zonules did not insert on the tips of the ciliary processes but, instead, inserted slightly posteriorly; the contour of the sulcus area was irregular; bands stretched from the base of the ciliary processes to the posterior surface of the iris, making the sulcus a potential space in some areas of the eye. Effects of this topography on IOL implantation are postulated.


Characteristics of calls to Israeli hotlines during the Gulf War.
The current study presents results of a survey of 3,215 calls received at seven centers of telephone emergency services (TES) in Israel during the Gulf War, when citizens of Israel experienced severe stress resulting from SCUD missile attacks. Whereas former surveys have shown that characteristics of calls to TES in Israel are generally not affected by external stressogenic events, a remarkable change was recorded in both the quantity and quality of calls received in TES centers in Israel during the Gulf War. The relative frequencies of problem categories presented by callers during the Gulf War revealed a significant increase in "environmental pressures," a category that reflected the stressful situation of the war, as opposed to intra- or interpersonal problems typical of peacetime calls. A comparison between this group of "war calls" and a control group of "nonwar calls," revealed that the two groups represented populations of callers differing in sociodemographic characteristics, expectations, and benefits from the calls. Results are discussed in reference to the unique role of TES as a source of psychological first-aid in a community crisis situation.


Passive coping is a risk factor for disabling neck or low back pain.
Despite evidence suggesting that coping is an important concept in the study of pain, its role in predicting the development of disabling pain has not been previously studied. To assess the relationship between coping and the development of disabling pain. From a random sample of adults, we formed a cohort of individuals with non-disabling neck and/or low back pain (n=571). Participants were followed 6 and 12 months after the index survey. Coping was measured with the Vanderbilt Pain Management Inventory. The Chronic Pain Questionnaire was used to measure the presence of disabling neck and/or low back pain. We used Cox proportional hazards regression analyses to investigate the role of passive coping in the development of disabling pain while controlling for confounders. Passive coping was a strong, independent risk factor for disabling neck and/or back pain. Those using moderate to high levels of passive coping strategies were at an over five-fold increased risk of developing disabling pain (Moderate: HRR=5.19, 95% CI=1.78-15.1; High: HRR=6.80, 95% CI=2.36-19.6). Active coping was not found to be a significant risk factor for disabling neck and/or back pain. Passive coping is a strong and independent predictor of disabling neck and/or back pain. This strong relationship identifies passive coping as a marker for risk of disability and can allow for the identification of individuals at risk and in need of intervention to aid in improving their overall adjustment.


Protective effects of montelukast on ischemia-reperfusion injury in rat ovaries subjected to torsion and detorsion: biochemical and histopathologic evaluation.
To reveal the effects of montelukast as an antioxidant and tissue protective agent and study the biochemical and histopathologic changes in experimental ischemia and ischemia-reperfusion (I/R) injury in rat ovaries. Experimental study. Experimental surgery laboratory in a university department. Forty-eight rats with experimentally induced ovarian torsion. Group 1: sham; Group 2: ovarian ischemia; Group 3: a 30-hour period of ischemia followed by a 3-hour reperfusion. Groups 4 and 5: rats administered 10 and 20 mg/kg doses of montelukast before a half-hour of ischemia, then ovarian ischemia applied; after a 3-hour period of ischemia, the bilateral ovaries removed. Groups 6 and 7: 3-hour period of ovarian ischemia applied, then 2.5 hours after the ischemia induction, rats given montelukast. Group 8: sham operation and 20 mg/kg of montelukast; at the end of a 3-hour period of ischemia, 3-hours of reperfusion continued. Measurement of ovarian tissue concentrations of superoxide dismutase (SOD), glutathione (GSH), lipid peroxidation (LPO) and myeloperoxidase (MPO) activity; and histopathologic examination of all ovarian rat tissue. Montelukast treatment normalized changes of LPO and MPO and stimulated an overproduction of endogenous SOD and GSH. The results of the histologic parameters showed that treatment with montelukast in the I/R group of rats ameliorated the development of ischemia and reperfusion tissue injury. Montelukast at different doses attenuates ovarian I/R-induced ovary tissue injury in rats.


Cutaneous metastasis from follicular carcinoma of the thyroid gland.
A 65-year-old man with a history of malignant melanoma presented a reddish nodule on the left temporal region of the scalp. Histologic features and immunoperoxidase staining on the skin biopsy specimen confirmed the diagnosis of metastatic thyroid follicular carcinoma. The patient presented recurrences of metastatic skin nodules, lung and bone metastases, and died after a 3-year follow-up.


Influence of vitamin E on polyamine metabolism in ozone-exposed rat lungs.
The influence of vitamin E (E) on lung polyamine metabolism of rats exposed to ozone (O3) was examined. Rats fed diets wither E-deficient or supplemented with 1000 IU E/kg were exposed to 0.5 +/- 0.05 ppm O3 or filtered room air continuously for 5 days. They were then sacrificed and their lungs were analyzed for biochemical changes. Lung E content was strongly associated with the dietary level, and increased (36%, P less than 0.05) after O3 exposure only in E-supplemented rats. Lung polyamine metabolism was not affected in the air-control rats by E level, but increased after O3 exposure in both dietary groups. The activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase were elevated above air controls. However, the increases were significant only for E-deficient rats when compared to E-supplemented rats. After O3 exposure, putrescine increased significantly in both dietary groups; spermidine increased but was significantly higher only in the E-deficient group; and spermine remained unchanged in both dietary groups. Elevated E content of supplemented rat lungs after O3 exposure may represent its mobilization under oxidant stress. Increased polyamine metabolism of E-deficient rats suggests either a greater sensitivity to injury by O3 or a possible antioxidant function for polyamines compensating for E deficiency.


Characterization of sequence elements involved in p53 stability regulation reveals cell type dependence for p53 degradation.
The growth suppressive properties of the tumor suppressor protein p53 are activated upon DNA damage. The activation of p53 is reflected in increased p53 levels which are, at least in part, the result of an extended half-life of the protein. Although this suggests that stabilization of p53 is an intrinsic feature of p53 activation, the mechanisms involved in p53 degradation and stabilization are poorly understood. Here we report on the identification of an internal deletion mutant of wild-type p53, termed delta62-96, which can be stably expressed in various cell lines. This deletion mutant has a turnover rate similar to wild-type p53 and its stability is upregulated by treatment with UV light. In cell lines that express endogenous mutant or no p53, however, delta62-96 appears to be stable, strongly indicating that these cell lines have lost the ability to degrade p53. Further characterization of delta62-96 by mutational analyses defines sequence and structural requirements for p53 degradation and indicates that none of the known p53 phosphorylation sites is essential with respect to p53 stability regulation upon UV-irradiation.


A comparative cranio-corpography study on the findings in the Romberg standing test versus the Unterberger/Fukuda stepping test in vertigo patients.
Cranio-corpography (CCG) stepping and standing tests are compared in a group of 202 neurotological patients. In these two vestibulo-spinal tests, performed by a simple and precise photo-optic system, the movement of the shoulders and the head--and not the movement of the feet, is taken as the parameter for the investigation. The two tests are complementary one to the other. The CCG should be an integral part of every neurotological laboratory.


Development and clinical application of sensitive enzyme immunoassay for macromolecular antigens--a review.
Radioimmunoassay has been a powerful tool to measure haptens and antigens which are important for the investigation and diagnosis of diseases, especially endocrine disorders. However, the use of radioisotopes in radioimmunoassay suffers from serious disadvantages. Radioisotope-labeled reagents are unstable and hazardous to health. The disposal of radioactive wastes is not easy. Furthermore, the sensitivity of radioimmunoassay is limited by the detection limit of radioisotope that depends upon the half-life. The detection limit of the most widely used radioisotope, 125I, with a half-life of 60 days is 5 to 10 amol, when it is carrier-free. By contrast, the use of enzymes has obvious advantages. Some enzymes are very stable and cause no health hazards or waste disposal problems, provided that appropriate substrates are chosen. The detection limits of some enzymes are lower than that of 125I and will be further improved in the future. Therefore, enzyme immunoassay is potentially more sensitive than radioimmunoassay. This article reviews the development and clinical application of sensitive enzyme immunoassay for macromolecular antigens, which has been replacing radioimmunoassay.


Synthesis and structures of M[N(TePPri2)2-Te,Te']n (n = 2, M = Zn, Cd, Hg; n = 3, M = Sb, Bi): the first ditelluroimidodiphosphinato p- and d-block metal complexes.
Reactions of Na[N(TePPri2)2] with the appropriate metal halide produce the air-stable complexes M[N(TePPri2)2-Te,Te']n (n = 2, M = Zn, Cd, Hg; n = 3, M = Sb, Bi), which adopt distorted tetrahedral (M = Zn, Cd, Hg) and octahedral (M = Sb, Bi) structures, respectively.


Primary subcutaneous follicular centre cell lymphoma with involvement of the galea: a case report and short review of the literature.
Primary cutaneous follicular centre cell lymphoma (FCCL) is a distinct subtype of cutaneous lymphoma that originates from germinal centre cells. Histologically, the disease is typified by a bottom-heavy infiltrate with a diffuse or follicular growth pattern situated in the mid or deep dermis. In some cases, the neoplastic infiltrate may involve the underlying subcutaneous tissue, but so far primary subcutaneous FCCL has not been reported. We report the first case of primary FCCL located primarily in the deep subcutis with extension into the galea and review the literature on primary subcutaneous B-cell lymphomas.


Development and survival of free-living stages of equine strongyles under laboratory conditions.
In a series of laboratory studies the optimum conditions for the development and survival of the free-living stages of strongyle parasites occurring in horses in tropical north Queensland were determined. No differences in behaviour were noted between the strongyle species. Development to the infective stage occurred only between 10 and 35 degrees C. The rate was affected by temperature, taking 15-24 days and 3 days, respectively, at the lowest and highest temperatures for the developing stages to reach the infective third stage. Yields of infective larvae were very low outside the range 20-33 degrees C, and were highest at 28 degrees C. Survival of infective larvae was good between 20 and 33 degrees C, and large numbers were recovered after 3 months in faeces incubated at 20-28 degrees C. At 33 and 37 degrees C larval survival was affected by the moisture content of the faeces, with infective larvae surviving better in dry than in moist faeces; even a residual moisture level of 40% significantly reduced the number of larvae recovered from faeces incubated at 37 degrees C for 1 month. Moisture also affected larval development, especially at the higher temperatures of 25-39 degrees C. When faecal moisture content fell to less than or equal to 20% by 3 days, larvae which had not yet reached the infective stage were still pre-infective at 7 days, while all larvae in faeces with adequate moisture had reached the infective third stage. It was not possible to determine the critical faecal moisture level below which larval development ceased, however, 28 degrees C (range 25-33 degrees C) was found to be the optimum temperature. Larval development was very rapid and yields of infective larvae highest at this temperature.


Aedes Dronc: a novel ecdysone-inducible caspase in the yellow fever mosquito, Aedes aegypti.
Caspases are cysteinyl-aspartate-specific proteases known for their role in apoptosis. Here, we describe the characterization of Aedes Dronc, a novel caspase in the yellow fever mosquito, Aedes aegypti. Aedes Dronc is predicted to contain an N-terminal caspase recruitment domain and is a homologue of Drosophila Dronc and human caspase-9. An increase in transcripts and caspase activity coincides with developmental changes in the mosquito, suggesting that Aedes Dronc plays a role in developmental apoptosis. Exposure of third instar larvae to ecdysone resulted in a significant increase in both transcript levels and caspase activity. We present here a functional characterization of the first caspase recruitment domain-containing caspase in mosquitoes, and will initiate studies on the role of apoptosis in the innate immune response of vectors.


The endolymphatic sac in a mouse mutant with cochleo-saccular degeneration. Electrophysiological and ultrastructural correlations.
The response of the endolymphatic sac to a disturbance in endolymph homeostasis was investigated by examining the sac in a mouse mutant, viable dominant spotting, which is known to exhibit primary strial dysfunction and cochleo-saccular degeneration. The function of the vascular stria was assessed by measuring the endocochlear potential and the sacs were then studied by light and transmission electron microscopy. The endolymphatic sac was found to be morphologically abnormal in these mutants, the main abnormality being the presence of granular epithelial cells, which showed clear histological signs of secretory activity. A stainable precipitate, believed to be secreted by the granular cells, was observed in the lumen of the endolymphatic sac in the mutants. The findings strengthen the view that the sac is involved in the regulation of endolymph volume and pressure.


Decreased phosphatidyl choline content in bronchoalveolar lavage fluids of children with bronchopulmonary dysplasia: a preliminary investigation.
Bronchoalveolar lavage (BAL) was performed on 12 infants who had recovered from neonatal acute respiratory failure and on 12 patients with bronchopulmonary dysplasia (BPD) in order to evaluate the concentration of phosphatidyl choline (PC) in BAL fluid. These two groups were similar at birth (mean birth weight: 1,980 and 1,750 g, respectively; mean gestational age: 33.4 and 32.1 weeks respectively). Mechanical ventilation based on oxygen requirement lasted longer in the group with BPD. BAL was performed at the end of the first year of life (at 8.5 and 10.3 months, respectively) and the results were compared to control values (from infants of the same age without neonatal disease). Whereas the protein concentration in BAL fluid was similar in the two groups, a dramatic decrease of the BAL PC was found in BPD: The mean values of BAL-PC over protein ratio were 0.9 in the group without pulmonary sequelae and 0.3 in the group with BPD. These preliminary results suggest an impairment of the pulmonary surfactant metabolism in this chronic lung disease following neonatal acute respiratory failure.


[Methodological problems of quantitative and combined evaluation of the asynergy and volume of the left heart ventricle by contrast ventriculography in patients with ischemic heart disease].
Regional analysis was performed in 24 patients with various forms of left ventricular (LV) asynergy. Three quantitative methods of regional analysis with different types of superposition (SP) of end-phasic contours (EPC) were compared: the radial method, taking into account the dislocation of basal structures, was more sensitive (p less than 0.02) in detecting apical asynergy, as compared to the chordal method, or the radial procedure using a different type of SP. The authors used the radial method of regional analysis for estimating LV volumes in 53 patients. The data obtained with this method were in good correlation with those of the conventional "area-length" technique. It is concluded that the radial method taking into account the dislocation of basal structures is useful in complex and quantitative analysis of regional as well as systemic parameters of LV function.


Emotional responses to the experience of cancer 'alarm' symptoms.
To qualitatively explore associations between emotional responses to experience of cancer 'alarm' symptoms and help-seeking in a community sample of adults. Interviewees (n = 62) were recruited from a community sample (n = 2042) of adults aged ≥50 years, who had completed a health survey that included a list of cancer alarm symptoms. Participants who had reported an alarm symptom both at baseline and 3-month follow-up (n = 271), and who had consented to contact (n = 215), constituted the pool for invitations to interview. Over a third of participants (37%) described an emotional response to their symptom experience. In all these cases, there was evidence of awareness of the risk of cancer. Emotional responses were usually either classified as mild ('worry') or severe ('fear'). Worry was often described in the context of a desire to seek medical help, either to rule out cancer or to minimise patient delay. In contrast, the 'fear' group described associations with death, the perceived incurability of cancer, and the consequence of a cancer diagnosis. Where the emotional reaction was fear, medical contact was seen as something to be avoided either because it had no value or because it was preferable not to be told a diagnosis. In this community sample, worry about the possibility of cancer was associated with help-seeking, either for reassurance or as part of a 'sensible' strategy to deal with the risk. In contrast, fear was associated with avoiding help-seeking or even thinking about cancer, which could lead to prolonged help-seeking intervals.


Antibodies to HSP70 and HSP90 in serum in non-small cell lung cancer patients.
Heat shock proteins (HSPs) are components of a physiologic stress response that are also over-expressed in various cancers including non-small cell lung cancer (NSCLC). During NSCLC serum-antibody screening of a NSCLC cDNA T7 phage library for immunogenic proteins we isolated HSP70 and HSP90 proteins. Isolation of these proteins suggested that corresponding antibodies could be elevated in NSCLC patient sera, a novel finding that could pilot their use as markers of NSCLC. We showed histochemically that patient sera were more reactive with each phage-expressed protein than normal sera. Antibody affinity for each phage-expressed protein was confirmed by limiting the dilution of individual sera assayed by Ab enzyme-linked immunosorbent assay (ELISA). Sera from 49 NSCLC patients assayed by Ab ELISA and normalized to 40 controls showed that HSP70 antibodies were significantly greater in patient sera than in normals (P=0.0002), while HSP90 antibodies were not significantly different (P=0.11). Analysis of the results with logistic regression and receiver operating characteristics (ROC) curves showed that HSP70 antibodies were modest markers of NSCLC (sensitivity 0.74 and specificity 0.73; area under the curve or AUC=0.731), while HSP90 antibodies appeared to be poor in both criteria with an AUC of 0.602. Further evaluation of HSP70 antibodies as potential markers of disease may be rational.


Second trimester cervical length and prolonged pregnancy (.).
To determine whether second trimester transvaginal ultrasound cervical length (CL) is associated with prolonged pregnancy (≥41 0/7 weeks) in nulliparous women who reach term (≥37 weeks) with a planned vaginal delivery. Retrospective cohort of nulliparous singletons 18 0/7-23 6/7 weeks gestation undergoing CL screening from 1/1/12 to 12/31/13. Women who delivered at term with spontaneous labor or reached 41 weeks were included. Primary outcome was incidence of prolonged pregnancy. Risk of prolonged pregnancy was assessed by CL quartile using odds ratio, adjusted for confounders (aOR) and a receiver operating characteristic (ROC) curve. 722 women were included, among them 171 (24%) had a prolonged pregnancy. There was a significant difference in BMI and race across CL quartiles. The aOR of having a prolonged pregnancy with CL in quartiles 2, 3, and 4 versus quartile 1 were 2.14(1.27-3.62), 2.72(1.59-4.65), and 1.69(1.02-3.03), respectively. CL ≥ 37 mm (beyond first quartile) was associated with a two-fold increased risk of prolonged pregnancy versus CL < 37 mm, (27% vs 15%, p < 0.01, aOR 2.17 (1.38-3.41)). ROC curve did not identify a CL cutoff that was predictive of prolonged pregnancy (AUC 0.544, p = 0.079). Although a longer second trimester CL is associated with an increased risk for prolonged pregnancy, it is not predictive.


The king's animals and the king's books: the illustrations for the Paris Academy's Histoire des animaux.
This essay explores the place of natural philosophy among the patronage projects of Louis XIV, focusing on the Mémoires pour servir a l'histoire naturelle des animaux (or Histoire des animaux) of the 1670s, one of a number of works of natural philosophy to issue from Louis XIV's printing house. Questions particular to the Histoire des animaux include the interaction between text and image, the credibility and authority of images of exotic animals, and the relationship between comparative anatomy and natural history, and between human and animal anatomy. At the same time that the Histoire des animaux contributed to Jean-Baptiste Colbert's management of patronage and of Louis's image, it was a work of natural philosophy, representing the collaborative efforts of the new Paris Academy of Sciences. It examined natural history and comparative anatomy in new ways, and its illustrations broke new ground in their depiction of animals in a natural setting. However, the lavishly formatted books were presentation volumes and did not gain wide circulation until their republication in 1733. Sources consulted include Colbert's manuscript memoires on the royal printers and engravers.


A novel LRRFIP1-ALK fusion in inflammatory myofibroblastic tumor of hip and response to crizotinib.
An inflammatory myofibroblastic tumor (IMT) is a rare invasive soft tissue mass with intramuscular penetration that is primarily treated via a surgical procedure. However, with unclear boundaries and a high rate of relapse, there is no standard treatment for recurrence or unresectable tumors. It is noteworthy that approximately half of IMTs harbor genetic rearrangements of the anaplastic lymphoma kinase (ALK). ALK inhibitors have been used successfully in the treatment of IMTs with a variety of ALK fusions. Here, we present a case of a 15-year-old patient with IMT around the hip. Next-generation sequencing (NGS) revealed an LRRFIP1-ALK fusion, which has not yet been reported in the literature. Crizotinib, an ALK inhibitor, was effective in the treatment of this patient, indicating that ALK inhibitors may be effective for IMT with LRRFIP1-ALK fusions. This report expands the list of gene fusions in IMTs and highlights a new target for treatment.


Aromatization of steroids in peripheral tissues.
The action of glucocorticoids on aromatase activity in human adipose tissue has been investigated. Oestrogen production was increased in tissue maintained in the presence of dexamethasone and cortisol. Dexamethasone was effective at concentrations as low as 1 nmol/l. In contrast, over the 40 h incubation period, cortisol was only effective at concentrations in excess of 500 nmol/l, although after conditions of prolonged incubation, induction of aromatase activity was measurable using cortisol concentrations as low as 28 nmol/l. There were apparent variations in both basal levels of aromatic activity and in response to glucocorticoids in adipose tissue taken from various sites within the body.


Blood zinc and copper concentrations in criminal and noncriminal schizophrenic men.
This study investigated the effects of zinc and copper on the behavior of schizophrenic patients by comparing blood zinc and copper levels in criminal and noncriminal schizophrenic patients. Of the total 88 subjects, 44 were patients with schizophrenia and no criminal record who were being treated at the Elazig Mental Hospital and 44 were schizophrenic patients who had committed a crime and were sent to the same hospital upon a court order for monitoring, detention, and treatment. Of the subjects with criminal records, 31 (70%) had committed a violent crime and 13 (30%) had committed a nonviolent crime. The mean plasma zinc value was 68 +/- 1.55 microg/dL in the criminal subjects and 81 +/- 2.73 microg/dL in the noncriminal subjects ( p = .001). The mean serum copper value was 104 +/- 1.80 microg/dL in criminal subjects and 93 +/- 2.92 microg/dL in noncriminal subjects (p = .02). Mean plasma zinc values were significantly lower in criminal subjects when compared to noncriminal subjects, while mean serum copper values were significantly higher in criminal subjects than noncriminal subjects.


Exact mobility edges in quasiperiodic systems without self-duality.
Mobility edge (ME), a critical energy separating localized and extended states in spectrum, is a central concept in understanding localization physics. However, there are few models with exact MEs, and their presences are fragile against perturbations. In the paper, we generalize the Aubry-André-Harper model proposed in (Ganeshanet al2015Phys. Rev. Lett.114146601) and recently realized in (Anet al2021Phys. Rev. Lett.126040603), by introducing a relative phase in the quasiperiodic potential. Applying Avila's global theory, we analytically compute localization lengths of all single-particle states and determine the exact expression of ME, which both significantly depend on the relative phase. They are verified by numerical simulations, and physical perception of the exact expression is also provided. We show that old exact MEs, guaranteed by the delicate self-duality which is broken by the relative phase, are special ones in a series controlled by the phase. Furthermore, we demonstrate that out of expectation, exact MEs are invariant against a shift in the quasiperiodic potential, although the shift changes the spectrum and localization properties. Finally, we show that the exact ME is related to the one in the dual model which has long-range hoppings.


A Newly Discovered Manuscript of Charles T. Jackson, MD, on the Preparation and Administration of Anesthetics for Humans and Animals.
A newly discovered handwritten manuscript of Charles T. Jackson, MD, contains instructions for the preparation and administration of sulfuric ether, information on Jackson's preferred mixture of ether and chloroform, an account of his experiments with other potential anesthetic agents, and his comments on etherizing cattle and other animals. Jackson's nine-page manuscript is believed to have been written in the autumn of 1851, around the time that he submitted his memorial on the discovery of etherization to Baron von Humboldt, and made a separate submission to the US Congress.


The role of perceived parenting in familial aggregation of anxiety disorders in children.
This study was designed to explore the role of perceived parenting style in the familial aggregation of anxiety disorders. We examined the association between parental and child anxiety diagnoses, and tested whether this association was partly due to a perceived parenting style. The study was conducted in a clinical sample as well as in a control sample. Parental lifetime and current anxiety diagnoses were significantly associated with child anxiety diagnoses. When maternal and paternal lifetime and current anxiety diagnoses were entered as separate predictors, only maternal current anxiety diagnoses appeared to be significant. Perceived parenting style was assessed with the dimensions "overprotection," "emotional warmth," "rejection," and "anxious rearing." Results indicated that only maternal and paternal 'overprotection' was significantly but negatively associated with child anxiety. However, further analyses showed that 'overprotection' did not have a significant mediating role in the familial aggregation of anxiety disorders.


Substitution of lysine for asparagine at position 15 in the alpha-subunit of the human insulin receptor. A mutation that impairs transport of receptors to the cell surface and decreases the affinity of insulin binding.
Mutations in the insulin receptor gene can compromise the ability of the receptor to mediate insulin action. Previously, in investigations of a patient with a genetic form of insulin resistance, we have identified a mutant allele encoding an insulin receptor in which lysine is substituted for asparagine at position 15 of the alpha-subunit. In the present study, we have characterized the Lys15-mutant receptor expressed by transfection of mutant cDNA into NIH-3T3 cells. The Lys15-mutation causes at least two defects in insulin receptor function. First, the mutation retards the post-translational processing of the receptor and impairs transport of the receptor to the plasma membrane, thereby reducing the number of receptors on the cell surface. Second, the mutation causes a 5-fold reduction in the affinity of the receptor to bind insulin. These two defects combine to render the target cell resistant to normal physiological concentrations of insulin. It seems likely that both functional defects associated with the Lys15-mutation can be explained by assuming that the mutation distorts the three-dimensional structure of the receptor. Presumably, the abnormal conformation interferes with the transport of the receptor through the endoplasmic reticulum and Golgi, and also inhibits the binding of insulin to its binding site on the receptor.


Atorvastatin increases miR-124a expression: a mechanism of Gamt modulation in liver cells.
Atorvastatin is used to control cholesterol and lipid levels in hyperlipidaemic and hypercholesterolaemic patients. Myopathy and hepatotoxicity, however, have been reported as side effects in a small percentage of statin users. This study aimed to investigate the cytotoxicity and the effect of atorvastatin on microRNA expression in HepG2 cells. The methylthiazol tetrazolium assay was used to assess hepatocyte viability and at 20 μM atorvastatin (24 h) treatment were 82 ± 1.5% viable (P = 0.0002). Levels of intracellular ATP in cells treated with 20 μM atorvastatin were reduced by 1.25-fold, P = 0.002. Cytotoxicity, measured by the release of intracellular lactate dehydrogenase, was increased from 0.95 ± 0.29 units in control cells to 1.12 ± 0.02 units (P = 0.002) in atorvastatin treated cells. A panel of 84-miRNA species was used to evaluate the effect of atorvastatin on miRNA expression. MiR-124a was significantly up-regulated by atorvastatin (12.94-fold). A significant decrease in GAMT expression (3.54-fold) was observed in atorvastatin treated cells following quantitative PCR analysis. In addition, western blotting data showed GAMT protein levels were significantly lower than the controls (3.02-fold) and analysis of creatine levels in treated cells showed a significant decrease in the atorvastatin treated culture supernatant compared to control culture supernatant (32.33 ± 3.51 μM/l vs. 59.67 ± 1.52μM/l, P = 0.0056). This is the first study to show that atorvastatin up-regulates miR-124a levels and consequently modulates GAMT expression in hepatocytes.


Vitamin D supplementation in chronic obstructive pulmonary disease patients with low serum vitamin D: a randomized controlled trial.
Vitamin D deficiency is frequently found in patients with chronic obstructive pulmonary disease (COPD). Vitamin D has antimicrobial, anti-inflammatory, and immunomodulatory effects. Therefore, supplementation may prevent COPD exacerbations, particularly in deficient patients. We aimed to assess the effect of vitamin D supplementation on exacerbation rate in vitamin D-deficient patients with COPD. We performed a multicenter, double-blind, randomized controlled trial. COPD patients with ≥1 exacerbations in the preceding year and a vitamin D deficiency (15-50 nmol/L) were randomly allocated in a 1:1 ratio to receive either 16,800 International Units (IU) vitamin D3 or placebo once a week during 1 y. Primary outcome of the study was exacerbation rate. Secondary outcomes included time to first and second exacerbations, time to first and second hospitalizations, use of antibiotics and corticosteroids, pulmonary function, maximal respiratory mouth pressure, physical performance, skeletal muscle strength, systemic inflammatory markers, nasal microbiota composition, and quality of life. The intention-to-treat population consisted of 155 participants. Mean ± SD serum 25-hydroxyvitamin D [25(OH)D] concentration after 1 y was 112 ± 34 nmol/L in the vitamin D group, compared with 42 ± 17 nmol/L in the placebo group. Vitamin D supplementation did not affect exacerbation rate [incidence rate ratio (IRR): 0.90; 95% CI: 0.67, 1.21]. In a prespecified subgroup analysis in participants with 25(OH)D concentrations of 15-25 nmol/L (n = 31), no effect of vitamin D supplementation was found (IRR: 0.91; 95% CI: 0.43, 1.93). No relevant differences were found between the intervention and placebo groups in terms of secondary outcomes. Vitamin D supplementation did not reduce exacerbation rate in COPD patients with a vitamin D deficiency.This trial was registered at clinicaltrials.gov as NCT02122627.


Selective conservation of an E-protein gene promoter during vertebrate evolution.
The murine E-protein gene ME1 encodes a non-tissue-specific, helix-loop-helix transcription factor that is associated with morphological development. ME1 gene expression is regulated by a TATA-less promoter that contains multiple Sp1 consensus elements, E-boxes, and a novel transcription initiation site. In this study, we compared DNA homologous to the ME1 promoter from vertebrate species ranging from frog to human. A region of striking sequence similarity was identified in a region corresponding to the ME1 transcription initiation site (ME1 Inr). Within this region, a poly d(A) tract and a 9-bp inverted repeat (5'-GTCCGCCTG) were highly conserved in all species that were examined. Protein complexes that recognized these DNA elements were present among distant vertebrates (frog, chick, monkey and human), and were able to bend the ME1 Inr to a similar extent (approximately 60 degrees) as the previously described murine MBP alpha and MBP beta proteins. Collectively, these results suggest that an ME1 Inr-like element and its associated proteins functioned in an ancestral vertebrate more than 350 million years ago.


Effect of positive surgical margins at radical prostatectomy on cancer-specific mortality in high/very high-risk prostate cancer patients with Gleason Grade Group 4-5.
The effect of positive surgical margins (PSM) on cancer specific mortality (CSM) in high/very high-risk (HR/VHR) prostate cancer (PCa) with aggressive Gleason Grade Group (GGG) is unknown. We tested PSM effect on CSM in this setting, in addition to testing of radiotherapy (RT) benefit in PSM patients. We relied on Surveillance, Epidemiology, and End Results database (2010-2015), focusing on HR/VHR patients with exclusive GGG 4-5 at radical prostatectomy (RP). Kaplan-Meier plots and multivariable Cox regression models tested the relationship between PSM and CSM. Moreover, the effect of RT on CSM was explored in PSM patients. Of 3383 HR/VHR patients, 15.1% (n = 511) exhibited PSM. Patients with PSM harbored higher rates of GGG 5 (60.1% vs. 50.9%, p < 0.001), pathologic tumor stage T3a (69.1% vs. 45.2%, p < 0.001) and lymph node involvement (14.1% vs. 9.4%, p < 0.001), relative to patients without PSM. PSM rates decreased over time (2010-2015) from 16.0% to 13.6%. Seven-year CSM-free survival rates were 91.6% versus 95.7% in patients with and without PSM, respectively. In multivariable Cox regression models, PSM was an independent predictor of CSM (hazard ratio = 1.6, p = 0.040) even after adjustment for age, prostate specific antigen, pathologic tumor stage and lymph node status. Finally, in PSM patients, RT delivery did not reduce CSM in either univariable or multivariable Cox regression models. In HR/VHR PCa patients with exclusive GGG 4-5, PSM at RP adversely affect survival. Moreover, RT has no protective effect on CSM. In consequence, lowest possible PSM rates are crucial in such patients.


Functional Expression Profile of Voltage-Gated K(+) Channel Subunits in Rat Small Mesenteric Arteries.
Multiple K v channel complexes contribute to total K v current in numerous cell types and usually subserve different physiological functions. Identifying the complete compliment of functional K v channel subunits in cells is a prerequisite to understanding regulatory function. It was the goal of this work to determine the complete K v subunit compliment that contribute to functional K v currents in rat small mesenteric artery (SMA) myocytes as a prelude to studying channel regulation. Using RNA prepared from freshly dispersed myocytes, high levels of K v 1.2, 1.5, and 2.1 and lower levels of K v 7.4 α-subunit expressions were demonstrated by quantitative PCR and confirmed by Western blotting. Selective inhibitors correolide (K v 1; COR), stromatoxin (K v 2.1; ScTx), and linopirdine (K v 7.4; LINO) decreased K v current at +40 mV in SMA by 46 ± 4, 48 ± 4, and 6.5 ± 2 %, respectively, and K v current in SMA was insensitive to α-dendrotoxin. Contractions of SMA segments pretreated with 100 nmol/L phenylephrine were enhanced by 27 ± 3, 30 ± 8, and 7 ± 3 % of the response to 120 mmol/L KCl by COR, ScTX, and LINO, respectively. The presence of K v 6.1, 9.3, β1.1, and β1.2 was demonstrated by RT-PCR using myocyte RNA with expressions of K vβ1.2 and K v 9.3 about tenfold higher than K vβ1.1 and K v 6.1, respectively. Selective inhibitors of K v 1.3, 3.4, 4.1, and 4.3 channels also found at the RNA and/or protein level had no significant effect on K v current or contraction. These results suggest that K v current in rat SMA myocytes are dominated equally by two major components consisting of K v 1.2-1.5-β1.2 and K v 2.1-9.3 channels along with a smaller contribution from K v 7.4 channels but differences in voltage dependence of activation allows all three to provide significant contributions to SMA function at physiological voltages.


Butane-2,3-dionethiosemicarbazone: an oxime with antioxidant properties.
Oximes are compounds generally used to reverse the acetylcholinesterase (AChE) inhibition caused by organophosphates (OPs). The aim of this study was to examine the capacity of the butane-2,3-dionethiosemicarbazone oxime to scavenge different forms of reactive species (RS) in vitro, as well as counteract their formation. The potential antioxidant and toxic activity of the oxime was assayed both in vitro and ex vivo. The obtained results indicate a significant hydrogen peroxide (H2O2), nitric oxide (NO) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity at 0.275, 0.5 and 5microM of oxime, respectively (p< or =0.05). The oxime exhibited a powerful inhibitory effect on dihydroxybenzoate formation (25microM) (p< or =0.05) and also decreased deoxyribose degradation induced by Fe2+ and via Fenton reaction (0.44 and 0.66mM, respectively) (p< or =0.05). The oxime showed a significant inhibitory effect on sigma-phenantroline reaction with Fe2+ (0.4mM) suggesting a possible interaction between the oxime and iron. A significant decrease in the basal and pro-oxidant-induced lipid peroxidation in brain, liver, and kidney of mice was observed both in vitro and ex vivo (p< or =0.05). In addition, in our ex vivo experiments the oxime did not depict any significant changes in thiol levels of liver, kidney and brain as well as did not modify the delta-aminolevulinate dehydratase (delta-ALA-D) activity in these tissues. Taken together our results indicate an in vitro and ex vivo antioxidant activity of the oxime possibly due to its scavenging activity toward different RS and a significant iron interaction.


FGF2 disruption enhances thermogenesis in brown and beige fat to protect against adiposity and hepatic steatosis.
Fibroblast growth factor 2 (FGF2) has been reported to play divergent roles in white adipogenic differentiation, however, whether it regulates thermogenesis of fat tissues remains largely unknown. We therefore aimed to investigate the effect of FGF2 on fat thermogenesis and elucidate the underlying mechanisms. FGF2-KO and wild-type (WT) mice were fed with chow diet and high-fat diet (HFD) for 14 weeks. The brown and white fat mass, thermogenic capability, respiratory exchange ratio, and hepatic fat deposition were determined. In vitro experiments were conducted to compare the thermogenic ability of FGF2-KO- with WT-derived brown and white adipocytes. Exogenous FGF2 was supplemented to in vitro-cultured WT brown and ISO-induced beige adipocytes. The FGFR inhibitor, PPARγ agonist, and PGC-1α expression lentivirus were used with the aid of technologies including Co-IP, ChIP, and luciferase reporter assay to elucidate the mechanisms underlying the FGF2 regulation of thermogenesis. FGF2 gene disruption results in increased thermogenic capability in both brown and beige fat, supporting by increased UCP1 expression, enhanced respiratory exchange ratio, and elevated thermogenic potential in response to cold exposure. Thus, the deletion of FGF2 protects mice from high fat-induced adiposity and hepatic steatosis. Mechanistically, in vitro investigations indicated FGF2 acts in autocrine/paracrine fashions. Exogenous FGF2 supplementation inhibits both PGC-1α and PPARγ expression, leading to suppression of UCP1 expression in brown and beige adipocytes. These findings demonstrate that FGF2 is a novel thermogenic regulator, suggesting a viable potential strategy for using FGF2-selective inhibitors in combat adiposity and associated hepatic steatosis.


Myofibrillar protein composite gels: effect of esterified potato starch, lard and peanut oil on the gel properties.
Heat-induced composite gels were prepared with 20 g kg-1 myofibrillar protein (MP) sol, 20 g kg-1 modified starch and 100 g kg-1 lipid pre-emulsified by MP in 0.6 mol L-1 NaCl, at pH 6.2. The effects of esterified potato starch (EPS) and emulsified lipid (lard or peanut oil) on the rheology, texture properties and nuclear magnetic resonance characterization of MP gel were evaluated. The addition of starch and lipid significantly improved the gel strength and water holding capacity (WHC) of the MP gel. Analysis of the relaxation time compared with the WHC tests showed that the variation range of the transverse T22 relaxation time of a gel was positively proportional to changes in WHC of the composite gel, and the lower the T22 relaxation time, the better the WHC of composite gel. Moreover, MP gel with starch and emulsified lard added at the same time has the lowest T2 relaxation time, and also the best WHC of the gel. Environmental scanning electron microscopy showed that emulsified oil droplets embedded the gaps in the protein network, and the gelatinized starch contributed to restrict the oil droplet size, resulting in thicker MP gel. Emulsified lipid and modified starch have an important influence on the rheology and microstructure of MP gels, indicating the subtle interaction between starch, lipid and protein. The results suggest the potential feasibility of modified starch and vegetable oil to improve the textural properties in comminuted meat products. © 2021 Society of Chemical Industry.


The effect of short-term epidural local anesthetic blockade on urinary levels of substance P in interstitial cystitis.
We investigated the effect of epidural local anesthetic blockade on urinary substance P levels in five patients suffering from painful flare-ups of interstitial cystitis. Urine was collected in 24-h intervals commencing at the onset of an epidural bolus of 0.25% bupivacaine followed by maintenance epidural infusions of 0.05% bupivacaine. Substance P was measured by radioimmunoassay. After initiation of the epidural infusion, urinary substance P levels increased and then declined in all patients. All patients reported a decrease in pain intensity. We hypothesize that acute release, followed by depletion, of substance P from bladder sensory nerve endings accounts for the transient increase of peptide levels in urine and may contribute to the decrease in pain intensity during a 3-day epidural infusion. Substance P levels in urine initially increased and then declined in a series of 5 patients who achieved pain control by epidural local anesthetic infusion during a flare-up of interstitial cystitis.


Recommended method for indium-111 platelet survival studies. International Committee for Standardization in Hematology. Panel on Diagnostic Applications of Radionuclides.
Radioactive indium (111In) has been introduced as an alternative to 51Cr as a platelet label because of its shorter half-life, higher photon yield and greater affinity for platelets. Furthermore, platelet labelling with 111In is possible at lower platelet counts than with 51Cr. In healthy individuals, the kinetics of simultaneously injected 111In-labeled and 51Cr-labeled platelets are similar. The document describes the technical and analytic aspects of platelet survival determination with 111In-labeled platelets and is intended to supplement the previously published recommendations for platelet survival studies.


Cutaneous Melanoma Systematic Diagnostic Workflows and Integrated Reflectance Confocal Microscopy Assessed with a Retrospective, Comparative Longitudinal (2009-2018) Study.
The increasing global burden of melanoma demands efficient health services. Accurate early melanoma diagnosis improves prognosis. To assess melanoma prevention strategies and a systematic diagnostic-therapeutical workflow (improved patient access and high-performance technology integration) and estimate cost savings. Retrospective analysis of epidemiological data of an entire province over a 10-year period of all excised lesions suspicious for melanoma (melanoma or benign), registered according to excision location: reference hospital (DP) or other (NDP). A systematic diagnostic-therapeutical workflow, including direct patient access, primary care physician education and high-performance technology (reflectance confocal microscopy (RCM)) integration, was implemented. Impact was assessed with the number of lesions needed to excise (NNE). From 40,832 suspicious lesions excised, 7.5% (n = 3054) were melanoma. There was a 279% increase in the number of melanomas excised (n = 203 (2009) to n = 567 (2018)). Identification precision improved more than 100% (5.1% in 2009 to 12.0% in 2018). After RCM implementation, NNE decreased almost 3-fold at DP and by half at NDP. Overall NNE for DP was significantly lower (NNE = 8) than for NDP (NNE = 20), p < 0.001. Cost savings amounted to EUR 1,476,392.00. Melanoma prevention strategies combined with systematic diagnostic-therapeutical workflow reduced the ratio of nevi excised to identify each melanoma. Total costs may be reduced by as much as 37%.


Link between unmet need and economic status in Bangladesh: gap in urban and rural areas.
Unmet need for family planning (FP) is a core concept in designing FP programmes and reduction of unmet need for FP can improve reproductive and maternal health services. Bangladesh is still away from achieving the target regarding unmet need for FP. This study aimed to explore the composite effect of economic status and place of residence on unmet need for FP among currently married women of reproductive age in Bangladesh after controlling the effect of other selected covariates. The study used the data extracted from the Bangladesh Demographic and Health Survey (BDHS) 2017-2018, which is a nationally representative survey implemented using a stratified two-stage cluster sample design. A total of 13,031 currently married women of reproductive age were included in the final analysis. Binary logistic regression model has been employed to identify the factors influencing the unmet need for FP. Model-I investigated the effect of composite variable place-wealth on unmet need for FP and Model-II examined the effect of place-wealth on unmet need for FP after adjusting for the effect of other selected covariates. The Odds Ratios with p-values were reported to identify significant covariates. The rate of unmet need for FP was 15.48%. The composite factor of economic status and place of residence had significant influence on unmet need for FP in both models. Generally, rural women were significantly more likely to have unmet need for FP than their urban counterparts. In particular, women from rural areas and belong to rich families had the highest likelihoods of unmet need for FP. The other selected covariates also had significant influence on unmet need for FP. This study shows that rural women had higher odds of unmet need for FP than urban women. The healthcare providers and stakeholders should take necessary actions to motivate women to use contraceptive specially the women who are residing in the rural areas.


Rescue of terminally differentiating teratocarcinoma cells by fusion to undifferentiated parental cells.
A new clonal CBA mouse teratocarcinoma cell line called H6 grows rapidly without calcium in suspension culture. When attached to a gelatin-coated surface in the presence of calcium, differentiation to large flat cells, which secrete plasminogen activator, occurs after exposure to retinoic acid. Differentiation is terminal after about six cell divisions. H6 variants resistant to 6-thioguanine, 5-bromodeoxyuridine, ouabain, chloramphenicol, retinoic acid, or combinations thereof, have been isolated. Cell hybridizations were made between undifferentiated stem cells and the differentiated derivatives of H6. These experiments indicate that the undifferentiated cells can "rescue" cells in the initial stages of differentiation and that the signs of differentiation are soon lost in such hybrids. Hybridization without "rescue" may also occur, as suggested by small abortive colonies of large cells.


Delivery of messenger RNA using poly(ethylene imine)-poly(ethylene glycol)-copolymer blends for polyplex formation: biophysical characterization and in vitro transfection properties.
Nucleic acid based therapies have so far mainly been focused on plasmid DNA (pDNA), small interfering RNA (siRNA), antisense and immunostimulatory oligonucleotides. Messenger RNA (mRNA) was the subject of only a few studies. The objective of this investigation was the preparation of new composite polyplexes with mRNA consisting of poly(ethylene imine) (PEI) and poly(ethylene imine)-poly(ethylene glycol)-copolymers (PEI-PEG) as blends. These complexes were designed to increase the stability of mRNA, to improve transfection efficiency and to reduce cytotoxicity. Hydrodynamic diameters of the polyplexes were measured by dynamic light scattering, polyplex stability was analyzed by gel retardation assay and transfection efficiency of luciferase (Luc) encoding mRNA was evaluated under in vitro conditions. Most of the polyplexes generated showed small particle sizes <200 nm and positive zeta-potentials of +20 mV to +30 mV. Stable complexes were formed even at low nitrogen to phosphate ratios. Polyplexes with mRNA Luc and blends of low molecular weight PEI(5 kDa) and PEI(25k Da)-PEG(20 kDa)₁-block-copolymer showed protein expression as high as polyplexes with PEI(25 kDa). Moreover, luciferase expression was significantly higher than that obtained with one of the components alone. These results suggest that delivery systems for pulmonary application of mRNA merit further investigation under in vitro and in vivo conditions.


The impact of surgical trainee participation on sinus surgery outcomes.
To determine the effect of otolaryngology trainee participation on clinical outcomes in patients who undergo endoscopic sinus surgery (ESS) for chronic rhinosinusitis. Secondary analysis of prospectively collected data. Patients enrolled in a sinus surgery outcomes study between May 2011 and March 2013 were stratified into two groups--those who were operated on by an attending alone and those operated on by an attending with a trainee present (resident, fellow, or both). Patients completed quality of life (QOL) surveys including the Chronic Sinusitis Survey (CSS), 22-item Sino-Nasal Outcome Test (SNOT-22), and EuroQol 5-dimension survey preoperatively and 1 year postoperatively. Operative time, estimated blood loss (EBL), complication rates, and survey scores were compared between groups. The study population consisted of 452 patients. The attending alone (n = 119) and trainee (n = 333) groups were statistically comparable in terms of patient demographics, disease severity, and extent of surgery. Mean operative time was significantly shorter in the attending-alone group (80.0 vs. 90.6 minutes, P < .01). Mean EBL (105 mL attending vs. 117 mL trainee, P = .39) and complication rates (3.3% attending vs. 0.6% trainee, P = .07) were similar between groups. Observed changes in QOL measures following ESS were comparable between groups, although absolute improvement in the SNOT-22 scores (19.0 attending vs. 24.5 trainee, P = .05) did show a trend toward greater improvement in the trainee group. Trainee participation in ESS is associated with prolongation in surgical time; however, such participation was not found to adversely affect patient safety or clinical outcomes. 2b.


Serum tenascin-C discriminates patients with active SLE from inactive patients and healthy controls and predicts the need to escalate immunosuppressive therapy: a cohort study.
The aim of this study was to examine whether circulating levels of the proinflammatory glycoprotein tenascin-C (TNC) are useful as an activity-specific or predictive biomarker in systemic lupus erythematosus (SLE). Serum TNC levels were determined by enzyme-linked immunosorbent assay at inception visit in a prospective cohort of 59 SLE patients, and in 65 healthy controls (HC). SLE patients were followed for a mean of 11 months, disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) and British Isles Lupus Assessment Group disease activity index (BILAG-2004), clinical and laboratory data were recorded every 3-6 months, and changes in glucocorticoids (GC) and immunosuppressants (IS) were recorded serially. We examined cross-sectionally the relationships between serum concentrations of TNC and SLE status, SLEDAI-2 K scores, strata of disease activity, and levels of conventional biomarkers [anti-double-stranded DNA (dsDNA), anti-nucleosome antibodies, C3 and C4]. We also explored the utility of TNC levels for predicting disease flares, defined as (i) new/increased GC, (ii) new/increased GC or IS, and (iii) increase in SLEDAI by ≥3 or (iv) BILAG A or B flare. There was no significant difference in the mean levels of TNC between the SLE patients and HC. However, in SLE patients with active disease (SLEDAI ≥6), the TNC levels were significantly higher than in the HC (p = 0.004) or in patients with no/low disease activity (p = 0.004). In SLE patients, TNC levels were significantly associated with positivity of anti-dsDNA (p = 0.03) and anti-nucleosome antibodies (p = 0.008). Flares defined by a need to escalate immunosuppressive therapy were captured more frequently and earlier than flares defined by standard activity indices. Higher baseline levels of serum TNC presented a significantly greater risk of flare (i) [hazard ratio (HR) 1.39, 95% confidence interval (CI) 1.11-1.73] or (ii) (HR 1.25, 95% CI 1.02-1.52) but not of flares (iii) or (iv). The baseline serum TNC level was the single most important independent predictor of flare (i) compared with conventional biomarkers. TNC is not disease-specific, but it seems to indicate the activity of SLE and may predict the need to escalate immunosuppressive therapy. TNC levels may thus serve as a useful activity-specific and predictive biomarker in SLE.


Cerebral microemboli and brain injury during carotid artery endarterectomy and stenting.
Cerebral microembolic signals detected by transcranial Doppler are frequent during carotid angioplasty with stenting and carotid endarterectomy (CEA). Their potential harmful effects on the brain are, however, unclear. The aim of this study was to relate the frequency and type of per-procedural microembolic signals to procedure-related ipsilateral ischemic strokes and new ipsilateral ischemic lesions on diffusion-weighted cerebral MRI. Eighty-five patients who were prospectively treated with CEA (61) or carotid angioplasty with stenting (30) for high-grade (>/=70%) internal carotid artery stenoses were monitored during the procedures using multifrequency transcranial Doppler with embolus detection and differentiation. Pre- and postprocedural cerebral diffusion-weighted cerebral MRIs were performed on a subset of patients. Solid and gaseous microemboli were independently associated with procedure-related ipsilateral ischemic strokes (solid: P=0.027, gaseous: P=0.037) or new ipsilateral diffusion-weighted cerebral MRI lesions (solid: P=0.043, gaseous: P=0.026). Microembolic signals were detected during all procedures except one (CEA); 17% and 21% of all emboli were solid during carotid angioplasty with stenting and CEA, respectively. Patients undergoing carotid angioplasty with stenting had more solid (P<0.001) and gaseous (P<0.001) emboli and more new ipsilateral ischemic strokes (P=0.033) compared with patients undergoing CEA. Echolucent plaques (P=0.020) and preprocedural diffusion-weighted cerebral MRI ischemic lesions (P=0.002) were associated with increased numbers of solid emboli. Solid and gaseous microemboli were increased in patients with procedure-related ipsilateral ischemic strokes or new diffusion-weighted cerebral MRI lesions, which suggests that both solid and gaseous emboli may be harmful to the brain during CEA and carotid angioplasty with stenting.


Distribution of Essential and Toxic Elements in Pelecus cultratus Tissues and Risk Assessment for Consumer Health.
Nowadays, the problem of inland water pollution is acute. It is caused by vast industrial growth and agricultural intensification. Concentrations of Cd, Pb, Zn, Cu, Mn, Fe, Mg, and Kwere determined in the muscles, liver, and gonads sabrefish from Rybinsk Reservoir areas with different anthropogenic loads. The tissue samples were analyzed by atomic absorption spectrometry. Heavy metals accumulated more intensively in the body of fish from more polluted areas of the reservoir. Among the analyzed elements, the maximum accumulation levels were found for K, Zn, and Fe and the minimum levels were observed for Cd and Pb. The gonads contained the largest concentration of Cd and Mn, the muscles contained the highest concentrations of Mg, and the other elements mainly accumulated in the liver of sabrefish. The THQ and HI values for all elements did not exceed 1, which suggests that there is no potential non-carcinogenic risk to human health. The target values of carcinogenic risk (TR) for cadmium ranged from 8.32 × 10-6 to 1.22 × 10-4 in the muscles. The increased content of cadmium in the gonads of sabrefish not only poses a risk to human health, but also to the reproduction of this species in the Rybinsk Reservoir.


Radiological and clinical assessment of the distraction achieved with remotely expandable growing rods in early onset scoliosis.
Magnetically controlled growing rods (MCGR) allow controlled distraction of the immature spine for the treatment of early onset scoliosis. This study's primary aim was to determine the disparity between 'true' (TD) and 'intended' (ID) distraction. The secondary aim was to assess truncal growth and development during sequential lengthening. Twenty-one patients with a maximum follow up of 37 months were included in the study. Patients in the study underwent three monthly distractions. The amount of TD was determined by measuring the expansion gap on dedicated fluoroscopic images of the actuator. The total TD to date was compared to the ID measurement reported on the external adjustment device (EAD). Weight, sitting and standing heights were recorded at each distraction. The average number of three monthly distractions was 8. The true to intended distraction ratio was calculated as 0.33. Patients who had undergone previous surgery gained less distraction with a ratio of 0.30 compared to patients undergoing MCGR as a primary procedure with a ratio of 0.35. Weight, sitting and standing heights increased in all patients by an average of 3.1 kg, 2.3 and 5.2 cm per year. The Cobb angle following surgical correction was maintained in 19 of 21 patients at the latest follow-up. The TI ratio of 0.33 suggests that for every unit of distraction registered on the EAD approximately 33 % of true distraction occurs in vivo. Increases in sitting and standing heights were observed in all patients in the study.


The relationship to knobs of the 92,000 D protein specific for knobby strains of Plasmodium falciparum.
A 92,000 D protein was identified associated with the membrane of host erythrocytes infected with the FCB1 Plasmodium falciparum strain from Colombia. The same protein was identified in the knob-forming Gambian (and the Malayan Camp) strain, but was not present in all the corresponding knobless strains. In the FCB1 strain as well as in the FCR3 strain the protein is synthesized during the ring-stage period. The cleavage products of the 92,000 D protein were investigated by peptide mapping following limited proteolytic digestion with Staphylococcus aureus V8 protease. The 92,000 D protein cleavage products from both the Colombian and the Gambian strains were identical. Moreover, both the proteins were sensitive to trypsin and chymotrypsin and also to treatment with neuraminidase. Enzymatic removal of the protein from the erythrocyte membrane by trypsin or chymotrypsin did not affect parasite maturation. The merozoites thus produced were fully invasive and the morphology of the knobs was unaltered. When the erythrocyte membrane was treated with trypsin before the time of synthesis of the 92,000 D protein, it was not possible to identify the protein in membranes of later stages of infected erythrocytes, indicating that the protein cannot be inserted into the membrane cytoskeleton compartment. Knobs, however, were formed more or less normally, suggesting that it is not the accumulation of this protein which products the knobs.


Human Oligodendrocyte Myelination Potential; Relation to Age and Differentiation.
Myelin regeneration in the human central nervous system relies on progenitor cells within the tissue parenchyma, with possible contribution from previously myelinating oligodendrocytes (OLs). In multiple sclerosis, a demyelinating disorder, variables affecting remyelination efficiency include age, severity of initial injury, and progenitor cell properties. Our aim was to investigate the effects of age and differentiation on the myelination potential of human OL lineage cells. We derived viable primary OL lineage cells from surgical resections of pediatric and adult brain tissue. Ensheathment capacity using nanofiber assays and transcriptomic profiles from RNA sequencing were compared between A2B5+ antibody-selected progenitors and mature OLs (non-selected cells). We demonstrate that pediatric progenitor and mature cells ensheathed nanofibers more robustly than did adult progenitor and mature cells, respectively. Within both age groups, the percentage of fibers ensheathed and ensheathment length per fiber were greater for A2B5+ progenitors. Gene expression of OL progenitor markers PDGFRA and PTPRZ1 were higher in A2B5+ versus A2B5- cells and in pediatric A2B5+ versus adult A2B5+ cells. The p38 MAP kinases and actin cytoskeleton-associated pathways were upregulated in pediatric cells; both have been shown to regulate OL process outgrowth. Significant upregulation of "cell senescence" genes was detected in pediatric samples; this could reflect their role in development and the increased susceptibility of pediatric OLs to activating cell death responses to stress. Our findings identify specific biological pathways relevant to myelination that are differentially enriched in human pediatric and adult OL lineage cells and suggest potential targets for remyelination enhancing therapies. ANN NEUROL 2022;91:178-191.


Whole body magnetic resonance imaging (WB-MRI) and brain MRI baseline surveillance in TP53 germline mutation carriers: experience from the Li-Fraumeni Syndrome Education and Early Detection (LEAD) clinic.
Individuals with Li-Fraumeni syndrome (LFS) have a significantly increased lifetime cancer risk affecting multiple organ sites. Therefore, novel comprehensive screening approaches are necessary to improve cancer detection and survival in this population. The objective of this study was to determine the diagnostic performance of whole body MRI (WB-MRI) and dedicated brain MRI screening as part of a comprehensive screening clinic called Li-Fraumeni Education and Early Detection (LEAD) at MD Anderson Cancer Center. Adult (≥21 year old) and pediatric (<21 year old) patients were referred to the LEAD clinic by healthcare providers or self-referred and screened at 6 month intervals. During the study period, 63 LFS individuals were seen in the LEAD clinic including 49 adults (11 male, 38 female) and 14 children (7 male, 7 female). Fifty-three of 63 potentially eligible individuals underwent baseline WB-MRI (41 adults and 12 children) with primary tumors detected in six patients, tumor recurrence in one patient and cancer metastases in one patient. Thirty-five of 63 patients (24 adults and 11 children) underwent baseline brain MRI with primary brain tumors detected in three individuals, also noted on subsequent WB-MRI scans. Three additional tumors were diagnosed that in retrospect review were missed on the initial scan (false negatives) and one tumor noted, but not followed up clinically, was prospectively found to be malignant. The high incidence of asymptomatic tumors identified in this initial screening (13%), supports the inclusion of WB-MRI and brain MRI in the clinical management of individuals with LFS.


Learned end-to-end high-resolution lensless fiber imaging towards real-time cancer diagnosis.
Recent advances in label-free histology promise a new era for real-time diagnosis in neurosurgery. Deep learning using autofluorescence is promising for tumor classification without histochemical staining process. The high image resolution and minimally invasive diagnostics with negligible tissue damage is of great importance. The state of the art is raster scanning endoscopes, but the distal lens optics limits the size. Lensless fiber bundle endoscopy offers both small diameters of a few 100 microns and the suitability as single-use probes, which is beneficial in sterilization. The problem is the inherent honeycomb artifacts of coherent fiber bundles (CFB). For the first time, we demonstrate an end-to-end lensless fiber imaging with exploiting the near-field. The framework includes resolution enhancement and classification networks that use single-shot CFB images to provide both high-resolution imaging and tumor diagnosis. The well-trained resolution enhancement network not only recovers high-resolution features beyond the physical limitations of CFB, but also helps improving tumor recognition rate. Especially for glioblastoma, the resolution enhancement network helps increasing the classification accuracy from 90.8 to 95.6%. The novel technique enables histological real-time imaging with lensless fiber endoscopy and is promising for a quick and minimally invasive intraoperative treatment and cancer diagnosis in neurosurgery.


Patient dependence and longitudinal changes in costs of care in Alzheimer's disease.
To examine the incremental effect of patients' dependence on others, on cost of medical and nonmedical care, and on informal caregiving hours over time. Data are obtained from 172 patients from the Predictors Study, a large, multicenter cohort of patients with probable Alzheimer disease (AD) followed annually for 4 years in 3 University-based AD centers in the USA. Enrollment required a modified Mini-Mental State Examination score >or=30. We examined the effects of patient dependence (measured by the Dependence Scale, DS) and function (measured by the Blessed Dementia Rating Scale, BDRS) on medical care cost, nonmedical care cost, and informal caregiving time using random effects regression models. A one-point increase in DS score was associated with a 5.7% increase in medical cost, a 10.5% increase in nonmedical cost, and a 4.1% increase in caregiving time. A one-point increase in BDRS score was associated with a 7.6% increase in medical cost, a 3.9% increase in nonmedical cost and an 8.7% increase in caregiving time. Both functional impairment and patient dependence were associated with higher costs of care and caregiving time. Measures of functional impairment and patient dependence provide unique and incremental information on the overall impact of AD on patients and their caregivers.


Treatment with recombinant Hsp72 suppresses collagen-induced arthritis in mice.
Although the level of heat shock protein (Hsp72) has been shown to be enhanced in rheumatoid arthritis (RA) synovial tissues and RA synovial fluid, it remains unclear what role extracellular Hsp72 plays in the pathogenesis of RA. This study was conducted to investigate the effects of recombinant human Hsp72 on collagen-induced arthritis (CIA) when administered therapeutically and elucidate its underlying mechanism. We demonstrated that recombinant Hsp72 significantly reduced disease severity. Hsp72-treated animals displayed significantly less cartilage and bone destruction than that in the controls. Hsp72 treatment also reduced the expression of tumor necrosis factor alpha and interleukin 6 in the sera. Furthermore, Hsp72 treatment significantly inhibited activation of nuclear factor kappa B (NF-κB) in synovial tissues of CIA mice. These findings suggest that recombinant Hsp72 effectively suppressed synovial inflammation and the development and progress of CIA, which is mediated through the reduction of production of proinflammatory cytokines and the suppression of activation of NF-κB pathway.