Large herbivores trigger spatiotemporal changes in forest plant diversity.
Large herbivores can exert top-down control on terrestrial plant communities, but the magnitude, direction, and scale dependency of their impacts remain equivocal, especially in temperate and boreal forests, where multiple disturbances often interact. Using a unique, long-term, and replicated landscape experiment, we assessed the influence of a high density of white-tailed deer (Odocoileus virginianus) on the spatiotemporal dynamics of diversity, composition, and successional trajectories of understorey plant assemblages in recently logged boreal forests. This experiment provided a rare opportunity to test whether deer herbivory represents a direct filter on plant communities or if it mainly acts to suppress dominant plants, which, in turn, release other plant species from strong negative plant-plant interactions. These two hypotheses make different predictions about changes in community composition and alpha and beta diversity in different vegetation layers and at different spatial scales. Our results showed that deer had strong effects on plant community composition and successional trajectories, but the resulting impacts on plant alpha and beta diversity patterns were markedly scale dependent in both time and space. Responses of tree and non-tree vegetation layers were strongly asymmetric. Deer acted both as a direct filter and as a suppressor of dominant plant species during early forest succession, but the magnitude of both processes was specific to tree and non-tree vegetation layers. Although our data supported the ungulate-driven homogenization hypothesis, compositional shifts and changes of alpha diversity were poor predictors of beta diversity loss. Our findings underscore the importance of long-term studies in revealing nonlinear temporal community trends, and they challenge managers to prioritize particular community properties and scales of interest, given contrasting trends of composition and alpha and beta diversity across spatial scales.


Prevalence and distribution of Dirofilaria immitis in domestic dogs from Ankara and vicinity in Turkey.
A total of 280 dogs in Ankara and vicinity were examined from November 2000 through December 2001 by the PetChek antigen ELISA and polycarbonate filter-acid phosphatase histochemical staining techniques for Dirofilaria immitis infection. Dirofilaria immitis (heartworm) infection was found in 26 dogs (9.3%), all of which were kept always outdoors and non prophylacted by their owners. The distribution of heartworm infected dogs was not uniform. Infection with D. immitis was correlated with differences in age and sex. But, no significant association was found.


NKG2D contributes to efficient clearance of picornavirus from the acutely infected murine brain.
Activated murine cytotoxic T cells express the NKG2D natural cytotoxicity receptor. This receptor recognizes major histocompatibility complex (MHC) class I-like molecules expressed on the surface of infected cells and serves to augment T cell-mediated cytotoxicity. The role of NKG2D-mediated augmentation in the clearance of central nervous system viral infections has not been explored. Using the Theiler's murine encephalomyelitis virus model, the authors found that NKG2D-positive CD8+ cytotoxic T cells enter the brain, that NKG2D ligands are expressed in the brain during acute infection, and that interruption of NKG2D ligand recognition via treatment with a function-blocking antibody attenuates the efficacy of viral clearance from the central nervous system.


Regulation of chondrocyte proliferation through GIT1-Rac1-mediated ERK1/2 pathway by PDGF.
There are many growth factors contributing to fracture healing after bone fractures. Platelet-derived growth factor (PDGF) released from platelets is a factor promoting cell division and proliferation, and first appears around the sites of fractures. Culture of chondrocytes in vitro are stimulated by PDGF to proliferation, its presence being upregulated in the extracellular matrix of cartilage; the main components include aggrecan and type II collagen. PDGF induces the expression of G the protein-coupled receptor kinase interacting protein 1 (GIT1), promoting Rac1 and ERK1/2 phosphorylation. Both knocking down GIT1 expression by siRNA and blocking phosphorylation of Rac1 inhibit this induced proliferation of chondrocyte. GIT1 and Rac1 control each other, having a synergistic effect on activation of the ERK1/2 pathway. The results suggest that PDGF regulates chondrocyte proliferation through activation of ERK1/2 pathway by upregulation of GIT1 expression and Rac1 phosphorylation.


Effects of sexual/gender minority- and race-based enacted stigma on mental health and substance use in female assigned at birth sexual minority youth.
People of color who are also sexual and gender minorities (SGM) experience forms of enacted stigma based on both their racial/ethnic identity and their SGM status. We set out to test the effects of enacted stigma specific to race/ethnicity and SGM identity on mental health and substance use problems among female assigned at birth (FAB) SGM of color. Data come from a community-based sample of FAB SGM who also identified as racial/ethnic minorities (N = 352). The effects of racial discrimination, SGM victimization, and sexual orientation microaggressions on depression symptoms, anxiety symptoms, alcohol-related problems, and marijuana-related problems were tested using linear regression and negative binomial models. Enacted stigma based on both race/ethnicity and SGM status were significant predictors of mental health outcomes and alcohol-related problems within the same model, which suggested that both uniquely contributed to poorer health. There was little support for interactive effects between the multiple forms of enacted stigma. Marijuana-related problems were best explained by enacted stigma based on race/ethnicity only. Racially diverse FAB SGM are at unique risk of experiencing multiple forms of discrimination and aggression based on their minority identities that each contribute negatively to their wellbeing. Consideration of the multiple forms of enacted stigma they face is necessary for understanding health disparities in these populations. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Interaction of exogenous liposomal insulin-like growth factor-I cDNA gene transfer with growth factors on collagen expression in acute wounds.
Growth factors have been shown to modulate the complex cascade of wound healing, however, interaction between different growth factors during dermal and epidermal regeneration is still not entirely defined. We have recently shown that exogenous liposomal gene transfer of cDNA results in physiologic expression and response in an acute wound. In the present study we determined the interaction between insulin-like growth factor-I (IGF-I), a mesenchymal growth factor, administered as liposomal cDNA, with other dermal and epidermal growth factors on collagen synthesis in an acute wound. Sprague-Dawley rats were given a scald burn to inflict an acute wound and divided into two groups to receive weekly subcutaneous injections of liposomes plus a beta-galactosidase containing plasmid (Lac Z [0.2 microg, vehicle]), or liposomes plus the IGF-I cDNA containing plasmid (2.2 microg) and Lac Z (0.2 microg). Immunological assays, histological and immunohistochemical techniques were used to determine growth factor concentration and different types of collagen (I, III, and IV) after IGF-I cDNA gene transfer. IGF-I cDNA transfer accelerated reepithelization and was associated with increased levels of IGF-I, fibroblast growth factor, keratinocyte growth factor, vascular endothelial cell growth factor, and platelet-derived growth factor protein expression. IGF-I cDNA had no effect on transforming growth factor-beta. IGF-I cDNA significantly increased type IV collagen while it had no effect on types I and III collagen. Exogenously administered IGF-I cDNA increased protein concentrations of keratinocyte growth factor, fibroblast growth factor, platelet-derived growth factor, and type IV collagen. We conclude that liposomal IGF-I gene transfer can accelerate wound healing without causing an increase in types I and III collagen expression.


Small cell osteosarcoma: clinicopathologic, immunohistochemical, and molecular analysis of 36 cases.
Small round cell osteosarcoma is a very rare type of osteosarcoma, histologically mimicking other small round cell malignancies of bone, most notably Ewing sarcoma. To distinguish small cell osteosarcoma from other primary small cell malignancies of bone, we evaluated the immunohistochemical (IHC) expression of CD99 and SATB2, a marker of osteoblastic differentiation. Second, we analyzed EWSR1 and FUS gene aberrations using fluorescence in situ hybridization and/or reverse transcription-polymerase chain reaction (RT-PCR) techniques to assess whether small cell osteosarcoma and Ewing sarcoma share the same genetic alteration analysis. Thirty-six cases of primitive small cell osteosarcoma of bone were included in this study. All the cases of small cell osteosarcoma showed strong nuclear expression of SATB2 associated with negativity for CD99 antibody or weak, cytoplasmic staining in few neoplastic cells. Reverse transcription-polymerase chain reaction was negative for EWS-FLI1 type 1-2, EWS-ERG type 1, and CIC-DUX4 in the 10 available cases of small cell osteosarcoma analyzed. Fluorescence in situ hybridization analysis was feasible with a readable signal in 13 cases of small cell osteosarcoma, and none of these cases showed any EWSR1 and FUS gene rearrangements. In conclusion, it appears extremely useful to combine IHC analysis of SATB2 and CD99 with molecular analysis of Ewing sarcoma-associated genetic aberrations, to differentiate small cell osteosarcoma from other small round cell malignancies of bone. The strong IHC expression of SATB2 associated with CD99 immunonegativity and the absence of EWSR1 and FUS gene rearrangements in small cell osteosarcoma argues against the existence of a morphologic/genetic continuum with Ewing sarcoma.


[Methodic recommendations for the determination of whole body protein synthesis rates in tracer studies].
Methodical recommendations are suggested--predominantly for laboratory and small animals (rats and young chickens)--for the determination of parameters of the protein metabolism of the whole body after single doses of a mixture of 15N labelled amino acids by means of the determination of the temporal course of cumulative 15N excretion in urine and the assessment of the tracer kinetic data in a compartment model. These recommendations are to make it possible to carry out purposefully such experiments under comparable conditions. The advantages of this method are: the non-invasive character of the method; the possibility of repeating the experiment with the same animal; the adaptability to other methods of investigation (e.g. measuring energy metabolism); the relatively low expenditure of labour and requirement of test animals; the relatively good reproducibility of the method. Thus this method is a good supplement to the flooding and permanent infusion methods and should be used wherever the determination of parameters of the protein metabolism of the total body is sufficient.


TOM: a web-based integrated approach for identification of candidate disease genes.
The massive production of biological data by means of highly parallel devices like microarrays for gene expression has paved the way to new possible approaches in molecular genetics. Among them the possibility of inferring biological answers by querying large amounts of expression data. Based on this principle, we present here TOM, a web-based resource for the efficient extraction of candidate genes for hereditary diseases. The service requires the previous knowledge of at least another gene responsible for the disease and the linkage area, or else of two disease associated genetic intervals. The algorithm uses the information stored in public resources, including mapping, expression and functional databases. Given the queries, TOM will select and list one or more candidate genes. This approach allows the geneticist to bypass the costly and time consuming tracing of genetic markers through entire families and might improve the chance of identifying disease genes, particularly for rare diseases. We present here the tool and the results obtained on known benchmark and on hereditary predisposition to familial thyroid cancer. Our algorithm is available at http://www-micrel.deis.unibo.it/~tom/.


Opioid prescribing for patients with cancer in the last year of life: a longitudinal population cohort study.
We linked UK cancer registry data with the corresponding electronic primary care medical records of 6080 patients who died of cancer over a 7-year period in a large United Kingdom city. We extracted all prescriptions for analgesics issued to each patient in the linked cohort during the 12 months before death and analysed the extent and duration of strong opioid treatment with clinical and patient characteristics. Strong opioids were prescribed for 48% of patients in the last year of life. Median interval between first prescription of a strong opioid and death was 9 weeks (interquartile range 3-23). Strong opioid prescribing was not influenced by cancer type, duration of illness, or gender but was adversely influenced by older age. Compared with patients who died in a hospice, those who died in a hospital were 60% less likely to receive a strong opioid in primary care before admission (relative risk ratio 0.4, CI 0.3-0.5, P < 0.01). The study provides the first detailed analysis of the relatively late onset and short duration of strong opioid treatment in patients with cancer before death in a representative UK cohort. This pattern of prescribing does not match epidemiological data which point to earlier onset of pain. Although persistent undertreatment of cancer pain is well documented, this study suggests that strategies for earlier pain assessment and initiation of strong opioid treatment in community-based patients with cancer could help to improve pain outcomes.


Effects of reduced milk intake on lymphocytes of neonatal rats.
Prolactin (PRL) is an immunoregulatory molecule. We previously reported that milk-PRL passes to the circulation of the neonatal rat and plays a role in neonatal immune system maturation. Neonatal rats that had ingested PRL-poor milk (bromocriptine treatment of the dam) from days 2-5 of life, showed changed patterns of immune system development. In order to rule out the possibility that these changes were due to reduced milk intake rather than to milk-PRL, in this current study we varied neonatal milk intake by adjusting litter size to 6 or 12 pups. At day 10, splenocytes and thymocytes were: 1. tested for in vitro proliferation to the mitogens phytohemagglutinin or to concanavalin A; 2. stained with monoclonal antibodies to surface differentiation antigens and analyzed by flow cytometry. We found that reduced milk intake (litter size of 12) led to decreased mitogen responsiveness, the opposite of what was seen after ingestion of PRL-poor milk. However, a reduction in milk had no significant affect on expression of surface differentiation antigens. Therefore, the changes in neonatal immune development following ingestion of PRL-poor milk cannot be attributed to a decrease in total milk volume.


The application and efficacy of combined neurofeedback therapy and imagery training in adolescents with Tourette syndrome.
We aimed to examine the effectiveness of combined neurofeedback therapy and imagery training in adolescent patients with refractory Tourette syndrome. Two patients, aged respectively 14 and 16 years, had been treated with haloperidol and tiapride; however, this medication was ineffective and accompanied by intolerable side effects. In this study, the patients completed 80 sessions of neurofeedback treatment followed by imagery training. The patients were assessed with behavior rating scales both before and after the treatment as well as during follow-up examinations to evaluate the effect of the combined therapy. Patients showed significant improvement in motor tic and vocal tic symptoms, exemplified by a reduction in the frequency and intensity of tics, indicating that neurofeedback, together with imagery training, has a positive therapeutic effect on adolescent patients with medication-refractory Tourette syndrome.


Neuronal ensembles sufficient for recovery sleep and the sedative actions of α2 adrenergic agonists.
Do sedatives engage natural sleep pathways? It is usually assumed that anesthetic-induced sedation and loss of righting reflex (LORR) arise by influencing the same circuitry to lesser or greater extents. For the α2 adrenergic receptor agonist dexmedetomidine, we found that sedation and LORR were in fact distinct states, requiring different brain areas: the preoptic hypothalamic area and locus coeruleus (LC), respectively. Selective knockdown of α2A adrenergic receptors from the LC abolished dexmedetomidine-induced LORR, but not sedation. Instead, we found that dexmedetomidine-induced sedation resembled the deep recovery sleep that follows sleep deprivation. We used TetTag pharmacogenetics in mice to functionally mark neurons activated in the preoptic hypothalamus during dexmedetomidine-induced sedation or recovery sleep. The neuronal ensembles could then be selectively reactivated. In both cases, non-rapid eye movement sleep, with the accompanying drop in body temperature, was recapitulated. Thus, α2 adrenergic receptor-induced sedation and recovery sleep share hypothalamic circuitry sufficient for producing these behavioral states.


Association of tic disorders with poor academic performance in central Spain: a population-based study.
To analyze the association between tic disorders and poor academic performance in school-aged children. This was a cross-sectional, observational study conducted in a randomly selected sample of mainstream school-aged children (aged 6-16 years). The sampling frame included different types of schools and educational levels. Children with poor academic performance (eg, repeating a grade, special needs), and tic disorders (defined based on Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision criteria) were identified. Children with and without tics and children with and without poor academic performance were compared in terms of clinical features (ie, medical history and neurologic and psychiatric comorbidities), school, and environmental characteristics. Logistic regression analyses were performed using school performance (dependent variable) and tic disorders (independent variable), after adjusting for confounding variables. The study cohort comprised 1867 children (mean age, 10.9 + 2.9 years; 1007 males [53.9%]). Tics were present in 162 children (8.6%), and poor academic performance was noted in 223 (11.9%). Overall poor academic performance was associated with age (OR, 1.71; P < .0001), television viewing (OR, 5.33; P = .04), attention deficit hyperactivity disorder (OR, 1.38; P < .0001), and family history of school dysfunction (OR, 2.43; P = .02) and was negatively associated with higher IQ score (OR, 0.90; P < .0001) and tic disorders (OR, 0.29; P = .01). After adjusting for other covariates, the presence of tic disorders was not associated with poor academic performance in our cohort. Early academic support and modification of environmental characteristics are needed for children at higher risk for school dysfunction, to enhance academic performance.


Congenital aortic stenosis: a novel technique for ventricular pacing during valvuloplasty.
The main objective of this study is to describe a new technique for rapid ventricular pacing to maintain balloon stability during balloon aortic valvuloplasty (BAV) without using transvenous temporary pacemaker electrode. The safety and efficacy of rapid right ventricular pacing to facilitate balloon stability during BAV has been previously reported. However, it necessitates an additional femoral venous access, an additional sheath, and a temporary pacemaker electrode. This was a prospective pilot study. Rapid ventricular pacing was performed through back-up guidewires inserted into the left ventricle for balloon advancement and by an adhesive patch placed on the back of the patient. The technique was performed during BAV procedure in all of 15 consecutive children diagnosed as congenital aortic stenosis. Pacing was performed at a rate decreasing systolic aortic pressure to the point of 40-50% of baseline. The technique was successful in all patients. Effective capture, stable pacing, and balloon stability were achieved in all children using very low outputs. No sustained arrhythmias or other procedure-related complications occurred. Mean aortic valve gradient decreased from 68.5 +/- 20.4 mm Hg to 20.4 +/- 10.2 mm Hg. Degree of aortic regurgitation progressed from grade 0 to 1 in three patients and remained unchanged in 12 patients. This study demonstrated that back-up guidewires can be used effectively and safely for pacing during BAV procedures. This technique omits probable complications related to a second vascular access and may shorten the procedure time and decreases costs by eliminating the use of an additional sheath and a temporary pacemaker electrode.


Generalized eta and omega squared statistics: measures of effect size for some common research designs.
The editorial policies of several prominent educational and psychological journals require that researchers report some measure of effect size along with tests for statistical significance. In analysis of variance contexts, this requirement might be met by using eta squared or omega squared statistics. Current procedures for computing these measures of effect often do not consider the effect that design features of the study have on the size of these statistics. Because research-design features can have a large effect on the estimated proportion of explained variance, the use of partial eta or omega squared can be misleading. The present article provides formulas for computing generalized eta and omega squared statistics, which provide estimates of effect size that are comparable across a variety of research designs.


Kaolinite in pharmaceutics and biomedicine.
Kaolinite Al2Si2O5(OH)4 is an abundant and inexpensive geomaterial regarded as one of the most common clay minerals in the earth's crust and the most widespread phase among the other kaolin polymorphs (halloysite, dickite and nacrite). Structurally, it is a hydrous aluminum phyllosilicate member belonging to the dioctahedral 1:1 kaolin mineral group. The particle size of the pseudohexagonal kaolinite platelets is normally <2μm (if compared to a human red blood cell of a typical diameter 6.2-8.2μm or to a virus particle of about 50nm diameter). The kaolinite platelets, either stacked together with a common booklet-like shape in a highly ordered structure (well crystallized) or disordered structure (poorly crystallized), consist of layers considered as a strong dipole of hydrophobic siloxane surface dominated by negative charges, and the other hydrophilic aluminol surface carries positive charges. Kaolinite has been used in many pharmaceutical applications as excipient or active ingredient, because it exhibits excellent physical, chemical and surface physicochemical properties. In addition to their classical pharmaceutical uses, kaolinite and its derivatives have been recently considered as a promising material in many biomedical innovation areas such as drug, protein and gene delivery based on the high interaction capacities with organic and biochemical molecules, bioadhesion and cellular uptake. Pharmaceutical kaolin grades are considerably demanded for usage as excipient in formulations of solid and semi-solid dosage forms. The most important functionalities of kaolin used as excipient are reported as diluent, binder, disintegrant, pelletizing and granulating, amorphizing, particle film coating, emulsifying and suspending agent. Because of its uninjured bioactivity, kaolinite has been also used as active agent for treatment of some common diseases. It can be topically administered as hemostatic agent, dermatological protector, anti-inflammatory agent and in pelotherapy, or orally as gastrointestinal protector, and antibacterial, antiviral, detoxification or antidiarrheal agent. With these premises, the future of kaolinite in health-care uses is strongly interesting, especially in the development of pharmaceutical and cosmetic industries. In biomedicinal investigations, it can be considered as a promising natural geomaterial for designing new derivatives that can contribute in the trials of discovering new therapeutic systems and treatment pathways of global challenge diseases such as cancer, viruses, antibiotic resistant bacteria, alzheimer, chronic skeletomuscular and geriatric diseases.


Integrative taxonomy of Serrasentis gibsoni n. sp. (Acanthocephala: Isthmosacanthidae) from flatfishes in the Gulf of Mexico.
The Isthmosacanthidae acanthocephalan species of the genus Serrasentis are parasites of marine teleosts and an elasmobranch. In this study, Serrasentis gibsoni n. sp. is described from the intestines of four flatfish species (Paralichthyidae), namely Ancyclopsetta quadrocellata, Cyclopsetta chittendeni, Syacium gunteri, and S. papillosum from 10 oceanic sites in the Gulf of Mexico (GoM). Twenty sequences of the 'barcoding' region of cytochrome C oxidase subunit I gene were obtained from 20 adults of Serrasentis gibsoni n. sp. Additionally, five sequences of the barcoding region were obtained from five adults of rhadinorhynchid Gorgorhynchus lepidus from C. chittendeni, S. papillosum and one species of Haemulidae, Haemulom aurolineatum, from five oceanic sites from the GoM. Two phylogenetic approaches were followed: Bayesian inference and maximum likelihood. In both phylogenetic reconstructions, the sequences of Serrasentis gibsoni n. sp. were recovered as a monophyletic group within the genus Serrasentis and placed as a sister group to G. lepidus. However, due to the lack of molecular data for species of the Isthmosacanthidae and Rhadinorhynchidea, these phylogenetic inferences must be taken with caution. Serrasentis gibsoni n. sp. is the first species of Serrasentis described from Paralichthyidae flatfish species from marine waters of the Americas and from the GoM. Based on the barcoding data set analyzed, Serrasentis gibsoni n. sp. appears to have high intraspecific genetic variation; thus, it is necessary to continue exploring the genetic diversity of this species to infer its intraspecific evolutionary patterns.


The conserved C-terminal I/LWEQ module targets Talin1 to focal adhesions.
The cytoskeletal protein Talin1 is a critical link between integrins and the actin cytoskeleton, where it is required for the structural and signaling functions of integrin-containing adhesion complexes. However, the elements in Talin1 that are responsible for localizing it to adhesion complexes are not known. In this report we have used a series of constructs based on the modular structure of Talin1 to determine the structural elements that specify the subcellular localization of Talin1. We show that the conserved actin-binding I/LWEQ module at the C-terminus of Talin1 is necessary and sufficient for targeting to focal adhesion complexes. We also used truncation and site-directed mutagenesis to demonstrate that this novel targeting function correlates with, but is separable from, the actin-binding properties of the Talin1 I/LWEQ module. In addition, we have shown that focal adhesion targeting, unlike actin binding, is not conserved among I/LWEQ module proteins. Finally, we have demonstrated that the subcellular localization of the Talin1 I/LWEQ module is regulated by an intrasteric interaction with an upstream alpha-helix, suggesting that both the actin binding and adhesion-targeting elements are masked in full-length Talin1. Our results define a novel role for the I/LWEQ module as the primary adhesion-complex targeting determinant of Talin1 and suggest that pathways that can relieve inhibition of I/LWEQ module function will be important for regulating the structural and signaling properties of adhesion complexes.


Memorable objects are more susceptible to forgetting: Evidence for the inhibitory account of retrieval-induced forgetting.
Retrieval of target information can cause forgetting for related, but non-retrieved, information - retrieval-induced forgetting (RIF). The aim of the current studies was to examine a key prediction of the inhibitory account of RIF - interference dependence - whereby 'strong' non-retrieved items are more likely to interfere during retrieval and therefore, are more susceptible to RIF. Using visual objects allowed us to examine and contrast one index of item strength -object typicality, that is, how typical of its category an object is. Experiment 1 provided proof of concept for our variant of the recognition practice paradigm. Experiment 2 tested the prediction of the inhibitory account that the magnitude of RIF for natural visual objects would be dependent on item strength. Non-typical objects were more memorable overall than typical objects. We found that object memorability (as determined by typicality) influenced RIF with significant forgetting occurring for the memorable (non-typical), but not non-memorable (typical), objects. The current findings strongly support an inhibitory account of retrieval-induced forgetting.


[Screening for cancer: what's new?].
Setting up of screening programmes for cancers has been the result of evaluation studies but even more of the existence (or non existence) of national policies for cancer control. We know for sure that mammographic screening can reduce breast cancer mortality in women from age 50 onwards, smear screening has a favourable impact on cervical cancer mortality and incidence, and faecal blood testing in stools may reduce colon cancer mortality. Other questions, considered for a long time as settled, are coming back, either because new data are available, such as in screening for breast cancer before age 50, or because new screening methods are being proposed, such as for lung cancer. Finally, the recognition of populations at very high genetic risk makes necessary the search for answers for example for familial breast and/or ovarian cancer. Last but not least is the methodological challenge: how can we rapidly provide answers, which implies the need for new approaches, in addition to randomized controlled trials?


Understanding challenges to medical and dental student research practices. An insight from a cross-sectional study of the public sector in Pakistan.
The objective of the study is to identify and comprehend the challenges experienced by the undergraduate medical and dental students in enrolled in public sector in Pakistan while conducting research. A cross-sectional study was carried out from April to June of 2023 among undergraduate students at public sector medical and dental schools in Khyber Pakhtunkhwa, Pakistan. A customized questionnaire was developed to gather information on the challenges faced by students when undertaking research. The survey was circulated online using Google Forms, and participation was entirely optional. Descriptive statistics were used to analyse the responses. Participants in the study were 58 male and 139 female students who were enrolled in the Bachelor of Medicine & Bachelor of Surgery (MBBS) and Bachelor of Dental Surgery (BDS) programs. The analysis found that 47% of students cited a lack of knowledge and research skills as a major barrier, while 40% cited time restrictions as a major issue. Mentorship and training issues were cited as major barriers by 51% of students, while a lack of institutional support was cited as a significant issue by 53% of students. Language issues made it difficult to produce research papers for 14% of students, while finding research opportunities was challenging for 38% of students. According to the research, undergraduate medical and dentistry students in the public sector encountered a number of challenges when conducting research. It was suggested that these issues be resolved by include research projects in the curriculum, providing specific interventions for enhancing research skills, establishing mentorship programs, and allocating funds for research activities.


Effects of Tribulus terrestris L. on Sport and Health Biomarkers in Physically Active Adult Males: A Systematic Review.
Tribulus terrestris L. (TT) is a plant used in traditional Chinese medicine, Ayurvedic medicine, and sports nutrition to improve health and performance. However, no conclusive evidence exists about the potential beneficial effects of TT on sport and health biomarkers in physically active adults. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the modified McMaster Critical Review Form for methodological quality assessment, we systematically reviewed studies indexed in Web of Science, Scopus, and PubMed, to assess the effects of TT on immunological, hematological, biochemical, renal, lipidic, hormonal behavior, and anti-inflammatory response in physically active adult males. Among 340 records identified in the search, a total of 7 studies met the inclusion and exclusion criteria. Overall, participants supplemented with TT displayed significant improvements in lipid profile. Inflammatory and hematological biomarkers showed moderate beneficial effects with no significant changes on renal biomarkers. No positive effects were observed on the immune system response. Additionally, no TT-induced toxicity was reported. In conclusion, there was no clear evidence of the beneficial effects of TT supplementation on muscle damage markers and hormonal behavior. More studies are needed to confirm the benefits of TT due to the limited number of studies available in the current literature.


Treatment of patients with achalasia with botulinum toxin: a multicenter prospective cohort study.
Botulinum toxin (BT) injection is an alternative treatment of achalasia. The aim of the study was to examine outcomes of patients treated with BT in the Czech Republic. Since 1997, 49 patients with achalasia have been treated with BT. We prospectively evaluated the effect of BT injection on 41 patients during a median follow-up of 24 months (range 9-62). Esophageal manometry was performed before and at 3-5 months after the injection. In 16 patients, BT was injected from the antegrade angle only (subgroup A), in 15 patients, BT was injected from both retrograde and antegrade angles (subgroup B) and, in 10 patients, BT injection was combined with subsequent balloon dilatation (subgroup C). Immediate clinical response was achieved in 93% of patients. Clinical remission was sustained beyond 3 months in 83% of patients (responders). Fourteen responders (41%) did not experience a relapse during the median of 22 months. Twenty responders (59%) experienced symptomatic relapse approximately 8 months after the injection. Ten relapsers underwent BT reinjection, five (50%) of them were asymptomatic for another 14 months. The remaining five (50%) patients reported a second relapse approximately 6 months after the reinjection. Median duration of the symptom-free period was 11.5 months after the first BT injection, and 10.5 months after the second (P = 0.21). We did not find any significant predictor of a favorable outcome; responders tended to be older and to have a lower basal lower-esophageal-sphincter pressure. Patients in subgroup C were more likely to be in remission at 1 and 2 years as compared with patients in subgroup A. BT injection is an effective treatment of achalasia in the short term. However, almost 70% of patients experience a relapse within 2 years. BT injection should therefore be reserved for patients at risk for more invasive procedures or for patients who prefer this treatment.


A comparison of skeletal, dentoalveolar and soft tissue characteristics in white and black Brazilian subjects.
This study aimed to compare skeletal, dentoalveolar and soft tissue characteristics in white and black Brazilian subjects presenting normal occlusions. The sample comprised the lateral cephalograms of 106 untreated Brazilian subjects with normal occlusion, divided into two groups: Group 1- 50 white subjects (25 of each gender), at a mean age of 13.17 years (standard deviation 1.07); and Group 2- 56 black subjects (28 of each gender), at a mean age of 13.24 years (standard deviation 0.56). Variables studied were obtained from several cephalometric analyses. Independent t tests were used for intergroup comparison and to determine sexual dimorphism. black subjects presented a more protruded maxilla and mandible, a smaller chin prominence and a greater maxillomandibular discrepancy than white subjects. Blacks presented a more horizontal craniofacial growth pattern than whites. Maxillary and mandibular incisors presented more protruded and proclined in black subjects. The nasolabial angle was larger in whites. Upper and lower lips were more protruded in blacks than in whites. The present study found a bimaxillary skeletal, dentoalveolar and soft tissue protrusion in black Brazilian subjects compared to white Brazilian subjects, both groups with normal occlusion. Upper and lower lips showed to be more protruded in blacks, but lip thickness was similar in both groups.


Clinical utility of noncontrast computed tomography attenuation value (hounsfield units) to differentiate adrenal adenomas/hyperplasias from nonadenomas: Cleveland Clinic experience.
Radiological characterization of an adrenal tumor as adenoma may decrease the need for follow-up imaging studies, biopsies, and unnecessary adrenalectomies. We retrospectively reviewed 299 adrenalectomies in 290 patients at Cleveland Clinic Foundation over a recent 5-yr period to assess the value of noncontrast Hounsfield units (HU) in characterizing whether an adrenal mass is adenoma or nonadenoma. The mean (+/- SD) HU value for the adrenocortical adenoma/hyperplasia group was 16.2 +/- 13.6 and significantly lower (P < 0.0001) than primary adrenocortical cancers (36.9 +/- 4.1), metastases (39.2 +/- 15.2), and pheochromocytomas (38.6 +/- 8.2). The sensitivity and specificity for 10- and 20-HU cutoff values to differentiate adenomas/hyperplasias from nonadenomas were 40.5 and 100% and 58.2 and 96.9%, respectively. The size of the adrenal tumor had less value with only 40.7 and 81.3% sensitivity and 94.7 and 61.4% specificity for 2- and 4-cm cutoff values. A combination of less than or equal to 4-cm adrenal mass size and noncontrast computed tomography HU less than or equal to 20 had 42.1% sensitivity and 100% specificity. Our study, the largest with surgical histopathology as the gold standard for diagnosis, supports a noncontrast computed tomography attenuation value of 10 HU as a safe cutoff value to differentiate adrenal adenomas/hyperplasias from nonadenomas.


Pressure induces major changes in the nature of Americium's 5f electrons.
Americium occupies a pivotal position in the actinide series with regard to the behavior of 5f electrons. High-pressure techniques together with synchrotron radiation have been used to determine the structural behavior up to 100 GPa. We have resolved earlier controversial findings regarding americium and find that our experimental results are in discord with recent theoretical predictions. We have two new findings: (1) that there exists a critical, new structural link between americium under pressure and its near neighbor, plutonium; and (2) that the 5f electron delocalization in americium occurs in two rather than one step.


A novel combined thermometric and amperometric biosensor for lactose determination based on immobilised cellobiose dehydrogenase.
A novel method for lactose determination in milk is proposed. It is based on oxidation of lactose by cellobiose dehydrogenase (CDH) from the basidiomycete Phanerochaete chrysosporium, immobilised in an enzyme reactor. The reactor was prepared by cross-linking CDH onto aminopropyl-silanised controlled pore glass (CPG) beads using glutaraldehyde. The combined biosensor worked in flow injection analysis (FIA) mode and was developed for simultaneous monitoring of the thermometric signal associated with the enzymatic oxidation of lactose using p-benzoquinone as electron acceptor and the electrochemically generated current associated with the oxidation of the hydroquinone formed. A highly reproducible linear response for lactose was obtained between 0.05 mM and 30 mM. For a set of more than 500 samples an R.S.D. of less than 10% was achieved. The assay time was ca. 2 min per sample. The sensor was applied for the determination of lactose in dairy milk samples (milk with a fat content of 1.5% or 3% and also "lactose free" milk). No sample preparation except dilution with buffer was needed. The proposed method is rapid, suitable for repeated use and allows the possibility to compare results from two different detection methods, thus providing a built-in quality assurance. Some differences in the response observed between the methods indicate that the dual approach can be useful in mechanistic studies of redox enzymes. In addition, a dual system opens up interesting possibilities for studies of enzyme properties and mechanisms.


An Association Between Large Optic Nerve Cupping and Cognitive Function.
To determine if a larger cup-to-disc ratio is associated with poor cognitive function in postmenopausal women without glaucoma or ocular hypertension. We used data from the Women's Health Initiative (WHI) hormone trial, originally designed to test effects of hormone therapy (HT) on various health outcomes. Large cup-to-disc ratio was defined as greater than 0.6 in either eye based on stereoscopic optic nerve photographs. Global cognitive function was assessed annually by Modified Mini-Mental State Examination (3MSE) in the WHI Memory Study. Exclusions were no information on optic nerve grading; no 3MSE scores at the time of the eye examination, ocular hypertension (intraocular pressure >23 mm Hg, Goldmann applanation tonometry), or glaucoma medication use. A generalized linear model for log-transformed 3MSE scores was used for determining the association between large cup-to-disc ratio and 3MSE scores, adjusting for age, race, diabetes, body mass index, cardiovascular disease, smoking, HT randomization, education, and diabetic retinopathy. Analyses included 1636 women (mean age ± standard deviation, 69.57 ± 3.64 years; 90.39% white). Of those, 122 women had large cup-to-disc ratio. The mean 3MSE scores in women with vs without large cup-to-disc ratio were 95.4 ± 6 vs 96.6 ± 5. In the adjusted model, women with large cup-to-disc ratio had statistically significantly lower 3MSE scores, compared with those without large cup-to-disc ratio, yielding the predicted mean difference in 3MSE scores of 0.75 with a standard error of 0.05 units (P = .04). Postmenopausal women who had large cup-to-disc ratio without glaucoma or ocular hypertension exhibited lower global cognitive function. Further investigation is warranted. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.


Biomimetic Inspired Hydrogels for Regenerative Vertebral Body Stenting.
This review aims to explore the potential of biomimetic hydrogels as an alternative to bone cement in vertebral body stenting (VBS), a minimally invasive treatment for vertebral compression fractures. The use of bone cement in VBS procedures can lead to complications such as incomplete fracture reduction and cement leakage. Biomimetic hydrogels have gained significant attention as potential biomaterial alternatives for VBS due to their unique properties, including tuneable therapeutic and mechanical properties. Over the past decade, there has been significant advancements in the development of biomimetic hydrogels for bone regeneration, employing a wide range of approaches to enhance the structural and functional properties of hydrogels. Biomimetic hydrogels hold significant promise as safer and reparative alternatives to bone cement for VBS procedures. However, further research and development in this field are necessary to explore the full potential of hydrogel-based systems for vertebral bone repair.


Possible molecular basis for changes in potassium handling in acute renal failure.
Renal potassium excretion is diminished in acute renal failure (ARF). The gastrointestinal tract can compensate for deficient renal potassium excretion in many patients with ARF. For both impaired renal potassium excretion and gastrointestinal compensation in ARF, little is known about the role of potassium channels. We hypothesized that specific changes in the expression of the secretory renal outer medullary potassium channel (ROMK), and the potassium channel regulator, channel-inducing factor (CHIF), in kidney and colon could contribute to changes in potassium handling. Sprague-Dawley rats underwent uninephrectomy and 35 minutes of renal ischemia, followed by varying periods of reperfusion. Renal function, serum and urine potassium levels, and aldosterone levels were measured. The expression of messenger RNA (mRNA) for ROMK and CHIF in the kidney and CHIF in the colon were measured by Northern blot hybridization. Serum creatinine level was increased at 24 hours and started to decline at 48 hours of renal ischemia reperfusion injury (IRI). Serum potassium level was increased at 24 hours, further elevated at 48 hours of IRI, and returned to normal at 7 days of IRI. Urine potassium level was reduced at 24 and 48 hours. Northern blot analysis indicated that the expression of ROMK1 mRNA in the cortex or medulla remained unchanged at 24 hours but profoundly decreased (by 70% to 80%) at 48 hours (n = 4; P < 0.01). The expression of CHIF mRNA in the kidney cortex or medulla decreased by 25% to 30% at 24 hours and 35% to 40% at 48 hours of IRI (n = 4; P < 0.05 for each group). CHIF mRNA expression in the distal colon was moderately increased at 24 hours (approximately twofold) and significantly enhanced at 48 hours (more than threefold; P < 0.01; n = 4) of IRI. Serum aldosterone level was increased approximately threefold at 48 hours of IRI (P < 0.01; n = 6). In conclusion, (1) suppression of ROMK and CHIF in the kidney may contribute to decreased renal potassium excretion in ARF; (2) enhanced expression of CHIF in the distal colon in IRI could be an adaptive response to increase potassium excretion in the colon and help modify hyperkalemia in ARF; and (3) increased aldosterone levels, as a response to hyperkalemia, could be upregulating colonic CHIF.


6K2-induced vesicles can move cell to cell during turnip mosaic virus infection.
To successfully infect plants, viruses replicate in an initially infected cell and then move to neighboring cells through plasmodesmata (PDs). However, the nature of the viral entity that crosses over the cell barrier into non-infected ones is not clear. The membrane-associated 6K2 protein of turnip mosaic virus (TuMV) induces the formation of vesicles involved in the replication and intracellular movement of viral RNA. This study shows that 6K2-induced vesicles trafficked toward the plasma membrane and were associated with plasmodesmata (PD). We demonstrated also that 6K2 moved cell-to-cell into adjoining cells when plants were infected with TuMV. 6K2 was then fused to photo-activable GFP (6K2:PAGFP) to visualize how 6K2 moved intercellularly during TuMV infection. After activation, 6K2:PAGFP-tagged vesicles moved to the cell periphery and across the cell wall into adjacent cells. These vesicles were shown to contain the viral RNA-dependent RNA polymerase and viral RNA. Symplasmic movement of TuMV may thus be achieved in the form of a membrane-associated viral RNA complex induced by 6K2.


American Joint Committee on Cancer Eighth Edition Changes in Staging Criteria: Implications for Data Collection.
The American Joint Committee on Cancer, in the eighth edition of its cancer staging manual, makes a number of changes to improve survival predictions in human malignancy. In this commentary, we examine the national collection of data for head and neck cancer. We outline and review the major changes made in head and neck cancer staging, identify the key data elements that will need to be collected with the new edition's criteria, and discuss the institutional adjustments currently being made to data collection under the new guidelines to improve the quality of data in our national cancer databases.


Successful treatment of large area oral verrucous hyperplasia using diode laser ablation combined with photodynamic therapy: A case report.
Oral verrucous hyperplasia (OVH) refers to a whitish or pink elevated plaque or mass on the oral mucosa with either verrucous or papillary surface. Given its potential of malignant transformation, it is crucial to pursue aggressive treatment and close surveillance to the lesion. Herein, we present a case of a 43-year-old male patient with large area OVH on the left buccal mucosa who was successfully treated using diode laser ablation combined with 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT). After two sessions of treatment, the lesions regressed completely, and no recurrence was observed at the 18-month follow-up. Therefore, diode laser ablation combined with ALA-PDT may be an efficient and safe treatment modality for large area OVH.


Evaluating the phylogenetic signal limit from mitogenomes, slow evolving nuclear genes, and the concatenation approach. New insights into the Lacertini radiation using fast evolving nuclear genes and species trees.
Estimating the phylogeny of lacertid lizards, and particularly the tribe Lacertini has been challenging, possibly due to the fast radiation of this group resulting in a hard polytomy. However this is still an open question, as concatenated data primarily from mitochondrial markers have been used so far whereas in a recent phylogeny based on a compilation of these data within a squamate supermatrix the basal polytomy seems to be resolved. In this study, we estimate phylogenetic relationships between all Lacertini genera using for the first time DNA sequences from five fast evolving nuclear genes (acm4, mc1r, pdc, βfib and reln) and two mitochondrial genes (nd4 and 12S). We generated a total of 529 sequences from 88 species and used Maximum Likelihood and Bayesian Inference methods based on concatenated multilocus dataset as well as a coalescent-based species tree approach with the aim of (i) shedding light on the basal relationships of Lacertini (ii) assessing the monophyly of genera which were previously questioned, and (iii) discussing differences between estimates from this and previous studies based on different markers, and phylogenetic methods. Results uncovered (i) a new phylogenetic clade formed by the monotypic genera Archaeolacerta, Zootoca, Teira and Scelarcis; and (ii) support for the monophyly of the Algyroides clade, with two sister species pairs represented by western (A. marchi and A. fitzingeri) and eastern (A. nigropunctatus and A. moreoticus) lineages. In both cases the members of these groups show peculiar morphology and very different geographical distributions, suggesting that they are relictual groups that were once diverse and widespread. They probably originated about 11-13 million years ago during early events of speciation in the tribe, and the split between their members is estimated to be only slightly older. This scenario may explain why mitochondrial markers (possibly saturated at higher divergence levels) or slower nuclear markers used in previous studies (likely lacking enough phylogenetic signal) failed to recover these relationships. Finally, the phylogenetic position of most remaining genera was unresolved, corroborating the hypothesis of a hard polytomy in the Lacertini phylogeny due to a fast radiation. This is in agreement with all previous studies but in sharp contrast with a recent squamate megaphylogeny. We show that the supermatrix approach may provide high support for incorrect nodes that are not supported either by original sequence data or by new data from this study. This finding suggests caution when using megaphylogenies to integrate inter-generic relationships in comparative ecological and evolutionary studies.


Atlas of the clinical genetics of human dilated cardiomyopathy.
Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.


Genomewide interaction and enrichment analysis on antidepressant response.
Genomewide association studies (GWASs) on antidepressant efficacy have yielded modest results. A possible reason is that response is influenced by other factors, which possibly interact with genetic variation. We used a GWAS model to predict antidepressant response, by including predictors previously known to affect response, such as quality of life (QoL). We also evaluated the association between genes, previously implicated in gene-environment (G × E) interactions, and response using an enrichment analysis. We examined a sample of 1426 depressed patients from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial: 774 responders, 652 non-responders and 418,865 single nucleotide polymorphisms (SNPs) were analysed. First, in a GWAS model, we investigated whether genetic variations interact with patients' levels of QoL to predict response, after controlling for demographic characteristics, severity and population stratification. Second, we conducted an enrichment analysis exploring whether candidate genes that have emerged from prior G × E interaction studies on depression are associated with treatment response. The GWAS model, with QoL as a moderator, yielded one SNP (rs520210) associated with response in the NEDD4L gene (p = 3.64 × 10⁻⁸). In the Caucasian sample only, we observed a drop in significance for this SNP. The enrichment analysis showed that SNPs within serotonergic genes contained more significant markers that predicted response, compared with a random set of genes in the genome. Our findings point to possible target genes, which are proposed for further independent replication. Our enrichment analysis provides further support, in a genomewide context, of the role of serotonergic genes in influencing antidepressant response.


Mechanical ventilation was associated with acidemia in a case series of salicylate-poisoned patients.
Despite little empiric evidence, mechanical ventilation (MV) in the setting of salicylate poisoning is considered by many to be harmful. When salicylate-poisoned patients are ventilated at conventional settings, the respiratory alkalosis is abolished, more salicylate is able to pass into the central nervous system (CNS), and neurotoxicity worsens. The objective of this study was to identify a relationship between MV, acidosis, and outcome in salicylate-poisoned patients. The authors electronically searched a poison control center (PCC) database (2001-2007) for patients with salicylate poisoning, defined as a serum concentration > 50 mg/dL, who had MV listed as a therapy. For the 7-year study period, a total of 3,144 salicylate-poisoning cases were identified. Eleven patients met the inclusion criteria of having both salicylate concentrations > 50 mg/dL and required MV; only 7 of them had post-MV data available. In all seven patients with post-MV blood gas data, the post-MV pH was < 7.4. In five of six patients with recorded PCO2, the post-MV PCO2 was > 50 mm Hg. Two of the seven patients in the study group died following intubation (two patients died within 3 hours [serum salicylate concentrations, 85 and 79 mg/dL, respectively]). Another patient sustained severe neurologic injury (serum salicylate concentration, 84 mg/dL). The other four patients were ultimately discharged home. In the three patients with the worst clinical outcome, deterioration was reported within hours of intubation. Inadequate MV of patients with salicylate poisoning is associated with respiratory acidosis, acidemia, and clinical deterioration in this series of cases. This supports warnings about the danger of improper MV in patients with salicylate poisoning. A prospective study should be performed.


[Experimental model of liver oxidative damage induction in rats by halothane].
The anesthetic halothane can be reductively metabolized to reactives intermediates that may initiate lipid peroxidation accompanied by hepatic injury. Hypoxia and phenobarbital pretreatment in rats increases metabolism of halothane, the oxidative stress, cause liver antioxidant enzymes changes and tissue damage. We investigated the effect of halothane on hepatic lipid peroxidation and on hepatic histology after increases reductive metabolism of halothane caused by hypoxia and phenobarbital pretreatment. Twenty-five male wistar rats were divided in five equals groups: CO (Control), HO14 (Halothane/Hypoxia), F (fenobarbital alone), O14 (Hypoxia alone) and H (Halothane alone). After 24 hours the rats were killed, their livers removed to determine chemoluminescence, thiobarbituric acid-reactive substances, catalase, superoxide dismutase, and blood samples were taken to determine AST and ALT. The histopathologic evaluation was performed with hematoxylin and eosin staining. Histopathologic scores are presented as 25th-75th percentile/range values and median +/- range. Halothane-hypoxic exposure resulted in a significant changes in the activities of antioxidant enzymes, and induced hepatic lipoperoxidation. Moreover it resulted in histopathologic liver injury as well as significant increase of serum activity of AST and ALT.


In vitro evaluation of the pollen extract, cernitin T-60, in the regulation of prostate cell growth.
Nine human-derived cancer and non-cancer continuous cell lines were employed to evaluate the relative in vitro activity of the pollen extract, Cernitin T-60. Responses of the cell lines to the drug were assessed by measuring growth and cell survival as determined by cell count. The results demonstrated that of the 9 continuous cell lines tested, only those derived from the human prostate were growth inhibited by the pollen extract, whereas the non-prostate derived cells exhibited variable degrees of resistance to the T-60. The selectivity of the drug for the prostate cell lines was even more pronounced in the hormone-independent models, suggesting that there might be a place for the pollen extract in the control of abnormal growth in hormone-insensitive cells.


Application of Sonoelastography in Differential Diagnosis of Benign and Malignant Thyroid Nodules.
Sonoelastography is a new ultrasound method which could be helpful to determine which thyroid nodule is malignant. We designed this study to evaluate the accuracy of sonoelastography in differentiating of benign and malignant thyroid nodules in Iranian patients. Forty thyroid nodules in forty consecutive patients who had been referred for sonography-guided fine-needle aspiration biopsy were evaluated. Gray scale ultrasound and elastosonography by real-time, freehand technique applied for all patients. Elastography findings were classified into four groups. Nodules which were classified as patterns 1 or 2 in elastogram evaluation were classified as benign and probably malignant if elastogram scans were patterns 3 and 4 of elastogram scan. Mean age ± standard deviation (SD) was 42.2 ± 12.6 years, and mean ± SD thyroid-stimulating hormone level was 1.4 ± 1.9 IU/ml. Thirty-five cases (87.5%) were female and 5 (12.5%) were male. Histological examination indicated 27 (67.5%) benign and 13 (32.5%) malignant nodules. The most elastogram score was 2 (50%) followed by score 3. The cut-off point of 2 considered as the best value to differentiate benign and malignant thyroid nodules with sensitivity and specificity of 61% and 78% (area under the curve = 0.76, 95% confidence interval: 0.6-0.92, P = 0.007). Sonoelastography could help to differentiate benign and malignant thyroid nodules. As our sample size was limited, larger studies are recommended.


Predicting functional status following amputation after lower extremity bypass.
Some patients who undergo lower extremity bypass (LEB) for critical limb ischemia ultimately require amputation. The functional outcome achieved by these patients after amputation is not well known. Therefore, we sought to characterize the functional outcome of patients who undergo amputation after LEB, and to describe the pre- and perioperative factors associated with independent ambulation at home after lower extremity amputation. Within a cohort of 3,198 patients who underwent an LEB between January, 2003 and December, 2008, we studied 436 patients who subsequently received an above-knee (AK), below-knee (BK), or minor (forefoot or toe) ipsilateral or contralateral amputation. Our main outcome measure consisted of a "good functional outcome," defined as living at home and ambulating independently. We calculated univariate and multivariate associations among patient characteristics and our main outcome measure, as well as overall survival. Of the 436 patients who underwent amputation within the first year following LEB, 224 of 436 (51.4%) had a minor amputation, 105 of 436 (24.1%) had a BK amputation, and 107 of 436 (24.5%) had an AK amputation. The majority of AK (75 of 107, 72.8%) and BK amputations (72 of 105, 70.6%) occurred in the setting of bypass graft thrombosis, whereas nearly all minor amputations (200 of 224, 89.7%) occurred with a patent bypass graft. By life-table analysis at 1 year, we found that the proportion of surviving patients with a good functional outcome varied by the presence and extent of amputation (proportion surviving with good functional outcome = 88% no amputation, 81% minor amputation, 55% BK amputation, and 45% AK amputation, p = 0.001). Among those analyzed at long-term follow-up, survival was slightly lower for those who had a minor amputation when compared with those who did not receive an amputation after LEB (81 vs. 88%, p = 0.02). Survival among major amputation patients did not significantly differ compared with no amputation (BK amputation 87%, p = 0.14, AK amputation 89%, p = 0.27); however, this part of the analysis was limited by its sample size (n = 212). In multivariable analysis, we found that the patients most likely to remain ambulatory and live independently despite undergoing a lower extremity amputation were those living at home preoperatively (hazard ratio [HR]: 6.8, 95% confidence interval [CI]: 0.94-49, p = 0.058) and those with preoperative statin use (HR: 1.6, 95% CI: 1.2-2.1, p = 0.003), whereas the presence of several comorbidities identified patients less likely to achieve a good functional outcome: coronary disease (HR: 0.6, 95% CI: 0.5-0.9, p = 0.003), dialysis (HR: 0.5, 95% CI: 0.3-0.9, p = 0.02), and congestive heart failure (HR: 0.5, 95% CI: 0.3-0.8, p = 0.005). A postoperative amputation at any level impacts functional outcomes following LEB surgery, and the extent of amputation is directly related to the effect on functional outcome. It is possible, based on preoperative patient characteristics, to identify patients undergoing LEB who are most or least likely to achieve good functional outcomes even if a major amputation is ultimately required. These findings may assist in patient education and surgical decision making in patients who are poor candidates for lower extremity bypass.


Hospital admissions and mortality for acute exacerbations of COPD during the COVID-19 pandemic: A nationwide study in France.
A global reduction in hospital admissions for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) was observed during the first months of the COVID-19 pandemic. Large-scale studies covering the entire pandemic period are lacking. We investigated hospitalizations for AECOPD and the associated in-hospital mortality at the national level in France during the first 2 years of the pandemic. We used the French National Hospital Database to analyse the time trends in (1) monthly incidences of hospitalizations for AECOPD, considering intensive care unit (ICU) admission and COVID-19 diagnoses, and (2) the related in-hospital mortality, from January 2016 to November 2021. Pandemic years were compared with the pre-pandemic years using Poisson regressions. The database included 565,890 hospitalizations for AECOPD during the study period. The median age at admission was 74 years (interquartile range 65-83), and 37% of the stays concerned women. We found: (1) a dramatic and sustainable decline in hospitalizations for AECOPD over the pandemic period (from 8,899 to 6,032 monthly admissions, relative risk (RR) 0.65, 95% confidence interval (CI) 0.65-0.66), and (2) a concomitant increase in in-hospital mortality for AECOPD stays (from 6.2 to 7.6% per month, RR 1.24, 95% CI 1.21-1.27). The proportion of stays yielding ICU admission was similar in the pre-pandemic and pandemic years, 21.5 and 21.3%, respectively. In-hospital mortality increased to a greater extent for stays without ICU admission (RR 1.39, 95% CI 1.35-1.43) than for those with ICU admission (RR 1.09, 95% CI 1.05-1.13). Since January 2020, only 1.5% of stays were associated with a diagnosis of COVID-19, and their mortality rate was nearly three-times higher than those without COVID-19 (RR 2.66, 95% CI 2.41-2.93). The decline in admissions for AECOPD during the pandemic could be attributed to a decrease in the incidence of exacerbations for COPD patients and/or to a possible shift from hospital to community care. The rise in in-hospital mortality is partially explained by COVID-19, and could be related to restricted access to ICUs for some patients and/or to greater proportions of severe cases among the patients hospitalized during the pandemic.


Earlier is not necessarily better in preemptive kidney transplantation.
While preemptive (before chronic dialysis) transplantation is associated with improved graft survival, it is unclear whether higher versus lower pretransplant kidney function is associated with even better graft survival after preemptive transplantation. We examined 671 first, preemptive, kidney-only transplantations at Hennepin County Medical Center and the University of Minnesota Medical Center 1984-2006. We estimated pretransplant glomerular filtration rate (eGFR, mL/min/1.73 m(2)) using the Modification of Diet in Renal Disease (MDRD) equation with Group 1: <10.0 (7.3 +/- 1.7, N = 324), Group 2: 10.0-14.9 (12.0 +/- 1.4, N = 217) and Group 3: >or=15.0 (21.1 +/- 10.0, N = 130). The mean difference in eGFR for Group 1 versus 3 was 13.8 pretransplant, 16.3 on day 1 and 13.9 on day 2 posttransplant. By week 1 and year 1 posttransplant, the differences between Groups 1 and 3 reduced to 6.3 and 4.5 mL/min/1.73 m(2), respectively. The adjusted relative risk (RR; Cox analysis) for graft failure was not significantly lower with higher pretransplant eGFR (reference eGFR <10.0); RR = 0.99 (95% confidence interval = 0.68-1.44, p = 0.9432) for eGFR 10.0-14.9; RR = 1.35 (0.89-2.05, p = 0.1588) for eGFR >or=15. Thus, early preemptive transplantation with higher eGFR does not necessarily improve graft survival after kidney transplantation, compared to preemptive transplantation with lower pretransplant eGFR.


Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients.
Three-hundred thirty-two cases of pleural diffuse malignant mesothelioma (DMM) seen at large centers in Ontario and Quebec from 1965 to 1984 were reviewed retrospectively. Previous asbestos exposure was found in 44% of patients. Diagnosis was most often made by exploratory thoracotomy; pleural biopsy or cytology were rarely contributory. The delay in diagnosis was often long (median time, 3.5 months) and thrombocytosis (platelets greater than or equal to 400,000/microL) was common (41% of cases). The median survival (MS) was only 9 months. Eleven clinical variables were analyzed for prognostic significance. The three most important prognostic factors using a univariate analysis were stage, weight loss, and histologic type. For 118 patients with complete data, multivariate analysis showed that the stage of disease, high platelet count, and asbestos exposure were the most important prognostic factors. There was no cure of DMM, and we did not find any drastic differences in survival among groups of patients subjected to the different therapeutic measures. Radical surgery and radiotherapy were ineffective and we confirmed the low response rate to chemotherapeutic agents. This large retrospective trial can serve as a baseline for future studies in this field. In particular, it provides the basis for appropriate stratification variables to be used in future therapeutic trials.


Development of a Novel Epitope Mapping System: RIEDL Insertion for Epitope Mapping Method.
To clarify the binding region of monoclonal antibodies (mAbs) to target molecules, it is very essential to understand the pharmacological function of each mAb. Although deletion mutants and point mutants are usefully utilized for epitope mapping, we often experience the difficulty of determining the mAb epitope against membrane proteins. We aimed to develop a novel method to determine the binding region of mAbs using epitope tag system. We first checked the reactivity of an anti-CD44 mAb (C44Mab-5) to several deletion mutants of CD44. We then employed the RIEDL tag system ("RIEDL" peptide and LpMab-7 mAb). We inserted the "RIEDL" peptide into the CD44 protein from the 21st to 41st amino acid (AA). The transfectants produced were stained by LpMab-7 and C44Mab-5 in flow cytometry. C44Mab-5 did not react with 30th-361st AA of the deletion mutant of CD44. Furthermore, the reaction of C44Mab-5 to RIEDL tag-inserted CD44 from 25th to 36th AA was lost, although LpMab-7 detected most of the RIEDL tag-inserted CD44 from 21st to 41st AA. The epitope of C44Mab-5 for CD44 was determined to be the peptide from 25th to 36th AA of CD44 using RIEDL insertion for epitope mapping (REMAP) method. The REMAP method might be useful for determining the critical epitope of functional mAbs against many target molecules.


[Efficacy of rasagiline in patients with advanced Parkinson's disease with motor fluctuation (azimut study)].
An open observational 3-month study of efficacy and safety of selective MAO B inhibitor rasagiline (АZIlect) in advanced Parkinson's disease (PD) patients with mоtor fluctuations on the long-term levodopa therapy (the "АZIMUT" study) has been conducted. Forty five non-demented patients with PD (mean age 64,7±8,4 years, mean duration of disease 9,5±4,0 years, mean Hoehn-Yahr stage 3,0±0,4, mean levodopa dose 673,9 mg/d) have been included in the study. All patients received rasagiline at a dose of 1 mg once daily as an adjunct to a stable anti-parkinsonian therapy. Patient's clinical state has been assessed at baseline and after 1 and 3 months of therapy. Forty two (93%) patients have completed the study. At the end of the third month of therapy, the daily off-time was decreased by 1,7 h. The ADL score (off-state) decreased by 22%, and the UPDRS-III score (on-state) decreased by 10%. The Global Clinical Improvement Scale revealed the marked improvement in 12% patients and moderate improvement in 43% patients. The severity of freezing of gait declined by 15%. Moreover, the initial severity of freezing seems to be a predictor of rasagiline clinical efficacy. The clinical effect of rasagiline steadily increased over 3 months. The fair tolerability of the drug and low rate of dyskinesias and other complications were demonstrated. In conclusion, the study has shown that rasagiline effectively reduces the off-time duration as well as the disability in off- and on-time and optimizes levodopa efficacy at the routine clinical practice setting.


The novel oral imatinib microemulsions: physical properties, cytotoxicity activities and improved Caco-2 cell permeability.
The objective of this study was to formulate imatinib (IM) loaded to water-in-oil (w/o) microemulsions as an alternative formulation for cancer therapy and to evaluate the cytotoxic effect of microemulsions Caco-2 and MCF-7. Moreover, permeability studies were also performed with Caco-2 cells. W/o microemulsion systems were developed by using pseudo-ternary phase diagram. According to cytotoxicity studies, all formulations did not exert a cytotoxic effect on Caco-2 cells. Furthermore, all formulations had a significant cytotoxic effect on MCF-7 cells and the cytotoxic effect of M3IM was significantly more than that of other microemulsions and IM solution (p < 0.05). The permeability studies of IM across Caco-2 cells showed that permeability value from apical to basolateral was higher than permeability value of other formulations. In conclusion, the microemulsion formulations as a drug carrier, especially M3IM formulation, may be used as an effective alternative breast cancer therapy for oral delivery of IM.


Generation of iPSCs carrying a common LRRK2 risk allele for in vitro modeling of idiopathic Parkinson's disease.
Induced pluripotent stem cells (iPSCs) have recapitulated several aspects of Parkinson's disease (PD), but most iPSCs are derived from familial cases, which account for only about 15% of patients. Thus, while the emphasis has justifiably been on using iPSCs to model rare familial cases, models for the most common forms of PD are critically lacking. Here, we report the generation of an iPSC-based model of idiopathic PD (iPD) with or without RS1491923, which is a common risk variant in the LRRK2 locus. Consistent with GWA studies, we found large variability in our datasets. However, iPSC-derived neurons carrying the risk allele emerged for displaying subtle disturbances of cellular degradative systems, in line with familial PD models. We also observed that treatment with the LRRK2 inhibitor CZC-25146 slightly reduced a marker of aSYN pathology in all iPD lines. Future iPSC-based studies may need to be structured similarly to large GWA studies in order to obtain relevant statistical power. However, results from this pilot study suggest that iPSC-based modeling represents an attractive way to investigate idiopathic diseases.


[The developing risks of the allergic child].
6% of infants are allergic to egg. 50% of them are at risk of becoming sensitive to pneumoallergens and of whom 50% develop asthma. These evolutionary risks which are the allergy "course" of the child may be avoided by a precise interrogation which is orientated towards detection by in vitro tests of F x 5 for foods and Phadiatop for pneumoallergens. The responsible allergens may themselves be shown by skin tests, measurement of specific IgE by CAP-RAST made by UNICAP.


Arthroscopic reattachment of an avulsion fracture of the tibial insertion of the posterior cruciate ligament.
We describe an arthroscopic technique for the treatment of isolated avulsion fracture of the tibial insertion of the posterior cruciate ligament. Arthroscopic examination of the injured joint permits visualization of the intra-articular structures and lavage of the joint. Such an approach reduces the risk of injury to the posterior neurovascular complex. K-wire fixation affords anatomic and rigid internal fixation while minimizing the potential for further damage to the osseous fragment.


Case-control studies of motor neuron disease: association with mechanical injuries.
Two case-control studies of motor neuron disease that involved 712 cases and 158 cases, respectively, showed that (1) mechanical injuries were two to three times more frequent in both sexes, heralding amyotrophic lateral sclerosis, progressive bulbar paralysis, and progressive muscular atrophy; (2) the head, neck, spine, and the extremities were more often traumatized; (3) traumatized parts were not correlated with the initial manifestation of the disease; and (4) more males were traumatized, but males still predominated among uninjured cases. These results suggested that mechanical injuries were not the cause, but probably one of the risk factors of the disease. No association was observed with smoking, drinking, residence, home space, drinking water, animals, experience as a war prisoner, stay on Guam, parental consanguinity, measles, polio, mumps, tuberculosis, rheumatism, prothesis of the total teeth, shell splinters retained in the body, occupational exposures to radiations, chemicals, or gases, atomic bombings, electric injuries, surgical operations, and occupations.


Role of rice heme oxygenase in lateral root formation.
Lateral roots (LRs) play important roles in increasing the absorptive capacity of roots as well as to anchor the plant in the soil. In rice, exposure to auxin, methyl jasmonate (MJ), apocynin, and CoCl2 has been shown to increase LR formation. This review provides evidence showing a close link between rice heme oxygenase (HO) and LR formation. The effect of auxin and MJ is nitric oxide (NO) dependent, whereas that of apocynin requires H2O2. The effect of CoCl2 on the LR formation could be by some other pathway unrelated to NO and H2O2. This review also highlights future lines of research that should increase our knowledge of HO-involved LR formation in rice.


Effect of aluminum on cellular division and photosynthetic electron transport in Euglena gracilis and Chlamydomonas acidophila.
The present study investigated aluminum's effect on cellular division and the photosynthetic processes in Euglena gracilis and Chlamydomonas acidophila at pH 3.0, at which Al is present mostly as Al(3+), AlSO(4) (+), and Al(SO(4))(2) (-). These algal species were exposed to 100, 188, and 740 microM Al, and after 24 h cell-bound Al was significantly different from control only for the highest concentration tested. However, very different effects of Al on algal cellular division, biomass per cell, and photosynthetic activity were found. Aluminum stimulated cell division but decreased at some level biomass per cell in C. acidophila. Primary photochemistry of photosynthesis, as Photosystem II quantum yield, and energy dissipation via nonphotochemical activity were slightly affected. However, for E. gracilis, under the same conditions, Al did not show a stimulating effect on cellular division or photosynthetic activity. Primary photochemical activity was diminished, and energy dissipation via nonphotochemical pathways was strongly increased. Therefore, when Al is highly available in aquatic ecosystems, these effects may indicate very different response mechanisms that are dependent on algal species.


Exaggeration of PFS by blinded, independent, central review (BICR).
Recent published studies have shown meaningful discrepancies between local investigator and blinded, independent, central review (BICR) assessed median progression-free survival (PFS). When the local review but not BICR shows progression, generally, no further assessments are carried out and patients are censored in the BICR analysis, leading to violation of the statistical assumptions of independence between censoring and outcome used in survival analysis methods. We carried out a simulation study to assess methodological reasons behind these discrepancies and corroborated our findings in a case study of three BRCA-mutated ovarian cancer trials. We briefly outline possible methodological solutions that may lead to improved estimation of the BICR medians. The Kaplan-Meier (KM) curve for the BICR PFS can often be exaggerated. The degree of bias is largest when there is reasonably strong correlation between BICR and local PFS, especially when PFS is long compared with assessment frequency. This can result in an exaggeration of the medians and their difference; however, the hazard ratio (HR) is much less susceptible to bias. Our simulation shows that when the true BICR median PFS was 19 months, and patients assessed every 12 weeks, the estimated KM curves were materially biased whenever the correlation between BICR and local PFS was 0.4 or greater. This was corroborated by case studies where, in the active arm, the BICR median PFS was between 6 and 11 months greater than the local median PFS. Further research is required to find improved methods for estimating BICR survival curves. In general, when there is a difference between local and BICR medians, the true BICR KM curve is likely to be exaggerated and its true median will probably lie somewhere between the observed local and BICR medians. Presentation of data should always include both BICR and local results whenever a BICR is carried out.


Application of Circular Dichroism and Fluorescence Spectroscopies To Assess Photostability of Water-Soluble Porcine Lens Proteins.
The eye lens is mainly composed of the highly ordered water-soluble (WS) proteins named crystallins. The aggregation and insolubilization of these proteins lead to progressive lens opacification until cataract onset. Although this is a well-known disease, the mechanism of eye lens protein aggregation is not well understood; however, one of the recognized causes of proteins modification is related to the exposure to UV light. For this reason, the spectroscopic properties of WS lens proteins and their stability to UV irradiation have been evaluated by different biophysical methods including synchrotron radiation circular dichroism, fluorescence, and circular dichroism spectroscopies. Moreover, dynamic light scattering, gel electrophoresis, transmission electron microscopy, and protein digestion followed by tandem LC-MS/MS analysis were used to study the morphological and structural changes in protein aggregates induced by exposure to UV light. Our results clearly indicated that the exposure to UV radiation modified the protein conformation, inducing a loss of ordered structure and aggregation. Furthermore, we confirmed that these changes were attributable to the generation of reactive oxygen species due to the irradiation of the protein sample. This approach, involving the photodenaturation of proteins, provides a benchmark in high-throughput screening of small molecules suitable to prevent protein denaturation and aggregation.


Analytical solutions for the electromagnetic fields of tightly focused laser beams of arbitrary pulse length.
The analytical solution for a monochromatic focused laser beam was recently published [Opt. Lett.31, 1447 (2006)]. The effect of introducing bandwidth by including a finite-length temporal pulse envelope is included exactly. This is done formally first in the frequency domain for an arbitrary pulse shape, and the specific case of a cosine-squared envelope is then solved analytically for all pulse lengths, thereby decreasing the computation time by 2 orders of magnitude. The inclusion of longer wavelengths reduces the fraction of laser energy in the focus from 86.5% to 83.5% for a 5 fs Ti:sapphire laser and 72.7% in a single-cycle pulse.


Qigong Exercise May Reduce Serum TNF-α Levels and Improve Sleep in People with Parkinson's Disease: A Pilot Study.
Background: Inflammatory cytokine levels are often elevated in people with Parkinson's disease (PD). People with PD often experience sleep disturbances that significantly impact quality of life. Past studies suggest inflammatory cytokines may be associated with various symptoms of PD. Benefits of Qigong, a mind-body exercise, have been shown in different neurological conditions, but there is still a lack of clinical evidence in the PD population. Methods: Ten people with PD were recruited and randomly assigned into two groups receiving six weeks of Qigong (experimental group) or sham Qigong (control group) intervention. The levels of TNF-α, IL-1β, and IL-6 in subjects' serum and sleep quality were measured before and after the intervention. Results: After the intervention, the serum level of TNF-α in the experimental group was significantly decreased in all subjects, while the level in the control group showed a trend to increase. Qigong exercise significantly improved sleep quality at night. There was a strong correlation between changes in the level of TNF-α and sleep quality. Conclusion: Qigong exercise decreased TNF-α level in people with PD and helped improve sleep quality. TNF-α may have a potential to influence the sleep quality in people with PD.


[Ultrasound evaluation of the anatomical relationships between common carotid arteries and internal jugular veins in children].
Relationships between common carotid arteries (CCA) and internal jugular veins (IJV) have been investigated both in adults and children. Overlapping of CCA and IJV are reported in 70 to 90% of cases; however we seldom observe overlapping cases in children. We evaluate the relationships between CCA and IJV in children. In this study, 100 children below 60 months undergoing tracheal intubation for general anesthesia were enrolled. The width of the CCA (AW), IJV (VW), and the distance from the internal edge of the CCA to the outer edge of the IJV (DAV) were measured using an ultrasound apparatus. The overlapping ratio was calculated as (AW + VW--DAV)/DAV. Mean (S. D) age was 15.5 (16.0) months, height was 70.8 (16.4) cm, and weight was 7.6 (3.8) kg; the AW was 4.4 (0.8) mm, and the VW was 7.4 (2.2) mm. The percentage of non-overlapping of CCA and IJV was 66.2% and overlapping less than 10% was 92%. The overlapping more than 20% was only in 3%. Puncturing the CCA did not occur. There appears to be little danger of puncturing the CCA during internal jugular venipuncture from the viewpoint of anatomical relationships between the CCA and IJV


Ethanol Enhances High-Salinity Stress Tolerance by Detoxifying Reactive Oxygen Species in Arabidopsis thaliana and Rice.
High-salinity stress considerably affects plant growth and crop yield. Thus, developing techniques to enhance high-salinity stress tolerance in plants is important. In this study, we revealed that ethanol enhances high-salinity stress tolerance in Arabidopsis thaliana and rice. To elucidate the molecular mechanism underlying the ethanol-induced tolerance, we performed microarray analyses using A. thaliana seedlings. Our data indicated that the expression levels of 1,323 and 1,293 genes were upregulated by ethanol in the presence and absence of NaCl, respectively. The expression of reactive oxygen species (ROS) signaling-related genes associated with high-salinity tolerance was upregulated by ethanol under salt stress condition. Some of these genes encode ROS scavengers and transcription factors (e.g., AtZAT10 and AtZAT12). A RT-qPCR analysis confirmed that the expression levels of AtZAT10 and AtZAT12 as well as AtAPX1 and AtAPX2, which encode cytosolic ascorbate peroxidases (APX), were higher in ethanol-treated plants than in untreated control plants, when exposure to high-salinity stress. Additionally, A. thaliana cytosolic APX activity increased by ethanol in response to salinity stress. Moreover, histochemical analyses with 3,3'-diaminobenzidine (DAB) and nitro blue tetrazolium (NBT) revealed that ROS accumulation was inhibited by ethanol under salt stress condition in A. thaliana and rice, in which DAB staining data was further confirmed by Hydrogen peroxide (H2O2) content. These results suggest that ethanol enhances high-salinity stress tolerance by detoxifying ROS. Our findings may have implications for improving salt-stress tolerance of agriculturally important field-grown crops.


Clinical review: Strict or loose glycemic control in critically ill patients--implementing best available evidence from randomized controlled trials.
Glycemic control aiming at normoglycemia, frequently referred to as 'strict glycemic control' (SGC), decreased mortality and morbidity of adult critically ill patients in two randomized controlled trials (RCTs). Five successive RCTs, however, failed to show benefit of SGC with one trial even reporting an unexpected higher mortality. Consequently, enthusiasm for the implementation of SGC has declined, hampering translation of SGC into daily ICU practice. In this manuscript we attempt to explain the variances in outcomes of the RCTs of SGC, and point out other limitations of the current literature on glycemic control in ICU patients. There are several alternative explanations for why the five negative RCTs showed no beneficial effects of SGC, apart from the possibility that SGC may indeed not benefit ICU patients. These include, but are not restricted to, variability in the performance of SGC, differences among trial designs, changes in standard of care, differences in timing (that is, initiation) of SGC, and the convergence between the intervention groups and control groups with respect to achieved blood glucose levels in the successive RCTs. Additional factors that may hamper translation of SGC into daily ICU practice include the feared risk of severe hypoglycemia, additional labor associated with SGC, and uncertainties about who the primarily responsible caregiver should be for the implementation of SGC.


[Compound Hurler-Scheie disease in 3 siblings].
The present paper describes 3 out of a total of 9 siblings, aged 9, 17, and 18, with the following symptoms: gargoyle-like facial features, clouding of the cornea in both eyes, dysostosis multiplex, slightly impaired intelligence, hepatosplenomegaly, umbilical hernia, and increased secretion of mucopolysaccharides in the urine, in particular dermatan and heparan sulfate. Some of the symptoms are mid-way between those of Hurler's and Scheie's syndromes, both having the same deficiency of the enzyme alpha-1-iduronidase. McKusik developed the theory that the genes responsible for the clinical pictures of Hurler's and Scheie's syndromes are alleles and hence cases such as those described here should be considered as allelomorphic compounds.


Strategies for extending charge separation in colloidal nanostructured quantum dot materials.
Semiconductor colloidal metal chalcogenides (II-VI) in the form of quantum dots (QDs) and different heterostructures (core/shell, alloys, etc.) are of extensive interest in scientific research for both a fundamental understanding and technological applications because of their quantized size and different optical properties; however, due to their small size, the exciton (bound electron and hole) experiences a strong Coulombic attraction, which has a remarkable impact on the charge separation and photophysical properties of QDs. Thus, to achieve an efficient charge separation, numerous attempts have been made via the formation of different heterostructures, QD/molecular adsorbate (either organic or inorganic) assemblies, etc. These hybrid materials ameliorated the absorption of the incident light as well as charge separation. This article reviews the strategies for extending charge separation in these colloidal nanocrystals (NCs), which is one of the crucial steps to elevate the solar to electrical energy conversion efficiency in a quantum dot-sensitized solar cell (QDSC). The article summarizes the benefits of co-sensitization and experimental shreds of evidence for the multiple charge transfer processes involved in a QDSC. Studies have shown that in the co-sensitization process, prolonged charge separation occurs via the dual behavior of the molecular adsorbate, sensitization (electron injection) and capture of holes from photoexcited QDs. This perspective emphases band edge engineering and control of charge carrier dynamics in various core/shell structures. The impact of colloidal alloy NCs on charge separation and interesting photophysical properties was recapitulated via the steady-state and time-resolved photoluminescence (PL) and femtosecond transient absorption spectroscopic techniques. Finally, the prolonged lifetime and extent of charge separation for these hybrid NCs (or the composites) assisted in the development of a better light harvester as compared to the case of their pure counterparts.


Long-term outcomes among octogenarians with aneurysmal subarachnoid hemorrhage.
Data evaluating the long-term outcomes, particularly with regard to treatment modality, of aneurysmal subarachnoid hemorrhage (SAH) in octogenarians are limited. The primary objectives were to evaluate the disposition (living at home vs institutional settings) and analyze the predictors of long-term survival and return to home for octogenarians after SAH. Data pertaining to patients age 80 and older who underwent microsurgical clipping or endovascular coiling for SAH were extracted from 100% nationwide Medicare inpatient claims and linked with the Minimum Data Set (2008-2011). Patient disposition was tracked for 2 years after index SAH admission. Multivariable logistic regression stratified by aneurysm treatment modality, and adjusted for patient factors including SAH severity, evaluated predictors of return to home at 60 and 365 days after SAH. Survival 365 days after SAH was analyzed with a multivariable Cox proportional hazards model. A total of 1298 cases were included in the analysis. One year following SAH, 56% of the patients had died or were in hospice care, 8% were in an institutional post-acute care setting, and 36% had returned home. Open microsurgical clipping (adjusted hazard ratio [aHR] 0.67, 95% confidence interval [CI] 0.54-0.81), male sex (aHR 0.70, 95% CI 0.57-0.87), tracheostomy (aHR 0.63, 95% CI 0.47-0.85), gastrostomy (aHR 0.60, 95% CI 0.48-0.76), and worse SAH severity (aHR 0.94, 95% CI 0.92-0.97) were associated with reduced likelihood of patients ever returning home. Older age (aHR 1.09, 95% CI 1.05-1.13), tracheostomy (aHR 2.06, 95% CI 1.46-2.91), gastrostomy (aHR 1.55, 95% CI 1.14-2.10), male sex (aHR 1.66, 95% CI 1.20-2.23), and worse SAH severity 1.51 (95% CI 1.04-2.18) were associated with reduced survival. In this national analysis, 56% of octogenarians with SAH died, and 36% returned home within 1 year of SAH. Coil embolization predicted returning to home, which may suggest a benefit to endovascular treatment in this patient population.


Salmonella enterica subsp. enterica Serovar Heidelberg Food Isolates Associated with a Salmonellosis Outbreak Have Enhanced Stress Tolerance Capabilities.
Salmonella enterica serovar Heidelberg is currently the 12th most common serovar of Salmonella enterica causing salmonellosis in the United States and results in twice the average incidence of blood infections caused by nontyphoidal salmonellae. Multiple outbreaks of salmonellosis caused by Salmonella Heidelberg resulted from the same poultry processor, which infected 634 people during 2013 and 2014. The hospitalization and invasive illness rates were 38% and 15%, respectively. We hypothesized that the outbreak strains of Salmonella Heidelberg had enhanced stress tolerance and virulence capabilities. We sourced nine food isolates collected during the outbreak investigation and three reference isolates to assess their tolerance to heat and sanitizers, ability to attach to abiotic surfaces, and invasiveness in vitro We performed RNA sequencing on three isolates (two outbreak-associated isolates and a reference Salmonella Heidelberg strain) with various levels of heat tolerance to gain insight into the mechanism behind the isolates' enhanced heat tolerance. We also performed genomic analyses to determine the genetic relationships among the outbreak isolates. Ultimately, we determined that (i) six Salmonella Heidelberg isolates associated with the foodborne outbreak had enhanced heat tolerance, (ii) one outbreak isolate with enhanced heat tolerance also had an enhanced biofilm-forming ability under stressful conditions, (iii) exposure to heat stress increased the expression of Salmonella Heidelberg multidrug efflux and virulence genes, and (iv) outbreak-associated isolates were likely transcriptionally primed to better survive processing stresses and, potentially, to cause illness.IMPORTANCE This study provides a deep analysis of the intrinsic stress tolerance and virulence capabilities of Salmonella Heidelberg that may have contributed to the length and severity of a recent salmonellosis outbreak. Additionally, this study provides a comprehensive analysis of the transcriptomic response of S. enterica strains to heat stress conditions and compares baseline stationary-phase gene expression among outbreak- and non-outbreak-associated Salmonella Heidelberg isolates. These data can be used in assay development to screen isolates for stress tolerance and subsequent survival. This study adds to our understanding of the strains associated with the outbreak and informs ongoing regulatory discussions on Salmonella in poultry.