[Cerebroprotective effect of 3-oxypyridine and succinic acid derivatives in experimental diabetes mellitus].
We studied an effect of original domestic derivatives of 3-oxypyridine and succinic acid (emoxipine, reamberin and mexidol) on changes in the cellular composition of cortical and diencephalic structures in the rat brain in relation to the hyperglycemia severity in rats with alloxan diabetes. The effect of 3-oxypyridine and succinic acid derivatives was compared with the results of alpha-lipoic acid treatment. We determined that administration of 14 optimal doses of any medication in this study prevented the decrease in neuronal count in the primary somatosensory cortex (Par1 field). This effect was particularly evident after treatment with 3-oxypyridine derivatives (emoxipine and mexidol). Additionally, a two-week administration of emoxipine and mexidol led to a decreased percentage of lipofuscin-positive neurons in the neocortex and field CA1 of the hippocampus. Concurrently, emoxipine and mexidol increased the number of basket neurons as well as oligodendrocytes and microglia in the studied structure of the Ammon's horn. Moreover, these two substances prevented the decrease in the number of astrocytes in the somatosensory cortex and the paraventricular nucleus of the hypothalamus. The cerebroprotective activity of reamberin and alpha-lipoic acid in alloxan diabetes was less effective than that of 3-oxypyridine derivatives. Also, reamberin and alpha-lipoic acid induced undesirable side-effects manifested in the decreased number of pyramid neurons in field CA1 in the hippocampus and the increased number of lipofuscin-positive neurons in the somatosensory cortex and the paraventricular nucleus of the hypothalamus. Changes in the cellular composition of cortical and diencephalic structures resulting from administration of medications used in this study did not depend on the ability of these substances to restrain the hyperglycemia in alloxan diabetes.


Spatial distribution, work patterns, and perception towards malaria interventions among temporary mobile/migrant workers in artemisinin resistance containment zone.
Mobile populations are at a high risk of malaria infection and suspected to carry and spread resistant parasites. The Myanmar National Malaria Control Programme focuses on preventive interventions and vector control measures for the temporary mobile/migrant workers in Myanmar Artemisinin Resistance Containment Zones. A prospective cross-sectional study was conducted in 2012 in Kawthaung and Bokepyin townships of Tanintharyi Region, Myanmar, covering 192 mobile/migrant aggregates. The objectives were to identify the spatial distribution of the mobile/migrant populations, and to assess knowledge, attitudes, perceptions, and practices concerning malaria prevention and control, and their preferred methods of interventions. The structure of the 192 migrant aggregates was investigated using a migrant mapping tool. Individual and household information was collected by structured interviews of 408 respondents from 39 aggregates, supplemented by 12 in-depth interviews of health care providers, authorities, volunteers, and employers. Data were analyzed by triangulating quantitative and qualitative data. The primary reasons for the limitation in access to formal health services for suspected malaria within 24 hours were identified to be scattered distribution of migrant aggregates, variable working hours and the lack of transportation. Only 19.6% of respondents reported working at night from dusk to dawn. Among study populations, 73% reported a perceived risk of contracting malaria and 60% reported to know how to confirm a suspected case of malaria. Moreover, only 15% was able to cite correct antimalarial drugs, and less than 10% believed that non-compliance with antimalarial treatment may be related to the risk of drug resistance. About 50% of study population reported to seeking health care from the public sector, and to sleep under ITNs/LLINs the night before the survey. There was a gap in willingness to buy ITNs/LLINs and affordability (88.5% vs. 60.2%) which may affect their sustained and consistent use. Only 32.4% across all aggregates realized the importance of community participation in effective malaria prevention and control. Community-based innovative approaches through strong collaboration and coordination of multi-stakeholders are desirable for relaying information on ITNs/LLINs, rapid diagnostic test, and artemisinin combination therapy and drug resistance successfully across the social and economic diversity of mobile/migrant aggregates in Myanmar.


Apoptosis of sinusoidal endothelial cells is a critical mechanism of preservation injury in rat liver transplantation.
In livers excised for transplantation, sinusoidal endothelium appears especially vulnerable to injury during organ preservation in the cold and subsequent reperfusion. The degree of endothelial cell injury correlates with functional impairment of the graft following transplantation. The mechanism of injury remains obscure, but endothelial cell damage has been described as coagulative necrosis secondary to irreversible physico-chemical damage. We investigated whether endothelial cell death is caused by apoptosis rather than by necrosis. Tissue from rat livers stored for varying periods in cold (1 degree C) Euro-Collins solution and then reperfused for 1 hour at 37 degrees C were studied for evidence of apoptosis by detection of DNA fragmentation using the in situ terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling (TUNEL) assay, DNA gel electrophoresis, and by transmission electron microscopy (EM). DNA fragmentation of the type characteristic of apoptosis was identified in 49.7% +/- 2.2% of sinusoidal lining cells after 8 hours of ischemia + reperfusion (viable graft) vs. 70.7% +/- 4.3% after 16 hours + reperfusion (nonviable graft) (P < .001). No such fragmentation was observed after cold preservation without reperfusion or in unpreserved, reperfused livers. EM demonstrated changes characteristic of apoptosis exclusively in endothelial cells. The study suggests that the apoptosis of sinusoidal endothelial cells is a pivotal mechanism of preservation injury in liver transplantation.


Prevalence and associated risk factors assessment of bovine fasciolosis in the Imbo Region, Burundi.
Fasciolosis is a zoonosis that limits the productivity of ruminants worldwide, but there is a lack of information on its occurrence in Burundi. Therefore, this study aimed to fill the information gap by determining the prevalence and risk factors associated with bovine fasciolosis in the Imbo Region of Burundi. Two prevalence studies were conducted in parallel in the five communes of the five provinces in the Imbo region. In the first study, a total of 426 fecal samples were collected from randomly selected cattle farms and microscopically examined to determine Fasciola egg burden. Survey data on cattle husbandry were collected from owners of these cattle and analyzed to determine the risk factors for bovine fasciolosis. In the second study, 467 cattle were randomly selected in abattoirs and their livers were examined postmortem to determine liver fluke burdens. Data were entered separately into Microsoft Excel and analyzed using R software. The overall prevalence of bovine fasciolosis was 47.7% (42.9-52.4, 95% CI) for microscopic examination and 33.2% (28.9-37.5, 95% CI) for postmortem examinations. The majority of positive cattle (60.6%) had light intensity infections as determined by eggs per gram of feces (epg). Postmortem examinations corroborated these results and indicated that 80% of cattle had light intensity infections. Chi-square analysis showed a statistical association with the presence of bovine fasciolosis and the age, sex, and origin of cattle and the practices of cattle owners (P < 0.05).


A time-motion study of inpatient rounds using a family-centered rounds model.
Family-centered rounds (FCR) have become increasingly prevalent in pediatric hospital settings. The objective of our study was to describe time use and discrete events during pediatric inpatient rounds by using a FCR model. We conducted a prospective observational study at Children's National Medical Center between September 2010 and February 2011. Investigators directly observed rounds on hospitalist and neurology services. Events were timed, and key features were recorded by using a Microsoft Access-based program. Associations with increased time spent during rounds were determined by using regression analyses. One hundred fifty-nine rounding encounters were observed. Rounds lasted 7.9 minutes on average per patient. An average of 1.3 minutes was spent between patients during rounds. Eighty-six (54%) encounters occurred outside the patient's room, 3% of the time because of the family's request. Infectious isolation was associated with rounds occurring outside the room (P<.0001). Participation of the parent, location of rounds inside or outside the patient's room, most teaching behaviors, and interruptions were not significantly associated with increased time spent during rounds. Teaching physical examination techniques by allowing multiple trainees to examine the patient was associated with increased rounding time (P= .02). The majority of rounds occurred outside the patient's room, yet rarely at the parent's request. Patients on infectious isolation were more likely to have rounds occur outside the patient's room. Neither parental participation nor most teaching behaviors were associated with increased time spent on rounds. These findings will enrich the evidence base needed to establish FCR best practices.


Post-ischemic coma in rat: effect of different pre-ischemic blood glucose levels on cerebral metabolic recovery after ischemia.
Hyper-, normo-, and hypoglycemic rats were exposed to 10 min of complete cerebral ischemia. Regional cerebral blood flow (CBF), blood-brain glucose transfer, and cerebral consumption of oxygen and glucose were measured before, as well as three and 60 minutes after ischemia. Three min after ischemia, no differences were observed between the 3 groups of rats. One h after ischemia, the hyperglycemic rats in comparison to those of the other groups had similar whole-brain CBF and glucose consumption but appreciately lower oxygen consumption, indicating continued non-oxidative use of glucose in the hyperglycemic group. In general, regional CBF values exceeded the control value by 100-200% 3 min after ischemia and were reduced to 50% of control at 1 h after ischemia, at which time the rats were still comatose. In the brain stem of hyperglycemic rats, blood flow, however, remained elevated after ischemia. Thus, the significantly increased mortality observed in rats hyperglycemic before, during and after ischemia (Siemkowicz & Hansen 1978) was the result, not of impaired postischemic CBF, but of ischemic or postischemic damage to brain cells. We suggest that the damaging factor in the hyperglycemic group is increased lactacidosis associated with prolonged anaerobic glycolysis.


Determinants of the specificity of rotavirus interactions with the alpha2beta1 integrin.
The human α2β1 integrin binds collagen and acts as a cellular receptor for rotaviruses and human echovirus 1. These ligands require the inserted (I) domain within the α2 subunit of α2β1 for binding. Previous studies have identified the binding sites for collagen and echovirus 1 in the α2 I domain. We used CHO cells expressing mutated α2β1 to identify amino acids involved in binding to human and animal rotaviruses. Residues where mutation affected rotavirus binding were located in several exposed loops and adjacent regions of the α2 I domain. Binding by all rotaviruses was eliminated by mutations in the activation-responsive αC-α6 and αF helices. This is a novel feature that distinguishes rotavirus from other α2β1 ligands. Mutation of residues that co-ordinate the metal ion (Ser-153, Thr-221, and Glu-256 in α2 and Asp-130 in β1) and nearby amino acids (Ser-154, Gln-215, and Asp-219) also inhibited rotavirus binding. The importance of most of these residues was greatest for binding by human rotaviruses. These mutations inhibit collagen binding to α2β1 (apart from Glu-256) but do not affect echovirus binding. Overall, residues where mutation affected both rotavirus and collagen recognition are located at one side of the metal ion-dependent adhesion site, whereas those important for collagen alone cluster nearby. Mutations eliminating rotavirus and echovirus binding are distinct, consistent with the respective preference of these viruses for activated or inactive α2β1. In contrast, rotavirus and collagen utilize activated α2β1 and show an overlap in α2β1 residues important for binding.


Through the Eyes of Patients: The Effect of Training General Practitioners and Nurses on Perceived Shared Decision-Making Support.
To examine the effects of training general practitioners and nurses in shared decision-making (SDM) support as perceived by cancer patients and survivors. An innovative, experimental design was adopted that included analogue patients (APs), that is, people who have or have had cancer and who imagine themselves in the position of the actor-patient presented in a video. Each AP assessed a video-recorded simulated consultation of a health care professional (HCP) conducted before or after an SDM support training program. The primary outcome was the APs' perceived SDM support with 13 self-developed items reflecting the perceived patient benefit of SDM support as well as the perceived HCP support behavior. Secondary outcomes included an overall rating of SDM support, AP-reported extent of SDM (CollaboRATE), satisfaction with the communication (Patient Satisfaction Questionnaire), conversation appreciation and helpfulness, as well as decision-making satisfaction and confidence (visual analog scale, 0-100). In addition, patient and HCP characteristics associated with AP-perceived SDM support were examined. APs (n = 131) did not significantly differentiate trained from untrained HCPs in their perceptions of SDM support nor in secondary outcomes. Agreement between APs' perceptions was poor. The higher the perceived comparability of the consultation with APs' previous personal experiences, the higher their rating of SDM support. We used a nonvalidated primary outcome and an innovative study design that should be tested in future work. Despite the limitations of the study design, the training seemed to not affect cancer patients' and survivors' perceived SDM support. The clinical relevance of the training on SDM support needs to be established. The variation in APs' assessments suggests patients differ in their perception of SDM support, stressing the importance of patient-tailored SDM support. Cancer patients and survivors did not significantly differentiate trained from untrained HCPs when evaluating SDM support, and agreement between their perceptions was poor.The clinical relevance of training GPs and nurses in SDM support needs to be established.Patient-tailored SDM support may be recommended, given the variation in APs' assessments and their possible diverging perceptions of SDM support.This innovative study design (having patients watch and assess videos of simulated consultations made in the context of training evaluation) needs to be further developed.


Edge effects on the orchid-bee fauna (Hymenoptera: Apidae) at a large remnant of Atlantic Rain Forest in southeastern Brazil.
Male orchid bees were sampled with chemical baits monthly from July 1999 to April 2000 at six sites situated at different distances from the forest edge (0 to 4,000 m) at Parque Estadual do Rio Doce, the largest remnant of Atlantic Forest in the state of Minas Gerais, southeastern Brazil. The main goal of this study was to assess the abundance, richness, and the community structure of the orchid-bee fauna at different distances from the edge. In all, 1,183 males from 20 species were collected. Only minor and insignificant variation in richness and abundance were observed among the sites. Two dominant species, Euglossa analis Westwood (Hymenoptera: Apidae) and Eulaema cingulata (Fabricius) (Hymenoptera: Apidae), showed strongly opposing habitat associations: while males of the former were most collected in the interior of the forest, the latter was most found at or close to the edge. The responses of individual species, such as these, and not composite measures of richness and abundance, are more informative regarding forest integrity and edge effects.


The efficiency of the EORTC scoring system for the prediction of recurrence and progression of non-muscle-invasive bladder cancer treated by bacillus Calmette-Guerin immunotherapy.
The authors determined the recurrence and progression at 1 year in patients with non-muscle-invasive urothelial carcinoma who underwent transurethral resection of bladder tumor (TURBT) and compared the results with the calculated risk according to the European Organization of Research and Treatment of Cancer (EORTC). Between 2002 and 2011, a total of 112 patients with NMIBC were treated with transurethral resection of bladder cancer. According to the EORTC scoring system, the patients were categorized in terms of number of tumors, tumor size, prior recurrence rate, T category, carcinoma in situ, and pathologic grade, and the scores were summed. According to the summed scores, the recurrence group and the progression group were divided into 3 subgroups: low, intermediate, and high risk, respectively. The recurrence rate and progression rate of each group were compared with the EORTC risk tables. The mean patient age was 63.9 years (range: 25-85) at diagnosis. Seventy-eight patients (68.4%) had a recurrent disease, 53 (47.3%) had a tumor larger than 3 cm in diameter, 55 (49.1%) had multiple lesions, 3 (0.26%) had carcinoma in situ, 44(39.3%) had stage T1 lesions, and 20 (17.8%) had a high-grade disease. The recurrence rates were 0, 14.2, 31.25, and 85.71% in groups with the predicted EORTC risks of 15, 24, 38, and 61%, respectively. There were 3 patients (0.2%) with progression of the diseases. The EORTC model successfully stratified recurrence and progression risks in this cohort. However, the discriminative ability of the EORTC tables decreased in these patients for progression.


Prophylactic mesh does not prevent parastomal hernia in long-term: Meta-analysis and trial sequential analysis.
Previous randomized clinical trials, systematic reviews, and meta-analyses evaluating parastomal hernia prevention with mesh placement during end colostomy formation have reported contradictory results. This review aimed to assess the efficacy of this strategy in long-term follow-up according to the latest available data. Medline, EMBASE, Cochrane Library, Web of Science, and Google Scholar were searched. Randomized clinical trials were included if they compared mesh with no mesh during initial end colostomy creation in adult patients to prevent parastomal hernia with a follow-up longer than 2 years. A meta-analysis was performed to evaluate parastomal hernia incidence (primary outcome), parastomal hernia repair rate, and mortality. Subgroup analysis included surgical approach and mesh position, and trial sequential analysis was performed. Eight randomized clinical trials involving 537 patients met the inclusion criteria. Based on long-term follow-up, the incidence of parastomal hernia was not reduced when a prophylactic mesh was placed (relative risk = 0.68 [95% confidence interval:0.46-1.02]; I2 = 81%, P =.06). The parastomal hernia repair rate was low; however, no difference was found between the groups (relative risk = 0.90 [95% confidence interval:0.51-1.56]; I2 = 0%; P = .70), and no difference was detected between the groups when mortality was assessed (relative risk = 1.03 [95% confidence interval: 0.77-1.39]; I2 = 21%; P = .83). Subgroup analyses did not show differences according to the surgical approach or mesh position used. Regarding trial sequential analysis, an optimal information size was not achieved. Prophylactic mesh placement during end colostomy formation does not prevent parastomal hernia in the long term. The parastomal hernia repair rate and mortality rate did not vary between the included groups. Heterogeneity among the included randomized clinical trials might restrict the reliability of the results.


[Early signs of alcoholic cardiomyopathy].
Early signs of alcoholic cardiopathy were studied spiroergometrically and electrocardiographically in 90 males, aged 25 to 40 years, with second-stage chronic alcoholism. A fairly high physical stress tolerance (600 kgm) was found in 75.6% of the patients. Some functional parameters (metabolic units, the "oxygen pulse" of exercise, oxygen debt liquidation time) were, however, disturbed in patients with a less than 5 years' history of the disease. In those cases where alcoholism had lasted for over 5 years, the aerobic reserve was more markedly decreased during exercise, while adaptation to exercise was delayed. Electrocardiographic changes brought out by exercise testing included the emergence of spiked and deformed P waves, a prolonged systolic index and extrasystole, and flattened T wave at rest, its duration showing a direct correlation to the magnitude of oxygen debt.


A Phosphate Uptake System Is Required for Xanthomonas citri pv. glycines Virulence in Soybean.
The genes encoding the phosphate uptake system in Xanthomonas citri pv. glycines 12-2 were previously found to be upregulated when in soybean leaves. This study thus explored the role of the phosphate uptake system on its virulence to soybean. While phoB and pstSCAB mutants were greatly impaired in both inciting disease symptoms and growth in soybean, the virulence and growth in soybean of a phoU mutant was not reduced when compared with the wild-type strain. The expression of phoB and pstSCAB was highly induced in phosphate-deficient media. In addition, the expression of phoB, assessed with a fusion to a promoterless ice nucleation reporter gene, was greatly increased in soybean leaves, confirming that the soybean apoplast is a phosphorus-limited habitat for X. citri pv. glycines. Global gene expression profiles of phoB and phoU mutants of X. citri pv. glycines conducted under phosphate-limitation conditions in vitro, using RNA-seq, revealed that PhoB positively regulated genes involved in signal transduction, the xcs cluster type II secretion system, cell motility, and chemotaxis, while negatively regulating cell wall and membrane biogenesis, DNA replication and recombination and repair, and several genes with unknown function. PhoU also positively regulated the same genes involved in cell motility and chemotaxis. The severity of bacterial pustule disease was decreased in soybean plants grown under high phosphate fertilization conditions, demonstrating that high phosphate availability in soybean plants can affect infection by X. citri pv. glycines by modulation of the expression of phosphate uptake systems. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.


Bulla Down Endoscopic Sphenoidotomy.
Surgical approach to the sphenoid sinus is still one of the most challenging steps in sinus surgery. The author describes a novel, simple, and safe technique to access sphenoid sinus to manage isolated sphenoid pathologies or approach skull base by removing the bulla ethmoidalis and temporarily lateralizing the middle turbinate during endoscopic sinus surgery. The current approach provides an effective method to access the sphenoid sinus without increasing morbidity and avoids unnecessary possible complications associated with turbinates' resection.


Annexin A2 Enhances Complement Activation by Inhibiting Factor H.
Factor H is a circulating protein that regulates activation of the alternative pathway (AP) of complement. Mutations and genetic variations of factor H are associated with several AP-mediated diseases, highlighting the critical role of factor H in AP regulation. AP-mediated inflammation is typically triggered by illness or tissue injury, however, and tissue injury can trigger AP activation in individuals with fully functional factor H. This suggests that factor H function is affected by local conditions within tissues. We hypothesized that inducible proteins impair the ability of factor H to locally control the AP, thereby increasing AP activation. We used purified murine factor H to immunoprecipitate binding partners from mouse kidneys. Using immunoaffinity liquid chromatography-mass spectrometry, we identified annexin A2 as a factor H binding partner. Further experiments showed that annexin A2 reduces the binding of factor H to cell surfaces. Recombinant annexin A2 impaired complement regulation by factor H and increased complement activation on renal cell surfaces in vitro and in vivo. In a murine model of acute pneumococcal otitis media, the administration of annexin A2 increased AP-mediated bacterial opsonization and clearance. In conclusion, the local production of annexin A2 within tissues suppresses regulation of the AP by factor H. Annexin A2 can contribute to AP-mediated tissue inflammation by locally impairing factor H function, but it can also improve complement-mediated bacterial clearance.


The relationship between anxiety disorders in adults and recalled childhood teasing.
This study investigated the relationship between retrospective accounts of childhood teasing and anxiety disorders as well as the relationship between experiences of teasing and more global psychological well-being. Participants (N=377) with social anxiety disorder (SAD), obsessive compulsive disorder (OCD), or panic disorder with or without agoraphobia (PD) were compared on levels of self-reported teasing history using the Teasing Questionnaire-Revised (TQ-R; Storch et al., 2004). Teasing frequency scores were higher for the SAD group compared to both PD and OCD groups. Across all groups, teasing scores were significantly related to increased social anxiety, depression, stress, and greater impairment in functioning. Teasing frequency accounted for unique variance in severity of SAD symptoms even after controlling for concurrent mood, anxiety and stress. These results support and extend previous findings linking childhood teasing to anxiety disorders in adulthood.


The microbial communities in male first catch urine are highly similar to those in paired urethral swab specimens.
Urine is the CDC-recommended specimen for STI testing. It was unknown if the bacterial communities (microbiomes) in urine reflected those in the distal male urethra. We compared microbiomes of 32 paired urine and urethral swab specimens obtained from adult men attending an STD clinic, by 16S rRNA PCR and deep pyrosequencing. Microbiomes of urine and swabs were remarkably similar, regardless of STI status of the subjects. Thus, urine can be used to characterize urethral microbiomes when swabs are undesirable, such as in population-based studies of the urethral microbiome or where multiple sampling of participants is required.


Cellular variant of extraskeletal myxoid chondrosarcoma with Ewing's sarcoma-like areas: a diagnostic pitfall in core needle biopsy.
Extraskeletal myxoid chondrosarcoma (EMC) is a rare mesenchymal soft tissue tumour that poses diagnostic difficulty as it lacks a characteristic immunophenotype, in addition to its wide morphological spectrum. Microscopically, EMC shows strands and cords of relatively small cells with acidophilic cytoplasm that are occasionally vacuolated. Small cells with scant cytoplasm may comprise some EMC. We describe a rare and challenging case of EMC, which shows an unusual morphology with small blue cells, raising the possibility of PNET/Ewing's sarcoma. The small cellular variant of EMC usually poses diagnostic difficulty, particularly during its evaluation in a core needle biopsy. Consideration of EMC, small cell variant, in evaluation of a blue cell tumour, may avoid a potential diagnostic pitfall. Proper diagnosis of EMC and its differentiation from PNET/Ewing's sarcoma is crucial due to a difference in management protocols and prognostic outcome.


[Clinical morphofunctional evaluation of gingival tissues status in cases of implant based dental prosthetics].
There was studied clinical morphofunctional gingival tissues status in the region of 60 intraosseous implants with the use of clinical and cytomorphometric methods in 20 patients on prosthetic stage of the treatment. Early inflammatory complications in periimplants soft tissues on initial stage of prosthetics making according to the data of cytomorphometry. High self-descriptiveness and objectivity of the method in comparison with clinical methods was proved.


Towards the functional high-resolution coordination chemistry of blood plasma human serum albumin.
Human serum albumin (HSA) is a monomeric, globular, multi-carrier and the most abundant protein in the blood. HSA displays multiple ligand binding sites with extraordinary binding capacity for a wide range of ions and molecules. For decades, HSA's ability to bind to various ligands has led many scientists to study its physiological properties and protein structure; indeed, a better understanding of HSA-ligand interactions in human blood, at the atomic level, will likely foster the development of more potent, and overall more performant, diagnostic and therapeutic tools against serious human disorders such as diabetes, cardiovascular disorders, and cancer. Here, we present a concise overview of the current knowledge of HSA's structural characteristics, and its coordination chemistry with transition metal ions, within the scope and limitations of current techniques and biophysical methods to reach atomic resolution in solution and in blood serum. We also highlight the overwhelming need of a detailed atomistic understanding of HSA dynamic structures and interactions that are transient, weak, multi-site and multi-step, and allosterically affected by each other. Considering the fact that HSA is a current clinical tool for drug delivery systems and a potential contender as molecular cargo and nano-vehicle used in biophysical, clinical and industrial fields, we underline the emerging need for novel approaches to target the dynamic functional coordination chemistry of the human blood serum albumin in solution, at the atomic level.


Eimeria infections in goats in Southern Portugal.
Coccidiosis caused by Eimeria species is a major form of intestinal infection affecting intensively and semi-intensively reared goats. The province of Alentejo is the main goat-producing area in Portugal. Therefore, all 15 Serpentina goat farms in Alentejo were analyzed regarding the occurrence and diversity of Eimeria species. Fecal samples obtained from 144 animals (52.1% dairy goats, 47.9% pre-pubertal goats) were examined using the modified McMaster technique to determine the number of oocysts per gram of feces. Eimeria spp. oocysts were present in 98.61% of the fecal samples and, overall, nine different Eimeria species were identified. The most prevalent species were E. ninakohlyakimovae (88%) and E. arloingi (85%), followed by E. alijevi (63%) and E. caprovina (63%). The average number of oocysts shed was significantly lower in dairy goats than in pre-adult animals. Astonishingly, no clinical signs of coccidiosis were observed in any of the animals examined, even though they were shedding high numbers of oocysts and were infected with highly pathogenic species. Thus, implementation of routine diagnostic investigation of the occurrence and diversity of caprine Eimeria species may be a useful tool for determination and better understanding of their potential economic impact on goat herds in southern Portugal.


Biogenic Amine Formation and Microbiological Quality of Anchovy (Engraulis encrasicolus) Treated with Lavender and Lemon Balm Ethanol Extracts.
Biogenic amine formation and bacterial growth of vacuum-packed European anchovy treated with 1% lemon balm (LB) or lavender (LD) ethanol extracts was investigated. The treated samples were stored at 2 ± 1 °C for 11 d and analyzed for biogenic amines, total viable count, fecal coliform count, and lactic acid bacterial count. The analyses were done on 0, 4, 7, 9, and 11 d of storage. Both LB and LD extracts proved effective in reducing most biogenic amines, with histamine reduced by 3-fold compared to control. The calculated biogenic amine index showed that LB extract was the most effective in inhibiting the biogenic amine formation. The reduction in total viable count was low and the bacterial contamination reached more than 7 log cfu/g at the end of the storage period for all the samples. Moreover, the reduction in fecal coliform and lactic acid bacterial count by LB and LD extracts was below 1 log cfu/g. Treatment of European anchovy with LB and LD extracts proved to be a very effective preservation technique to reduce the biogenic amine formation and lower the risk of histamine fish poisoning but is not effective in reduction of bacterial load. Consequently, LB and LD extracts could be used to reduce the biogenic amine formation which provides additional safety prior to spoilage for histamine sensitive fish species.


A longitudinal study of epigenetic variation in twins.
DNA methylation is a key epigenetic mechanism involved in the developmental regulation of gene expression. Alterations in DNA methylation are established contributors to inter-individual phenotypic variation and have been associated with disease susceptibility. The degree to which changes in loci-specific DNA methylation are under the influence of heritable and environmental factors is largely unknown. In this study, we quantitatively measured DNA methylation across the promoter regions of the dopamine receptor 4 gene (DRD4), the serotonin transporter gene (SLC6A4/SERT) and the X-linked monoamine oxidase A gene (MAOA) using DNA sampled at both ages 5 and 10 years in 46 MZ twin-pairs and 45 DZ twin-pairs (total n=182). Our data suggest that DNA methylation differences are apparent already in early childhood, even between genetically identical individuals, and that individual differences in methylation are not stable over time. Our longitudinal-developmental study suggests that environmental influences are important factors accounting for interindividual DNA methylation differences, and that these influences differ across the genome. The observation of dynamic changes in DNA methylation over time highlights the importance of longitudinal research designs for epigenetic research.


Suppression of agrin-22 production and synaptic dysfunction in Cln1 (-/-) mice.
Oxidative stress in the brain is highly prevalent in many neurodegenerative disorders including lysosomal storage disorders, in which neurodegeneration is a devastating manifestation. Despite intense studies, a precise mechanism linking oxidative stress to neuropathology in specific neurodegenerative diseases remains largely unclear. Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating neurodegenerative lysosomal storage disease caused by mutations in the ceroid lipofuscinosis neuronal-1 (CLN1) gene encoding palmitoyl-protein thioesterase-1. Previously, we reported that in the brain of Cln1 (-/-) mice, which mimic INCL, and in postmortem brain tissues from INCL patients, increased oxidative stress is readily detectable. We used molecular, biochemical, immunohistological, and electrophysiological analyses of brain tissues of Cln1 (-/-) mice to study the role(s) of oxidative stress in mediating neuropathology. Our results show that in Cln1 (-/-) mice oxidative stress in the brain via upregulation of the transcription factor, CCAAT/enhancer-binding protein-δ, stimulated expression of serpina1, which is an inhibitor of a serine protease, neurotrypsin. Moreover, in the Cln1 (-/-) mice, suppression of neurotrypsin activity by serpina1 inhibited the cleavage of agrin (a large proteoglycan), which substantially reduced the production of agrin-22, essential for synaptic homeostasis. Direct whole-cell recordings at the nerve terminals of Cln1 (-/-) mice showed inhibition of Ca(2+) currents attesting to synaptic dysfunction. Treatment of these mice with a thioesterase-mimetic small molecule, N-tert (Butyl) hydroxylamine (NtBuHA), increased agrin-22 levels. Our findings provide insight into a novel pathway linking oxidative stress with synaptic pathology in Cln1 (-/-) mice and suggest that NtBuHA, which increased agrin-22 levels, may ameliorate synaptic dysfunction in this devastating neurodegenerative disease.


Genetic and epidemiological relationships among Campylobacter isolates from humans.
84 Campylobacter jejuni isolates from Swedish patients with domestic infection were characterized with pulsed-field gel electrophoresis (PFGE), and the subtype information considered in relation to epidemiological data. Based on pattern combinations from restriction cleavage with SmaI and SalI, 52 different PFGE types were identified. Types with an average pattern similarity of at least 82% and 63% were assembled in groups and clusters, respectively. The 2 largest clusters included 71% of the isolates. The distribution in time varied between different groups and clusters, where some were isolated sporadically during the whole period and others appeared more concentrated in time. Types in 1 cluster were significantly more often isolated in summer than other types in the study. Isolates from children showed lower pattern similarity to other isolates than isolates from adults. Sets of type and time related cases, possibly representing small outbreaks, were identified when indistinguishable PFGE patterns were found in isolates from temporally related cases. Our results indicate that although a large number of genotypes may be found among C. jejuni strains infecting humans, a large proportion of these may be genetically related, and that different genotypes may appear during different seasons and infect individuals of different ages.


Imaging time-resolved electrothermal atomization laser-excited atomic fluorescence spectrometry for determination of mercury in seawater.
In this study, direct determination of mercury at the nanogram per liter level in the complex seawater matrix by imaging time-resolved electrothermal atomization laser-excited atomic fluorescence spectrometry (ITR-ETA-LEAFS) is described. In the case of mercury, the use of a nonresonant line for fluorescence detection with only one laser excitation is not possible. For measurements at the 253.652 nm resonant line, scattering phenomena have been minimized by eliminating the simultaneous vaporization of salts and by using temporal resolution and the imaging mode of the camera. Electrothermal conditions (0.1 M oxalic acid as matrix modifier, low atomization temperature) have been optimized in order to suppress chemical interferences and to obtain a good separation of specific signal and seawater background signal. For ETA-LEAFS, a specific response has been obtained for Hg with the use of time resolution. Moreover, an important improvement of the detection limit has been obtained by selecting, from the furnace image, pixels collecting the lowest number of scattered photons. Using optimal experimental conditions, a detection limit of 10 ng L(-1) for 10 μL of sample, close to the lowest concentration level of total Hg in the open ocean, has been obtained.


A germline clone screen for meiotic mutants in Drosophila melanogaster.
Using an FLP/FRT-based method to create germline clones, we screened Drosophila chromosome arms 2L and 3R for new female meiotic mutants. The screen was designed to recover mutants with severe effects on meiotic exchange and/or segregation. This screen yielded 11 new mutants, including six alleles of previously known meiotic genes (c(2)M and ald/mps1). The remaining five mutants appear to define at least four new genes whose ablation results in severe meiotic defects. Three of the novel meiotic mutants were identified at the molecular level. Two of these, mcm5(A7) and trem(F9), define roles in meiotic recombination, while a third, cona(A12), is important for synaptonemal complex assembly. Surprisingly, five of the nine mutants for which the lesion has been identified at the molecular level are not the result of mutations characteristic of EMS mutagenesis, but rather due to the insertion of the transposable element Doc. This study demonstrates the utility of germline clone-based screens for the discovery of strong meiotic mutants, including mutations in essential genes, and the use of molecular genetic techniques to map the loci.


Observations of radionuclide imaging in hypertrophic pulmonary osteoarthropathy.
99mTc pyrophosphate was employed in the study of patients with hypertrophic pulmonary osteoarthropathy. Several facts emerge when comparing the radionuclide, radiographic and clinical findings. Radionuclide imaging reveals the presence and extent of subperiosteal activity with greater clarity than does radiography. Synovitis associated with the syndrome is readily disclosed, and the regression of the skeletal manifestions following excision of the pulmonary lesion can be documented.


Development of scales of severity of facial cleft impairment.
The reliability and validity of human judgments in rating the severity of cleft-related facial impairment were examined in this series of studies. The goal of the research was to develop scales for rating the severity of facial cleft impairment using psychophysical methods for measuring human judgment. The principle findings were: (1) Four photographic categorized scales with high inter-group reliability and satisfactory content and construct validity were developed; (2) Raters used objective stimulus characteristics of the face to scale impairment; (3) Ratings of facial attractiveness decreased as the severity of impairment increases; (4) Full face ratings of the severity of impairment correlated highly with ratings of the same photographs cropped below the eyes. The implications of these findings for clinical and research application are discussed.


[Subhepatic abscess as a late complication of missed intraperitoneal gallstone after laparoscopic cholecystectomy].
Laparoscopic cholecystectomy is the treatment of choice in symptomatic cholelithiasis. Despite its many advantages over the conventional laparotomic approach, accidental perforation of the gallbladder with spilled stones and bile leakage is frequent during this procedure. Complications from missed gallstones are uncommon, although they can sometimes lead to severe consequences. Great effort must be made to achieve laparoscopic retrieval of all the gallstones missed into the peritoneal cavity and conversion to an open procedure should be used only in selected cases. We report a case of subhepatic abscess as a late complication of a missed gallstone during a previous laparoscopic cholecystectomy.


TADPOLE Challenge: Accurate Alzheimer's disease prediction through crowdsourced forecasting of future data.
The Alzheimer's Disease Prediction Of Longitudinal Evolution (TADPOLE) Challenge compares the performance of algorithms at predicting the future evolution of individuals at risk of Alzheimer's disease. TADPOLE Challenge participants train their models and algorithms on historical data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. Participants are then required to make forecasts of three key outcomes for ADNI-3 rollover participants: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog 13), and total volume of the ventricles - which are then compared with future measurements. Strong points of the challenge are that the test data did not exist at the time of forecasting (it was acquired afterwards), and that it focuses on the challenging problem of cohort selection for clinical trials by identifying fast progressors. The submission phase of TADPOLE was open until 15 November 2017; since then data has been acquired until April 2019 from 219 subjects with 223 clinical visits and 150 Magnetic Resonance Imaging (MRI) scans, which was used for the evaluation of the participants' predictions. Thirty-three teams participated with a total of 92 submissions. No single submission was best at predicting all three outcomes. For diagnosis prediction, the best forecast (team Frog), which was based on gradient boosting, obtained a multiclass area under the receiver-operating curve (MAUC) of 0.931, while for ventricle prediction the best forecast (team EMC1 ), which was based on disease progression modelling and spline regression, obtained mean absolute error of 0.41% of total intracranial volume (ICV). For ADAS-Cog 13, no forecast was considerably better than the benchmark mixed effects model (BenchmarkME ), provided to participants before the submission deadline. Further analysis can help understand which input features and algorithms are most suitable for Alzheimer's disease prediction and for aiding patient stratification in clinical trials. The submission system remains open via the website: https://tadpole.grand-challenge.org/.


Tunable microwave generation based on a dual-wavelength single-longitudinal-mode fiber laser using a phase-shifted grating on a triangular cantilever.
Frequency tunable microwave signal generation, based on a dual-wavelength single-longitudinal-mode (SLM) erbium-doped fiber (EDF) laser, incorporating a phase-shifted fiber Bragg grating (PS-FBG) with two π-phase shifts, is demonstrated. In the proposed configuration, the PS-FBG with two ultranarrow transmission bands is embedded in a triangular cantilever to serve as a wavelength spacing tunable filter with a fixed center wavelength by applying various strains on the cantilever. A section of unpumped EDF is employed as a saturable absorber to ensure SLM operation in each of the two lasing lines. By beating the two wavelengths at a photodiode, a tunable microwave signal ranging from 8.835 to 24.360 GHz is successfully achieved.


Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease.
Congenital heart defects constitute the most common human birth defect, however understanding of how these disorders originate is limited by our ability to model the human heart accurately in vitro. Here we report a method to generate developmentally relevant human heart organoids by self-assembly using human pluripotent stem cells. Our procedure is fully defined, efficient, reproducible, and compatible with high-content approaches. Organoids are generated through a three-step Wnt signaling modulation strategy using chemical inhibitors and growth factors. Heart organoids are comparable to age-matched human fetal cardiac tissues at the transcriptomic, structural, and cellular level. They develop sophisticated internal chambers with well-organized multi-lineage cardiac cell types, recapitulate heart field formation and atrioventricular specification, develop a complex vasculature, and exhibit robust functional activity. We also show that our organoid platform can recreate complex metabolic disorders associated with congenital heart defects, as demonstrated by an in vitro model of pregestational diabetes-induced congenital heart defects.


Coaxial PCL/PEG-thiol-ene microfiber with tunable physico-chemical properties for regenerative scaffolds.
Tissue regeneration requires scaffolds that exhibit mechanical properties similar to the tissues to be replaced while allowing cell infiltration and extracellular matrix production. Ideally, the scaffolds' porous architecture and physico-chemical properties can be precisely defined to address regenerative needs. We thus developed techniques to produce hybrid fibers coaxially structured with a polycaprolactone core and a 4-arm, polyethylene glycol thiol-norbornene sheath. We assessed the respective effects of crosslink density and sheath polymer size on the scaffold architecture, physical and mechanical properties, as well as cell-scaffold interactions in vitro and in vivo. All scaffolds displayed high elasticity, swelling and strength, mimicking soft tissue properties. Importantly, the thiol-ene hydrogel sheath enabled tunable softness and peptide tethering for cellular activities. With increased photopolymerization, stiffening and reduced swelling of scaffolds were found due to intra- and inter-fiber crosslinking. More polymerized scaffolds also enhanced the cell-scaffold interaction in vitro and induced spontaneous, deep cell infiltration to produce collagen and elastin for tissue regeneration in vivo. The molecular weight of sheath polymer provides an additional mechanism to alter the physical properties and biological activities of scaffolds. Overall, these robust scaffolds with tunable elasticity and regenerative cues offered a versatile and effective platform for tissue regeneration.


The design of experiments using isotopes for the determination of the rates of disposal of blood-borne substrates in vivo with special reference to glucose, ketone bodies, free fatty acids and proteins.
1. The two well-known methods of estimating rates of irreversible disposal (R) of blood-borne substrates in vivo by isotope experiments involve estimating the specific radioactivity (S) of the substrate in blood either after single intravenous injection of labelled substrate or during its infusion at a constant rate. The value of R is calculated from the S-time curve, usually by assuming: (i) a metabolic steady state with respect to substrate, (ii) the passage of all substrate through the blood, and (iii) the absence of certain types of recycling via blood. 2. In a theoretical investigation we show how experiments can be performed and R calculated from analyses of blood when one or more of the above assumptions is unjustified, by using glucose, ketone bodies, plasma free fatty acids and proteins as examples. In general the methods require single injection procedures, with estimation of the total quantity of label in the substrate in blood and the substrate concentration instead of only S. Such values give estimates of R with standard errors even when only one blood specimen is taken from each of a group of animals, as is convenient when working with small animals or substrates in low concentration, and when the animals are in a non-steady state in which constant infusion procedures are invalid. 3. Similar methods give the fraction of label injected as one compound which passes through another (the isotopic yield). 4. The methods are not always applicable, and cannot be applied to plasma proteins in some pathological conditions. A questionnaire for assessing their applicability is given.


Analysis of published sprout seed sanitization studies shows treatments are highly variable.
Consumption of raw sprouts has caused many foodborne illness outbreaks in the last decade, and most outbreaks have been linked to contaminated seeds. Many seed sanitization treatments have been studied as a means to reduce the risk of illness associated with sprouts. Published data on seed sanitization were analyzed collectively to identify factors that influenced the efficacy of seed sanitization and to determine the variability associated with various sanitization processes. Temperature and duration of the sanitization treatment were found to produce a negligible effect on log microbial reductions. Salmonella, Escherichia coli O157:H7, and total aerobic microorganisms were all inactivated at similar rates. Data were fit to triangular or uniform distributions for 16 different chemical treatments. Among the most effective treatments were 8% hydrogen peroxide (uniform distribution [2.5, 4.5]), 20,000 ppm of chlorine (triangular distribution [1, 2.5, 6.5]), and 1% Ca(OH)2 (triangular distribution [0.5, 4, 5]). Chemical treatments where more published data were available showed more variability.


[Climate, brain, and degeneration in Cabanis].
This analysis of the arguments defended by Cabanis in "Rapports du physique et du moral de l'homme" takes as its point of departure his eighth and ninth Memoirs, which focus on analyzing the influences of regime and climate. These writings afford a new reading of the arguments Cabanis used to explain the relation between the physical traits and moral habits of individuals and races. The article analyzes his debts to natural history, especially Buffon's theory of degeneration; to the Hippocratic tradition, above all the humor theory; and to studies of brain anatomy and pathology. Lastly, it examines the role that the human and moral sciences of medicine and hygiene play in the regeneration of the human species.


Deciphering the genetic predisposition to primary sclerosing cholangitis.
Genetic variants within the major histocompatibility complex (MHC) on chromosome 6 have been shown to confer risk for primary sclerosing cholangitis (PSC) ~30 years ago. However, robust genetic associations outside this genetic region have been difficult to establish. By genome-wide association analysis, a surprising large overlap of genetic risk loci outside of the MHC with prototypical autoimmune diseases has been recognized. In this article, we review the present knowledge of susceptibility loci in PSC, by assessing the robustness of the findings and speculating on potential mechanistic roles of predicted risk genes in PSC pathogenesis. We suggest a model where the primary insult is likely to resemble the tissue injury in most autoimmune conditions. Functional insight into risk pathways could offer novel therapeutic opportunities, and we speculate on specific opportunities that may arise based on current knowledge.


Biocompatible coatings with high albumin affinity.
A process was developed to coat complex medical devices with a thin, transparent, biocompatible film. The film is based on silicone rubber (SR) but has higher albumin affinity than SR. Two polymer forms have been developed: one substitutes hydroxyl groups (OH), the other, 16 carbon acyl groups (C16) in the siloxane side chains. Oxymercuration/demercuration or hydroboration reactions can be used. SEM reveals film surfaces are smooth, uniform, and featureless. ATR/FTIR spectra and advancing/receding water contact angle measurements confirm the presence of surface OH groups and suggest the presence of surface acyl groups. Albumin adsorption and retention are markedly enhanced for surface OH and C16 concentrations as low as 5% reaction yield. Kinetics, isotherm, and competitive albumin/fibrinogen adsorption studies suggest that surface hydroxylation, and perhaps C16 acylation as well, markedly improve the albumin affinity, but not the fibrinogen affinity, of this material. The SR film can be durably coated on several materials, making it possible to favorably treat many blood-contacting devices, using a simple immersion process.


Ionization thresholds of small carbon clusters: tunable VUV experiments and theory.
Small carbon clusters (Cn, n = 2-15) are produced in a molecular beam by pulsed laser vaporization and studied with vacuum ultraviolet (VUV) photoionization mass spectrometry. The required VUV radiation in the 8-12 eV range is provided by the Advanced Light Source (ALS) at the Lawrence Berkeley National Laboratory. Mass spectra at various ionization energies reveal the qualitative relative abundances of the neutral carbon clusters produced. By far the most abundant species is C3. Using the tunability of the ALS, ionization threshold spectra are recorded for the clusters up to 15 atoms in size. The ionization thresholds are compared to those measured previously with charge-transfer bracketing methods. To interpret the ionization thresholds for different cluster sizes, new ab initio calculations are carried out on the clusters for n = 4-10. Geometric structures are optimized at the CCSD(T) level with cc-pVTZ (or cc-pVDZ) basis sets, and focal point extrapolations are applied to both neutral and cation species to determine adiabatic and vertical ionization potentials. The comparison of computed and measured ionization potentials makes it possible to investigate the isomeric structures of the neutral clusters produced in this experiment. The measurements are inconclusive for the n = 4-6 species because of unquenched excited electronic states. However, the data provide evidence for the prominence of linear structures for the n = 7, 9, 11, 13 species and the presence of cyclic C10.


Prevalence of bovine herpesvirus-1, bovine viral diarrhea, parainfluenza-3, goat respiratory syncytial, bovine leukemia, and bluetongue viral antibodies in sheep.
Sera from healthy sheep were collected in January and March 1982 from flocks of sheep located in southwestern and southeastern Louisiana. These sera were tested for bovine herpesvirus-1 (BHV-1), bovine viral diarrhea virus (BVDV), parainfluenza-3 (PI-3) virus, and goat respiratory syncytial virus (GRSV) antibodies by microtitration virus-neutralization test. The sera were tested also for bovine leukemia virus (BLV) and bluetongue virus (BTV) antibodies by immunodiffusion tests. The number of flocks with seropositive sheep for each virus were: 2/8 (25%) for BVDV; 8/8 (100%) for PI-3 virus; 7/8 (87.5%) for GRSV; and 6/8 (75%) for BTV. Seropositive rates for each virus for the individual sheep tested were: 4/158 (2.5%) for BVDV; 117/158 (74.1%) for PI-3 virus; 77/158 (48.7%) for GRSV; and 21/158 (13.3%) for BTV. All sheep were seronegative for BHV-1 and BLV.


Hemichondrodiastasis for the treatment of genu varum deformity associated with bone dysplasias.
Hemichondrodiastasis has been reported for treatment of angular deformities in children close to skeletal maturity. The use of distraction through the physis in younger children was not recommended. The authors report three children 3 to 7 years of age who underwent bilateral proximal tibial hemichondrodiastasis for correction of genu varum due to bone dysplasia. Ilizarov external fixators were applied in all cases. The patients underwent gradual angular correction at a rate of 0.5 mm/d. Distraction was continued until a normal mechanical axis was achieved. Normal alignment was achieved in two patients and slight overcorrection in the third. The patients were followed for 3 to 11 years, and no adverse affects on the physis were identified. This is the first report of physeal distraction in patients this young. Our results are good, and we believe that hemichondrodiastasis can be safely used for correction of angular deformities in young children.


BET 1: Prednisolone for the treatment of acute gouty arthritis.
A short cut review was carried out to establish whether corticosteroids are safe and effective in managing the symptoms of acute gouty arthritis. Five studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that corticosteroids are an effective and safe alternative to non steroidal anti inflammatory drugs (NSAIDs) in patients presenting with acute gouty arthritis.


Outcomes of cleft palatal repair for internationally adopted children.
Families in the United States adopted approximately 230,000 foreign-born children over the past two decades. Age at adoption and the presence of a cleft palate impact speech and language development. The authors' purpose is to document speech outcome after palatal closure in internationally adopted children. The authors reviewed internationally adopted children with cleft lip-cleft palate or cleft palate who had two-flap palatoplasty from 1987 to 2010. Data collected included date of birth, cleft palatal type, age at palatoplasty, palatal fistula, postoperative speech assessment, and need for secondary surgery. The authors identified 55 children adopted with unrepaired cleft palate. Palatal types were Veau I (n = 1), II (n = 1), III (n = 37), or IV (n = 16). Median age at palatoplasty was 25.6 ± 11.8 months; palatal fistula occurred in five patients (9 percent). Speech outcome was successful in 28 patients (51 percent), whereas a secondary operation was recommended for 27 patients (49 percent). Need for a secondary operation was independent of palatal type (p = 0.6). Children who required a pharyngeal flap were significantly older at the time of palatoplasty compared with those who did not (p = 0.009). There was a significant association between increasing age at palatoplasty and need for a secondary operation (OR, 1.07; 95 percent CI, 1.01 to 1.13; p = 0.01). Pharyngeal flap significantly improved speech (p < 0.001). International adoption with late palatoplasty can result in disordered speech. Velopharyngeal insufficiency is associated with increasing age at palatoplasty. The authors recommend palatoplasty and speech therapy soon after adoption. Risk, III.


Bone-conducted sound in a dolphin's mandible: Experimental investigation of elastic waves mediating information on sound source position.
Mammals use binaural or monaural (spectral) cues to localize acoustic sources. While the sensitivity of terrestrial mammals to changes in source elevation is relatively poor, the accuracy achieved by the odontocete cetaceans' biosonar is high, independently of where the source is. Binaural/spectral cues are unlikely to account for this remarkable skill. In this paper, bone-conducted sound in a dolphin's mandible is studied, investigating its possible contribution to sound localization. Experiments are conducted in a water tank by deploying, on the horizontal and median planes of the skull, ultrasound sources that emit synthetic clicks between 45 and 55 kHz. Elastic waves propagating through the mandible are measured at the pan bones and used to localize source positions via either binaural cues or a correlation-based full-waveform algorithm. Exploiting the full waveforms and, most importantly, reverberated coda, it is possible to enhance the accuracy of source localization in the vertical plane and achieve similar resolution of horizontal- vs vertical-plane sources. The results noted in this paper need to be substantiated by further experimental work, accounting for soft tissues and making sure that the data are correctly mediated to the internal ear. If confirmed, the results would favor the idea that dolphin's echolocation skills rely on the capability to analyze the coda of biosonar echoes.


[Morphology of lymph nodes in secondary immunodeficiency provoked by acute diffuse peritonitis].
Lymph nodes of 30 patients operated because of acute diffuse peritonitis are studied histologically and immunologically. Two types of the lymph node response are found during the reactive stage. The response of the 1st type (the beginning of peritonitis) is characterized by the activation of T- and B-immunity systems. The signs of the depression are characteristic for the 2nd type. Immunodeficiency is enhanced in toxic and terminal stages. The most informative index of the immunodeficiency degree is a decrease of the ratio T-helper/T-suppressor cytotoxic lymphocytes. There is a close correlation between the state of patients and immunomorphological changes of lymph nodes and blood. Peritonitis results in the development of vitium cordis when intoxication associated with immune disturbances strengthens both the inflammation and intoxication.


Association between heavy metals and metabolic syndrome in drinking water and surface soil: case-control study in Iran.
Although obesity is a major risk factor for metabolic syndrome (MetS), not all obese people develop MetS that is directly related to obesity. This suggests that the risk of MetS is influenced by other genetic or environmental agents such as heavy metals. The aim of this study was to investigate the relationship between heavy metals in drinking water and surface soil, and its relationship with the incidence of MetS. To determine the sampling points of drinking water and surface soil, from the location of 150 people selected for inclusion in the study, 16 points were selected randomly for heavy metal concentration analysis. Results were indicated that mean concentrations of V, Mn, Ni, As, Cd, and Sr in drinking water of MetS group were higher than control group. The concentration of heavy metals in drinking water, except for Mn and Sr, did not show a significant difference between case and control groups. The results of this study showed that concentration of heavy metals in drinking water and surface soil was positively associated with the incidence of MetS.


Role of T lymphocytes in rat 2,4,6-trinitrobenzene sulphonic acid (TNBS) induced colitis: increased mortality after gammadelta T cell depletion and no effect of alphabeta T cell depletion.
Indirect evidence suggests that CD4+ T cells have a pathogenic while gammadelta T cells have a protective role in the initiation and perpetuation of inflammatory bowel disease. To define the role of T cell subsets in a rat colitis model (2,4,6-trinitrobenzene sulphonic acid (TNBS)) we analysed colitis severity after effective depletion of T helper cells, alphabeta T cells, or gammadelta T cells. T helper cells, alphabeta T cells, or gammadelta T cells were depleted using previously described monoclonal antibodies directed at the CD4 molecule (OX38), the CD2 molecule (OX34, both depleting CD4+ T cells), the alphabeta T cell receptor (R73), and the gammadelta T cell receptor (V65). Depletion was verified by flow cytometry and/or immunohistology. Colitis was induced using intracolonic application of TNBS. Surprisingly, depletion of T helper cells or alphabeta T cells had no influence on survival, macroscopic or microscopic scores, or myeloperoxidase activity following colitis induction. In contrast, depletion of gammadelta T cells resulted in significantly increased mortality (V65: 73%, n=15) compared with controls (30%, n=13; p<0.03). In addition, colitis was histologically more severe in the gammadelta T cell depleted group compared with controls (p<0.05). T helper cells or alphabeta T cells did not influence the initiation or perpetuation of rat TNBS colitis. In contrast, gammadelta T cells had a protective role in rat TNBS colitis as depletion caused increased mortality.


Mycoplasma pneumoniae modulates STAT3-STAT6/EGFR-FOXA2 signaling to induce overexpression of airway mucins.
Aberrant mucin secretion and accumulation in the airway lumen are clinical hallmarks associated with various lung diseases such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. Mycoplasma pneumoniae, long appreciated as one of the triggers of acute exacerbations of chronic pulmonary diseases, has recently been reported to promote excessive mucus secretion. However, the mechanism of mucin overproduction induced by M. pneumoniae remains unclear. This study aimed to determine the mechanism by which M. pneumoniae induces mucus hypersecretion by using M. pneumoniae infection of mouse lungs, human primary bronchial epithelial (NHBE) cells cultured at the air-liquid interface, and the conventionally cultured airway epithelial NCI-H292 cell line. We demonstrated that M. pneumoniae induced the expression of mucins MUC5AC and MUC5B by activating the STAT6-STAT3 and epidermal growth factor receptor (EGFR) signal pathways, which in turn downregulated FOXA2, a transcriptional repressor of mucin biosynthesis. The upstream stimuli of these pathways, including interleukin-4 (IL-4), IL-6, and IL-13, increased dramatically upon exposure to M. pneumoniae. Inhibition of the STAT6, STAT3, and EGFR signaling pathways significantly restored the expression of FOXA2 and attenuated the expression of airway mucins MUC5AC and MUC5B. Collectively, these studies demonstrated that M. pneumoniae induces airway mucus hypersecretion by modulating the STAT/EGFR-FOXA2 signaling pathways.


An examination of the strength and electromyographic responses after concentric vs. eccentric exercise of the forearm flexors.
The purpose of this study was to examine the strength and electromyographic (EMG) responses in exercised and nonexercised limbs after concentric (CON) vs. eccentric (ECC) exercise of the forearm flexors. Twenty-five men (mean ± SD age, 23.6 ± 3.8 years; height, 179.7 ± 6.6 cm; body weight, 87.4 ± 14.6 kg) performed 6 sets of 10 maximal CON isokinetic (CON exercise) or ECC isokinetic (ECC exercise) muscle actions of the dominant (DOM) forearm flexors on 2 separate randomly ordered visits. Each subject performed isometric maximal voluntary contractions (MVCs) of both the DOM and nondominant (NONDOM) forearm flexors before (PRE) and immediately after (POST) the exercise interventions. The DOM limb was the only limb exercised for both interventions. A bipolar EMG signal was detected from the biceps brachii during each MVC. The results showed that there were significant 17 and 21% decreases in maximal strength after the CON exercise and ECC exercise, respectively. When collapsed across exercise conditions, strength for the DOM and NONDOM limbs significantly decreased 36 and 4% after exercise, respectively. Accompanied with the strength losses, normalized EMG amplitude for the DOM and NONDOM limbs also reduced 21 and 7%, respectively. These findings suggested that the CON exercise and ECC exercise interventions caused similar strength losses for the exercised arm. There was also a strength loss in the contralateral nonexercised arm that was likely because of neural factors.


Incidence of Perthes' disease in children born between 1973 and 1993.
Background and purpose - The incidence of Perthes' disease as reported in the literature varies widely between and within countries. The etiology of the disease is still unknown. Both environmental and genetic factors have been suggested to play a part in either causing the disease or increasing the susceptibility of an individual. We determined the incidence of Perthes' disease in Sweden and investigated possible relationships to parental socioeconomic status, ethnicity, marital status, mothers' age when giving birth, parity, number of siblings, and smoking habits. Patients and methods - Six Swedish population-based registers were used, together covering all children born in Sweden from 1973 through 1993. Results - The incidence of Perthes' disease in Sweden was 9.3 per 100,000 subjects. The ratio between boys and girls was 3.1:1. The educational level of the father and the mother of a child with Perthes' disease was lower than in the controls. The incidence was lower when the fathers were in the highest income bracket (above the 90th percentile). A higher proportion of parents of Nordic lineage had children with Perthes' disease than parental pairs with one or both who were not of such lineage. Interpretation - This study confirms that there is an association between the incidence of Perthes' disease and the socioeconomic status of the parents.


Coenzyme Q10 in combination with triple therapy regimens ameliorates oxidative stress and lipid peroxidation in chronic gastritis associated with H. pylori infection.
Chronic gastritis associated with H. pylori infection causes oxidative stress in the stomach. This study aimed to evaluate the therapeutic effects of coenzyme q10 among gastric patients infected by H. pylori. By a clinical trial, chronic gastric patients infected by H. pylori were randomly divided into 2 groups: intervention and placebo. The placebo group received a standard triple therapy regimen, and the intervention group received the triple regimen + coenzyme Q10 (CoQ10). Mean inflammation score; serum levels of 3 serum markers were then compared. A total of 100 participants of whom 67% were female were evaluated. The mean age of participants was 59.4 ± 11.4 years. The mean inflammation score was considerably decreased at the end of the study, in the intervention group. The mean levels of total antioxidant capacity (TAC) and glutathione peroxidase (GPx) at the end of the study were reduced among the triple therapy group (P < .05, P =.03 respectively). The mean levels of TAC and GPx were significantly higher among the intervention group at the end of the study compared with those at the start of the study. The combination of triple therapy with CoQ10 demonstrated an effective outcome on the mucosal inflammation, and stress oxidative in patients with chronic gastritis.


Blood haemoglobin is an independent predictor of B-type natriuretic peptide (BNP).
BNP (B-type natriuretic peptide) and anaemia are both associated with adverse outcome in patients with chronic heart failure. Whether low haemoglobin levels are independently predictive of elevated BNP levels in subjects without heart failure is unknown. In the present study, we examined the relationship between haemoglobin and BNP levels in 234 patients with suspected coronary heart disease without a history of chronic heart failure, adjusting for known predictors of BNP levels. By univariate analysis, haemoglobin levels were inversely related to logarithmically transformed BNP values (r = -0.30, P < 0.0001). After adjustment for patient age, gender, body mass index, history of myocardial infarction, use of diuretics, angiotensin-converting enzyme inhibitors and beta-blockers, estimated creatinine clearance rate, extent of coronary disease, left ventricular ejection fraction and left ventricular end-diastolic pressure, blood haemoglobin remained an independent predictor of plasma BNP (standardized beta-coefficient = -0.253, P < 0.0001). A similar relationship was observed between haematocrit and BNP (standardized beta-coefficient -0.215, P < 0.0001). We conclude that haemoglobin levels are independently predictive of plasma BNP levels in patients with suspected coronary heart disease without heart failure. Anaemia may contribute to elevated BNP levels in the absence of heart failure, and may represent an important confounder of the relationship between BNP, cardiac function and prognosis.


Links of Prosodic Stress Perception and Musical Activities to Language Skills of Children With Cochlear Implants and Normal Hearing.
A major issue in the rehabilitation of children with cochlear implants (CIs) is unexplained variance in their language skills, where many of them lag behind children with normal hearing (NH). Here, we assess links between generative language skills and the perception of prosodic stress, and with musical and parental activities in children with CIs and NH. Understanding these links is expected to guide future research and toward supporting language development in children with a CI. Twenty-one unilaterally and early-implanted children and 31 children with NH, aged 5 to 13, were classified as musically active or nonactive by a questionnaire recording regularity of musical activities, in particular singing, and reading and other activities shared with parents. Perception of word and sentence stress, performance in word finding, verbal intelligence (Wechsler Intelligence Scale for Children (WISC) vocabulary), and phonological awareness (production of rhymes) were measured in all children. Comparisons between children with a CI and NH were made against a subset of 21 of the children with NH who were matched to children with CIs by age, gender, socioeconomic background, and musical activity. Regression analyses, run separately for children with CIs and NH, assessed how much variance in each language task was shared with each of prosodic perception, the child's own music activity, and activities with parents, including singing and reading. All statistical analyses were conducted both with and without control for age and maternal education. Musically active children with CIs performed similarly to NH controls in all language tasks, while those who were not musically active performed more poorly. Only musically nonactive children with CIs made more phonological and semantic errors in word finding than NH controls, and word finding correlated with other language skills. Regression analysis results for word finding and VIQ were similar for children with CIs and NH. These language skills shared considerable variance with the perception of prosodic stress and musical activities. When age and maternal education were controlled for, strong links remained between perception of prosodic stress and VIQ (shared variance: CI, 32%/NH, 16%) and between musical activities and word finding (shared variance: CI, 53%/NH, 20%). Links were always stronger for children with CIs, for whom better phonological awareness was also linked to improved stress perception and more musical activity, and parental activities altogether shared significantly variance with word finding and VIQ. For children with CIs and NH, better perception of prosodic stress and musical activities with singing are associated with improved generative language skills. In addition, for children with CIs, parental singing has a stronger positive association to word finding and VIQ than parental reading. These results cannot address causality, but they suggest that good perception of prosodic stress, musical activities involving singing, and parental singing and reading may all be beneficial for word finding and other generative language skills in implanted children.


Up-regulation of intestinal nuclear factor kappa B and intercellular adhesion molecule-1 following traumatic brain injury in rats.
Nuclear factor kappa B (NF-kappaB) regulates a large number of genes involved in the inflammatory response to critical illnesses, but it is not known if and how NF-kappaB is activated and intercellular adhesion molecule-1 (ICAM-1) expressed in the gut following traumatic brain injury (TBI). The aim of current study was to investigate the temporal pattern of intestinal NF-kappaB activation and ICAM-1 expression following TBI. Male Wistar rats were randomly divided into six groups (6 rats in each group) including controls with sham operation and TBI groups at hours 3, 12, 24, and 72, and on d 7. Parietal brain contusion was adopted using weight-dropping method. All rats were decapitated at corresponding time point and mid-jejunum samples were taken. NF-kappaB binding activity in jejunal tissue was measured using EMSA. Immunohistochemistry was used for detection of ICAM-1 expression in jejunal samples. There was a very low NF-kappaB binding activity and little ICAM-1 expression in the gut of control rats after sham surgery. NF-kappaB binding activity in jejunum significantly increased by 160% at 3 h following TBI (P<0.05 vs control), peaked at 72 h (500% increase) and remained elevated on d 7 post-injury by 390% increase. Compared to controls, ICAM-1 was significantly up-regulated on the endothelia of microvessels in villous interstitium and lamina propria by 24 h following TBI and maximally expressed at 72 h post-injury (P<0.001). The endothelial ICAM-1 immunoreactivity in jejunal mucosa still remained strong on d 7 post-injury. The peak of NF-kappaB activation and endothelial ICAM-1 expression coincided in time with the period during which secondary mucosal injury of the gut was also at their culmination following TBI. TBI could induce an immediate and persistent up-regulation of NF-kappaB activity and subsequent up-regulation of ICAM-1 expression in the intestine. Inflammatory response mediated by increased NF-kappaB activation and ICAM-1 expression may play an important role in the pathogenesis of acute gut mucosal injury following TBI.


Videolaryngoscopy Bails us out of Difficult Intubation Scenarios in Syndromic Children: A Case Series.
Airway management in children with craniofacial anomalies can be complicated and may require multiple attempts with conventional direct laryngoscopy (DL). Videolaryngoscopes (VLs) have a well-established role in difficult airway management in adults; however, their role remains to be fully elucidated in paediatric age group. There is a relative paucity in the literature regarding the role of VLs in cases of syndromic children, and it is not clear whether they should be used as an initial option or as a rescue device. Herein, we report a series of cases of children with Pierre Robin sequence, Beckwith-Wiedemann syndrome, and Hurler's syndrome wherein VLs proved beneficial after multiple failed DL attempts. Following initial failed attempts to intubate using DL, these children were subsequently intubated using VLs. Therefore, VLs should be used for initial intubation attempts in syndromic children with potential difficult airways.


Green Bio-Assisted Synthesis, Characterization and Biological Evaluation of Biocompatible ZnO NPs Synthesized from Different Tissues of Milk Thistle (Silybum marianum).
The purpose of the current study was green synthesis of ZnO-nanoparticles (NPs) from different tissues of Silybum marianum (L.) Gaernt. (i.e., seeds, wild plant, in vitro derived plantlets and callus cultures) followed by extensive characterization and evaluation of their biological potency. ZnO-NPs thus synthesized were subjected to characterization using standard techniques such as XRD, FTIR and SEM. Thermal stability of synthesized NPs was also evaluated using thermo-gravimetric analysis. Highly stable crystalline NPs with size ranging between 30.8 and 46.0 nm were obtained from different tissues of S. marianum. These NPs have revealed a wide range of biological applications showing antioxidant, moderate α-amylase inhibitor, antibacterial and cytotoxic potencies. The highest antibacterial activity (20 ± 0.98 mm) was shown by seed extract-mediated ZnO NPs against Staphylococcus aureus (ATCC-6538). Seed extract-mediated ZnO NPs also showed the most potent antioxidant activity (27.7 ± 0.9 µgAAE/mg, 23.8 ± 0.7 µgAAE/mg and 12.7 ± 1.9% total antioxidant capacity (TAC), total reducing power (TRP) and DPPH-free radical scavenging assay (FRSA), respectively). All of the synthesized ZnO NPs also showed cytotoxic activity against the hepato-cellular carcinoma (HepG2) human cells. Interestingly, these ZnO NPs were also highly biocompatible, as evidenced by the brine shrimp lethality and human red blood cells hemolytic assays. Among all of the NPs synthesized and used, the effect of seed extract-mediated NPs was found to be most promising for future applications.


Zika virus and neurologic autoimmunity: the putative role of gangliosides.
An increasing number of severe neurological complications associated with Zika virus (ZIKV), chiefly Guillain-Barré syndrome (GBS) and primary microcephaly, have led the World Health Organization to declare a global health emergency. Molecular mimicry between glycolipids and surface molecules of infectious agents explain most of the cases of GBS preceded by infection, while a direct toxicity of ZIKV on neural cells has been raised as the main mechanism by which ZIKV induces microcephaly. Gangliosides are crucial in brain development, and their expression correlates with neurogenesis, synaptogenesis, synaptic transmission, and cell proliferation. Targeting the autoimmune response to gangliosides may represent an underexploited opportunity to examine the increased incidence of neurological complications related to ZIKV infection.


Species-Specific Auditory Forebrain Responses to Non-Learned Vocalizations in Juvenile Blackbirds.
Species recognition mediates the association of individuals with conspecifics. Learned cues often facilitate species recognition via early social experience with parents and siblings. Yet, in some songbirds, the production of species-typical vocalizations develops in the absence of early social experiences. Here, we investigate the auditory-evoked neural responses of juvenile red-winged blackbirds (Agelaius phoeniceus), a nonparasitic (parental) species within the Icterid family and contrast these results with a closely related Icterid parasitic species that lacks parental care, the brown-headed cowbird (Molothrus ater). We demonstrate that immediate early gene (IEG) activity in the caudomedial mesopallium (CMM) is selectively evoked in response to conspecific non-learned vocalizations in comparison to 2 types of heterospecific non-learned vocalizations, independent of the acoustic similarity patterns between the playback stimuli. This pattern, however, was not detected in the caudomedial nidopallium (NCM). Because the red-winged blackbird is a parental species, the conspecific non-learned vocalization is presumably a familiar sound to the juvenile red-winged blackbird, whereas the heterospecific non-learned vocalizations are novel. We contrast results reported here with our recent demonstration of selective IEG induction in response to non-learned conspecific vocalizations in juvenile parasitic brown-headed cowbirds, in which conspecific non-learned vocalizations are presumably novel. In this case, selective IEG induction from conspecific non-learned vocalization occurred within NCM but not within CMM. By comparing closely related species with stark differences in the early exposure to conspecifics, we demonstrate that CMM and NCM respond to familiar vs. novel non-learned vocalizations in a manner that parallel previously reported regional responses to learned vocalizations such as conspecific songs.


Effects of intravenous gamma immunoglobulins treatment on severe peritonitis in rats.
Generalized purulent peritonitis is characterized by an early exposure of the immune system to a large number of bacterial antigens. The hypothesis that intravenous IgG treatment may improve the outcome of severe experimental peritonitis was studied. Peritonitis was induced in rats by cecal ligation and perforation. Continuous intravenous fluid infusion, broad-spectrum antibiotics, and twenty-four hours treated forty rats after the induction of the disease they were re-operated and the perforated cecum was excised. Twenty of these animals received in addition specific rat IgG in two intravenous infusions (0.4 gr./kg), two and twenty four hours after the induction of peritonitis. Elevated WBC counts and mild metabolic acidosis was found one day after the induction of peritonitis. IgG treatment was associated with lower WBC counts in the following days and with higher pH than in the control group (p < 0.05 for both parameters). All peritoneal cultures and 90% of blood cultures were positive 24 hours after the initial operation. These rates decreased in the following days and in the IgG treatment rats the peritoneal cavity and blood were sterile earlier than in the control animals (p < 0.05). Serum IgG was depleted in the control animals within 48 hours after the induction of peritonitis, while in the IgG treated animals its levels were remarkably elevated. IgG administration significantly improved the survival, which was 70% in the IgG treatment rats as compared to 40% in the control rats. These results indicate that intravenous IgG has beneficial effects on severe experimental peritonitis.


Neuroplasticity, axonal guidance and micro-RNA genes are associated with morphine self-administration behavior.
Neuroadaptations in the ventral striatum (VS) and ventral midbrain (VMB) following chronic opioid administration are thought to contribute to the pathogenesis and persistence of opiate addiction. In order to identify candidate genes involved in these neuroadaptations, we utilized a behavior-genetics strategy designed to associate contingent intravenous drug self-administration with specific patterns of gene expression in inbred mice differentially predisposed to the rewarding effects of morphine. In a Yoked-control paradigm, C57BL/6J mice showed clear morphine-reinforced behavior, whereas DBA/2J mice did not. Moreover, the Yoked-control paradigm revealed the powerful consequences of self-administration versus passive administration at the level of gene expression. Morphine self-administration in the C57BL/6J mice uniquely up- or down-regulated 237 genes in the VS and 131 genes in the VMB. Interestingly, only a handful of the C57BL/6J self-administration genes (<3%) exhibited a similar expression pattern in the DBA/2J mice. Hence, specific sets of genes could be confidently assigned to regional effects of morphine in a contingent- and genotype-dependent manner. Bioinformatics analysis revealed that neuroplasticity, axonal guidance and micro-RNAs (miRNAs) were among the key themes associated with drug self-administration. Noteworthy were the primary miRNA genes H19 and micro-RNA containing gene (Mirg), processed, respectively, to mature miRNAs miR-675 and miR-154, because they are prime candidates to mediate network-like changes in responses to chronic drug administration. These miRNAs have postulated roles in dopaminergic neuron differentiation and mu-opioid receptor regulation. The strategic approach designed to focus on reinforcement-associated genes provides new insight into the role of neuroplasticity pathways and miRNAs in drug addiction.


The improved PCR of the fstA (ferric siderophore receptor) gene differentiates the fish pathogen Aeromonas salmonicida from other Aeromonas species.
The members of the genus Aeromonas are autochthonous of aquatic ecosystems and several species have been associated to septicaemia, ulcerative and haemorrhagic diseases in fish, causing significant mortality in both wild and farmed, freshwater and marine fish species. The species Aeromonas salmonicida is generally recognized as the most important fish pathogen responsible for epidemic outbreaks of furunculosis in salmonids, also being able to produce infections in other cultured fish such as turbot, halibut, sea bream or goldfish. New species, i.e. Aeromonas aquariorum, Aeromonas tecta and Aeromonas piscicola, have recently been discovered and isolated from diseased fish. The species A. piscicola and Aeromonas bestiarum are practically impossible to differentiate phenotypically and genetically (when using the 16S rRNA gene) from each other and from A. salmonicida. In the present study, two previously described PCR protocols, based on the fstA and gyrB genes, for the specific detection of A. salmonicida were re-evaluated with the type strains of all Aeromonas species and with a set of A. piscicola and A. bestiarum strains. Contrary to what had been published previously it was demonstrated that the gyrB-PCR is not specific for A. salmonicida because of cross-reactions with other Aeromonas species. However, in agreement with previous results, A. salmonicida was detected on the basis of the fstA-PCR, for which an improved protocol was proposed.


Are the phenotypic traits of hatchling lizards affected by maternal allocation of steroid hormones to the egg?
In lizards as in many other kinds of animals, strong maternal effects on the phenotypic traits of hatchlings are frequently reported. One plausible non-genetic mechanism that might produce such differences among clutches involves maternal allocation of steroid hormones. Lizard eggs often display considerable inter-clutch variation in the quantities of maternally allocated steroids, and exogenous application of such steroids has been reported to influence the phenotypic traits (especially, sex) of hatchlings. We examined correlations between naturally occurring yolk steroid levels and offspring traits in the scincid lizard Bassiana duperreyi, and also conducted experimental trials (exogenous application of testosterone or 17beta-oestradiol to eggs) to test for causal effects of hormones. Although exogenous hormones readily reversed sex of the hatchling lizards, no other phenotypic traits of the hatchlings (morphology, locomotor performance) were significantly correlated with naturally occurring levels of testosterone, dihydrotestosterone or estrogen, nor were these phenotypic traits significantly affected by exogenous application of hormones. Hence, our results do not support the hypothesis that reproducing female lizards manipulate the phenotypic traits of their offspring by differential allocation of steroid hormones.


The boss as human shield.
As employees strive to do their jobs, they face threats to productivity from all quarters-disruptive technology, meddlesome superiors, senseless organizational practices, and abusive clients and customers. Sutton, of Stanford University, reminds us that the best bosses identify and slay those dragons, thereby protecting the time and the dignity of their people and enabling them to focus on real work. Self-awareness is the key to defending employees effectively. Good leaders resist their own tendency to exercise power: They keep meetings short, listen to their followers, and make it safe to disagree with the boss. They also work to reduce outside distractions by, for example, championing mornings free of e-mail or streamlining performance-review processes. When their own bosses are the problem, they occasionally defy orders. Once in a while, they encourage their people to overtly comply with misguided demands from on high without actually buying in to them. Good bosses fight enemies. They take the heat for their teams. They have their employees' backs. Stepping on to this battlefield requires humility, intelligence, and bravery. In leading the charge to make the workplace safe and productive, however, you may risk martyrdom. Don't lose sight of the need to retain your own political power as you defend against the institutional forces that threaten your employees. And remember that preserving your own well-being will ensure that you have the energy to fight the good fight.


Computationally Driven Two-Dimensional Materials Design: What Is Next?
Two-dimensional (2D) materials offer many key advantages to innovative applications, such as spintronics and quantum information processing. Theoretical computations have accelerated 2D materials design. In this issue of ACS Nano, Kumar et al. report that ferromagnetism can be achieved in functionalized nitride MXene based on first-principles calculations. Their computational results shed light on a potentially vast group of materials for the realization of 2D magnets. In this Perspective, we briefly summarize the promising properties of 2D materials and the role theory has played in predicting these properties. In addition, we discuss challenges and opportunities to boost the power of computation for the prediction of the "structure-property-process (synthesizability)" relationship of 2D materials.


Facility-based approach for the management of acute ST segment elevation myocardial infarction with cardiogenic shock in a rural medical centre: the Durango model.
Cardiogenic shock (CS) complicates 5%-15% of cases of acute myocardial infarction (AMI) with inpatient mortality greater than 40%. The implementation of standardised protocols may improve clinical outcomes in patients with AMI-CS. The Durango model is a prospective single-centre registry designed to enable early identification of patients with STEMI-CS to facilitate primary reperfusion therapy with a shock team management algorithm in a rural level II heart attack centre. This prospective registry includes all patients >18 years of age presenting with STEMI with or without CS beginning on 1 February 2023. The primary outcome measures are adherence to model-based documentation of SCAI shock Classification prehospital and in the ED with appropriate STEMI shock alert for AMI and stages C, D, E shock; use of mechanical circulatory support Pre-PCI and door to support time <90 min. This study was approved by the Institutional Review Board with a waiver of informed consent. The findings will be submitted for publication in a peer-review open access journal on completion of the study. The Durango model will demonstrate that the implementation of a STEMI shock team can be feasible in a rural medical centre through comprehensive education of a diverse group providers with different levels of experience, continuous model/device proficiency training and performance feedback.


Surgical implantation of a bioengineered internal anal sphincter.
Fecal incontinence is a common disorder that can have devastating social and psychologic consequences. However, there are no long-term ideal solutions for such patients. Although loss of continence is multifactorial, the integrity of the internal anal sphincter (IAS) has particular significance. We previously described the development of 3-dimensional bioengineered constructs using isolated smooth muscle tissue from donor C57BL/6 IAS. We hypothesized that the bioengineered ring constructs would retain cellular viability and promote neovascularization upon implantation into a recipient mouse. Internal anal sphincter ring constructs were surgically implanted into the subcutaneous tissue of syngeneic C57BL/6 mice and treated with either fibroblastic growth factor 2 (0.26 microg daily) or saline controls using a microosmotic pump. Internal anal sphincter constructs were harvested after 25 days (range, 23-26 days) and assessed morphologically and for tissue viability. Gross morphology showed that there was no rejection. Rings showed muscle attachment to the back of the mouse with no sign of inflammation. Fibroblastic growth factor 2 infusion resulted in a significantly improved histologic score and muscle viability compared with the control group. Three-dimensional bioengineered IAS rings can be successfully implanted into the subcutaneous tissue of recipient mice. The addition of fibroblastic growth factor 2 led to improved muscle viability, vascularity, and survival. This approach may become a feasible option for patients with fecal incontinence.


Effects of oxygen and carbon dioxide on the retinal vasculature in humans.
Mixtures of carbon dioxide and oxygen are commonly used in the treatment of central retinal artery obstruction to improve retinal oxygenation. While oxygen alone causes retinal vasoconstriction, it is thought that the carbon dioxide balances this effect, even causing a net vasodilatation. To test this hypothesis, normal, healthy volunteers were given 100% oxygen, a mixture of 95% oxygen and 5% carbon dioxide, and a mixture of 5% carbon dioxide in air to breathe. The caliber of large, fluorescein-filled retinal arteries and veins was then measured using computer processing of digitized television images. The marked decrease in arterial and venous caliber caused by 100% oxygen was not reversed by the subsequent addition of 5% carbon dioxide. Moreover, 5% carbon dioxide in air did not cause substantial vasodilatation of the retinal vasculature. The efficacy of adding 5% carbon dioxide to oxygen to treat retinal vascular obstructive diseases is questioned.