Hysteroscopic resection of abnormally invasive placenta residuals.
To present our experience in hysteroscopic removal of abnormally invasive placenta (AIP) residuals using bipolar energy. Case series. University hospital. Sixteen patients with AIP residuals after 17 pregnancies. Cases were identified by ultrasound, treated with hysteroscopic bipolar electrosurgery and oral contraceptives, and followed up by ultrasound or hysteroscopy. Nine subsequent pregnancies were described. Complete removal of AIP residuals was achieved by hysteroscopic bipolar electrosurgery in all cases except one. No perioperative complications occurred. AIP residual recurred in one patient after a subsequent pregnancy and was successfully treated using the same procedure. AIP residual is a rare condition. Management by hysteroscopic resection using bipolar energy is safe and feasible.


Increased physical growth after successful antireflux operation.
Gross vesicoureteral reflux with infection can retard renal growth. Resumption of renal growth or even accelerated growth has been reported after successful surgical repair of reflux in children. No published reports examining the effect on physical growth are available. The preoperative and postoperative physical growth curves were examined in 35 consecutive pediatric patients undergoing ureteroneocystostomy for reflux. The significant (average 81%) increase in the postoperative physical growth percentile is presented and discussed.


Amino acid sequence of iron-superoxide dismutase from Pseudomonas ovalis.
The amino acid sequence of iron-superoxide dismutase from Pseudomonas ovalis was deduced by the analyses of peptides derived from limited hydrolysis of the aminoethylated or pyridylethylated apoprotein with trypsin, Staphylococcus aureus V8 protease, and dilute acid hydrolysis. The polypeptide chain contains 195 amino acid residues and has a calculated Mr of 21,421. The sequence is highly homologous (65% identity) to the recently published sequence of the iron-superoxide dismutase from Photobacterium leiognathi. It is also homologous to the known sequences of the manganese-superoxide dismutase by sharing 33-53% identical residues. Alignment of the superoxide dismutase sequences and the available structural information from X-ray crystallography suggest that the ligands to the iron in the P. ovalis superoxide dismutase are His-26, His-74, Asp-156 and His-160, which align with the ligands to the manganese in the Thermus thermophilus manganese-superoxide dismutase. The sequence information of the P. ovalis dismutase will facilitate refinement of the X-ray crystallographic data that are now available at 2.9 A resolution.


[A Buddhist view of health and care].
Buddhism has an original anthropology without dolorism or sacrifice, based on which a care ethic is deployed. The Buddhist way leads to freeing the spirit of the illusions that lead it astray and considers the body as a precious material support for the spirit. Pain and illness are treated while paying great attention to the person's suffering, whether conscious or not.


The Impact of Lymphovascular Space Invasion on Recurrence and Survival in Iranian Patients With Early Stage Endometrial Cancer.
The aim of this study was to assess the impact of lymphovascular space involvement (LVSI) on recurrence and survival in early stage of endometrial cancer (EC). Patients with EC referred to Imam Khomeini Hospital in Tehran were examined and enrolled over a 10-year period (2004 - 2015). The effect of LVSI on recurrence and overall survival was analyzed using the Kaplan-Meier and log-rank test methods. A total of 160 patients with early stage EC were identified. Out of 160 women with EC, 135 (84.4%) underwent primary surgery. One hundred and twenty-one (76.2%) patients were not found to have LVSI, whereas 38 (23.8%) were found to have LVSI. Of the 38 patients with LVSI, 21 (55.3%) had endometrioid cell type tumor, 10 (26.3%) had serous, one (2.6%) had clear cell and six (15.8%) had adeno-squamous cell type tumor. The presence of LVSI represents a factor strongly associated with high risk of recurrence and poor survival in early stage EC. Patients with lower International Federation of Obstetrics and Gynecology (FIGO) stages may be at increased risk of recurrence and a poor overall survival if the pathological findings confirm the presence of LVSI. Thus, LVSI should be added to the traditional factors used to decide whether patients with early stage EC are at high risk of recurrence and adjuvant therapy planning.


Conflict in a word-based approach-avoidance task is stronger with positive words.
Valence and motivational direction are linked. We approach good things and avoid bad things, and experience overriding these links as conflicting. Positive valence is more consistently linked with approach than negative valence is linked with avoidance. Therefore, avoiding positive stimuli should produce greater behavioral and neural signs of conflict than approaching negative stimuli. In the present event-related potential study, we tested this assumption by contrasting positive and negative conflict. We used the manikin task, in which we read positive and negative words that they needed to approach and avoid. Consistent with our prediction, positive conflict prolonged reaction times more than negative conflict did. A late (500-1000 ms following word onset) event-related potential that we identified as the Conflict slow potential, was only sensitive to positive conflict. The results of this study support the notion that avoiding positive stimuli is more conflicting than approaching negative stimuli. The fact that the conflict slow potential is typically sensitive to response conflict rather than stimulus conflict suggests that the manikin task primarily requires people to override prepotent responses rather than to identify conflicting stimuli. Thus, the present findings also shed light on the psychological processes subserving conflict resolution in the manikin task.


Temporary use of silicone stents for severe airway stenosis in untreated malignant lymphoma.
Airway stenting has become a popular method for palliation of airway stenosis; however, little has been reported about their use for patients with malignant lymphoma that occasionally causes a life-threatening condition. The aim of the study was to evaluate the efficacy and safety of airway stenting in chemoradiotherapy naive patients with severe airway stenosis due to malignant lymphoma. Patients who underwent airway stent placement from April 2007 to July 2011 in a single center were retrospectively reviewed. All stenting procedures were performed using rigid and flexible bronchoscopes under general anesthesia. We performed 174 airway stenting procedures (silicone stents in 154 procedures and metallic in 20 procedures) for 150 patients during the study period. Of the patients, 7 had untreated malignant lymphomas (4 diffuse large B-cell lymphomas, 2 lymphoblastic lymphomas, 1 mucosa-associated lymphoid tissue lymphoma). All patients underwent stenting using the silicone Y-stent (6 on the main carina and 1 on the primary right carina). Dyspnea was relieved immediately in 6 of 7 patients including the mechanically ventilated patient. Stents could be removed in all patients (median 90 d after stenting; range, 32 to 245 d) because of the tumor response to tumor-specific therapy. One granuloma formation and 1 mucus retention triggered the decision to remove the stents. Airway stenting using silicone stents is safe and effective in palliation of airway stenosis in patients with untreated malignant lymphoma, and permits postprocedural tumor-specific therapy. The response to tumor-specific therapy can be expected, and so removable stents should be selected.


Human paranasal sinuses and selective brain cooling: a ventilation system activated by yawning?
The function of the paranasal sinuses has been a controversial subject since the time of Galen, with many different theories advanced about their biological significance. For one, the paranasal sinuses have been regarded as warmers of respiratory air, when in actuality these structures appear to function in cooling the blood. In fact, human paranasal sinuses have been shown to have higher volumes in individuals living in warmer climates, and thus may be considered radiators of the brain. The literature suggests that the transfer of cool venous blood from the paranasal sinuses to the dura mater may provide a mechanism for the convection process of cooling produced by the evaporation of mucus within human sinuses. In turn, the dura mater may transmit these temperature changes, initiated by the cool venous blood from the heat-dissipating surfaces of the sinuses, to the cerebrospinal fluid compartments. Furthermore, it has recently been demonstrated in cadaveric dissections that the thin bony posterior wall of the maxillary sinus serves as an origin for both medial and lateral pterygoid muscle segments, an anatomic finding that had been previously underappreciated in the literature. The present authors hypothesize that the thin posterior wall of the maxillary sinus may flex during yawning, operating like a bellows pump, actively ventilating the sinus system, and thus facilitating brain cooling. Such a powered ventilation system has not previously been described in humans, although an analogous system has been reported in birds.


Perspectives on coping among patients with head and neck cancer receiving radiation.
To describe coping among patients with laryngeal and oropharyngeal cancer during definitive radiation with or without chemotherapy. Qualitative content analysis conducted within a larger study. Two radiation oncology outpatient clinics in Baltimore, MD. 21 patients with oropharyngeal or laryngeal cancer. Interviews with open-ended questions were conducted during treatment. Questions covered topics such as coping during treatment, treatment-related issues, and resources. Coping, treatment, and coping resources. Patients' self-assessments suggested they were coping or that coping was rough or upsetting. Issues that required coping varied over four time points. Physical side effects were problematic during and one month after treatment completion. Patients used coping to manage the uncertainties of physical and psychological aspects of their experience. Family and friend support was a common coping strategy used by patients, with the intensity of side effects corresponding with the support provided across time points. Findings confirm previous research, but also provide new information about ways in which patients with head and neck cancer cope with their illness experience. Emergent themes provide insight into patients' feelings, issues, and assistance received with coping. Patients with head and neck cancer need education on the amount and severity of side effects and should be appraised of potential difficulties with scheduling, driving, and other logistic issues. Patients also should be informed of helpful types of support and coping strategies. Additional research is needed to expand the findings related to patients' coping with treatment and to explore the experiences of family and friends who provide social support.


Mercury poisoning. A case report and comment on 6 other cases.
The diagnosis of mercury poisoning requires a high index of suspicion. Mercury poisoning in a patient involved in illicit gold extraction is reported and 6 other cases considered. Some of the clinical features and treatment of this condition are discussed.


Concerted action of human carboxyl ester lipase and pancreatic lipase during lipid digestion in vitro: importance of the physicochemical state of the substrate.
The pancreatic enzyme carboxyl ester lipase (CEL) has been shown to hydrolyse a large number of different esters, including triacylglycerols, cholesteryl esters and retinyl esters with an absolute requirement for bile salts. Some of the lipids that are substrates for CEL can also be hydrolysed by pancreatic lipase. In order to investigate the relative roles of human CEL and pancreatic lipase, the two enzymes were incubated on a pH-stat with isotope-labelled lipid substrate mixtures in physicochemical forms resembling the state of the dietary lipids in human intestinal contents. In the first set of experiments, cholesteryl oleate (CO) and retinyl palmitate (RP) were solubilised in an emulsion of triolein (TO) stabilised by egg phosphatidylcholine and bile salts. Lipase (always added together with its cofactor, colipase) hydrolysed TO, with monoolein and oleic acid as end-products, whereas CEL alone could not hydrolyse TO in the presence of phosphatidylcholine (PC). Lipase alone did not hydrolyse CO or RP, but CEL did hydrolyse these esters if lipase was present. Release of [3H]glycerol from labelled TO increased only slightly if CEL was added compared to lipase alone, suggesting that monoolein hydrolysis was slow under these conditions. In the second set of experiments, CO and RP were dissolved in bile salt/monoolein/oleic acid dispersions with varying bile salt concentrations. CEL hydrolysed CO and RP more rapidly in a system with a high bile salt concentration containing mixed micelles than in a system with a low bile salt concentration, where the lipids were dispersed in the form of mixed micellar and non-micellar aggregates; both types of aggregate have been reported to exist in human intestinal contents. In conclusion, these data suggest that the main function of CEL under physiological conditions is to hydrolyse cholesteryl and retinyl esters, provided that the triacylglycerol oil phase is hydrolysed by pancreatic lipase, which probably causes a transfer of the substrate lipids of CEL from the oil emulsion phase to an aqueous bile salt/lipolytic product phase. Depending on the bile salt/lipolytic product ratio, the substrate will reside in either micellar or non-micellar lipid aggregates, of which the micellar state is preferred by CEL.


Feasibility of a breath test with a substrate of natural 13C-abundance and isotope-selective non-dispersive infrared spectrometry: a preliminary study.
Isotope-selective non-dispersive infrared spectrometry (NDIRS) is a cheaper alternative to isotope ratio mass spectrometry (IRMS). We checked on the efficiency of NDIRS to perform a breath test with naturally (13)C-enriched maize starch. Fifty-six healthy volunteers were examined. After a basal fasted sample of their expiratory air was collected, the subjects ate a test breakfast of 50 g (CF50 group, n = 9) or 100 g (CF100 group, n = 47) cornflakes with 175 g yoghurt. For 6 h thereafter, exhaled air was collected every 30 min for the NDIRS measurement of (13)CO(2) concentration. The time-course of the curves of (13)CO(2) concentration resembled those obtained previously with IRMS. A dose-response to the amount of ingested cornflakes was observed--the maximum postprandial net increment in (13)CO(2) was statistically significantly higher in the CF100 than CF50 group: 4.78 +/- 0.13 versus 3.12 +/- 0.17 per thousand (P < 0.001), whereas the time needed to reach the maximum did not differ after the intake of 50 g (233 +/- 13 min) or 100 g (248 +/- 9 min) cornflakes. The 5-h area-under-the-curve of cumulative (13)CO(2) net recovery (AUC(60-360)) was statistically significantly greater after ingestion of 100 g compared to 50 g cornflakes (97.6 +/- 2.2 versus 61.7 +/- 2.2 micromol, P < 0.001) and it also exhibited a stable between-subject variability. The obtained proof of technical feasibility of a breath test with the use of naturally (13)C-enriched starch and NDIRS provides background for future research on the clinical usefulness of this method for a non-invasive assessment of the pancreatic exocrine function.


Evaluation of the U.K. 2-week referral rule for skin cancer.
In 1997 the U.K. government introduced the target that all patients seen in primary care, and whose general practitioner suspected a possible diagnosis of any cancer, would be seen by a specialist within 2 weeks. Several individual departmental reports suggest that this has generated a high volume of 'urgent' referrals and has been unachievable without impact on other patients. To determine the views of dermatologists, with audit and database information where possible, on the overall impact of the 2-week rule referral standard for suspected skin cancers. A questionnaire was sent to consultant dermatologists in the U.K. requesting views and numerical data. There were 139 responses, some on a departmental basis, representing 272 individuals (nearly two-thirds of all consultant dermatologists in post in the U.K). Based on 52 formal audit studies or database information, the overall proportion of confirmed skin cancers among 2-week rule referrals was 12%, but only 42% of tumours were referred by this route. Correct suspicion of melanoma was generally better than that of squamous cell carcinoma. Information on standard referral proformas was only considered to be 'usually adequate' by 34% of departments. Considering all replies, only 27% of respondents felt that the 2-week rule works well; the major problems are an excess of benign lesions, the lack of opportunity to prioritize referrals and the displacement of other urgent problems. There are significant problems with the perception and application of the 2-week referral standard for possible skin cancers, including a high volume of nonrelevant lesions and displacement of other urgent conditions. Increasing the specificity of referral guidelines, and increased education regarding recognition of benign lesions, are the favoured options for improvement.


A spatiotemporally weighted intelligent method for exploring fine-scale distributions of surface dissolved silicate in coastal seas.
The transfer of dissolved silicate (DSi) from land to coastal environments is a crucial part of global biogeochemical cycling. However, the retrieval of coastal DSi distribution is challenging due to the spatiotemporal non-stationarity and nonlinearity of modeling processes and the low resolution of in situ sampling. To explore the coastal DSi changes in a higher spatiotemporal resolution, this study developed a spatiotemporally weighted intelligent method based on a geographically and temporally neural network weighted regression (GTNNWR) model, a Data-Interpolating Empirical Orthogonal Functions (DINEOF) model, and satellite observations. For the first time, the complete surface DSi concentrations of 2182 days at the 500-meter and 1-day resolution in the coastal sea of Zhejiang Province, China, were obtained (Testing R2 = 78.5 %) by using 2901 in situ records with concurrent remote sensing reflectance. The long-term and large-scale distributions of DSi reflected the changes in coastal DSi under the influences of rivers, ocean currents, and biological effects across multiple spatiotemporal scales. Benefiting from the high-resolution modeling, this study found that the surface DSi concentration had at least 2 declines during a diatom bloom process, which can provide crucial signals for the timely monitoring and early warning of diatom blooms and guide the management of eutrophication. It was also indicated that the correlation coefficient between the monthly DSi concentration and the Yangtze River Diluted Water velocities reached -0.462**, quantitatively revealing the significant influence of the terrestrial input. In addition, the daily-scale DSi fluctuations resulting from typhoon transits were finely characterized, which greatly reduces the monitoring cost compared with the field sampling. Therefore, this study developed an effective data-driven-based method to help explore the fine-scale dynamic changes of surface DSi in coastal seas.


Bio-engineering inslulin-secreting cells from embryonic stem cells: a review of progress.
According to the Edmonton protocol, human islet transplantation can result in insulin independency for periods longer than 3 years. However, this therapy for type 1 diabetes is limited by the scarcity of cadaveric donors. Owing to the ability of embryonic stem cells to expand in vitro and differentiate into a variety of cell types, research has focused on ways to manipulate these cells to overcome this problem. It has been demonstrated that mouse embryonic stem cells can differentiate into insulin-containing cells, restoring normoglycaemia in diabetic mice. To this end, mouse embryonic stem cells were transfected with a DNA construct that provides resistance to neomycin under the control of the regulatory regions of the human insulin gene. However, this protocol has a very low efficiency, needing improvements for this technology to be transferred to human stem cells. Optimum protocols will be instrumental in the production of an unlimited source of cells that synthesise, store and release insulin in a physiological manner. The review focuses on the alternative source of tissue offered by embryonic stem cells for regenerative medicine in diabetes and some key points that should be considered in order for a definitive protocol for in vitro differentiation to be established.


An Ia-positive mouse T-cell clone is functional in presenting antigen to other T cells.
In this report we present data demonstrating the endogenous expression of I-region associated (Ia) antigens on a cloned line of mouse T cells, CTLL, as well as transcription of the invariant chain gene in these cells. We demonstrate further that this Ia-bearing T-cell clone, CTLL, can utilize the expressed Ia molecules to present antigen to Ia-restricted antigen-specific T cells.


Serum microRNA-196 and microRNA-200 in pancreatic ductal adenocarcinoma of patients with diabetes mellitus.
Our aim was to compare expressions of 6 microRNAs (miRNAs) in patients with pancreatic ductal adenocarcinoma (PAC) and non-cancer patients, moreover according to the presence or absence of diabetes mellitus. Expressions of miRNA-192, -196, -200, -21, -30 and -423 were measured in 77 patients with PAC and 64 non-cancer patients (34 patients with type 2 DM and 30 control persons). 60 patients with PAC (78%) had DM or prediabetes and it was of new-onset (less than 2 years before the cancer diagnosis) in 44 out of them. The expressions of all microRNAs were 1.4-3.7 times higher (significantly) in the PAC group compared to non-cancer patients. No difference was found between PAC diabetic and PAC non-diabetic patients. MicroRNA-200 was significantly higher in PAC patients with significant body weight loss against those without weight loss. Adding miRNA-196 and -200 to the current marker CA 19-9 improved the discriminative ability of the test (compared to CA 19-9 alone). MicroRNA-196 and -200 could be used as additional markers in PAC diagnosis.


Endoscopic submucosal dissection in tumors extending to the dentate line compared to proximal rectal tumors: a systematic review with meta-analysis.
Endoscopic submucosal dissection (ESD) is a validated treatment for early rectal tumors, but whether this therapy is efficient or not for rectal tumors extending to the dentate line (RTDL) remains unclear. We performed a systematic review and meta-analysis to assess the effectiveness and safety of ESD in RTDL compared to non-RTDL. A search in PubMed, Scopus and the Cochrane library up to April 2020 was conducted to identify studies that compared ESD in both localizations (RTDL and non-RTDL), reporting at least one main outcome (en bloc, complete resection, recurrence). Secondary outcomes were adverse event occurrence. Five observational studies including 739 patients with a total of 201 RTDL and 538 non-RTDL were considered. The proportion of female sex (66% vs. 36.9%, P < 0.001) and tumor size [mean difference = 7.75, 95% confidence interval (CI): 3.01-12.49, P = 0.001] were higher in the RTDL group. There were no differences in en bloc resection rates between RTDL and non-RTDL groups [odds ratio (OR): 0.95, 95% CI: 0.50-1.79, P = 0.087]. The complete resection rate was significantly higher in the non-RTDL group (OR: 1.72, 95% CI: 1.18-2.53, P = 0.005, I2 = 0%). However, recurrence rates were comparable (RD: -0.04, 95% CI: -0.07 to 0.00, P = 0.06, I2 = 0%). Concerning adverse events, there were no differences in terms of perforation (OR: 0.9, 95% CI: 0.26-3.08, P = 0.86, I2 = 0%) or delayed bleeding (OR: 0.64, 95% CI: 0.17-2.42, P = 0.51, I2 = 35%). Anal pain rate was 28% (95% CI: 21.4-35.8%). ESD is an effective and safe therapeutic approach for RTDL with comparable recurrence rate to non-RTDL. The lower complete resection rate in RTDL needs to be clarified in studies.


Diethylaminoethanol-cellulose in the treatment of absorptive hyperoxaluria.
There were 22 patients in whom oxalate stones formed and who had absorptive hyperoxaluria treated with diethylaminoethanol-cellulose. In more than 2 years this form of treatment did not seem to have any serious side effects. It achieved a decrease of urinary oxalate values in all patients in whom oxalate hyperabsorption had been found. Diethylaminoethanol-cellulose is an anionic exchanger capable of retaining oxalate in vitro and in vivo.


Methylene Blue halves the long-term recurrence rate in acute pilonidal sinus disease.
To study the potential benefits of intraoperative methylene blue (MB) use in pilonidal sinus surgery, the correlation between long-term recurrence rate and intraoperative MB use in pilonidal sinus surgery was investigated. Explicit investigations of MB effects in sinus surgery are scarce and inconclusive; an effect on long-term recurrence rate has never been systematically investigated. A random selection of 247 patients out of 1,960 patients with primary sinus surgery was drawn, and the patients were subjected to a telephone interview according to a specific questionnaire. The interview covered a recurrence follow-up time of 14.9 years after surgery (mean, standard deviation=3.8 years, range 8.6-25.4 years). Recurrence was less likely to occur when MB was used intraoperatively (32 of 197, [16% actuarial 20-year recurrence rate, Kaplan-Meier estimate] recurrences with MB vs 15 of 50, 30% [actuarial 20-year recurrence rate, Kaplan-Meier estimate] recurrences without MB; p=0.018; log-rank test). This effect was especially pronounced in acute abscess-forming disease (8 of 46, 17% [actuarial 20-year recurrence rate, Kaplan-Meier estimate] recurrences with MB; 11 of 33, 33% [actuarial 20-year recurrence rate, Kaplan-Meier estimate] recurrences without MB; p=0.078; log-rank test) compared to chronic disease (24 of 151, 16% [actuarial 20-year recurrence rate, Kaplan-Meier estimate]) recurrences with MB; 4 of 17, 24% [actuarial 20-year recurrence rate, Kaplan-Meier estimate] recurrences without MB; p=0.35; log-rank test). MB application halves the long-term risk of recurrence for pilonidal sinus patients. This significant reduction in recurrence rate can be achieved by a single careful injection of non toxic inexpensive dye into the sinus at the start of the operation. MB application should therefore be considered as an integral part of pilonidal sinus surgery.


Prevalence of Shiga toxin-producing Escherichia coli in food products of animal origin as determined by molecular methods.
In this study we report on the prevalence and distribution of Shiga toxin-producing Escherichia coli (STEC) in food products of animal origin, collected in the Piedmont region of Italy, as determined by a combination of quantitative PCR (qPCR) protocols, applied directly to the samples, and of culture-dependent isolation and subsequent molecular identification and characterization of isolates. The qPCR protocols were developed and optimized in this study and targeted the rpoB gene (as a marker for total E. coli) and the stx₁, stx₂ and eaeA genes (as markers for potentially virulent E.coli). They were then used to test for STEC in 101 food samples, before and after enrichment. A STEC prevalence of 42% (21/50) for dairy products and 70% (36/51) for meat products was obtained. A total of 54 STEC isolates were recovered from dairy and meat samples, resulting in a prevalence of 36% and 27% in dairy and meat products, respectively, by the culture method. A large number of strains carried the stx₂ gene (39 out of the 54 STEC strains) compared to strains that carried stx₁ (30 out of 54); only 11 out of 54 strains contained the eaeA gene, while 14 strains contained both stx₁ and stx₂. Eight of the 54 isolates belonged to the O157 serogroup, and none belonged to serogroups O26, O145, O111 or O103. Strains isolated from meat products were diverse, as determined by Enterobacterial repetitive intergenic consensus-PCR (ERIC), while those isolated from dairy products were more similar and grouped together by cluster analysis. The results of the qPCR approach showed a high prevalence of STEC in dairy and meat based products, mainly fermented, indicating a possible safety risk for these types of food commodities.


Overexpression of Far1, a cyclin-dependent kinase inhibitor, induces a large transcriptional reprogramming in which RNA synthesis senses Far1 in a Sfp1-mediated way.
The FAR1 gene encodes an 830 residue bifunctional protein, whose major function is inhibition of cyclin-dependent kinase complexes involved in the G1/S transition. FAR1 transcription is maximal between mitosis and early G1 phase. Enhanced FAR1 transcription is necessary but not sufficient for the pheromone-induced G1 arrest, since FAR1 overexpression itself does not trigger cell cycle arrest. Besides its well established role in the response to pheromone, recent evidences suggest that Far1 may also regulate the mitotic cell cycle progression: in particular, it has been proposed that Far1, together with the G1 cyclin Cln3, may be part of a cell sizer mechanism that controls the entry into S phase. Far1 is an unstable protein throughout the cell cycle except during G1 phase. Far1 levels peak in newborn cells as a consequence of a burst of synthetic activity at the end of the previous cycle, and the amounts per cell remain roughly constant during the G1 phase. Phosphorylation (at serine 87) by Cdk1-Cln complexes primes Far1 for ubiquitin-mediated proteolysis. By coupling a genome-wide transcriptional analysis of FAR1-overexpressing and far1Δ cells grown in ethanol- or glucose-supplemented minimal media with a range of phenotypic analysis, we show that FAR1 overexpression not only coordinately increases RNA and protein accumulation, but induces strong transcriptional remodeling, metabolism being the most affected cellular property, suggesting that the Far1/Cln3 sizer regulates cell growth either directly or indirectly by affecting metabolism and pathways known to modulate ribosome biogenesis. A crucial role in mediating the effect of Far1 overexpression is played by the Sfp1 protein, a key transcriptional regulator of ribosome biogenesis, whose presence is mandatory to allow a coordinated increase in both RNA and protein levels in ethanol-grown cells.


Excellent short-term results of hip resurfacing in a selected population of young patients.
Hip resurfacing (HR) is an alternative option to total hip arthroplasty (THA) in a population of selected patients (young and/or active). The short-term survivorship rate is as least as good as that for THA with no abnormal increase in serum metal ion levels. A continuous prospective series of 502 hip resurfacings in 481 patients mean age 48.7 years old (±10.3; 18-68) (Conserve Plus, Wright Medical Technology) was analyzed clinically, radiologically and biologically (total blood chrome, cobalt and titanium metal ion levels). Mean follow up was 4.1 years (1.9-4.9). There were no dislocations. There were 5 cases of revision surgery with component replacement (including 2 infections). Implant survivorship using implant removal as the criteria (excluding infection) was 99.4% at 4 years (CI 95%: 98.1-99.8). The evaluation of metal ion levels showed a significant increase in cobalt from a preoperative level of 0.24 μg/L (0.01-3.6) to 0.86 μg/L (0.01-5.7) at the final follow-up (P<0.001). Chrome and titanium levels went from 0.68 μg/L (0.01-4.4) and 2.36 μg/L (0.39-7) to 1.28 μg/L (0.1-5.5) and 4.49 μg/L (1.29-8.21) respectively (P<0.001). All clinical scores had significantly improved at the final follow-up. Mean frontal plane cup inclination was 42.7° (35-62). In a selected population of young and/or active patients, the short-term results of hip resurfacing are excellent. At the postoperative 4-year follow-up the rate of complications (in particular the absence of dislocations) was less than that for THA in young and/or active patients. Certain conditions must be respected to obtain these results; frontal plane cup inclination of between 40 and 45°, a femoral head diameter of at least 48 mm and good quality femoral bone. IV.


No longer giving life through death.
Pragmatic approaches to safe motherhood consider the needs of both clients and providers: the sociological and physical environments within which a woman lives and moves through to reach a level of care that fulfills her health needs; and the conditions of formal and traditional health care systems within which a health care provider works and moves through to reach a level of professional satisfaction and quality care that fulfills her/his needs and responsibilities. These movements toward higher levels of 'care' are interdependent; without one, the other falters. Clients and providers are partners in this 'dance' of health. Five approaches employed by the MotherCare Project shape maternal health programs. Presented in geometric form, they each describe movements leading client and provider to more satisfying positions in receiving and giving health care, respectively. Strategies to enhance these movements are the subject of the subsequent chapters of this supplement.


The memory modulatory effect of agmatine in passive avoidance task coincides with alterations of hippocampal CaMKII-α and ERK signaling in mice.
Agmatine is a polyamine suggested to act as a supposed neurotransmitter in the brain. Evidence has indicated that acute agmatine administration might modulate memory. The present study aimed to investigate the effect of repeated agmatine treatment on passive avoidance memory, hippocampal calcium-calmodulin-dependent protein kinase II-alpha (CaMKII-α), and Extracellular Signal-Regulated Kinase (ERK) signaling pathways in naive mice. Adult male NMRI mice were treated with agmatine (10, 20, 30, 40, and 80 mg/kg/ip) or saline for 11 days. Acquisition and retention tests of passive avoidance memory were performed on days 10 and 11, respectively. Following the memory retention test, the hippocampi were assessed for the levels of CaMKII-α and ERK using the western blotting technique. The results revealed the dose-dependent effect of agmatine on the passive avoidance memory. Accordingly, the memory was impaired in lower doses, but was improved in higher ones. Agmatine in none of the doses affected the nociception of the mice in tail-flick test. Furthermore, agmatine increased the phosphorylation of CaMKII-α and ERK in the hippocampus at memory enhancing doses, while ERK phosphorylation decreased following the impairing doses of agmatine. Thus, the dose-dependent effect of agmatine on memory might be related to its modulatory effect on CaMKII-α and ERK signal transduction, eventually regulating the memory process.


Burden of serious fungal infections in Nepal.
There are few reports of serious fungal infections in Nepal though the pathogenic and allergenic fungi including Aspergillus species are common in the atmosphere. Herein, we estimate the burden of serious fungal infections in Nepal. All published papers reporting fungal infection rates from Nepal were identified. When few data existed, we used specific populations at risk and fungal infection frequencies in those populations to estimate national incidence or prevalence. Of the 27.3 M population, about 1.87% was estimated to suffer from serious fungal infections annually. We estimated the incidence of fungal keratitis at 73 per 100,000 annually. Chronic obstructive pulmonary disease is common with 215,765 cases, contributing to 1119 cases of invasive aspergillosis annually. Of 381,822 adult asthma cases, we estimated 9546 patients (range 2673-13,364) develop allergic bronchopulmonary aspergillosis and 12,600 have severe asthma with fungal sensitisation. Based on 26,219 cases of pulmonary tuberculosis, the annual incidence of new chronic pulmonary aspergillosis (CPA) cases was estimated at 1678 with a 5 year period prevalence of 5289, 80% of CPA cases. Of 22,994 HIV patients with CD4 counts <350 not on antiretrovirals, Pneumocystis pneumonia was estimated at 990 cases annually. Cases of oral and oesophageal candidiasis in HIV/AIDS patients were estimated at 10,347 and 2950, respectively. There is a significant burden of serious fungal infections in Nepal. Epidemiological studies are necessary to validate these estimates.


Patulin induces colorectal cancer cells apoptosis through EGR-1 dependent ATF3 up-regulation.
Patulin is a fungal mycotoxin of Aspergilus and Penicillium that is commonly found in rotting fruits and exerts its potential toxic effect mainly by reactive oxygen species (ROS) generation. However, the effect of patulin on cancer cells as well as its intracellular mechanism has been controversial and not clearly defined yet. In this study, patulin was found to induce G1/S accumulation and cell growth arrest accompanied by caspase-3 activation, PARP cleavage and ATF3 expression in human colon cancer cell line HCT116. Ser/Thr phosphorylation of a transcription factor, EGR-1, was increased while its expression did not change upon patulin treatment to the cells. Knockdown of ATF3 and EGR-1 using their respective siRNAs showed EGR-1 dependent ATF3 expression. Moreover, treatment of the cells with antioxidants N-acetylcysteine (NAC) and glutathione (GSH) revealed that patulin induced ATF3 expression and apoptosis were dependent on ROS generation. ATF3 expression was also increased by patulin in other colorectal cancer cell types, Caco2 and SW620. Collectively, our data present a new anti-cancer molecular mechanism of patulin, suggesting EGR-1 and ATF3 as critical targets for the development of anti-cancer chemotherapeutics. In this regard, patulin could be a candidate for the treatment of colorectal cancers.


Modelling baculovirus infection of insect cells in culture.
Infection of insect cells with baculovirus is a potentially attractive means for producing both viral insecticides and recombinant proteins. The continuation of mathematical modelling studies such as those reviewed in this paper are essential in order to realise the full potential of the system. Through mathematical models it is possible to predict complex behaviours such as those observed when infecting cells at low MOI or when propagating virus in a continuous culture system. A purely empirical analysis of the same phenomena is very difficult if not impossible.The present three models are - despite their complexity and the effort that has gone into developing them - all first generation models. They summarise, to a large extent, our present quantitative understanding of the interaction between baculovirus and insect cells, when looked upon as a black box system. The binding and initial infection processes are still quantitatively poorly understood and further work in this area is much needed. On the longer term, a second generation of models is likely to consider interior processes such as viral DNA and RNA accumulation in much more detail using a structured model of the infection cycle.


Human auditory cortex responses to rising versus falling glides.
A 24-channel SQUID magnetometer was used to record signals from the right auditory cortex to tone glides with 16 different centre frequencies (ranging from 0.5 to 2 kHz), sweeping over one octave. The stimulus sequence, presented with an interstimulus onset interval of 0.6 s, consisted of infrequent 'deviant' rising (falling) glides and frequent 'standard' falling (rising) glides; the rising glides were identical to the falling glides but presented in the reverse direction. Deviant glides elicited significantly larger responses than standards at a latency of about 100 ms. This amplitude difference presumably arises from a mismatch response to the deviants. These results suggest that the auditory cortex extracts the direction of frequency transition even when the stimuli do not contain same frequencies.


Carotid artery mobilization prior to pharyngeal flap inset for patients with 22q11.2 deletion syndrome.
The management of velopharyngeal insufficiency (VPI) in patients with 22q11.2 deletion syndrome (22q11DS) poses a significant clinical challenge due to presence of a large velopharyngeal gap and a relatively high rate of internal carotid artery (ICA) medialization. To our knowledge, we are the first group to have successfully managed VPI in a series of seven pediatric patients with 22q11DS with medialized ICAs via a novel surgical technique involving carotid artery mobilization followed by pharyngeal flap insertion. Thus far, we have found this technique to be reliably safe with no significant morbidity and caregivers have reported postoperative improvement in speech, swallowing and nasal regurgitation symptoms. Herein, we provide a detailed description of our novel surgical approach, including an instructional video, for correction of VPI in patients with medialized ICAs, who have previously had limited management options.


Adolescents' perceptions of a health survey using multimedia computer-assisted self-administered interview.
To ascertain young people's perceptions of an adolescent health survey when administered by multimedia computer assisted self-administered Interview (M-CASI) through analysis of (1) questionnaire item responses and (2) focus group interviews. Auckland, New Zealand, 1999. Pilot testing of a 488-item branching questionnaire delivered using a youth-oriented and user-friendly M-CASI interface in a variety of settings using both desktop and laptop computers. Post pilot focus groups of participants identifying their perceptions and experiences of the survey. 110 school students aged 12 to 18 years. The mean number of questions answered by participants was 316 with the median time to completion being 48 minutes. On average 65% of the total number of questions were seen and of these 1.5% were deliberately not answered. A high level of acceptability and enjoyment of M-CASI was found in the analysis of focus group responses and agreed with the item responses relating to M-CASI within the questionnaire itself. Participants identified privacy and confidentiality as being particularly important for the honesty of their responses. The passive matrix screens of the computers were popular as they could only be viewed from in front. M-CASI is an acceptable instrument for the administration of a youth health survey. Laptop computers with passive matrix screens are able to enhance perceptions of privacy and confidentiality, which may improve honesty of responses. M-CASI is now feasible and offers advantages in health surveying.


Functional damage of dopamine nerve terminals following intrastriatal kainic acid injection.
The release of [3H]dopamine ([3H]DA) previously taken up into rat striatal slices was studied one week after a monolateral intrastriatal injection of kainic acid (KA). Different releasing stimuli (electrical pulses, veratrine, high-K+) were applied. The electrically evoked release in the KA-lesioned striata was drastically reduced with respect to the unlesioned contralateral striata. In contrast, KA had no effect on the release of [3H]DA evoked by veratrine or high-K+. In unlesioned striatal slices, depolarized with 15 mM KCl, apomorphine reduced and (-)sulpiride increased the release of [3H]DA. The effect of apomorphine was antagonized by (-)sulpiride indicating the presence of an autoreceptor system similar to that seen in unlesioned striata stimulated electrically. However, the effects of apomorphine and of (-)sulpiride were dramatically reduced in K+-depolarized slices prepared from KA-lesioned striata. The results suggest that the axon terminals in KA-treated areas remain intact in several of their properties but may be damaged in some critical processes.


Estrogenic involvement in social learning, social recognition and pathogen avoidance.
Sociality comes with specific cognitive skills that allow the proper processing of information about others (social recognition), as well as of information originating from others (social learning). Because sociality and social interactions can also facilitate the spread of infection among individuals the ability to recognize and avoid pathogen threat is also essential. We review here various studies primarily from the rodent literature supporting estrogenic involvement in the regulation of social recognition, social learning (socially acquired food preferences and mate choice copying) and the recognition and avoidance of infected and potentially infected individuals. We consider both genomic and rapid estrogenic effects involving estrogen receptors α and β, and G-protein coupled estrogen receptor 1, along with their interactions with neuropeptide systems in the processing of social stimuli and the regulation and expression of these various socially relevant behaviors.


Working with the primary care physician.
In this article, the authors illustrate a model of an effective ongoing and active collaboration among a group of pediatricians and child and adolescent psychiatrists. They demonstrate how regular meetings and active collaborative interventions broadened each other's understanding and treatment of children. The close relationship, trust, and understanding that developed as a result of this project had a marked impact on the treatment provided by both types of specialist. The concept of the developmentally informed pediatrician is the basic tenet of this project, which continues to have important implications for the training and practice of today's pediatricians.


Triglyceride-glucose index and the risk of heart failure: Evidence from two large cohorts and a mendelian randomization analysis.
The relationship between triglyceride-glucose (TyG) index, an emerging marker of insulin resistance, and the risk of incident heart failure (HF) was unclear. This study thus aimed to investigate this relationship. Subjects without prevalent cardiovascular diseases from the prospective Kailuan cohort (recruited during 2006-2007) and a retrospective cohort of family medicine patients from Hong Kong (recruited during 2000-2003) were followed up until December 31st, 2019 for the outcome of incident HF. Separate adjusted hazard ratios (aHRs) summarizing the relationship between TyG index and HF risk in the two cohorts were combined using a random-effect meta-analysis. Additionally, a two-sample Mendelian randomization (MR) of published genome-wide association study data was performed to assess the causality of observed associations. In total, 95,996 and 19,345 subjects from the Kailuan and Hong Kong cohorts were analyzed, respectively, with 2,726 cases of incident HF in the former and 1,709 in the latter. Subjects in the highest quartile of TyG index had the highest risk of incident HF in both cohorts (Kailuan: aHR 1.23 (95% confidence interval: 1.09-1.39), PTrend <0.001; Hong Kong: aHR 1.21 (1.04-1.40), PTrend =0.007; both compared with the lowest quartile). Meta-analysis showed similar results (highest versus lowest quartile: HR 1.22 (1.11-1.34), P < 0.001). Findings from MR analysis, which included 47,309 cases and 930,014 controls, supported a causal relationship between higher TyG index and increased risk of HF (odds ratio 1.27 (1.15-1.40), P < 0.001). A higher TyG index is an independent and causal risk factor for incident HF in the general population. URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR-TNRC-11,001,489.


Pneumothorax in pulmonary Langerhans cell histiocytosis.
Pulmonary Langerhans cell histiocytosis (PLCH) is a smoking-related interstitial lung disease characterized by development of cystic changes that predispose to occurrence of pneumothorax. To determine the frequency, recurrence rate, and optimal management of pneumothorax associated with PLCH. Retrospective study. Tertiary care, referral medical center. One hundred two adults >or= 18 years old with histologically confirmed PLCH seen at Mayo Clinic Rochester over a 23-year period from 1976 to 1998. None. Sixteen of 102 patients (16%) with PLCH had pneumothorax; mean age at the time of diagnosis was 29.4 years (range, 18 to 52 years), and all had smoked cigarettes. There were 37 episodes of pneumothoraces (1 to 5 episodes per patient); 10 patients (63%) had more than one episode. Median age at diagnosis of PLCH was significantly younger in patients with pneumothorax when compared to those without pneumothorax (27 years vs 41.5 years, p < 0.001), but pulmonary function parameters and survival after diagnosis were not significantly different. Rate of recurrent pneumothorax was 58% to the ipsilateral side when the episode was managed by observation or chest tube without pleurodesis, and 0% after surgical management with pleurodesis. These data support the early use of surgical therapy with pleurodesis in managing patients with PLCH and spontaneous pneumothorax.


Editorial Commentary: Biomechanics of Cutting Studies-Knowledge and Deficiencies: Knee Joint Stability and the Posterolateral Corner.
Injury to the posterolateral corner of the knee is a difficult condition to treat. We know a lot about the anatomy and different methods with which we can reconstruct this complex area of the knee. Despite these advances, injuries to this area still do not lead to great surgical outcomes.


Combination and Novel Pharmacologic Agents for OAB.
To evaluate recent literature on combination and novel pharmacologic therapies for overactive bladder (OAB). Combination therapies demonstrating greater efficacy than monotherapy include combination anticholinergics, anticholinergic plus β-3 agonist, and anticholinergic with behavioral modification, percutaneous tibial nerve stimulation, or sacral neuromodulation. Promising novel therapies include new bladder selective anticholinergics, new β-3 agonists, and gabapentin. OAB is a symptom complex caused by dysfunction in the interconnected neural, muscular, and urothelial systems that control micturition. Although several therapeutic targets and treatment options exist, complete resolution is not always achieved, discontinuation rate for medical therapy is high, and few patients subsequently progress to third-line treatment options. Recent literature suggests combination therapy diversifying therapeutic targets is more effective than targeting a single pathway and novel treatments targeting additional pathways have promising results.


An unprecedented fully reduced {MoV 60} polyoxometalate: from an all-inorganic molecular light-absorber model to improved photoelectronic performance.
Fully reduced polyoxometalates are predicted to give rise to a broad and strong absorption spectrum, suitable energy levels, and unparalleled electronic and optical properties. However, they are not available to date. Here, an unprecedented fully reduced polyoxomolybdate cluster, namely Na8[MoV 60O140(OH)28]·19H2O {MoV 60}, was successfully designed and obtained under hydrothermal conditions, which is rare and is the largest fully reduced polyoxometalate reported so far. The MoV 60 molecule describes one Keggin {ε-Mo12} encapsulated in an unprecedented {Mo24} cage, giving rise to a double truncated tetrahedron quasi-nesting architecture, which is further face-capped by another four {Mo6} tripods. Its crystalline stability in air, solvent tolerance, and photosensitivity were all shown. As a cheap and robust molecular light-absorber model possessing wide light absorption, MoV 60 was applied to build a co-sensitized solar cell photoelectronic device along with N719 dyes and the optimal power conversion efficiency was 28% higher than that of single-dye sensitization. These results show that MoV 60 polyoxometalate could serve as an ideal model for the design and synthesis of all-inorganic molecular light-absorbers for other light-driven processes in the future.


[An external cardiac pacemaker for prevention of atrial fibrillation].
The paper presents an account of and the technical data of a new external pacemaker to be used to prevent atrial fibrillations. It shows it expedient to design such devices and presents their characteristics.


Sexual Harassment: Knowledge, Prevalence, Pattern, and Impacts Among Egyptian Female College Students.
Sexual harassment (SH) is an uprising problem worldwide, especially in Egypt. This study aims to determine the magnitude, patterns, and circumstances of SH among female students at Suez Canal University. A cross-sectional study was conducted on a representative female student sample (N = 644) from all the faculties using a self-administered anonymous questionnaire. The high prevalence of SH among college students in this study could be a consequence of the absence of knowledge about the legal framework. It mostly happened at all times of the day and night in the streets, and the least amount happened on the campus. Most of the harassers were younger than 20 years old and strangers. The majority of harassed females and surrounding people displayed negative reactions. None of the harassed females notified the authorities. The majority blamed men, and half claimed the SH act was due to the absence of religious principles. Moreover, the ignorance of the majority is with Egyptian law against SH. Both psychological and social impacts are significantly experienced by the harassed females. Thus, it is urgent to establish an institutional program (e.g., psycho-educative sessions during classes and peer training) or national awareness campaigns. Such programs and trainings aim to increase the awareness of students about the SH legal framework and how to deal with such acts, either as a victim or a witness, and how to provide the needed psychological assistance.


Collagenase--a marker enzyme in human bladder cancer?
Collagenase activity in human bladder carcinomas was measured against 14C-labeled collagen as substrate. Enzymes activity in vivo increased with the degree of penetration of the bladder wall. It was not detectable or low in the cases of superficially infiltrating tumours (A, B1 B2) and high in the cases of deeply infiltrating tumours (C, D). These results suggest that collagenase activity of advanced tumours is predominantly expressed in the pervesical layer of the bladder wall. A quantitative estimate of this enzyme may thus help to distinguish between Stage C and Stage C tumour.


Anesthesia for ventricular assist device placement in pediatric patients: experience from a single center.
The use of a ventricular assist device (VAD) as a bridge to heart transplantation in the pediatric population has evolved over the past decades This article presents our institution's clinical experience in the anesthetic management of pediatric patients with end-stage heart failure who underwent implantation of a VAD between June 2009 and August 2012. Between February 2011 and August 2012, implantation of a VAD was performed in 10 children of mean age 8.6 years. This retrospective review analyzed their perioperative anesthetic care. All patients had end-stage heart failure due to dilated cardiomyopathy. We used invasive arterial and central venous pressure monitoring and intraoperative transesophageal echocardiography in conjunction with intravenous administration of either ketamine (1 mg/kg) and midazolam (n = 3) or thiopental (3-5 mg/kg; n = 7). The mean intraoperative fentanyl dose was 434 ± 264.27 μg. Anesthesia was maintained with sevoflurane. Dopamine, dobutamine, and epinephrine were infused in 8, 10, and 5 patients, respectively. Inhaled nitric oxide was administered to all patients. The amounts of perioperative blood, fresh frozen plasma, and thrombocyte suspension transfusions were be 2.3 ± 0.82 (range, 1-4), 1.6 ± 0.69 (range, 1-3), and 2.4 ± 1.42 (range, 0-4) units, respectively. On average, patients were extubated 23 hours after arrival in the intensive care unit and exited there on day 6. Six patients were successfully bridged to heart transplantation, 2 died during the follow-up, and 2 patients remain on VAD support. VAD is increasingly being used as a bridge to heart transplantation in the pediatric population. Anesthesiologists must be vigilant about the pathophysiology of heart failure, the operative procedure, and the implanted device.


A tuberous sclerosis complex signalling node at the peroxisome regulates mTORC1 and autophagy in response to ROS.
Subcellular localization is emerging as an important mechanism for mTORC1 regulation. We report that the tuberous sclerosis complex (TSC) signalling node, TSC1, TSC2 and Rheb, localizes to peroxisomes, where it regulates mTORC1 in response to reactive oxygen species (ROS). TSC1 and TSC2 were bound by peroxisomal biogenesis factors 19 and 5 (PEX19 and PEX5), respectively, and peroxisome-localized TSC functioned as a Rheb GTPase-activating protein (GAP) to suppress mTORC1 and induce autophagy. Naturally occurring pathogenic mutations in TSC2 decreased PEX5 binding, and abrogated peroxisome localization, Rheb GAP activity and suppression of mTORC1 by ROS. Cells lacking peroxisomes were deficient in mTORC1 repression by ROS, and peroxisome-localization-deficient TSC2 mutants caused polarity defects and formation of multiple axons in neurons. These data identify a role for the TSC in responding to ROS at the peroxisome, and identify the peroxisome as a signalling organelle involved in regulation of mTORC1.


Role of ultrasonography in an impalpable tissue larynx model during a simulated front-of-neck access scenario: a randomized simulation study.
A large vertical incision is recommended when performing front-of-neck access in patients with impalpable neck landmarks during a cannot intubate-cannot oxygenate (CICO) scenario. We investigated the impact of ultrasonography on vertical incision size of a front-of-neck access on an ultrasound-compatible impalpable porcine larynx model. Emergency medicine and anesthesia trainees were randomized to the Ultrasound (US, n = 21) and Non-Ultrasound (NUS, n = 21) groups. Within 1 week after a teaching session on airway ultrasound and Scalpel-Bougie-Tube (SBT) technique, participants were instructed to perform cricothyroidotomy on the model during a simulated cannot intubate-cannot oxygenate scenario. The primary outcome was a vertical size incision. Secondary outcomes were procedural completion time, horizontal size incision, tissue injury severity, and correct tube placement. The ultrasound group performed a significantly smaller vertical incision [median (IQR), 35.0 (15, 40) vs 65.0 (52, 100) mm (95% CI) - 30.0 (- 55.1, - 4.9), p = 0.02] and took longer total time to complete the procedure [median (IQR), 200.5 (126, 267) vs 93.5 (71.0, 167.5) secs (95% CI) 91.0 (3.73, 178.3), p = 0.04]. Tissue injury severity and correct tube placement were similar between groups. Ultrasound-guided identification of the cricothyroid membrane significantly reduced the recommended vertical incision size with similar success rates. However, there was an increased time when performing a Scalpel-Bougie-Tube cricothyroidotomy on an impalpable porcine larynx model by physicians in training. Ultrasonography should not be used in an emergency scenario of airway rescue. Its potential use to pre-mark the cricothyroid membrane should be considered in difficult airway management of impalpable neck.


All-terrain vehicle injury prevention: healthcare providers' knowledge, attitudes, and the anticipatory guidance they provide.
All-terrain vehicles (ATVs) continue to be an increasing cause of injuries and deaths in children, especially in rural communities. More children die in the United States each year from ATV-related events than from bicycle crashes. The purpose of this study was to determine the ATV anticipatory guidance practices of primary care providers, as well as their attitudes, knowledge, and the barriers faced in educating families about the risk of ATV use. An electronic survey was administered to primary care providers belonging to state medical societies. More than 60% of respondents (Total N = 218) believed that ATV anticipatory guidance was important to provide to pediatric patients and their families. However, 78% stated they provide ATV safety counseling less than 10% of the time during regular pediatric exams, and only 12% stated they do so greater than 25% of the time. Families rarely ask providers for advice on ATV safety issues; 84% of providers were asked once a year or less. ATV knowledge scores were low (median score 2 of 12); however, those with previous ATV exposure had significantly higher scores. Many respondents affirmed insufficient knowledge (47%) and inadequate resources (63%), but the most commonly identified barrier was that it was not a routine part of their practice. Providers in the study demonstrated limited knowledge, reported multiple barriers, and provided little or no ATV safety counseling. However, they consider ATV anticipatory guidance important for their patients. Armed with increased knowledge and appropriate resources, providers could play a significant role in promoting ATV safety.


Erratum: Concentrations and kinetics of renal biomarkers in dogs with gastric dilatation-volvulus with and without 24-h intravenous lidocaine.
[This corrects the article DOI: 10.3389/fvets.2023.1115783.].


The diagnosis of large joint sepsis.
The microbial aetiology of large joint sepsis is changing now that joint replacement therapy is becoming common place. The clinical history and examination may give important clues about the likelihood of infection and the possible involvement of unusual organisms. Newly introduced technology to improve the sensitivity of tests for the presence of micro-organisms in synovial fluid has not yet made a significant contribution to routine management. New imaging techniques such as magnetic resonance imaging are likely to improve patient management, but their utility is still under assessment. Arthroscopic biopsy to obtain material for culture and histology is particularly important in suspected chronic septic arthritis. Prosthetic joint infections present a particular challenge to microbiologists since the organisms involved are often found in small numbers and are common skin contaminants. Optimal microbiological management involves the taking of multiple (> or = 5) samples, careful processing to resuscitate organisms whilst avoiding contamination, and careful interpretation of results in the light of the clinical and histological picture.


Distribution and partial characterization of the plasma lipoproteins in the hedgehog (Erinaceus europaeus L.), a hibernator with potential use in the study of the hormonal regulation of lipoprotein metabolism.
The hedgehog is a hibernator in which yearly cycles of several endocrine activities and seasonal variations of plasma lipids have already been demonstrated. We have consequently undertaken a study of plasma lipids and lipoproteins in this animal, bled during late April and May. Plasma cholesterol levels (178 +/- 30 mg/100 ml) were comparable with those in normal humans, while triacylglycerol was lower (46 +/- 17 mg/100 ml) and phospholipids higher (252 +/- 35 mg/100 ml). The main characteristics of the plasma lipoprotein spectrum, as determined by sequential and density gradient preparative ultracentrifugation, analytical ultracentrifugation and gel filtration chromatography, were (1) a low concentration of very-low-density components (d less than 1.006 g/ml, about 20 mg/100 ml); (2) a continuity between the low (1.006-1.063 g/ml) and high (1.063-1.21 g/ml) density components, the former (about 150 mg/100 ml) exhibiting a considerable heterogeneity upon polyacrylamide gel electrophoresis while the latter were largely predominating (570 mg/100 ml); (3) the presence, at a density of 1.087 g/ml, of a band migrating electrophoretically like human low-density lipoproteins, a finding consistent with the results of apolipoprotein electrophoresis, which showed the presence of a high-molecular-weight counterpart to apolipoprotein B, in both the low- and high-density ranges defined above; (4) the presence, throughout the entire density spectrum, of an apolipoprotein with molecular weight and mobility in polyacrylamide/urea gels similar to human apolipoprotein A-I, and (5) the presence of very-high-density lipoproteins (d 1.178-1.259 g/ml) responsible for the transport of approximately 15% of plasma cholesterol and 20% of phospholipids.


Mobilization and removing of cadmium from kidney by GMDTC utilizing renal glucose reabsorption pathway.
Chronic exposure to cadmium compounds (Cd(2+)) is one of the major public health problems facing humans in the 21st century. Cd(2+) in the human body accumulates primarily in the kidneys which leads to renal dysfunction and other adverse health effects. Efforts to find a safe and effective drug for removing Cd(2+) from the kidneys have largely failed. We developed and synthesized a new chemical, sodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6 pentahydroxyhexyl)amino)-4-(methylthio) butanoate (GMDTC). Here we report that GMDTC has a very low toxicity with an acute lethal dose (LD50) of more than 10,000mg/kg or 5000mg/kg body weight, respectively, via oral or intraperitoneal injection in mice and rats. In in vivo settings, up to 94% of Cd(2+) deposited in the kidneys of Cd(2+)-laden rabbits was removed and excreted via urine following a safe dose of GMDTC treatment for four weeks, and renal Cd(2+) level was reduced from 12.9μg/g to 1.3μg/g kidney weight. We observed similar results in the mouse and rat studies. Further, we demonstrated both in in vitro and in animal studies that the mechanism of transporting GMDTC and GMDTC-Cd complex into and out of renal tubular cells is likely assisted by two glucose transporters, sodium glucose cotransporter 2 (SGLT2) and glucose transporter 2 (GLUT2). Collectively, our study reports that GMDTC is safe and highly efficient in removing deposited Cd(2+) from kidneys assisted by renal glucose reabsorption system, suggesting that GMDTC may be the long-pursued agent used for preventive and therapeutic purposes for both acute and chronic Cd(2+) exposure.


Significance of transient receptor potential vanilloid 4 and aquaporin 5 co-expression in the rat uterus at term.
Aquaporins (AQPs) are channel proteins that facilitate the rapid passive movement of water. In our studies it was proved that the decreased AQP5 expression is followed by the increase of uterine contractility. The transient receptor potential vanilloid 4 (TRPV4) is a calcium channel, which is activated in response to osmotic changes. Our aim was to determine the possible role of AQP5 in this osmotic regulation of TRPV4, thus in pregnant uterine contraction. We used RT-PCR and Western blot techniques for the detection of the TRPV4 expression during pregnancy in rat uterus. The localization of AQP5 and TRPV4 was determined by immunohistochemical studies. The role of TRPV4 in uterus contraction was investigated in an isolated organ bath system. In vitro uterus contractions were stimulated with KCl and its effect was investigated with the selective TRPV4 agonist (RN1747) and antagonist (RN1734). The TRPV4 expression continuously increased from day 18 to the last day of pregnancy. The co-expression of TRPV4 and AQP5 in the myometrium and endometrium was determined in the late pregnant uterus. The TRPV4 antagonist and agonist significantly decreased and increased uterine contraction, respectively, especially on the last day of pregnancy. We presume the decreased AQP5 expression triggers hypertonic stress, which activates TRPV4 and increases uterus contraction on the day of labor. Based on these findings, we suppose the TRPV4 effect on uterus contraction is AQP5 control, which could be a new target in preterm birth therapy.


Comparison of two semen extenders in terms of in vitro development of bovine embryos following IVF.
In order to conform with current EC standards with regard to antibiotic cover, the Norwegian Cattle Association is currently investigating the use of Biladyl as an alternative to the milk-based extender which has been traditionally used in Norway. A study was carried out to investigate the effect of using semen frozen with either milk extender or Biladyl on the outcome of in vitro fertilization and embryo culture. Semen from 6 Norwegian Red bulls was used. There was a significant difference p < 0.05 in terms of cleavage rate between the 2 extenders for 1 bull, 78.2% vs 94.9% for milk and Biladyl extenders, respectively, and for the overall total of 71.3% vs 76.1% for milk and Biladyl extenders, respectively. There were no significant differences in terms of blastocyst yield amongst any of the bulls. In conclusion, the results suggest that Biladyl can be used as a replacement for the traditional milk-based extender without any adverse effects on blastocyst yields following in vitro fertilization.


Wear of ion-implanted pure titanium against UHMWPE.
Six specimens were manufactured from commercially pure titanium (grade IV) to resemble femoral head prostheses, and five of them ion implanted to increase the wear properties. Together with three cobalt-chrome controls they were run for one million cycles on a 10-station joint simulator. For the first time both the polymer and metallic wear were quantified in the same study. The purpose of the investigation was to estimate the potential for using commercially pure titanium as a bearing surface against ultrahigh-molecular-weight polyethylene for total joint application. It was concluded that the wear properties of titanium were improved by ion implantation, and that these positive effects could probably be enhanced with development of a better polishing technique, and by finding methods of extending the penetration depth of the nitrogen ions.


High surface area porous carbons prepared from hydrochars by phosphoric acid activation.
In the present work, a new route for preparation of high-performance porous carbons under mild conditions was reported. The high surface area (2700 m2/g) and large pore volume (1.98 cm3/g) porous carbons were prepared from hydrochars by conventional phosphoric acid activation method. The hydrochars described here can be obtained from sulfuric acid hydrolysis of rice husk via dehydration, polymerization and carbonization. A specific capacitance of 130 F g(-1) was achieved by using the porous carbon, indicating that the porous carbon prepared by this route has good electrochemical performance. Furthermore, the localized graphitic nature of the porous carbon was proved by X-ray diffraction pattern.


Normal skeletal pattern formation in chick limb bud with a mesenchymal hole is mediated by adjustment of cellular properties along the anterior-posterior axis in the limb bud.
The chick limb bud has plasticity to reconstruct a normal skeletal pattern after a part of mesenchymal mass is excised to make a hole in its early stage of development. To understand the details of hole closure and re-establishment of normal limb axes to reconstruct a normal limb skeleton, we focused on cellular and molecular changes during hole repair and limb restoration. We excised a cube-shaped mass of mesenchymal cells from the medial region of chick hindlimb bud (stage 23) and observed the following morphogenesis. The hole had closed by 15 h after excision, followed by restoration of the limb bud morphology, and the cartilage pattern was largely restored by 48 h. Lineage analysis of the mesenchymal cells showed that cells at the anterior and posterior margins of the hole were adjoined at the hole closure site, whereas cells at the proximal and distal margins were not. To investigate cell polarity during hole repair, we analyzed intracellular positioning of the Golgi apparatus relative to the nuclei. We found that the Golgi apparatus tended to be directed toward the hole among cells at the anterior and posterior margins but not among cells at identical positions in normal limb buds or cells at the proximal and distal hole margins. In the manipulated limb buds, the frequency of cell proliferation was maintained compared with the control side. Tbx3 expression, which was usually restricted to anterior and posterior margins of the limb bud, was temporarily expanded medially and then reverted to a normal pattern as limb reconstruction proceeded, with Tbx3 negative cells reappearing in the medial regions of the limb buds. Thus, mesenchymal hole closure and limb reconstruction are mainly mediated by cells at the anterior and posterior hole margins. These results suggest that adjustment of cellular properties along the anteroposterior axis is crucial to restore limb damage and reconstruct normal skeletal patterns.


Do spouse burden of care, family resilience, and coping affect family function in gynecologic cancer in Korea?: a cross-sectional study.
This study aimed to investigate family functioning among spouses of gynecologic cancer patients in Korea. McCubbin and McCubbin's Family Resilience Model (1993) guided the study focus on burden of care, family resilience, coping, and family functioning. An online survey collected data from 123 spouses of gynecologic cancer patients through convenience sampling from online communities for gynecologic cancer patients in Korea. Burden of care, family resilience (social support, family hardiness, and family problem-solving communication), coping, and family functioning were measured by self-report. The patients (44.7%) and their spouses (47.2%) were mostly in the 41 to 50-year age group. Stage 1 cancer was 44.7%, and cervical cancer was the most common (37.4%) followed by ovarian cancer (30.9%) and uterine cancer (27.6%) regarding the cancer characteristics of the wife. Family function, burden of care, family resilience, and coping were all at greater than midpoint levels. Family functioning was positively related with social support (r=.44, p<.001), family hardiness (r=.49, p<.001), problem-solving communication (r=.73, p<.001), and coping (r=.56, p<.001). Multiple regression identified significant factors for family functioning (F=25.58, p<.001), with an overall explanatory power of 61.7%. Problem-solving communication (β=.56, p<.001) had the greatest influence on family function of gynecologic cancer families, followed by coping (β=.24, p<. 001) and total treatment period of the wife (β=.17, p=.006). Nurses need to assess levels of family communication and spousal coping to help improve gynecologic cancer patients' family function, especially for patients in longer treatment.


Antibody-Drug Conjugates in Uro-Oncology.
Currently available treatment options for patients with refractory metastatic prostate, bladder, or kidney cancers are limited with the prognosis remaining poor. Advances in the pathobiology of tumors has led to the discovery of cancer antigens that may be used as the target for cancer treatment. Antibody-drug conjugates (ADCs) are a relatively new concept in cancer treatment that broaden therapeutic landscape. ADCs are examples of a 'drug delivery into the tumor' system composed of an antigen-directed antibody linked to a cytotoxic drug that may release cytotoxic components after binding to the antigen located on the surface of tumor cells. The clinical properties of drugs are influenced by every component of ADCs. Regarding uro-oncology, enfortumab vedotin (EV) and sacituzumab govitecan (SG) are currently registered for patients with locally advanced or metastatic urothelial cancer following previous treatment with an immune checkpoint inhibitor (iCPI; programmed death receptor-1 [PD-1] or programmed death-ligand 1 [PD-L1]) inhibitor) and platinum-containing chemotherapy. The EV-301 trial showed that EV significantly prolonged the overall survival compared with classic chemotherapy. The TROPHY-U-01 trial conducted to evaluate SG demonstrated promising results as regards the objective response rate and duration of response. The safety and efficacy of ADCs in monotherapy and polytherapy (mainly with iCPIs) for different cancer stages and tumor types are assessed in numerous ongoing clinical trials. The aim of this review is to present new molecular biomarkers, specific mechanisms of action, and ongoing clinical trials of ADCs in genitourinary cancers. In the expert discussion, we assess the place of ADCs in uro-oncology and discuss their clinical value.


Minimally Invasive Surgical Approaches to Gastric Resection.
Minimally invasive gastric resections carry several advantages, including less intraoperative blood loss, faster recovery time, reduced pain, and decreased hospital length of stay and quicker return to work. Numerous trials have proved that laparoscopic and robotic-assisted gastrectomy provides equivalent surgical and oncologic outcomes to open approaches. As with any minimally invasive approach, advanced minimally invasive training and good judgment by a surgeon are paramount in selecting patients in whom a minimally invasive approach is feasible. With increasing research in patient populations with more advanced disease, the indications are likely to continue to expand.


Transgenerational inheritance of impaired larval T cell development in zebrafish.
Evidence for transgenerational inheritance of epigenetic information in vertebrates is scarce. Aberrant patterns of DNA methylation in gametes may set the stage for transmission into future generations. Here, we describe a viable hypomorphic allele of dnmt1 in zebrafish that causes widespread demethylation of CpG dinucleotides in sperm and somatic tissues. We find that homozygous mutants are essentially normal, with the exception of drastically impaired lymphopoiesis, affecting both larval and adult phases of T cell development. The phenotype of impaired larval (but not adult) T cell development is transmitted to subsequent generations by genotypically wildtype fish. We further find that about 200 differentially methylated regions in sperm DNA of transmitting and non-transmitting males, including hypermethylated sites associated with runx3 and rptor genes, whose reduced activities are associated with impaired larval T cell development. Our results indicate a particular sensitivity of larval T cell development to transgenerationally inherited epimutations.


Invention and modification of a new tool use behavior: ant-fishing in trees by a wild chimpanzee (Pan troglodytes verus) at Bossou, Guinea.
Wild chimpanzees are known to have a different repertoire of tool use unique to each community. For example, "ant-dipping" is a tool use behavior known in several chimpanzee communities across Africa targeted at driver ants (Dorylus spp.) on the ground, whereas "ant-fishing," which is aimed at carpenter ants (Camponotus spp.) in trees, has primarily been observed among the chimpanzees of Mahale in Tanzania. Although the evidence for differences between field sites is accumulating, we have little knowledge on how these tool use behaviors appear at each site and on how these are modified over time. This study reports two"ant-fishing" sessions which occurred 2 years apart by a young male chimpanzee at Bossou, Guinea. Ant-fishing had never been observed before in this community over the past 27 years. During the first session, at the age of 5, he employed wands of similar length when ant-fishing in trees to those used for ant-dipping on the ground, which is a customary tool use behavior of this community. Two years later, at the age of 7, his tools for ant-fishing were shorter and more suitable for capturing carpenter ants. This observation is a rare example of innovation in the wild and does provide insights into problem-solving and learning processes in chimpanzees.


The Idd13 congenic interval defines the number of merocytic dendritic cells, a novel trait associated with autoimmune diabetes susceptibility.
When antigens derived from apoptotic cells are presented by conventional dendritic cells (cDC), T cell tolerance is induced. Surprisingly, the presentation of apoptotic cell antigens by an unconventional DC subset, termed merocytic dendritic cells (mcDC), can reverse T cell anergy. The potency of mcDC at breaking T cell tolerance has been demonstrated in the context of tumors and autoimmunity, suggesting that modulating the number of mcDC in vivo may be of clinical interest. To identify the genetic determinants that define the number of mcDC, we performed a linkage analysis between NOD and C57BL/6 mouse strains, where autoimmune-prone NOD mice show an increased proportion of mcDC relative to the non-autoimmune-prone C57BL/6 mice. We identified a locus on chromosome 2 significantly linked to both the proportion and the absolute number of mcDC in the spleen. Interestingly, the dominant interval on chromosome 2 overlaps with a locus previously associated with diabetes protection, namely Idd13. Using NOD.Idd13 congenic mice, we validate the impact of the Idd13 congenic interval in defining the proportion and number of mcDC in the spleen. These results show that the decreased number of mcDC is conferred by C57BL/6 alleles at the Idd13 locus, which is linked to diabetes resistance.


Analysis of mechanisms of activation and repression at bacterial promoters.
In bacteria, the expression of transcription units is controlled by regulatory regions, that contain one or more promoters and binding sites for regulatory proteins that activate or repress expression in response to different signals. In this chapter, we explain the diverse approaches that can be used to understand the mechanisms by which the different factors intervene, and how the effects are integrated. Bioinformatics, genetics and biochemistry must be combined to understand the organisation of regulatory regions and the mechanisms by which transcription initiation is controlled.


Joint design of kT-points trajectories and RF pulses under explicit SAR and power constraints in the large flip angle regime.
In Magnetic Resonance Imaging at ultra-high field, kT-points radiofrequency pulses combined with parallel transmission are a promising technique to mitigate the B1 field inhomogeneity in 3D imaging applications. The optimization of the corresponding k-space trajectory for its slice-selective counterpart, i.e. the spokes method, has been shown in various studies to be very valuable but also dependent on the hardware and specific absorption rate constraints. Due to the larger number of degrees of freedom than for spokes excitations, joint design techniques based on the fine discretization (gridding) of the parameter space become hardly tractable for kT-points pulses. In this article, we thus investigate the simultaneous optimization of the 3D blipped k-space trajectory and of the kT-points RF pulses, using a magnitude least squares cost-function, with explicit constraints and in the large flip angle regime. A second-order active-set algorithm is employed due to its demonstrated success and robustness in similar problems. An analysis of global optimality and of the structure of the returned trajectories is proposed. The improvement provided by the k-space trajectory optimization is validated experimentally by measuring the flip angle on a spherical water phantom at 7T and via Quantum Process Tomography.


Complete Genome of Agrobacterium fabrum Strain 1D1416.
This work reports the draft genome of Agrobacterium fabrum strain 1D1416. The assembled genome is composed of a 2,837,379-bp circular chromosome, a 2,043,296-bp linear chromosome, a 519,735-bp AT1 plasmid, a 188,396-bp AT2 plasmid, and a 196,706-bp Ti virulence plasmid. The nondisarmed strain produces gall-like structures in citrus tissue.


Longitudinal changes in three normal facial types.
The purpose of this study was to describe and compare the dentofacial relationships of three normal facial types (long, average, and short). Comparisons of the absolute and incremental changes between 5 years and 25.5 years of age were made both longitudinally and cross-sectionally. The subjects consisted of 20 males and 15 females for whom complete sets of data were available for the period of this study. All subjects had clinically acceptable occlusion and had not undergone previous orthodontic treatment. Descriptive statistics summarized the changes in 48 parameters, including that of height for males and females at 5, 10, 15, and 25.5 years of age. Longitudinal comparisons of the growth curves evaluated the curve profiles and curve magnitudes for the three facial types for both males and females. The analysis of variance was also used to compare the absolute and incremental changes at ages 5, 10, 15, and 25.5 years. The investigation resulted in the following findings. (1) Most persons (77%) have been categorized as having the same facial type at 5 and at 25.5 years of age. There is a strong tendency to maintain the original facial type with age. (2) Comparisons of the growth curves of the different parameters--with the exception of the incremental curves for MP:SN and Pog:NB in males--consistently demonstrated parallelism of the curves, regardless of the facial type. On the other hand, comparisons of curve magnitude indicated significant differences among the three facial types. (3) The persons within each facial type expressed a relatively large variation in the size and relationships of the various dentofacial structures. (4) Significant differences in the dentofacial parameters were present between males and females with the same facial type. The differences among facial types were not identical in males and females. (5) Longitudinal analysis of the data lends more consistent and, therefore, more meaningful results than cross-sectional comparisons when facial growth trends need to be evaluated. This is because growth changes are often subtle and of magnitudes not readily observed when the data are evaluated cross-sectionally. Standards that are age-, sex- and facial type-specific are presented.


Mesenchymal stem cells microvesicles stabilize endothelial barrier function partly mediated by hepatocyte growth factor (HGF).
Mesenchymal stem cells microvesicles (MSC-MVs) stabilize endothelial barrier function in acute lung injury (ALI); however, the detailed mechanism remains to be further defined. Hepatocyte growth factor (HGF), which is derived from MSC-MVs, might have a key role in the restoration of endothelial barrier function by MSC-MVs. MSCs with lentiviral vector-mediated HGF gene knockdown (siHGF-MSC) were generated. A co-culture model of pulmonary microvascular endothelial cells and MSC-MVs collected from MSCs or siHGF-MSCs after 24 h of hypoxic culture was utilized. Then, endothelial paracellular and transcellular permeabilities were detected. VE-cadherin, and occludin protein expression in the endothelial cells was measured using Western blot. Endothelial cell proliferation was analysed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. Endothelial cell apoptosis was analysed using TUNEL assay. Finally, IL-6 and IL-10 production was determined via an enzyme-linked immunosorbent assay (ELISA). Treatment with MSC-MVs significantly decreased LPS-induced endothelial paracellular and transcellular permeabilities, and the effect was significantly inhibited after HGF gene knockdown in MSC-MVs. Furthermore, treatment with MSC-MVs increased the expression of the endothelial intercellular junction proteins VE-cadherin and occludin. Treatment with MSC-MVs also decreased endothelial apoptosis and induced endothelial cell proliferation. Finally, the treatment reduced IL-6 production and increased IL-10 production in the conditioned media of endothelial cells. However, the effects of the treatment with MSC-MVs were inhibited after HGF gene knockdown. MSC-MVs protect the barrier functions of pulmonary microvascular endothelial cells, which can be partly attributed to the presence of HGF in the MSC-MVs.


Acute hepatitis of unknown aetiology among children around the world.
By 26 August 2022, the number of cases of acute hepatitis of unknown etiology (AHUA) has drastically increased to 1115 distributed in 35 countries that fulfill the World Health Organization definition. Several hypotheses on the cause of AHUA have been proposed and are being investigated around the world. In the recent United Kingdom (UK) report, human adenovirus (HAdV) with adeno-associated virus (AAV) co-infection is the leading hypothesis. However, there is still limited evidence in establishing the causal relationship between AHUA and any potential aetiology. The leading aetiology continues to be HAdV infection. It is reported that HAdV genomics is not unusual among the population in the UK, especially among AUHA cases. Expanding the surveillance of HAdV and AAV in the population and the environment in the countries with AUHA cases is suggested to be the primary action. Metagenomics should be used in detecting other infectious pathogens on a larger scale, to supplement the detection of viruses in the blood, stool, and liver specimens from AUHA cases. It is useful to develop a consensus-specific case definition of AHUA to better understand the characteristics of these cases globally based on all the collected cases.


Guillain-Barré syndrome after allogeneic hematopoietic stem cell transplantation.
Guillain-Barré syndrome is a rare complication in the setting of hematopoietic stem cell transplantation. We report three children with T cell lymphoma/leukemia in whom this syndrome developed soon after they received unrelated donor transplants. The rapid onset of symptoms raises the concern that the bone marrow transplant conditioning regimen (ie, total body irradiation, cyclophosphamide and cytosine arabinoside) might have precipitated the clinical syndrome of ascending polyneuropathy. Although central nervous system toxicity has been well described with high-dose cytosine arabinoside therapy, peripheral neuropathy of the Guillain-Barré type has been reported only infrequently. We review possible factors contributing to the development of this syndrome in these three patients.


Sedentary Time and White Matter Hyperintensity Volume in Older Adults.
Cerebrovascular disease in the form of white matter hyperintensities (WMH) increases with age and is associated separately with sedentary time and reduced kidney function. A better understanding of the relationships among these variables would help clarify whether sedentary time should be considered more closely in older adults at particular levels of kidney function to reduce the risk of WMH. We analyzed information from 94 healthy community-dwelling older adults to determine the association of sedentary time and WMH in nondemented, nondepressed older adults, and whether level of kidney function was an effect modifier of the relationship between sedentary time and WMH. Sedentary behavior was measured using the Sedentary Behavior Questionnaire. White matter hyperintensity was assessed using whole-brain 3T magnetic resonance imaging T1- and T2-weighted images. Kidney function was calculated by the epi-chronic kidney disease formula for estimated glomerular filtration rate (eGFR). Exposures or predictors were sedentary time, age, sex, education in years, Framingham stroke risk 10-yr prediction score, and eGFR. The analytical approach was multiple linear regression. Adjusting for age, sex, education in years, Framingham stroke risk 10-yr prediction score, greater sedentary time was associated with greater WMH but this effect was dependent on level of eGFR (sedentary time-eGFR interaction b = -0.0005, P = 0.022). At eGFR values of 69, 81, and 93 mL·min per 1.73 m (the 25th, 50th, and 75th percentiles), sedentary time b coefficients were b = 0.021 (95% confidence interval [CI], 0.011-0.031), b = 0.015 (95% CI, 0.008-0.022), and b = 0.009 (95% CI, 0.003-0.016). The effect weakened linearly as eGFR increased, with no significant association at eGFR ≥97 mL·min per 1.73 m. Findings suggest that sedentary time is associated with WMH in persons with an eGFR ≤96 mL·min per 1.73 m and that this association is stronger with lower levels of kidney function.


Barriers to responsible innovation of nanotechnology applications in food and agriculture: A study of US experts and developers.
The use of nanotechnology and engineered nanomaterials in food and agriculture (nano-agrifood) sectors is intended to provide several potential benefits to consumers and society, such as the provision of more nutritious processed foods, edible food coatings to extend shelf lives of fresh cut produce, and more sustainable alternatives to traditional agrochemicals. The responsible innovation of nano-agrifoods may be particularly important to pursue given previous case studies involving other agrifood technologies that experienced significant public consternation. Here, we define responsible innovation following Stilgoej et al. (2013) that establishes processes to iteratively review and reflect upon one's innovation, engage stakeholders in dialogue, and to be open and transparent throughout innovation stages - processes that go beyond primary focuses of understanding environmental, health, and safety impacts of nano-enabled products and implementing safe-by-design principles. Despite calls for responsible nano-innovation across diverse sectors, it has not yet been clear what types of barriers are faced by nano-agrifood researchers and innovators in particular. This study therefore identifies and builds the first typology of barriers to responsible innovation as perceived by researchers and product developers working in nano-agrifood sectors in the United States. Our findings report 5 key barriers to responsible innovation of nano-agrifoods: Lack of Data (reported by 70% of all interview participants, and represented 34.6% of all barrier-related excerpts), Lack of Product Oversight (reported by 60% of participants, and represented 28.7% of excerpts), Need for Ensuring Marketability & Use (reported by 70% of participants, and represented 21.3% of all barrier-related excerpts), Need for Increased Collaboration (reported by 40% of participants, and represented 10.3% of excerpts), and finally Lack of Adequate Training & Workforce (reported by 30% of participants, and represented by 5.1% of excerpts). We also relate these key barriers across three main nano-innovation phases, including 1) Scientific and Technical R&D, 2) Product Oversight, and 3) Post-commercialization Marketability & Use, and discuss how these barriers may impact stakeholders as well as present opportunities to align with principles of responsible innovation. Overall, these findings may help illuminate challenges that researchers and innovators face in the pursuit of responsible innovation relevant for the field of nanotechnology with relevancy for other emerging food and agricultural technologies more broadly.


Human leukocyte antigen class I (A, B) and class II (DRB1) allele and haplotype frequencies in Iranian patients with Buerger's disease.
The aim of this study was to investigate the human leukocyte antigen (HLA) class I (HLA-A and HLA-B) and II (HLA-DRB1) allele and haplotype frequencies in a group of Iranian patients with Buerger's disease (BD) in comparison with a normal healthy control group. A total of 70 unrelated male patients and 100 healthy controls from Sina Hospital, Tehran, Iran, belonging to the same ethnic background, were enrolled in this case-control study. HLA-A, B, and DRB1 typing were performed by polymerase chain reaction with sequence-specific primers (PCR-SSP). The results of this case-control study showed that the frequency of the HLA-A*03:01 (odds ratio (OR) = 2.88, P value (Pv) = .002), HLA-A*29:01 (OR = 15.31, Pv < .001), HLA-DRB1*04:02 (OR = 3.41, Pv < .001), and HLA-DRB1*16:01 (OR = 8.16, Pv < .001) was significantly higher in BD patients compared with healthy controls, whereas the frequency of the HLA-DRB1*01:01 (OR = 0.03, Pv < .001) was significantly lower in BD patients. The most frequent extended haplotypes in our patients were HLA-A*02:01-B*55:01-DRB1*04:03. This study is the first study evaluating an association between the HLA pattern and BD in the patients with BD from North West and North Iran.


Fluorometric estimation of surface associated microbial abundance.
Surface associated microbes have historically been difficult to accurately and effectively enumerate. In the current study, we propose a rapid and simple method for estimating abundance of surface associated microbial cells by fluorescence of SYBRGreen stained bacteria and in vivo chlorophyll a fluorescence of benthic diatoms in 24 and 48-well microtiter plates. The effectiveness of this high-throughput technique is demonstrated by assessing sensitivity of a clinical strain of Vibrio cholerae, a benthic bacterial isolate and the benthic microalgae Cylindrotheca closterium to three antibiotics--tylosin, lincomycin and ciproflaxacin. We report on the significant linear relationships between spectral chl a fluorescence and cell abundance and between microalgal growth rates derived from cell counts and fluorescence. Additionally, we provide a simplified and improved method for preparation of a silica gel matrix (SGM), which is an ideal plating media for fluorescence applications. These findings indicate that spectrofluorometry is an inexpensive tool for rapidly estimating abundance of surface associated microbiota and can be employed for assessing antibiotic sensitivity.


pH-Controlled assembly and disassembly of a cryptand/paraquat [2]pseudorotaxane.
Strong complexation between a pyridine-containing cryptand and paraquat can be reversibly switched off (and back on) by adding acid (and then base).