Parental views of children's physical activity: a qualitative study with parents from multi-ethnic backgrounds living in England.
Guidelines recommend children and young people participate in at least 60 min of physical activity (PA) every day, however, findings from UK studies show PA levels of children vary across ethnic groups. Since parents play an instrumental role in determining children's PA levels, this article aims to explore parental views of children's PA in a multi-ethnic sample living in a large city in the North-West of England. Six single-ethnic focus groups were conducted with 36 parents of school-aged children (4 to 16 years) with a predominantly low socio-economic status (SES). Parents self-identified their ethnic background as Asian Bangladeshi (n = 5), Black African (n = 4), Black Somali (n = 7), Chinese (n = 6), White British (n = 8) and Yemeni (n = 6). Focus group topics included understanding of PA, awareness of PA guidelines, knowledge of benefits associated with PA and perceived influences on PA in childhood. Data were analysed thematically using QSR NVivo 9.0. Parents from all ethnic groups valued PA and were aware of its benefits, however they lacked awareness of PA recommendations, perceived school to be the main provider for children's PA, and reported challenges in motivating children to be active. At the environmental level, barriers to PA included safety concerns, adverse weather, lack of resources and lack of access. Additional barriers were noted for ethnic groups from cultures that prioritised educational attainment over PA (Asian Bangladeshi, Chinese, Yemeni) and with a Muslim faith (Asian Bangladeshi, Black Somali, Yemeni), who reported a lack of culturally appropriate PA opportunities for girls. Parents from multi-ethnic groups lacked awareness of children's PA recommendations and faced barriers to promoting children's PA out of school, with certain ethnic groups facing additional barriers due to cultural and religious factors. It is recommended children's PA interventions address influences at all socio-ecological levels, and account for differences between ethnic groups.


Molecular docking and inhibition kinetics of α-glucosidase activity by labdane diterpenes isolated from tora seeds (Alpinia nigra B.L. Burtt.).
Current approach against type 2 diabetes involves α-glucosidase inhibitors like acarbose associated with many side effects. Therefore, as an alternative to the existing drug, many natural products mainly from plant sources have been investigated which inhibit α-glucosidase. Here, we have selected medicinally important Alpinia nigra to explore its α-glucosidase inhibitory activity. Organic extracts of seeds and two purified natural diterpenes I: (E)-labda-8(17), 12-diene-15, 16-dial and II: (E)-8β, 17-epoxylabd-12-ene-15, 16-dial from A. nigra were investigated towards inhibition of α-glucosidase activity. Dose-dependent inhibition pattern were observed for seed extracts and both the compounds. Further, inhibition kinetics studies of the diterpenes indicated a non-competitive type of inhibition against α-glucosidase. Docking studies were carried out which revealed that both the diterpenes interacted within the active site of N-terminal and C-terminal domain of human maltase-glucoamylase enzyme, respectively. This is the first report of α-glucosidase inhibitory activity of these isolated diterpenes and their higher inhibitory potential than any terpenoids studied till date against α-glucosidase.


flippant-An R package for the automated analysis of fluorescence-based scramblase assays.
The lipid scrambling activity of protein extracts and purified scramblases is typically measured using a fluorescence-based assay. While the assay has yielded insight into the scramblase activity in crude membrane preparations, functional validation of candidate scramblases, stoichiometry of scramblase complexes as well as ATP-dependence of flippases, data analysis in its context has remained a task involving many manual steps. With the extension package "flippant" to R, a free software environment for statistical computing and graphics, we introduce an integrated solution for the analysis and publication-grade graphical presentation of dithionite scramblase assays and demonstrate its utility in revisiting an originally manual analysis from the publication record, closely reproducing the reported results. "flippant" allows for quick, reproducible data analysis of scramblase activity assays and provides a platform for review, dissemination and extension of the strategies it employs.


Development of Correction for Signal-to-Noise Ratio Using a T2* With Improved Phase Method.
This study aims to improve the signal-to-noise ratio (SNR) of the phase image focusing T2 and to develop an improved phase (iPhase) image acquired high SNR. The iPhase images of phantom and brain were acquired with multi-echo spoiled gradient-echo. The phantom component was a gadopentetate dimeglumine (Gd-DTPA) solution made of different concentrations (0.1, 0.5, and 1 wt%) and Gd-DTPA (0.1, 0.5, and 1 wt%) with agar (1.0 wt%). We applied the iPhase image to susceptibility weighed image (SWI) and evaluated SNR of SWI. In phantom study, SNRs of conventional SWI at each sample were 19.8, 15.7, 7.4, 20.0, 17.4, and 27.3, respectively. Signal-to-noise ratios of SWI derived from iPhase method were 29.5, 33.7, 21.7, 28.5, 24.3, and 14.7, respectively. Then, the SNR showed an improvement of 196% at maximum (for the Gd-DTPA 1 wt% sample). In healthy volunteer study, SWI derived from iPhase method had the good contrast between white matter and gray matter. The iPhase image was able to improve the phase SNR. Moreover, iPhase method makes it possible to obtain a high SNR image when applying to SWI.


A context-based approach to predict intelligibility of meaningful and nonsense words in interrupted noise: Model evaluation.
The context-based Extended Speech Transmission Index (cESTI) by Van Schoonhoven et al. (2022) was successfully used to predict the intelligibility of meaningful, monosyllabic words in interrupted noise. However, it is not clear how the model behaves when using different degrees of context. In the current paper, intelligibility of meaningful and nonsense CVC words in stationary and interrupted noise was measured in fourteen normally hearing adults. Intelligibility of nonsense words in interrupted noise at -18 dB SNR was relatively poor, possibly because listeners did not profit from coarticulatory cues as they did in stationary noise. With 75% of the total variance explained, the cESTI model performed better than the original ESTI model (R2 = 27%), especially due to better predictions at low interruption rates. However, predictions for meaningful word scores were relatively poor (R2 = 38%), mainly due to remaining inaccuracies at interruption rates below 4 Hz and a large effect of forward masking. Adjusting parameters of the forward masking function improved the accuracy of the model to a total explained variance of 83%, while the predicted power of previously published cESTI data remained similar.


Cardiac troponin T levels are associated with poor short- and long-term prognosis in patients with acute cardiogenic pulmonary edema.
The clinical determinants of increased cardiac troponin T (cTnT) in patients with acute cardiogenic pulmonary edema are not well defined, and the ability of this marker to predict long-term mortality has not yet been documented. Eighty-four patients with acute cardiogenic pulmonary edema without acute myocardial infarction were prospectively enrolled. cTnT was measured in samples obtained 6 and 12 hours after admission. cTnT levels of 0.1 ng/mL or greater were found in 46 patients (55%). Thirty-two patients (38%) died during follow-up. The area under the receiver operating characteristic curve for cTnT was 0.70 and 0.69 at 6 and 12 hours (P =.47), and the cTnT cutoff value of 0.1 ng/mL was 66% and 69% sensitive and 63% and 71% specific, respectively, in predicting subsequent mortality. Patients were assigned to group 1 if they had cTnT lower than 0.1 ng/mL and to group 2 if they had cTnT levels of 0.1 ng/mL or greater. A history of coronary artery disease was present in 72% of group 2 versus 50% of group 1 patients (P =.04). Patients in group 2 were also older than those in group 1 (mean age, 68 years vs 61 years; P =.021). The 3-year survival in group 1 was 76% compared with 29% in group 2 (log-rank test, P <.001). In a Cox proportional hazards model, elevated cTnT emerged as the only prognostic marker of long-term mortality (risk ratio [RR] = 2.31; 95% CI, 1.011-5.280; P =.047). A cTnT level of 0.1 ng/mL or greater was associated with poor long-term survival and emerged as a powerful independent predictor of mortality in patients with acute cardiogenic pulmonary edema.


[Clinicopathological features and BRAF V600E and MYD88 L265P mutation status of nodal marginal zone lymphoma].
Objective: To investigate the clinicopathological features as well as BRAF V600E and MYD88 L265P mutation status of nodal marginal zone B cell lymphoma (NMZL). Methods: Thirty-two cases of NMZL were diagnosed from September 2009 to February 2021 at the Henan Provincial People's Hospital and Peking University School of Basic Medical Sciences. The clinicopathologic characteristics were obtained and analyzed. BRAF V600E and MYD88 L265P mutation status were identified using PCR and Sanger sequencing, respectively. Results: There were 20 males and 12 females patients with a median age of 69 years (ranging 36-82 years). The most prevalent clinical manifestation was multiple lymph nodes enlargement in head and neck (22/32, 68.8%), followed by inguinal (12/32, 37.5%), axillary (11/32, 34.4%), mediastinum (5/32, 15.6%) and retroperitoneal lymph nodes (4/32, 12.5%). Most of the patients were in Ann Arbor stage Ⅰ/Ⅱ (21 cases). The morphologic features included diffuse (24/32, 75.0%), nodular (5/32, 15.6%), interfollicular (2/32,6.3%) and perifollicular (1/32,3.1%) types. The tumor cells showed monocyte-like, centrocyte-like, small lymphocyte-like and plasma cell-like differentiation. Immunophenotyping revealed diffuse expression of CD20 in all tumor cells, whereas CD43 (11/32, 34.4%), bcl-2 (20/32, 62.5%), MNDA (13/32, 40.6%) and CD5 (2/32, 6.3%) were partially expressed. Ki-67 proliferation index varied from 10% to 40%. BRAF V600E mutation was found in two cases (2/32, 6.3%), but MYD88 L265P mutation was not detected. Eighteen patients survived and three died at the end of follow-up period which ranged 6 to 110 months. Conclusions: The morphologic features of NMZL varies across individuals, it should be differentiated from various B-cell lymphomas; however immunological biomarkers with high specificity for NMZL are still lacking. No MYD88 L265P mutation is found in NMZL. Some cases may harbor BRAF V600E mutation and yet the prevalence remains indeterminate; further researches are warranted.


Forming Giant-sized Polymersomes Using Gel-assisted Rehydration.
Polymer vesicles, or polymersomes, are being widely explored as synthetic analogs of lipid vesicles based on their stability, robustness, barrier properties, chemical versatility and tunable physical characteristics. Typical methods used to prepare giant-sized (> 4 µm) vesicles, however, are both time and labor intensive, yielding low numbers of intact polymersomes. Here, we present for the first time the use of gel-assisted rehydration for the rapid and high-yielding formation of giant (>4 µm) polymer vesicles (polymersomes). Using this method, polymersomes can be formed from a wide array of rehydration solutions including several different physiologically-compatible buffers and full cell culture media, making them readily useful for biomimicry studies. This technique is also capable of reliably producing polymersomes from different polymer compositions with far better yields and much less difficulty than traditional methods. Polymersome size is readily tunable by altering temperature during rehydration or adding membrane fluidizers to the polymer membrane, generating giant-sized polymersomes (>100 µm).


The microtubule plus-end tracking proteins SPR1 and EB1b interact to maintain polar cell elongation and directional organ growth in Arabidopsis.
The microtubule plus-end tracking proteins (+TIPs) END BINDING1b (EB1b) and SPIRAL1 (SPR1) are required for normal cell expansion and organ growth. EB proteins are viewed as central regulators of +TIPs and cell polarity in animals; SPR1 homologs are specific to plants. To explore if EB1b and SPR1 fundamentally function together, we combined genetic, biochemical, and cell imaging approaches in Arabidopsis thaliana. We found that eb1b-2 spr1-6 double mutant roots exhibit substantially more severe polar expansion defects than either single mutant, undergoing right-looping growth and severe axial twisting instead of waving on tilted hard-agar surfaces. Protein interaction assays revealed that EB1b and SPR1 bind each other and tubulin heterodimers, which is suggestive of a microtubule loading mechanism. EB1b and SPR1 show antagonistic association with microtubules in vitro. Surprisingly, our combined analyses revealed that SPR1 can load onto microtubules and function independently of EB1 proteins, setting SPR1 apart from most studied +TIPs in animals and fungi. Moreover, we found that the severity of defects in microtubule dynamics in spr1 eb1b mutant hypocotyl cells correlated well with the severity of growth defects. These data indicate that SPR1 and EB1b have complex interactions as they load onto microtubule plus ends and direct polar cell expansion and organ growth in response to directional cues.


Blood pressure reduction and cardiovascular prevention: an update including the 2003-2004 secondary prevention trials.
In a meta-analysis published in June 2003, we reported that new and old classes of antihypertensive drugs had similar long-term efficacy and safety. Furthermore, we observed that in clinical trials in hypertensive or high-risk patients gradients in systolic blood pressure (SBP) accounted for most differences in outcome. To test whether our previous conclusions would hold, we updated our quantitative overview with new information from clinical trials published before 2005. To compare new and old antihypertensive drugs, we computed pooled odds ratios from stratified 2 x 2 contingency tables. In a meta-regression analysis, we correlated these odds ratios with corresponding between-group differences in SBP. We then contrasted observed odds ratios with those predicted from gradients in SBP. The main finding of our overview was that reduction in SBP largely explained cardiovascular outcomes in the recently published actively controlled trials in hypertensive patients and in placebo-controlled secondary prevention trials. The published results suggested that dihydropyridine calcium-channel blockers might offer a selective benefit in the prevention of stroke and inhibitors of the renin-angiotensin system in the prevention of heart failure. For prevention of myocardial infarction, the published results were more equivocal, because of the benefit of amlodipine over placebo or valsartan in 2 trials, whereas other placebo-controlled trials of calcium-channel blockers or angiotensin converting enzyme inhibitors did not substantiate the expected benefit with regard to cardiac outcomes. In conclusion, the hypothesis that new antihypertensive drugs might influence cardiovascular prognosis over and beyond their antihypertensive effect remains unproven. Our overview emphasizes the need of tight blood pressure control, but does not allow determining to what extent blood pressure must be lowered for optimal cardiovascular prevention.


Two-dimensional crystallization: self-assembly, pseudopolymorphism, and symmetry-independent molecules.
The self-assembly of a series of 1,3-disubstituted benzenes has been scrutinized by scanning tunneling microscopy (STM) and computational modeling. Small changes in the functional groups (e.g., ester, thioester, ketone) resulted in dramatic changes in packing patterns. Remarkably, several of the molecules gave rise to monolayers with more than one molecule in the asymmetric unit and displayed multiple packing patterns. This constitutes the most complex behavior observed to date in this type of monolayer and illuminates several issues of importance in three-dimensional crystallization. Intermolecular interactions associated with the observation of multiple molecules in the asymmetric unit and stabilization of pseudopolymorphs were identified. The geometry and electrostatic properties of the isolated molecule and monolayer density were found to be critical in determining which packing motif was adopted.


[Schoenlein-Henoch syndrome in adults--current aspects].
Schoenlein-Henoch purpura is characterized clinically by palpable purpura, mainly on the legs, with varying degrees of gastrointestinal, articular and renal involvement. Renal involvement is often more severe in the adult than in children and it often determines the outcome of the disease. Schoenlein-Henoch purpura is also characterized by an IgA-vasculitis, which may be triggered by several non-specific antigenic factors. Its pathogenesis is still unclear, but a dysfunction of the IgA immune system has been demonstrated. We discuss the anatomo-clinical, therapeutic and etiopathogenic aspects of this syndrome according to today's knowledge.


Pharmacokinetics of the cephalosporin SM-1652 in mice, rats, rabbits, dogs, and rhesus monkeys.
The pharmacokinetics of SM-1652 were studied in mice, rats, rabbits, dogs, and rhesus monkeys. The plasma half-lives of SM-1652, administered intravenously at a dose of 20 mg/kg, were 11.0 min in mice, 26.0 min in rats, 65.8 min in rabbits, 72.6 min in dogs, and 150.9 min in monkeys. The 24-h urinary excretion of SM-1652 was 30 to 35% of the dose in mice and rats, 70 to 75% in rabbits and dogs, and 45% in monkeys. Biliary excretion of the antibiotic over a 24-h period was 60 and 19% in rats and rabbits, respectively; it was 19% in dogs over a 9-h period after SM-1652 administration. Approximately 95% of the intravenous dose of SM-1652 was recovered as the unchanged form in the urine and bile of rats and rabbits. The binding of SM-1652 to serum protein was 44.0% in mice, 46.0% in rats, 90.4% in rabbits, 93.2% in monkeys, 30.0% in dogs, and 96.3% in humans.


Non-intubated thoracoscopic surgery for decortication of empyema under thoracic epidural anesthesia: a case report.
General anesthesia is the main strategy for almost all thoracic surgeries. However, a growing body of literature has reported successful cases of non-intubated thoracic surgery with regional anesthesia. This alternative strategy not only prevents complications related to general anesthesia, such as lung injury, incomplete re-expansion and intubation related problems, but also accords with trends of shorter hospital stay and lower overall costs. We experienced a successful case of non-intubated thoracoscopic decortication for a 68-year-old man who was diagnosed as empyema while the patient kept spontaneously breathing with moderate sedation under thoracic epidural anesthesia. The patient showed a fast recovery without concerns of general anesthesia related complications and effective postoperative analgesia through thoracic epidural patient-controlled analgesia device. This is the first report of non-intubated thoracoscopic surgery under thoracic epidural anesthesia in Korea, and we expect that various well designed prospective studies will warrant the improvement of outcomes in non-intubated thoracoscopic surgery.


Office management of minor burns.
About 2 million people are burned in the United States each year. About 80% of these are treated as outpatients. Flame burns are the most common type of burn injury in adults, and scald burns are the primary type in children. Primary care providers must be familiar with burn assessment so burn injuries can be triaged appropriately to a regional burn center, an acute care (facility, or office management. Assessment includes extent and depth of burns, location of burns, patient reliability, and the home situation. Office management involves emergency care, debridement and dressings, topical antimicrobials, and pain control. Patient education for care in the home environment is essential for optimal healing.


Wrist Arthrotomy Saline Load Test.
Failure to recognize a potential wrist arthrotomy may lead to missed septic arthritis and devastating sequelae. The saline load test is routinely used to recognize traumatic arthrotomies of other joints; however, there are limited data optimizing this test for the wrist. The purpose of this study was to investigate and perform saline load testing to identify traumatic arthrotomies of the wrist. This was a cadaveric study of 15 wrists. Traumatic arthrotomies were created using a blunt trocar through the 3-4 portal. A 3-mL syringe with 0.1 mL markings was used to inject methylene blue dyed saline into the wrist through the 1-2 portal. Once extravasation was visible from the atherectomized site, the volume was recorded. The mean (range) volume injected to identify the arthrotomy of all wrists was 1.22 mL (range, 0.1-3.1 mL). Multivariate regression demonstrated that cadaver age, laterality, and extension range of motion were not significantly associated with the injected saline volume at extravasation (P > .05, each). Greater joint range of motion was independently associated with higher saline volume load for extravasation (odds ratio: 1.049; 95% confidence interval: 1.024-1.075; P = .003). We found that 2.68 and 3.02 mL of methylene blue dyed saline offered 95% and 99% sensitivity, respectively, for diagnosing traumatic wrist arthrotomy. The maximum volume of saline needed to recognize an arthrotomy was 3.1 mL. We recommend this be the minimum volume used to evaluate a traumatic wrist arthrotomy.


Serum biomarkers of oxidative stress in dogs with idiopathic inflammatory bowel disease.
The objective of this work was to study and compare a panel of various serum biomarkers evaluating both the antioxidant response and oxidative damage in dogs with idiopathic inflammatory bowel disease (IBD). Eighteen dogs with IBD and 20 healthy dogs were enrolled in the study. Trolox equivalent antioxidant capacity (TEAC), cupric reducing antioxidant capacity (CUPRAC), ferric reducing ability of the plasma (FRAP), total thiol concentrations, and paraoxonase 1 (PON1) activity were evaluated in serum to determine antioxidant response. To evaluate oxidative status, ferrous oxidation-xylenol orange (FOX), thiobarbituric acid reactive substances (TBARS) and reactive oxygen species production (ROS) concentrations in serum were determined. Mean concentrations of all antioxidant biomarkers analyzed, with exception of FRAP, were significantly lower (P < 0.0001) in the sera of dogs with IBD than in healthy dogs. The oxidant markers studied were significantly higher (P < 0.0001) in sera of dogs with IBD than in healthy dogs. These findings support the hypothesis that oxidative stress could play an important role in the pathogenesis of canine IBD.


Length of Hospital Stay of COVID-19 Patients managed at the Lagos State Isolation Centres during the First Wave of the Pandemic.
Lagos State has the highest number of COVID-19 cases in Nigeria. We assessed the factors predicting the length of hospital stay of COVID-19 patients admitted in 15 isolation centres across the state. We reviewed the electronic medical records of all COVID-19 patients admitted and discharged between February 27, 2020, and September 30, 2020. Logistic and linear regressions were used to assess factors predicting the length of hospital stay. A total of 3153 records were reviewed, of which 2623 (83.2%) met the inclusion criteria. The mean age of patients admitted was 40.5 (Sd 14.8) years. The age range was four days-97 years. A total of 1258 (48.0%) were symptomatic, while 2056 (78.4%) and 567 (21.6%) presented with mild and severe disease, respectively. Cough (22.0%), fever (17.3%) and breathlessness (12.3%) were the most common symptoms at presentation. Generally, the median length of hospital stay was 11 (IQR 9, 14) days. A total of 1609 (61.3%) had a prolonged length of hospital stay. The odds for prolonged hospital stay was higher among elderly patients (AOR 12.1 95%CI 7.6-19.4, p<0.001), male (AOR 1.2 95%CI 1.0-1.4, p=0.031) and patients with severe disease (AOR 1.3 95% CI 1.0-1.7, p=0.042). Age, hypertension and shortness of breath made the most significant contribution to predicting the length of hospital stay (P<0.05). Age, gender, hypertension and breathlessness predicted the length of hospital stay. Proactive measures should be instituted in managing COVID-19 patients.


Glucopyranosylidene-spiro-imidazolinones, a New Ring System: Synthesis and Evaluation as Glycogen Phosphorylase Inhibitors by Enzyme Kinetics and X-ray Crystallography.
Epimeric series of aryl-substituted glucopyranosylidene-spiro-imidazolinones, an unprecedented new ring system, were synthesized from the corresponding Schiff bases of O-perbenzoylated (gluculopyranosylamine)onamides by intramolecular ring closure of the aldimine moieties with the carboxamide group elicited by N-bromosuccinimide in pyridine. Test compounds were obtained by Zemplén O-debenzoylation. Stereochemistry and ring tautomers of the new compounds were investigated by NMR, time-dependent density functional theory (TDDFT)-electronic circular dichroism, and DFT-NMR methods. Kinetic studies with rabbit muscle and human liver glycogen phosphorylases showed that the (R)-imidazolinones were 14-216 times more potent than the (S) epimers. The 2-naphthyl-substituted (R)-imidazolinone was the best inhibitor of the human enzyme (Ki 1.7 μM) and also acted on HepG2 cells (IC50 177 μM). X-ray crystallography revealed that only the (R) epimers bound in the crystal. Their inhibitory efficacy is based on the hydrogen-bonding interactions of the carbonyl oxygen and the NH of the imidazolinone ring.


Psychological distress 35 years after the Chornobyl accident in the Lithuanian clean-up workers.
The adverse effects on the health of the Chornobyl nuclear power plant accident clean-up workers have been reported previously. However, there is a lack of studies on the mental health of Chornobyl clean-up workers. The current study explored psychological distress in a sample of Lithuanian clean-up workers 35 years after the accident. In total, 107 Lithuanian Chornobyl clean-up workers (Mage = 62.5) and 107 controls were included in the study. The Hospital Anxiety and Depression Scale (HAD) was used for the assessment of anxiety and depression. The depression symptoms were significantly higher in the clean-up workers compared to the control group. The prevalence of severe depression symptoms was 23.4% and 4.7% in the Chornobyl clean-up workers and control groups, respectively. The risk for severe depression was associated with Chornobyl clean-up work (adjusted OR = 5.9). No differences in the anxiety symptoms were found between clean-up workers and controls. The study revealed the deteriorated mental health of the Lithuanian Chornobyl clean-up workers 35 years after the disaster - in particular, high levels of depression. Psychosocial support programmes for clean-up workers should be provided to mitigate the adverse effects of the disaster.


In vitro biomechanical properties of sole tissues: Comparison between healthy and ulcerated bovine claws.
Sole ulcers are reportedly one of the most prevalent diseases associated with lameness in dairy cattle, significantly affecting animal welfare and farm profitability. The degree to which sole soft tissues, healthy or ulcerated, are able to maintain their structure and function when subjected to compressive forces remains unknown. Therefore, the aims of the present study were to assess sole tissue biomechanics in healthy and ulcerated claws and to describe correlated histology. Cylindrical samples were harvested from zones 4 and 6, as described by the international foot map, from hind lateral healthy (n = 12) and ulcerated bovine claws (n = 8; animals n = 12). Tissue biomechanics and morphology were evaluated via compressive tests and hematoxylin-eosin-phloxine-saffron staining, respectively. A 2-sample t-test was used to compare zones' mechanical properties between healthy and ulcerated tissues, and the Cochran-Mantel-Haenszel test was used to measure the effect of claw zone on histology. The fibril modulus (Ef) and permeability (k) respectively increased and decreased in ulcerated claws (Ef = 0.201 ± 0.104 MPa; k = 0.128 ± 0.069 mm2/MPa·s) compared with healthy claws (Ef = 0.105 ± 0.050 MPa; k = 0.452 ± 0.365 mm2/MPa·s) only for zone 6. Histology scores equal to or greater than 3 were associated with macroscopic presence of ulceration. A higher proportion of adipose tissue (30% or more) was associated with zone 6 compared with zone 4, but no difference was seen between healthy and ulcerated claws. Ulcerated claws had a higher prevalence of exostoses compared with healthy ones (33% vs. 8%). Sole soft tissues showed, as hypothesized, a viscoelastic behavior using unconfined compression testing, which, however, may not reflect in vivo loading conditions. Clinical and histological signs of sole ulceration were not associated with decreased strength of the supportive apparatus of the distal phalanx in zone 4 in this study.


[A complicated case of Nocardia brain abscess for differential diagnosis].
Nocardia brain abscess is rare and has uncertain clinical features. Radiological differential diagnosis based on the metabolic feature of Nocardia is discussed. A 73-year-old man presented with a history of otitis media and was treated with antibiotics for 2 weeks. Computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated an irregular ring-enhancement mass in the left cerebellar hemisphere. This lesion presented as a homogeneous high-intensity area in diffusion-weighted MRI. We also found decreased N-acetyl-aspartate (NAA) peak and increased choline and lipid peaks in proton MR spectroscopy (1H-MRS). We performed an aspiration. Nocardia asiatica in the mass lesion was found by genetic analysis. The patient was treated with a sulfamethoxazole/trimethoprim (ST) mixture and minocycline (MINO) intravenously for 6 months. There has been no recurrence for 2 years. To our knowledge, this case is the first case of Nocardia asiatica brain abscess in Japan. We considered these MRS findings to be compatible with Nocardia brain abscess as mainly observed in aerobic metabolism. But we also detected a lactate peak in the abscess. Further research is required.


A3 adenosine receptor signaling contributes to airway inflammation and mucus production in adenosine deaminase-deficient mice.
Adenosine signaling has been implicated in chronic lung diseases such as asthma and chronic obstructive pulmonary disease; however, the specific roles of the various adenosine receptors in processes central to these disorders are not well understood. In this study, we have investigated the role(s) of the A(3) adenosine receptor in adenosine-dependent pulmonary inflammation observed in adenosine deaminase (ADA)-deficient mice. The A(3) receptor (A(3)R) was found to be expressed in eosinophils and mucus-producing cells in the airways of ADA-deficient mice. Treatment of ADA-deficient mice with MRS 1523, a selective A(3)R antagonist, prevented airway eosinophilia and mucus production. Similar findings were seen in the lungs of ADA/A(3) double knockout mice. Although eosinophils were decreased in the airways of ADA-deficient mice following antagonism or removal of the A(3)R, elevations in circulating and lung interstitial eosinophils persisted, suggesting signaling through the A(3)R is needed for the migration of eosinophils into the airways. These findings identify an important role for the A(3)R in regulating lung eosinophilia and mucus production in an environment of elevated adenosine.


Decellularized extracellular matrix: a step towards the next generation source for bioink manufacturing.
In tissue engineering, the need for hierarchical assembly of three-dimensional (3D) tissues has become increasingly important, considering that new technology is essential for advanced tissue fabrication. 3D cell printing has emerged as a powerful technology to recapitulate the microenvironment of native tissue, allowing for the precise deposition of multiple cells onto the pre-defined position. Parallel to these technological advances, the search for an appropriate bioink that can provide a suitable microenvironment supporting cellular activities has been in the spotlight. In this respect, the decellularized extracellular matrix (dECM) becomes a popular candidate as a well-qualified source of bioink because of its capability to inherit the intrinsic cues from a native ECM. Yet, few studies have been reported and its potential has been partially understood in the field of 3D cell printing. In this review, our focus is on a dECM as a prospective bioink to facilitate 3D cell printing-based tissue engineering. We begin this review with a brief description of the important role of the ECM. Next, the representative methods of decellularization and conventional applications of a dECM are introduced, followed by the recent achievements in dECM bioinks and their future directions.


Cross talk between progesterone receptors and retinoic acid receptors in regulation of cytokeratin 5-positive breast cancer cells.
Half of estrogen receptor-positive breast cancers contain a subpopulation of cytokeratin 5 (CK5)-expressing cells that are therapy resistant and exhibit increased cancer stem cell (CSC) properties. We and others have demonstrated that progesterone (P4) increases CK5+ breast cancer cells. We previously discovered that retinoids block P4 induction of CK5+ cells. Here we investigated the mechanisms by which progesterone receptors (PR) and retinoic acid receptors (RAR) regulate CK5 expression and breast CSC activity. After P4 treatment, sorted CK5+ compared to CK5- cells were more tumorigenic in vivo. In vitro, P4-treated breast cancer cells formed larger mammospheres and silencing of CK5 using small hairpin RNA abolished this P4-dependent increase in mammosphere size. Retinoic acid (RA) treatment blocked the P4 increase in CK5+ cells and prevented the P4 increase in mammosphere size. Dual small interfering RNA (siRNA) silencing of RARα and RARγ reversed RA blockade of P4-induced CK5. Using promoter deletion analysis, we identified a region 1.1 kb upstream of the CK5 transcriptional start site that is necessary for P4 activation and contains a putative progesterone response element (PRE). We confirmed by chromatin immunoprecipitation that P4 recruits PR to the CK5 promoter near the -1.1 kb essential PRE, and also to a proximal region near -130 bp that contains PRE half-sites and a RA response element (RARE). RA induced loss of PR binding only at the proximal site. Interestingly, RARα was recruited to the -1.1 kb PRE and the -130 bp PRE/RARE regions with P4, but not RA alone or RA plus P4. Treatment of breast cancer xenografts in vivo with the retinoid fenretinide reduced the accumulation of CK5+ cells during estrogen depletion. This reduction, together with the inhibition of CK5+ cell expansion through RAR/PR cross talk, may explain the efficacy of retinoids in prevention of some breast cancer recurrences.


[Comparison of hysteroscopy and curettage in incomplete pregnancy with cesarean scar pregnancy].
Objectives: To evaluate the value of hysteroscopy in the diagnosis and treatment of cesarean scar pregnancy (CSP) incomplete abortion. Methods: A total of 42 patients with incomplete cesarean circumcision from January 2014 to March 2017 were retrospectively analyzed.Twenty-one patients underwent bilateral uterine artery embolization.Twenty patients underwent hysteroscopy Electrocardiose resection of pregnancy tissue and coagulation hemostasis, the control group of 22 patients underwent conventional uterine artery embolization surgery. Results: One patient in the study group was changed to laparoscopic surgery.In the control group, 2 patients were changed to laparoscopic surgery and 2 patients underwent laparotomy.The duration of hospitalization, the amount of postoperative bleeding and the duration of bleeding were significantly lower in the study group than in the control group.The recovery time of HCG in the study group was significantly shorter than that in the control group. Conclusion: Compared with traditional uterine artery embolization, hysteroscopic resection of cesarean section scar residual tissue less bleeding, higher success rate of surgery, less trauma, faster recovery, treatment Cesarean section scar scar pregnancy abortion is the ideal method.


Management of Diabetic Macular Edema.
Diabetic macular edema is a common condition frequently encountered by ophthalmologists. In this piece we briefly review its definition, pathogenesis, clinical aspects, imaging, and treatment.


[A case of tuberculous peritonitis in a hemodialysis patient revealed by severe diarrhea and stomachache].
A 53-year-old woman was admitted to our hospital due to abdominal pain, diarrhea, and shunt occlusion caused by dehydration. She had undergone hemodialysis due to diabetic nephropathy over a ten-year period. She was hospitalized again with fever and a persistent high serum CRP level. We started antibiotic administration using cefotiam hexetil hydrochloride because of ascites and peritoneum thickening observed by abdominal computed tomography. Although her symptoms, such as abdominal pain and diarrhea, improved after the administration of antibiotics, the ascites and the peritoneum thickening did not improve. On the fourth hospital day, we attempted ascites aspiration to investigate the etiology of the peritonitis. Cytological examination suggested tuberculous peritonitis because of predominant macrophage cell proliferation, a high level of ADA concentration, and a high level of CA125 of ascites. Although QuantiFERON-tuberculosis (QFT) and the Gaffky scale were negative, we started multidrug therapy (isoniazid + rifampicin + pyrazinamide + ethambutol) on the 20th hospital day. She was finally diagnosed as mycobacterium tuberculous peritonitis based on biopsy of the tissue of the ileum and the results of colonoscopy. Administration of antituberculosis chemotherapy improved abdominal fullness and ascites and the patient was discharged on the 97th hospital day. Moreover Kuno et al. reported that serum soluble interleukin-2 receptor(sIL-2R) and CA-125 levels can be used to monitor the response to anti-tuberculosis treatment. In this case, we use these markers to monitor the response to treatment. We experienced a case of tuberculous peritonitis undergoing hemodialysis. Tuberculosis should be suspected when patients undergoing dialysis have long-term fever of unknown etiology. There are many reports stating that the sensitivity and specificity of QuantiFERON-tuberculosis (QFT) and sputum culture are low in latent tuberculosis infection of dialysis patients. Accordingly it is necessary to diagnose mycobacterium tuberculous peritonitis comprehensively by the clinical symptoms and image analysis.


The effect of the use of different selective media on the ability to recover salmonellae from seagull faeces.
Solid media were compared for their ability to recover salmonellae from seagull faecal material after pre-enrichment in buffered peptone water and enrichment in Rappaport's broth. Of the 847 specimens examined 96 were found to be positive for salmonellae. Use of Brilliant Green agar containing sulphamandelate supplement resulted in the detection of salmonellae from each of the 96 samples found to be positive and was the most efficient medium tested. Brilliant Green agar lacking the supplement was the least effective medium, salmonellae being isolated from only 80 samples using this medium. All of the media tested were shown to support the growth of a wide range of salmonella serotypes, although Salmonella typhi and S. dublin did not form colonies on those media which contained Brilliant Green. Hynes' modification of deoxycholate citrate agar was shown to be considerably less inhibitory to salmonellae after ageing for four days. Ageing of other media had no significant affect on their ability to support the growth of salmonellae.


Linkage analysis of candidate obesity genes among the Mexican-American population of Starr County, Texas.
Recent advances in the molecular basis of body fat regulation have identified several genes in which genetic variation may influence obesity and related measures in human populations. Genes that have been shown to have a regulatory function in the control of body fat utilization, eating behavior, and/or metabolic rate in rodent models of obesity include leptin (LEP), leptin receptor (LEPR), neuropeptide Y (NPY), NPY Y1 receptor (NPYY1), glucagon-like peptide-1 (GLP-1), GLP-1 receptor (GLP1R), and uncoupling protein 1 (UCP1). We have typed microsatellite markers located within or near these seven candidate obesity genes in 302 non-diabetic individuals from 59 Mexican-American families from Starr County, Texas. Sib pair linkage analysis was used to examine linkage between these genes and obesity status (obese siblings only; n = 170 pairs) and several obesity-related quantitative variables (all siblings; n = 545 total sibling pairs). Significant linkage (P = 0.042) was found between obesity and NPY within the obese sibling pairs. No other candidate gene was linked to obesity status in this subsample. Consistent with the obese sib pair linkage results, NPY showed evidence of linkage to body weight (P = 0.020), abdominal circumference (P = 0.031), hip circumference (P = 0.012), diastolic blood pressure (P = 0.005), and a composite measure of body mass and size (P = 0.048) in the entire sibling sample. Other significant linkages observed were between LEP and waist/hip ratio (P = 0.010), total cholesterol (P = 0.030), and HDL cholesterol (P = 0.026) and between LEPR and fasting blood glucose (P = 0.018) and diastolic blood pressure (P = 0.003). These results support further investigation of NPY, LEP, and LEPR to identify genetic variation that may influence obesity status, glucose and lipid metabolism, and blood pressure in Mexican Americans.


Cyclic AMP as a negative regulator of hormonally induced lactogenesis in mouse mammary gland organ culture.
In organ cultures of mammary glands from mice in midpregnancy, addition of both insulin and prolactin induces a marked accumulation of alpha-lactalbumin, whereas the augmentation of casein synthesis requires the presence of insulin, prolactin, and cortisol. Addition of 0.5 mM dibutyryl cyclic AMP resulted in complete inhibition of alpha-lactalbumin accumulation and partial inhibition of casein synthesis. Furthermore, either cholera toxin at 0.1-1.0 microgram/ml (a stimulator of adenylate cyclase) or 3-isobutyl-1-methylxanthine (an inhibitor of phosphodiesterase) in combination with 2 mM cyclic AMP, produced a similar pattern of inhibition of alpha-lactalbumin and casein synthesis in cultured tissue. During culture of mammary explants in medium containing no hormone, or insulin alone, or insulin, prolactin, and cortisol, the tissue content of cyclic AMP decreased rapidly, reaching half the initial level in 24-48 hr. These results indicate that cyclic AMP plays "negative" regulatory function in hormonal induction of milk protein synthesis during the development of the mammary gland.


A preliminary open trial on interferon stimulator (SNMC) derived from Glycyrrhiza glabra in the treatment of subacute hepatic failure.
The efficacy of the interferon stimulator named Stronger Neo Minophagen-C (SNMC) derived form the plant G. glabra was studied at a dose of 40 or 100 ml daily for 30 days followed by thrice weekly intravenously for 8 wk in 18 patients of subacute hepatic failure due to viral hepatitis. The survival rate amongst these patients was 72.2 per cent, as compared to the earlier reported rate of 31.1 per cent in 98 patients who received supportive therapy (P < 0.01). Death in four of the five patients was due to associated infections leading to hepatorenal failure and terminal coma. Further studies are necessary to standardize the dose and duration of therapy with SNMC in subacute hepatic failure.


Optimum design of double-layer target for proton acceleration by ultrahigh intense femtosecond lasers considering relativistic rising edge.
Advances in laser technology have led to ever-increasing laser intensities. As a result, in addition to the amplified spontaneous emission and pedestal, it has become necessary to accurately treat the relativistic rising edge component. This component has not needed much consideration in the past because of its not relativistic intensity. In the previous study, a thin contamination layer was blown away from the target by the rear sheath field due to the relativistic rising edge component, and the target bulk was accelerated by the sheath field due to the main pulse. These indicated that the proton acceleration is not efficient in the target normal sheath acceleration by the ultrahigh intense femtosecond laser if the proton-containing layer is as thin as the contamination layer. Here we employ a double-layer target, making the second (rear) layer thick enough not to be blown away by the rising edge, so that the second layer is accelerated by the main pulse. The first layer is composed of heavy ions to reduce the total thickness of the target for efficient proton acceleration. We investigate an optimal design of a double-layer target for proton acceleration by the ultrahigh intense femtosecond laser considering the relativistic rising edge using two-dimensional particle-in-cell simulations. We also discuss how to optimize the design of such a double-layer target and find that it can be designed with two conditions: the first layer is not penetrated by hole boring, and the second layer is not blown away by the rising edge.


Characterization of Trichome-Expressed BAHD Acyltransferases in Petunia axillaris Reveals Distinct Acylsugar Assembly Mechanisms within the Solanaceae.
Acylsugars are synthesized in the glandular trichomes of the Solanaceae family and are implicated in protection against abiotic and biotic stress. Acylsugars are composed of either sucrose or glucose esterified with varying numbers of acyl chains of differing length. In tomato (Solanum lycopersicum), acylsugar assembly requires four acylsugar acyltransferases (ASATs) of the BAHD superfamily. Tomato ASATs catalyze the sequential esterification of acyl-coenzyme A thioesters to the R4, R3, R3', and R2 positions of sucrose, yielding a tetra-acylsucrose. Petunia spp. synthesize acylsugars that are structurally distinct from those of tomato. To explore the mechanisms underlying this chemical diversity, a Petuniaaxillaris transcriptome was mined for trichome preferentially expressed BAHDs. A combination of phylogenetic analyses, gene silencing, and biochemical analyses coupled with structural elucidation of metabolites revealed that acylsugar assembly is not conserved between tomato and petunia. In P. axillaris, tetra-acylsucrose assembly occurs through the action of four ASATs, which catalyze sequential addition of acyl groups to the R2, R4, R3, and R6 positions. Notably, in P. axillaris, PaxASAT1 and PaxASAT4 catalyze the acylation of the R2 and R6 positions of sucrose, respectively, and no clear orthologs exist in tomato. Similarly, petunia acylsugars lack an acyl group at the R3' position, and congruently, an ortholog of SlASAT3, which catalyzes acylation at the R3' position in tomato, is absent in P. axillaris Furthermore, where putative orthologous relationships of ASATs are predicted between tomato and petunia, these are not supported by biochemical assays. Overall, these data demonstrate the considerable evolutionary plasticity of acylsugar biosynthesis.


Effect of a broad-host range plasmid on growth dynamics of Escherichia coli and Pseudomonas putida.
Host-plasmid interactions were studied for the broad-host range plasmid, pTJS26, a derivative of RK2. To isolate host and plasmid contributions to the growth dynamics and plasmid stability, separate experiments were performed with host and recombinant cells for two different gram-negative hosts, Pseudomonas putida and Escherichia coli, at two different temperatures, 30 and 37 degrees C. At the lower temperature (30 degrees C) the growth kinetics were not affected by the plasmid, but plasmid instability was observed. At the higher temperature (37 degrees C) growth rates and yields were lower than that for the hosts, but the plasmid was stable. This behavior can be explained by a combination of two phenomena. First, the copy number control mechanism may be temperature sensitive and, second, plasmid segregation may be inefficient. For both E. coli and P. putida the growth dynamics of the recombinant system was dictated by the presence of the plasmid.


Effect of bipolar disorder on left frontal cortical responses to goals differing in valence and task difficulty.
The behavioral activation system (BAS) dysregulation theory of bipolar disorder predicts that bipolar individuals will show an excessive increase in approach motivation during reward striving. Building on past research showing that the left frontal cortical region is involved in approach motivation, we predicted that individuals with bipolar disorder would evidence increased relative left frontal cortical activity in response to goal striving, particularly in response to positive challenges. Right-handed individuals (age 18-24) with a bipolar spectrum diagnosis (n = 41) and individuals with no major affective psychopathology (n = 53) were presented with cues indicating that, on a given trial, an easy, medium, or hard anagram (scrambled word) would be presented in 7 seconds and that they would receive money or avoid losing money for the correct solution (10 anagrams of each of the 6 types). During this preparation period, electroencephalogram (EEG) alpha power was measured and hemispheric asymmetry indexes were computed. Compared with the nonbipolar individuals, individuals with bipolar disorder showed greater relative left frontal cortical activation in preparation for the hard/win trials. Whereas nonbipolar individuals showed a decrease in left frontal cortical activation from medium to hard win trials, bipolar individuals did not. In addition, among bipolar individuals, current self-reported activation related to greater left frontal activation to the hard/win trials. These results provide support for an integrative biopsychosocial model of bipolar disorder, BAS dysregulation theory, and suggest that relative left frontal activity, which may be involved in mania, is triggered by challenging and potentially rewarding events.


Close resemblance between chemokine receptor expression profiles of lymphoproliferative disease of granular lymphocytes and their normal counterparts in association with elevated serum concentrations of IP-10 and MIG.
T-cell large granular lymphocyte (T-LGL) leukemia and chronic natural killer (NK) cell lymphocytosis (CNKL) are major subtypes of lymphoproliferative disease of granular lymphocytes (LDGL). To clarify the mechanism of LGL proliferation and the relationship with the chemokine system in LDGL, we enrolled 22 T-LGL leukemia patients and 8 CNKL cases, analyzed the expression profiles of chemokine receptors, and measured the serum concentrations of the corresponding chemokines. There were no significant differences in chemokine receptor expression profiles between T-LGL leukemia patients and healthy donors. An association of CCR5 and CXCR3 expression levels on LGLs was recognized in T-LGL leukemia patients (r = 0.84; P < .001). Among the chemokines, serum IP-10 and MIG levels were significantly higher in LDGL patients than in healthy donors (P < .05, and P < .001, respectively), and MIG expression was associated with the number of circulating LGLs (r = 0.73; P < .01). The chemokine receptor phenotypes of LDGL cells are essentially similar to those of normal T-cells and NK cells. The roles of IP-10 and MIG in the pathophysiology of LDGL need further examination.


Synonymy and problematic species of Eiconaxius Spence Bate, 1888, with descriptions of new species (Crustacea: Decapoda: Axiidea: Axiidae).
The genus Eiconaxius Spence Bate, 1888, is rediagnosed. Eiconaxiopsididae Sakai, 2011 and its type genus, Eiconaxiopsis Sakai, 2011 are shown to be based largely on an error-the dactylus of pereopod 3 of the type species, Eiconaxiopsis heinrichi Sakai, 2011 is not as was originally illustrated but similar to all other species of Eiconaxius. The synonymies of Eiconaxiopsis with Eiconaxius and Eiconaxiopsididae with Axiidae are confirmed. Eiconaxius faxoni Sakai, 2011 is made an objective junior synonym of Eiconaxius albatrossae Kensley, 1996 (both share the same types). Eiconaxius malaku sp. nov. is erected to replace Eiconaxius indonesicus Sakai, 2011 (nomen nudum). Eiconaxius parvus Spence Bate, 1888 is redescribed based on numerous specimens from Fiji, and Wallis and Futuna. Eiconaxius vaubani sp. nov., which differs from all other species of the genus in the shape of the rostrum and proportions of pereopod 4, is described.


Knockdown of SLC39A4 Expression Inhibits the Proliferation and Motility of Gallbladder Cancer Cells and Tumor Formation in Nude Mice.
Gallbladder cancer (GBC) is a common malignancy of the biliary tract and is characterized by rapid progression and early metastasis. Elucidating the molecular mechanisms of GBC could help to develop better treatment strategies. Human GBC cell lines (GBC-SD and NOZ) were applied to determine the capacity of the proliferation and migration of cells using the MTT assay, colony formation, wound-healing assay as well as the Transwell™ assay. A nude xenograft was used to evaluate tumor growth in vivo. Using two types of GBC cell lines, we found that absence of solute carrier family (SLC) 39A4 (which encodes the zinc transporter ZRT/IRT-like protein [ZIP]4), could suppress the proliferation and migration of cells. Additionally, absence of ZIP4 could impair growth of xenografts in nude mice. While, over-expression of SLC39A4 could promote the GBC cell proliferation and migration, and inhibit apoptosis. We revealed that SLC39A4 might affect GBC progression by modulating the signaling pathways responsible for the survival, energy supply and metastasis of cells, and indicated that SLC39A4 could serve as a novel therapeutic target for GBC. SLC39A4 promoted the viability and motility of GBC cells, and tumor formation in nude mice. We demonstrated an oncogenic potential for SLC39A4.


Single-stage anterior autogenous bone grafting and instrumentation in the surgical management of spinal tuberculosis.
Results of single-stage anterior autogenous bone grafting and instrumentation for spinal tuberculosis were reported. To determine the efficacy of anterior instrumentation following radical debridement and autogenous bone grafting in patients with spinal tuberculosis over a 3-year period at a single institution. Patients with spinal tuberculosis have been not always successfully treated by radical debridement and bone grafting with or without supplementary posterior instrumentation and fusion, although most surgeons use posterior instrumentation to support anterior strut grafts. In this prospective study, the authors evaluated 39 patients (22 male and 17 female; average age, 48 years) with spinal tuberculosis, who underwent single-stage anterior radical debridement, autogenous bone grafting, and instrumentation. The average follow-up period was 39.9 months (range, 30-54 months). A solid fusion was achieved in all cases; there were 2 cases of draining fistula formation. Of all 28 patients with preoperative kyphosis, the deformity was corrected from an average of 13.5 degrees on admission to an average of 1.9 degrees after surgery. No significant loss of deformity correction was noted in these patients. There was no other recurrence of the tuberculous infection. The authors think that the single-stage anterior autogenous bone grafting and instrumentation are a safe and effective method in the surgical management of spinal tuberculosis.


Cytogenetic and epidemiological profiles of Down syndrome in a Moroccan population: a report of 852 cases.
Trisomy 21 or Down syndrome is the most common type of autosomal chromosome abnormality, with an incidence of one out of 700 live births. Down syndrome is associated with psychomotor delay, characteristic facial features, and sometimes, cardiac, digestive and ocular malformations. The aim of this study was to estimate the proportions of various cytogenetic types of trisomy 21, and to study the link between maternal age and trisomy 21 in the Moroccan population, in order to provide data on the cytogeneticity and epidemiology of Down syndrome in Morocco. A retrospective analysis was performed on the case records of 852 patients who were confirmed as Down syndrome by cytogenetic analysis at the Department of Medical Genetics, National Institute of Health, Morocco. Among the 852 cases of Down syndrome presenting over a period of 15 years, free trisomy 21 was present in 820 cases (96.24 percent). 27 patients had translocation and five cases were mosaics. The median maternal age of the Moroccan mothers at the birth of the affected child was 35.39 years. The identification of specific types of chromosomal abnormalities in Down syndrome children is important as it assists with patient management and family counselling.


Effects of Calcium Powder Mixtures and Binding Ingredients as Substitutes for Synthetic Phosphate on the Quality Properties of Ground Pork Products.
This study aimed to investigate the combined effect of using natural calcium mixtures and various binding ingredients as replacers for synthetic phosphate in ground pork products. We performed seven treatments: control (0.3% phosphate blend), treatment 1 (0.5% natural calcium mixtures [NCM, which comprised 0.2% oyster shell calcium and 0.3% egg shell calcium powder] and 0.25% egg white powder), treatment 2 (0.5% NCM and 0.25% whey protein concentrate), treatment 3 (0.5% NCM and 0.25% concentrated soybean protein), treatment 4 (0.5% NCM and 0.25% isolated soybean protein), treatment 5 (0.5% NCM and 0.25% carrageenan), and treatment 6 (0.5% NCM and 0.25% collagen powder). All the treatment mixtures had higher pH and lower cooking loss than the control, which was treated with phosphate. We found that NCM and binding ingredients had no negative effects on the moisture content, lightness, and yellowness of the cooked ground pork products. Treatments 3 and 4 showed significantly lower CIE a* values than the control. Treatments 2 and 6 improved the textural properties of the products. In conclusion, the combination of NCM with whey protein concentrate or collagen powder could be suitable for producing phosphate-free meat products.


Axial rotation of sliding actin filaments revealed by single-fluorophore imaging.
In the actomyosin motor, myosin slides along an actin filament that has a helical structure with a pitch of approximately 72 nm. Whether myosin precisely follows this helical track is an unanswered question bearing directly on the motor mechanism. Here, axial rotation of actin filaments sliding over myosin molecules fixed on a glass surface was visualized through fluorescence polarization imaging of individual tetramethylrhodamine fluorophores sparsely bound to the filaments. The filaments underwent one revolution per sliding distance of approximately 1 microm, which is much greater than the 72 nm pitch. Thus, myosin does not "walk" on the helical array of actin protomers; rather it "runs," skipping many protomers. Possible mechanisms involving sequential interaction of myosin with successive actin protomers are ruled out at least for the preparation described here in which the actin filaments ran rather slowly compared with other in vitro systems. The result also indicates that each "kick" of myosin is primarily along the axis of the actin filament. The successful, real-time observation of the changes in the orientation of a single fluorophore opens the possibility of detecting a conformational change(s) of a single protein molecule at the moment it functions.


Ribonuclease-sensitive ribosomal vaccine of Pseudomonas aeruginosa.
In mice, active protection against Pseudomonas aeruginosa could be induced with two fractions derived from a crude preparation of ribosomes from P. aeruginosa. The two fractions were obtained by gel filtration chromatography of the crude ribosomal preparation on Sepharose CL-2B. In fraction I, less than 1% of the ribonucleic acid (RNA) applied to the column was recovered. Fraction II contained RNA and protein in a ratio of 1.94. The presence of ribosomes in this fraction was confirmed by analysis on a sucrose density gradient. The protection by fraction I was not affected by treatment with ribonuclease; in contrast, incubation of fraction II with ribonuclease completely abolished active protection. Fraction I contained lipopolysaccharide (LPS) as was indicated by the presence of 2-keto-3-deoxyoctonic acid. No LPS was found in fraction II. The adjuvant dimethyl dioctadecyl ammonium bromide enhanced the protection by fraction II; however, immunity by a low dose of fraction I was abolished by dimethyl dioctadecyl ammonium bromide. Protection by fractions I and II appeared to be restricted to the homologous serotype of P. aeruginosa. These results indicate that RNA is required for protection by fraction II. Active protection by fraction I is likely due to LPS.


Effects of the multidrug resistance-1 gene on drug resistance in primary immune thrombocytopenia.
Primary immune thrombocytopenia (ITP) is an autoimmune disorder that is characterized by low platelet count. Glucocorticoids (GCs) resistance is a great challenge in the treatment of ITP. P-glycoprotein (P-gp) is a widely studied protein, which is associated with drug resistance. However, in ITP, the functional activity and immune regulation mechanism of P-gp remain uncertain. In this study, we evaluated the expression and functional activity of P-gp in different lymphocyte subsets, explored the correlation between P-gp function and GCs resistance and investigated the role of P-gp in ITP pathogenesis. Results indicated that the functional activity and mRNA level of P-gp were significantly higher in GCs-nonresponsive patients than in GCs-responsive patients with ITP. However, these differences in P-gp were only significant in CD8+ T cells. P-gp function was related to disease activity rather than GCs therapy. P-gp was involved in secreting granzyme B and perforin, maintaining autoreactive lymphocytes survival and enhancing autologous platelets lysis in ITP. In conclusion, over-functional P-gp might play an important role in the pathogenesis of ITP and induce GCs resistance in nonresponsive ITP patients. The blockage of P-gp could be a promising therapeutic approach for GCs-resistant patients with ITP.


The Impact of the Innovative Knowledge of Customers on Their Recommendation Intentions.
This article provides a systematic way to examine the impact of the innovative knowledge of customers on their recommendation intentions from firm design perspective and investigates the moderating effects of guidance methods and design materials provided combining different aspects of cognitive fit, media richness, and sticky information theories. We use the EQXIU platform, conduct two experiments, and find that there are significant differences between the novice customers and expert customers in their recommendation intentions. Experts are more prone to no-template materials, whereas novices are more inclined to use modules and templates. Therefore, to inspire innovation, firms should offer personalized opportunities based on customers' knowledge levels to enhance their experience. Firms should also design the innovative activities taking into consideration the knowledge levels of their customers. At last, limitations of this study and directions for further research are discussed.


Referred pain: characteristics, possible mechanisms, and clinical management.
Referred pain is a common but less understood symptom that originates from somatic tissues. A comprehensive recognition of referred pain is important for clinicians when dealing with it. The purpose of this study is to summarize the current understanding of referred pain, including its pathogenesis, characteristics, diagnosis, and treatment. Referred pain arises not only from pathologies primarily involving local tissue but also from lesions in distant structures. Central sensitization of convergent neurons and peripheral reflexes of dichotomizing afferent fibers are two theories proposed to explain the pathological mechanism of referred pain. Because syndromes related to referred pain of different origins overlap each other, it is challenging to define referred pain and identify its originating lesions. Although various approaches have been used in the diagnosis and treatment of referred pain, including conservative treatment, blockade, radiofrequency, and surgery, management of referred pain remains a clinical challenge. Unlike radicular pain and neuropathic pain, referred pain is a less studied area, despite being common in clinics. Referred pain can derive from various spinal structures, and blockage helps identify the primary pathology. Due to the heterogeneity of referred pain, treatment outcomes remain uncertain. Further studies are needed to improve our understanding of referred pain.


Wound prophylaxis in thoracic surgery: a new approach.
A prospective double blind, randomised study was performed in 100 patients undergoing major elective thoracic surgery to assess a new method of prophylaxis of wound infection using one preincisional intraparietal infiltration of cefuroxime sodium along the line of proposed incision as the sole protection against wound infection. A significant (p less than 0.01) reduction in the incidence of wound infection occurred in the antibiotic treated group (2%) compared with the control group (20%), who received by the same route the same volume of saline only. The groups were comparable with respect to age, sex, pathological condition, and operative variables. The use of additional antibiotics was significantly greater in the control group (p less than 0.01), largely owing to a much greater incidence of postoperative pulmonary infection in the control group (60%) than in the antibiotic treated group (40%). No morbidity was associated with this technique. The organisms found in oesophageal and bronchial operative luminal specimens did not correlate with postoperative wound or pulmonary infection or with organisms causing these infections. Reductions in wound and pulmonary infection rates equivalent to those produced by conventional multiple dose parenteral regimens were achieved by this technique.


Chitinase effects on immune cell response in neuromyelitis optica and multiple sclerosis.
Recent studies conducted in arthritis, asthma, and inflammatory bowel disease suggest that chitinases are important in inflammatory processes and tissue remodeling. To investigate the role of chitinases in multiple sclerosis (MS) and neuromyelitis optica (NMO). Levels of chitotriosidase, acid mammalian chitinase (AMCase), and chitinase 3-like-1 (CHI3L1) were measured using ELISA, in cerebrospinal fluid (CSF) and in serum from 24 patients with relapsing remitting (RR) MS, 24 patients with secondary progressive (SP) MS, 12 patients with NMO, 24 patients with other inflammatory neurological diseases (OIND), and 24 healthy controls (HCs). The number of anti-MOG cytokine-secreting cells was studied using ELISPOT. Eotaxins, MCP-1, RANTES, and IL-8 were assessed using ELISA. Cell transmigration was determined using an in vitro blood-brain barrier (BBB) model, in the presence and absence of chitinases. CSF chitinase levels were significantly increased in patients with RRMS and NMO compared with HCs and patients with SPMS and OIND. In contrast, no significant differences were detected in serum chitinase levels between groups. Chitinase CSF levels showed correlation with anti-MOG IL-13-producing cells, and eotaxin levels. In vitro experiments showed macrophage chitinase secretion was significantly increased by IL-13, but not by IL-5, IL-6, IL-12, or IFN-γ. Moreover, chitinases enhanced IL-8, RANTES, MCP-1, and eotaxin production, increasing migratory capacity in eosinophils, T cells, and macrophages across an in vitro BBB model. Chitinases increased in the CSF from patients with NMO in response to IL-13. These enhanced levels could contribute to central nervous system inflammation by increasing immune cell migration across the BBB.


Adaptation of an L-proline adenylation domain to use 4-propyl-L-proline in the evolution of lincosamide biosynthesis.
Clinically used lincosamide antibiotic lincomycin incorporates in its structure 4-propyl-L-proline (PPL), an unusual amino acid, while celesticetin, a less efficient related compound, makes use of proteinogenic L-proline. Biochemical characterization, as well as phylogenetic analysis and homology modelling combined with the molecular dynamics simulation were employed for complex comparative analysis of the orthologous protein pair LmbC and CcbC from the biosynthesis of lincomycin and celesticetin, respectively. The analysis proved the compared proteins to be the stand-alone adenylation domains strictly preferring their own natural substrate, PPL or L-proline. The LmbC substrate binding pocket is adapted to accommodate a rare PPL precursor. When compared with L-proline specific ones, several large amino acid residues were replaced by smaller ones opening a channel which allowed the alkyl side chain of PPL to be accommodated. One of the most important differences, that of the residue corresponding to V306 in CcbC changing to G308 in LmbC, was investigated in vitro and in silico. Moreover, the substrate binding pocket rearrangement also allowed LmbC to effectively adenylate 4-butyl-L-proline and 4-pentyl-L-proline, substrates with even longer alkyl side chains, producing more potent lincosamides. A shift of LmbC substrate specificity appears to be an integral part of biosynthetic pathway adaptation to the PPL acquisition. A set of genes presumably coding for the PPL biosynthesis is present in the lincomycin--but not in the celesticetin cluster; their homologs are found in biosynthetic clusters of some pyrrolobenzodiazepines (PBD) and hormaomycin. Whereas in the PBD and hormaomycin pathways the arising precursors are condensed to another amino acid moiety, the LmbC protein is the first functionally proved part of a unique condensation enzyme connecting PPL to the specialized amino sugar building unit.


[Peritoneal tuberculosis simulating advanced ovarian carcinoma: a case report].
Disseminated peritoneal tuberculosis accounts for 1-3% of tuberculosis disease, represented by high frequency of lung defects in endemic countries. The authors report one case in a 43-year-old woman, the initial interpretation of which, based on pleural and peritoneal exudate, showed suspected latero-uterine mass and significant elevated serum CA 125 level, mimicking disseminated ovarian carcinoma. Only after exploring laparotomy with biopsy was disseminated peritoneal tuberculosis identified, thus correcting the diagnosis. Symptomatology, X-ray defect, and cynetic of serum CA 125 level were left in totality after 3 months of antituberculosis multidrugs. This is a diagnostic trap, which presents a new interest for such pathology as tuberculosis, which is on the increase again in the West.


Highly Stable Rare Earth Metal-Organic Frameworks for Fluorescence Recognition of Folic Acid, Proton Conduction, and Magnetic Refrigeration.
Four new isostructural rare earth metal-organic frameworks (RE-MOFs) were synthesized and full characterized, namely, {[(CH)2NH2]3[RE2(BTDBA)2(HCOO)]·5H2O·2DMF}n (H4BTDBA = (4',4'''-(benzo[c][1,2,5]thiadiazole-4,7-diyl)bis([1,1'-biphenyl]-3,5-dicarboxylic acid); RE = Eu (JXUST-34), Gd (JXUST-35), Tb (JXUST-36), and Dy (JXUST-37)). The single-crystal structures analysis shows that JXUST-34-37 are chain-based three-dimensional structures. Importantly, JXUST-34 exhibits excellent water, organic solvents, and acid-base stability, which can be used as a fluorescence sensor for folic acid and Al3+ with detection limits of 0.02 mM and 0.05 μM, respectively. The presence of free [(CH)2NH2]+ cations in the channels can engage the proton carrier during proton conduction. JXUST-34-37 display good proton conductivity, and the conductivities vary with relative humidity and temperatures, among which JXUST-37 has the highest conductivity of 9.66 × 10-3 S·cm-1 at 60 °C and 98% RH. The magnetic studies show that the -ΔSm of JXUST-35 reaches 16.13 J kg-1 K-1 at 2 K and ΔH = 7 T. JXUST-34-37 show multifunctional properties of fluorescence sensing, high proton conductivity, and magnetic refrigeration, which provides a new clue for the development of fluorescent-responsive, magnetic-refrigerant, and proton-conductive RE-MOF materials.


Involvement of Membrane Blebbing in Immunological Disorders and Cancer.
Cellular blebbing is a unique form of dynamic protrusion emanating from the plasma membrane which can be either apoptotic or nonapoptotic in nature. Blebs have been observed in a wide variety of cell types and in response to multiple mechanical and chemical stimuli. They have been linked to various physiological and pathological processes including tumor motility and invasion, as well as to various immunological disorders. They can form and retract extremely rapidly in seconds or minutes, or slowly over hours or days. This review focuses on recent evidence regarding the role of blebbing in cell locomotion with particular emphasis on its role in tumor metastasis, indicating the role of specific causative molecules. The phenomenon of blebbing has been observed in endocrine-resistant breast cancer cells in response to brief exposure to extracellular alkaline pH, which leads to enhanced invasive capacity. Genetic or pharmacological targeting of cellular blebs could serve as a potential therapeutic option to control tumor metastasis.


The effect of raloxifene on left ventricular hypertrophy in postmenopausal women: A prospective, randomized, and controlled study.
In healthy women, there is a progressive age-related increase in myocardial mass that is not seen in their male counterparts and occurs primarily in postmenopausal women. Raloxifene is a selective estrogen receptor modulator that has estrogenic actions on bone and the cardiovascular system. The aim of this study was to investigate the effect of raloxifene on myocardial hypertrophy in postmenopausal patients. A total of 22 postmenopausal osteoporotic women were included in this open-label, randomized, prospective, controlled study. Patients were randomized into two groups: 11 of the patients (group 1) were treated with raloxifene 60 mg/day, and the other 11 patients (group 2) were defined as the control group. Quantitative 2-dimensional and M-mode echocardiographic examination was performed in all patients at the beginning and repeated at the end of the 6-month follow-up period. Left ventricle mass (LVM) and left ventricle mass index (LVMI) were calculated for all patients. The mean age of the patients was 57.2±3.9 years, and baseline clinical characteristics and echocardiographic parameters were similar between the two groups. After 6 months of raloxifene treatment, there was no difference in echocardiographic parameters of LVM and LVMI compared with the control group (201.2±25.9 gr vs. 169.7±46.2 gr, p=0.14 and 120.4±25.9 gr/m2 vs. 105.5±26.3 gr/m2, p=0.195, respectively). There was also no significant difference in LVM and LVMI in the within-group analysis of both groups. Raloxifene therapy does not affect myocardial hypertrophy in postmenopausal women after 6 months of treatment.


Transmural changes in size, contractile and electrical properties of SHR left ventricular myocytes during compensated hypertrophy.
Some hypertrophic stimuli provoke responses from myocytes that vary across the thickness of the left ventricular wall. The Spontaneously Hypertensive Rat (SHR) is a well-established genetic model of hypertension and whole heart hypertrophy. Details of transmural responses to hypertension in the SHR are few, but are needed if the properties of this model are to be fully understood. We therefore tested the hypothesis that left ventricular myocytes of the SHR do not respond uniformly to their hypertensive environment. The volume, contraction and action potentials of enzymically isolated sub-epicardial (EPI) mid-myocardial (MID) and sub-endocardial (ENDO) myocytes from the left ventricle of 20-week-old SHR and normotensive Wistar-Kyoto (WKY) control rats were compared. Compared to WKY, as a single population, SHR myocytes displayed concentric hypertrophy (larger volumes with smaller length:width) increased t-tubule spacing, larger and prolonged cell shortening and intracellular calcium ([Ca2+]i) transients and longer action potentials. However, these responses differed across the left ventricular wall. MID myocytes showed significantly less hypertrophy than EPI and ENDO myocytes. EPI myocytes showed the largest (and significant) increases in cell shortening, [Ca2+]i transients and action potential duration, whilst MID myocytes showed the smallest (and non-significant) changes in these parameters. Real time reverse transcription polymerase chain reaction analysis on cardiac tissue suggest that increased expression of mRNA for fibronectin-1 and protein kinase Cepsilon are involved in the hypertrophic response of the whole heart. Our findings show that in the SHR, the effect of hypertension upon the morphology, mechanical activity and electrical activity of left ventricular myocytes is dependent upon their transmural location. Therefore, in addition to the overall compensating response to hypertension, i.e. increased contractility, there are likely to be regionally specific alterations in mechano-electric interactions that may influence the properties of this important model, e.g. its pre-disposition to arrhythmia whilst still in a compensated state.


Effect of Linker Length on Cell Capture by Poly(ethylene glycol)-Immobilized Antimicrobial Peptides.
Development of antimicrobial peptide (AMP)-functionalized materials has renewed interest in using poly(ethylene glycol) (PEG)-mediated linking to minimize unwanted interactions while engendering the peptides with sufficient flexibility and freedom of movement to interact with the targeted cell types. While PEG-based linkers have been used in many AMP-based materials, the role of the tether length has been minimally explored. Here, we assess the impact of varying the length of PEG-based linkers on the binding of bacterial cells by surface-immobilized AMPs. While higher surface densities of immobilized AMPs were observed using shorter PEG linkers, the increased density was insufficient to fully account for the increased binding activity of peptides. Furthermore, effects were specific to both the peptide and cell type tested. These results suggest that simple alterations in linking strategies-such as changing tether length-may result in large differences in the surface properties of the immobilized AMPs that are not easily predictable.


Evaluation of Deep Learning-Based Automated Detection of Primary Spine Tumors on MRI Using the Turing Test.
Recently, the Turing test has been used to investigate whether machines have intelligence similar to humans. Our study aimed to assess the ability of an artificial intelligence (AI) system for spine tumor detection using the Turing test. Our retrospective study data included 12179 images from 321 patients for developing AI detection systems and 6635 images from 187 patients for the Turing test. We utilized a deep learning-based tumor detection system with Faster R-CNN architecture, which generates region proposals by Region Proposal Network in the first stage and corrects the position and the size of the bounding box of the lesion area in the second stage. Each choice question featured four bounding boxes enclosing an identical tumor. Three were detected by the proposed deep learning model, whereas the other was annotated by a doctor; the results were shown to six doctors as respondents. If the respondent did not correctly identify the image annotated by a human, his answer was considered a misclassification. If all misclassification rates were >30%, the respondents were considered unable to distinguish the AI-detected tumor from the human-annotated one, which indicated that the AI system passed the Turing test. The average misclassification rates in the Turing test were 51.2% (95% CI: 45.7%-57.5%) in the axial view (maximum of 62%, minimum of 44%) and 44.5% (95% CI: 38.2%-51.8%) in the sagittal view (maximum of 59%, minimum of 36%). The misclassification rates of all six respondents were >30%; therefore, our AI system passed the Turing test. Our proposed intelligent spine tumor detection system has a similar detection ability to annotation doctors and may be an efficient tool to assist radiologists or orthopedists in primary spine tumor detection.


Case report of Darier disease localized to the vulva in a 5-year-old girl.
A 5-year-old girl with Darier disease had numerous verrucous papules coalescing into plaques on both labia majora of approximately one year's duration. She was diagnosed as having genital warts, raising the suspicion of sexual abuse. Subsequently, a biopsy specimen from one of the vulvar lesions revealed histologic characteristics consistent with a diagnosis of Darier disease. The case is unusual for the age of onset and the site of initial involvement, and stresses the importance of including acantholytic disorders such as Darier disease in the differential diagnosis of a child with clinically verrucous lesions.


Morphologically indistinguishable hybrid Carassius female with 156 chromosomes: A threat for the threatened crucian carp, C. carassius, L.
The crucian carp Carassius carassius (Linnaeus, 1758), is native to many European freshwaters. Despite its wide distribution, the crucian carp is declining in both the number and sizes of populations across much of its range. Here we studied 30 individuals of a putative pure population from Helsinki, Finland. Despite clear external morphological features of C. carassius, an individual was of a higher ploidy level than the others. We therefore applied a set of molecular genetic (S7 nuclear and cytochrome b mitochondrial genes) and cytogenetic tools (sequential fluorescent 4', 6-diamidino-2-phenylindole [DAPI], Chromomycin A3 [CMA3], C-banding and in situ hybridization [FISH] with both 5S and 28S ribosomal DNA probes) to determine its origin. While all examined characteristics of a diploid representative male (CCAHe2Fi) clearly corresponded to those of C. carassius, a triploid individual (CCAHe1Fi) was more complex. Phylogenetic analysis revealed that the nuclear genome of CCAHe1Fi contained three haploid sets: two C. gibelio and one C. carassius. However the mitochondrial DNA was that of C. gibelio, demonstrating its hybrid origin. The FISH revealed three strong (more intensive) 5S rDNA loci, confirming the triploid status, and an additional 24 weak (less intensive) signals were observed in the chromosome complement of CCAHe1Fi. On the other hand, only two strong and 16 weak 5S rDNA signals were visible on the chromosomes of the CCAHe2Fi male. 28S rDNA FISH revealed four strong signals in both CCAHe1Fi and CCAHe2Fi individuals. CMA3 staining revealed four to six CMA3-positive bands of CCAHe1Fi, while that of diploids contained only two to four. The fact that a polyploid hybrid Carassius female with a strong invasive potential may share morphological characters typical for endangered C. carassius highlights a need to combine genetic investigations of Carassius cryptic diversity with conservation measures of C. carassius in Europe.


Adrenocortical oncocytoma.
Adrenocortical oncocytoma is an exceedingly rare pathological variant of an adrenal neoplasm. The pathogenesis of oncocytic neoplasms is poorly understood. Females have been reported to be affected 2.5 times more frequently than males, and left-sided lesions are more common than those on right side. This case describes a 20 years old female with right lumbar pain. She found to have a right adrenal gland mass measuring about 6 x 5 cm. A computed tomogram showed hypodense mass lesion 6 x 4.2 cm involving right adrenal gland. Differential diagnosis of non-functional adrenal adenoma was made. A laparoscopic right adrenalectomy was performed using the 3-ports lateral transperitoneal approach. Histopathology showed adrenocortical oncocytoma of adrenal gland.


Nitrous oxide cryotherapy for treatment of esophageal squamous cell neoplasia: initial multicenter international experience with a novel portable cryoballoon ablation system (with video).
Early esophageal squamous cell neoplasia (ESCN) can be successfully treated by EMR, endoscopic submucosal dissection (ESD), or radiofrequency ablation. A new portable, battery-powered cryotherapy system using nitrous oxide (cryoballoon focal ablation system [CbFAS]) has been used for Barrett's esophagus. It consists of a small hand-held device containing liquid nitrous oxide, which converts to gas within a low-pressure-compliant through-the-scope balloon and freezes targeted mucosa in contact with the balloon. This study evaluated the feasibility of endoscopic eradication of early ESCN with the CbFAS. Patients with early ESCN (defined as low-grade intraepithelial neoplasia [LGIN], high-grade intraepithelial neoplasia [HGIN], or early T1 squamous mucosal cancer) were treated with the CbFAS. After chromoendoscopy, all Lugol's unstained lesions (USLs) were targeted with 8, 10, or 12 seconds of ice per site, and treatment was repeated until biopsy samples demonstrated eradication of ESCN. Postprocedure adverse events were recorded. Ten patients (4 men; median age, 69.5 years) with LGIN (n=2), HGIN (n=7), or esophageal squamous cell carcinoma (ESCC; n=1, after EMR) in 24 USLs were treated. The median maximum diameter of the largest USL was 1.5 cm (interquartile range, 1-2 cm), and median total length of all neoplastic USLs was 2 cm (range, 1-10 cm). Patients with focal disease received a median of 2 cryoablations, whereas 4 patients with large and/or multifocal circumferential neoplasia had 6 to 12 ablations per procedure. The median procedure time was 34 minutes (range, 18-57 minutes). Treatment was completed in all patients. No major adverse events occurred. Four patients developed mild self-limited chest pain requiring narcotic analgesics immediately after the procedure. Two patients who received circumferential ablation developed a stricture responding to dilation, with no recurrence. Complete endoscopic and pathologic response was achieved in all patients at 3 months. One year follow-up biopsy specimens in 7 patients showed no USL or ESCN. All patients were disease free at last visit, with a median follow-up time of 10.7 months (interquartile range, 4-14 months). We report the first application of nitrous cryoballoon ablation for curative treatment of early primary or recurrent ESCN. Our initial experience suggests that efficacy is high and the safety profile is reasonable. Prospective trials are needed to optimize cryogen dosimetry and assess safety and efficacy.


Spatio-Temporal Point Path Analysis and Optimization of a Galvanoscopic Scanning Laser Projector.
Galvanoscopic scanning laser projectors are powerful vector graphic devices offering a tremendous local brightness advantage compared to standard video projection systems. However, such devices have inherent problems, such as temporal flicker and spatially inaccurate rendering. We propose a method to generate an accurate point-based projection with such devices. To overcome the mentioned problems, we present a camera-based method to automatically analyze the laser projector's motion behavior. With this information, a model database is generated that is used to optimize the scanning path of projected point sequences. The optimization considers the overall path length, its angular shape, acceleration behavior, and the spatio-temporal point neighborhood. The method minimizes perceived visual flickering while guaranteeing an accurate spatial point projection at the same time. Comparisons and timing measurements prove the effectiveness of our method. An informal user evaluation shows substantial visual quality improvement as well.


Hormonal contraception in women with endometriosis: a systematic review.
A systematic review was carried out of studies of women with endometriosis, to examine the evidence for efficacy of the use of hormonal contraception to improve disease-related pain and decrease postoperative risk of disease recurrence. A search of the Medline/PubMed and Embase databases was performed to identify all published English language studies on hormonal contraceptive therapies (combined hormonal contraceptives [CHCs], combined oral contraceptives [COCs], progestin-only pills [POPs] and progestin-only contraceptives [POCs]) in women with a validated endometriosis diagnosis, in comparison with placebo, comparator therapies or other hormonal therapies. Main outcome measures were endometriosis-related pain (dysmenorrhoea, pelvic pain and dyspareunia), quality of life (QoL) and postoperative rate of disease recurrence during treatment. CHC and POC treatments were associated with clinically significant reductions in dysmenorrhoea, often accompanied by reductions in non-cyclical pelvic pain and dyspareunia and an improvement in QoL. Only two COC preparations (ethinylestradiol [EE]/norethisterone acetate [NETA] and a flexible EE/drospirenone regimen) demonstrated significantly increased efficacy compared with placebo. Only three studies found that the postoperative use of COCs (EE/NETA, EE/desogestrel and EE/gestodene) reduced the risk of disease recurrence. There was no evidence that POCs reduced the risk of disease recurrence. CHCs and POCs are effective for the relief of endometriosis-related dysmenorrhoea, pelvic pain and dyspareunia, and improve QoL. Some COCs decreased the risk of disease recurrence after conservative surgery, but POCs did not. There is insufficient evidence, however, to reach definitive conclusions about the overall superiority of any particular hormonal contraceptive.


Testing Distinct Three-Dimensional Effects in Laparoscopy: A Prospective Randomized Trial Using the Lübecker Toolbox Curriculum.
The use of stereoscopic laparoscopic systems in minimally invasive surgery (MIS) allows a three-dimensional (3D) view of the surgical field, which improves hand-eye coordination. Depending on the stereo base used in the construction of the endoscopes, 3D systems may differ regarding the 3D effect. Our aim was to investigate the influence of different stereo bases on the 3D effect. This was a prospective randomized study involving 42 MIS-inexperienced study participants. We evaluated two laparoscopic 3D systems with stereo bases of 2.5 mm (system A) and 3.8 mm (system B) for differences in learning MIS skills using the Lübeck Toolbox (LTB) video box trainer. We evaluated participants' performance regarding the times and repetitions required to reach each exercise's goal. After completing the final exercise ("suturing"), participants performed the exercise again using a two-dimensional (2D) representation. Additionally, we retrospectively compared our study results with a preliminary study from participants completing the LTB curriculum with a 2D system. The median number of repetitions until reaching the goals for LTB exercises 1, 2, 3, and 6 for system A were: 18 (range 7-53), 24 (range 8-46), 24 (range 13-51), and 21 (range 10-46), respectively, and for system B were: 12 (range 2-30), 16 (range 6-43), 17 (range 4-47), and 15 (range 6-29), respectively (p = not significant). Changing from a 3D to a 2D representation after completing the learning curve led to a longer average time required, from 95.22 to 119.3 s (p < 0.0001), for the last exercise (exercise 6; "suturing"). When comparing the results retrospectively with the learning curves acquired with the 2D system, there was a significant reduction in the number of repetitions required to reach the LTB exercise goals for exercises 1, 3, and 6 using the 3D system. Stereo bases of 2.5 and 3.8 mm provide acceptable bases for designing 3D systems. Additionally, our results indicated that MIS basic skills can be learned quicker using a 3D system versus a 2D system, and that when the 3D effect is eliminated, the corresponding compensatory mechanisms must be relearned.


Construct Validity of the Emotion Matching Task: Preliminary Evidence for Convergent and Criterion Validity of a New Emotion Knowledge Measure for Young Children.
Current emotion knowledge measures examine only one component of the multifaceted construct. We examined the reliability and the construct validity of a new measure of emotion knowledge (EK), the Emotion Matching Task (EMT). The EMT consists of four parts which measure the components of receptive emotion knowledge, expressive emotion knowledge, emotion situation knowledge, and emotion expression matching. First, we compared the EMT and its parts to two widely used EK measures-the Kusche Emotional Inventory (KEI) and Denham's Affective Knowledge Test (AKT, 1986) in order to establish convergent validity. The EMT and its four parts were strongly correlated with both measures of emotion knowledge. Regression analyses revealed moderate to strong predictive validity for EMT. Compared to KEI and AKT, the EMT was a more robust predictor of teacher rated emotion regulation and parent reported effortful control. Compared to KEI and AKT, the EMT correlated similarly with verbal ability and age.


Poliomyelitis in Spain, 1982-1984: virologic and epidemiologic studies.
The authors present a detailed study of poliomyelitis in Spain for the years 1982, 1983, and 1984. The 50 cases reported have been epidemiologically classified following World Health Organization guidelines. Virus was isolated from 43 of these cases. Intratypic characterization was done using specifically absorbed antisera classifying the strains as non-Sabin-like and Sabin-like. The neutralizing antibodies in whole and fractionated sera were also determined. The largest number of paralytic poliomyelitis cases, 28, was found in children in the first year of life. Thirty of the cases were unvaccinated children. Poliomyelitis was not detected in adults during the period described. Wild strains isolated were type I and III, primarily from Gypsies. There was a significant incidence of vaccine-associated cases in recipients, as well as in contacts during 1982 and 1983. The cases were located in the Mediterranean and Southern zone. In 1984, total and vaccine-associated cases dropped dramatically.


Raman spectroscopy for noninvasive glucose measurements.
We report the first successful study of the use of Raman spectroscopy for quantitative, noninvasive ("transcutaneous") measurement of blood analytes, using glucose as an example. As an initial evaluation of the ability of Raman spectroscopy to measure glucose transcutaneously, we studied 17 healthy human subjects whose blood glucose levels were elevated over a period of 2-3 h using a standard glucose tolerance test protocol. During the test, 461 Raman spectra were collected transcutaneously along with glucose reference values provided by standard capillary blood analysis. A partial least squares calibration was created from the data from each subject and validated using leave-one-out cross validation. The mean absolute errors for each subject were 7.8%+/-1.8% (mean+/-std) with R2 values of 0.83+/-0.10. We provide spectral evidence that the glucose spectrum is an important part of the calibrations by analysis of the calibration regression vectors.


Peak outward acceleration and ball release in cricket.
The purpose of this study was to investigate the utility of peak outward acceleration (POA) measured from an inertial sensor worn at the wrist as an indicator of the critical end point of the bowling action – ball release, a critical element when assessing illegal actions. Twenty-one finger-spin and fast bowlers from nine countries were recruited from the ICC under-19 Cricket World Cup to take part in this research. Bowlers delivered a cross section of their standard deliveries while wearing an inertial sensor placed on their wrists. Ball release was determined by a validated motional analysis ball release (MABR) protocol and compared to the simultaneously collected POA. POA was shown to be highly correlated with MABR (R(2) = 0.98) and a Bland-Altman plot indicated that all 148 trials were within the 3.42 frame (0.014 s) limits of agreement. POA when measured by an inertial sensor worn on the wrist during bowling had a close relationship with an established method of identifying ball release in a biomechanical laboratory regardless of bowler and delivery type. Further, accuracy can be achieved with the adoption of a simple regression equation applied to the POA and as such is a valid measure of ball release in cricket bowlers.


Preparedness for emerging infectious diseases: pathways from anticipation to action.
Emerging and re-emerging infectious disease (EID) events can have devastating human, animal and environmental health impacts. The emergence of EIDs has been associated with interconnected economic, social and environmental changes. Understanding these changes is crucial for EID preparedness and subsequent prevention and control of EID events. The aim of this review is to describe tools currently available for identification, prioritization and investigation of EIDs impacting human and animal health, and how these might be integrated into a systematic approach for directing EID preparedness. Environmental scanning, foresight programmes, horizon scanning and surveillance are used to collect and assess information for rapidly responding to EIDs and to anticipate drivers of emergence for mitigating future EID impacts. Prioritization of EIDs - using transparent and repeatable methods - based on disease impacts and the importance of those impacts to decision-makers can then be used for more efficient resource allocation for prevention and control. Risk assessment and simulation modelling methods assess the likelihood of EIDs occurring, define impact and identify mitigation strategies. Each of these tools has a role to play individually; however, we propose integration of these tools into a framework that enhances the development of tactical and strategic plans for emerging risk preparedness.