Portuguese Adaptation of a Faux Pas Test and a Theory of Mind Picture Stories Task.
Developmental concepts of 'Theory of Mind' (ToM) suggest that this cognitive domain is an innate human capacity requiring input from the social environment to mature. Research suggests substantial individual differences in ToM, depending on childhood experiences, genetics, and the presence or absence of a neuropsychiatric disorder. None of the existing ToM tests for adult populations have been made available in Portuguese. Accordingly, the main objective of this study was to evaluate the psychometric properties of the Portuguese versions of the Faux Pas (FP) Recognition Test and the ToM Picture Stories Task. Both tests were given to a sample of 200 Portuguese adults (125 women and 75 men) aged between 18 and 60 years. The psychometric analyses of the results indicate that the Portuguese version of the FP Recognition Test is appropriate for use in research and clinical settings, providing a composite score that reliably measures the ability to infer the thoughts and feelings of others in a 'faux pas' situation (Cronbach's α = 0.82). However, the ToM Picture Stories Task did not show acceptable psychometric qualities.


Short-term field research on air pollution within the boundaries of the large city in the Baltic region.
Air quality in urban and suburban areas is strongly affected by the level of local urbanization, climatic conditions and industrial activity. Monitoring the main air pollutants such as nitrogen oxides, carbon monoxide and particulate matter may help control the most polluted areas of the site and take measures to reduce pollution. Uncontrolled emissions from other chemical pollutants, including volatile organic compounds and odorous contamination sources like ammonia, may cause both a chronic human disease and damage to flora and fauna. The conducted field research is aimed at determining air pollution within the areas of the large city (residential territory, recreation territory and the areas close to intense transport streets) polluted with the gaseous pollutants of varying nature (CO, NO2, ozone, sulfur dioxide, VOC and NH3) as well as particulate matter in different seasons of the year. Studies on Vilnius district air quality were carried out in 17 urban locations (sites) and based on two-phase measurements. The first phase was initiated in 2016-2017 and the second one took place in 2019-2020. It was observed that in the areas close to intense transport streets, the concentration of pollutants can increase more than 3 times, thus reaching up to 36.0 µg/m3 of PM10 (particulate matter) and up to 48.0 µg/m3 of nitrogen dioxide. During the summer period, ammonia concentrations can increase up to 3 times, reaching up to 11.0 µg/m3 from farming and/or industrial activities.


Retrospective analysis of survival outcomes and the role of cisplatin-based chemotherapy in patients with urethral carcinomas referred to medical oncologists.
Primary carcinomas of the urethra (PCU) are rare and often advanced when diagnosed. Treatment standards are lacking. We studied treatment response and survival in a cohort of patients with PCU, with emphasis on modern platinum-containing chemotherapy regimens plus surgery for advanced disease. This was a retrospective chart review of consecutive patients with PCU seen by medical oncologists at our institution over a recent 5-year period. Outcome was measured as best response to chemotherapy. Kaplan-Meier estimates were generated for survival and Cox proportional hazard was used for prognostic factors for survival. The 44 patients (64% women) included had a median age at diagnosis of 66.5 years. The most prevalent histologic subtypes of PCU were squamous cell carcinoma and adenocarcinoma. At diagnosis, 43% already had lymph node-positive [lymph node (LN)+] disease, and 16% had distant metastases. The entire cohort's overall survival (OS) was 31.7 months. The response rate to platinum-containing neoadjuvant chemotherapy was 72%. Twenty-one patients with locally advanced or LN+ PCU underwent chemotherapy plus surgery. Their median OS from chemotherapy initiation was 25.6 months. Four of 9 patients (44%) with LN+ PCU at diagnosis were alive at our review, with a minimum follow-up of more than 3 years. Modern platinum-containing regimens appear to be effective in advanced PCU. Preoperative chemotherapy is associated with prolonged disease-free survival in a subgroup of LN+ cases.


Helicopter Neonatal Transport: First Golden Hour at Birth Is Useful Tool Guiding Activation of Appropriate Resources.
A lack of consensus exists about the appropriate criteria to activate a helicopter during neonatal transport. The aim of the present study was to explore the possible guiding criteria to justify helicopter activation for neonatal transport (NETS). This was a retrospective study of the Gaslini Genoa NETSs from February 1995 to December 2019. The flight and driving times and the reason for helicopter neonatal transport activation were obtained for every subject from the online NETS clinical database. Driving and flight data (mean and standard deviation [SD]) were compared using the Student t-test (P < .05). Five thousand eight hundred sixty-six transported newborn infants were identified. A significant difference emerged between the overall ground (mean = 99.2 minutes [SD = 15.7 minutes]) and overall helicopter transport times (mean = 27.8 minutes [SD = 11.9 minutes], P < .0001). Considering the "golden hour," the chance to stabilize the patient within this time frame could have been possible for 4 of 5 neonatal care centers when using a helicopter. On the basis of our observations, we suggest including the golden hour as 1 of the guiding criteria justifying helicopter activation, especially if applied to the reason of transport and the quality of assistance the newborn will receive while waiting for the NETS team.


Spheres, coiled bodies and nuclear bodies.
Of several distinct aggregations or nuclear bodies in the nucleus, two of the most prominent are the sphere organelle and the coiled body. Recent molecular studies indicate that the coiled body found in interphase nuclei may be identical to the sphere organelle found in the amphibian oocyte nucleus. This is not the first time an interphase nuclear body has been suspected of being the same as a structure in the oocyte nucleus; the first such structure was the nucleolus. Both the sphere organelle and the nucleolus are attached to site-specific loci on oocyte lampbrush chromosomes. Because of their unique morphologies and utility in reproducibly identifying specific genetic elements, they have been referred to as lampbrush chromosomal landmarks. The discovery of the way nucleoli arise has led to an understanding of their function, and for this reason I discuss current models for the genesis of spheres.


The effect of chronic lithium treatment on hippocampal progenitor cells: Transcriptomic analysis and systems pharmacology.
To identify the genomics underpinning the increased volume of the hippocampus after long-term administration of lithium (Li) in bipolar disorder patients, hypothesizing the possible contribution of cell growth and differentiation pathways to this complication. RNA-seq profiles of four samples of hippocampal progenitor cells chronically treated with a high dose of Li and three samples chronically treated with the therapeutic dose were retrieved from NCBI-GEO. The raw data underwent filtration, quality control, expression fold change, adjusted significance, functional enrichment, and pharmacogenomic analyses. CCND1, LOXL2, and PRNP were identified as the genes involved in the drug response and the chronic effects of Li in the hippocampal cells. GSK-3β was also a hub in the pharmacogenomic network of Li. In addition, ZMPSTE24 and DHX35 were identified as the important genes in lithium therapy. As shown by gene ontology results, these findings conclude that lithium may increase the size of the hippocampus in bipolar patients by stimulating the generation of new neurons and promoting their differentiation into neuroblasts, neurons, or microglia.


Roles of Endogenous Retroviruses in Early Life Events.
A retrovirus that infected our ancestors 100 million years ago became a human gene that is expressed in embryos and cancers, and can be detected in the blood of pregnant women. Accumulating evidence suggests potential roles for endogenous retroviruses in early life events, which may affect adult health.


Role of sonography in the evaluation of carotid artery stents.
To study the ability and accuracy of sonography to visualize carotid artery stents and assess criteria for carotid artery stent stenosis. Duplex Doppler sonographic examinations were performed on 143 patients in whom 158 carotid artery stents were placed. Follow-up sonography to evaluate 24 of these stents within 24 h of stent placement was compared with post-procedure angiography. Another 23 stents were evaluated with sonography and with follow-up angiography more than 24 h after the procedure. The remainder of the 111 stents were evaluated exclusively with sonography after stent placement. Sonography was used to evaluate stent visibility, stent-media separation, and degree of stent stenosis. Wallstents were the best-visualized stents and Acculink the worst, but the differences were not statistically significant. Of 4 patients with stent-media separation >3 mm, 2 (50%) developed stenosis (40%-59%) at 6 and 12 months from stent placement. The other 2 stents with stent-media separation had not developed stenosis at 6 months' follow-up. A comparison of angiography and sonography performed on the date of stent placement revealed 19 true-negative sonography studies, 4 false-positive studies, 1 true-positive study, and no false-negative studies. A comparison of follow-up angiograms performed more than 24 h after the procedure with follow-up sonography revealed 17 true-negative studies, 1 false-positive study, 5 true-positive studies, and no false-negative studies. Sonography allows accurate evaluation of stent placement within the vessel and visualization of stent-media distance. Stent-media separation may be an early detection sign for stent stenosis development. Velocity criteria developed for non-stented vessels, when applied to stented vessels, correlate well with angiographic findings. Doppler velocity measurements when compared with visible stent assessment may reduce false-positives.


Opposing Action of Hedgehog and Insulin Signaling Balances Proliferation and Autophagy to Determine Follicle Stem Cell Lifespan.
Egg production declines with age in many species, a process linked with stem cell loss. Diet-dependent signaling has emerged as critical for stem cell maintenance during aging. Follicle stem cells (FSCs) in the Drosophila ovary are exquisitely responsive to diet-induced signals including Hedgehog (Hh) and insulin-IGF signaling (IIS), entering quiescence in the absence of nutrients and initiating proliferation rapidly upon feeding. Although highly proliferative FSCs generally exhibit an extended lifespan, we find that constitutive Hh signaling drives FSC loss and premature sterility despite high proliferative rates. This occurs due to Hh-mediated induction of autophagy in FSCs via a Ptc-dependent, Smo-independent mechanism. Hh-dependent autophagy increases during aging, triggering FSC loss and consequent reproductive arrest. IIS is necessary and sufficient to suppress Hh-induced autophagy, promoting a stable proliferative state. These results suggest that opposing action of diet-responsive IIS and Hh signals determine reproductive lifespan by modulating the proliferation-autophagy balance in FSCs during aging.


Adaptation of a high-performance liquid chromatographic method for quantitative determination of homocysteine in urine.
A modification of the Bio-Rad total homocysteine HPLC-test is presented in order to enable not only plasma homocysteine measurements but also the quantification of homocysteine in urine samples using the same principle of measurement. Coelution of the internal standard provided in the test kit with an endogenous compound in urine demands for an alternative analytical procedure. Therefore, we introduced 3-mercaptopropionic acid as a substitute for the internal standard. The analytical method validation was performed for the matrix of urine specimens. The applicability of this method was demonstrated in a clinical study with volunteers after homocysteine thiolactone hydrochloride loading.


Estimation of gestational age in neonates using clavicular-pubis length on routine chest-abdomen radiographs.
Neonatal diseases differ depending on gestational age and weight. In the setting of an emergency in the neonatal intensive care unit (NICU), relevant clinical information is often not available when the first neonatal radiograph is obtained. When reading an initial chest-abdomen radiograph, the paediatric radiologist needs gestational age data for best radiologic practice. A transverse diameter of the chest has been previously described to estimate gestational age (GA). To determine the strength of the correlation between GA/weight and clavicular-pubis length (CPL) on admission radiographs; to obtain a quadratic formula based on the correlation of CPL with GA and to demonstrate if a more simplified formula used by our group works as efficiently as the formula provided by the regression analysis. A retrospective study was approved by the institutional review board and informed consent was waived. The length from the medial aspect of the clavicle to the pubic bone was measured on the initial portable chest-abdomen radiographs of 260 patients admitted to the NICU in 2016. Regression analysis was performed to investigate the association between CPL and GA/birth weight. One hundred eleven females and 149 males with GA between 23 and 42 weeks were evaluated. CPL was statistically associated with both GA (P<0,01) and birth weight. The estimation can be expressed with an equation of the model: GA (weeks) = (CPL in cm - 1.98)/0.42. A simplified formula: GA (weeks) = (CPL in cm) ×2+2, strongly correlates with the equation model. In patients in whom it is not known, GA can be estimated by measuring the length between medial clavicle and symphysis pubis using the formulae we propose.


Discriminant functions for sex estimation of modern Japanese skulls.
The purpose of this study is to generate a set of discriminant functions in order to estimate the sex of modern Japanese skulls. To conduct the analysis, the anthropological measurement data of 113 individuals (73 males and 40 females) were collected from recent forensic anthropological test records at the National Research Institute of Police Science, Japan. Birth years of the individuals ranged from 1926 to 1979, and age at death was over 19 years for all individuals. A total of 10 anthropological measurements were used in the discriminant function analysis: maximum cranial length, cranial base length, maximum cranial breadth, maximum frontal breadth, basion-bregmatic height, upper facial breadth, bizygomatic breadth, bicondylar breadth, bigonial breadth, and ramal height. As a result, nine discriminant functions were established. The classification accuracy ranged from 79.0 to 89.9% when the measurements of the 113 individuals were substituted into the established functions, from 77.8 to 88.1% when a leave-one-out cross-validation procedure was applied to the data, and from 86.7 to 93.0% when the measurements of 50 new individuals (25 males and 25 females), unrelated to the establishment of the discriminant functions, were used.


Minicolumn size and human cortex.
Minicolumns in primates are small when compared with those of other mammals, both in absolute and relative terms. The data suggest that minicolumns in the earliest primates were especially narrow and increased in accordance with encephalization so that the largest minicolumns in this mammalian order are found in apes and humans. Among the evolutionary strategies that led to the successful human brain was a combination of enhanced cortical volume based on increases in the number of ontogenetic units, along with enlargement of the individual minicolumns. However, continued encephalization of the large human brain presents serious problems that may limit future growth. When further increases in brain size can no longer be sustained, the alternative for further adaptations will have to be done at the level of brain organization. A downsizing of minicolumns may be among those responses. This has the advantage of permitting increases in the number of processing units without adding surface area. However, it is argued that narrow minicolumns process information differently, which raises questions about the relation between minicolumn size and behavior. There is evidence that minicolumns may be smaller in extant humans within selected populations, and the implications of this are briefly considered.


Correction to: A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency.
The original version of the article contained error regarding the presentation of the institutional authors in the PDF and html versions.


Outbreak of acute larval cyathostominosis - A "perfect storm" of inflammation and dysbiosis.
Cyathostomins are prevalent and pathogenic intestinal helminths of horses, causing acute and chronic disease, including acute larval cyathostominosis, which has a mortality rate of 50%. Factors determining individual susceptibility to acute larval cyathostominosis are unknown. Investigation of these factors could lead to novel treatment and prevention strategies. To investigate clinicopathological and faecal microbiota changes associated with disease in individual horses in an acute larval cyathostominosis outbreak. Case series. The study population was a herd of 23 mixed breed horses in Ireland. The outbreak occurred in November 2018. Fourteen horses were clinically affected. Clinical status was monitored and recorded. Blood and faecal sampling allowed clinicopathological, faecal 16s rRNA gene sequencing and faecal egg count analyses. Two horses were euthanised, whilst 12 recovered. Common clinical signs included loose faecal consistency, weight loss and pyrexia. Consistent clinicopathological findings were borderline anaemia, leucocytosis, thrombocytosis, hyperfibrinogenaemia, hyperglobulinaemia and a reverse A: G ratio. Decreased alpha-diversity of the faecal microbiota and greater relative abundance of the genus Streptococcus, class Bacilli, order Lactobacillales and family Streptococcaceae, and family Prevotelleceae was found in clinically affected horses compared to their clinically normal cohorts. An increase in obligate fibrolytic bacteria was seen in the clinically normal group compared to the clinical group. Histopathological findings of the colon and caecum revealed a severe necrotising typhlocolitis associated with cyathostomin larvae and bacterial overgrowth in the mucosa of the large intestine. The study population in this outbreak is small. There are several confounding factors limiting this to a descriptive case series. Faecal microbiota has been shown to reflect the large intestinal microbiota but do not represent changes directly. These findings suggest that acute larval cyathostominosis is associated with dysbiosis of the gut microbiota as well as the inflammatory stimulus of numerous emerging larvae leading to structural and functional pathology of the large intestine.


Parenteral methotrexate or gold for rheumatoid arthritis: a follow up.
The forty participants in a double blind controlled trial of parenteral methotrexate or gold for RA were followed up two years later. Fifty percent had remained on the original medication, 13/20 on MTX and 7/20 on gold. Only 5 and 3 of them respectively had no active joint swelling. No major differences between the two groups were seen.


Posterior Meniscal Root Repair With Transtibial Double Tunnel Pullout Technique and Anchor Fixation.
Meniscus root tears are tears that occur within 1 cm of the meniscus root attachment to the tibia. If not repaired, root tears will lead to altered knee biomechanics and accelerated degenerative changes in the knee. In this surgical technique, we demonstrate repair of a meniscus root tear with an all-inside suture repair of the posterior meniscus that is then passed through 2 transtibial tunnels and then fixed with an anchor. After surgery, patients are non-weightbearing for 4 weeks and can return to activity by 6 months.


Building a Human Thymus: A Pointillist View.
In this issue of Immunity, Zeng et al. use single-cell RNA sequencing analyses of rare samples to shed light on the emergence of thymic stromal cell types, the first developing T lymphocytes, and their possible pre-thymic precursors in the early human fetus.


Foreign matter salpingitis 3 years after typhlitis.
This case suggests that typhlitis may cause delayed abdominal pathology. A history of this condition should be considered in the work-up of any patient with gastrointestinal or genitourinary pathology.


Preoperative systemic inflammatory markers are prognostic indicators in recurrent adrenocortical carcinoma.
Recurrent adrenocortical carcinoma (ACC) has a poor prognosis with minimal clinical and biochemical factors to guide management. The aim of this study was to evaluate the prognostic significance of systemic inflammatory response in patients with recurrent ACC. Patients who underwent resection for recurrent ACC were retrospectively analyzed. Preoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio (LMR), and mean platelet volume were calculated. Twenty-five patients (age at operation 52.2 ± 9.5 years) were identified. We observed a statistically significant shorter disease-specific survival (DSS) in patients with LMR less than 4 (41 ± 7.4 months vs 71 ± 12.3, P = .023) and male sex (26.6 ± 4.2 months vs 57.6 ± 9.5 months, P = .079), while time-to-recurrence (TTR) less than 12 months (40 ± 7.7 months vs 70.3 ± 13.1 months, P = .059) had a trend on univariate analysis for worse DSS. On multivariable analysis, LMR < 4 (hazard ratio [HR] 4.18; 95% confidence interval [CI]: 1.18-14.76; P = .027) and TTR less than 12 months (HR 2.77 95% CI: 1-7.62; P = .049) were found to be significantly associated with worse DSS. Preoperative LMR greater than 4 and TTR greater than 12 months are associated with longer DSS. Patients with LMR greater than 4 and TTR greater than 12 months may benefit from a more aggressive therapeutic approach and may require less frequent surveillance.


The prevalence and characteristics of water-pipe smoking among high school students in Saudi Arabia.
To identify the prevalence and predictors of the water-pipe (WP) smoking epidemic in the Kingdom of Saudi Arabia (KSA). A cross-sectional study conducted with 16-18 year-old high school students in Riyadh, Saudi Arabia. Of the 1272 participants, 414 (33.0%) reported having tried WP smoking. Of this group, 141 (34.1%) were female and 273 (65.9%) were male. Further, 129 (10.2%) students were current WP smokers who had used at least one rock in the past month; 20 were female (1.6%) and 120 were male (8.6%). Regarding age, 276 (68.1%) students who tried WP smoking at least once began when they were over 11 years of age, whereas 129 (31.9%) began WP smoking at or before 11 years of age. Adjusted odds ratios showed that trying WP smoking at least once was associated with smoking after the age of 11 (p=0.021, OR 7.7; CI: 1.4-43.6) and accepting water-pipes from a friend (p=0.024, OR 10.6; CI: 1.4-83.4). A high prevalence of WP smoking exists among male and female high schools students in Riyadh, KSA. WP smoking was reported to begin in early adulthood.


Improved survival rates in children over 1 year of age with stage III or IV neuroblastoma following an intensive chemotherapeutic regimen.
Combined chemotherapeutic regimens of (1) cyclophosphamide (40 mg/kg x two days), (2) cisplatinum (20 mg/m2 x five days) plus VM-26 (100 mg/m2), and (3) Adriamycin (60 mg/m2) plus DTIC (250 mg/m2 x five days) were prescribed for 42 Japanese children greater than 1 year of age with stage III or IV neuroblastoma. The protocol was separated into three forms (A, B, and C) from the combination pattern of three such high-dose courses. The cumulative survival rates for those with stages III and IV 48 months after initiation of therapy were 76.2% and 20.1%, respectively, and the overall rate was 36.7%. The tumor disappeared during the course of treatment in 25 of 42 children (59.5%). The 48-month survival rate was superior in patients greater than 5 years of age than younger patients (P less than .01). Even in patients with a tumor originating in the suprarenal region, the 48-month survival rate was 30.5%. Among 12 patients in whom the N-myc oncogene was measured, one of five with one to ten copies of amplification died, whereas all seven with greater than ten copies died or had a recurrence. Thus, the present chemotherapeutic regimens, in particular alternate administration of each high-dose course, considerably improved the survival of patients with stage III neuroblastoma. More aggressive protocols are needed for those with stage IV neuroblastoma who are greater than 1 year of age, particularly in those with an amplified N-myc oncogene.


Minimal femoral cortical thickness necessary to prevent perforation by ultrasonic tools in joint revision surgery.
Ultrasonic tools are effective in removing cement in revision surgery and almost eliminate perforation of the femoral shaft, a dangerous complication associated with cement removal using drills, chisels, osteotomes, and other tools. Clinically, the ultrasonic tool used to remove cement could not be passed through a relatively normal femoral cortex; however, a perforation occurred in a patient with a femoral cortex less than 1 mm thick. The purpose of this study was to determine how thin the femoral cortex can be and yet allow the safe use of ultrasonic tools to remove cement without the risk of perforation. A cement mantle was constructed in the intramedullary canal of human cadaver femurs. Each specimen was mounted on a jig, which was then fastened to a Materials Testing System (Minneapolis, MN). The average load generated across the cortex by the ultrasonic tools while removing cement was measured. Loads of varying magnitudes were then applied by the ultrasonic tools to femoral cortices of varying thickness. When the cortex measured 3 mm thick, perforation did not occur. When the cortex measured 2 mm, perforation was possible but required loads three to six times greater than those normally used to remove cement.


Addition of docetaxel to S-1 results in significantly superior 5-year survival outcomes in Stage III gastric cancer: a final report of the JACCRO GC-07 study.
A phase III trial comparing S-1 and docetaxel with S-1 alone as postoperative chemotherapy for pathologically Stage III gastric cancer was conducted and clarified the superiority of the doublet in terms of 3-year relapse-free survival as the primary endpoint (67.7% versus 57.4%, hazard ratio [HR] 0.715, 95% confidence interval [CI] 0.587-0.871; p = 0.0008). This final report analyzed 5-year survival outcomes along with the incidence and pattern of late recurrences. Patients with histologically confirmed Stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive adjuvant chemotherapy with either S-1 plus docetaxel or S-1 alone. The same 912 patients who were evaluated for 3-year survival outcomes in the previous report were analyzed. Five-year overall survival rate of the S-1 plus docetaxel group (67.91%) was significantly superior to that in the S-1 group (60.27%; HR 0.752, 95% CI 0.613-0.922; p = 0.0059). The incidence of late recurrence at > 3 years after randomization was similar in both groups (7.3% versus 7.2%). Peritoneal dissemination was the most common pattern of late recurrence. Addition of docetaxel significantly suppressed relapse through the lymphatic (6.8% [95% CI 4.52-9.17] versus 15% [95% CI 11.76-18.30]; p < 0.0001) and hematogenous (10.2% [95% CI 7.37-12.94] versus 15.7% [95% CI 12.36-19.01]; p < 0.0137) pathways throughout the 5 years of follow-up. The survival benefit of postoperative chemotherapy with S-1 and docetaxel in terms of 5-year overall survival rate was confirmed for patients with pathologically Stage III gastric cancer, although late recurrences were not prevented.


Yarn design for functional tissue engineering.
Tissue engineering requires the ability to design scaffolds with mechanical properties similar to those of the native tissue. Here, B. mori silk yarns are used as a model system to demonstrate the potential benefits and drawbacks of several textile methods used to fabricate tissue engineering scaffolds. Fibers are plied, twisted, cabled, braided, and/or textured to form several geometries with a wide range of mechanical outcomes. Predictable changes in ultimate tensile strength and stiffness are demonstrated following processing and as a function of test environment. The mechanical effects of increasing turns per inch and combining groups of fibers into higher-order yarn structures are demonstrated. Braids, one of the most commonly used textile structures, are shown to be limited by a change in stiffness following the locking-angle and therefore, potentially not the ideal structure for tissue engineering. Cabled yarns appear to allow the most flexibility in mechanical outcomes with a highly organized geometry. Twisted yarns, while more economical than cabled yarns, result in a higher stiffness and lower percent elongation at break than cabled yarns.


Human leukemias with mutated FLT3 kinase are synergistically sensitive to FLT3 and Hsp90 inhibitors: the key role of the STAT5 signal transduction pathway.
17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of the molecular chaperone heat shock protein 90, results in cell type-specific inhibition of proliferation of leukemic cells. GTP14564 is a tyrosine kinase inhibitor actively against FLT3. The current study evaluated the single and combined effects of 17-AAG and GTP14564, and the role of FLT3 in their inhibitory effects. The importance of FLT3 mutations was demonstrated using small interfering RNA (siRNA) targeted to FLT3. Similar to FLT3 siRNA, GTP14564 inhibited FLT3 internal tandem duplication (ITD) cells (MV4;11) and FLT3 amplified wild-type cells (SEMK2-M1), but not wild-type FLT3 cells (RS4;11). However, when RS4;11 cells were stimulated with FLT3-ligand, phosphorylation of STAT5 and GTP14564 inhibition were observed. Responses to GTP14564 in all cell types were directly related to the level of STAT5 phosphorylation in the cells. We observed synergistic effects of combined 17-AAG and GTP14564 in cell lines with FLT3-ITD and amplified wild-type FLT3. Combined treatment with 17-AAG and GTP14564 reduced the levels of p-FLT3 and p-STAT5, enhanced G0/G1 arrest and apoptosis in FLT3-ITD and amplified wild-type FLT3. The combination of 17-AAG with FLT3 kinase inhibitors can enhance targeted therapy in leukemias with FLT3 mutations, such as MLL fusion gene leukemias.


Influence of physicochemical properties on the patterns of association of a series of aliphatic esters of halofantrine with plasma lipoproteins.
Although the association of lipophilic drugs with plasma lipoproteins has not been fully characterized, there are several reports of lipoprotein association being influential in pharmacokinetic and pharmacodynamic profiles of important therapeutic agents. The current studies utilized a series of aliphatic esters of halofantrine to evaluate the role of several physicochemical properties on the interaction of the different compounds with plasma lipoproteins. Density gradient ultracentrifugation techniques were employed to determine drug association in triglyceride rich (TRL), low-density (LDL) and high-density lipoproteins (HDL), under both fasted and post-prandial conditions. Compound solubility in medium or long chain triglycerides was a useful indicator of the extent of drug-lipoprotein association, particularly for the triglyceride rich lipoproteins (chylomicrons and very low-density lipoproteins). This is likely a function of the compounds being solubilized within the apolar (triglyceride and cholesterol ester) lipid core. However, molecular size also played an important role in determining lipoprotein distribution, particularly for association with the more protein abundant lipoproteins, such as HDL. Lipoprotein association of Hf analogues containing longer unsaturated esters was best correlated with total lipoprotein surface area rather than with lipoprotein core lipid volumes.


A rare case of Haemophilus parainfluenzae septic knee following prolotherapy injections.
Prolotherapy injections are becoming increasingly popular as a non-surgical treatment option for many chronic musculoskeletal conditions. Proposed benefits include reduced pain, reduced joint laxity and increased tendon strength. While a number of studies report that prolotherapy reduces pain and increases function for many conditions, the academic evidence remains extremely weak. Here, we discuss a case of a complex intra-articular knee infection in a young, previously healthy, female following prolotherapy injections for management of a partial-thickness anterior cruciate ligament (ACL) tear. To the best of our knowledge, this is the first report of its kind describing a potential complication of intra-articular prolotherapy injections.


In Search of Calcifications : Histologic Analysis and Diagnostic Yield of Stereotactic Core Needle Breast Biopsies.
Stereotactic core needle biopsy (SCNB) is used in the diagnostic assessment of suspicious mammographic calcifications to rule out breast ductal carcinoma in situ (DCIS). With advances in imaging technology and increased biopsy tissue volume, the detection rate of calcifications and DCIS in SCNB is unclear. This retrospective study included 916 consecutive SCNBs for calcifications performed on 893 patients in a 2-year period. We found the cancer detection rate was 27.1% (DCIS, 23.7%; invasive, 3.4%). The detection rate for calcifications was 74.8% with the standard 3 levels. Additional leveling of calcification-negative cases further increased the detection of both calcifications (to 99.4% of cases) and DCIS (to 32.9% of cases). Lobular neoplasia (LN) was diagnosed in 41 cases. Twenty-five (61.0%) cases of LN were incidental without associated calcification. Of 32 invasive carcinomas detected on SCNB, 87.5% were T1a or less, and calcifications were associated with atypical ductal hyperplasia/DCIS or LCIS. The common benign lesions associated with calcifications were fibrocystic change (32.5%), fibroadenomatous change (30.2%), and columnar cell change and hyperplasia (8.2%). We determined the up-to-date detection rates of calcification and DCIS in SCNB, as well as the common benign and malignant breast lesions associated with calcifications. Additional levels significantly increase the detection rate when standard levels show only stromal or scant/absent calcifications. Lobular neoplasia is often an incidental finding in SCNB for calcifications. When calcifications are present with LN, they are commonly florid, pleomorphic LCIS, or with concurrent invasive carcinoma.


Delay in seeking induced abortion: a review and theoretical analysis.
Second-trimester abortion is known to be associated with increased morbidity and mortality rates. In this paper, possible reasons for delayed abortion are examined by: (1) reviewing the available literature to seek a synthesis of current findings, (2) discussing the findings within the theoretical context of decision-making under conflict which offers a conceptual framework for further understanding delay in seeking abortion, and (3) pointing to some methodologic problems in studies of delay in seeking abortion.


Allergy screening in asthma and allergic rhinitis. Which allergens should be used?
To detect atopy by a screening method employing skin prick testing with a limited number of allergens, the test results of 939 patients with allergic airways diseases were analysed. It was found that an allergen panel consisting of cat, timothy and house dust mite could detect 85% of atopic patients with asthma and/or rhinitis. For subgroups of patients the results were even more favourable. Thus 98% of atopic patients with seasonal allergic rhinitis were detected by an allergen panel consisting of timothy, birch and mugwort. It is concluded that screening methods using only three of four allergens could be used for detecting atopy in patients with airways diseases. The method should be most valuable for in vitro tests used in combination with standardized questionnaires.


Comparative analysis of membrane fouling mechanisms induced by operation modes of membrane bioreactors with aerobic granular sludge.
This experimental work investigated fouling characteristics induced by two different configurations of membrane bioreactor (MBR), which are submerged MBR and sidestream MBR with aerobic granular sludge. Submerged membrane bioreactor with granular sludge (Sub-MGSBR) ran the longest operation time 61 days with a steady overall TMP increase rate; Sidestream membrane bioreactor with granular sludge (SS-MGSBR) performed only 39 days, which exhibited Sub-MGSBR had more efficiently retarding membrane fouling. In both membrane bioreactors with flocculent sludge (MFSBRs) as a control, membrane foulants were compact, and cake resistance was the dominant fouling factor. In MGSBRs, however, pore blocking resistance turned out the key fouling factor. Especially in Sub-MGSBR, it went beyond 75%, and there was the most conglomeration of microorganisms of foulants with the highest porosity. Extracellular polymeric substances (EPS) content of foulants proved membrane fouling was hardly just for granules accumulation into cake but microorganisms' growth in MGSBRs.


A three-in-one nanoplatform with photo/chemodynamic activities combined with glutathione depletion for treating bacterial infections.
The misuse of antibiotics leading to bacterial multidrug resistance is responsible for severe infectious diseases and a significant cause of mortality worldwide, resulting in numerous human disasters. Photodynamic antibacterial therapy (PDAT) is a promising strategy against multiantibiotic-resistant bacteria, but its antibacterial activity is greatly limited by reduced glutathione (GSH) in bacteria. In this study, we constructed a nanoplatform through the formation of metal chelating complexes (FeP) between ferric and pyrophosphate ions, with subsequent adsorption of the photosensitizer ZnPc(COOH)8 (octa-carboxyl substituted zinc phthalocyanine) mediated by polylysine (PL) on the surface. The nanocomplexes FeP@PL:ZnPc(COOH)8 exhibited the capacity of GSH depletion and chemodynamic activity, which synergistically enhanced PDAT efficacy. FeP@PL:ZnPc(COOH)8 possessed the excellent antibacterial activity in vivo and in vitro, which might be attributed to the increased production of reactive oxygen species (ROS), reduced GSH level in bacteria, improved bacterial uptake, and enhanced destruction of the bacterial outer membrane. Moreover, FeP@PL:ZnPc(COOH)8 exhibited accelerated wound healing efficacy and the ability to recognize bacteria-infected wounds, rendering it an effective theranostic nanoplatform for bacterial infections. The construction strategy of nanocomplexes in this study holds theoretical and practical significance for high-efficiency synergistic photodynamic and chemodynamic antibacterial therapy.


Functional food packaging for reducing residual liquid food: Thermo-resistant edible super-hydrophobic coating from coffee and beeswax.
Edible super-hydrophobic coatings have attracted great attentions as they can avoid the waste of liquid foods, such as honey and milk, adhered to the inside of containers. However, the poor thermal stabilities of edible super-hydrophobic coatings restrict their applications. In this work, a thermo-resistant edible super-hydrophobic coating has been fabricated using beeswax and coffee, which are approved by U.S. Food and Drug Administration. This coating surface has the similar micro/nanoscale structure to that of the leaf surface. A variety of liquid foods can freely roll on this coating surface in spherical. This special wetting property effectively reduces the residue of liquid foods, when they are poured out of the containers. With the introduction of coffee lignin, the thermal stability and adhesive force of the coating increases significantly. The apparent contact angle of this coating can remain to be above 150° after a long-time heating and flushing. This thermo-resistant edible super-hydrophobic coating can solve the problem that original edible super-hydrophobic coating is not resistant to high temperature, and has a broad application prospect in the field of functional food packaging.


Characterization of the major Woronin body protein HexA of the human pathogenic mold Aspergillus fumigatus.
In filamentous fungi, the septal pore controls the exchange between neighbouring hyphal compartments. Woronin bodies are fungal-specific organelles that plug the pore in case of physical damage. The Hex protein is their major and essential component. Hex proteins of different size are predicted in the data base for pathogenic and non-pathogenic Aspergillus species. However, using specific monoclonal antibodies, we identified 2 dominant HexA protein species of 20 and 25kDa in A. fumigatus, A. terreus, A. nidulans, and A. oryzae. HexA and Woronin bodies were found in A. fumigatus hyphae, but also in resting conidia. Using monoclonal antibodies, a GFP-HexA fusion protein, and an RFP protein fused to the putative peroxisomal targeting sequence of HexA, we analyzed the spatial localization and dynamics of Woronin bodies in A. fumigatus as well as their formation from peroxisomes. In intact hyphae, some Woronin bodies were found in close proximity to the septal pore, while the majority was distributed in the cytoplasm. Septum-associated Woronin bodies show a minimal lateral movement, while the cytosolic Woronin bodies are highly dynamic. The distribution of Woronin bodies and their co-localization pattern with peroxisomes revealed no evidence that Woronin bodies arise predominantly at the apical tip of A. fumigatus hyphae. We found that Woronin bodies are able to plug septal pores of A. fumigatus in case of damage. Woronin bodies therefore contribute to the stress resistance and potentially also to the virulence of A. fumigatus, which renders them a potential target for future anti-fungal strategies.


A 5.6-Mb deletion in 15q14 in a boy with speech and language disorder, cleft palate, epilepsy, a ventricular septal defect, mental retardation and developmental delay.
We report a male patient with speech and language disorder, cleft palate, epilepsy, a ventricular septal defect, mental retardation and developmental delay. Characteristic facial features include low-set ears, a beak-like nose, a prominent nasal bridge, a long philtrum, a narrow forehead, a long face, a pointed chin and dental position abnormalities. Array-comparative genomic hybridization (CGH) analysis demonstrated the presence of a 5.6-Mb deletion in 15q14 (chromosome 15: 3,18,33,000-3,74,77,000bp). The present case provides the evidence that 15q14 deletion outside the region encompassing the CHRNA7 gene can cause generalized epilepsy, and a locus in 15q14 is associated with speech and language disorder.


Comparison of protein constituents between atria and ventricles from various vertebrates by two-dimensional gel electrophoresis.
1. Protein constituents of cardiac muscles of 23 species were examined by two-dimensional gel electrophoresis in order to find the difference in protein components between atria and ventricles. 2. Protein compositions of atria were similar to those of ventricles, however, differences were found in myosin and some other proteins in most species. 3. A major protein with molecular weights of 12,000-15,000 daltons was distributed only in atria from mammals. 4. The atrioventricular difference suggested that the ventricular tissue was more specialized in mammals than in birds, as compared with the atrial tissue.


Maternal HBsAg carriers and pregnancy outcomes: a retrospective cohort analysis of 85,190 pregnancies.
Nowadays, a positive HBV carrier status is common among pregnant women, especially in endemic areas (such as China), little is known about the impact of maternal HBV infection on the risk of adverse pregnancy outcomes. Pregnant women with HBV infection often develop obstetric complications, such as pregnancy-induced hypertension (PIH) syndrome, postpartum hemorrhage, and gestational diabetes mellitus (GDM), and their infants often exhibit neonatal complications. This study undertook a retrospective cohort analysis to explore the association of HBV carrier status with adverse pregnancy outcomes. A cohort of 85,190 women including 9699 HBsAg-positive and 73,076 HBsAg-negative pregnancies was retrospectively analyzed. It's found that HBsAg-positive pregnancies may result in higher risk of various maternal outcomes such as ICP (OR 3.4,95%CI 2.80 to 4.13), postpartum hemorrhage (OR 1.16,95%CI 1.00 to 1.34). Interestingly, there was a decreased risk of Preeclampsia (OR 0.91,95%CI 0.87 to 0.96), premature rupture of membrane (OR 0.91,95%CI 0.87 to 0.96) and gestational hypertension (OR 0.828,95%CI 0.701 to 0.978). And in vaginal delivery subgroup analysis, It's found that the HBsAg-positive group had a higher risk of placental abruption (OR, 1.44; 95% CI, 1.16-1.79). The present results suggest that compared with HBV positive pregnancies were more likely to be ICP and postpartum hemorrhage. HBV-positive pregnant women underwent vaginal delivery were more likely to have placental abruption and premature birth compared with HBV-negative women. Obstetricians should be aware of ICP, postpartum hemorrhage, placental abruption and premature birth in HBV-positive pregnant women.


A phase II study of mitomycin C, cisplatin and continuous infusion 5-fluorouracil (MCF) in the treatment of patients with carcinoma of unknown primary site.
Carcinoma of unknown primary site remains a common clinical diagnosis, accounting for between 5 and 10% of all cancer patients. Numerous combination chemotherapy regimens have been used in the management of carcinoma of unknown primary site, resulting in response rates of 0-48%. We present the results of a single centre phase II study of the use of the combination of mitomycin C (7 mg m(-2) on day 1 of cycles 1, 3 and 5) cisplatin (60 mg m(-2) on day 1) and continuous infusion 5-fluorouracil (300 mg m(-2) daily), MCF, delivered as a 21-day cycle, in patients with carcinoma of unknown primary site. Thirty-one patients with a diagnosis of carcinoma of unknown primary site were treated in Aberdeen Royal Infirmary between 1997 and 2001 with MCF. In total, 136 cycles of MCF were delivered (median of 5 cycles per patient). Toxicity was acceptable, with 19% grade 3 or 4 neutropenia, 16% grade 3 or 4 thrombocytopenia and 13% grade 3 or 4 nausea and vomiting. No cases of neutropenic sepsis were seen and there were no treatment-related deaths, however, six patients developed thrombotic complications. The overall response rate was 27% (CR 3%; PR 23%). Median time to progression was 3.4 months (95% CI 1.1-5.6 months) and median overall survival was 7.7 months (95% CI 5.7-9.8 months). Survival at 1 year was 28%, and at 2 years, 10%. MCF is a tolerable regimen with comparable toxicity, response rates and survival data to most platinum-based combination chemotherapy regimens in use for this devastating disease.


The cytokinesis-block micronucleus technique: a detailed description of the method and its application to genotoxicity studies in human populations.
The development of the cytokinesis-block (CB) technique has transformed the human-lymphocyte micronucleus assay (MN) into a reliable and precise method for assessing chromosome damage. Recent studies in our laboratory have confirmed that this method is a sensitive indicator of in vivo radiation exposure in (a) patients undergoing fractionated partial-body radiotherapy and (b) rodents exposed to uniform whole-body irradiation, thus supporting the application of the cytokinesis-block micronucleus (CBMN) assay for biological dosimetry. To further define the use of this assay in biomonitoring we performed extensive studies to determine the spontaneous level of MN in normal human populations and its relationship to various life-style factors. We have also developed a new variation to the CBMN assay that permits the conversion of excision-repairable lesions to MN within one cell-cycle using cytosine arabinoside. With this method the slope of the in vitro dose-response curves was increased by a factor of 1.8 for X-rays, 10.3 for ultraviolet (UV, 254 nm) radiation and approximately 40-fold for methylnitrosourea. Consequently the CBMN assay can now be used to measure not only whole chromosome loss or chromosome breaks but also excision-repair events. The versatility and simplicity of the CBMN assay together with new developments in automation should ensure its successful application in monitoring exposed populations as well as in identifying mutagen-sensitive individuals within a population.


Why they leave: Small town rural realities of northern physician turnover.
This study seeks to explore influential factors leading to physician turnover in designated Rural Northern Physician Group Agreement (RNPGA) communities in Northern Ontario, as well as physician's perceptions of the RNPGA contract and effects of the Northern Ontario School of Medicine (NOSM) on physician retention in these communities. Twelve qualitative semi-structured interviews were completed with rural physicians who had RNPGA contracts within the past 5 years but had left their practice community. Data collected from recorded interviews were analysed using a thematic analysis approach in order to identify common themes. A range of factors influencing physician's decisions to leave were identified including lack of partner career prospects, burnout and lack of opportunities and amenities. Common challenges were sometimes also perceived as rewards of rural practice. The concern of lack of flexibility of the RNPGA contract was identified, as well as a perceived lack of presence of NOSM graduates in RNPGA communities. A variety of factors influence physician turnover in RNPGA communities. These may be considered by communities hoping to inform recruitment and retention policy. Renewal of the RNPGA contract may require consideration for availability of part-time positions, increasing the number of physicians funded and incentivising physician wellness. NOSM may consider mandatory postgraduate programme placements in RNPGA communities and further development of infrastructure in these communities to improve learner, graduate and institutional engagement.


Provision of a personalized survivorship care plan and its impact on cancer-related health literacy among childhood cancer survivors in Hong Kong.
To evaluate the short-term effectiveness of a personalized survivorship care plan (SCP) in improving cancer-related literacy among childhood cancer survivors, and to identify characteristics of survivors who demonstrated minimal gain from the intervention. We recruited survivors diagnosed with cancer at ≤18 years old and were >2 years post treatment. The intervention included a personalized SCP and 30-minute health risk counseling. The participants' knowledge of their cancer diagnosis and potential treatment-related late effects (LEs) was assessed at baseline, immediately post intervention, and 1-3 months post intervention. Generalized estimating equation was used to test for changes in the awareness scores, with interacting terms (time*factor) added to identify differences in the score trajectory across clinically relevant subgroups. In total, 248 survivors completed the intervention (mean age: 19.4 [SD = 6.7] years; 54.1% male; 66.1% hematological malignancies), of whom 162 completed all assessments. There was significant increase in survivors' awareness of their cancer diagnoses (mean adjusted score: baseline 66.9, post intervention 86.3; p < .001) and potential LEs (baseline 30.9, post intervention 66.3; p < .001). The proportion of survivors who demonstrated awareness of their potential LEs increased from 9.7% to 54.3%. The interaction analysis showed that there was significantly less improvement in awareness among survivors of non-central nervous system (non-CNS) solid tumors (p = .032), lower socioeconomic status (p = .014), and parents of pediatric survivors (vs. adult survivors; p = .013). The provision of a personalized SCP showed preliminary effectiveness in improving survivors' understanding of their treatment-related LEs. Health counseling with SCP should be reinforced in vulnerable subgroups. Future work includes evaluating its long-term impact on lifestyle and health outcomes.


Human stem cells turned into detailed lab replicas of embryos.
Mock embryos created by multiple groups recapitulate developmental events beyond implantation.


Respiratory infections and lung function in an Australian Aboriginal community.
To investigate the association between serological evidence of past infections with common respiratory pathogens and lung function in members of an isolated community of Aborigines from tropical coastal north-western Australia. FEV(1) and FVC were assessed by dry bellows spirometer. Serum IgG titres to 11 common respiratory pathogens were assayed. Smoking history was assessed by questionnaire. Reciprocal positive IgG titres were taken as >or=10 for all pathogens with the exception of Legionella spp. (>or=40) and Burkholderia pseudomallei (>or=20). Linear regression analysis examined associations between titres and lung function after adjustment for age, height, gender and smoking, separately for adults (age > 17 years) and children. An increased total number of positive IgG titres was significantly associated with reduced FEV(1) (P = 0.01) and FEV(1)/FVC ratio (P = 0.01) suggesting the presence of airflow obstruction. This association was independent of age, gender, height, weight and smoking status. The burden of past respiratory infections may be an important determinant of airway function in this Aboriginal community.


Cannabis hyperemesis syndrome: A case report review of treatment.
Cannabis is the most common illegal substance used in the world. The psychoactive nature of cannabis is primarily due to delta-9-tetrahydrocannabinol (THC). Some research suggests that prolonged cannabinoid use increases its half-life and fat solubility in the body, slowing gastric emptying, leading towards feelings of nausea and vomiting. We describe a case where a 32 year old male has excessive nausea and vomiting after prolonged use of daily cannabis. A 32 year old Hispanic male with no significant past medical history presented to the emergency department with five days history of nausea and vomiting associated with abdominal pain. The vomitus is associated with diffuse abdominal pain and is alleviated by taking hot showers. Vital signs were normal and physical exam showed some abdominal tenderness. CBC and CMP were normal, and urine toxin screen revealed positivity for THC. The patient was admitted with possible diagnoses of cannabis induced hyperemesis. He was placed on Lorazepam and he took multiple hot showers, which improved his nausea. The next day he was discharged home in stable condition. Our patient reported the vomiting episodes were associated with the regular usage of cannabis over 19 years. One theory on the effectiveness of hot showers states that it may correct the disequilibrium of the thermoregulatory system in the hypothalamus. Another theory suggests that the concept of peripheral vasodilation and redistribution of blood flow from the splanchnic circulation to peripheral musculature helps decrease vomiting. This research gap shows that further studying of cannabis and its effects are still needed.


Closure of the calcified patent ductus in the elderly: avoidance of ductal clamps and shunts.
A technique for closure of the calcified ductus in the adult is described that avoids systemic heparinization or the use of shunts or bypass. An aortotomy is performed and the ductus is closed from within the aorta. Use of a running suture technique and closure from the inside should allow for a short clamp time, and therefore avoid the occurrence of paraplegia.


The Ku complex is modulated in response to viral infection and other cellular changes.
The complex of Ku with DNA is demonstrated to have multiple forms as assayed by gel retardation analysis. In CV1 cells this variation of complex can be modulated in response to viral infection with SV40. By Western blot analysis, a correlation can be made between modification of the complex formed on DNA in response to viral infection with variation of the 85 kDa subunit of Ku. Modification of the 85 kDa subunit can also be seen when cells are exposed to various extracellular stimuli including variation in serum levels, PMA and CaPO4.


Do all animals sleep?
Some animals never exhibit a state that meets the behavioral definition of sleep. Others suspend or greatly reduce 'sleep' behavior for many weeks during the postpartum period or during seasonal migrations without any consequent 'sleep debt.' Rats die from one form of sleep deprivation, but sleep loss has not been shown to cause death in well-controlled studies in other vertebrate species. Some marine mammal species do not show evidence for REM sleep, and convincing evidence for this state in reptiles, fish and insects is lacking. The enormous variation in the nature of rest and sleep states across the animal kingdom and within the mammalian class has important implications for understanding the evolution and functions of sleep.


Recalcitrant digital calcinosis cutis successfully treated with intralesional sodium thiosulfate under digital nerve blockade.
Dystrophic calcinosis cutis can be associated with severe pain, decreased mobility, increased risk of infection and significantly decreased quality of life. We report a case of recalcitrant calcinosis cutis on the background of eosinophilic fasciitis, which achieved rapid reduction in calcium deposits following a novel injecting protocol of intralesional sodium thiosulfate.


Liver metastases from gastric cancer represent systemic disease in comparison with those from colorectal cancer.
The aim of this retrospective study was to clarify the difference in behavior and outcome after initial hepatectomy between gastric cancer liver metastases (GCLM) and colorectal cancer liver metastases (CCLM). Data for patients undergoing curative hepatectomy for liver-only metastases from colorectal cancer (n = 193) and gastric cancer (n = 26) performed at single institution with the same criteria regarding the status of liver metastases were reviewed. Post-hepatectomy recurrence pattern, re-resection for recurrence, and three different endpoints were evaluated. There was no significant difference between the GCLM and the CCLM in the incidence of recurrence (69% vs. 63%, P = 0.553) and recurrence-free survival (median, 15.2 months vs. 16.5 months, P = 0.230) following initial hepatectomy for liver metastases. However, the GCLM had a higher frequency of systemic unresectable recurrences than the CCLM. Time to surgical failure (median, 15.2 months vs. 39.7 months, P = 0.006) and overall survival (median, 20.1 months vs. 66.2 months, P < 0.001) were significantly shorter in the GCLM than in the CCLM. GCLM shows more systemic and aggressive oncological behavior than CCLM after curative hepatectomy even when metastases are confined only to the liver at the time of initial hepatectomy.


[Use of biophysical techniques to evaluate the physiologic effects of injected hyaluronic acid].
To evaluate the effects of intradermal injection of native hyaluronic acid on physiology of aged skin using bioengineering methods. 10 female patients aged 44-69 were included. Study duration was 24 weeks. Each patient received 3 treatments (at week 0, 2 and 4) with native hyaluronic acid (Hyalsystem Merz Pharmaceuticals, Frankfurt/Main, Germany) and 4 examinations (week 0, 4, 12 and 24). Biophysical properties assessed were skin elasticity and surface roughness, as well as skin thickness and density. Skin elasticity increased while skin surface roughness was reduced. High frequency ultrasound revealed an increase of skin thickness, whereas skin density decreased during treatment and slightly increased above baseline at week 24. The evaluation of the effects of an intradermal injection of hyaluronic acid on aged skin showed an improvement of skin elasticity and skin surface roughness.


Elimination of CoASH interference from acetyl-CoA cycling assay by maleic anhydride.
A method for the removal of CoASH from tissue extracts by maleic anhydride is described. It eliminates CoASH interference in the acetyl-CoA cycling assay using phosphotransacetylase and citrate synthase. Maleyl-CoA thioether does not hydrolyze under the conditions of the assay and allows a reduction in the number of blank samples during acetyl-CoA determination. The levels of acetyl-CoA in whole rat brain, isolated synaptosomes, and mitochondria were found to be 61, 8.6, and 31.3 pmol/mg of protein, respectively.


Active and Repressed Chromatin Domains Exhibit Distinct Nucleosome Segregation during DNA Replication.
Chromatin domains and their associated structures must be faithfully inherited through cellular division to maintain cellular identity. However, accessing the localized strategies preserving chromatin domain inheritance, specifically the transfer of parental, pre-existing nucleosomes with their associated post-translational modifications (PTMs) during DNA replication, is challenging in living cells. We devised an inducible, proximity-dependent labeling system to irreversibly mark replication-dependent H3.1 and H3.2 histone-containing nucleosomes at desired loci in mouse embryonic stem cells so that their fate after DNA replication could be followed. Strikingly, repressed chromatin domains are preserved through local re-deposition of parental nucleosomes. In contrast, nucleosomes decorating active chromatin domains do not exhibit such preservation. Notably, altering cell fate leads to an adjustment of the positional inheritance of parental nucleosomes that reflects the corresponding changes in chromatin structure. These findings point to important mechanisms that contribute to parental nucleosome segregation to preserve cellular identity.


The genetic toxicology of Gene-Tox non-carcinogens.
The Gene-Tox Program has identified 61 chemicals that have been tested in chronic rodent carcinogenesis bioassays and found to be inactive. The genetic toxicology data of these 61 non-carcinogens is reviewed and summarized. A large proportion of these chemicals have been tested to a limited extent in genetic toxicity bioassays: 32 in 2 tests or less. Of the remaining 29 chemicals, 28% have been tested in 9 or more tests which encompass a range of genetic endpoints: gene mutation, chromosomal effects, other genetic endpoints, and cell transformation. The genetic toxicity of 12 chemicals with sufficient data is discussed in detail: benzoin, caffeine caprolactam, ethanol, halothane, hycanthone methanesulfonate, malathion, maleic hydrazide, methotrexate, 1-naphthylamine, 4-nitro-o-phenylenediamine, and p-phenylenediamine. A new technique for the evaluation of multiple test data, the "genetic activity profile", has been applied to 6 of these chemicals, allowing the qualitative and quantitative information to be compared collectively. In the evaluation of the genotoxicity effects of these non-carcinogens, a number of discrepancies between the results from genetic toxicity bioassays and chronic rodent bioassays have been uncovered. These discrepancies are discussed in light of current knowledge on the strengths and weaknesses of both genetic toxicity bioassays and chronic rodent bioassays.


Hepatic stellate cell/myofibroblast subpopulations in fibrotic human and rat livers.
Hepatic stellate cells (HSC) are commonly considered the precursor population of septal myofibroblasts (MF) in cirrhosis. We studied the distribution and expression profile of mesenchymal (myo)fibroblast-like populations in fibrotic and cirrhotic liver, in an attempt to elucidate their possible interrelationships. Fibrotic/cirrhotic livers (from 22 human explants and from two rat models: carbon tetrachloride intoxication, bile duct-ligation) were studied by means of immunohistochemistry (single and double immunostaining) with antibodies raised against desmin, alpha-smooth muscle actin (alpha SMA), glial fibrillary acidic protein (GFAP), neural-cell adhesion molecule (N-CAM), synaptophysin, neurotrophins, neurotrophin receptors and alpha B-crystallin (ABCRYS). Septal MF showed the same expression profile as portal MF, in human and rat, being alpha SMA/ABCRYS/brain-derived nerve growth factor/GFAP-expression, with additional N-CAM- and desmin-expression in rat portal/septal MF. Perisinusoidally located HSC stained with all tested markers, MF at the septal/parenchymal interface showed an expression profile, intermediate between the profiles of HSC and portal/septal MF. In advanced fibrosis and in cirrhosis, regardless of cause or species, three distinct mesenchymal (myo)fibroblast-like liver cell subpopulations can be discerned: portal/septal MF, interface MF and perisinusoidally located HSC. The fact that septal MF share more characteristics with portal MF than with HSC might suggest descent.


Developing a risk prediction model for breast cancer: a Statistical Utility to Determine Affinity of Neoplasm (SUDAN-CA Breast).
Breast cancer risk prediction models are widely used in clinical settings. Although most of the well-known models were designed based on data collected from western population, yet they have been utilized for surveillance purposes in many limited-resource countries. Given the genetic variations in risk factors that exist between different races, we therefore aimed to develop and validate a tool for breast cancer risk assessment among Sudanese women. Using cross-sectional design, 153 subjects were eligible to participate in our study. Data were collected from the only couple of tertiary centers in Sudan. They underwent multiple logistic regression using purposeful selection method to build the model. Various adjustments were made to determine significant predictors. Overall performance, calibration and discrimination were assessed by R 2, O/E ratio and c-statistic, respectively. SUDAN predictors of breast cancer were: age, menarche, family history, vegetables and fruits weekly servings, and type of cereals that traditional cuisine is made of. Both Nagelkerke R 2 (0.495) and O/E ratio (0.78) were good. c-statistic expressed the excellent discriminatory power of the model (0.864, p < 0.001, 95% CI 0.81-0.92). Our findings suggest that SUDAN provides a simple, efficient and well-calibrated tool to predict and classify women's lifetime risks of developing breast cancer. Input from our model could be deployed to guide utilization of the more advanced screening modalities in resource-limited settings to maximize cost effectiveness. Consequently, this might improve the stage at which the diagnosis is usually made.


Quantitative analysis of polycyclic aromatic hydrocarbons (PAHs) in water by surface-enhanced Raman spectroscopy (SERS) combined with Random Forest.
Polycyclic aromatic hydrocarbons (PAHs) have strong carcinogenicity, teratogenicity, mutagenicity and other adverse effects on human beings. They are one of the most dangerous pollutants, which have attracted great attention in the past decades. In this work, aiming at the actual problems that water environment is polluted and human health is threatened by PAHs, surface enhanced Raman spectroscopy (SERS) combined with Random Forest (RF) calibration models were used to quantitative analysis of phenanthrene and fluoranthene in water. Firstly, the SERS data was collected after samples mixed with Ag NPs, after 31 PAHs samples were prepared. Secondly, it was discussed how spectral preprocessing integration strategies affect on the prediction performance of the RF calibration models. And then, the effect of mutual information (MI) variable selection method on the performance of RF calibration models was explored. Finally, the RF calibration models were established for phenanthrene and fluoranthene. For the prediction set, a lowest mean relative error (MRE) and a largest determination coefficient (R2) were obtained. For quantitative analysis of phenanthrene, the final prediction performance results show that R2p is 0.9780, and MREp is 0.0369 based on the D1st-WT-RF calibration model. For fluoranthene, WT-D1st-MI-RF is a better calibration model, and corresponding to R2p and MREp are 0.9770 and 0.0694, respectively. Hence, a rapid and accurate quantitative method of PAHs is established for the real-time detection of water environmental pollution, which is intended to provide new ideas and methods for the quantitative analysis of PAHs in water.


Single-cell trajectory analysis reveals a CD9 positive state to contribute to exit from stem cell-like and embryonic diapause states and transit to drug-resistant states.
Bromo- and extra-terminal domain (BET) inhibitors (BETi) have been shown to decrease tumor growth in preclinical models and clinical trials. However, toxicity and rapid emergence of resistance have limited their clinical implementation. To identify state changes underlying acquisition of resistance to the JQ1 BETi, we reanalyzed single-cell RNAseq data from JQ1 sensitive and resistant SUM149 and SUM159 triple-negative breast cancer cell lines. Parental and JQ1-resistant SUM149 and SUM159 exhibited a stem cell-like and embryonic diapause (SCLED) cell state as well as a transitional cell state between the SCLED state that is present in both treatment naïve and JQ1 treated cells, and a number of JQ1 resistant cell states. A transitional cell state transcriptional signature but not a SCLED state transcriptional signature predicted worsened outcomes in basal-like breast cancer patients suggesting that transit from the SCLED state to drug-resistant states contributes to patient outcomes. Entry of SUM149 and SUM159 into the transitional cell state was characterized by elevated expression of the CD9 tetraspanin. Knockdown or inhibition of CD9-sensitized cells to multiple targeted and cytotoxic drugs in vitro. Importantly, CD9 knockdown or blockade sensitized SUM149 to JQ1 in vivo by trapping cells in the SCLED state and limiting transit to resistant cell states. Thus, CD9 appears to be critical for the transition from a SCLED state into treatment-resistant cell states and warrants exploration as a therapeutic target in basal-like breast cancer.


Evolutionary changes of an intestinal Lactobacillus reuteri during probiotic manufacture.
Probiotic bacteria are frequently used to treat intestinal diseases or to improve health; however, little is known about the evolutionary changes of these bacteria during probiotic manufacture and the bacterial ability to colonize the intestine. It has been observed that when bacteria adapt to a new environment, they lose some traits required to thrive in the original niche. In this study, a strain of Lactobacillus reuteri was isolated from mouse duodenum and subjected to 150 serial passes in milk to simulate the industrial propagation of probiotic bacteria. The strains adapted to milk outperformed their ancestor when grown in milk; we also showed evidence of reduced intestinal colonization of milk-adapted strains. Whole-genome sequencing showed that bacterial adaptation to milk selects mutants with altered metabolic functions.


Complex Trait Analyses of the Collaborative Cross: Tools and Databases.
The Collaborative cross (CC) is a powerful mouse resource for investigating complex genetic traits. Here we discuss various tools and techniques for gene mapping and identification using the CC. The data analyses procedures are illustrated with examples.


Internal signals cause large changes in food intake in one-way crossed intestines rats.
Fifteen pairs of parabiotic rats had either a surgical operation in which a 15 or 30 cm segment of upper small intestine was disconnected from the digestive tract of one rat in the pair and reconnected to the transected duodenum of its partner or had control surgery. Food eaten by one rat in the pair went to the rat's own stomach, traveled through 5 cm of its upper duodenum and then crossed into the isolated segment of the partner's small intestine. After traversing the 15 or 30 cm isolated segment, the remaining unabsorbed food crossed back into the lower duodenum of the rat that fed. Food eaten by the partner went through its own digestive tract, but bypassed the isolated segment of its own upper small intestine. The operation produced a large and sustained change in food intake of both rats in a pair. For the rats with 30 cm crossed segments, the rat that lost intestinal chyme into its partner ate 3.6 times as much food as did its partner for a period of many months. At sacrifice, the rats that ate more, weighed less and had less body fat. These large changes in food intake may be caused by internal changes associated with changes in the amount of food absorbed into each rat or by differential stimulation of the lower digestive tracts. The results clearly show that there is a major internal control mechanism for the amount of food eaten.


Flow cytometry deoxyribonucleic acid determinations and cytology of bladder washings: practical experience.
Flow cytometry deoxyribonucleic acid measurements of bladder washings, routine bladder irrigation cytology and cystoscopic results were compared in a prospective fashion during 33 months of clinical urology practice. Of the 204 patients (286 specimens) studied 74 had bladder tumors or a history of bladder tumors and 130 had other genitourinary pathological conditions, including hematuria, cystitis, benign prostatic hypertrophy or prostatic carcinoma. Flow cytometry and cytology agreed with the cystoscopic findings in 93 per cent of the cases, whereas flow cytometry agreed with cytology in 84.6 per cent. When combined, flow cytometry and cytology were negative in only 1 case when several papillomas or grade I papillary carcinomas were present on cystoscopy, yielding a diagnostic accuracy of 99 per cent. The false negative rates for flow cytometry and cytology were 4.3 and 5.2 per cent, respectively, with false positive rates of 4.2 and 3.1 per cent, respectively. As expected the specimens that were missed by cytology were low grade tumors and those missed by flow cytometry were usually ulcerated invasive tumors. We believe that flow cytometry is a valuable adjunct to cytology and cystoscopy in the diagnosis, management and followup of patients with known or suspected bladder cancer. In addition, criteria for the diagnosis of cancer are changed such that specimens with a deoxyribonucleic acid tail and a large amount of hyperdiploid cells without a distinct stem line are considered suspicious and indicative of bladder pathology but they are not synonymous with the presence of carcinoma.


Targeting RNA polymerase primary σ70 as a therapeutic strategy against methicillin-resistant Staphylococcus aureus by antisense peptide nucleic acid.
Methicillin-resistant Staphylococcus aureus (MRSA) causes threatening infection-related mortality worldwide. Currently, spread of multi-drug resistance (MDR) MRSA limits therapeutic options and requires new approaches to "druggable" target discovery, as well as development of novel MRSA-active antibiotics. RNA polymerase primary σ⁷⁰ (encoded by gene rpoD) is a highly conserved prokaryotic factor essential for transcription initiation in exponentially growing cells of diverse S. aureus, implying potential for antisense inhibition. By synthesizing a serial of cell penetrating peptide conjugated peptide nucleic acids (PPNAs) based on software predicted parameters and further design optimization, we identified a target sequence (234 to 243 nt) within rpoD mRNA conserved region 3.0 being more sensitive to antisense inhibition. A (KFF)₃K peptide conjugated 10-mer complementary PNA (PPNA2332) was developed for potent micromolar-range growth inhibitory effects against four pathogenic S. aureus strains with different resistance phenotypes, including clinical vancomycin-intermediate resistance S. aureus and MDR-MRSA isolates. PPNA2332 showed bacteriocidal antisense effect at 3.2 fold of MIC value against MRSA/VISA Mu50, and its sequence specificity was demonstrated in that PPNA with scrambled PNA sequence (Scr PPNA2332) exhibited no growth inhibitory effect at higher concentrations. Also, PPNA2332 specifically interferes with rpoD mRNA, inhibiting translation of its protein product σ⁷⁰ in a concentration-dependent manner. Full decay of mRNA and suppressed expression of σ⁷⁰ were observed for 40 µM or 12.5 µM PPNA2332 treatment, respectively, but not for 40 µM Scr PPNA2332 treatment in pure culture of MRSA/VISA Mu50 strain. PPNA2332 (≥1 µM) essentially cleared lethal MRSA/VISA Mu50 infection in epithelial cell cultures, and eliminated viable bacterial cells in a time- and concentration- dependent manner, without showing any apparent toxicity at 10 µM. The present result suggested that RNAP primary σ⁷⁰ is a very promising candidate target for developing novel antisense antibiotic to treat severe MRSA infections.


[Simultaneous treatment for benign prostate hyperplasia and its concomitant diseases].
To investigate the surgical treatment of benign prostate hyperplasia (BPH) and its concomitant diseases at the same time. One hundred and fourteen operations were performed for BPH patients, including transurethral resection/vapor of the prostate (TURP/TUVP), inguinal herniorrhaphy, internal urethrotomy, transurethral resection of bladder tumor (TURBt) or vesical litholapaxy, and the data were reviewed. The procedures were successful in all cases. A follow-up of 3 to 60 months found a good outcome of TURP. There was no recurrence in 30 cases of inguinal hernia and 39 cases of vesical calculus. Of the 25 cases of urethral stricture, 1 had an obvious hypotension during the operation and 4 needed urethral dilatation after operation. Six of the 20 cases of bladder tumor underwent a second TURBt due to the recurring tumor which was far from prostatic urethra. Inguinal hernia, urethral stricture, bladder tumor or vesical calculus can be treated simultaneously during TURP.


The postcode lottery lives on.
The postcode lottery was something that the National Institute for Health and Care Excellence, as it is now called, was originally set up to eradicate back in 1999.


A synergistic hydrothermal-deep eutectic solvents (DES) pretreatment for acquiring xylooligosaccharides and lignin nanoparticles from Eucommia ulmoides wood.
To achieve an effective deconstruction for preparation of xylooligosaccharides (XOS) and lignin nanoparticles (LNPs) from Eucommia ulmoides, a synergistic pretreatment was successfully developed. Herein, the hemicelluloses were preferentially dissociated in acetic acid-catalyzed hydrothermal pretreatment (HTP) for preparation of XOS, and the hydrothermally-pretreated substrate was then subjected to deep eutectic solvents (DES) delignification for fabrication of LNPs. Results showed that the optimal yield (33.88% based on xylan) of XOS is obtained under the given HTP condition (170 °C, 0.5 h). NMR characterization showed that the linkages of lignin were mainly composed of β-O-4, β-β, β-5, etc. Besides, GPC analysis showed that the molecular weight of DES lignin fractions was lower (1130-1200 g/mol) than those of corresponding parent lignin fractions (8500-9620 g/mol). Further TEM characterization indicated that the optimal LNPs fraction has a narrow size distribution and the corresponding size is ranged from 60 to 110 nm. In short, the synergistic pretreatment could be used as a green and cost-effective approach for the development of bio-based chemicals and biomaterials from Eucommia ulmoides biomass.


Field surgery of the eye and para-orbital tissues.
Ocular disease and injury remain a common occurrence in cattle. In many instances medical management is sufficient for resolution and amelioration of clinical signs. In selected cases, surgical intervention is required. Fortunately, field surgery remains a viable option for most cases of bovine ocular disease. While the surgical techniques are not new, thorough physical examination, proper preparation of the patient, appropriate perioperative management, and good surgical technique will assure the best results possible.


Ultrastructural analysis of midgut cells from Culex quinquefasciatus (Diptera: Culicidae) larvae resistant to Bacillus sphaericus.
The larvicidal action of the entomopathogen Bacillus sphaericus towards Culex quinquefasciatus is due to the binary (Bin) toxin present in crystals, which are produced during bacterial sporulation. The Bin toxin needs to recognize and bind specifically to a single class of receptors, named Cqm1, which are 60-kDa alpha-glucosidases attached to the apical membrane of midgut cells by a glycosylphosphatidylinositol anchor. C. quinquefasciatus resistance to B. sphaericus has been often associated with the absence of the alpha-glucosidase Cqm1 in larvae midgut microvilli. In this work, we aimed to investigate, at the ultrastructural level, the midgut cells from C. quinquefasciatus larvae whose resistance relies on the lack of the Cqm1 receptor. The morphological analysis showed that midgut columnar cells from the resistant larvae are characterized by a pronounced production of lipid inclusions, throughout the 4th instar. At the end of this stage, resistant larvae had an increased size and number of these inclusions in the midgut cells, while only a small number were observed in the cells from susceptible larvae. The morphological differences in the midgut cells of resistant larvae found in this work suggested that the lack of the Cqm1 receptor, which also has a physiological role as being an alpha-glucosidase, can be related to changes in the cell metabolism. The ultrastructural effects of Bin toxin on midgut epithelial cells from susceptible and resistant larvae were also investigated. The cytopathological alterations observed in susceptible larvae treated with a lethal concentration of toxin included breakdown of the endoplasmic reticulum, mitochondrial swelling, microvillar disruption and vacuolization. Some effects were observed in cells from resistant larvae, although those alterations did not lead to larval death, indicating that the receptor Cqm1 is essential to mediate the larvicidal action of the toxin. This is the first ultrastructural study to show differences in the cell morphology of resistant larvae and further investigation is needed to understand the impact of the lack of expression of midgut enzymes on the physiology of resistant insects.


Corrigendum to "Endovascular treatment of acute basilar artery occlusion caused by vertebral artery stump syndrome: A clinical analysis of 37 cases" [Heliyon 9 (4X), (March 2023) Article e14956].
[This corrects the article DOI: 10.1016/j.heliyon.2023.e14956.].


Relation between clinically measured tonic accommodation and refractive status in 6- to 14-year-old children.
Previous studies have shown a relation between refractive status and tonic accommodation (TA), with corrected hyperopes displaying a significantly higher TA than corrected myopes. TA measurements in those studies were made on adult subjects, under laboratory conditions with an infrared or laser optometer. The study reported here used a different measurement method and younger subjects. The TA of 113 (19 hyperopic, 61 emmetropic, 33 myopic) children, ages 6 to 14 years, was measured by a clinical method described earlier. Analysis of variance indicated significant (p less than 0.25) between-group mean differences similar to the adult-subject data cited above. Clinical implications of the data and the measurement method are discussed.


Pulmonary hypertension in infants with bronchopulmonary dysplasia.
Seventeen children with oxygen-dependent bronchopulmonary dysplasia, right ventricular hypertrophy, and Doppler echocardiographic evidence of pulmonary hypertension were studied by cardiac catheterization. Fifteen of these patients had pulmonary hypertension when placed in room air; six of these 15 patients were shown to have large systemic-to-pulmonary collateral vessels. The hemodynamic responses to oxygen and hydralazine were evaluated. Five patients developed normal pulmonary artery pressure while receiving supplemental oxygen and were not studied further. Of the remaining ten patients, the six patients with large, hemodynamically significant collateral vessels all had deleterious reactions to hydralazine. Two of the four patients without collateral pulmonary circulation responded to hydralazine with further reductions in mean pulmonary artery pressure. Five of the ten patients who had persistent pulmonary hypertension while receiving oxygen have died. Cardiac catheterization and angiography may provide important diagnostic, therapeutic, and prognostic information in patients with pulmonary hypertension complicating bronchopulmonary dysplasia.


KCND2: A prognostic biomarker and regulator of immune function in gastric cancer.
Gastric cancer is a highly heterogeneous disease, which makes it challenging to develop effective targeted therapies. Although the potassium voltage-gated channel subfamily D (KCND) channels, particularly KCND2 (also known as Kv4.2), have found evidence of involvement in the occurrence and development of various cancers, there are still some limitations in our understanding of KCND2's roles in gastric cancer. We analyzed the correlation between KCND2 expression and clinical features as well as immune infiltration using the Cancer Genome Atlas (TCGA) database. Functional assays of KCND2 were conducted using Cell counting Kit-8 (CCK8), clone formation assay and cell cycle analysis. Additionally, immunofluorescence, flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR) techniques were used to investigate tumor proliferation and immune cell infiltration at different levels of KCND2 expression in vivo. KCND2 was markedly elevated in gastric cancer and its expression appeared to link to different grades, T stages, and N stages. In addition, KCND2 was an independent predictor of prognosis, and its elevated levels in TCGA database revealed a more unfavorable prognosis for patients with gastric cancer. KCND2 strengthened the viability at the cellular level by boosting the proliferation of gastric cancer cells and reducing their death rate. Additionally, it also highlights that KCND2 the abilities of proliferating of gastric cancer cells by stimulating NF-κB both in cell and animal levels. In addition, the findings provided proof that in animal levels, KCND2 might regulate the immune system by associating with promoting M2 macrophages, which are known to play critical roles in cancer progression. Mechanistically, KCND2 was found to lead to the infiltration of M2 macrophages through activation of NF-κB, ultimately promoting the advancement of gastric cancer. Overall, these findings suggest that KCND2 is likely to be available as an underlying therapeutic target for gastric cancer.


Surgical treatment of otosclerosis using a unique stapes prosthesis without a hook.
During stapes surgery, the Teflon wire piston prosthesis is prone to postoperative 'slips' and subsequent necrosis and fracture of the long process of the incus. We invented and used a novel cup-shaped apatite prosthesis to reduce the incidence of necrosis of the long process of the incus and analysed the postoperative results. Thirty-one ears in 25 patients with otosclerosis who underwent stapes surgery with our apatite prosthesis were evaluated. The air conduction improved by 24.0 dB (the average) from pre- to post-operation. Additionally, 84.8% of patients achieved an air-bone gap of ≤10 dB for the 4-frequency measurements (p < .01). Our findings indicate that our new prosthesis was associated with a good postoperative prognosis in patients with otosclerosis. Our unique prosthesis yielded good outcomes for the treatment of otosclerosis even in the short term.


Anesthetic care of parturients with single ventricle physiology.
Understanding the management of the parturient with single ventricle physiology starts with knowledge of the lesion, the patient's current stage of surgical palliation, her current functional status, and the impact of pregnancy and labor on her cardiac physiology. A multidisciplinary team approach, described in this article, is crucial to a positive outcome.


Influence of aflatoxin B1 on seed germination, seedling growth, chlorophyll and carotenoid contents of mustard (brassica juncea L. var. pusa bold) seeds.
Five different concentrations (100, 250, 500, 1000 and 2000 μg/L of aflatoxin B1 were found to be inhibitory to seed germination and seedling growth (root and shoot lengths) of mustard seeds (variety Pusa bold). These also lowered the levels of chlorophyll and carotenoids in the emerging leaves during seedling growth. The inhibitory effect was correlated with the concentration of applied toxin.


Structural studies of UBXN2A and mortalin interaction and the putative role of silenced UBXN2A in preventing response to chemotherapy.
Overexpression of the oncoprotein mortalin in cancer cells and its protein partners enables mortalin to promote multiple oncogenic signaling pathways and effectively antagonize chemotherapy-induced cell death. A UBX-domain-containing protein, UBXN2A, acts as a potential mortalin inhibitor. This current study determines whether UBXN2A effectively binds to and occupies mortalin's binding pocket, resulting in a direct improvement in the tumor's sensitivity to chemotherapy. Molecular modeling of human mortalin's binding pocket and its binding to the SEP domain of UBXN2A followed by yeast two-hybrid and His-tag pull-down assays revealed that three amino acids (PRO442, ILE558, and LYS555) within the substrate-binding domain of mortalin are crucial for UBXN2A binding to mortalin. As revealed by chase experiments in the presence of cycloheximide, overexpression of UBXN2A seems to interfere with the mortalin-CHIP E3 ubiquitin ligase and consequently suppresses the C-terminus of the HSC70-interacting protein (CHIP)-mediated destabilization of p53, resulting in its stabilization in the cytoplasm and upregulation in the nucleus. Overexpression of UBXN2A causes a significant inhibition of cell proliferation and the migration of colon cancer cells. We silenced UBXN2A in the human osteosarcoma U2OS cell line, an enriched mortalin cancer cell, followed by a clinical dosage of the chemotherapeutic agent 5-fluorouracil (5-FU). The UBXN2A knockout U2OS cells revealed that UBXNA is essential for the cytotoxic effect achieved by 5-FU. UBXN2A overexpression markedly increased the apoptotic response of U2OS cells to the 5-FU. In addition, silencing of UBXN2A protein suppresses apoptosis enhanced by UBXN2A overexpression in U2OS. The knowledge gained from this study provides insights into the mechanistic role of UBXN2A as a potent mortalin inhibitor and as a potential chemotherapy sensitizer for clinical application.


What Constitutes Student Well-Being: A Scoping Review Of Students' Perspectives.
Student well-being has recently emerged as a critical educational agenda due to its wide-reaching benefits for students in performing better at school and later as adults. With the emergence of student well-being as a priority area in educational policy and practice, efforts to measure and monitor student well-being have increased, and so has the number of student well-being domains proposed. Presently, a lack of consensus exists about what domains are appropriate to investigate and understand student well-being, resulting in a fragmented body of work. This paper aims to clarify the construct of student well-being by summarising and mapping different conceptualisations, approaches used to measure, and domains that entail well-being. The search of multiple databases identified 33 studies published in academic journals between 1989 and 2020. There were four approaches to conceptualising student well-being found in the reviewed studies. They were: Hedonic, eudaimonic, integrative (i.e., combining both hedonic and eudaimonic), and others. Results identified eight overarching domains of student well-being: Positive emotion, (lack of) Negative emotion, Relationships, Engagement, Accomplishment, Purpose at school, Intrapersonal/Internal factors, and Contextual/External factors. Recommendations for further research are offered, including the need for more qualitative research on student well-being as perceived and experienced by students and for research to be conducted in a non-western context.


Treatment of sections of chick retina with acetylcholinesterase increases the enkephalin and substance P immunoreactivity.
Frozen sections 10 microns thick were cut from the retina of chicks which had been kept either in total darkness or in a well lit room. The sections were incubated with acetylcholinesterase before antibodies to [Leu] enkephalin, substance P or somatostatin were applied. Sections of bovine adrenals were treated similarly but they were developed only with antibodies to [Leu]enkephalin. There were low numbers of immunoreactive amacrine cells and processes when any of the three antibodies were used on sections of dark-adapted retinae. When the sections were treated with acetylcholinesterase, however, the enkephalin-like and substance P-like immunoreactivity was enhanced while there was no effect on somatostatin. Counts of immunofluorescent cells indicated that the numbers had increased to levels like those found in light-adapted retinae. The adrenal also showed an enhanced enkephalin-like immunoreaction after treatment with the enzyme. Incubation with buffer alone or with enzyme together with 10 mM acetylcholine abolished the reaction. Acetylcholinesterase treatment of sections from light-adapted retinae had no discernible effect on the already high immunoreaction found using any of the three antisera. It is concluded that the peptidase activity of acetylcholinesterase has the capacity to hydrolyze proteins of which some may be the precursor molecules for the enkephalins and substance P. Since the amacrine cells that contain the enkephalin-like and the substance P-like immunoreactivity were found to contain acetylcholinesterase, it is possible that the action found here in vitro represents a physiological function of the enzyme. The immunoreactivity on which there was no effect, somatostatin, does not co-exist with acetylcholinesterase. A second conclusion that may be drawn from these data is that the dark-adapted retinae lose immunoreactive peptide because of the rate of processing; the results suggest that there is adequate precursor molecule available to maintain "control" levels.


Prothrombin fragment 1+2 as a sensitive marker of intraventricular thrombus formation in a patient with dilated cardiomyopathy: comparison with echocardiography.
A 50-year-old man with dilated cardiomyopathy was admitted to our hospital due to heart failure symptoms. Although prothrombin fragment 1+2 (F1+2) was significantly elevated, there was no thrombus in the left ventricle by echocardiography. However, anticoagulation therapy was started because of a possibility of thrombus formation. On the 4th day, F1+2 was persistently elevated and echocardiography detected intraventricular thrombi. After surgical removal of thrombi, F1+2 level decreased rapidly. F1+2 elevation preceded echocardiographic detection of intraventricular thrombi. Therefore, when F1+2 is significantly elevated, echocardiography should be performed meticulously and repeatedly to detect a thrombus.


Novel modifications in the series of O-(2-phthalimidoethyl)-N-substituted thiocarbamates and their ring-opened congeners as non-nucleoside HIV-1 reverse transcriptase inhibitors.
The structure-activity relationships (SARs) of N-aryl-O-(2-phthalimidoethyl)thiocarbamates (C-TCs) and their imide ring-opened congeners (O-TCs) as non-nucleoside HIV-1 reverse transcriptase inhibitors were further investigated. The SAR strategy involved modifications of the N-phenyl ring followed by the hybridization of the most promising N-aryl and O-(2-phthalimidoethyl) substructures. The role of stereochemistry and tert-butyl substitution of the phthalimidoethyl moiety on activity was also investigated. Seventy-six analogues were prepared by parallel solution-phase synthesis. Twenty-two C-TCs displayed nanomolar activity against wild-type HIV-1 and a number of analogues were effective against the Y181C mutant. Compound 56 combined the highest activity so far identified against Y181C (EC(50)=1.3 microM) with good potency against the K103R mutant (EC(50)=4.8 microM). Docking simulations helped to rationalize the SARs.


Genic heterogeneity and genetic monitoring of mouse outbred stocks.
An outbred stock of Swiss:SE mice has been surveyed for genic heterogeneity at 12 loci, encoding biochemical polymorphisms in mice. Using horizontal starch-gel electrophoresis, 6 loci (Es-1, Es-2, Es-3, Es-5, Trf, Dip-1) revealed no genic heterogeneity within the total sample of 289 male mice examined. The other 6 loci (Mpi-1, Mup-1, Hbb, Gpi-1, Pgm-1, Ldr-1) each showed a 2-allelic variation within each of the 3 stock units (pavillions) involved. A pavillion effect on the observed genotype numbers was found for Pgm-1 and Gpi-1 (P less than 0.10). Inadequate genotyping may have occurred at Gpi-1 and Ldr-1, as suggested by a 'week effect' on the observed genotype numbers (P less than 0.05). For studying long-term genetic changes within outbred stocks, a routine monitoring procedure using biochemical polymorphisms is recommended.