Characterization of Two GAS1 Genes and Their Effects on Expression and Secretion of Heterologous Protein Xylanase B in Kluyveromyces lactis.
β-1,3-glucanosyltransferases play essential roles in cell wall biosynthesis in yeast. Kluyveromyces lactis has six putative β-1,3-glucanosyltransferase genes. KlGAS1-1 and KlGAS1-2 are homologs of Saccharomyces cerevisiae gene GAS1. RT-qPCR indicated the transcription level of KlGAS1-1 was significantly reduced while heterologous protein (thermostable xylanase B) secretion was enhanced during medium optimization. To evaluate if these two events were related, and to improve xylanase B secretion in K. lactis, we constructed KlGAS1-1 and KlGAS1-2 single deletion strains and double deletion strain, respectively. KlGAS1-1 gene deletion resulted in the highest xylanase B activity among the three mutants. Only the double deletion strain showed morphology similar to that of the GAS1 deletion mutant in S. cerevisiae. The two single deletion strains differed in terms of cell wall thickness and xylanase B secretion. Transcription levels of β-1,3-glucanosyltransferase genes and genes related to protein secretion and transport were assayed. The β-1,3-glucanosyltransferase genes displayed transcription complementation in the cell wall synthesis process. KlGAS1-1 and KlGAS1-2 affected transcription levels of secretion- and transport-related genes. Differences in protein secretion ratio among the three deletion strains were associated with changes of transcription levels of secretion- and transport-related genes. Our findings indicate that KlGAS1-1 deletion is an effective tool for enhancing industrial-scale heterologous protein secretion in K. lactis.


Corneal cells for regeneration.
In cases of corneal epithelial stem cell deficiency where ocular surface reconstruction is required, corneal epithelial replacement using a tissue engineering technique shows great potential. Autologous cultivated corneal epithelial stem cell sheets are the safest and most reliable forms of sheet we can use for such treatment; however, they are not useful for treating bilaterally affected ocular surface disorders. In order to treat such cases, we must choose either an allogeneic cultivated corneal epithelial sheet or an autologous cultivated oral mucosal epithelial sheet. If we use the former, the threat of immunological reaction must be dealt with. Therefore, it is imperative that we have a basic understanding of the immunological aspects of ocular surface reconstruction using allogeneic tissues. When using an autologous cultivated oral mucosal epithelial sheet, a basic understanding of ocular surface epithelial biology is required as the sheet is not exactly the same as corneal epithelium.


Decannulation and Functional Outcome After Tracheostomy in Patients with Severe Stroke (DECAST): A Prospective Observational Study.
Tracheostomy is performed in ventilated stroke patients affected by persisting severe dysphagia, reduced level of consciousness, or prolonged mechanical ventilation. The study aim was to determine the frequency and predictors of successful decannulation and long-term functional outcome in tracheotomized stroke patients. A prospective single-center observational study recruited ventilated patients with ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Follow-up visits were performed at hospital discharge, 3, and 12 months. Competing risk analyses were performed to identify predictors of decannulation. We included 53 ventilated stroke patients who had tracheostomy. One year after tracheostomy, 19 patients were decannulated (median [IQR] time to decannulation 74 [58-117] days), 13 patients were permanently cannulated, and 21 patients died without prior removal of the cannula. Independent predictors for decannulation in our cohort were patient age (HR 0.95 [95% CI: 0.92-0.99] per one year increase, p = 0.003) and absence of sepsis (HR 4.44 [95% CI: 1.33-14.80], p = 0.008). Compared to surviving patients without cannula removal, decannulated patients had an improved functional outcome after one year (median modified Rankin Scale score 4 vs. 5 [p < 0.001]; median Barthel index 35 vs. 5 [p < 0.001]). Decannulation was achieved in 59.4% of stroke patients surviving the first 12 months after tracheostomy and was associated with better functional outcome compared to patients without decannulation. Further prospective studies with larger sample sizes are needed to confirm our results.


Analyzing international events through the lens of statistical physics: The case of Ukraine.
During the last few years, statistical physics has received increasing attention as a framework for the analysis of real complex systems; yet, this is less clear in the case of international political events, partly due to the complexity in securing relevant quantitative data on them. Here, we analyze a detailed dataset of violent events that took place in Ukraine since January 2021 and analyze their temporal and spatial correlations through entropy and complexity metrics and functional networks. Results depict a complex scenario with events appearing in a non-random fashion but with eastern-most regions functionally disconnected from the remainder of the country-something opposing the widespread "two Ukraines" view. We further draw some lessons and venues for future analyses.


Regan variant alkaline phosphatase in gastrointestinal carcinoma.
A fast-moving alkaline phosphatase band on polyacrylamide gel electrophoresis has been found in 6 patients with carcinoma of the liver and gastrointestinal tract. This isoenzyme resembled the placental isoenzyme in its inhibition by L-phenylalanine, its resistance to L-homoarginine inhibition and its molecular weight. However, it differed from the placental and Regan isoenzymes in its sensitivity to L-leucine and ethylenediaminetetra-acetic acid, its lower retardation by neuraminidase, its electrophoretic mobility and its decreased heat stability. The latter two properties also distinguished it from the Nagao isoenzyme. It was identified as the Regan Variant. The Regan Variant has hitherto been reported largely in hepatocellular carcinoma. In the presented paper we report its appearance in the sera of patients who have neoplasms in a variety of primary sites in the gastrointestinal tract. It is emphasized that, while the presence of the Regan Variant in serum may be taken as evidence of carcinoma, no conclusions can be drawn as to the site of the disease.


Embryonic porcine liver as a source for transplantation: advantage of intact liver implants over isolated hepatoblasts in overcoming homeostatic inhibition by the quiescent host liver.
Cell therapy as an alternative to orthotopic liver transplantation represents a major challenge, since negligible proliferation of isolated hepatocytes occurs after transplantation because of the stringent homeostatic control displayed by the host liver. Thus, different modalities of liver injury as part of the pretransplant conditioning are a prerequisite for this approach. The major objective of the present study was to test whether xenotransplantation of pig fetal liver fragments, in which potential cell-cell and cell-stroma interactions are spared, might afford more robust growth and proliferation compared with isolated pig fetal hepatoblasts. After transplantation into SCID mice, fetal liver tissue fragments exhibited marked growth and proliferation, in the setting of a quiescent host liver, compared with isolated fetal hepatoblasts harvested at the same gestational age (embryonic day 28). The proliferative advantage of fetal pig liver fragments was clearly demonstrated by immunohistochemical and morphometric assays and was observed not only after implantation into the liver but also into extrahepatic sites, such as the spleen and the subrenal capsule. The presence of all types of nonparenchymal liver cells that is crucial for normal liver development and regeneration was demonstrated in the implants. Preservation of the three-dimensional structure in pig fetal liver fragments enables autonomous proliferation of transplanted hepatic cells in the setting of a quiescent host liver, without any requirement for liver injury in the pretransplant conditioning. The marked proliferation and functional maturation exhibited by the pig fetal liver fragments suggests that it could afford a preferable source for transplantation.


A receptor-like binding macromolecule for 1 alpha, 25-dihydroxycholecalciferol in cultured mouse bone cells.
1alpha, 25-Dihydroxycholecalciferol (1,25-(OH)2D3), the active form of vitamin D, like other steroid hormones, initiates its action by binding to cytoplasmic receptors in target cells. Although the 1,25-(OH)2D3 receptor has been well studied in intestine, little information beyond sucrose gradient analyses is presently available from mammalian bone. We, therefore, employed primary cultures of mouse calvarial cells to characterize the mammalian receptor in bone. A hypertonic molybdate-containing buffer was found to protect receptor binding. On hypertonic sucrose gradients, the 1,25-(OH)2-[3H]D3 binder sedimented at 3.2 S. Scatchard analysis of specific 1,25-(OH)2[3H]D3 binding sites at 0 degrees C yielded an apparent Kd of 0.26 nM and an Nmax of 75 fmol/mg of cytosol protein. Competitive binding experiments revealed the receptor to prefer 1,25-(OH)2D3 greater than 25-(OH)-D3 = 1 alpha-(OH)-D3 greater than 24R,25-(OH)2D3; vitamin D3, dihydrotachysterol, sex steroids, and glucocorticoids exhibited negligible binding. As shown in other systems, the receptor could be distinguished from a 25-(OH)-[3H]D3 binder which sedimented at approximately 6 S. In summary, cultured mouse calvarial cells possess a macromolecule with receptor-like properties. This system appears to be an ideal model for the investigation of 1,25-(OH)2D3 receptor binding and action in mammalian bone.


Transcriptomic recurrence score improves recurrence prediction for surgically treated patients with intermediate-risk clear cell kidney cancer.
Risk stratification of kidney cancer patients after nephrectomy may tailor surveillance intensity and selection for adjuvant therapy. Transcriptomic approaches are effective in predicting recurrence, but whether they add value to clinicopathologic models remains unclear. Data from patients with clear cell renal cell carcinoma (ccRCC) was downloaded from The Cancer Genome Atlas. Clinicopathologic variables were used to calculate SSIGN (stage, size, grade, and necrosis) scores. The 16 gene recurrence score (RS) signature was generated using RNA-seq data. Transcriptomic risk groups were calculated using the original thresholds. SSIGN groups were divided into low, intermediate, and high risk. Disease-free status was the primary endpoint assessed. SSIGN and RS were calculated for 428 patients with non-metastatic ccRCC. SSIGN low-, intermediate-, and high-risk groups demonstrated 2.7%, 15.2%, and 27.5%, 3-year recurrence risk, respectively. On multivariable analysis, the RS was associated with disease-free status (sub-distribution hazard ratio (sHR) 1.43 per 25 RS [95% CI (1.00-1.43)], p = 0.05). By risk groups, RS further risk stratified the SSIGN intermediate-risk group (sHR 2.22 [95% CI 1.10-4.50], p = 0.03). SSIGN intermediate-risk patients with low and high RS had a 3-year recurrence rate of 8.0% and 25.2%, respectively. Within this risk group, the area under the curve (AUC) at 3 years was 0.69 for SSIGN, 0.74 for RS, and 0.78 for their combination. Transcriptomic recurrence scores improve risk prediction even when controlling for clinicopathologic factors. Utility may be best suited for intermediate-risk patients who have heterogeneous outcomes and further refinement for clinical utility is warranted.


Vascular endothelial growth factor is involved in neoangiogenesis in Hirudo medicinalis (Annelida, Hirudinea).
Vascular endothelial growth factor (VEGF) is fundamental in vertebrates for correct development of blood vessels. However, there are only few data about the presence of VEGF in invertebrates. In this study the role of VEGF in neovessel formation is investigated in Hirudo medicinalis. The leech is able to respond to administration of human VEGF by formation of new vessels. The response of H. medicinalis to this growth factor is explained by the presence of two specific VEGF-like receptors (Flt-1/VEGFR-1 and Flk-1/VEGFR-2) as demonstrated by immunohistochemistry and biochemical analysis. The VEGF-like produced by this annelid following surgical stimulation determines not only blood vessel formation, proliferation of vascular endothelial cells but also an increase of cytoplasmic calcium levels. The administration of specific VEGF receptor antibodies can inhibit angiogenesis in leeches previously stimulated with VEGF.


Analysis of thyroid hormones in raw and treated waste water.
An analytical method for the quantification of thyroid hormones (3,5,3',5'-tetraiodo-L-thyronine, 3,3',5-triiodo-L-thyronine, 3,3',5'-triiodothyronine, 3,5-diiodothyronine, 3,3'-diiodothyronine) in different water matrices has been developed. The method, consisting of solid phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), was validated for tap and surface water as well as raw and treated waste water. The limits of quantifications (LOQs) were lowest in tap water, where they ranged from 1.1 to 13.3 ng L(-1), and highest in raw wastewater (10.5-84.9 ng L(-1)). Of the target analytes 3,5,3',5'-tetraiodo-L-thyronine (T(4)) could be quantified in the influent and effluent of a waste water treatment plant (WWTP) in Finland. The study showed that despite a relatively high removal rate during treatment (66%), part of the incoming T(4) will reach the aquatic environment and, due to the high endocrine activity of this compound, further studies are needed in order to assess its environmental fate and impact on natural ecosystems.


Fleeting Amyloid-like Forms of Rim4 Ensure Meiotic Fidelity.
Berchowitz et al. establish that transient amyloid-like forms of Rim4, a yeast RNA-binding protein with a predicted prion domain, translationally repress cyclin CLB3 in meiosis I, thereby ensuring homologous chromosome segregation. These findings suggest that prion domains might enable formation of tightly regulated amyloid-like effectors in diverse functional settings.


Olanzapine for the Treatment of Breakthrough Vomiting in Children Receiving Moderate and High Emetogenic Chemotherapy.
The efficacy of olanzapine (mean dose 0.09 mg/kg/dose) was evaluated in 31 children 2-18 years of age, for chemotherapy induced breakthrough vomiting. Among 42 chemotherapy blocks with emesis, complete and partial responses were observed in 34 (80.9%) and 6 (14.3%) blocks, respectively, while 1/31(2.4%) patient had refractory vomiting. Mild sedation and transient transaminitis were the observed side effects.


The interactions of ticlopidine and aspirin in normal subjects.
This trial was performed on 24 health volunteers in order to study the possible interactions between aspirin and ticlopidine. The results confirm the inhibitory activity of aspirin on collagen-induced aggregation and that of ticlopidine on ADP-induced aggregation. If aspirin does not modify the inhibitory effect of ticlopidine on ADP-induced aggregation, ticlopidine on the other hand potentiates the effect of aspirin on collagen-induced aggregation.


Neuroendocrine alterations in a high-dose, extended-access rat self-administration model of escalating cocaine use.
One approach for studying cocaine addiction has been to permit escalating patterns of self-administration (SA) by rats by prolonging daily drug availability. Rats provided long access (LgA) to high cocaine doses, but not rats provided shorter cocaine access (ShA), progressively escalate their cocaine intake and display characteristics of human addiction. The purpose of the present study was to investigate the effects of 14 days of ShA or LgA, high-dose cocaine SA on plasma corticosterone (CORT), prolactin (PRL), and related mRNAs. Acutely, cocaine SA increased plasma CORT and reduced plasma PRL levels. SA training produced circadian increases in CORT that appeared to occur in anticipation of cocaine availability. With repeated LgA, high-dose SA, the daily CORT area under the curve (AUC) progressively decreased, apparently due to tolerance to cocaine's effects on CORT and a reduction in basal CORT levels. In contrast, the daily CORT AUC in ShA rats increased across testing despite constant rates of SA. When measured 12 days after SA testing, pro-opioimelanocortin and glucocorticoid receptor mRNA levels in the anterior pituitary were lower in LgA rats than in ShA rats. The effects of SA on PRL remained constant across SA testing in LgA rats, but increased in duration in ShA rats. Anterior pituitary dopamine D2 receptor mRNA levels were lower in LgA rats than in ShA rats. These findings indicate that the transition to escalating patterns of SA may be associated with altered levels of hormones and gene expression within neuroendocrine systems. Such changes may underlie the onset of human addictive disease.


Effects of dietary supplementation of probiotic Shewanella colwelliana WA64, Shewanella olleyana WA65 on the innate immunity and disease resistance of abalone, Haliotis discus hannai Ino.
The effects of dietary administration of two probiotics, Shewanella colwelliana WA64 and Shewanella olleyana WA65, on the innate immunity of abalone (Haliotis discus hannai Ino), and survival of juvenile abalone challenged with Vibrio harveyi have been studied. Two groups of abalone were fed with three different diets: one control, and two diets supplemented with 10(9) cell g(-1) of probiotic WA64 (WA64 diet) and WA65 (WA65 diet) for up to four weeks. Results showed that abalone fed diets containing S. colwelliana WA64 and S. olleyana WA65 had led to an enhanced cellular and humoral immune response, notably higher haemocytes, respiratory burst activity, serum lysozyme activity and total protein levels were recorded after one week of probiotic administration. On the other hand, mortality after the challenges with V. harveyi in the group fed with control diet ranged from 77 to 80%, while mortality rates observed in the groups fed with diets supplemented with WA64 and WA65 ranged from 27 to 50% and 30-43%, respectively. The results demonstrated potential for S. colwelliana WA64 and S. olleyana WA65 to improve innate immunity and disease resistance in H. discus hannai.


AFM images of short oligonucleotides on a surface of supported lipid films.
Atomic force microscopy (AFM) was used to study the topography of lipid films on a gold support with immobilized 19 mer single stranded DNA (ssDNA) chemically modified by oleylamine and after hybridization with complementary DNA. The topography of various surfaces was analyzed, including alkanethiol layer chemisorbed on a gold support, lipid films formed on alkanethiol layer without and with immobilized single or double stranded DNA (dsDNA). The value of root means square roughness (RMS) for each surface was determined. RMS value for sBLM with immobilized ssDNA was 2.98 nm, while slightly higher value of 3.37 nm was typical for dsDNA. The analysis of AFM images revealed that both ssDNA and dsDNA form clusters. The clusters formed by ssDNA are not uniform, but that formed by dsDNA are almost of circular shape with diameter of 13.6+/-0.5 nm. Formation of the clusters could be consequence of lower hydration of lipids and DNA at an air. The water deficit and hence increased ion concentration probably facilitate the attraction between oligonucleotides.


Decrease expression of microRNA-20a promotes cancer cell proliferation and predicts poor survival of hepatocellular carcinoma.
Growing evidences indicate microRNAs play important roles in cancer development, progression, metastasis and may constitute robust biomarkers for cancer prognosis. The aim of this study was to identify the clinical and functional association of microRNA-20a (miR-20a) in hepatocellular carcinoma (HCC). MiR-20a was detected using Taqman real-time polymerase chain reaction. Kaplan-Meier and Cox proportional regression analyses were utilized to determine the association of miR-20a with survival of patients. The potential functions of miR-20a on proliferation were evaluated by proliferation and flow cytometry analysis. The direct target gene of miR-20a was also identified by luciferase reporter assays. MiR-20a was lower in primary HCC than normal liver, and were further decreased in those with post-liver transplantation (LT) HCC recurrence compared with those with non-recurrence (p = 0.001). Patients with lower miR-20a expression had significantly poorer recurrence-free survival (RFS, Log rank p < 0.001) and overall survival (OS, Log rank p < 0.001). Multivariate analysis revealed that lower miR-20a was an independent predictor of poor prognosis. MiR-20a restoration could suppress HepG2 and SMMC-7721 cells proliferation and induce cell cycle G1 arrest and apoptosis. Subsequent investigations revealed that miR-20a directly targeted myeloid cell leukemia sequence 1 (Mcl-1) and reduced the endogenous protein level of Mcl-1 in HCC cells. MiR-20a is decreased in HCCs and correlates with HCC recurrence and prognosis. Down-regulation of miR-20a increases the proliferation abilities of HCC cells. Our findings suggest miR-20a may represent a novel potential therapeutic target and biomarker for survival of HCC patients.


Modeling the cancer patient with genetically engineered mice: prediction of toxicity from molecule-targeted therapies.
Current trends foretell the use of cancer treatments customized to each patient. Genetic and molecular profiling of tumors and an increasing number of molecule-targeted therapies contribute to making this a reality. However, as targets of anticancer therapies become specific proteins or pathways, unanticipated side effects may emerge. In addition, the chronic use of these treatments may contribute to the development of degenerative toxicity not predicted by short-term clinical trials. Here we review and propose how genetically engineered mouse models can serve as valuable tools to predict targeted therapy toxicity, as well as to identify allelic variants that predispose individuals to side effects.


Unilateral cleft lip/palate children: the incidence of type 6 septal deformities in their parents.
The overall incidence of pathological septal deformity has been found to be significantly higher in unilateral cleft lip/palate (UCLP) children than in control children. Of the seven types of septal deformity according to Mladina's classification, type 6 has been found to be the most frequent in UCLP children, occurring in only 3.7% of the control children. To investigate the incidence of type 6 septal deformity in the parents of UCLP children. UCLP children (N=62) and their parents (N=91) were examined for type 6 septal deformities. Type 6 was found in at least one parent of a UCLP child in 58% of cases. However, it was not found in the parents whose UCLP children did not show a type 6 septal deformity. Type 6 septal deformity is almost a rule in children suffering from UCLP. Type 6 was not seen in the parents whose UCLP children did not show a type 6 septal deformity. There is a morphogenetic predisposition for the development of CLP in children whose parents carry a type 6 septal deformity.


Pulmonary vascular resistance and compliance in individuals with trisomy 18.
Individuals with trisomy 18 (T18) usually have congenital heart disease, often with pulmonary hypertension, which is associated with poor outcomes. This study aimed to explore the characteristics of pulmonary circulation including pulmonary vascular resistance (Rp) and compliance (Cp) among them. We retrospectively reviewed cardiac catheterization data in subjects with T18, trisomy 21 (T21), and without chromosomal anomaly (control group) who were referred due to heart failure associated with ventricular septal defect between 2000 and 2020. Pulmonary hemodynamic parameters including Rp and Cp were compared between these groups. We studied 20 subjects with T18, 88 subjects with T21, and 240 control subjects. There was no significant difference in age (T18: 4.6 [3.0-6. 9] vs. T21: 2.8 [1.9-4.0] vs. control: 2.9 [1.6-3.2] months, p = 0.06) and mean pulmonary arterial pressure (T18: 41 [33-49] vs. T21: 35 [30-41] vs. control: 36 [28-43] mmHg, p = 0.121) between the groups. The pulmonary to systemic blood flow ratio (Qp/Qs) (p = 0.983), Rp (p = 0.449), and Cp (p = 0.195) did not differ between T18 and control groups. However, Qp/Qs and Cp in T18 group were significantly greater than that in T21 group (T18: Qp/Qs: 3.4 [2.3-5.2] vs. T: 21 2.3 [1.7-3.7], p = 0.001. Cp: 3.5 [2.3-5.5] vs. 2.3 [1.6-3.1] mmHg/mL/m2 , p = 0.007), while Rp was identical between the groups (T18: 2.0 [1.6-3.3] vs. T21: 2.3 [1.7-3.7], p = 0.386). The pulmonary circulation in T18 subjects differed from that observed in T21 subjects, and identical to that observed in control subjects. Pulmonary hypertension is expected to be normalized after reasonable corrective surgery in T18 patients with congenital heart disease.


Assessing the Variations in Breast/Ovarian Cancer Risk for Chinese BRCA1/2 Carriers.
Cancer risks vary in different BRCA1/2 mutations. We are interested in identifying regions associated with elevated/reduced risks of breast/ovarian cancers in the Chinese population and comparing with previously reported Caucasian-based breast/ovarian cancer cluster regions (OCCR/BCCR). We also aim to characterize the distribution and estimate the cancer risks of different Chinese recurrent mutations. A total of 3,641 cancer-free women and 4,278 female cancer patients were included in the study. Germline BRCA1/2 status was detected with amplicon-based next-generation sequencing. We calculated the odds ratio (OR) of breast cancer and OR of ovarian cancer, and their ratio of the two ORs (ROR) for each region. ROR >1 indicated elevated odds of breast cancer and/or decreasing odds of ovarian cancer, and vice versa. The frequency, distribution, and penetrance of six known Chinese founder mutations were characterized, respectively. Haplotype analysis and age estimation were performed on the most prevalent founder mutation BRCA1: c.5470_5477del. A total of 729 subjects were detected with germline BRCA1/2 deleterious mutations. The putative Chinese OCCR/BCCR partially overlapped with Caucasian-based OCCR/BCCR and shared structural-functional characteristics. The six known Chinese founder mutations greatly vary in both distribution and penetrance. The two widely spread mutations are estimated to convey low penetrance, while the area-restricted founder mutations seemed to confer higher/complete penetrance. BRCA1: c.5470_5477del is estimated to have emerged ∼2,090 years ago (70 B.C.) during the Han dynasty. BRCA1/2 carriers with different genotypes have significantly different cancer risks. An optimal risk assessment should be mutation specific, rather than concerning a single figure.


The impact of e-cigarette and cigarette prices on e-cigarette and cigarette sales in California.
Although numerous studies have examined the impact of cigarette prices on cigarette demand, research examining the impact of e-cigarette and cigarette prices on e-cigarette demand is relatively limited. This study estimated the impact of e-cigarette and cigarette prices on e-cigarette and cigarette sales in California. Using the 2012-2017 Nielsen Retail Scanner Data, we constructed e-cigarette prices, cigarette prices, and per capita e-cigarette and cigarette sales by year, quarter, and Nielsen scantrack market in California. E-cigarettes were categorized as disposable or reusable. Separate fixed-effects models estimated the impact of e-cigarette and cigarette prices on per capita disposable e-cigarette, reusable e-cigarette, and cigarette sales controlling for year, quarter, market, and smoke-free air law coverage. Average prices were $5.86 per pack of 20 cigarettes, $9.80 per disposable e-cigarette, and $19.11 per reusable e-cigarette. When prices of disposable e-cigarettes, reusable e-cigarettes, and cigarettes increased by 1%, per capita sales of the products decreased by 0.37%, 0.20%, and 0.21% respectively. Cigarette prices were positively associated with per capita sales of reusable e-cigarettes, indicating reusable e-cigarettes are substitutes for cigarettes. Reusable e-cigarette prices were positively associated with per capita sales of disposable e-cigarettes, indicating disposable e-cigarettes are substitutes for reusable e-cigarettes. No statistically significant association was found between disposable/reusable e-cigarette prices and cigarette sales. Our results suggest that raising prices of disposable e-cigarettes, reusable e-cigarettes, and cigarettes such as via tobacco excise tax increases would result in reduced sales for the products. Policymakers should consider the substitution between e-cigarettes and cigarettes when designing tobacco control policies.


Hepatocellular Carcinoma in Transplantable Child-Pugh A Cirrhotics: Should Cost Affect Resection vs Transplantation?
There is no consensus regarding the optimal surgical treatment for transplantable hepatocellular carcinoma (HCC) patients with well-compensated cirrhosis. Our aim was to compare outcomes between Child-Pugh A (CPA) cirrhotics who underwent liver resection or transplantation for HCC. Clinicopathologic data were retrospectively collected for all surgically treated HCC patients between 7/1992 and 12/2015. Disease-free survival (DFS) and overall survival (OS) were calculated from the time of operation or diagnosis (intention-to-treat analysis including patients removed from the transplant list). The average overall cost including pre-operative and post-operative procedures was calculated for each group. Of the 513 surgically treated HCC patients, 184 had CPA cirrhosis and fulfilled the Milan criteria (MC). Of those, 95 (52%) were resected and 89 (48%) were transplanted. Twenty-two patients were removed from the transplant list. Transplanted patients were younger (p < 0.001), had a higher MELD score (p < 0.001) and a higher frequency of hepatitis C (p < 0.001). Length of stay and postoperative complication rates were similar between groups. DFS was longer for transplanted patients (3-, 5-, and 10-year DFS rates 48, 44, 31% vs 96, 94, 94%, respectively, p < 0.001). OS was similar between groups (3-, 5-, and 10-year OS rates 76, 62, 41% vs 82, 77, 53%, respectively, p = 0.07). Only size of greatest lesion and T stage were independent predictors of OS. The cost was much higher for the transplant group, even when accounting for the treatment of recurrences ($37,391 vs $137,996). Since OS is similar between CPA cirrhotics within the MC undergoing resection or transplantation for HCC, but cost is significantly higher for transplantation. Resection should be considered for first-line treatment.


Thermage: the nonablative radiofrequency for rejuvenation.
Thermage is a noninvasive nonablative device that uses monopolar radiofrequency energy to bulk heat underlying skin while protecting the epidermis to produce skin tightening. It is used for the treatment of rhytids on the face including the periorbital region and lower face, and more recently, for off-face applications. Studies have shown that it can impart mild tightening of periorbital mid, and lower facial laxity. Other radiofrequency devices have also shown objective improvements in cellulite of the buttocks and thigh regions. Thermage is an efficacious and safe nonsurgical alternative for treating mild skin laxity.


Improved cardiac function after catheter ablation in a patient with type B Wolff-Parkinson-White syndrome with an old myocardial infarction.
A 67-year-old man was admitted to hospital for the treatment of exertional dyspnea. He suffered from congestive heart failure due to an old inferior myocardial infarction with type B Wolff-Parkinson-White syndrome. Asynchronous wall motion caused by pre-excitation through a right-side bypass tract caused his cardiac function to deteriorate. Catheter ablation of the bypass tract increased the ejection fraction, and improved his symptoms, prior to surgical revascularization.


Tumoral calcinosis: clinical and metabolic response to phosphorus deprivation.
Two patients with extensive tumoral calcinosis were treated with aluminium hydroxide. Initial metabolic studies showed positive calcium and phosphorus balances which became negative with aluminium hydroxide treatment. One subject, who had renal impairment, developed transient hypercalcaemia, parathyroid suppression, low levels of 1,25-dihydroxyvitamin D and calcium malabsorption during treatment with aluminium hydroxide. The second patient developed calcium malabsorption due to vitamin D deficiency. When she was replete with vitamin D there were supranormal levels of 1,25-(OH)2D in the serum and enhanced calcium absorption during treatment with aluminium hydroxide. Both subjects developed hypercalciuria and there was dissolution of many of the calcific tumours. The patient with renal impairment accumulated aluminium in the bone.


Spine Metastases in Immunocompromised Mice after Intracardiac Injection of MDA-MB-231-SCP2 Breast Cancer Cells.
Breast cancer cells frequently metastasize to bone, where their interaction with bone remodeling cell types enhances osteolytic bone destruction. Importantly, however, whereas skeletal analyses of xenograft models are usually restricted to hindlimb bones, human skeletal metastases are far more frequent in the spine, where trabecular bone mass is higher compared to femur or tibia. Here, we addressed whether breast cancer cells injected into immunocompromised mice metastasize to the spine and if this process is influenced by the amount of trabecular bone. We also took advantage of mice carrying the Col1a1-Krm2 transgene, which display severe osteoporosis. After crossing this transgene into the immunocompromised NSG background we injected MDA-MB-231-SCP2 breast cancer cells and analyzed their distribution three weeks thereafter. We identified more tumor cells and clusters of different size in spine sections than in femora, which allowed influences on bone remodeling cell types to be analyzed by comparing tumor-free to tumor-burdened areas. Unexpectedly, the Col1a1-Krm2 transgene did not affect spreading and metastatic outgrowth of MDA-MB-231-SCP2 cells, suggesting that bone tumor interactions are more relevant at later stages of metastatic progression.


Open field locomotor activity and anxiety-related behaviors in mucopolysaccharidosis type IIIA mice.
Mucopolysaccharidosis (MPS) IIIA, or Sanfilippo syndrome, is a lysosomal storage disorder characterized by severe and progressive neuropathology. Following an asymptomatic period, patients may present with sleep disturbances, cognitive decline, aggressive tendencies and hyperactivity. A naturally-occurring mouse model of MPS IIIA also exhibits many of these behavioral features and has been recently back-crossed onto a C57BL/6 genetic background. To more thoroughly characterize the behavioral phenotype of congenic MPS IIIA mice, we assessed exploratory activity and unconditioned anxiety-related behavior in the elevated plus maze (EPM) and open field locomotor activity. Although MPS IIIA male mice were less active in the EPM at 18 and 20 weeks of age, they were more likely to explore the open arms than their normal counter-parts suggesting reduced anxiety. Repeated EPM testing reduced exploration of the open arms in MPS IIIA mice. In the open field test, significant reductions in activity were evident in naïve-tested male MPS IIIA mice from 10 weeks of age. Female normal and MPS IIIA mice displayed similar exploratory activity in the open field test. These differences in anxiety and locomotor activity will allow us to evaluate the efficacy of therapeutic regimes for MPS IIIA as a forerunner to developing safe and effective therapies for Sanfilippo patients.


Chimeric Antigen Receptor T-Cell (CAR T-Cell) Therapy for Primary and Secondary Central Nervous System Lymphoma: A Systematic Review of Literature.
Relapsed/refractory central nervous system (CNS) lymphoma, whether primary or secondary, is associated with poor prognosis with currently available treatment modalities, including high-dose chemotherapy-autologous stem cell transplantation. The pivotal ZUMA-1 and JULIET trials that led to FDA approval of Axicabtagene ciloleucel and Tisagenlecleucel for relapsed refractory large cell lymphoma excluded patients with CNS involvement due to concerns of increased toxicity. However, TRANSCEND study for Lisocabtagene maraleucel in relapsed refractory large cell lymphoma allowed patients with CNS involvement and reported manageable CNS toxicities in these patients. In the real-world experience, chimeric antigen receptor T-cell (CAR T) therapy has been deemed safe and effective for these patients with poor prognosis. In this systematic review, we analyzed available literature to evaluate the role of CAR T-cell therapy in both primary and secondary CNS lymphoma using Embase, Cochrane, and PubMed databases. A total of 14 studies, including 8 retrospective analyses and 6 prospective studies/clinical trials, were included in the qualitative synthesis to study the safety and efficacy of CAR T. Based on our analysis, CAR T-cell therapy appears to be associated with reasonable efficacy and a manageable safety for primary and secondary CNS lymphoma.


[Psychosomatic aspects in otorhinolaryngology-historical milestones].
This investigation examined the development of psychosomatics in the field of otolaryngology in Germany using the examples of psychogenic deafness and chronic tinnitus by means of literature research. The focus of the study was on the period 1948-2022. A literature search was carried out in the PubMed database from 1948 and antiquarian ENT textbooks were evaluated. The search terms used were "ENT and psychosomatics," "tinnitus," "retraining therapy," "analytical psychology," "behavioral therapy," and "sensory systems." Psychosomatic phenomena were mentioned in the treatment of nasal diseases and ear ailments in writings of Byzantine and medieval medicine. Even older are references to tinnitus in ancient Egyptian and Indian scripts. From the nineteenth to the mid-twentieth century, psychological abnormalities in ENT symptoms were assigned to the term hysteria. From the middle of the twentieth century, a paradigm shift in the assessment of psychosomatic disorders in otolaryngology became apparent. In the 1950s, a broad psychosomatic discussion was opened in individual lectures and book contributions on mental abnormalities in ENT diseases. With the implementation of the Psychosomatics Working Group of the German Society of Otorhinolaryngology, Head and Neck Surgery, psychosomatics in the field of ENT received the framework for scientific and clinical activity at the turn of the millennium. Psychosomatics is scientifically represented and part of the continuing education regulations for otolaryngology in Germany and at European level. It shows high standards in research, qualification of otolaryngologists, and patient care. As of 2022, psychosomatics in otolaryngology has been steadily developing for over 70 years. The standards achieved are to be further expanded and research on cognition, affectivity, and sensory analogies intensified.


Changes and socioeconomic factors associated with attitudes towards domestic violence among Vietnamese women aged 15-49: findings from the Multiple Indicator Cluster Surveys, 2006-2011.
Understanding factors associated with domestic violence-supportive attitudes among Vietnamese women is important for designing effective policies to prevent this behavior. Previous studies have largely overlooked risk factors associated with domestic violence-supportive attitudes by women in Vietnam. This paper explores and identifies socioeconomic factors that contribute to domestic violence-supportive attitudes among Vietnamese women using data from the Multiple Indicator Cluster Surveys (MICS). Secondary data from two cross-sectional studies (MICS 3, 2006, and MICS 4, 2011) with representative samples (9,471 and 11,663 women, respectively) in Vietnam were analyzed. The prevalence of supportive attitudes toward domestic violence and associations with age, residence region, area, education level, household wealth index, ethnicity, and marital status were estimated using descriptive statistics and multivariate Poisson models, giving estimates of relative risk. Overall, the prevalence of acceptance of domestic violence declined between 2006 and 2011 in Vietnam (65.1% vs. 36.1%). Socioeconomic factors associated with women's condoning of domestic violence were age, wealth, education level, and living area. In particular, younger age and low educational attainment were key factors associated with violence-supportive attitudes, and these associations have become stronger over time. Higher educational attainment in women is an important predictor of women's attitudes toward domestic violence. To date, Doi Moi and the Vietnamese government's commitment to the Millennium Development Goals may have positively contributed to lowering the acceptance of domestic violence. Tailored interventions that focus on education will be important in further changing attitudes toward domestic violence.


Biomechanical femoral neck fracture experiments--a narrative review.
Orthopaedic implants can be introduced in clinical practice if equivalency to an already approved implant can be demonstrated. A preclinical laboratory test can in theory provide the required evidence. Due to the lack of consensus on the optimum design of biomechanical experiments, setups vary considerably. This review aims to make femoral neck fracture models more accessible for evaluation to orthopaedic surgeons without any particular background in biomechanics. Additionally, the clinical relevance of the different setups is discussed. This is a narrative review based on a non-systematic search in PubMed, Scopus and Cochrane. Biomechanical femoral neck fracture experiments should aim at optimizing the recreation of the in vivo situation. The bone quality of the experimental femurs should resemble the hip fracture population, hence cadaveric bones should be preferred to the available synthetic replica. The fracture geometry must be carefully selected to avoid bias. The load applied to the specimen should result in forces within the range of in vivo measured values and the magnitude should be related to the actual weight of the donor. A well designed biomechanical experiment can prevent harmful devices from being introduced in clinical practice, however, positive results can never exclude the necessity of subsequent clinical studies.


Cardia carcinomas of intestinal type are associated with histologic changes in the gastric mucosa.
BACKGROUND: Previous studies of Japanese patients showed that distal gastric carcinomas (of the corpus or the antrum) were associated with histologic changes in the non-neoplastic gastric mucosa. These changes (cells with ciliated metaplasia, with large and small mucus-negative vacuoles, intramucosal glandular cysts, and extensive intestinal metaplasia) were often found in carcinomas of intestinal type.METHODS: In the present work, similar mucosal changes were searched for in surgical specimens carrying a carcinoma of the cardia. A total of 12 079 archival histologic sections, corresponding to 563 gastrectomies performed in Japanese patients, were analyzed.RESULTS: Of the specimens with cardia carcinoma of intestinal type seen in Tokyo ( n = 169) and in Matsuyama ( n = 168), 53.3% and 63.1% contained intramucosal cysts; 39.6% and 51.8%, ciliated metaplastic cells; 34.9% and 30.4%, large vacuolated cells; and 7.7% and 11.9%, small vacuolated cells; and 69.8% and 68.5% had high intestinal metaplasia scores, respectively. These percentages were significantly higher than those for cardia carcinomas of diffuse type in Tokyo ( n = 153) and in Matsuyama ( n = 73), in which 30.7% and 34.2% of the specimens had intramucosal cysts; 17.6% and 17.8%, ciliated metaplastic cells; 14.4% and 9.6%, large vacuolated cells; and 3.9% and 4.1%, small vacuolated cells; and 43.1% and 39.7% had high intestinal metaplasia scores, respectively.CONCLUSION: Thus, similarly to carcinomas of the corpus or the antrum, cardia carcinomas of intestinal type are associated with histologic changes in the gastric mucosa. The possibility that these changes are evoked by environmental factors was entertained.


Architecture and assembly of the Gram-positive cell wall.
The bacterial cell wall is a mesh polymer of peptidoglycan--linear glycan strands cross-linked by flexible peptides--that determines cell shape and provides physical protection. While the glycan strands in thin 'Gram-negative' peptidoglycan are known to run circumferentially around the cell, the architecture of the thicker 'Gram-positive' form remains unclear. Using electron cryotomography, here we show that Bacillus subtilis peptidoglycan is a uniformly dense layer with a textured surface. We further show it rips circumferentially, curls and thickens at free edges, and extends longitudinally when denatured. Molecular dynamics simulations show that only atomic models based on the circumferential topology recapitulate the observed curling and thickening, in support of an 'inside-to-outside' assembly process. We conclude that instead of being perpendicular to the cell surface or wrapped in coiled cables (two alternative models), the glycan strands in Gram-positive cell walls run circumferentially around the cell just as they do in Gram-negative cells. Together with providing insights into the architecture of the ultimate determinant of cell shape, this study is important because Gram-positive peptidoglycan is an antibiotic target crucial to the viability of several important rod-shaped pathogens including Bacillus anthracis, Listeria monocytogenes, and Clostridium difficile.


Induction of structural chromosome aberrations and sister chromatid exchanges in human lymphocytes in vitro by aristolochic acid.
The medicinal use of Aristolochia clematitis has been known for some time. The main active agent of this medicinal plant is aristolochic acid, a nitrophenanthrenecarbonic acid. Very recently, however, the Federal Health Office withdrew the licence for all drugs containing aristolochic acid, because of the well-founded suspicion that aristolochic acid may be a very potent carcinogen. We investigated the induction of structural chromosome aberrations and sister chromatid exchanges (SCEs) by aristolochic acid in human lymphocytes in vitro. Cells were treated with the agent tested throughout culture time and during the G0 phase of the cell cycle. We tested concentrations over a range of 1 to 20 micrograms/ml. Both treatment conditions resulted in an increased aberration frequency. The induction of gaps and breaks as well as the induction of SCEs showed a dose-dependent increase. The number of SCEs per metaphase was enhanced by a factor of 2 to 3. If conventional cytogenetic methods had been applied in time, one would have recognized the mutagenic risk of aristolochic acid earlier.


Alpha-pinene modulates inflammatory response and protects against brain ischemia via inducible nitric oxide synthase-nuclear factor-kappa B-cyclooxygenase-2 pathway.
Cerebral ischemia-reperfusion leads to brain tissue injury. Inflammation and apoptosis play pivotal roles in the pathology. α-Pinene is an organic compound of many aromatic plants and is known as a potent agent to possess antioxidant, and anti-inflammatory properties. Here, we sought to identify the anti-inflammatory and anti-apoptosis mechanism by which α-Pinene improves brain ischemia injury. Male Wistar rats underwent MCAO surgery for 1 h and different doses of alpha-pinene (25, 50, and 100 mg/kg) were intraperitoneally injected immediately after reperfusion to test this hypothesis. IV, NDS, gene and protein expression of inducible nitric oxide synthase (iNOS), cyclogenase-2 (COX-2), nuclear factor kappa B (NF-κB) p65, and caspase-3 were assessed 24 h after reperfusion. Results demonstrated that NF-κB p65, iNOS, and COX-2 gene and protein expression increased in the hippocampus, cortex, and striatum after 24 h of reperfusion, and alpha-pinene significantly inhibited NF-kB p65, iNOS, and COX-2 expression. Also, alpha-pinene significantly reduced the ischemia/reperfusion-induced caspase-3 activation in CA1 area of hippocampus. Results showed that alpha-pinene protects the cerebral against ischemic damage caused by MCAO, and this effect may be through the regulating iNOS -NF-kappa B- COX-2 and caspase-3 inflammatory and apoptotic pathways.


Seated postural organization during bilateral upper limb symmetric and asymmetric pushing tasks in individuals after stroke compared to healthy controls.
Asymmetric weight distribution in sitting has been reported in people after stroke. However, postural strategies used during bilateral symmetric and asymmetric movements performed while seated require more evidence to inform rehabilitation strategies. How do symmetric and asymmetric effort levels exerted during upper limb (UL) pushing movements affect seated postural organization parameters (weight bearing (WB) between hands and hemibody sides, and forward trunk displacement) of stroke compared to healthy individuals? How are these parameters associated? Using an instrumented exerciser, 19 post-stroke individuals were compared to 17 healthy individuals when executing four bilateral UL pushing movements in a seated position: symmetrical pushing at 30 % and 15 % of their maximal force (MF) and asymmetrical pushing with 15 % of their MF for one UL vs. 30 % of the MF for the other UL and vice versa. Anterior and vertical forces of the push, as well as vertical forces under each foot and thigh were compared between groups, sides and conditions. Forward trunk displacement was compared between groups and conditions. Correlations were used to determine the association between trunk displacement, hands and hemibody vertical forces. Increasing pushing effort caused increased WB on thighs and decreased on WB on feet during the 30 % MF symmetric condition compared to the 15 % MF and asymmetric conditions (p < 0.05). Individuals post-stroke showed WB asymmetry and greater forward trunk displacement when compared to healthy persons (p < 0.05). For both groups, hemibody WB and trunk displacement showed moderate association (r > - 0.5) in the asymmetric condition executed with more resistance on the paretic or non-dominant hand. Individuals post-stroke presented a similar WB pattern to that of healthy persons during symmetric and asymmetric bilateral UL movements with greater forward trunk displacement and asymmetry. Increased effort and asymmetric force between both UL had effects on seated postural organization strategy.


Workplace violence and burnout among Chinese nurses during the COVID-19 pandemic: does the sense of coherence mediate the relationship?
Workplace violence has always been a critical issue worldwide before and after the COVID-19 pandemic, which can lead to burnout and turnover. In addition, the burnout and mental stress of nurses during the COVID-19 period have been widely described. To our knowledge, no studies have examined the mediating effect of the sense of coherence on the relationship between workplace violence and burnout among Chinese nurses over time. Therefore, this study aimed to explore the relationship between workplace violence and burnout among Chinese nurses and how the sense of coherence mediates the association. Using a convenience sampling method, 1190 nurses from 4 tertiary grade-A comprehensive hospitals were investigated between September 2021 and December 2021 in 3 provinces of China. The Workplace Violence Scale, Burnout Inventory, and Sense of Coherence scale were used to collect data. Data analysis was conducted using descriptive statistics, Pearson correlation, and regression analysis to estimate direct and indirect effects using bootstrap analysis. The mean total scores for workplace violence and burnout were 1.67 ± 1.08 and 47.36 ± 18.39, respectively. Workplace violence was significantly negatively correlated with the sense of coherence (r = -0.25) and positively correlated with burnout (r = 0.27). Additionally, a higher level of workplace violence was associated with higher burnout (β = 1.13, 95% CI: 0.68 ~ 1.56). A higher sense of coherence was also associated with lower burnout (β = -0.98, 95% CI: -1.03 ~ -0.92). Workplace violence showed an effect on burnout through a sense of coherence. The direct, indirect and total effects were 1.13, 1.88 and 3.01, respectively. The mediating effect of the sense of coherence accounted for 62.45% of the relationship between workplace violence and burnout. We found that the sense of coherence mediated most workplace violence on burnout. It is imperative for hospital managers to improve nurses' sense of coherence to reduce the occurrence of burnout during COVID-19. Future intervention studies should be designed to strengthen nurses' sense of coherence.


Transcription activation at the Escherichia coli melAB promoter: interactions of MelR with its DNA target site and with domain 4 of the RNA polymerase sigma subunit.
Activation of transcription initiation at the Escherichia coli melAB promoter is dependent on MelR, a transcription factor belonging to the AraC family. MelR binds to 18 bp target sites using two helix-turn-helix (HTH) motifs that are both located in its C-terminal domain. The melAB promoter contains four target sites for MelR. Previously, we showed that occupation of two of these sites, centred at positions -42.5 and -62.5 upstream of the melAB transcription start point, is sufficient for activation. We showed that MelR binds as a direct repeat to these sites, and we proposed a model to describe how the two HTH motifs are positioned. Here, we have used suppression genetics to confirm this model and to show that MelR residue 273, which is in HTH 2, interacts with basepair 13 of each target site. As our model for DNA-bound MelR suggests that HTH 2 must be adjacent to the melAB promoter -35 element, we searched this part of MelR for amino acid side-chains that might be able to interact with sigma. We describe genetic evidence to show that MelR residue 261 is close to residues 596 and 599 of the RNA polymerase sigma(70) subunit, and that they can interact. Similarly, MelR residue 265 is shown to be able to interact with residue 596 of sigma(70). In the final part of the work, we describe experiments in which the MelR binding site at position -42.5 was improved. We show that this is detrimental to MelR-dependent transcription activation because bound MelR is mispositioned so that it is unable to make 'correct' interactions with sigma.


High risk lymphoblastic leukemia in children: prognostic factors and management.
Most of the presenting clinical and biological features that have prognostic significance in childhood acute lymphoblastic leukemia are closely related, although they are not equally important. The predictive value of these factors can vary with the efficacy of the therapy delivered. Although there are no uniform criteria to define a high-risk group, an initially high leukocyte count and an age less than 1 or greater than 10 years at diagnosis are universally accepted as the most powerful indicators of a poor outcome. With advances in immunology and genetics, blast cell immunophenotypes and karyotypic abnormalities have emerged as independently significant prognostic factors. With this information, therapy can be tailored for patients at various risks of treatment failure. Using early aggressive therapy, more than 60% of patients are expected to be long-term survivors, but better therapy is still needed for those at high risk of relapse. Innovative approaches, such as bone marrow transplantation, phenotype-specific treatment, or pharmacokinetic-directed therapy, are being tested.


First principles study on the potential of functionalized porous silicon to capture adverse agents to human health: The role played by the interface interactions.
Porous Silicon (PSi) is an ideal material to build biosensors due to its large surface area and biocompatibility. However, it lacks of selectivity. By adhering bilayer lipids, active sites are added for vital biochemical processes. Such processes are promoted by different proteins, which aid to detect pollutants and drugs, among other. The present work is a systematic theoretical study at the density functional theory level on PSi models, functionalized with H and OH. Several concentrations of such functional groups were assessed at the pores to elucidate the reactivity via Fukui indexes of electrophilic and nucleophilic attack. The 1,2-dimyristoyl-sn-glycero-3-phosphocholine(DMPC) lipid was used as a probe system to interact with the PSi. The attraction was evaluated as electrostatic with a van der Waals contribution. The adsorption was highly selective to the degree of functionalization at the pore. The PSi facets (100) and (001) showed different mechanisms of interaction with the DMPC lipid. The theoretical absorption spectra addressed that the DMPC lipid could be identified with intensity variations coming from the degree of functionalization at the pore, which may be further rationalized experimentally. The present methodology may aid to tailor novel materials to capture and identify adverse agents present in the environment.


What can be learned from the residual efficacy of three formulations of insecticides (pirimiphos-methyl, clothianidin and deltamethrin mixture, and clothianidin alone) in large-scale in community trial in North Benin, West Africa?
In Alibori and Donga, two departments of high malaria incidence of Northern Benin, pirimiphos-methyl, mixture deltamethrin + clothianidin, as well as clothianidin were used at large scale for IRS. The present study aimed to assess the residual efficacy of these products. Immatures of Anopheles gambiae sensu lato (s.l.) collected in the communes of Kandi and Gogounou (Department of Alibori), Djougou and Copargo (Department of Donga) were reared until adulthood. Females aged 2-5 days were used for susceptibility tube tests following the WHO protocol. The tests were conducted with deltamethrin (0.05%), bendiocarb (0.1%), pirimiphos-methyl (0.25%) and clothianidin (2% weight per volume). For cone tests performed on cement and mud walls, the An. gambiae Kisumu susceptible strain was used. After the quality control of the IRS performed 1-week post-campaign, the evaluation of the residual activity of the different tested insecticides/mixture of insecticides was conducted on a monthly basis. Over the three study years, deltamethrin resistance was observed in all the communes. With bendiocarb, resistance or possible resistance was observed. In 2019 and 2020, full susceptibility to pirimiphos-methyl was observed, while possible resistance to the same product was detected in 2021 in Djougou, Gogounou and Kandi. With clothianidin, full susceptibility was observed 4-6 days post-exposure. The residual activity lasted 4-5 months for pirimiphos-methyl, and 8-10 months for clothianidin and the mixture deltamethrin + clothianidin. A slightly better efficacy of the different tested products was observed on cement walls compared to the mud walls. Overall, An. gambiae s.l. was fully susceptible to clothianidin, while resistance/possible resistance was observed the other tested insecticides. In addition, clothianidin-based insecticides showed a better residual activity compared to pirimiphos-methyl, showing thus their ability to provide an improved and prolonged control of pyrethroid resistant vectors.


Development of "Hunger Neurons" and the Unanticipated Relationship Between Energy Metabolism and Mother-Infant Interactions.
Over the course of a lifetime, the perinatal period plays an outsized role in the function of physiological systems. Here, we discuss how neurons that regulate energy metabolism contribute to the infant's relationship with the mother. We focus our discussion on Agrp neurons, which are located in the arcuate nucleus of the hypothalamus. These neurons heavily regulate energy metabolism. Because offspring transition from a period of dependence on the caregiver to independence, we discuss the importance of the caregiver-offspring relationship for the function of Agrp neurons. We present evidence that in the adult, Agrp neurons motivate the animal to eat, while in the neonate, they motivate the offspring to seek the proximity of the caregiver. We specifically highlight the peculiarities in the development of Agrp neurons and how they relate to the regulation of metabolism and behavior over the course of a lifetime. In sum, this review considers the unique insights that ontogenetic studies can offer toward our understanding of complex biological systems, such as the regulation of energy metabolism and mother-infant attachment.


The development of a Chinese version of the tobacco use subscale of the behavioral risk factor surveillance system (BRFSS).
To provide a culturally and linguistically specific survey instrument for tobacco consumption in Taiwan, we evaluated the reliability and validity of a Chinese translation of the 1993 US Tobacco Use Subscale of Behavioral Risk Factor Surveillance System (TU-BRFSS). An integrative translation was followed by a pilot study of 100 randomly selected adults from throughout Taiwan. Telephone interviews took place in July, 2004. Validity was assessed by Content Validity Index (CVI) computed on the basis of expert review and the averaged scores of back-translation. Of 29 questions, 25 met the CVI criteria for retention in the instrument. In the back-translation assessment, 85% of the average scores taken from the expert evaluations were above 4 (scale of 1-5). Three of four percent agreements between the referent question and 4 other questions were 100%. The Chinese version of the TU-BRFSS, with appropriate content, semantics, and conceptual equivalence, appears valid and reliable for future surveillance and research in Taiwan and other Chinese populations.


Molecular cloning and characterization of a gene encoding a 13.1 kDa antigenic protein of Naegleria fowleri.
An antigen-related gene was cloned from a cDNA expression library of Naegleria fowleri by immunoscreening with sera obtained from mice that were either immunized with an amoebic lysate or infected with trophozoites. The coding nucleotide sequence of the cloned gene consisted of 357 bases that were translated into 119 amino acids. This gene was designated as nfa1. The predicted amino acid sequence of Nfa1 protein has two potential glycosylation and three potential phosphorylation sites, and its predicted secondary structure consists of four helices and three corners. The deduced amino acid sequence of Nfa1 protein shares 43% identity with the myohemerythrin (myoHr) protein from a marine annelid, Nereis diversicolor, including 100% identity in conserved regions and iron-binding residues. A phylogenetic tree constructed from amino acid sequences placed the N. fowleri Nfa1 protein outside of a cluster of myoHr proteins from eight invertebrates. A purified recombinant protein that migrated as a 13.1 kDa species in SDS-PAGE was produced. This recombinant protein exhibited a strong immunoreactivity with infected, immune, and anti-Nfal sera. In addition, an anti-Nfa1 serum reacted with an amoeba lysate in immunoblotting analysis. The present nfal gene encoding the myoHr-like protein is the first myoHr gene cloned from protozoa, and the Nfal antigen may be useful in diagnostic studies


Ultrasonography of the knee.
Sonography is a useful modality in the diagnosis of a wide variety of knee disorders, including lesions of the articular cartilage, tendons and ligaments, menisci, synovial space, and adjacent vessels and muscles. Sonography is noninvasive, rapidly performed, widely available, readily accepted by patients, uses no ionizing radiation, and is relatively inexpensive compared to other conventional imaging studies of the menisci, making it a potentially attractive screening examination for knee injuries. Although it is difficult to state the exact place of sonography in the diagnostic workup of knee disorders, we feel that sonography is vastly underutilized. With additional refinements in ultrasound technology and scanning techniques, we expect further expansion of its role in the evaluation of the knee.


Modulation of immune genes in the mucosal-associated lymphoid tissues of cobia by Sarcodia suae extract.
Rachycentron canadum (cobia) is a marine fish species of high economic value in aquaculture due to its fast growth rate and good feed conversion efficacy. Regrettably, the industry has been affected by significant setbacks from high mortality due to diseases. Consequently, an improved perception of innate immunity correlated to each mucosal-associated lymphoid tissue (MALT) in teleost fish is necessary to understand hosts' response towards infections better. The utilization of polysaccharides in seaweed to stimulate the immune system has gathered unprecedented attention. The present study examined the immunostimulatory effects of Sarcodia suae water extracts (SSWE) on in vivo gill-, gut- and skin-associated lymphoid tissues (GIALT, GALT, and SALT) via immersion and oral ingestions. The GIALT genes (TNF-α, Cox2, IL-1β, IL-6, IL-8, IL-17 A/F1-3, IL-11, IL-12, IL-15, IL-18, MHCIa, IgM, and IgT) except IL-10 recorded positive upregulations in a dose-dependent manner post 24 h immersion in SSWE, indicating the algae extract contained bioactive compounds that could stimulate the immune genes. The upregulation of IL-12, IL-15, and IL-18 in the gills and hindgut post-SSWE immersion indicated that the extract could promote Th1-related responses in the MALTs. The modulation of immune gene expressions in the feeding trial was less potent than in the SSWE immersion. These findings indicated that the SSWE stimulated robust immune responses in both the GIALT and GALT of cobia. This suggests that the SSWE could be further explored as an effective immersive stimulant for fish, enhancing their immune system against pathogens.


Gentamicin-resistant staphylococci: genetics of an outbreak in a dermatology department.
The genetics of gentamicin resistance in Staphylococcus aureus strains isolated during an outbreak of infection in dermatology department have been studied. The predominant strain of S. aureus did not appear to possess a plasmid mediating gentamicin resistance though one isolate yielded a plasmid coding for penicillin and gentamicin. Three distinct plasmids were isolated from other phage types of S. aureus which appeared towards the end of the epidemic. There appeared to be a stepwise loss of gentamicin resistance in the predominant strain.


Exact closed-form solution to jet flow of a polymer arising in the electrospun nanofiber elaboration process.
In the present paper, we obtain the exact solution to the jet flow of a polymer arising in the electrospun nanofiber elaboration process. This allows us to improve on the approximate solutions of Colantoni and Boubaker (2014) and He, Kong, Chen, Hu, and Chen (2014). Our corrected and far simpler solution is more useful for extracting the salient physics inherent in the electrospun nanofiber elaboration process. We then consider the more robust formulation of the problem, in which the velocity of the jet and the radius of the jet depend strongly on one another, obtaining the solution in this case as well. All of the results obtained are rather simple, and give us closed-form exact solutions (rather than complicated approximations), and hence these results both maintain accuracy and have the possibility of being useful for future studies into the physics of such mechanical processes. The results also agree nicely with experimental and numerical results present in the literature.


Ultrasound-guided brain abscess aspiration in neonates.
Four cases of brain abscess in neonates are described, diagnosed by ultrasonography and CT. All abscesses were confirmed surgically. One patient was operated on 5 weeks after diagnosis because of initial parental refusal. The etiology in all cases was meningitis superimposed on an hypoxic-ischemic insult. Two cases had a single abscess while the other two had multiple lesions. All cases were operated on with intraoperative ultrasound examination through the fontanelle. The case with delayed aspiration showed complete evolution from localized cerebritis to complete capsule formation with mass effect. One abscess was sterile, and in the others grew Klebsiella pneumoniae and Enterobacter aerogenes. The microorganism initially isolated from the lumbar CSF was also found in the abscess. Even after sterilization of the lumbar CSF, all abscesses were still present. Ultrasound examination and CT are compared.


The reproducibility of single photon absorptiometry in a clinical setting.
The reproducibility of single photon absorptiometry (SPA) results for detection of changes in bone mineral content (BMC) was evaluated in a clinical setting. During a period of 18 months with 4 different sources, the calibration scans of an aluminium standard had a variation of less than 1% unless the activity of the 125I source was low. The calibration procedure was performed weekly and this was sufficient to correct for drift of the system. The short term reproducibility in patients was assessed with 119 duplicate measurements made in direct succession. The best reproducibility (CV = 1.35%) was found for fat corrected BMC results expressed in g/cm, obtained at the site proximal to the 8 mm space between the radius and ulna. Analysis of all SPA scans made during 1 year (487 scans) showed a failure of the automatic procedure to detect the space of 8 mm between the forearm bones in 19 scans (3.9%). A space adjacent to the ulnar styloid was taken as the site for the first scan in these examinations. This problem may be recognized and corrected relatively easy. A significant correlation was found between BMC of the lower arm and BMC of the lumbar spine assessed with dual photon absorptiometry. However, the error of estimation of proximal BMC (SEE = 20.0%) and distal BMC (SEE = 19.4%) made these measurements of little value to predict BMC at the lumbar spine in individuals. The short term reproducibility in patients combined with the long term stability of the equipment in our clinical setting showed that SPA is a reliable technique to assess changes in bone mass at the lower arm of 4% between 2 measurements with a confidence level of 95%.


Determining the optimal number of lymph nodes harvested during esophagectomy.
We examined the impact of the number of lymph nodes (LNs) removed during esophagectomy on outcomes in esophageal cancer (EC). From a comprehensive EC database we identified patients who underwent curative resection from 1994 to 2011. The impact of total LNs retrieved on disease-free survival (DFS) and overall survival (OS) was investigated. In total, 635 patients were identified. Patients were divided on the basis of total number of LNs removed (<8, 9-12, 13-20, and >20). The 5-year OS and DFS rates for the group by LN category were (43%, 42%, 55%, and 36%, P=0.1836) and (44%, 37%, 46%, and 36%, P=0.5166), respectively. Total number of LNs assessed did not correlate with reduced risk of recurrence or improved survival. On multivariate analysis controlling for age, sex, histology, neoadjuvant therapy, only removal of 13-20 LN's correlated to improved oncologic outcomes. In a tertiary cancer center, we demonstrated that only removal of 13-20 LNs during esophagectomy correlated to improved survival. While the importance of standardized pathologic examination and adequate nodal staging is of utmost importance for patients with EC undergoing esophagectomy the optimum number of LNs removed clearly warrants further investigation.


An evaluation of the results of convalescent plasma therapy applied to pregnant women diagnosed as COVID-19- positive in a pandemic center: A prospective cohort study.
Convalescent plasma (CP) might be an additional treatment modality in COVID-19. The aim of this study was to compare CP-related clinical characteristics and perinatal outcomes in pregnant women with mild or moderate-severe COVID-19. This prospective cohort study included 36 pregnant women (12 mild and 24 moderate-severe), who underwent CP therapy. The CP obtained from recently recovered donors was transfused to patients together with maximum supportive care and antiviral agents. The groups were then compared in respect of clinical characteristics, laboratory parameters, obstetric complications, and neonatal outcomes. Significant differences were determined between the groups in respect of systemic corticosteroids in COVID-19 treatment (41.7%, 87.5%, p = 0.004), oxygen (O2) support (0%, 91.7%, p < 0.001), chest imaging (41.7%, 58.3%, p = 0.02), intensive care unit admission (0%, 20.8%, p = 0.03) and length of hospitalization (5.5 versus 9.5 days, p < 0.001). The O2 saturation levels before and after administration of CP were significantly lower in the moderate-severe COVID-19 group (p < 0.05). The O2 therapy time before and after administration of CP and total O2 therapy time were significantly lower in the mild COVID-19 group (p < 0.05). Platelet, plateletcrit and lymphocyte counts were significantly higher in both the mild and moderate-severe COVID-19 groups after treatment compared to the pretreatment values (p < 0.05). Although data on the results of CP treatment in pregnant women are somewhat limited, it has been suggested that early CP treatment may be associated with improvements in laboratory and ventilatory parameters in pregnant women with mild and moderate-severe COVID-19. Nevertheless, there is a need for further, randomized controlled studies on this subject with the inclusion of greater numbers of patients.


Novel biomarkers of bronchopulmonary dysplasia and bronchopulmonary dysplasia-associated pulmonary hypertension.
To quantify and compare levels of potential biomarkers in neonates with (i) Bronchopulmonary dysplasia (BPD); (ii) BPD-associated pulmonary hypertension (BPD-PH); (iii) PH without BPD; and (iv) neonates without lung disease at ~36 weeks postmenstrual age. Multiple potential biomarkers were measured in plasma samples of 90 patients using a multi-spot enzyme-linked immunosorbent assay. Statistical tests done included one-way ANOVA to compare levels of biomarkers between different groups. Higher levels of ICAM-1 were present in infants with BPD and correlated with its severity. Infants with BPD have significantly higher levels of ANG-2 and lower levels of ANG-1. Infants with PH have higher levels of: IL-6, IL-8, IL-10, and TNF-α. Infants with BPD-PH have significantly lower levels of MCP-1 and higher levels of IL-1β than infants with PH without BPD. ICAM-1 may be used as a specific biomarker for diagnosis of BPD and its severity.


An evaluation of chest X-ray in the context of community-based screening of child tuberculosis contacts.
There are no published data on the critical review of chest X-ray (CXR) findings of children in the context of community-based contact screening. To describe the quality, findings and inter-observer agreement of CXRs in child TB contacts in Indonesia. We performed antero-posterior (AP) and lateral CXR in children who had had close contact with a pulmonary TB case. The CXRs were interpreted independently by four reviewers. A total of 530 CXRs of 265 children were reviewed. Most (63%) of the children were asymptomatic at the time of CXR. Only 60% of the CXRs were reported as moderate to good quality by all reviewers, and inter-observer agreement on quality was slight to moderate (weighted κ = 0.16-0.35) for AP view. The majority of the CXRs were reported as normal (range 65-77%), with fair to moderate inter-observer agreement (κ = 0.25-0.46). Hilar lymphadenopathy (6-16%) was the most common CXR abnormality reported with poor inter-observer agreement (κ = -0.03 to 0.25). The CXRs of child TB contacts investigated in the community were characterised by low quality, low agreement and low yield. Our findings support guidelines that CXR is not routinely indicated in asymptomatic child TB contacts in this setting.


cAMP response element-binding protein (CREB) and nuclear factor κB mediate the tamoxifen-induced up-regulation of glutamate transporter 1 (GLT-1) in rat astrocytes.
Tamoxifen (TX), a selective estrogen receptor modulator, exerts antagonistic effects on breast tissue and is used to treat breast cancer. Recent evidence also suggests that it may act as an agonist in brain tissue. We reported previously that TX enhanced the expression and function of glutamate transporter 1 (GLT-1) in rat astrocytes, an effect that was mediated by TGF-α. To gain further insight into the mechanisms that mediate TX-induced up-regulation of GLT-1 (EAAT2 in humans), we investigated its effect on GLT-1 at the transcriptional level. TX phosphorylated the cAMP response element-binding protein (CREB) and recruited CREB to the GLT-1 promoter consensus site. The effect of TX on astrocytic GLT-1 was attenuated by the inhibition of PKA, the upstream activator of the CREB pathway. In addition, the effect of TX on GLT-1 promoter activity was abolished by the inhibition of the NF-κB pathway. Furthermore, TX recruited the NF-κB subunits p65 and p50 to the NF-κB binding domain of the GLT-1 promoter. Mutation of NF-κB (triple, -583/-282/-251) or CRE (-308) sites on the GLT-1 promoter led to significant repression of the promoter activity, but neither mutant completely abolished the TX-induced GLT-1 promoter activity. Mutation of both the NF-κB (-583/-282/-251) and CRE (-308) sites led to a complete abrogation of the effect of TX on GLT-1 promoter activity. Taken together, our findings establish that TX regulates GLT-1 via the CREB and NF-κB pathways.


Space-occupying benign lesions in spleen: experiences in a single institute.
To introduce a practical reference for the diagnosis and treatment of space-occupying benign lesions in children's spleens. Ten cases were collected from 1988 to 2007, and analysis of some related literature were included with special attention to the criteria of the diagnosis and the indications of splenectomy, particularly to the age for operation. The age of patients on admission ranged from 5 to 15 years, with the mean age of 10 years. All chose the operation to mitigate the fear of either accidental rupturing or malignancy. The clinical diagnosis depended on ultrasonographic or other imaging findings, while the final diagnosis was based on pathological study of operative specimens. The final diagnosis of the five patients undergoing operation was benign tumors (angioma group), and the other five were cystic (mainly congenital). Eight children underwent primary splenectomy, and the other two underwent partial or secondary splenectomy, all with satisfactory results. Seven were followed up for more than 2 years and recovered uneventfully. Preoperative imaging examinations and postoperative pathology mutually confirmed space-occupying benign lesions in the spleen. The age of the children, size and character of the lesion, as well as the risk of rupturing and malignancy are reasonable indications of surgery. Splenectomy, unless with contra-indications, is a feasible choice of treatment.


The motherhood experience in the context of social vulnerability: a comprehensive approach to social phenomenology.
to understand the future expectations and experience of vulnerable mothers from pregnancy to their child's early years. this qualitative study used the social phenomenology of Alfred Schütz as a framework. From January to April 2011, nine mothers from the 2009 program "Chile Grows with You" were interviewed at health centers in an urban Santiago de Chile community. analysis of the "lived type" led to an understanding of the mothers' real-world experience. Unexpected pregnancies in extremely vulnerable mothers are associated with feelings of hopelessness then resignation. There is no plan for the future; the mother lives in the present with great uncertainty. from the mothers' stories, significant patterns were identified in their experiences, yielding insights into society from these women's perspectives. For humanized, comprehensive nursing care, this expertise directs interventions designed to overcome despair in women excluded because of their invisibility and poverty.


Nutritive value of Leucaena leucocephala for growing bull calves.
Twelve cross-bred (Holstein X Gir) bull calves (11-12 months of age) were divided into two groups and fed over a 90 day period on two levels of leucaena. Animals in Group I were offered leucaena ad lib. whilst those in Group 2 received a restricted amount of leucaena plus a mixture of sorghum straw and molasses (75:25) fed ad lib. Digestibilities of dry matter, crude protein, acid detergent fibre and neutral detergent fibre for leucaena are presented. The live weight gain was significantly (P less than 0.05) higher in animals fed leucaena ad lib. than in those fed a restricted amount of the forage. The animals did not show any symptoms of toxicity during the experimental period.


Ethnoracial Variation in Depression Symptoms.
While there is a long-standing tradition of research on the predictors of depression among women exposed to violence, little of this research has been conducted across ethnic and racial groups. A cross-sectional study comparing a total of 191 women with a history of intimate partner violence were recruited from commercial, medical, and educational settings and by contact with agencies serving the needs of abused women, for example, shelters, community outreach. The study examined intimate partner violence and the adjustment of mothers of children ages 5 to 12 to explore both commonalities and differences in the ways in which four groups of women (African American, Biracial, Latina, and White women) cope with violence in their lives. In addition to demographic information, depression symptoms were assessed by self-report with the Center for Epidemiologic Studies Depression scale. The findings indicate that Latina women had significantly higher depression symptoms than did African American and White women. While it is important to assess the mental health needs of all abused women, these results show additional need for Latina women, those with low income and high violence exposure.


Dendritic and axonal localization of cytotoxic T-lymphocyte antigen-2 alpha protein in mouse brain.
Cytotoxic T-lymphocyte antigen-2 alpha (CTLA-2alpha) is a novel cysteine proteinase inhibitor protein originally discovered and expressed in mouse activated T-cells and mast cells. Expressed recombinant CTLA-2alpha is shown to exhibit selective inhibition of cathepsin L-like cysteine proteinases. We have recently reported the expression pattern of CTLA-2alpha mRNA in mouse brain by in situ hybridization, demonstrating that it is mainly enriched within neuronal populations. In this study we present the distribution profile of the protein by immunohistochemical analysis. Results showed that CTLA-2alpha protein is preferentially localized in dendritic and axonal compartments. In telencephalon, strong labeling was detected in dendrites in the cerebral cortices, stratum radiatum and stratum lacunosum moleculare and within axonal fibers of stratum lucidum where mossy fibers emanating from all parts of the granule cell layer of dentate gyrus terminate at pyramidal neurons and interneurons. In diencephalon, moderate staining was found in all thalamic nuclei but was strong in medial habenular nucleus and the hypothalamic nuclei including suprachiasmatic nucleus, optic chiasm, arcuate nucleus and median eminence. In mesencephalon, strong immunoreactivity was detected in superior colliculus, inferior colliculus and paramedian raphe nucleus. In the rhombencephalon, the pontine nucleus and transverse fibers of the pons revealed strong staining but were moderate in vestibular nuclei. Strong immunoreactivity was also observed in the internal white matter, granule cell layer and Purkinje cell layer within cerebellum. On Western blot analysis, a band of 14 kDa for CTLA-2alpha from protein extracts of the cerebrum, cerebellum, pons and medulla was detected. The distribution pattern and functional considerations of CTLA-2alpha in the brain are discussed.


Laryngotracheal trauma: observations on its pathogenesis and its prevention following prolonged orotracheal intubation in the adult.
The authors have clinically examined the larynges of 117 patients who were successfully extubated in a Respiratory Care Unit, and have examined the larynges at autopsy from an additional 68 patients who failed to survive in the same Respiratory Care Unit. Based on these observations, our understanding of the pathogenesis of laryngotracheal trauma has allowed us to modify our clinical management in order to minimize such damage. Influence of this study on the management of patients is described.


Surgical Treatment of Aortic Prosthetic Valve Endocarditis: A 20-Year Single-Center Experience.
Despite progress in diagnostic methods and treatment, aortic prosthetic valve endocarditis (PVE) remains a life-threatening disease. We report the outcome of all operations for aortic PVE performed at our institution over the past 20 years. Eighty-seven operations performed in 84 patients between 1993 and 2013 were included in this retrospective study. An aortic homograft was used in 56 (64%) cases, a mechanical prosthesis was used in 20 (23%) cases, and a bioprosthesis was used in 11 (13%) cases. Early and late complications and mortality were compared between the first and second decades of our experience. Predictors of mortality were identified with Cox regression. Mean follow-up was 5.5 years (range 0-17 years). Nine patients (10%) died within 30 days, and severe perioperative complications occurred in 36 patients (41%). Overall cumulative survival was 80% at 5 years and 65% at 10 years. Four (12.9%) of the patients treated with mechanical or biological prostheses had a recurrent episode of endocarditis, compared with none of the patients treated with homografts (p = 0.006). During the second decade, 30-day mortality was lower (3.6% versus 22%; p = 0.007) and 5-year cumulative survival was higher (88% versus 66%; p = 0.027). Age, preoperative serum creatinine, and severe perioperative complications were independent predictors of mortality during follow-up. Aortic PVE is associated with a high rate of early complications and substantial early mortality. Patients who survive the immediate postoperative period have satisfactory long-term survival. The risk of recurrent endocarditis is low, especially in patients treated with homografts. The results have improved during the past decade.


Nanocrystalline silver dressing and subatmospheric pressure therapy following neoadjuvant radiation therapy and surgical excision of a feline injection site sarcoma.
CLINICAL SUMMARY: This is the first clinical report of use of a combination of nanocrystalline silver and subatmospheric pressure therapy to treat a resistant wound infection, following tumour removal and radiation therapy, in a difficult-to-manage surgical site in a cat. The therapy was well tolerated and the authors suggest it is a valid treatment protocol for management of non-healing or infected wounds in the cat.


Characteristics of university students supported by counseling services: Analysis of psychological tests and pulse rate variability.
Mental health is an essential issue during adolescence. The number of students who use counseling services is increasing in universities. We attempted to confirm the characteristics of the students who access counseling services using both psychological tests and pulse rate variability (PRV) for better support for students' academic success. We recruited the participants for this study from the students who had counseling sessions at Kanazawa University (Group S). As a control group, we also recruited students who had no experience in counseling services (Group H). We obtained health information from the database of annual health checkups. Participants received the Wechsler Adult Intelligence Scale (WAIS)-III, Autism-Spectrum Quotient (AQ), Sukemune-Hiew (S-H) Resilience Test, and State-Trait Anxiety Inventory-JYZ (STAI). We also studied the 12-Item Short-Form Health Survey (SF-12v2) for testing Health-Related Quality of Life (HRQOL). As a physiological test, we examined the spectral analyses of pulse rate variability (PRV) by accelerating plethysmography. We performed a linear analysis of PRV for low-frequency power (LF: 0.02-0.15 Hz) and high-frequency power (HF: 0.15-0.50 Hz). We also conducted a non-linear analysis of PRV for the largest Lyapunov exponent (LLE). Additionally, we examined participants' blood for autoantibodies against glutamate decarboxylase (GAD) 65. A total of 105 students participated in this study. Group S had 37 participants (Male: 26, Female: 11), and Group H had 68 participants (Male: 27, Female 41). There were five males and one female in Group S who had diagnoses of autism spectrum disorder (ASD), and three males in Group S were diagnosed with attention deficit hyperactivity disorder (ADHD) by medical institutes. Additionally, four males and two females in Group S had diagnoses of ASD with ADHD by medical institutes. A male with ASD in Group S had epilepsy. The students of Group S had characteristics as follows: 1) lower power of Working Memory Index (WMI) despite high Full-Scale Intelligent Quotient (FSIQ), 2) higher ASD traits especially in Male, 3) lower resilience powers, 4) higher anxiety trait, 5) lower Health-Related Quality of Life (HRQOL) in Role/social component in both Male and Female, 6) lower HRQOL in Mental component in Male 7) shifting of autonomic nervous balance toward higher sympathetic activity. We could confirm the characteristics of students who visited counseling rooms for mental support (Group S). We also found gender differences in specificities of Group S. The educational system is changing rapidly to adjust social requests. These changes make conflict with the features of students of Group S. We should think about appropriate supports for the students who would pioneer the future of humanity.


PRKAR1A-negative familial Cushing's syndrome: two case reports.
Determining the etiology of Cushing's syndrome is very challenging to endocrinologists, with most of the difficulty arising from subtype differentiation of adrenocorticotropic hormone-dependent Cushing's syndrome. We present the pitfalls of evaluating a rare cause of adrenocorticotropic hormone-independent Cushing's syndrome in the transition period between adolescence and adulthood. A sibling pair with familial isolated primary pigmented nodular adrenocortical disease is described. The index case, a 20-year-old Chinese woman, presented with premenopausal osteoporosis with T12 compression fracture and young hypertension. Biochemical analysis confirmed adrenocorticotropic hormone-independent Cushing's syndrome (elevated 0800 h plasma cortisol 808 nmol/L with suppressed adrenocorticotropic hormone level <5 pg/ml). Computed tomography of her adrenal glands revealed a 0.7-cm left adrenal hypodense nodule. After a left adrenalectomy, she had residual hypercortisolism (progressive weight gain, new T10 compression fracture, and not glucocorticoid-dependent postoperatively). Completion of contralateral adrenalectomy was performed upon recognition of typical histologic characteristics of primary pigmented nodular adrenocortical disease found in an initial left adrenalectomy specimen. Similarly, her younger brother developed adrenocorticotropic hormone-independent Cushing's syndrome at age 18 years, with typical cushingoid habitus, but no osteoporosis or hypertension. His adrenal computed tomographic scans showed micronodularities over bilateral adrenal glands. He was successfully treated with bilateral adrenalectomy. Screening for Carney's complex and PRKAR1A gene mutation was negative. Signs and symptoms of Cushing's syndrome resolved after bilateral adrenalectomy for both patients. They were placed on lifelong glucocorticoid and mineralocorticoid replacement therapy and long-term surveillance for Carney's complex. The cases of these two patients illustrate the difficulties involved in diagnosing primary pigmented nodular adrenocortical disease, a variant of adrenocorticotropic hormone-independent Cushing's syndrome that is managed with bilateral adrenalectomy. A high index of suspicion for this disease is needed, especially in adolescents with adrenocorticotropic hormone-independent Cushing's syndrome who have a significant family history, features of Carney's complex, and no resolution of Cushing's syndrome after unilateral adrenalectomy. Patients with primary pigmented nodular adrenocortical disease can either have bilateral/multiple adrenal nodules or normal adrenal glands visualized by computed tomography. Long-term surveillance is imperative in patients with confirmed Carney's complex and in those who have not undergone complete genetic testing to exclude this hereditary disorder.


Alkaline phosphatase as a model for studying metal-protein interactions in pulmonary toxicity.
An attempt has been made to study the biochemical properties of lung alkaline phosphatase so that it may serve as a model for measuring the toxicity of air pollutants, especially metals. Lung was shown to be a better source of this enzyme in comparison to other organs in rats. The optimum pH, metal requirements, substrate specificity, and affinity constants were characterized with different substrates, and the effect of different metals was studied. The involvement of zinc in the lung enzyme was not indicated as shown by Sephadex G-200 elution profile of postmitochondrial supernatant of 65Zn-treated animals.


Recent advances in degradable lactide-based shape-memory polymers.
Biodegradable polymers are versatile polymeric materials that have a high potential in biomedical applications avoiding subsequent surgeries to remove, for example, an implanted device. In the past decade, significant advances have been achieved with poly(lactide acid) (PLA)-based materials, as they can be equipped with an additional functionality, that is, a shape-memory effect (SME). Shape-memory polymers (SMPs) can switch their shape in a predefined manner upon application of a specific external stimulus. Accordingly, SMPs have a high potential for applications ranging from electronic engineering, textiles, aerospace, and energy to biomedical and drug delivery fields based on the perspectives of new capabilities arising with such materials in biomedicine. This study summarizes the progress in SMPs with a particular focus on PLA, illustrates the design of suitable homo- and copolymer structures as well as the link between the (co)polymer structure and switching functionality, and describes recent advantages in the implementation of novel switching phenomena into SMP technology.


Abnormal neutrophil maturation in a neutrophil defect with morphologic abnormality and impaired function.
Neutrophils from a patient with recurrent pyogenic infections since infancy were found to have morphologic abnormalities and impaired functions. The neutrophils had an abnormal nuclear shape, no or few secondary granules, and no alkaline phosphatase activity. Primary granules were normal in number and structure, and were positive for peroxidase. Immature granulocytes were structurally normal. The neutrophils were impaired in chemotaxis and bactericidal capacity. The patient's marrow cells formed increased numbers of granulocytic colonies of small size in culture. Her peripheral leukocytes produced elevated levels of CSA and adherent marrow cells did not inhibit colony formation. These data indicate an intrinsic neutrophil defect which allows normal proliferation of precursor cells, but results in abnormal morphogenesis and impaired function as the cells mature.


Functional outcomes in symptomatic versus asymptomatic patients undergoing incisional hernia repair: Replacing one problem with another? A prospective cohort study in 1312 patients.
Incisional hernias can be associated with pain or discomfort. Surgical repair especially mesh reinforcement, may likewise induce pain. The primary objective was to assess the incidence of pain after hernia repair in patients with and without pre-operative pain or discomfort. The secondary objectives were to determine the preferred mesh type, mesh location and surgical technique in minimizing postoperative pain or discomfort. A registry-based prospective cohort study was performed, including patients undergoing incisional hernia repair between September 2011 and May 2019. Patients with a minimum follow-up of 3-6 months were included. The incidence of hernia related pain and discomfort was recorded perioperatively. A total of 1312 patients were included. Pre-operatively, 1091 (83%) patients reported pain or discomfort. After hernia repair, 961 (73%) patients did not report pain or discomfort (mean follow-up = 11.1 months). Of the pre-operative asymptomatic patients (n = 221), 44 (20%, moderate or severe pain: n = 14, 32%) reported pain or discomfort after mean follow-up of 10.5 months. Of those patients initially reporting pain or discomfort (n = 1091), 307 (28%, moderate or severe pain: n = 80, 26%) still reported pain or discomfort after a mean follow-up of 11.3 months postoperatively. In symptomatic incisional hernia patients, hernia related complaints may be resolved in the majority of cases undergoing surgical repair. In asymptomatic incisional hernia patients, pain or discomfort may be induced in a considerable number of patients due to surgical repair and one should be aware if this postoperative complication.


Decreased nerve distribution in mixed venous-lymphatic malformation.
In order to investigate the nerve distribution in mixed venous-lymphatic malformations (MVLMs), 57 postoperative patients diagnosed with MVLMs of the tongue were selected. Immunohistochemistry staining for neurofilament (NF) was used to detect sensory nerve fibers. Distribution of NF in samples from MVLMs was compared with distribution of NF in normal tongue tissue, venous malformations, lymphatic malformations and venular malformations. Results showed that the number of NF-positive nerve fibers in MVLMs was comparable to that in venous malformations and lymphatic malformations. The number of nerve fibers in MVLMs was significantly lower than in normal tissues. NF distribution in MVLMs was not affected by the patient's age or the coexistence of infection. These data suggest that the decreased distribution of sensory nerve fibers in MVLMs may be involved in the pathogenesis of MVLM of the tongue.