Primary sclerosing cholangitis: role of extrahepatic biliary resection.
Most centers advocate orthotopic liver transplantation (OLT) for patients with primary sclerosing cholangitis (PSC) and cirrhosis. Management of PSC patients without cirrhosis remains controversial. We examined the results of extrahepatic biliary resection (EHBR) for PSC. Between 1981 and 2006, 126 patients with PSC underwent EHBR (n = 77) or OLT (n = 49). Data on biliary drainage procedures, perioperative morbidity, and longterm survival were collected and analyzed. Of 77 patients undergoing EHBR, mean preoperative bilirubin level was 5.6 mg/dL. Nine (11.7%) patients had cirrhosis. Most patients had preoperative biliary drainage (ERCP, 61.0%; PTC, 67.5%). At operation, 73 (94.8%) patients underwent EHBR, including hepatic duct bifurcation. Most patients also had insertion of bilateral transhepatic silicone elastomer biliary stents; 4 (5.2%) underwent EHBR with stent insertion plus hepatectomy. For EHBR patients, perioperative complication rate was 38.7% and 30-day mortality was 3.9%. Bilirubin levels significantly decreased postoperatively (mean drop 3.8 mg/dL; p < 0.01). At 3 years, 57.1% of patients had no PSC-related readmissions, and 16.2% had more than 3. At a median followup of 10.5 years, 5- and 10-year survival was 76.4% and 52.7%, respectively. Cholangiocarcinoma did not develop in any patients, and only seven required OLT. Factors associated with worse survival included postoperative bilirubin >or= 2 mg/dL and history of cirrhosis (both p < 0.001). In patients undergoing EHBR, noncirrhotic patients had significantly better longterm outcomes versus cirrhotic patients (10-year survival, 60.2% versus 12.0%; p < 0.001). In contrast, 10-year survival of OLT patients with cirrhosis was 57.0%. Noncirrhotic patients with PSC can be successfully managed with EHBR. EHBR for noncirrhotic patients is associated with low perioperative morbidity, few readmissions, no new cholangiocarcinomas, and 10-year survival > 60%. OLT should be reserved for patients with PSC and associated hepatic cirrhosis.


It's all in the milk: chondroitin sulfate as potential preventative therapy for necrotizing enterocolitis.
Necrotizing enterocolitis (NEC) is a devastating condition affecting up to 5% of neonatal intensive care unit (NICU) admissions. Risk factors include preterm delivery, low birth weight, and antibiotic use. The pathogenesis is characterized by a combination of intestinal ischemia, necrosis of the bowel, reperfusion injury, and sepsis typically resulting in surgical resection of afflicted bowel. Targeted medical therapy remains elusive. Chondroitin sulfate (CS) holds the potential to prevent the onset of NEC through its anti-inflammatory properties and protective effect on the gut microbiome. The purpose of this review is to outline the many properties of CS to highlight its potential use in high-risk infants and attenuate the severity of NEC. The purpose of this review is to (1) discuss the interaction of CS with the infant microbiome, (2) review the anti-inflammatory properties of CS, and (3) postulate on the potential role of CS in preventing NEC. IMPACT: NEC is a costly medical burden in the United States. Breast milk is the best preventative measure for NEC, but not all infants in the NICU have access to breast milk. Novel therapies and diagnostic tools are needed for NEC. CS may be a potential therapy for NEC due to its potent anti-inflammatory properties. CS could be added to the formula in an attempt to mitigate breast milk disparities.


Equine estrogens induce apolipoprotein E and glial fibrillary acidic protein in mixed glial cultures.
Premarin, which contains several equine estrogens, as well as estradiol (E2) as a minor component, is widely used for replacement therapy of estrogen deficits, but little is known of its direct actions on brain cells. In mixed glial cultures, apolipoprotein E (apoE) and glial fibrillary acidic protein (GFAP) are induced by estrogens. GFAP induction showed an inverted-U shape E2 dose response, with a maximum induction at 1 pM, whereas apoE mRNA induction was greatest at 100 pM. GFAP and ApoE mRNAs were induced by equine estrogens in the following order: E2=equilin>estrone>17 alpha-dihydroequilenin. However, the induction of apoE secretion by 17 alpha-dihydroequilenin was as effective as by the other estrogens. The greater response of apoE secretion than GFAP mRNA induction to 17 alpha-dihydroequilenin might be therapeutically important because of the glial scarring during brain lesions, in which GFAP induction has a major role in inhibiting neurite outgrowth, whereas apoE secretion supports neurite outgrowth.


[Death of acute pulmonary embolism after multiple maxillofacial fractures operation: a case report].
Acute pulmonary embolism after surgery of multiple maxillofacial fractures is rare. This paper reported a case of multiple maxillofacial fractures who experienced acute pulmonary embolism after operation and died.


[Brill's Disease in Eastern Slovakia (author's transl)].
A report is presented on the epidemiological, clinical and serological findings obtained in 37 patients in the southern part of Eastern Slovakia who were diagnosed as having Brill's disease. All patients presented with a recurrence of classical louse-borne typhus; in no case did the disease occur for the first time. It is recommended that all patients with a febrile illness of uncertain aetiology be subjected to a routine serological examination for louse-borne typhus in epidemic areas. Careful supervision is necessary since if such late recurrences are not detected they can result in a renewed spread of the disease in an environment where lice prevail. This was demonstrated in one of the patients in this study.


Tiredness, depression, and sleep disorders in frontline healthcare workers during COVID-19 pandemic in Vietnam: A field hospital study.
The COVID-19 outbreak witnessed in the autumn of 2021 led to unprecedented changes in healthcare systems in some emerging countries. Many field-hospitals, temporary sites of care for COVID-19 patients, were built around the country and followed by the healthcare workers who were mobilized. This study aimed to measure sleep disorders, depression, and fatigue in volunteers working at field hospitals during the COVID-19 outbreak. This was a cross-sectional study. The self-report questionnaire was used for each study subject. Sleep characters, including STOP's elements were questioned. Healthcare workers' burnout was detected by using Pichot's questionnaire. One hundred front-line healthcare workers (FHWs), predominantly last year and graduated medical students, were included in the study (86% female subjects). The mean sleep-time of FHWs before, while working, and during the isolation period after working at COVID-19 field hospitals were: 7.78 ± 1.48, 5.71 ± 1.40, and 8.78 ± 2.31 h per day, respectively. Burnout was not a crucial issue for these volunteer subjects. The mean scores of Pichot's Fatigue Scale and Pichot's Depression Scale, measured after 4 weeks working at field hospitals, were 4.18 ± 5.42 and 2.54 ± 3.36, respectively. Thirteen participants were suspected of depression. The fatigue scores decreased significantly in the group who claimed short sleep latency. The factor that increased the depression score was "anxious feeling" (p = 0.001). Other significant factors were "short sleep latency," "observed sleep apnea," "tiredness, daily sleepiness" and "snoring." Appropriate work schedule, better sleep conditions, and mental health support could be helpful for FHWs. The mandatory 2 weeks of isolation after working in field hospitals provided opportunity for FHWs' recovery.


β-carotene alleviates LPS-induced inflammation through regulating STIM1/ORAI1 expression in bovine mammary epithelial cells.
β-carotene has anti-inflammatory properties. STIM1(Stromol interaction molecule 1)/ORAI1 (Orai calcium release-activated calcium modulator 1) is an important inflammatory receptor, participating in the regulation of intracellular calcium signals by inflammation. The aim of this study was to clarify the correlation between STIM1/ORAI1-mediated Ca2+ signaling and inflammation and the anti-inflammatory effect of β-carotene on lipopolysaccharide (LPS)-induced bovine mammary epithelial cells (BMECs). The results showed that LPS activated SOCE channels and induced Ca2+ influx via up-regulating the expression of STIM1 and ORAI1, leading to cell injury. STO-609, BTP2, STIM1 or ORAI1 sclienced attenuated LPS-induced inflammation by inhibiting NF-κB signaling. However, overexpression of STIM1 or ORAI1 induced inflammatory response by activating NF-κB signaling pathway, and which had synergistic effect with LPS. β-carotene inhibited NF-κB activation by decreasing STIM1/ORAI1 expression, and thus alleviated LPS-induced inflammation in BMECs. Therefore, SOCE-targeting inhibitors are promising as new anti-inflammatory agents, and β-carotene may be considered for the prevention of mastitis in dairy cows.


miR-128 represses L1 retrotransposition by binding directly to L1 RNA.
Long interspersed element 1 (LINE-1 or L1) retrotransposons compose 17% of the human genome. Active L1 elements are capable of replicative transposition (mobilization) and can act as drivers of genetic diversity. However, this mobilization is mutagenic and may be detrimental to the host, and therefore it is under strict control. Somatic cells usually silence L1 activity by DNA methylation of the L1 promoter. In hypomethylated cells, such as cancer cells and induced pluripotent stem cells (iPSCs), a window of opportunity for L1 reactivation emerges, and with it comes an increased risk of genomic instability and tumorigenesis. Here we show that miR-128 represses new retrotransposition events in human cancer cells and iPSCs by binding directly to L1 RNA. Thus, we have identified and characterized a new function of microRNAs: mediating genomic stability by suppressing the mobility of endogenous retrotransposons.


Abdominal surgery in neonatal foals.
Abdominal surgery in foals under 30 days old has become more common with improved neonatal care. Early recognition of a foal at risk and better nursing care have increased the survival rates of foals that require neonatal care. The success of improved neonatal care also has increased the need for accurate diagnosis and treatment of gastrointestinal, umbilical, and bladder disorders in these foals. This chapter focuses on the early and accurate diagnosis of specific disorders that require abdominal exploratory surgery and the specific treatment considerations and prognosis for these disorders.


Infantile cortical hyperostosis with osteomyelitis of the humerus.
A case is presented in which a delay in diagnosis and treatment of osteomyelitis occurred because of diagnostic confusion between the patient's osteomyelitis and his coincident infantile cortical hyperostosis.


A review of photogrammetry with applications to implant film calibration and seed matching.
The basic concepts of photogrammetry, the science of making geometric measurements from photographs, are reviewed with an emphasis on applications to implant dosimetry. A seed matching algorithm is developed using those concepts.


Kidney synthesizes less metallothionein than liver in response to cadmium chloride and cadmium-metallothionein.
Acute exposure to Cd produces liver injury, whereas chronic exposure results in kidney injury. Tolerance to the hepatotoxicity is observed during chronic exposure to Cd due to the induction of metallothionein (MT). The nephrotoxicity produced by chronic Cd exposure purportedly results from renal uptake of Cd-metallothionein (CdMT) synthesized in liver. The change in target organ from liver to kidney might be due to a lower amount of MT synthesized in the kidney in response to CdMT. Therefore, the purpose of the present study was to quantitate hepatic and renal MT induced by CdCl2 and CdMT. MT levels in mice were quantitated using the Cd-heme assay 24 hr after administration of CdCl2 (0.5-3.0 mg Cd/kg) and CdMT (0.1-0.5 mg Cd/kg). In both liver and kidney, MT reached higher levels following administration of CdCl2 (220 and 60 micrograms/g, respectively) than of CdMT (25 and 35 micrograms/g, respectively), probably because higher dosages of CdCl2 than CdMT are tolerated. CdMT produced 19 and 3 micrograms MT/micrograms Cd in liver and kidney, respectively, while CdCl2 produced 11 and 6 micrograms MT/micrograms Cd, respectively. In conclusion, induction of MT occurs in both the liver and kidney after administration of CdCl2 and CdMT. However, the kidney is less responsive than the liver to the induction of MT by both forms of Cd, which may contribute to making the kidney the target organ of toxicity during chronic Cd exposure.


Quality of reporting in oncology studies: A systematic analysis of literature reviews and prospects.
The present review gives an overview of systematic reviews published in peer reviewed Journals analysing quality of reporting in oncology studies. PUBMED and Cochrane library were searched to identify systematic reviews assessing quality of reporting for randomized controlled trials (RCTs) and observational studies (OBS). Recommendations and primary endpoints used to assess the quality of reporting were described. Intrinsic quality of reporting was analyzed using an Overall Quality Score for literature Reviews (OQSR). Main evaluation themes were overall quality of reporting (20/58) and reporting of Health-Related Quality Of Life (HRQOL) in RCTs (7/58). Reporting recommendations used were not detailed in 56.9% of reviews. Insufficient reporting for the methodological description (randomization, blinding details, and allocation concealment) and the rationale for using specific measure of HRQOL were highlighted. OQSR was significantly higher for reviews published between 2010 and 2014 (after the PRISMA Publication), as compared to those published between 1996-2009 (median OQSR 10 (10-11) versus median OQSR 9 (6-10) respectively, p=0.0053). Intrinsic quality of reporting is satisfactory and has been improved in the last years.


The prevalence and effective factors of crash helmet usage among motorcyclists in Iran.
Crash helmet plays an important role in protecting the deriver's head during crashes and reduces the rate of severe injuries and fatalities. Although it has been proved that wearing the crash helmet can save the deriver's life by around 42%; previous studies showed that the rate of wearing crash helmet has not been acceptable in Iran. Due to the huge number of motorcyclists on the roads in Iran, the use of crash helmet is an important area of research. The aim of this study was to assess the factors that could possibly relate to or affect the use of crash helmet by the motorcyclists. This is an observational study on 414 motorcyclists in Shiraz, Southern Iran. All participants completed a questioner containing demographic features, crash helmet use, motorcycle license, and the reasons for using motorcycles. All the participants were males and aged from 16 to 64 years with mean age 27±9.28. The results of logistic regression model revealed that only the drivers who had motorcycle license (OR=2.73, C.I: 1.40-7.24), employed the motorcycle for reasons other than pleasure (OR=3.18, C.I: 1.42-7.37) and been driving for 10 or more years (OR=1.92 95% C.I: 1.12-3.30) had greater rate of wearing crash helmet. Interestingly, educational levels, age, and other demographical variables had no relationship with crash helmet usage. It is believed that in order to increase the rate of crash helmet use, it is necessary to enact obligatory requirement for driving license by motorcyclists and increase the legal age for motorcycle driving.


Genome-wide association study of antibody response to smallpox vaccine.
We performed a genome-wide association study (GWAS) of antibody levels in a multi-ethnic group of 1071 healthy smallpox vaccine recipients. In Caucasians, the most prominent association was found with promoter SNP rs10489759 in the LOC647132 pseudogene on chromosome 1 (p=7.77×10(-8)). In African-Americans, we identified eight genetic loci at p<5×10(-7). The SNP association with the lowest p-value (rs10508727, p=1.05×10(-10)) was in the Mohawk homeobox (MKX) gene on chromosome 10. Other candidate genes included LOC388460, GPR158, ZHX2, SPIRE1, GREM2, CSMD1, and RUNX1. In Hispanics, the top six associations between genetic variants and antibody levels had p-values less than 5×10(-7), with p=1.78×10(-10) for the strongest statistical association (promoter SNP rs12256830 in the PCDH15 gene). In addition, SNP rs4748153 in the immune response gene PRKCQ (protein kinase C, theta) was significantly associated with neutralizing antibody levels (p=2.51×10(-8)). Additional SNP associations in Hispanics (p≤3.40×10(-7)) were mapped to the KIF6/LOC100131899, CYP2C9, and ANKLE2/GOLGA3 genes. This study has identified candidate SNPs that may be important in regulating humoral immunity to smallpox vaccination. Replication studies, as well as studies elucidating the functional consequences of contributing genes and polymorphisms, are underway.


The impact of cataract, cataract types, and cataract grades on vision-specific functioning using Rasch analysis.
To determine the impact of cataracts and their types and grades on vision-specific functioning. Prospective population-based cross-sectional study. The Singapore Indian Eye Study examined 3400 of 4497 (75.6% response rate) ethnic Indians 40 years of age and older living in Singapore. Three thousand one hundred sixty-eight (93.2%) fulfilled inclusion criteria with complete information for final analysis. Cataracts were assessed on slit-lamp examination and were graded according to the Lens Opacity Classification System III. Vision-specific functioning scores were explored with the Visual Function scale, validated using Rasch analysis. Two hundred sixty-nine (8.5%) and 740 (23.4%) of the study participants had unilateral and bilateral cataracts, respectively, and 329 (10.4%), 800 (25.2%), and 128 (4.1%) participants had nuclear, cortical, and posterior subcapsular (PSC) cataracts, respectively. In multivariate linear regression models, the presence of bilateral rather than unilateral cataract (β = -0.12; 95% confidence interval, -0.20 to 0.00) was associated independently with poorer vision-specific functioning, even after adjusting for undercorrected refractive error (β = -0.11; 95% confidence interval, -0.21 to 0.00). Bilateral nuclear, cortical, and PSC cataracts also were associated with poorer vision-specific functioning (β = -0.31, -0.15, and -1.15, respectively), with combinations of them having even greater impact. Significantly poorer vision-specific functioning occurred at Lens Opacity Classification System grades 4 (nuclear opalescence), 5 (nuclear color), 3 (cortical), and 1 (PSC) or higher. People with bilateral but not unilateral cataracts experience difficulty with performing vision-specific daily activities independent of refractive error, with PSC cataracts and cataract combinations having the greatest impact. Cataract types cause poorer vision-specific functioning beginning at different severity grades.


Insulin-like growth factor-I augments interleukin-8 promoter activity through induction of activator protein-1 complex formation.
We previously established that stimulation by IGF-I of interleukin (IL)-8 expression in leukocytes required activation of extracellular-regulated kinase (ERK) and basal activity of c-Jun N-terminal kinase (JNK). In this study, we tested the hypothesis that IGF-I stimulates IL-8 expression at the transcriptional level through induction of Fos/Jun activator protein (AP)-1 complex formation. Inhibition studies using the transcriptional inhibitor actinomycin D and IL-8 promoter activation studies indicate that IGF-I act at the transcriptional level. Using gel shift assays we demonstrate that IGF-I induces the formation of active c-Jun/c-Fos AP-1 complexes. Promoter activation studies using mutated IL-8 promoter constructs show that the AP-1 response element is required for promoter activation by IGF-I whereas CAAT-enhancer binding protein (C/EBP) and nuclear factor of kappa B (NFkappaB) sites were not essential. These results indicate that IGF-I can augment IL-8 expression through activation of AP-1 independent of other inducible transcription factors which have shown to be involved in IL-8 regulation by immune stimuli. This finding is in agreement with our previous observation that IGF-I is able to enhance basal IL-8 production in peripheral blood mononuclear cells (PBMC) in the absence of other stimuli.


Association between circulating tumor necrosis factor receptors and oral bacterium in patients receiving hemodialysis: a cross-sectional study.
High levels of tumor necrosis factor (TNF) receptors (TNFRs; TNFR1 and TNFR2), markers of inflammation, have been reported as significant predictors of mortality in hemodialysis patients. Porphyromonas gingivalis is a major pathogenic bacterium involved in periodontitis, which induces systemic inflammation. We investigated the association between the abundance of P. gingivalis in saliva and serum TNFR levels in hemodialysis patients. A cross-sectional study was conducted on 121 hemodialysis patients visiting a clinic in the Tokyo metropolitan area. Medical interviews and examinations, comprehensive dental examinations, bacterial examinations for P. gingivalis in saliva, and measurements of circulating TNFR levels were conducted. Multiple linear regression analysis was performed to evaluate the association between the number of P. gingivalis and circulating TNFR levels. TNFR1 and TNFR2 were positively correlated with high-sensitivity C-reactive protein (hsCRP). Severe periodontitis was significantly associated with the number of P. gingivalis in saliva but not serum TNFR levels. The number of P. gingivalis was significantly associated with both TNFR1 and TNFR2 levels in sera after adjusting for age, sex, body mass index, smoking status, history of diabetes, prior cardiovascular disease events, serum levels of hsCRP and albumin, and severity of periodontitis [for TNFR1: coefficient 0.76, 95% confidence interval (CI) 0.14-1.37, p = 0.02; for TNFR2: coefficient 0.95, 95% CI 0.09-1.80, p = 0.03]. Circulating TNFR levels are associated with the number of P. gingivalis in saliva after adjusting for relevant clinical factors.


Discovery and SAR of novel 4-thiazolyl-2-phenylaminopyrimidines as potent inhibitors of spleen tyrosine kinase (SYK).
A series of SYK inhibitors based on the phenylamino pyrimidine thiazole lead 4 were prepared and evaluated for biological activity. Lead optimization provided compounds with nanomolar K(i)'s against SYK and potent inhibition in mast cell degranulation assays.


Facile reflux synthesis of polyethyleneimine-capped fluorescent carbon dots for sequential bioassays toward Cu2+ /H2 S and its application for a logic system.
In this work, we present a novel facile strategy for green synthesis of polyethyleneimine (PEI)-capped carbon dots (PEI-CDs), in which citric acid and PEI were chosen as reactants and highly fluorescent PEI-CDs could be readily obtained via a simple one-pot refluxing under 120 °C within 2 H. Fluorescence studies indicate that the as-prepared PEI-CDs exhibit strong fluorescence emission at 446 nm with excitation at 365 nm. Upon the sequential addition of Cu2+ and H2 S, PEI-CDs result in an interesting "ON-OFF-ON" three-state emission responses, promising a bifunctional sensory platform. Moreover, the Cu2+ /H2 S-facilated reversible fluorescence changes of PEI-CDs have demonstrated the design of an INHIBIT logic system based on Boolean logic.


Seed Dormancy in Arabidopsis Is Controlled by Alternative Polyadenylation of DOG1.
DOG1 (Delay of Germination 1) is a key regulator of seed dormancy in Arabidopsis (Arabidopsis thaliana) and other plants. Interestingly, the C terminus of DOG1 is either absent or not conserved in many plant species. Here, we show that in Arabidopsis, DOG1 transcript is subject to alternative polyadenylation. In line with this, mutants in RNA 3' processing complex display weakened seed dormancy in parallel with defects in DOG1 proximal polyadenylation site selection, suggesting that the short DOG1 transcript is functional. This is corroborated by the finding that the proximally polyadenylated short DOG1 mRNA is translated in vivo and complements the dog1 mutant. In summary, our findings indicate that the short DOG1 protein isoform produced from the proximally polyadenylated DOG1 mRNA is a key player in the establishment of seed dormancy in Arabidopsis and characterizes a set of mutants in RNA 3' processing complex required for production of proximally polyadenylated functional DOG1 transcript.


Gastric metastases of breast cancer: Histopathological and molecular characterization of a single Institution case series.
The metastatic spread of breast carcinoma to the stomach is a rare event and often represents a diagnostic challenge. In the present study, 23 cases of gastric metastases from breast cancer were retrospectively identified dating back until 2007. Primitive histotype, localization, gross appearance, microscopic architecture were analyzed. Cytokeratins 7 and 20, sex hormones, HER2 and Ki67 expression was evaluated. According to the results, the series was characterized by an enrichment of lobular primitive histotype (43.7%). In most cases gastric metastases were described as parietal nodules, polypoid masses or ulcerated lesions, mainly involving the antro-angular region. In a relatively high rate (10.5%) of cases, endoscopic examinations resulted negative for macroscopic lesions. More than half of the cases (52.2%) microscopically resembled primitive poorly cohesive gastric cancer. Because gross and histological findings can be deceiving, immunohistochemistry may be essential for the diagnosis of gastric metastases from breast cancer. Accordingly with the results of our analysis and literature review, an immunohistochemical panel composed of cytokeratins 7 and 20, Estrogen and Progesteron Receptors would drastically improve diagnostic accuracy. Interaction among the clinician, endoscopist and the pathologist is also essential to provide the patient the best therapeutic option.


Psychosocial consequences in offspring of women with breast cancer.
Breast cancer (BC) accounts for 24% of female cancers, with approximately one quarter of women likely to have offspring aged less than 25 years. Recent publications demonstrate negative psychosocial well-being in these offspring. We prospectively assessed for psychological distress and unmet needs in offspring of BC patients. Eligible offspring aged 14 to 24 years were consented and completed the Kessler-10 Questionnaire and Offspring Cancer Needs Instrument. Demographic and BC details were obtained. Over a 7-month period, 120 offspring from 74 BC patients were included. Fifty-nine mothers had nonmetastatic BC (nMBC), and 27 had metastatic BC (MBC) with median time from diagnosis of 27.6 and 36.1 months, respectively. The prevalence of high/very high distress was 31%, with significantly higher scores reported by female offspring (P = .017). Unmet needs were reported by more than 50% of offspring with the majority of needs relating to information about their mother's cancer. Greater unmet needs were seen in female offspring and offspring with none or one sibling for several domains (practical assistance, time-out, dealing with feelings, and support from friends; P < .05). Greater unmet needs were seen in regard to feelings for MBC patients' offspring compared with nMBC but were similar for other unmet needs. Our study confirms high levels of psychological distress in offspring of BC patients, with female offspring reporting significantly higher emotional distress and unmet needs. More than 50% of respondents reported unmet needs in areas that can potentially be supported, including greater information provision, improving practical issues, and enabling sufficient recreational time.


A new series of N-[2,4-dioxo-6-d-ribitylamino-1,2,3,4-tetrahydropyrimidin-5-yl]oxalamic acid derivatives as inhibitors of lumazine synthase and riboflavin synthase: design, synthesis, biochemical evaluation, crystallography, and mechanistic implications.
The penultimate step in the biosynthesis of riboflavin is catalyzed by lumazine synthase. Three metabolically stable analogues of the hypothetical intermediate proposed to arise after phosphate elimination in the lumazine synthase-catalyzed reaction were synthesized and evaluated as lumazine synthase inhibitors. All three intermediate analogues were inhibitors of Mycobacterium tuberculosis lumazine synthase, Bacillus subtilis lumazine synthase, and Schizosaccharomyces pombe lumazine synthase, while one of them proved to be an extremely potent inhibitor of Escherichia coli riboflavin synthase with a Ki of 1.3 nM. The crystal structure of M. tuberculosis lumazine synthase in complex with one of the inhibitors provides a model of the conformation of the intermediate occurring immediately after phosphate elimination, supporting a mechanism in which phosphate elimination occurs before a conformational change of the Schiff base intermediate toward a cyclic structure.


Plasmodium Secretion Induces Hepatocyte Lysosome Exocytosis and Promotes Parasite Entry.
The invasion of a suitable host hepatocyte by Plasmodium sporozoites is an essential step in malaria infection. We demonstrate that in infected hepatocytes, lysosomes are redistributed away from the nucleus, and surface exposure of lysosome-associated membrane protein 1 (LAMP1) is increased. Lysosome exocytosis in infected cells occurs independently of sporozoite traversal. Instead, a sporozoite-secreted factor is sufficient for the process. Knockdown of SNARE proteins involved in lysosome-plasma membrane fusion reduces lysosome exocytosis and Plasmodium infection. In contrast, promoting fusion between the lysosome and plasma membrane dramatically increases infection. Our work demonstrates parallels between Plasmodium sporozoite entry of hepatocytes and infection by the excavate pathogen Trypanosoma cruzi and raises the question of whether convergent evolution has shaped host cell invasion by divergent pathogens.


Instar development and disengagement rate of engorged female winter ticks, Dermacentor albipictus (Acari:Ixodidae), following single- and trickle-exposure of moose (Alces alces).
Seven hand-reared moose (Alces alces) calves and one yearling were infested with 30,000 larvae each of the winter tick. Dermacentor albipictus, either by single- or trickle-exposure (1000/day). They were examined weekly for instar changes from September/October until late May. By 2 and 3 weeks post-exposure, most larvae on single- and trickle-infested moose, respectively, had fed and molted to nymphs. Thereafter, tick development was similar between both infestation techniques. Nymphs dominated the tick population from October to mid-February, and adults from mid-February to May. The peak of host disengagement by engorged females was late March in both years. Weights of engorged females from calf moose declined over time during the disengagement period.


A hierarchical outcomes approach to test assessment.
This report describes a hierarchical classification system for clinical endpoints in diagnostic technology assessment. The model requires classification of investigative outcomes into 1 of 6 categories, including technical efficacy, diagnostic accuracy efficacy, diagnostic thinking efficacy, therapeutic efficacy, clinical outcome efficacy, and societal efficacy. Evaluations at successive levels indicate a broader understanding of the test's value. The purpose of this classification system is to help readers of the medical literature consider various aspects of test performance, and to identify aspects of a test that require additional investigation. It is also designed to be used as a template for systematic reviews of diagnostic tests. In this review, examples from the medical literature are discussed to highlight important concepts from the hierarchy model and their relevance to emergency medicine.


Phorbol ester-induced podosomes in normal human bronchial epithelial cells.
Spreading and migration of the basal cells neighboring a wound is essential for airway epithelial repair. To gain insight into the molecular mechanisms that govern these cellular processes, we asked whether normal human airway epithelial cells can form podosomes, a cellular structure discovered from cancer and mesenchymal cells that controls migration and invasion. Herein, we report that phorbol-12, 13-dibutyrate (PDBu), a protein kinase C activator, induced reorganization of cytoskeletal structure in primary normal human bronchial epithelial cells, and in normal human airway epithelial BEAS2B cells. Z-stack scanning confocal microscopy showed that PDBu-induced podosome-like structures contain actin-rich columns that arise from the ventral surface of the cell, and also revealed the presence of circular ruffles/waves at the dorsal cell surface. The molecular components of these cytoskeletal structures were determined with immunofluorescent staining. Using in situ zymography, we demonstrated that PDBu-induced podosomes were capable of degrading fibronectin-gelatin-sucrose matrix. PDBu also increased epithelial cell invasion across Transwell chamber. Podosomes and circular dorsal ruffles may be important for epithelial cell migration and invasion, thus contributing to respiratory epithelial repair and regeneration.


Neural Monitoring of the External Branch of the Superior Laryngeal Nerve During Transoral Thyroidectomy.
There is no study regarding intraoperative neural monitoring (IONM) of the external branch of the superior laryngeal nerve (EBSLN) during transoral thyroidectomy. The objective of this study was to evaluate the feasibility and success rate of electrical identification of the EBSLN during transoral robotic or endoscopic thyroidectomy. Case series study. We studied a cohort of 76 patients (87 nerves at risk, (NARs)) who underwent transoral robotic or endoscopic thyroidectomy and simultaneous intermittent IONM between July 2017 and May 2019. We performed the standard IONM procedure plus routine neural monitoring of the EBSLN. IONM and surgical outcome data were prospectively collected. Sixty-one patients underwent the robotic procedure, and 15 patients underwent the endoscopic procedure. Thirty-seven external branches of the superior laryngeal nerves at risk (42.5%) were electrically identified using electromyography signals (31 NARs, 35.6%) or cricothyroid muscle twitches (6 NARs, 6.9%). The mean pre-(S1) and post-dissection (S2) amplitudes of the EBSLN were 372 ± 147 and 351 ± 159 μV, respectively. The identification rates were not different between the robotic and endoscopic procedures. In comparing the early 20 NARs (18 patients) and the later 67 NARs (58 patients), the identification rate was higher in the later cases, although the difference was not statistically significant (25.0% vs. 47.8%, P = .079). IONM of the EBSLN is feasible and useful in identifying and preserving the nerve during transoral thyroidectomy, although the identification rate of the nerve is relatively low. 4 Laryngoscope, 131:E671-E676, 2021.


Breast cancer genetic counseling after diagnosis but before treatment: a pilot study on treatment consequences and psychological impact.
Female breast cancer patients carrying a BRCA1/2-mutation have an increased risk of second primary breast and ovarian tumors. Little is known about the psychological impact and treatment consequences of rapid genetic counseling and testing offered between breast cancer diagnosis and surgery. Female breast cancer patients, who had received rapid genetic counseling (and optional testing) (RGC(T)) at The Netherlands Cancer Institute between 2004 and 2008, received a questionnaire in 2009. BRCA-mutations were found in 10 of the 26 participants. Six mutation-carriers (60%) had an immediate bilateral mastectomy, compared with 25% of those without a mutation. Five patients (19%) reported having frequent worries about cancer recurrence; none indicated that such worries impaired daily functioning. Six patients had clinically relevant levels of breast cancer-specific distress at the time of assessment. These results suggest that RGC(T) in high-risk breast cancer patients may influence surgical treatment, without causing long-term psychosocial distress in the majority. These results are important, since rapid genetic counseling and testing are expected to be offered to newly diagnosed breast cancer patients with increasing frequency in order to inform these women and their surgeons about the possible familial/hereditary nature of their disease before deciding on treatment.


Engaging Fathers in the Promotion of Healthy Lifestyle Behaviors.
Parental engagement is an important component in lifestyle behavior change interventions for children as parents are uniquely positioned to establish a healthy environment and model healthy eating and physical activity habits for their children. Despite both mothers and fathers being important agents of behavioral change for their children, fathers are typically underrepresented in programming interventions. Physical activity may be an important strategy for fathers to become involved in lifestyle change with their children as, compared to mothers, fathers traditionally tend to be comfortable engaging in physical activity with their children.


Characterization of endogenous folate and incorporation of labelled folates into the brain of the South African fruit bat.
Folate in the brain of the South African fruit bat consists of 10-formyltetrahydropteroyglutamic acid and the tri-, tetra- and penta- forms of 5-methyltetrahydropteroylglutamic acid. Following parenteral injection, only 5-[3H]-methyltetrahydropteroylglutamic acid was taken up by the brain, but none of a dose of 14C-labelled tetrahydropteroylglutamic acid was detectable. Only trace smounts of the 5-methyltetrahydropteroylglutamic acid were converted into the formyl compounds and a small amount of methyltetrahydropteroyltriglutamic acid appeared after 96 h. There was no significant difference in vitamin B-12-deficient animals.


A combination of P300 and eye movement data improves the accuracy of auxiliary diagnoses of depression.
Exploratory eye movements (EEMs) and P300 are often used to facilitate the clinical diagnosis of depression. However, There were few studies using the combination of EEMs and P300 to build a model for detecting depression and predicting a curative effect. Sixty patients were recruited for 2 groups: high frequency repetitive transcranial magnetic stimulation(rTMS) combined with paroxetine group and simple paroxetine group. Clinical efficacy was evaluated by the Hamilton Depression scale-24(HAMD-24), EEMs and P300. The classification model of the auxiliary diagnosis of depression and the prediction model of the two treatments were developed based on a machine learning algorithm. The classification model with the greatest accuracy for patients with depression and healthy controls was 95.24% (AUC = 0.75, recall = 1.00, precision = 0.95, F1-score = 0.97). The root mean square error (RMSE) of the model for predicting the efficacy of high frequency rTMS combined with paroxetine was 3.54 (MAE [mean absolute error] = 2.56, R2 = -0.53). The RMSE of the model for predicting the efficacy of paroxetine was 4.97 (MAE = 4.00, R2 = -0.91). Based on the machine learning algorithm, P300 and EEMs data was suitable for modeling to distinguish depression patients and healthy individuals. However, it was not suitable for predicting the efficacy of high frequency rTMS combined with paroxetine or to predict the efficacy of paroxetine.


An augmented fixation method for distal fibular fractures in elderly patients: a biomechanical evaluation.
This biomechanical investigation compared two fixation techniques for distal fibular fractures. Elderly cadaver lower extremities with simulated fibula fractures underwent fixation either with a plate and intramedullary Kirschner wires (K-wires) with or without the addition of three screws inserted through the four cortices of the fibula and the tibia. The specimens were axially loaded to body weight on a materials testing machine, and the supinated foot was externally rotated to failure. Displacement at the fracture site was monitored with an extensometer. Comparing the augmented technique with the technique without additional screws, mean stiffness was 460 +/- 100 and 320 +/- 200 N-mm/deg, strength at failure was 31 +/- 10 and 19 +/- 7 N-m, strength at 30 degrees external rotation was 15 +/- 5 and 10 +/- 6 N-m, and axial deformation was 0.04 +/- 0.06 mm and 0.10 +/- 0.04 mm, respectively. All differences were statistically significant.


Vermicomposting of Taro (Colocasia esculenta) with two epigeic earthworm species.
The bioconversion potential of two epigeic species (Eisenia foetida Sav. and Eudrilus eugeniae Kinberg) of earthworms was assessed in terms of efficiency and sustainability of vermicomposting of Taro (Colocasia esculenta (Linn) Schott in Schott and Endl). In different vermireactors, each run in triplicates with one of the two species of earthworms, and 60 g of 6:1 Colocasia:cowdung as feed, vermicasts were produced with steadily increasing output in all the reactors. E. eugeniae was found to be more efficient producer of vermicasts than E. foetida. In all reactors, the earthworms grew well, increasing their weights and number.


Histologic and radiographic analysis of ductal carcinoma in situ diagnosed using stereotactic incisional core breast biopsy.
Stereotactic incisional core breast biopsy (SCBB) is a highly specific technique for diagnosing ductal carcinoma in situ (DCIS) in patients with suspicious mammographic microcalcifications. However, its sensitivity for excluding the presence of coexisting occult invasive disease in this setting is not fully established. We correlated SCBB findings to subsequent lumpectomy/mastectomy (lx/mx) results in 122 cases of DCIS. In 29 of these cases, the SCBB showed microscopic invasion (n = 15) or foci that were suspicious for invasion (n = 14). Likelihood for invasive disease in subsequent lx/mx samples from each case then was compared with various parameters, including DCIS grade, extent and mammographic findings. Overall, 13% of cases in which the SCBB showed DCIS only (i.e., without any evidence of invasion), had invasive disease in the subsequent excision. This finding was significantly correlated with DCIS grade (low: 0/26 [0%], intermediate: 2/31 [6%], high: 10/36 [28%], P <.001). Invasive lesions were usually small (nine T1a, one T1b, and two T1c) and typically present within more extensive fields of DCIS (no invasion: 1.5 cm DCIS size; invasion: 2.8 cm mean DCIS size, P =.01). This was reflected by greater extent of involvement in the SCBB (5/8 cases with invasion had >15 ducts involved, versus 4/23 with <15 ducts involved, P =.03). SCBB that were suspicious or positive for microinvasion demonstrated invasion in most subsequent excision (susp: 7/14 [50%], microinv: 11/15 [73%]), generally of significant extent (11/18 T(1b-c)). 1. Patients with SCBB showing high grade DCIS and DCIS suspicious or positive for microinvasion have a significant and high likelihood, respectively, of harboring occult invasive neoplasm. They should accordingly be carefully evaluated radiographically, and possibly with sentinel node biopsy to facilitate axillary staging. 2. Likelihood of occult invasion is correlated with overall DCIS size/extent.


Concomitant valvotomy and subclavian-main pulmonary artery shunt in neonates with pulmonary atresia and intact ventricular septum.
Our current approach to the management of neonates with pulmonary atresia and intact ventricular septum is to perform a transarterial pulmonary valvotomy through a left anterolateral thoracotomy followed by a polytetrafluoroethylene shunt between the left subclavian artery and the pulmonary trunk at the site of the pulmonary arteriotomy. From October, 1983, to December, 1985, 7 consecutive neonates with pulmonary atresia and intact ventricular septum were managed in this fashion. Mean age was 5.1 days (5 patients, less than 48 hours old), and mean weight was 3.3 kg (range, 2.5-4.3 kg). Right ventricular morphology was type I (tripartite) in 4 patients, type II (absent trabecular portion) in 2, and type III (absent trabecular and infundibular portions) in 1. The mean right ventricular to left ventricular peak systolic pressure ratio was 1.5. One patient who initially had valvotomy alone required a left subclavian-pulmonary trunk shunt the next day for hypoxemia. All other patients had a valvotomy and shunt during the same procedure. There were no operative or hospital deaths. Follow-up of 3.5 to 34 months (mean, 17.5 months) confirmed shunt patency in all patients. Three of 4 patients undergoing postoperative catheterization have shown good right ventricular growth; 2 have undergone successful repair at 10 and 23 months. There have been 3 late deaths at 3.5, 4, and 8 months. Two other patients are doing well and are awaiting postoperative catheterization. This procedure permits synchronous valvotomy and shunting without the need for cardiopulmonary bypass in these critically ill neonates.(ABSTRACT TRUNCATED AT 250 WORDS)


All-Inside Arthroscopic Modified Broström Technique to Repair Anterior Talofibular Ligament Provides a Similar Outcome Compared With Open Broström-Gould Procedure.
To introduce an all-inside modified Broström technique to suture the anterior talofibular ligament (ATFL) and inferior extensor retinaculum (IER) under arthroscopy and to compare its outcomes with those of the conventional open procedure. All patients who underwent arthroscopic or open repair of the ATFL between June 2014 and December 2017 were included in this study. Visual analog scale (VAS), Karlsson and Peterson (K-P), American Orthopedic Foot and Ankle Society (AOFAS) ankle/hindfoot, and Tegner activity scores, as well as manual anterior drawer test (ADT), were used to evaluate the patients preoperatively and ≥2 years after surgery. The Sefton grading system was used to assess the level of satisfaction after surgery. Detailed surgical data and intraoperative findings were documented at the time of surgery. A total of 67 patients, 31 in the arthroscopic group and 36 in the open group, were included in this study (43 men and 24 women, mean body mass index 24.00, range 19.53 to 30.03). The surgical duration in the arthroscopic group (median, 34 minutes; range, 25 to 74) was significantly shorter than that in the open group (mean, 43.08 ± 8.11 minutes; 95% confidence interval [CI] 40.34 to 45.83) (P = .007). At the last follow-up, the subjective functional scores and ADT results improved significantly in both cohorts (P < .001). However, no significant difference was found in the VAS score (1.74 ± 1.24, 95% CI 1.29 to 2.2, in the open group versus 1.58 ± 1.2, 95% CI 1.18 to 1.99, in the arthroscopic group; P = .581), AOFAS score (91.71 ± 5.46, 95% CI 89.71 to 93.71, versus 90.67 ± 5.59, 95% CI 88.78 to 92.56; P = .444), K-P score (87.52 ± 7.59, 95% CI 84.73 to 90.3, versus 88.75 ± 5.56, 95% CI 86.87 to 90.63; P = .446), and ADT evaluation (normal: 96.77% versus 94.44%, P = .557) between the arthroscopic and open groups, respectively. In addition, 28 cases (90.32%) in the arthroscopic group and 32 (88.89%) in the open group achieved satisfactory results based on the Sefton grading system (P = .736). Seventeen patients (47.2%) in the open group and 18 patients (58.1%) in the arthroscopic group underwent Tegner evaluation after surgery, which showed no significant difference (5, interquartile range [IQR] 1 in the open group versus 5, IQR 3 in the arthroscopic group; P = .883). Complications were reported in 4 (11.1%) and 2 (6.5%) patients who underwent open and arthroscopic surgeries, respectively (P = .813). Both open and arthroscopic modified Broström surgeries generated favorable outcomes, with a significant improvement compared with the preoperative condition. Compared with the open Broström-Gould procedure, the all-inside arthroscopic modified Broström technique produced equivalent functional and clinical results at a minimum of 2 years after the operation, with a shorter surgical duration. Arthroscopic repair might be a safe and viable alternative to open surgery for lateral ankle stabilization. III.


Recognition of a non-standard base pair by thermostable DNA polymerases.
Examination of several commercially available thermostable DNA polymerases identifies 9 degrees N DNA polymerase as single enzyme that could incorporate two components of an expanded genetic alphabet, 2,4-diaminopyrimidine and xanthosine as deoxynucleoside triphosphate opposite their cognate base in a DNA template.


The physiology and metabolism of the human gastric pathogen Helicobacter pylori.
Helicobacter pylori is a spiral Gram-negative microaerophilic bacterium that causes one of the most common infections in humans; approximately 30-50% of individuals in Western Europe are infected and the figure is nearly 100% in the developing world. It is recognized as the major aetiological factor in chronic active type B gastritis, and gastric and duodenal ulceration and as a risk factor for gastric cancer. H. pylori normally inhabits the mucus-lined surface of the antrum of the human stomach where it induces a mild inflammation, but its presence is otherwise usually asymptomatic. A variety of virulence factors appear to play a role in pathogenesis. These include the vacuolating cytotoxin VacA, cytotoxin-associated proteins, urease and motility. All are under intense study in an attempt to understand how the bacterium colonizes and persists in the gastric mucosa, and how H. pylori infections lead to the disease state. Although an explosion of research on H. pylori has occurred within the past 15 years, most efforts have been directed at aspects of the bacterium and disease process which are of direct clinical relevance. Consequently, our knowledge of many aspects of the physiology and metabolism of H. pylori is relatively poor. This should change rapidly now that the complete genome sequence of a pathogenic strain has been determined. This review focuses attention on these more fundamental areas of Helicobacter biology. Analysis of the genome sequence and some detailed metabolic studies have revealed solute transport systems, an incomplete citric acid cycle and several incomplete biosynthetic pathways, which largely explain the complex nutritional requirements of H. pylori. The microaerophilic nature of the bacterium is of particular interest and may be due in part to the involvement of oxygen-sensitive enzymes in central metabolic pathways. However, the biochemical basis for the requirement for CO2 has not been completely explained and a major surprise is the apparent lack of anaplerotic carboxylation enzymes. Although genes for glycolytic enzymes are present, physiological studies indicate that the Entner-Doudoroff and pentose phosphate pathways are more active. The respiratory chain is remarkably simple, apparently with a single terminal oxidase and fumarate reductase as the only reductase for anaerobic respiration. NADPH appears to be the preferred electron donor in vivo, rather than NADH as in most other bacteria. H. pylori is not an acidophile, and must possess mechanisms to survive stomach acid. Many studies have been carried out on the role of the urease in acid tolerance but mechanisms to maintain the protonmotive force at low external pH values may also be important, although poorly understood at present. In terms of the regulation of gene expression, there are few regulatory and DNA binding proteins in H. pylori, especially the two-component 'sensor-regulator' systems, which indicates a minimal degree of environmentally responsive gene expression.


Influence of anthropometric features on peroneus longus graft diameter in Anterior Cruciate Ligament reconstruction: A cohort study.
Anterior Cruciate Ligament (ACL) is the most common ligament injury during sports activities that was treated with ACL reconstruction. Nowadays, peroneus longus is used in ACL reconstruction. However, it is difficult to predict the peroneus longus graft diameter for ACL reconstruction. Thus, preoperative measurements are very important to predict peroneus longus autograft for ACL reconstruction. A cohort retrospective study was conducted using consecutive sampling method from February 2016 until October 2017 in our center. We recorded patients' characteristics include gender, age, body weight, height, and Body Mass Index (BMI) preoperatively. We measured peroneus longus graft diameter intraoperatively, and analysed data using Spearman correlation. Thirty-nine patients met inclusion criteria. There were 28 males and 11 females in the peroneus group. From the patients' mean characteristics, age was 25.10 ± 9.16, body weight 71.23 ± 14.17, height 169.13 ± 8.81, and BMI 20.96 ± 3.44. Intraoperative peroneus longus diameter measurement was 8.56 ± 0.82. Spearman correlation showed significant correlation between intraoperative peroneus longus diameter with patient's height, body weight, and BMI with p < 0.05. Patients' characteristics including gender, height, weight, and BMI in preoperative measurements can predict peoneus longus graft diameter intraoperatively.


Proposal to modify Rule 27 of the International Code of Nomenclature of Prokaryotes.
We propose emendation of Rule 27(2)(b) of the International Code of Nomenclature of Prokaryotes so that for new combinations the basonym and its reference must be given. We also propose minor changes to Note 1 and Note 2 of Rule 27.


Correction: Selective photoregulation of the activity of glycogen synthase and glycogen phosphorylase, two key enzymes in glycogen metabolism.
Correction for 'Selective photoregulation of the activity of glycogen synthase and glycogen phosphorylase, two key enzymes in glycogen metabolism' by Mireia Díaz-Lobo, et al., Org. Biomol. Chem., 2015, 13, 7282-7288.


Hydrothorax: unusual complication of ventriculoperitoneal shunts.
A case is presented in which puncture of the pleura and hydrothorax occurred during placement of a ventriculoperitoneal shunt. Treatment of this complication is outlined.


Differential regulation of prostaglandin synthesis in neonatal rat microglia and astrocytes by somatostatin.
The aim of the present study was to investigate the role of somatostatin in the regulation of brain inflammation. We used lipopolysaccharide-induced prostaglandin E2 production in neonatal rat microglia and in astrocytes as a model of brain inflammation. Our data show an unexpected differential effect of somatostatin on lipopolysaccharide-induced prostaglandin E2 synthesis in rat microglia vs. in astrocytes. Somatostatin markedly inhibited the lipopolysaccharide-induced prostaglandin E2 synthesis in microglia whereas, on the contrary, in astrocytes the lipopolysaccharide-induced prostaglandin E2 production was actually enhanced by somatostatin. These novel observations imply that somatostatin may regulate brain inflammation in a dual manner.


Nursing Students' Intention to Work as Community Health Nurse in China and Its Predictors.
To identify nursing students' intention and the predictors of intention to work as a community health nurse in China. A cross-sectional investigation was conducted. A questionnaire based on the Theory of Planned Behavior was delivered by Wechat to a convenience sample of 810 students. In the study, 345 students (42.6%) expressed the intention to be a community health nurse, and the program type, students' attitude, subjective norm and perceived behavioral control were significant predictors of this intention. The results highlight the necessity of community health nursing education reform in curriculum, teaching methods and nursing educators training, so as to improve students' ability and acceptance of community health nursing. Working as community health nurse is not favored by students, and the current situation of community health nursing and nursing education system in China has not helped students recognize the attractive complexity in community care.


Trends in breast cancer incidence and mortality in Denmark, 1943-1982.
The trend in breast cancer incidence and mortality was examined using data from the Danish Cancer Registry and the national mortality statistics respectively. The study population comprised 65,870 incident cases and 33,817 deaths from breast cancer in Denmark between 1943 and 1982. The incidence rate remained almost constant up to around 1960, whereafter it rose steadily. Comparatively little change was observed in mortality. Possible explanations for the differing trends in incidence and mortality include under-reporting of breast cancer from death certificates and improvement in survival. A multivariate statistical analysis showed that the increase in incidence was due mostly to a cohort effect, though calendar time may have had a slight effect as well.


Poetry as an engagement strategy: A novice teacher experience of its use within lectures.
It has been acknowledged the traditional lecture format is a familiar teaching methodology and that there is still much to be learnt from using this in class room based lectures. Whilst the first author was a postgraduate student undertaking a programme in Nurse Education at a University in the Republic of Ireland, poetry was used to challenge undergraduate nursing students' attitudes towards older persons in a large group format. The students were in Year 3 of a Bachelor of Nursing Science General and Intellectual Disability Programmes. Feedback was obtained from the students that comprised of three main themes; Aids Recall of Information; Enriched Learning Experiences, Challenges Attitudes to Person Centred Care. Thus, the paper aims to evaluate using poetry as an engaging teaching strategy within a lecture format for the first time as a novice teacher when drawing out nursing students' attitudes towards older persons with a focus on supporting them in embracing key care skills in the clinical setting. This paper should provide other student educationalists the opportunity to see the value of poetry as a teaching strategy and provide practical tips on its use within the classroom.


Factor associated with progression to chronic arterial hypertension in women with preeclampsia in Yaoundé, Cameroon.
Hypertensive diseases in pregnancy are the leading medical problem during pregnancy. Some of the women affected remain hypertensive after pregnancy and the post-partum period. This study aimed to assess the factors associated to the persistence of hypertension after preeclampsia. This was a retrospective cohort study which included all women who had preeclampsia. The minimal follow-up period was 12 months. We excluded from the study all women who had superimposed preeclampsia. Sociodemographic data and past history were recorded and a physical exam was performed for all participants. Multivariate logistic regression was used to determine factors independently associated to the persistence of hypertension. Our cohort consisted of 136 women. The mean follow-up period was 3.7 years. Thirty two women (23.53%) remained hypertensive. This represented an incidence rate of 2.85% per year. Old age (≥ 40 years), housewife occupation, multigravidity (> 4), onset of preeclampsia before 34 weeks' gestation, obesity and the presence of hypertension in siblings were factors independently associated to persistent hypertension. Many women affected by preeclampsia remain hypertensive after pregnancy. It is important to provide adequate follow-up for this patients in order to intervene on the factors leading to this outcome.


Cross-kingdom amplification using bacteria-specific primers: complications for studies of coral microbial ecology.
PCR amplification of pure bacterial DNA is vital to the study of bacterial interactions with corals. Commonly used Bacteria-specific primers 8F and 27F paired with the universal primer 1492R amplify both eukaryotic and prokaryotic rRNA genes. An alternative primer set, 63F/1542R, is suggested to resolve this problem.


The Sézary syndrome.
Symptoms of the Sézary syndrome are described in a case history. Sézary's syndrome is a lymphoproliferative process of the skin, which eventually develops into an erythrodermia. Strange lymphocytes with a cerebriform chromatin structure, often with T-cell characteristics, circulate in the blood stream. In few instances they are also found in lymphnodes and bone marrow. This primarily benign disease can become malignant, possibly due to an overaggressive cytostatic therapy. Besides the hitherto unknown endogenous causes, exogenous factors cannot be excluded.


Correction: A novel derivative of betulinic acid, SYK023, suppresses lung cancer growth and malignancy.
[This corrects the article DOI: 10.18632/oncotarget.3701.].


Instrumental activities of daily living and mild cognitive impairment.
Functional impairments are a necessary requirement for the diagnosis of a dementia along with observed cognitive impairment. Comparatively, functional abilities are often relatively intact in those with mild cognitive impairment (MCI). The current research examined the associations between memory clinic participants classified as cognitively intact, amnestic MCI, and mixed/dysexecutive MCI, using Jak-Bondi criteria, and Instrumental Activities of Daily Living - Compensation Scale (IADL-C) abilities, an informant-based questionnaire that quantifies functional abilities. The associations between functional abilities as assessed with the IADL-C and performance on neuropsychological tests were also investigated. IADLC scores were obtained along with a comprehensive neuropsychological protocol on memory clinic participants (n = 100) classified as cognitively normal (CN), amnestic MCI (aMCI), or a combined mixed/dysexecutive (mixed/dys) MCI. Regression analyses were employed to determine how the IADLC related to neuropsychological test performance. On the IADLC, greater functional impairment was commonly observed in the mixed/dys MCI group compared to CN participants. Furthermore, the mixed/dys MCI group had lower scores on activities such as Money and Self-Management, Travel and Event Memory subscales compared to the CN group. Linear regression analyses found greater functional impairment in relation to lower scores on executive and episodic memory tests. Greater functional impairment as assessed with the IADL-C appears to be disproportionately associated with dysexecutive difficulty, and to a lesser degree, episodic memory.


Prostate carcinoma cell death resulting from inhibition of proteasome activity is independent of functional Bcl-2 and p53.
The ATP/ubiquitin-dependent 26S proteasome is a central regulator of cell cycle progression and stress responses. While investigating the application of peptide aldehyde proteasome inhibitors to block signal-induced IkappaBalpha degradation in human LNCaP prostate carcinoma cells, we observed that persistent inhibition of proteasomal activity signals a potent cell death program. Biochemically, this program included substantial upregulation of PAR-4 (prostate apoptosis response-4), a putative pro-apoptotic effector protein and stabilization of c-jun protein, a potent pro-death effector in certain cells. We also observed modest downregulation of bcl-XL, a pro-survival effector protein. However, in contrast to some recent reports stable, high level, expression of functional bcl-2 protein in prostate carcinoma cells failed to signal protection against cell death induction by proteasome inhibitors. Also in disagreement to a recent report, no evidence was found for activation of the JNK stress kinase pathway. A role for p53, a protein regulated by the proteasome pathway, was ruled out, since comparable cell death induction by proteasome inhibitors occurred in PC-3 cells that do not express functional p53 protein. These data signify that the ubiquitin/proteasome pathway represents a potential therapeutic target for prostate cancers irrespective of bcl-2 expression or p53 mutations.


Bone structure determined by HR-MDCT does not correlate with micro-CT of lumbar vertebral biopsies: a prospective cross-sectional human in vivo study.
Osteoporosis is characterized by a deterioration of bone structure and quantity that leads to an increased risk of fractures. The primary diagnostic tool for the assessment of the bone quality is currently the dual-energy X-ray absorptiometry (DXA), which however only measures bone quantity. High-resolution multidetector computed tomography (HR-MDCT) offers an alternative approach to assess bone structure, but still lacks evidence for its validity in vivo. The objective of this study was to assess the validity of HR-MDCT for the evaluation of bone architecture in the lumbar spine. We conducted a prospective cross-sectional study to compare the results of preoperative lumbar HR-MDCT scans with those from microcomputed tomography (μCT) analysis of transpedicular vertebral body biopsies. For this purpose, we included patients undergoing spinal surgery in our orthopedic department. Each patient underwent preoperative HR-MDCT scanning (L1-L4). Intraoperatively, transpedicular biopsies were obtained from intact vertebrae. Micro-CT analysis of these biopsies was used as a reference method to assess the actual bone architecture. HR-MDCT results were statistically analyzed regarding the correlation with results from μCT. Thirty-four patients with a mean age of 69.09 years (± 10.07) were included in the study. There was no significant correlation for any of the parameters (bone volume/total volume, trabecular separation, trabecular thickness) between μCT and HR-MDCT (bone volume/total volume: r = - 0.026 and p = 0.872; trabecular thickness: r = 0.074 and r = 6.42; and trabecular separation: r = - 0.18 and p = 0.254). To our knowledge, this is the first study comparing in vivo HR-MDCT with μCT analysis of vertebral biopsies in human patients. Our findings suggest that lumbar HR-MDCT is not valid for the in vivo evaluation of bone architecture in the lumbar spine. New diagnostic tools for the evaluation of osteoporosis and preoperative orthopedic planning are urgently needed.


Unveiling microbial preservation under hyperacidic and oxidizing conditions in the Oligocene Rio Tinto deposit.
The preservation of biosignatures on Mars is largely associated with extensive deposits of clays formed under mild early Noachian conditions (> 3.9 Ga). They were followed by widespread precipitation of acidic sulfates considered adverse for biomolecule preservation. In this paper, an exhaustive mass spectrometry investigation of ferric subsurface materials in the Rio Tinto gossan deposit (~ 25 Ma) provides evidence of well-preserved molecular biosignatures under oxidative and acidic conditions. Time of flight secondary ion mass spectrometry (ToF-SIMS) analysis shows a direct association between physical-templating biological structures and molecular biosignatures. This relation implies that the quality of molecular preservation is exceptional and provides information on microbial life formerly operating in the shallow regions of the Rio Tinto subsurface. Consequently, low-pH oxidative environments on Mars could also record molecular information about ancient life in the same way as the Noachian clay-rich deposits.


Evolutionary history of Mo25 gene in plants, a component of RAM/MOR signaling network.
Change in cell morphogenesis is an important feature for proper development of eukaryotes. It is necessary for cell polarity and asymmetry and is essential for asymmetric cell division. RAM/MOR is a conserved signaling network that coordinates cell polarity determinants important for asymmetric cell division and cell polarity establishment. Mo25 is a scaffold protein that acts as a master regulator of the germinal center kinase (GCK) which triggers the downstream signaling of this network. Little is known about RAM/MOR network or Mo25 protein homologs in plants. Here, we provide a glimpse of the evolutionary gene history of Mo25 in green plants. Our data showed that a duplication of Mo25 occurred at the basis of land plants (Embryophyta), forming the groups Mo25A and Mo25B. Further duplication events occurred in other plant lineages and one subgroup of sequences seemed to be rapidly diverging. This subgroup contained an A. thaliana paralog (AtMo25-1) which lacks intron and is expressed in a similar fashion of retrogenes (i.e. low expression levels and narrow expression breadth), suggesting that this paralog was duplicated by retroposition. We also showed that all AtMo25 proteins are structurally similar to each other and to the human homolog, although differences in residues in the interface between human Mo25 and MST3 are observed in the A. thaliana homologs. Expression profile of AtMo25 homologs suggest that they are required at different developmental contexts, possibly interacting with different partners. Finally, we discuss whether Mo25 duplication in Embryophyta could be an evolutionary novelty important for the terrestrial environment conquest and whether the duplicated paralogs are undergoing neo- or subfunctionalization.


Issues in replicating the trauma--Stren conversion.
The Trauma--Stren (T-S) conversion procedure was examined at a large state university and the construct related to personality and cognitive process variables. Significantly more respondents reported T-S conversion than in the original studies. Conversion was not significantly correlated with personal variables. The presence of experiences in which an event was reported as simultaneously traumatic and strenful is reported, and the criteria for clearly identifying the conversion phenomenon are questioned.


The role of saccular afferents in vertical optokinetic nystagmus in primates. A study in relation to optokinetic nystagmus in microgravity.
After bilateral sacculectomies, the squirrel monkey's vertical optokinetic nystagmus showed a gain increase of slow-phase down-nystagmus and a gain decrease of the slow-phase up-nystagmus. The nystagmus beating field of the former shifted upward but that of the latter did not change clearly. These results are in general agreement with the findings in man during the recent shuttle flight and indicate the functional linkage of saccular afferents to the vertical optokinetic nystagmus.


Plexiform neurofibroma of the penis associated with erectile dysfunction due to arterial steeling.
Solitary involvement of the genitourinary tract by Von Recklinghousen disease (VRD) is extremely rare. This report documents the management of a case of a plexiform neurofibroma on the penile shaft associated with erectile dysfunction. The literature surrounding VRD and its effects on the genital area was also investigated. Methods. After a complete preoperative investigation of the nature of the mass and of the erectile dysfunction, the neurofibroma was completely excised with preservation of the neurovascular bundle. At 6-months postoperative follow-up, there was no sign of tumor recurrence and the glans sensation was maintained. The erectile dysfunction persisted postoperatively and failed to respond to medical treatment. A complete excision of penile neurofibromas is mandatory to prevent recurrence or malignant degeneration and can be safely performed preserving the neurovascular bundle.


Metabolites of gut microbiota fermenting Poria cocos polysaccharide alleviates chronic nonbacterial prostatitis in rats.
Chronic nonbacterial prostatitis (CNP) is a common urology disease. Our previous research found Poria cocos polysaccharides (PPs) alleviated CNP and suggested the effect was related to gut bacteria. We investigated the crucial bacteria and their metabolites responsible for the anti-CNP effect to discover possible mechanisms. The results showed that after the fermentation of PPs by human fecal microbiota, Parabacteroides, Fusicatenibacter, and Parasutterella were significantly enriched. Haloperidol glucuronide and 7-ketodeoxycholic acid generated by these bacteria could be responsible for the increased expression of Alox15 and Pla2g2f and the reduced expression of Cyp1a1 and Hsd17b7 in colon epithelium. The ratio of dihydrotestosterone to estradiol in serum was regulated, and CNP was alleviated. Our results suggested that Parabacteroides, Fusicatenibacter, and Parasutterella could be the essential bacteria in CNP alleviation and their metabolites of PPs 7-ketodeoxycholic acid and haloperidol glucuronide could be the signal molecules of the "gut-prostate axis".


[Kidney trauma in a 13 years old child with voluminous bilateral hydronephrosis (author's transl)].
This is a report of a case of bilateral renal trauma. Acute rupture of the right kidney and bilateral hydronephrosis with significant parenchymal destruction are described. Unusual surgical cure is reported.


Individual and Contextual Factors Associated with Teenage Pregnancy in Colombia: A Multilevel Analysis.
To analyze municipal- and individual-level factors related to the prevalence of teenage pregnancy in Colombia during 2015. We analyzed 660,767 births registers, of which 21.5% recorded adolescent women. At an individual level, marital status, educational level, area of residence, and access to health services were included in the analysis. At the contextual level, Colombian municipal socioeconomic characteristics and proxies of violence and poverty were analyzed. A multilevel logistic regression model was generated with a Markov Chain Monte Carlo estimation method using 100,000 simulations in MLwiN 2.32 software. Multilevel modeling revealed an increased risk of teenage pregnancy in municipalities with the highest numbers of people expelled by forced displacement (OR 1.21; CI 95%, 1.13-1.29) and with unsatisfied basic needs (OR 1.09; CI 95%, 1.02-1.17). At an individual level, the majority of the teenage women were unmarried and/or had an unstable partnership, a low level of educational, a subsidized health regimen, and resided in the municipal seat. Municipal contextual variables related to poverty, violence, and social inequity contribute to an increase in teenage pregnancy in Colombia. At the individual level, marital status, educational level, and area of residence is associated with teenage pregnancy. It is therefore imperative to include municipal contextual characteristics in the design of the national political agenda.


Effect of a diffusional barrier to a metabolite across hepatocytes on its kinetics in "enzyme-distributed" models: a computer-aided simulation study.
The effect of a diffusional barrier to a metabolite between the blood and hepatocytes on elimination kinetics of formed and preformed metabolites was predicted under various enzymic distributions in the liver by computer-aided simulation. Sequential metabolism by which the primary metabolite (MI) is generated from the parent drug (D) and further metabolized to the terminal metabolite (MII) by enzymes A and B, respectively, was chosen for the simulation. Moreover, four models of enzyme distribution patterns were defined with regard to the hepatic blood flow path. The extraction ratios for the preformed and formed metabolites (designated as Em and Ep----m, respectively) were simulated by varying both the average intrinsic clearance of enzyme B (CLint,B) and the permeability of hepatocytes for MI (Pm), while keeping the average intrinsic clearance of enzyme A (CLint,A) equal to hepatic blood flow (Q). When a rapid equilibrium of MI between the blood and hepatocytes held, i.e., Pm was large relative to Q, Em was equal to or higher than Ep----m for all models, as previously shown by Pang and Stillwell. By contrast, it was found that when a diffusional barrier for MI existed, i.e., Pm was small relative to Q, Em was equal to or lower than Ep----m. Furthermore, it was observed that the smaller Pm became, the larger the difference between Em and Ep----m became. We further simulated the effect of the intrinsic clearance (CLint,C) for a metabolic pathway, which competes for that by enzyme A, on the Ep----m value. In the model assuming even distribution of all the enzymes along the flow path, irrespective of the CLint,C value, a similar effect of Pm on Ep----m was observed when the Pm value was relatively small (Pm less than Q). By contrast, in the case of uneven enzymic distributions of enzymes A and B, the effect of the CLint,C value on the relationship between Pm and Ep----m occurred to some extent. From these simulations, it was concluded that lower membrane permeability (Pm) both diminishes the entry of preformed metabolite into the hepatocytes and accelerates the removal of intracellularly formed metabolite (through sequential metabolism) by diminishing its efflux, yielding lower Em than Ep----m. When Pm becomes small (Pm less than 1/10Q), these mechanisms for lower Em than Ep----m predominate over other mechanisms such as the presence of a competing metabolic route and uneven distribution of enzymes.


An improved approach to diagnosing and treating conjunctival mucoepidermoid carcinoma.
The current case of conjunctival mucoepidermoid carcinoma offers features that expand the biologic spectrum afforded by this tumor. More focused strategies should be developed for its earlier histopathologic diagnosis and improved management (historical recurrence rate of 85%). A 63-year-old woman with a history of rheumatoid arthritis and idiopathic sclerosing cholangitis developed scleral thinning, anterior chamber cells and flare, and uveal prolapse. Biopsies of the epibulbar lesion were initially misinterpreted as a squamous cell carcinoma but on review harbored CK7-positive cells and contained rare goblet cells brought out with Alcian blue and mucicarmine staining. Intraocular extension exhibited micro-and macrocysts with minimal goblet cells. Focal CK7 immunopositivity in any epibulbar squamous dysplasia or in invasive carcinoma should lead to suspicion of a mucoepidermoid carcinoma. Behaviorally aggressive or rapidly recurrent epithelial squamous tumors with "inflammatory" features or unusual clinical characteristics should be initially stained at multiple levels for the detection of parsimonious mucus secretion. Surgical options include wide excision and partial sclerectomy with cryotherapy for superficial invasion and/or interferon therapy. Results with radiotherapy and cryotherapy for deep scleral invasion have been unpredictable or unacceptable compared with surgery.


Alpha- and gamma-tocopherol levels in lipoproteins fractionated by affinity chromatography.
Alpha- and gamma-tocopherol levels of nine women were measured in whole serum and in serum lipoproteins separated by heparin affinity chromatography. Alpha-tocopherol levels (mean +/- SD) in whole serum, low density plus very low density lipoproteins and high density lipoproteins were 10.8 +/- 2.7, 6.4 +/- 1.6 and 4.6 +/- 1.4 (micrograms/ml), respectively. Corresponding values (micrograms/ml) for gamma-tocopherol were 1.2 +/- 0.5, 0.7 +/- 0.3 and 0.6 +/- 0.2. Recoveries of serum alpha- and gamma-tocopherol from the heparin columns were 102 +/- 5% and 105 +/- 7%, respectively. Serum alpha-tocopherol was linearly correlated with components of high density lipoprotein (apolipoproteins, high density lipoprotein cholesterol), but not with serum total lipids or indices of low density lipoprotein, even though high density lipoprotein carried less than half of the serum alpha-tocopherol. However, serum gamma-tocopherol was highly correlated with indices of serum lipids, such as serum cholesterol (r = 0.92, p = 0.005). The coefficient for the correlation of low density lipoprotein (+ very low density lipoprotein) tocopherol with high density lipoprotein tocopherol was r = 0.66 (p = 0.06) for alpha-tocopherol and r = 0.84 (p = 0.004) for gamma-tocopherol. These differences in the relationships of the two tocopherols to lipids and lipoproteins support the view that when the two tocopherols are present at normal dietary levels, gamma-tocopherol partitions between lipoproteins based on their relative lipid content, but a portion of the alpha-tocopherol in high density lipoprotein is specifically bound.


Diabetic cardiomyopathy.
Diabetes mellitus is associated with a specific cardiomyopathy. This is evident from the clinical-pathological work and the epidemiologic data from the Framingham study. Noninvasive studies of diabetics have shown alterations in systolic and diastolic function that may ultimately lead to clinical heart failure. The relationship of these cardiac changes to the type of diabetes, its duration, and its severity is not settled. However, a correlation between changes in heart function and other complications of diabetes has been demonstrated. Insufficient prospective data is available from noninvasive studies to establish the frequency of progression from subclinical cardiac dysfunction to overt congestive failure. The pathogenesis of this disorder is still uncertain. Pathological studies have shown changes in the intramural arteries, arterioles, and capillaries but their functional significance is uncertain. Experimental studies have shown interstitial changes leading to an apparently less compliant left ventricle in the diabetic dog and monkey. In the diabetic rat reversible changes were found in myocardial function, related to changes in contractile proteins and intracellular calcium metabolism. In both species, the response to anoxia or ischemia was altered in the presence of diabetes. However, irreversible depression of the contractile element was not found in most animal studies of isolated diabetes. In contrast, the combination of hypertension and diabetes leads to substantial cardiac damage and circulatory congestion, both in clinical and experimental investigations. Clearly much more work must be carried out to understand the pathogenesis, treatment, and ultimately the prevention of diabetic cardiomyopathy.


The tryptophan-kynurenine pathway in immunomodulation and cancer metastasis.
The activation of the kynurenine pathway in cancer progression and metastasis through immunomodulatory pathways has drawn attention to the potential for kynurenine pathway inhibition. The activation of the kynurenine pathway, which results in the production of kynurenine metabolites through the degradation of tryptophan, promotes the development of intrinsically malignant properties in cancer cells while facilitating tumour immune escape. In addition, kynurenine metabolites act as biologically active substances to promote cancer development and metastasis. A literature review was conducted to investigate the role of the tryptophan-kynurenine pathway in immunomodulation and cancer metastasis. Evidence suggests that several enzymes and metabolites implicated in the kynurenine pathway are overexpressed in various cancers. As such, the tryptophan pathway represents a promising target for cancer treatment. However, downstream signalling pathways, including aryl hydrocarbon receptor activation, have previously induced diverse biological effects in various malignancies, which resulted in either the promotion or the inhibition of metastasis. As a result, a thorough investigation of the kynurenine pathway and its regulatory mechanisms is necessary in order to properly comprehend the effects of kynurenine pathway activation involved in cancer development and metastasis.


Increased blood pressure responses to central angiotensin II in spontaneously hypertensive rats.
The blood pressure responses following infusions of angiotensin II (ANG II) into the brain ventricles (i.v.t.) have been tested in spontaneously hypertensive (SH) rats and in normotensive Wistar Kyoto (WK) rats. The mean arterial blood pressure increases were significantly higher in SH rats than in WK rats. Propranolol treatment reduced blood pressure increases to i.v.t. ANG II in WK, but not in SH rats. The higher sensitivity to i.v.t. ANG II in SH rats supports a role of central ANG II in the maintenance of high blood pressure in SH rats.


[Complex medico-genetic study of the Western Siberian population. II. Population-genetic study of fluorescent chromosome polymorphism in Northern Khanty].
Polymorphisms of fluorescent variants of 469 human karyotypes from five subpopulations of the Northern Khanty were studied. Significant frequency variability of Q-polymorphic variants of chromosomes was shown. Wahlund's variance for 12 chromosome polymorphic segments was 0.0121, while the total inbreeding coefficient was 0.0069 with a negative nonrandom component. Heterozygosity estimated for chromosome fluorescent polymorphism (0.189) agrees well with that for blood group systems and less for enzymes. The frequencies of Q-polymorphic variants corresponded to Hardy-Weinberg equilibrium, except for chromosome 13 which gave the significant excess of heterozygotes. Possible explanations of this phenomenon are discussed.


Photodynamic diagnosis of non-muscle-invasive bladder cancer with hexaminolevulinate cystoscopy: a meta-analysis of detection and recurrence based on raw data.
Studies on hexaminolevulinate (HAL) cystoscopy report improved detection of bladder tumours. However, recent meta-analyses report conflicting effects on recurrence. To assess available clinical data for blue light (BL) HAL cystoscopy on the detection of Ta/T1 and carcinoma in situ (CIS) tumours, and on tumour recurrence. This meta-analysis reviewed raw data from prospective studies on 1345 patients with known or suspected non-muscle-invasive bladder cancer (NMIBC). A single application of HAL cystoscopy was used as an adjunct to white light (WL) cystoscopy. We studied the detection of NMIBC (intention to treat [ITT]: n=831; six studies) and recurrence (per protocol: n=634; three studies) up to 1 yr. DerSimonian and Laird's random-effects model was used to obtain pooled relative risks (RRs) and associated 95% confidence intervals (CIs) for outcomes for detection. BL cystoscopy detected significantly more Ta tumours (14.7%; p<0.001; odds ratio [OR]: 4.898; 95% CI, 1.937-12.390) and CIS lesions (40.8%; p<0.001; OR: 12.372; 95% CI, 6.343-24.133) than WL. There were 24.9% patients with at least one additional Ta/T1 tumour seen with BL (p<0.001), significant also in patients with primary (20.7%; p<0.001) and recurrent cancer (27.7%; p<0.001), and in patients at high risk (27.0%; p<0.001) and intermediate risk (35.7%; p=0.004). In 26.7% of patients, CIS was detected only by BL (p<0.001) and was also significant in patients with primary (28.0%; p<0.001) and recurrent cancer (25.0%; p<0.001). Recurrence rates up to 12 mo were significantly lower overall with BL, 34.5% versus 45.4% (p=0.006; RR: 0.761 [0.627-0.924]), and lower in patients with T1 or CIS (p=0.052; RR: 0.696 [0.482-1.003]), Ta (p=0.040; RR: 0.804 [0.653-0.991]), and in high-risk (p=0.050) and low-risk (p=0.029) subgroups. Some subgroups had too few patients to allow statistically meaningful analysis. Heterogeneity was minimised by the statistical analysis method used. This meta-analysis confirms that HAL BL cystoscopy significantly improves the detection of bladder tumours leading to a reduction of recurrence at 9-12 mo. The benefit is independent of the level of risk and is evident in patients with Ta, T1, CIS, primary, and recurrent cancer.


Gender differences in plaque characteristics of nonculprit lesions in patients with coronary artery disease.
Although numerous reports suggest sex-related differences in atherosclerosis, limited data describing gender-associated differences in plaque morphology and composition are currently available. The aim of the present study was to compare coronary nonculprit plaque characteristics in women and men with coronary artery disease (CAD) by optical coherence tomography (OCT). This was a retrospective study. A total of 187 nonculprit plaques were identified in 103 patients with CAD who underwent OCT imaging of all 3 coronary arteries. These patients included 77 (74.8%) men and 26 (25.2%) women. Female patients were significantly older than males (mean age, 70.8 ± 7.3 vs 60.8 ± 9.8 years; P < 0.001) and less likely to be current smokers (P = 0.007). OCT analysis included the presence of lipid-rich plaque, maximum lipid arc, lipid-core length, lipid index (LI), fibrous cap thickness, and the incidence of thin-cap fibroatheroma (TCFA). Nonculprit plaques in men exhibited greater lipid-core length and LI compared with those of women (9.4 ± 4.5 vs. 7.3 ± 4.3 mm, P = 0.024; 1615.1 ± 893.8 vs. 1237.8 ± 859.8, P = 0.035, respectively). In the univariate linear regression model, sex and current smoker were all associated with a larger LI, whereas only use of statin was independent risk factor for a larger LI in multivariate analysis. Coronary nonculprit plaques in male patients with CAD contain larger lipid cores than those of female patients.


Utilizing gemstone spectral CT imaging to evaluate the therapeutic efficacy of radiofrequency ablation in lung cancer.
To evaluate the therapeutic efficacy of radiofrequency ablation (RFA), quantitative water-based, and iodine-based images of gemstone spectral computed tomography (CT) were analyzed. 30 patients underwent lung RFAs from March 2012 to March 2013. Through enhanced chest scans, we obtained the tumor size values by conventional CT images, and quantitatively analyzed the densities of iodine and water in lung tumors from water-based and iodine-based material decomposition images. Tumors in 22 cases increased in size after RFA while there was no detectable change in the remaining 8 cases. Through water-based material decomposition images, the water content in the tumors increased from (1014.76 ± 6.83 mg/mL) to (1022.71 ± 10.16 mg/mL) after RFA, and this difference was significant (t = -2.329, p < 0.05). Through iodine-based material decomposition images, the iodine content in the tumors was 2.49 ± 0.74 mg/mL before RFA. The tumors were mostly or completely necrotized after RFA and the iodine content in the area of necrosis reduced to 0.45 ± 0.29 mg/m (t = 11.072, p = 0.000). By comparing the tumor size, water content and iodine content before and after RFA, we can visualize the morphology and metabolic states of the tumors and evaluate the therapeutic efficiency.


A lightweight CNN and Transformer hybrid model for mental retardation screening among children from spontaneous speech.
Mental retardation (MR) is a group of mental disorders characterized by low intelligence and social adjustment difficulties. Early diagnosis is beneficial for the timely intervention of children with MR to ease the degree of disability. Children with MR always have impaired speech functions compared to normal children, which is significant for clinical diagnosis. On the basis of this, our study proposes a spontaneous speech-based framework (MT-Net) for screening MR, which merges mobile inverted bottleneck convolutional blocks (MBConv) and visual Transformer blocks. MT-Net takes log-mel spectrograms converted from raw interview speech as data source, and utilizes MBConv and visual Transformer to learn low-level and high-level features well. In addition, SpecAugment, a data augmentation strategy, has been used to expand our audio dataset to further enhance the performance of MT-Net. The experimental results show that our proposed MT-Net outperforms Transformer networks (ViT) and convolutional neural networks (ResNet18, MobileNetV2, EfficientNetV2), achieving accuracy of 91.60% after using SpecAugment. Our proposed MT-Net has fewer parameters, low computing consumption and high prediction accuracy, which is expected to be an auxiliary screening tool for MR.


Comparison of panel-reactive antibody levels in Caucasian and African American renal transplant candidates.
PRA levels from 58 Caucasian and 70 African American ESRD patients were compared against a panel of cryopreserved lymphocytes from 60 donors (40 Caucasian, 15 African American, 5 others) to determine whether there was significant racial influence on PRA outcome. African Americans were found to have significantly higher mean PRA levels than Caucasians (27% vs. 18%, P = 0.02). Restricting this analysis to only 1 degree transplant candidates showed predictably lower mean PRAs: 6% in Caucasians and 15% in African Americans, but the difference between the two groups remained significant (P = 0.015). The percentage of patients with PRA > or = 10% was also greater among African Americans than Caucasians (43% vs. 24%, P = 0.026). For patients not previously transplanted, the difference between these frequencies remained significant: 11% in Caucasians, 30% in African Americans (P = 0.025). Untransplanted African American patients with positive PRAs (> or = 10%) had significantly higher PRA against African American cell donors (mean = 55%) than against Caucasian cell donors (mean = 44%) (mean difference = 10.6%, P = 0.0056). African Americans were more frequently transfused than Caucasians. The percentage of patients not previously transplanted receiving 0, 1-5, and > 5 transfusions were 69%, 22%, and 9% for Caucasians and 43%, 44%, and 13% for African Americans (P = 0.03). This higher transfusion rate is the most likely contributor to the elevated PRA levels observed in African Americans.


Analysis on the thermal performance of low-temperature radiant floor coupled with intermittent stratum ventilation (LTR-ISV) for space heating.
With increasing energy use and outbreaks of respiratory infectious diseases (such as COVID-19) in buildings, there is a growing interest in creating healthy and energy-efficient indoor environments. A novel heating system named low-temperature radiant floor coupled with intermittent stratum ventilation (LTR-ISV) is proposed in this study. Thermal performance, indoor air quality, energy and exergy performance were investigated and compared with conventional radiant floor heating (CRFH) and conventional radiant floor heating with mixing ventilation (CRFH + MV). The results indicated that LTR-ISV had a more uniform operative temperature distribution and overall thermal sensation, and air mixing was enhanced without generating additional draft sensation. Compared with CRFH and CRFH + MV, the indoor CO2 concentration in LTR-ISV can be reduced by 1355 ppm and 400 ppm, respectively. Airborne transmission risk can also be reduced by 5.35 times. The coefficient of performance for CRFH, CRFH + MV, and LTR-ISV during working hours was 4.2, 2.5, and 3.4, respectively. The lower value of LTR-ISV was due to the high energy usage of the primary air handing unit. In the non-working hours, LTR-ISV was 0.6 and 1.3 higher compared to CRFH and CRFH + MV, respectively. The exergy efficiency of LTR-ISV, CRFH, and CRFH + MV was 81.77 %, 76.43 %, and 64.71 %, respectively. Therefore, the LTR-ISV system can meet the requirements of high indoor air quality and thermal comfort and provides a reference for the energy-saving use of low-grade energy in space heating.


Comparing Analytic Hierarchy Process and Discrete-Choice Experiment to Elicit Patient Preferences for Treatment Characteristics in Age-Related Macular Degeneration.
In this study, we conducted an analytic hierarchy process (AHP) and a discrete choice experiment (DCE) to elicit the preferences of patients with age-related macular degeneration using identical attributes and levels. To compare preference-based weights for age-related macular degeneration treatment attributes and levels generated by two elicitation methods. The properties of both methods were assessed, including ease of instrument use. A DCE and an AHP experiment were designed on the basis of five attributes. Preference-based weights were generated using the matrix multiplication method for attributes and levels in AHP and a mixed multinomial logit model for levels in the DCE. Attribute importance was further compared using coefficient (DCE) and weight (AHP) level ranges. The questionnaire difficulty was rated on a qualitative scale. Patients were asked to think aloud while providing their judgments. AHP and DCE generated similar results regarding levels, stressing a preference for visual improvement, frequent monitoring, on-demand and less frequent injection schemes, approved drugs, and mild side effects. Attribute weights derived on the basis of level ranges led to a ranking that was opposite to the AHP directly calculated attribute weights. For example, visual function ranked first in the AHP and last on the basis of level ranges. The results across the methods were similar, with one exception: the directly measured AHP attribute weights were different from the level-based interpretation of attribute importance in both DCE and AHP. The dependence/independence of attribute importance on level ranges in DCE and AHP, respectively, should be taken into account when choosing a method to support decision making.


CD44-targeted nanoparticles for co-delivery of docetaxel and an Akt inhibitor against colorectal cancer.
New strategies to develop drug-loaded nanocarriers with improved therapeutic efficacy are needed for cancer treatment. Herein we report a novel drug-delivery nanosystem comprising encapsulation of the chemotherapeutic drug docetaxel (DTX) and recombinant fusion of a small peptide inhibitor of Akt kinase within an elastin-like recombinamer (ELR) vehicle. This combined approach is also precisely targeted to colorectal cancer cells by means of a chemically conjugated DNA aptamer specific for the CD44 tumor marker. This 53 nm dual-approach nanosystem was found to selectively affect cell viability (2.5 % survival) and proliferation of colorectal cancer cells in vitro compared to endothelial cells (50 % survival), and to trigger both apoptosis- and necrosis-mediated cell death. Our findings also show that the nanohybrid particles remain stable under physiological conditions, trigger sustained drug release and possess an adequate pharmacokinetic profile after systemic intravenous administration. In vivo assays showed that these dual-approach nanohybrids significantly reduced the number of tumor polyps along the colorectal tract in a murine colorectal cancer model. Furthermore, systemic administration of advanced nanohybrids induced tissue recovery by improving the morphology of gastrointestinal crypts and the tissue architecture. Taken together, these findings indicate that our strategy of an advanced dual-approach nanosystem allows us to achieve successful controlled release of chemotherapeutics in cancer cells and may have a promising potential for colorectal cancer treatment.