Incidence of cystoid macular edema after uncomplicated phacoemulsification.
We determined the incidence and causes of clinical and angiographic cystoid macular edema (CME) after uncomplicated phacoemulsification and intraocular lens implantation in otherwise normal eyes. This study comprised 252 eyes of 252 patients who had uncomplicated phacoemulsification with continuous curvilinear capsulorhexis and in-the-bag acrylic intraocular lens implantation. The presence of clinical and angiographic CME was evaluated 45 days after surgery, using fundus fluorescein angiography. Age, sex, cataract type, iris color, and real phacoemulsification time of the patients were also recorded. The mean age of the patients was 69.86 (range 60-82) years). Clinical CME was not detected in any eye at any postoperative visit. There were 23 cases with angiographic CME (9.1%). There were no significant differences between the groups who were later found to be angiographically CME-positive or CME-negative in any variable recorded (p >0.05). The incidences of clinical and angiographic CME after uncomplicated phacoemulsification were 0 and 9.1%, respectively. These results indicate that the occurrence of clinical CME has greatly reduced after uncomplicated phacoemulsification operations, but the incidence of angiographic CME is still nearly equal to the incidence of the extracapsular technique.


Identification of metaplastic variants generated by transfection of a nonmetastatic rat mammary epithelial cell line with DNA from a metastatic rat mammary cell line.
The rat mammary 37 epithelial cell line yields non-metastasizing adenomas in syngeneic rats. On cellular DNA transfection, a series of cell lines have been isolated that grow in drug-selective medium. Representative transfected cell lines all yield tumors in rats that consist predominantly of spindle cells, but two also contain epithelial-like cells and glandlike elements (C18P, C19P). Immunocytochemical staining for milk fat globule membrane antigens, human callus keratin, and laminin confirms the identity of the epithelial cells and suggests a (myo)epithelial origin for the spindle cells. Some of the transfected cell lines also generate well-differentiated metaplastic elements in their tumors. One cell line (CT4-41) produces rhabdomyoblastic and possibly smooth-muscle-related elements; two (C18P, C19P) produce squamous metaplasia and sebaceous elements; and two (CL1-31, C11P) produce cartilaginous elements. The identities of the heterologous elements are confirmed by immunocytochemical staining for myoglobin, actin (CT4-41), keratin (C18P, C19P), type II collagen, and type II keratan sulfate (CL1-31). Those cell lines that have acquired the ability to metastasize from subcutaneous sites (CT4-41, C18P) reproduce the same metaplastic elements in their metastases. Thus, a cloned mammary epithelial cell line can be made to generate many of the well-differentiated, heterologous elements observed in human breast carcinomas, and this change is often associated with the rat cells acquiring metastatic properties.


Cytochrome P450 1A1 exon 7 polymorphism and susceptibility to lung cancer in the Chinese population: an updated meta-analysis and review.
Although many epidemiologic studies have investigated the cytochrome P450 1A1 (CYP1A1) exon 7 gene polymorphism and its association with lung cancer (LC), definitive conclusions cannot be drawn. To clarify the effects of CYP1A1 exon 7 polymorphism on the risk of LC, an updated meta-analysis was performed in the Chinese population. Related studies were identified from PubMed, Springer Link, Ovid, the Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and the Chinese Biology Medicine (CBM) databases until October 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associations. A total of 25 articles including 3,540 LC cases and 5,284 controls were included in this meta-analysis. Overall, significant association was found between CYP1A1 exon 7 polymorphism and LC risk when all studies in the Chinese population were pooled into this meta-analysis (GG versus AA: OR = 1.71, 95% CI: 1.46-2.01; GG versus AG: OR = 1.41, 95% CI: 1.21-1.64; GG + AG versus AA: OR = 1.37, 95% CI: 1.16-1.62; GG versus AA + AG: OR = 1.52, 95% CI: 1.32-1.76). In subgroup analyses stratified by ethnicity, source of controls, and geographical locations, significantly increased risk was found in Chinese Han people, in population-based studies, in hospital-based studies, in South China, and in North China. This meta-analysis provides the evidence that CYP1A1 exon 7 polymorphism may contribute to LC development in the Chinese population, and studies with a larger sample size and wider population spectrum are warranted to verify this finding.


Pilot study of decision support tools on breast cancer chemoprevention for high-risk women and healthcare providers in the primary care setting.
Breast cancer chemoprevention can reduce breast cancer incidence in high-risk women; however, chemoprevention is underutilized in the primary care setting. We conducted a pilot study of decision support tools among high-risk women and their primary care providers (PCPs). The intervention included a decision aid (DA) for high-risk women, RealRisks, and a provider-centered tool, Breast Cancer Risk Navigation (BNAV). Patients completed validated surveys at baseline, after RealRisks and after their PCP clinical encounter or at 6-months. Referral for high-risk consultation and chemoprevention uptake were assessed via the electronic health record. The primary endpoint was accuracy of breast cancer risk perception at 6-months. Among 40 evaluable high-risk women, median age was 64.5 years and median 5-year breast cancer risk was 2.19%. After exposure to RealRisks, patients demonstrated an improvement in accurate breast cancer risk perceptions (p = 0.02), an increase in chemoprevention knowledge (p < 0.01), and 24% expressed interest in taking chemoprevention. Three women had a high-risk referral, and no one initiated chemoprevention. Decisional conflict significantly increased from after exposure to RealRisks to after their clinical encounter or at 6-months (p < 0.01). Accurate breast cancer risk perceptions improved and was sustained at 6-months or after clinical encounters. We discuss the side effect profile of chemoprevention and the care pathway when RealRisks was introduced to understand why patients experienced increased decision conflict. Future interventions should carefully link the use of a DA more proximally to the clinical encounter, investigate timed measurements of decision conflict and improve risk communication, shared decision making, and chemoprevention education for PCPs. Additional work remains to better understand the impact of decision aids targeting both patients and providers. ClinicalTrials.gov Identifier: NCT02954900 November 4, 2016 Retrospectively registered.


Cigarette smoking and risk of prostate cancer in middle-aged men.
Cigarette smoking may increase the risk of prostate cancer by affecting circulating hormone levels or through exposure to carcinogens. Although there are plausible mechanisms that could explain an association between smoking and prostate cancer, previous studies are inconsistent. The goal of this population-based case-control study was to assess this association in middle-aged men. Cases (n = 753) were men ages 40-64 years diagnosed with prostate cancer from 1993 to 1996 identified using the Seattle-Puget Sound Cancer Registry. Age-matched controls without prostate cancer from the same region (n = 703) were identified using random digit dialing. Participants completed detailed in-person interviews. Logistic regression was used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to assess the prostate cancer-cigarette smoking relationship. Current smokers had an increased risk (OR = 1.4, 95% CI 1.0-2.0) relative to nonsmokers. A dose-response relationship was noted between number of pack-years smoked and prostate cancer risk (trend P = 0.03). The OR = 1.6 (95% CI 1.1-2.2) for men with >40 pack-years of smoking, with a stronger association observed in men with more aggressive disease (OR = 2.0, 95% CI 1.3-3.1). Smoking cessation resulted in a decline in risk (trend P = 0.02). Smoking is associated with a moderately increased relative risk of prostate cancer. Furthermore, a dose-response relationship exists between number of pack-years smoked and cancer risk. Given that smoking cessation seems to reduce these risks, results from this study have public health ramifications and suggest that prostate cancer should be added to the list of tumors for which cigarette smoking is a risk factor.


Langevin Poisson-Boltzmann equation: point-like ions and water dipoles near a charged surface.
Water ordering near a charged membrane surface is important for many biological processes such as binding of ligands to a membrane or transport of ions across it. In this work, the mean-field Poisson-Boltzmann theory for point-like ions, describing an electrolyte solution in contact with a planar charged surface, is modified by including the orientational ordering of water. Water molecules are considered as Langevin dipoles, while the number density of water is assumed to be constant everywhere in the electrolyte solution. It is shown that the dielectric permittivity of an electrolyte close to a charged surface is decreased due to the increased orientational ordering of water dipoles. The dielectric permittivity close to the charged surface is additionally decreased due to the finite size of ions and dipoles.


Malignant melanoma: from cell kinetics to micrometastases.
Malignant melanoma (MM) micrometastases are basically seen in three locations inside the peritumoral dermis. They are localized (i) inside the interstitial sector of the dermal stroma; (ii) abutted to the external surface of the microvasculature; and (iii) more rarely present inside vascular channels. Single-cell and paucicellular micrometastases may be disclosed using immunohistochemistry even in the absence of larger microsatellites, which represent micronodular nests of metastatic cells. The presence of microsatellites is frequently tied to markers of MM aggressiveness including thickness and the Ki-67 index. Micrometastases may be present in the same conditions, but even as early as thin MM showing a small growth fraction. Microsatellites as well as micrometastases appear to predict locoregional extension and decreased relapse-free interval, but not distant metastasis and overall survival. These considerations have implications for patient care since patients with microsatellites and micrometastases are now included in the clinical stage III category of the disease. Their implication as a prognostic factor is not fully dependent on or linked to other markers of MM aggressiveness.


Role of the AKT pathway in microRNA expression of human U251 glioblastoma cells.
Activation of the AKT (serine-threonine kinase) pathway is a common feature in glioblastoma cells. Downstream factors of the AKT pathway are involved in cell proliferation, apoptosis, cellular migration and angiogenesis. Micro-RNAs (miRNAs) are highly conserved small non-coding RNAs that block targeted mRNA expression at the post-transcriptional level. The aim of this study was to investigate the role of the AKT pathway in regulating miRNA. The changes of miRNA expression profile in human glioblastome U251 cells after AKT small interfering RNA transfection were examined by a microarray, and confirmed by Northern blotting. Down-regulation of AKT expression by siRNA decreased the activity of AKT pathway in U251 cells. Interruption of AKT pathway suppressed the expression of NF-kappaB and c-Myc, furthermore, the expression of a set of miRNAs was also changed after AKT siRNA transfection. There are putative binding sites of NF-kappaB and c-Myc in the promoters of several up-regulated miRNAs, indicating these transcription factors may also be involved in the regulation of miRNA expression, thus affecting the activity of AKT pathway in tumorigenesis. We provide new components of the regulatory function of AKT pathway to better understand the regulatory network mediated by downstream transcription factors. The understanding of the regulatory function of AKT pathway is crucial in tailored therapy of gliomas.


Health Care Use and Spending for Medicaid Enrollees in Federally Qualified Health Centers Versus Other Primary Care Settings.
To compare health care use and spending of Medicaid enrollees seen at federally qualified health centers versus non-health center settings in a context of significant growth. Using fee-for-service Medicaid claims from 13 states in 2009, we compared patients receiving the majority of their primary care in federally qualified health centers with propensity score-matched comparison groups receiving primary care in other settings. We found that health center patients had lower use and spending than did non-health center patients across all services, with 22% fewer visits and 33% lower spending on specialty care and 25% fewer admissions and 27% lower spending on inpatient care. Total spending was 24% lower for health center patients. Our analysis of 2009 Medicaid claims, which includes the largest sample of states and more recent data than do previous multistate claims studies, demonstrates that the health center program has provided a cost-efficient setting for primary care for Medicaid enrollees.


Prevention of adolescent substance abuse through the development of personal and social competence.
The initiation of substance use typically begins during adolescence and appears to be the result of the complex interplay of social, personality, cognitive, attitudinal, behavioral, and developmental factors. Traditional smoking, alcohol, and drug education programs have attempted to increase students' knowledge of the risks associated with using these substances in the hope that this would deter use. Other programs have attempted to enrich the personal and social development of students through what has been referred to as "affective" education. Unfortunately, the inescapable conclusion to be drawn from the substance abuse prevention literature is that few of these programs have demonstrated any degree of success in terms of the actual prevention of substance use/abuse. Traditional educational approaches to substance abuse prevention appear to be inadequate because they are based on faulty assumptions and are too narrow in their focus. The "affective" education approaches, on the other hand, appear to have placed too little emphasis on the acquisition of the kind of skills that are likely to increase general personal competence and enable students to cope with the various interpersonal and intrapersonal pressures to begin using tobacco, alcohol, or drugs. From the perspective of social learning theory (Bandura 1977) and problem behavior theory (Jessor and Jessor 1977), substance use is conceptualized as a socially learned, purposive, and functional behavior which is the result of the interplay of social (environmental) and personal factors. One potentially effective approach to substance abuse prevention might involve enhancing general personal competence and teaching adolescents the kind of problem-specific skills and knowledge which will increase their ability to resist the various forms of pro-substance-use social pressure. Brief reviews of the social skills training literature and the literature related to techniques for coping with anxiety not only provide evidence for the feasibility of teaching these kinds of skills, but also provide guidelines concerning the most effective approaches to use. Similarly, several of the most successful smoking prevention programs have included components designed to increase adolescents' ability to resist the various pro-use social pressures, particularly pressure from their peers. Our own research has involved testing a broad-spectrum prevention strategy which focuses both on the enhancement of personal competence through the development of basic "life skills" and the acquisition of problem-specific skills and knowledge designed to increase adolescents' ability to resist the various forms of social pressure to engage in the use of one or more substances.(ABSTRACT TRUNCATED AT 400 WORDS)


Coping strategies among urban poor: evidence from Nairobi, Kenya.
In Kenya, it is estimated that 60 to 80% of urban residents live in slum or slum-like conditions. This study investigates expenditures patterns of slum dwellers in Nairobi, their coping strategies and the determinants of those coping strategies. We use a dataset from the Indicator Development for Surveillance of Urban Emergencies (IDSUE) research study conducted in four Nairobi slums from April 2012 to September 2012. The dataset includes information related to household livelihoods, earned incomes of household members, expenditures, shocks, and coping strategies. Food spending is the single most important component, accounting for 52% of total households' income and 42% of total expenditures. Households report a variety of coping strategies over the last four weeks preceding the interview. The most frequently used strategy is related to reduction in food consumption, followed by the use of credit, with 69% and 52% of households reporting using these strategies respectively. A substantial proportion of households also report removing children from school to manage spending shortfalls. Formal employment, owning a business, rent-free housing, belonging to the two top tiers of income brackets, and being a member of social safety net reduced the likelihood of using any coping strategy. Exposure to shocks and larger number of children under 15 years increased the probability of using a coping strategy. Policies that contain food price inflation, improve decent-paying job opportunities for the urban poor are likely to reduce the use of negative coping strategies by providing urban slum dwellers with steady and reliable sources of income. In addition, enhancing access to free primary schooling in the slums would help limit the need to use detrimental strategies like "removing" children from school.


Rare Surgical Complication of In Vitro Fertilisation Treatment: Bladder Injury During Oocyte Retrieval.
Current literature suggests that surgical complications from oocyte retrievals (ORs) are uncommon. Here, we present a rare case of bladder injury during OR and its subsequent management. A 37-year-old nulliparous woman underwent assisted reproductive therapy (ART) for primary infertility secondary to anovulatory cycle. During OR, there was an inadvertent puncture of the bladder, with active intra-bladder bleeding seen on transvaginal ultrasound. Bladder washout followed by continuous drainage was instituted with antibiotic coverage over several days. Bladder integrity ascertained through computer tomography urogram and cystoscopy were unremarkable. She was discharged well and continued with her fertility treatment. Transvaginal OR is associated with few complications. Bladder injury, albeit rare, can present with massive hematuria and hemodynamic instability. Early identification of the injury is key to management with insertion of the indwelling urinary catheter, hemodynamic resuscitation and bladder irrigation. With a urological multi-disciplinary approach, most bladder injuries can be resolved non-invasively.


Myocardial expression of Toll-like receptor 4 predicts the response to immunosuppressive therapy in patients with virus-negative chronic inflammatory cardiomyopathy.
We sought to determine whether myocardial expression of Toll-like receptor 4 (TLR4) may predict the response to immunosuppression. Endomyocardial biopsies from 237 patients with virus-negative inflammatory cardiomyopathy treated with immunosuppression were retrospectively examined for the expression of TLR4, differentiating those patients responding to immunosuppression (n = 193) from non-responder patients (n = 44). A semiquantitative evaluation of the immunoreactivity (grading from 0 to 4) for TLR4 and human leucocyte antigen (HLA)-DR was performed together with real-time PCR and western blot for TLR4. Cardiomyocyte apoptosis and necrosis was evaluated by in situ ligation with hairpin probes. A focal intense positive cytoplasmic immunostaining for TLR4 was observed in cardiomyocytes of all responders (P < 0.001 vs. non-responders). A grading 2 or above (2+) at baseline showed a sensitivity of 100% and 90.9% specificity with a positive predictive value of 98% as a predictor of an immunosuppression-positive response. Real-time PCR and western blot analysis for TLR4 were 4.3-fold and 4.6-fold higher, respectively, in responders vs. non-responders. Correlation between TLR4 grading and TLR4 mRNA molecular and protein expression was highly significant. HLA-DR did not discriminate between the two groups. Cardiomyocyte death by apoptosis was 3.7-fold higher in responders vs. non-responders and significantly correlated with TLR4 expression, while necrosis was comparable. Intensity of baseline TLR4 expression correlated with the variation in ejection fraction after 6 months of immunosuppression. TLR4 is highly expressed in human myocarditis responding to immunosuppression. It can be considered as a new sensitive marker in patient selection predicting a good response to immunosuppressive therapy.


Recent progress in the study of one-dimensional gravitating systems.
We review recent developments in the study of two different interacting gravitational systems: the system of parallel planar mass sheets and the system of concentric spherical mass shells. The approach to equilibrium of a system of parallel planar mass sheets is investigated. Parallels with three-dimensional systems are described. Mass segregation and kinetic energy equipartition in a two-component system of planar mass sheets is demonstrated via numerical simulation. The existence of two distinct phases is demonstrated in the system of spherical mass shells. The nature of the transition in the microcanonical, canonical, and grand canonical ensembles is studied both theoretically in terms of mean-field theory and via dynamical simulation.


Urea-induced drying of hydrophobic nanotubes: comparison of different urea models.
In a previous study, we performed the molecular dynamics (MD) simulations of various carbon nanotubes solvated in 8 M urea and observed a striking phenomenon of urea-induced drying of hydrophobic nanotubes, which resulted from the stronger dispersion interaction of urea than water with nanotube (Das, P.; Zhou, R. H. J. Phys. Chem. B2010, 114, 5427-5430). In this paper, we have compared five different urea models to investigate if the above phenomenon is sensitive to the urea models used. We demonstrate through MD simulations that the drying phenomenon and its physical mechanism are qualitatively independent of the urea models. Consistent with our previous study, our current analyses with both interaction potential energy and association free energy indicate that there is a "dry state" inside the carbon nanotubes, which is caused by the urea's preferential binding to nanotubes through stronger dispersion interactions. These results also have implications for understanding the urea-induced protein denaturation by providing further evidence of the potential existence of a "dry globule"-like transient state during protein unfolding and the "direct interaction mechanism" (whereby urea attacks protein directly, rather than disrupts water structure as a "water breaker"). In addition, our study highlights the crucial role of dispersion interaction in the selective absorption of molecules in hydrophobic nanopores and may have significance for nanoscience and nanotechnology.


The impact of diabetes mellitus on the emergence of multi-drug resistant tuberculosis and treatment failure in TB-diabetes comorbid patients: a systematic review and meta-analysis.
The existence of Type 2 Diabetes Mellitus (DM) in tuberculosis (TB) patients is very dangerous for the health of patients. One of the major concerns is the emergence of MDR-TB in such patients. It is suspected that the development of MDR-TB further worsens the treatment outcomes of TB such as treatment failure and thus, causes disease progression. To investigate the impact of DM on the Emergence of MDR-TB and Treatment Failure in TB-DM comorbid patients. The PubMed database was systematically searched until April 03, 2022 (date last searched). Thirty studies met the inclusion criteria and were included in this study after a proper selection process. Tuberculosis-Diabetes Mellitus patients were at higher risk to develop MDR-TB as compared to TB-non-DM patients (HR 0.81, 95% CI: 0.60-0.96, p < 0.001). Heterogeneity observed among included studies was moderate (I2 = 38%). No significant change was observed in the results after sub-group analysis by study design (HR 0.81, 95% CI: 0.61-0.96, p < 0.000). In the case of treatment failure, TB-DM patients were at higher risk to experience treatment failure rates as compared to TB-non-DM patients (HR 0.46, 95% CI: 0.27-0.67, p < 0.001). The results showed that DM had a significant impact on the emergence of MDR-TB in TB-diabetes comorbid patients as compared to TB-non-DM patients. DM enhanced the risk of TB treatment failure rates in TB-diabetes patients as compared to TB-non-DM patients. Our study highlights the need for earlier screening of MDR-TB, thorough MDR-TB monitoring, and designing proper and effective treatment strategies to prevent disease progression.


Palladium-catalyzed enantioselective 1,3-rearrangement of racemic allylic sulfinates: asymmetric synthesis of allylic sulfones and kinetic resolution of an allylic sulfinate.
Described is an asymmetric synthesis of cyclic and acyclic allylic S-aryl and S-alkyl sulfones through a highly selective palladium(0)-catalyzed 1,3-rearrangement of racemic allylic sulfinates. Treatment of racemic cyclic and acyclic allylic S-tolyl- and S-tert-butylsulfinates with Pd(2)(dba)(3).CHCl(3) as precatalyst and N,N'-(1R,2R)-1,2-cyclohexanediylbis[2-(diphenylphosphino)benzamide] as ligand for the palladium atom afforded the corresponding isomeric allylic S-tolyl and S-tert-butyl sulfones of 93-99% ee in 82-96% yield. The rearrangement of the allylic sulfinates most likely proceeds in an intermolecular fashion via formation of a cationic pi-allylpalladium complex and the sulfinate ion. The racemic allylic sulfinates were obtained from the corresponding racemic alcohols and racemic tolylsulfinyl chloride and racemic tert-butylsulfinyl chloride, respectively, in high yields. Rearrangement of the racemic tert-butylsulfinic acid 2-cyclooct-1-enyl ester with Pd(2)(dba)(3).CHCl(3) and the bisphosphane was accompanied by a highly selective kinetic resolution of the substrate and gave at 50% conversion the (R)-configured sulfinate as mixture of the S(S) and R(S) diastereomers of 92% ee and 85% ee and the (S)-configured 3-tert-butylsulfonyl cyclooctene sulfone 15a with 98% ee in almost quantitative yields.


Inhibitors of articular calcium crystal formation.
The coexistence of calcium phosphate and calcium pyrophosphate crystals in osteoarthritis is a well-described phenomenon. In addition to deposition in articular cartilage, the crystals induce numerous changes to biochemical parameters in the surrounding fluid. This survey discusses crystal-inhibitor interactions whereby defining the molecular structure of crystals assists in an optimal inhibitor design. Crystal growth studies in the presence and absence of a test compound can generate data on crystal face changes. Together with knowledge of the inhibitors' molecular structure, computer modeling can portray crystal-inhibitor interactions. Few inhibitors have been tested in both in vitro and in vivo phases. One exception is phosphocitrate. This compound inhibits both the development of specific calcium crystals and crystal-induced intracellular changes. Animal studies confirm a strong action on pathologic calcification. The recently described phosphocitrate in a mixed calcium and sodium salt, yet to be tested in a guinea pig osteoarthritis model, appears to be an even more powerful inhibitor.


Intrathoracic Pressure Regulation Augments Stroke Volume and Ventricular Function in Human Hemorrhage.
Obtaining intravenous (i.v.) access for fluid administration is a critical step in treating hemorrhage. However, expertise, supplies, and personnel to accomplish this task can be delayed or even absent in austere environments. An alternative approach that can "buy time" and improve circulation when i.v. fluids are absent is needed. Preclinical studies show that intrathoracic pressure regulation (ITPR) can increase perfusion in hypovolemia in the absence of i.v. fluid. We compared ITPR with placebo in humans undergoing a 15% hemorrhage under general anesthesia. Paired healthy volunteers (n = 7, aged 21 - 35 years) received either ITPR or placebo on different study days. Institutional review board informed consent was obtained. Subjects were anesthetized using propofol, intubated, and mechanically ventilated and hemorrhaged (10 mL/kg). Twenty minutes after hemorrhage, ITPR (-12 cm H2O vacuum) or placebo (device but no vacuum) was administered for another 60 min. Intravenous fluid was administered when systolic blood pressure was less than 85 mmHg. Hemodynamics, cardiac function by echocardiography, and volumetric data were compared. Data were expressed in Δmean ± SEM before and after ITPR/placebo intervention. There were no differences in mean arterial pressure (ITPR, 2.1 ± 3 mmHg; placebo, -0.7 ± 3 mmHg) or fluid infused (ITPR, 17.4 ± 4 mL/kg; placebo, 18.6 ± 5 mL/kg). Urinary output and plasma volume also were not significantly different. Intrathoracic pressure regulation augmented stroke volume (ITPR, 22 ± 5 mL, placebo, 6 ± 4 mL; P < 0.05), ejection fraction (ITPR, 4% ± 1%; placebo, 0% ± 1%), and diastolic function (ΔE/e') (ITPR, -0.8 ± 0.4 vs. placebo, +0.81 ± 0.6; P < 0.05). Intrathoracic pressure regulation did not improve mean arterial pressure in healthy volunteers aged 21 to 35 years. However, ITPR augmented stroke volume, which could be caused by improved ventricular function.


Pharmacological characterization of the calcium influx pathways involved in nitric oxide production by endothelial cells.
To characterize the calcium influx pathways implicated in the sustained elevation of endothelial intracellular calcium concentration, required for the synthesis and release of relaxing factors. We evaluated the effect of the newly synthesized pyrazole derivatives, described as selective inhibitors for ORAI (BTP2/Pyr2 and Pyr6) and TRPC3 (Pyr3 and Pyr10) channels, upon endothelium- and extracellular calcium-dependent relaxations stimulated by acetylcholine and thapsigargin, in pre-constricted rat thoracic aortic rings. Acetylcholine and thapsigargin responses were completely reverted by Pyr2 and Pyr6 (1 to 3μM). Pyr3 (0.3 to 3μM) caused a rapid reversal of acetylcholine (6.2±0.08mg.s-1) and thapsigargin (3.9±0.25mg.s-1) relaxations, whereas the more selective TRPC3 blocker Pyr10 (1 to 3μM) had no effect. The recently described TRPC4/5 selective blocker, ML204 (1 to 3μM), reverted completely acetylcholine relaxations, but minimally thapsigargin induced ones. Noteworthy, relaxations elicited by GSK1016790A (TRPV4 agonist) were unaffected by pyrazole compounds or ML204. After Pyr2 and Pyr6 pre-incubation, acetylcholine and thapsigargin evoked transient relaxations similar in magnitude and kinetics to those observed in the absence of extracellular calcium. Sodium nitroprusside relaxations as well as phenylephrine-induced contractions (denuded aorta) were not affected by any of pyrazole compounds (1 to 3μM). These observations revealed a previously unrecognized complexity in rat aorta endothelial calcium influx pathways, which result in production and release of nitric oxide. Pharmacologically distinguishable pathways mediate acetylcholine (ORAI/TRPC other than TRPC3/TRPC4 calcium-permeable channels) and thapsigargin (TRPC4 not required) induced calcium influx.


A quantitative study of the pathological changes in cortical neurons in sporadic Creutzfeldt-Jakob disease.
The frequency of morphological abnormalities in neuronal perikarya was studied in the cerebral cortex in cases of sporadic CJD (sCJD) and in elderly control patients. Three hypotheses were tested, namely that the proportion of neurons exhibiting abnormal morphology was increased: (i) in sCJD compared with control patients; (ii) in sCJD, in areas with significant prion protein (PrP) deposition compared with regions with little or no PrP deposition; and (iii) when neurons were spatially associated with a PrP deposit compared with neurons between PrP deposits. Changes in cell shape (swollen or atrophic cell bodies), nuclei (displaced, indistinct, shrunken or absent nuclei; absence of nucleolus), and cytoplasm (dense or pale cytoplasm, PrP positive cytoplasm, vacuolation) were commonly observed in all of the cortical areas studied in the sCJD cases. The proportion of neurons exhibiting each type of morphological change was significantly increased in sCJD compared with age-matched control cases. In sCJD, neuronal abnormalities were present in areas with little PrP deposition, but at significantly lower frequencies compared with areas with significant densities of PrP deposits. Abnormalities of cell shape, nucleus and the presence of cytoplasmic vacuolation were increased when the neurons were associated with a PrP deposit, but fewer of these neurons were PrP-positive compared with neurons between deposits. The data suggest significant neuronal degeneration in the cerebral cortex in sCJD in areas without significant PrP deposition and a further phase of neuronal degeneration associated with the appearance of PrP deposits.


UV and pigmentation: molecular mechanisms and social controversies.
Ultraviolet radiation (UVR) is an essential risk factor for the development of premalignant skin lesions as well as of melanoma and non-melanoma skin cancer. UVR exerts many effects on the skin, including tanning, carcinogenesis, immunomodulation, and production of vitamin D. Vitamin D (vit D) is important in the maintenance of healthy bones as well as other purported beneficial effects, amongst which is the potential for reducing risk of malignancy--though oral supplementation is fully capable of maintaining systemic levels. The known medical harm from UV exposure relates primarily to cancer of the skin--the most common organ in man to be affected by cancer. In this review, we summarize the knowledge about the ultraviolet (UV) response in regards to inflammation, immunosuppression, carcinogenesis and the tanning response. We also discuss vit D and UV, as well as public health implications of tanning behavior and commercial interests related to the promotion of UV exposure. As the most ubiquitous human carcinogen, UVR exposure represents both a challenge and enormous opportunity in the realm of skin cancer prevention.


The Complement System and Preeclampsia.
Preeclampsia affects 3-4% of pregnancies with few treatment options to reduce maternal and fetal harm. Recent evidence that targeting the complement system may be an effective therapeutic strategy in prevention or treatment of preeclampsia will be reviewed. Studies in humans confirm the safety and efficacy of C5 blockade in complement-mediated disorders of pregnancy, including preeclampsia. Animal models mimic the placental abnormalities and/or the maternal symptoms which characterize preeclampsia. These models in mouse and rat have defined a role for complement and its regulators in placental dysfunction, hypertension, proteinuria, endothelial dysfunction, fetal growth restriction, and angiogenic imbalance, thus informing future human studies. Targeting excessive complement activation, particularly the terminal complement complex (C5b-9) and C5a may be an effective strategy to prolong pregnancy in women with preeclampsia. Continued research is needed to identify the initiator(s) of activation, the pathways involved, and the key component(s) in the pathophysiology to allow development of safe and effective therapeutics to target complement without compromising its role in homeostasis and host defense.


Highly efficient activation of peroxymonosulfate by ZIF-67 anchored cotton derived for ciprofloxacin degradation.
Metal-organic framework (MOF) and MOF-derived materials have attracted extensive research interest as environmental catalysts. In this study, a composite material (ZIF-67/CCot-8) was successfully prepared using cotton fiber as a substrate and growing ZIF-67 in situ. This material exhibited excellent catalytic performance and significantly improved the efficiency of antibiotics degradation. ZIF-67/CCot-8 at a concentration of 0.05 g/L, combined with 0.2 mM peroxymonosulfate (PMS), removed approximately 97% of ciprofloxacin (CIP) and 99% of tetracycline and sulfamethoxazole within 15 min. The high catalytic efficiency of this catalyst is mainly attributed to the uniform distribution of ZIF-67-derived nanoparticles on the surface of the cotton fibers, providing abundant active sites and thereby significantly enhancing the efficiency of antibiotics degradation. Radical quenching experiments and electron paramagnetic resonance analyses revealed that sulfate radicals (SO4•) and singlet oxygen (1O2) were the main active species. Mass spectrometry was used to elucidate the CIP degradation pathway. The growth of the roots and stems of soybean sprouts in different water environments (tap water, treated water, and untreated water) was also observed. The results demonstrated a significant improvement in the inhibition of plant growth in the post-degradation CIP solution, indicating a substantial reduction in the toxicity of the degraded aqueous solution. To validate the practicality of the ZIF-67/CCot-8/PMS system, a continuous-flow water-treatment device was designed. This system removed 98% of the CIP solution within 180 min, demonstrating its excellent durability. This study presents a potential pathway for effective antibiotics removal using MOF-derived materials.


The genomes of bovine papillomaviruses types 3 and 4 are colinear.
The 7.2 kb genomic DNA of bovine papillomavirus type 3 (BPV-3) was molecularly cloned using its unique EcoRI site, and the 7.3 kb genome of BPV-4 was cloned using its single BamHI site. The viral genomes were compared by liquid hybridization, Southern blot hybridization and heteroduplex mapping. Low stringency hybridization conditions revealed that the genomes are colinear but the sequences are extensively mismatched. The relative alignment of the restriction endonuclease maps of the two viral genomes has been determined. It was found that the genomes as linearized for cloning are out of phase by 1.7 kb, so that the single EcoRI site of BPV-3 appears to coincide with the BPV-4 EcoRI site at 0.22 map units. It is concluded that the genomes of BPV-3 and BPV-4, both of which cause true epithelial warts, share the same physical organization but exhibit sequence divergence.


Melatonin Against Environmental Plant Stressors: A Review.
Harsh or extreme environmental conditions largely determine the vegetative and reproductive development of plants. In the case of cultivated plants, their growth and yield are clearly diminished if they are exposed to severe conditions such as drought, waterlogging, extreme heat or cold, UV radiation, or toxic substances in the soil such as salts, heavy metals and pesticides. Melatonin has been studied for decades as a molecule capable of reducing the negative effects of abiotic stressors by increasing tolerance to these adverse growth conditions. This work presents a review of the most outstanding studies with various plant species in each of the above-mentioned stress situations, including proteomic and post-translational studies. Melatonin mediates plant responses to abiotic stress, generally inducing an antioxidative response, and also regulating a complex gene response adapted to individual stressors. Plants are able to increase their endogenous melatonin levels through the application of exogenous melatonin or through the inductive mechanism of endogenous melatonin biosynthesis. In such ways, plants are able to cope with the stressful situation at hand, accommodating their metabolism, morphology and physiology in order to increase overall survival and induce greater tolerance to stress. The agronomic implications of the use of melatonin are discussed.


Ventricular SK2 upregulation following angiotensin II challenge: Modulation by p21-activated kinase-1.
Effects of hypertrophic challenge on small-conductance, Ca2+-activated K+(SK2) channel expression were explored in intact murine hearts, isolated ventricular myocytes and neonatal rat cardiomyocytes (NRCMs). An established experimental platform applied angiotensin II (Ang II) challenge in the presence and absence of reduced p21-activated kinase (PAK1) (PAK1cko vs. PAK1f/f, or shRNA-PAK1 interference) expression. SK2 current contributions were detected through their sensitivity to apamin block. Ang II treatment increased such SK2 contributions to optically mapped action potential durations (APD80) and their heterogeneity, and to patch-clamp currents. Such changes were accentuated in PAK1cko compared to PAK1f/f, intact hearts and isolated cardiomyocytes. They paralleled increased histological and echocardiographic hypertrophic indices, reduced cardiac contractility, and increased SK2 protein expression, changes similarly greater with PAK1cko than PAK1f/f. In NRCMs, Ang II challenge replicated such increases in apamin-sensitive SK patch clamp currents as well as in real-time PCR and western blot measures of SK2 mRNA and protein expression and cell hypertrophy. Furthermore, the latter were enhanced by shRNA-PAK1 interference and mitigated by the PAK1 agonist FTY720. Increased CaMKII and CREB phosphorylation accompanied these effects. These were rescued by both FTY720 as well as the CaMKII inhibitor KN93, but not its inactive analogue KN92. Such CREB then specifically bound to the KCNN2 promoter sequence in luciferase assays. These findings associate Ang II induced hypertrophy with increased SK2 expression brought about by a CaMKII/CREB signaling convergent with the PAK1 pathway thence upregulating the KCNN2 promoter activity. SK2 may then influence cardiac electrophysiology under conditions of cardiac hypertrophy and failure.


Modelling excitable cells using cycle-linear hybrid automata.
Cycle-linear hybrid automata (CLHAs), a new model of excitable cells that efficiently and accurately captures action-potential morphology and other typical excitable-cell characteristics such as refractoriness and restitution, is introduced. Hybrid automata combine discrete transition graphs with continuous dynamics and emerge in a natural way during the (piecewise) approximation process of any nonlinear system. CLHAs are a new form of hybrid automata that exhibit linear behaviour on a per-cycle basis but whose overall behaviour is appropriately nonlinear. To motivate the need for this modelling formalism, first it is shown how to recast two recently proposed models of excitable cells as hybrid automata: the piecewise-linear model of Biktashev and the nonlinear model of Fenton-Karma. Both of these models were designed to efficiently approximate excitable-cell behaviour. We then show that the CLHA closely mimics the behaviour of several classical highly nonlinear models of excitable cells, thereby retaining the simplicity of Biktashev's model without sacrificing the expressiveness of Fenton-Karma. CLHAs are not restricted to excitable cells; they can be used to capture the behaviour of a wide class of dynamic systems that exhibit some level of periodicity plus adaptation.


Estimating the resolution limit of the map equation in community detection.
A community detection algorithm is considered to have a resolution limit if the scale of the smallest modules that can be resolved depends on the size of the analyzed subnetwork. The resolution limit is known to prevent some community detection algorithms from accurately identifying the modular structure of a network. In fact, any global objective function for measuring the quality of a two-level assignment of nodes into modules must have some sort of resolution limit or an external resolution parameter. However, it is yet unknown how the resolution limit affects the so-called map equation, which is known to be an efficient objective function for community detection. We derive an analytical estimate and conclude that the resolution limit of the map equation is set by the total number of links between modules instead of the total number of links in the full network as for modularity. This mechanism makes the resolution limit much less restrictive for the map equation than for modularity; in practice, it is orders of magnitudes smaller. Furthermore, we argue that the effect of the resolution limit often results from shoehorning multilevel modular structures into two-level descriptions. As we show, the hierarchical map equation effectively eliminates the resolution limit for networks with nested multilevel modular structures.


Emotion, directed forgetting, and source memory.
We investigated the role of emotion on item and source memory using the item method of directed forgetting (DF) paradigm. We predicted that emotion would produce source memory impairment because emotion would make it more difficult to distinguish between to-be-remembered (R items) and to-be-forgotten items (F items) by making memory strength of R and F items similar to each other. Participants were presented with negatively arousing, positively arousing, and neutral pictures. After each picture, they received an instruction to remember or forget the picture. At retrieval, participants were asked to recall both R and F items and indicate whether each item was an R or F item. Recall was higher for the negatively arousing than for the positively arousing or neutral pictures. Further, DF occurred for the positively arousing and neutral pictures, whereas DF was not significant for the negatively arousing pictures. More importantly, the negatively arousing pictures, particularly the ones with violent content, showed a higher tendency of producing misattribution errors than the other picture types, supporting the notion that negative emotion may produce source memory impairment, even though it is still not clear whether the impairment occurs at encoding or retrieval.


Relevance of infiltration analgesia in pain relief after total knee arthroplasty.
The aim of the study was to assess the effect of different types of anesthesia on pain intensity in early postoperative period. A total of 87 patients (77 women, 10 men) scheduled for total knee arthroplasty (TKA) were assigned to receive either subarachnoid anesthesia alone or in combination with local soft tissue anesthesia, local soft tissue anesthesia and femoral nerve block and pre-emptive infiltration together with local soft tissue anesthesia. We assessed the pain intensity, opioid consumption, knee joint mobility, and complications of surgery. Subjects with pre-emptive infiltration and local soft tissue anesthesia had lower pain intensity on the first postoperative day compared to those with soft tissue anesthesia and femoral nerve block (P=0.012, effect size 0.68). Subjects who received pre-emptive infiltration and local soft-tissue anesthesia had the greatest range of motion in the operated knee at discharge (mean 90 grades [SD 7], P=0.01 compared to those who received subarachnoid anesthesia alone, and P=0.001 compared to those with subarachnoid together with soft tissue anesthesia). Despite the differences in postoperative pain and knee mobility, the results obtained throughout the postoperative period do not enable us to favour neither local nor regional infiltration anesthesia in TKA. Level of Evidence II, Prospective Comparative Study.


The future of community nursing: Hospital in the Home.
With an increasing ageing population who often have multiple long-term conditions, there is a growing need to provide an alternative type of care to the traditional hospital-based model. 'Hospital in the Home' is a model that provides integrated care for patients in their home. The @home service was established in 2013 by Guy's and St Thomas' NHS Foundation Trust. The service provides health care in patients' home, supporting early discharge from hospital as well as preventing avoidable admissions and readmissions saving valuable hospital bed days and reducing length of stay. This article describes the service available with the use of a case study of a 78-year-old lady who was referred by the London Ambulance Service with exacerbation of chronic obstructive pulmonary disease (COPD). This case study highlights the ability to assess, treat and manage an acutely unwell patient with newly diagnosed heart failure in the community without the need for hospitalisation. This type of integrated care model with a multidisciplinary team is a feasible alternative to the traditional models of care in both the acute and community settings.


Dual-aptamer-based biosensing of toxoplasma antibody.
A panel of seven aptamers to antitoxoplasma IgG is first discovered in this report. The aptamers are selected using systematic evolution of ligands by exponential enrichment (SELEX) technology, cloned, and identified by sequencing and affinity assay. Among them, two aptamers (TGA6 and TGA7) with the highest affinities are employed as capture probe and detection probe in developing a quantum dots-labeled dual aptasensor (Q-DAS). In the presence of antitoxoplasma IgG, an aptamer-protein-aptamer sandwich complex (TGA6-IgG-TGA7) is formed and captured on a multiwell microplate, whose fluorescence can be read out using quantum dots as the fluorescence label, ensuring highly sensitive and specific sensing of antitoxoplasma IgG. The operating characteristics of the proposed assay are guaranteed using dual aptamers as the recognizing probes when compared with antibody-based immunoassay. Q-DAS has a linearity within the range of 0.5-500 IU with a lowest detection of 0.1 IU. Receiver operating curves of 212 clinical samples show a 94.8% sensitivity and 95.7% specificity when the cutoff value is set as 6.5 IU, indicating the proposed Q-DAS is a promising assay in large-scale screening of toxoplasmosis.


Correlation of anterior segment optical coherence tomography measurements with graft trephine diameter following descemet stripping automated endothelial keratoplasty.
To assess repeatability of the Zhongshan Assessment Program (ZAP) software measurement of Anterior Segment Optical Coherence Tomography (ASOCT) images and correlate with graft trephine diameter following Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) METHODS: Retrospectively evaluated interventional case series. 121 consecutive eyes undergoing DSAEK over a 26 month period underwent ASOCT imaging 1 month after their surgery. ASOCT images were processed using ZAP software which measured the graft and cornea parameters including anterior and posterior graft arc length and cord length, posterior cornea arc length (PCAL) and anterior chamber width. The graft measurements showed good repeatability on ASOCT using ZAP with high intra class coefficient and small variation in the coefficient of variation. On ASOCT, the mean recipient PCAL was 12.99+/-0.69 mm and the anterior chamber width was 11.16+/-0.57 mm. The mean Graft anterior arc length was 9.69+/-0.66 mm and the mean Graft anterior cord length was 8.92+/-2.94 mm. The mean graft posterior arc length was 9.24+/-0.75 mm and the mean graft posterior cord length was 8.15+/-0.57 mm. Graft posterior arc length (rho=0.788, p< 0.001) correlated best with intra-operative graft trephine diameter. The mean ratio of posterior graft arc length to PCAL was 0.712 +/- 0.056. We have validated the repeatability of the ZAP software for DSAEK graft measurements from ASOCT images and shown that the graft arc length parameters calculated from the ASOCT images correlate well with the intra-operative graft trephine diameter. This software may help surgeons determine the optimal DSAEK graft size based on pre-operative ASOCT measurements of the recipient eye.


Evaluation of different media and methods of cultivation on the production and viability of entomopathogenic fungi, Verticillium lecanii (Zimm.) Viegas.
For mass production of V. lecanii, three types of cultivation methods including liquid, solid and diphasic production systems were investigated. In the liquid state of production, six media were tested in stationary culture conditions. Among the six media tested, Molasses Yeast Broth (MYB) supported maximum sporulation (8.33 x 10(8) spores mL(-1)) and biomass production (746 mg/100 mL). In the MYB, 4% molasses concentration was found to produce highest spore count (8.56 x 10(8) spores mL(-1)) and biomass (776 mg/100 mL) followed by 5 and 6% molasses. Among the six solid substrates tested, rice grains supported highest spore production (1.14 g/100 g). In diphasic state of production, combination of MYB and rice grains produced the greatest amount of spores, (1.70 g/100 g). Results of this study indicated that diphasic method using MYB as liquid medium and rice as solid substrate are the best method and media for mass production of V1-7 isolate of V. lecanii.


Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg-Strauss syndrome.
Churg-Strauss syndrome (CSS) is classified among the so-called antineutrophil cytoplasmic antibody-associated systemic vasculitides (AASVs) because of its clinicopathologic features that overlap with the other AASVs. However, while antineutrophil cytoplasmic antibodies (ANCAs) are consistently found in 75-95% of patients with Wegener's granulomatosis or microscopic polyangiitis, their prevalence in CSS varies widely and their clinical significance remains uncertain. We undertook this study to examine the prevalence and antigen specificity of ANCAs in a large cohort of patients with CSS. Moreover, we evaluated the relationship between ANCA positivity and clinicopathologic features. Immunofluorescence and enzyme-linked immunosorbent assay were used to determine the presence or absence of ANCAs in 93 consecutive patients at the time of diagnosis. The main clinical and pathologic data, obtained by retrospective analysis, were correlated with ANCA status. ANCAs were present by immunofluorescence in 35 of 93 patients (37.6%). A perinuclear ANCA (pANCA) pattern was found in 26 of 35 patients (74.3%), with specificity for myeloperoxidase (MPO) in 24 patients, while a cytoplasmic ANCA pattern, with specificity for proteinase 3, was found in 3 of 35 patients (8.6%). Atypical patterns were found in 6 of 30 patients with anti-MPO antibodies (20.0%). ANCA positivity was associated with higher prevalences of renal disease (51.4% versus 12.1%; P < 0.001) and pulmonary hemorrhage (20.0% versus 0.0%; P = 0.001) and, to a lesser extent, with other organ system manifestations (purpura and mononeuritis multiplex), but with lower frequencies of lung disease (34.3% versus 60.3%; P = 0.019) and heart disease (5.7% versus 22.4%; P = 0.042). ANCAs are present in approximately 40% of patients with CSS. A pANCA pattern with specificity for MPO is found in most ANCA-positive patients. ANCA positivity is mainly associated with glomerular and alveolar capillaritis.


A study of the effectiveness of chemosurgery with trichloroacetic acid for Japanese cedar pollenosis in terms of the chemical mediator levels in the nasal discharge and results of nasal provocation testing.
The purpose of the present study was to investigate the effectiveness of chemosurgery with 80w/v% trichloroacetic acid (TCA) for the treatment of Japanese cedar pollenosis. The effectiveness of this treatment was evaluated in terms of the levels in the nasal washings of the chemical mediators histamine and eosinophil cationic protein, and the reactivity in the nasal provocation test. Patients of cedar pollenosis were divided into two groups, the TCA-treated group (n=90) and the group that was not treated with TCA (nonTCA-treated group) (n=79), according to whether or not they received TCA treatment. In both the groups, the levels of the two aforementioned mediators in the nasal washings were measured during the pollen dispersal season. In addition, allergen provocation tests were performed using the disk method in volunteers from both the groups during the non-pollen dispersal season. The results of the above two determinations were compared statistically between the two groups. The results revealed significantly lower levels of the two mediators in the TCA-treated group than in the nonTCA-treated group (p<0.01). There was also a greater tendency for the subjects in the TCA-treated group as compared to those in the nonTCA-treated group to show negative reactivity in the allergen provocation test (p<0.01). Regional suppression of the allergic reaction to Japanese cedar pollen appears to occur as a result of chemosurgery with TCA performed as a day surgery.


Palatal piezosurgical window osteotomy for maxillary sinus augmentation.
This technical note describes a new surgical technique for a palatal approach to the maxillary sinus for a vertical augmentation prior to dental implant placement. In 12 fully or partially edentulous patients (seven women, five men), 16 palatal sinus elevations were performed. After elevation of palatal full-thickness flap a rectangular access window was cut with a piezosurgical device. The raised sinus cavity was augmented with a synthetic nano-structured hydroxyapatite-based graft material. No harm occurred to the greater palatine artery or the sinus membrane. The vestibular and periimplant gingiva were preserved and there was no disharmonious soft tissue distortion or massive scar formation. Swelling and bleeding were minimal. Primary stability was achieved for all but one implant. This technique may be an alternative to other sinus augmentation approaches in cases where enough transversal width of the posterior alveolar crest is available.


[Shifts in several aspects of phospholipid metabolism in the brains of white rats with radiation sickness].
Sublethal (400) and lethal (1600) doses of roentgen decrease the level of neutral phospholipids of rat brain and increase that of acid phospholipids. With the development of radiation disease the content of free glycerine and glycerophosphate increases and the glycerokinase and glycolytic pathways of glycerophosphate biosynthesis are activated together with the intensification of the direct and reverse reactions catalyzed by glycerophosphate dehydrogenase. The permeability of the artificial bimolecular phospholipid membranes prepared from rat brain phospholipid extracts is significantly increased at the end of the radiation.


Genome-wide association study of the seed transmission rate of soybean mosaic virus and associated traits using two diverse population panels.
Genome-wide association analyses identified candidates for genes involved in restricting virus movement into embryonic tissues, suppressing virus-induced seed coat mottling and preserving yield in soybean plants infected with soybean mosaic virus. Soybean mosaic virus (SMV) causes significant reductions in soybean yield and seed quality. Because seedborne infections can serve as primary sources of inoculum for SMV infections, resistance to SMV seed transmission provides a means to limit the impacts of SMV. In this study, two diverse population panels, Pop1 and Pop2, composed of 409 and 199 soybean plant introductions, respectively, were evaluated for SMV seed transmission rate, seed coat mottling, and seed yield from SMV-infected plants. The phenotypic data and genotypic data from the SoySNP50K dataset were analyzed using GAPIT and rrBLUP. For SMV seed transmission rate, a single locus was identified on chromosome 9 in Pop1. For SMV-induced seed coat mottling, loci were identified on chromosome 9 in Pop1 and on chromosome 3 in Pop2. For seed yield from SMV-infected plants, a single locus was identified on chromosome 3 in Pop2 that was within the map interval of a previously described quantitative trait locus for seed number. The high linkage disequilibrium regions surrounding the markers on chromosomes 3 and 9 contained a predicted nonsense-mediated RNA decay gene, multiple pectin methylesterase inhibitor genes (involved in restricting virus movement), two chalcone synthase genes, and a homolog of the yeast Rtf1 gene (involved in RNA-mediated transcriptional gene silencing). The results of this study provided additional insight into the genetic architecture of these three important traits, suggested candidate genes for downstream functional validation, and suggested that genomic prediction would outperform marker-assisted selection for two of the four trait-marker associations.


Impaired left ventricular filling in patients with essential hyperhidrosis: an echo-Doppler study.
Essential hyperhidrosis is a well recognized dermatologic and neurologic disorder, characterized by excessive sweating of the eccrine sweat glands. It is also associated with cardiac autonomic dysfunction because sympathetic fibers to eccrine glands of palms of the hand arise from stellate and upper thoracic ganglia, which also innervate the heart. In this study, we investigated cardiac function in patients with essential hyperhidrosis by conventional and tissue Doppler imaging methods. Eighteen subjects with essential hyperhidrosis and eighteen control subjects were included in this study. Pulsed-wave Doppler parameters of the left and right ventricles, which represent diastolic filling abnormalities, were obtained by conventional Doppler and tissue Doppler imaging. Isovolumetric relaxation time, isovolumetric contraction time, ejection time and myocardial performance index were also calculated. Mitral inflow peak early (E(M)) and late (A(M)) velocities and E(M)/A(M) ratio, which represent diastolic filling of left ventricle, were significantly lower in hyperhidrotic subjects than in controls. Also, mitral lateral annulus early and late velocities and early/late velocity ratio, reflecting diastolic filling of left ventricle, were significantly lower in hyperhidrotic subjects than those of controls. However, there were no differences between hyperhidrotic subjects and control subjects with regard to the other echocardiographic indices of left and right ventricle diastolic functions. In conclusion, decreased mitral inflow suggests left ventricle diastolic dysfunction in patients with essential hyperhidrosis. This indicates that hyperactivity of sympathetic nervous system in patient with hyperhidrosis may alter cardiac function in long term.


The differences between the localizations of MUC1, MUC5AC, MUC6 and osteopontin in quail proventriculus and gizzard may be a reflection of functional differences of stomach parts.
Mucins are high molecular weight glycoproteins which constitute the major component of the mucus layer and are produce by many epithelial tissues in vertebrates. Osteopontin (OPN) is an adhesive phosphorylated glycoprotein that is expressed by a broad range of tissues and cells. Although gastric mucins MUC1, MUC5AC, MUC6 and OPN have been widely used in histological studies and in diagnostic pathology in order to diagnose gastric carcinomas, their localizations in the stomach of quail have not yet been studied. In this study, the localizations of MUC1, MUC5AC, MUC6 and OPN in the proventriculus and gizzard of Japanese quail during the post-hatching period were compared at light microscope levels by applying immunohistochemical methods. In all ages studied, the immunoreactivity of MUC5AC was present in the lining epithelium of both folds and superficial proventricular glands in the proventriculus, whereas MUC1, MUC6 and OPN reactivity was found in the oxynticopeptic cells of profound proventricular glands. In addition, some cells in the fold epithelium of the proventriculus showed a positive reaction to OPN. The immunoreactivity of MUC1 in gizzard was different from that of MUC5AC. Although MUC5AC was expressed in the cells of both the surface epithelium and profound glands of the gizzard, MUC1 was only localized in the profound glands of the gizzard. However, MUC6 and OPN immunoreactivity was absent in the gizzard. The results indicated that the differences between the localizations of MUC1, MUC5AC, MUC6 and OPN in quail proventriculus and gizzard may be a reflection of functional differences of stomach parts. Although the biological significances of the expressions of MUC1, MUC5AC, MUC6 and OPN in the quail stomach remains unknown, these notable glycoproteins may be associated with barrier function, host defence, and/or secretion.


Chapter II: New Fathers' and Mothers' Daily Stressors and Resources Influence Parent Adjustment and Family Relationships.
To understand new fathers' experiences and well-being, we examine links between fathers and their partners' replenishing and stressful daily experiences-exercise, sleep, work, chores, general stress, and parenting stress-and their own and their partners' well-being and family relations. Fathers and mothers of ten-month old infants (N=143/140 mothers/fathers) in the U.S. reported on daily experiences for eight consecutive days. Results of multilevel models indicated that more replenishing and fewer stressful daily experiences were generally linked to more parent happiness, better couple relations, and greater closeness with the infant. Several gender differences also emerged that may reflect different stress and coping processes or different social roles for mothers and fathers; most striking was that on days that fathers spent more time on chores, mothers reported greater couple closeness but fathers reported more arguments. This exploration of new parents' daily experiences demonstrates the value of the method to generate intervention-relevant insights, as well as the importance of examining fathers' (and mothers') experiences in the context of couple-level dynamics.


Location of Peptide-Induced Submicron Discontinuities in the Membranes of Vesicles Using ImageJ.
Cell penetrating peptide transportan 10 and antimicrobial peptide melittin formed submicron pores in the lipid membranes of vesicles which are explained by the leakage of water-soluble fluorescent probes from the inside of vesicles to the outside. It is hypothesized that these submicron pores induce submicron discontinuities in the membranes. Considering this hypothesis, a technique has developed to locate the submicron discontinuities in the membranes of giant unilamellar vesicles (GUVs) using ImageJ. In this technique, at first the edges of membrane of a 'single GUV' are detected and then these edges are used to locate the submicron discontinuities. Two continuous rings are observed after applying the ImageJ in GUVs which indicated the edges of membrane. In contrast, the submicron discontinuations are detected at the edges of transportan 10 and melittin induced pore formed membranes. This investigation might be helpful for the elucidation of mechanism of the peptide-induced pore formation in the membranes of vesicles.


Obtaining and characterization of monoclonal antibodies against recombinant extracellular domain of human epidermal growth factor receptor 2.
Human epidermal growth factor receptor 2 (HER2) is an important biomarker for detection and treatment of different types of cancers such as breast, ovarian, stomach cancer. In this study, we developed a monoclonal antibody against the extracellular domain (ECD) of HER2 biomarker of breast cancer. For this purpose, the ECD-HER2 gene was amplified and cloned into an expression vector. Gene was generated in Escherichia coli BL21 (DE3) strain for expression of recombinant protein. The expressed protein was separated by SDS-PAGE and detected by anti-his monoclonal antibody in immunoblotting. Hybridoma cells were obtained by fusing myeloma cells with mouse spleen cells injected with recombinant ECD-HER2 and screened by ELISA for the production of monoclonal antibody. The results indicate that out of three candidate hybridoma cells one clone (1E7) was producing the highest titer and antibody specificity was envisioned in ELISA results. In vivo scaling up culture of hybridoma cells in BALB/C mice lead to significant increase in the monoclonal antibody concentration up to 16 mg/ml. Immunochemical methods demonstrated the specificity of developed antibody against ECD-HER2 protein.


Correlations between First 72 h Hypophosphatemia, Energy Deficit, Length of Ventilation, and Mortality-A Retrospective Cohort Study.
Hypophosphatemia may prolong ventilation and induce weaning failure. Some studies have associated hypophosphatemia with increased mortality. Starting or restarting nutrition in a critically ill patient may be associated with refeeding syndrome and hypophosphatemia. The correlation between nutrition, mechanical ventilation, and hypophosphatemia has not yet been fully elucidated. A retrospective cohort study of 825 admissions during two consecutive years was conducted. Using the electronic medical chart, demographic and clinical data were obtained. Hypophosphatemia was defined as a phosphate level below 2.5 mg/dL (0.81 mmol/L) in the first 72 h of ICU admission. Comparisons between baseline characteristics and outcomes and multivariate analysis were performed. A total of 324 (39.27%) patients had hypophosphatemia during the first 72 h of ICU admission. Patients with hypophosphatemia tended to be younger, with lower APACHE-II, SOFA24, and ΔSOFA scores. They had a longer length of stay and length of ventilation, more prevalent prolonged ventilation, and decreased mortality. Their energy deficit was lower. There was no effect of hypophosphatemia severity on these results. In multivariate analysis, hypophosphatemia was not found to be statistically significant either with respect to mortality or survivor's length of ventilation, but lower average daily energy deficit and SOFA24 were found to be statistically significant with respect to survivor's length of ventilation. Hypophosphatemia had no effect on mortality or length of ventilation. Lower average daily energy deficit is associated with a longer survivor's length of ventilation.


Compensatory Role of Inositol 5-Phosphatase INPP5B to OCRL in Primary Cilia Formation in Oculocerebrorenal Syndrome of Lowe.
Inositol phosphatases are important regulators of cell signaling, polarity, and vesicular trafficking. Mutations in OCRL, an inositol polyphosphate 5-phosphatase, result in Oculocerebrorenal syndrome of Lowe, an X-linked recessive disorder that presents with congenital cataracts, glaucoma, renal dysfunction and mental retardation. INPP5B is a paralog of OCRL and shares similar structural domains. The roles of OCRL and INPP5B in the development of cataracts and glaucoma are not understood. Using ocular tissues, this study finds low levels of INPP5B present in human trabecular meshwork but high levels in murine trabecular meshwork. In contrast, OCRL is localized in the trabecular meshwork and Schlemm's canal endothelial cells in both human and murine eyes. In cultured human retinal pigmented epithelial cells, INPP5B was observed in the primary cilia. A functional role for INPP5B is revealed by defects in cilia formation in cells with silenced expression of INPP5B. This is further supported by the defective cilia formation in zebrafish Kupffer's vesicles and in cilia-dependent melanosome transport assays in inpp5b morphants. Taken together, this study indicates that OCRL and INPP5B are differentially expressed in the human and murine eyes, and play compensatory roles in cilia development.


Knowledge translation in audiology: promoting the clinical application of best evidence.
The impetus for evidence-based practice (EBP) has grown out of widespread concern with the quality, effectiveness (including cost-effectiveness), and efficiency of medical care received by the public. Although initially focused on medicine, EBP principles have been adopted by many of the health care professions and are often represented in practice through the development and use of clinical practice guidelines (CPGs). Audiology has been working on incorporating EBP principles into its mandate for professional practice since the mid-1990s. Despite widespread efforts to implement EBP and guidelines into audiology practice, gaps still exist between the best evidence based on research and what is being done in clinical practice. A collaborative dynamic and iterative integrated knowledge translation (KT) framework rather than a researcher-driven hierarchical approach to EBP and the development of CPGs has been shown to reduce the knowledge-to-clinical action gaps. This article provides a brief overview of EBP and CPGs, including a discussion of the barriers to implementing CPGs into clinical practice. It then offers a discussion of how an integrated KT process combined with a community of practice (CoP) might facilitate the development and dissemination of evidence for clinical audiology practice. Finally, a project that uses the knowledge-to-action (KTA) framework for the development of outcome measures in pediatric audiology is introduced.


Molecular flexibility in computational protein design: an algorithmic perspective.
Computational protein design (CPD) is a powerful technique for engineering new proteins, with both great fundamental implications and diverse practical interests. However, the approximations usually made for computational efficiency, using a single fixed backbone and a discrete set of side chain rotamers, tend to produce rigid and hyper-stable folds that may lack functionality. These approximations contrast with the demonstrated importance of molecular flexibility and motions in a wide range of protein functions. The integration of backbone flexibility and multiple conformational states in CPD, in order to relieve the inaccuracies resulting from these simplifications and to improve design reliability, are attracting increased attention. However, the greatly increased search space that needs to be explored in these extensions defines extremely challenging computational problems. In this review, we outline the principles of CPD and discuss recent effort in algorithmic developments for incorporating molecular flexibility in the design process.


Determination of ocean surface wave shape from forward scattered sound.
Forward scattered sound from the ocean surface is inverted for wave shape during three periods: low wind, mix of wind and swell, and stormy. Derived wave profiles are spatially limited to a Fresnel region at or near the nominal surface specular reflection point. In some cases, the surface wave profiles exhibit unrealistic temporal and spatial properties. To remedy this, the spatial gradient of inverted waves is constrained to a maximum slope of 0.88. Under this global constraint, only surface waves during low wind conditions result in a modeled surface multipath that accurately matches data. The power spectral density of the inverted surface wave field saturates around a frequency of 8 Hz while upward looking SONAR saturates at 1 Hz. Each shows a high frequency spectral slope of -4 that is in agreement with various empirical ocean wave spectra. The improved high frequency resolution provided by the scattering inversion indicates that it is possible to remotely gain information about high frequency components of ocean waves. The inability of the inversion algorithm to determine physically realistic surface waves in periods of high wind indicates that bubbles and out of plane scattering become important in those operating scenarios.


The Regulations and Mechanisms of Laparoscopic Sleeve Gastrectomy (LSG) for Obesity and Type 2 Diabetes: A Systematic Review.
Obesity and diabetes mellitus are becoming 2 of the most leading risk factors that threaten public health worldwide. Obesity is a very strong but preventable risk factor for getting type 2 diabetes. Laparoscopic sleeve gastrectomy (LSG) has been a main approach to the surgical management of morbid obesity and type 2 diabetes but its role remains undefined. Here, we overviewed the clinical outcomes and regulatory mechanisms of LSG, aiming at providing thorough theoretical supports and effective technical guidance to the pathogenesis, prognosis, treatment and prevention of type 2 diabetes with obesity. Futher more, the prospectives and main drawbacks (such as considerable heterogeneity and unicity, little comparability and relevance) of LSG are also discussed.


Long-term clinical and radiographic outcomes of cervical disc replacement with the Prestige disc: results from a prospective randomized controlled clinical trial.
The purpose of this study was to determine long-term clinical outcomes in patients undergoing anterior cervical surgery in which a cervical disc prosthesis was used to treat single-level degenerative cervical disc disease. In this prospective, nonblinded study, 541 patients at 32 investigational sites were randomly assigned to 1 of 2 treatment groups. The results of the investigational group, in which patients received the Prestige disc prosthesis, were compared with those of the control group, in which patients underwent an instrumented interbody fusion. Data were collected preoperatively, intraoperatively, and at 1.5, 3, 6, 12, 24, 36, and 60 months postoperatively. To date, 271 patients have completed 5 years of clinical follow-up (144 investigational and 127 control patients). Significant improvements in Neck Disability Index (NDI) scores, Physical Component Summary scores of the 36-Item Short-Form Health Survey, and neck and arm pain scores were achieved by 1.5 months in both groups and sustained at 5 years. The mean NDI improvements from preoperative scores were 35.4, 36.3, and 38.4 at 24, 36, and 60 months, respectively, in the investigational group. The corresponding mean NDI improvements were 33.9, 31.3, and 34.1 in the control group. The intergroup differences at both 36 and 60 months were significant (p = 0.008 and 0.022, respectively). The overall rates of maintenance or improvement in neurological status in the investigational group were 91.6%, 92.8%, and 95.0%, respectively, at 24, 36, and 60 months compared with 83.6%, 83.2%, and 88.9% in the control group (p = 0.006, 0.004, and 0.051, respectively). The implant effectively maintained angular motion, averaging more than 7.3 degrees at 36 months and 6.5 degrees at 60 months after surgery. No implant migration was observed up to 60 months. There were statistically significant differences between the investigational and control groups with regard to the rate of revision and supplemental fixation surgical procedures performed subsequent to the index procedure. Additional surgical procedures for adjacent-segment disease were observed in both treatment groups. Rates for surgery at adjacent levels trended lower in the investigational group (8 patients [11 surgeries]) compared with those in the control group (13 patients [16 surgeries]), but the differences were not statistically significant (p = 0.376). Some of the second surgeries involved both index and adjacent levels. The Prestige disc maintains improved clinical outcomes and segmental motion after implantation at 5-year follow-up.


Death anxiety and death denial: Nigerian and Australian students' metaphors of personal death.
Ninety-two Nigerian students and 114 Australian students completed Templer's (1970) Death Anxiety Scale (DAS) and Feifel and Nagy's (1981) death fantasy measure of positive and negative death metaphors. They were each also asked to write his or her own metaphor of personal death. Results of the DAS showed that the two groups did not differ significantly on the level of conscious death anxiety, but Nigerian students' scores were significantly higher on both positive and negative personal death metaphors scales. Also, significantly more Nigerian students wrote personal metaphors of their own and more often used a neutral metaphor to describe their personal death. Australian students more often used a positive or a negative metaphor. The Nigerian students thus evidenced less death denial than the Australian students did.


Tensile Strength of Artificially Cemented Sandstone Generated via Microbially Induced Carbonate Precipitation.
Artificially bio-cemented sands treated with microbially induced calcite precipitation are weakly cemented rocks representing intermediate materials between locked and carbonate sands. Variations in cementation significantly affect the strength of sample, particularly tensile stregth. The modes of fracture and the surface characteristics resulting from the indirect tensile strength tests (Brazilian tests) are strongly correlated with the specimen strength and consequently the degree of cementation. This study examines the tensile strength of bio-cemented fine and coarse sands (average particle diameter 0.18 and 1.82 mm, respectively) and investigates failure modes by recording fracture evolution at both sides of specimen and surface characteristics of the reconstructed surfaces. The dimensionless slope parameter Z2 provided the best fit with respect to tensile strength while the power spectral density was a good indicator of surface anisotropy. Finally, wavelet decomposition allowed for comparison of fracture surface characteristics of the two sands ignoring the grain size effects.


Risk of breast cancer with oral contraceptive use in women with a family history of breast cancer.
Oral contraceptive (OC) use is weakly associated with breast cancer risk in the general population, but the association among women with a familial predisposition to breast cancer is less clear. To determine whether the association between OC use and risk of breast cancer is influenced by family history of the disease. Historical cohort study of 426 families of breast cancer probands diagnosed between 1944 and 1952 at the Tumor Clinic of the University of Minnesota Hospital. Follow-up data on families were collected by telephone interview between 1991 and 1996. A total of 394 sisters and daughters of the probands, 3002 granddaughters and nieces, and 2754 women who married into the families. Relative risk (RR) of breast cancer associated with history of OC use by relationship to proband. After accounting for age and birth cohort, ever having used OCs was associated with significantly increased risk of breast cancer among sisters and daughters of the probands (RR, 3.3; 95% confidence interval [CI], 1.6-6.7), but not among granddaughters and nieces of the probands (RR, 1.2; 95% CI, 0.8-2.0) or among marry-ins (RR, 1.2; 95% CI, 0.8-1.9). Results were essentially unchanged after adjustment for parity, age at first birth, age at menarche, age at menopause, oophorectomy, smoking, and education. The elevated risk among women with a first-degree family history of breast cancer was most evident for OC use during or prior to 1975, when formulations were likely to contain higher dosages of estrogen and progestins (RR, 3.3; 95% CI, 1.5-7.2). A small number of breast cancer cases (n = 2) limited the statistical power to detect risk among women with a first-degree relative with breast cancer and OC use after 1975. These results suggest that women who have ever used earlier formulations of OCs and who also have a first-degree relative with breast cancer may be at particularly high risk for breast cancer. Further studies of women with a strong family history who have used more recent lower-dosage formulations of OCs are needed to determine how women with a familial predisposition to breast cancer should be advised regarding OC use today. JAMA. 2000;284:1791-1798.


Studies on mechanism of reaction and density behavior during anhydrous D-fructose mutarotation in the supercooled liquid state.
Recently, we have studied the mutarotation kinetics in D-fructose by means of dielectric spectroscopy. In the present work we investigate density behavior of D-fructose during mutarotation process. By performing volume measurements at temperature T = 303 K and pressure p = 10 MPa we are able to monitor kinetics of this process. As a result we found nearly the same value of the rate constant as previously determined from dielectric measurements. However, these two experimental methods monitor different molecular aspects of mutarotation phenomenon in D-fructose. Dielectric spectroscopy is sensitive to the decay of former ring as well as to the forming of another, while specific volume measurements are sensitive to the forming of new tautomers only. Calculations of activation energy of mutarotation in D-fructose led us to the conclusion, that mechanism of this reaction in amorphous phase could be based on internal proton transfer. Moreover it was found that the main mutarotation path in quenched D-fructose melt is transformation of α,β-furanose to β-pyranose.


Differential expression of prostaglandin E receptor subtype EP2 in rat uterus during early pregnancy.
PGE2 is essential for mammalian female reproduction. This study was to examine the expression of EP2 gene in the rat uterus during early pregnancy, delayed implantation and artificial decidualization by in situ hybridization and immunohistochemistry. There was no detectable EP2 mRNA expression in the uterus from days 1 to 4 of pregnancy (day 1 = day of vaginal sperm). A low level of EP2 immunostaining was observed in the luminal and glandular epithelium from days 1 to 4 of pregnancy. Both EP2 mRNA and protein expression were highly detected in the luminal epithelium at implantation sites on day 6 of pregnancy. EP2 expression decreased from day 7 of pregnancy and was undetectable on days 8 and 9 of pregnancy. After delayed implantation was terminated by estrogen treatment and the embryo implanted, both EP2 mRNA and protein expression were strongly observed in the luminal epithelium at the implantation site. There was no detectable EP2 expression in both control and decidualized uteri. In conclusion, these data suggest that EP2 expression at implantation site may play an important role during embryo implantation in rats.


Work status and burn specific health after work-related burn injury.
Work status is a valid indicator of post burn health. There is limited information on this issue after work-related burn injury. To investigate long-term health- and work status after work-related burns. Eighty-six former patients treated for severe work-related burn injuries an average of 9.0 years previous to follow-up were questioned about their present work status. They were also assessed with the Burn Specific Health Scale-Brief (BSHS-B) and a pain scale adopted from the abbreviated Burn Specific Health Scale. At follow-up 71 (83%) of the former patients were working, nine (10%) were on sick leave or had a disability pension, and six (7%) were unemployed. Those who were not working reported a poorer outcome in three of the BSHS-B psychosocial domains (Body Image, Affect and Interpersonal Relationships) and in two of the BSHS-B physical domains (Treatment Regimens and Work). They also reported significantly more pain. Only a small group of former patients with work-related accidents were not working in the sample studied after a long follow-up period. The unemployed reported more pain and worse perceived health, particularly in psychosocial domains.


Neighborhood and family influences on educational attainment: results from the Ontario child health study follow-up 2001.
This study uses multilevel models to examine longitudinal associations between contextual influences (neighborhood and family) assessed in 1983 in a cohort of 2,355 children, 4-16 years of age, and educational attainment in 2001. Variation in educational attainment in 2001 attributable to between-neighborhood and between-family differences was 8.17% and 36.88%, respectively. The final model explained 33.64% of the variance in educational attainment, with unique variances of 14.53% for neighborhood and family-level variables combined versus 10.94% for child-level variables. Among the neighborhood and family-level variables, indicators of status (5.29%) versus parental capacity/family process (4.03%) made comparable predictions to attainment while children from economically disadvantaged families did not benefit educationally from living in more affluent areas.


T-lymphocytes: a target for stimulatory and inhibitory effects of zinc ions.
The trace element zinc is a crucial cofactor for many proteins involved in cellular processes like differentiation, proliferation and apoptosis. Zinc homeostasis is tightly regulated and disturbance of this homeostasis due to genetic defects, zinc deficiency, or supplementation influences the development and the progression of various infectious and autoimmune diseases. The immune system is strongly impaired during zinc deficiency, predominantly the cell-mediated response by T-lymphocytes. During zinc deprivation T-lymphocyte development, polarization into effector cells, and function are impaired. This leads to reduced T-cell numbers, a decreased ratio of type 1 to type 2 T-helper cells with reduced production of T-helper type 1 cytokines like interferon-gamma, and compromised T-cell mediated immune defense. Accordingly, disturbed zinc homeostasis increases the risk for infections, and zinc supplementation restores normal immune function. Furthermore, several disorders, like mycobacterial infections, asthma, diabetes, and rheumatoid arthritis are accompanied by decreased zinc levels and in some cases disease progression can be affected by zinc supplementation. On the molecular level, apoptosis of T-cell precursors is influenced by zinc via the Bcl-2/Bax ratio, and zinc ions inhibit caspases-3, -6, -7, and -8. In mature T-cells, zinc interacts with kinases involved in T-cell activation, like protein kinase C and the lymphocyte protein tyrosine kinase (Lck), while higher zinc concentrations are inhibitory, reducing the activities of the interleukin-1 receptor-associated kinase (IRAK) and calcineurin. Taken together, zinc homeostasis influences T-lymphocytes via several molecular targets, leading to a modulation of T-cell-dependent immune responses.


Predicting Metastasis Risk in Pancreatic Neuroendocrine Tumors Using Deep Learning Image Analysis.
The prognosis of patients with pancreatic neuroendocrine tumors (PanNET), the second most common type of pancreatic cancer, varies significantly, and up to 15% of patients develop metastasis. Although certain morphological characteristics of PanNETs have been associated with patient outcome, there are no available morphology-based prognostic markers. Given that current clinical histopathology markers are unable to identify high-risk PanNET patients, the development of accurate prognostic biomarkers is needed. Here, we describe a novel machine learning, multiclassification pipeline to predict the risk of metastasis using morphological information from whole tissue slides. Digital images from surgically resected tissues from 89 PanNET patients were used. Pathologist-annotated regions were extracted to train a convolutional neural network (CNN) to identify tiles consisting of PanNET, stroma, normal pancreas parenchyma, and fat. Computationally annotated cancer or stroma tiles and patient metastasis status were used to train CNN to calculate a region based metastatic risk score. Aggregation of the metastatic probability scores across the slide was performed to predict the risk of metastasis. The ability of CNN to discriminate different tissues was high (per-tile accuracy >95%; whole slide cancer regions Jaccard index = 79%). Cancer and stromal tiles with high evaluated probability provided F1 scores of 0.82 and 0.69, respectively, when we compared tissues from patients who developed metastasis and those who did not. The final model identified low-risk (n = 76) and high-risk (n = 13) patients, as well as predicted metastasis-free survival (hazard ratio: 4.71) after adjusting for common clinicopathological variables, especially in grade I/II patients. Using slides from surgically resected PanNETs, our novel, multiclassification, deep learning pipeline was able to predict the risk of metastasis in PanNET patients. Our results suggest the presence of prognostic morphological patterns in PanNET tissues, and that these patterns may help guide clinical decision making.


Nasogastric Tube Feeding Experiences in Pediatric Oncology Patients and Their Mothers: A Qualitative Study.
The aim of this qualitative research study is to reveal children's and their mothers' views and experiences related to nasogastric tube feeding, which is the most frequently performed nutrition delivery method in pediatric oncology. The present study was carried out at an university pediatric oncology inpatient service. A total of three children and 14 mothers participated in the study. The analysis of the data was conducted according to Kolcaba's Comfort Theory. The findings resulting from the content analysis were explained under four main themes: (1) physical: includes the inability to be fed orally, nasogastric tube intervention, comfort because of feeding, medication administration, and satisfaction; (2) psychospiritual: includes anxiety, fear, distorted body image, and compliance; (3) sociocultural: includes conflicts with the child about feeding and advice on feeding via the nasogastric tube to other mothers and children; and (4) environmental: includes unrestricted/freedom of feeding. Gastroenterology professionals can also provide basic counseling and resources to children and mothers about the importance of maintaining an optimal weight and of enteral nutrition.


Effects of different levels of hatchery wastes on the performance, carcass and tibia ash and some blood parameters in broiler chicks.
This experiment was conducted to evaluate the effects of different levels of Hatchery Wastes (HW) on performance, tibia ash, blood calcium and phosphorus concentrations in broiler chickens. Birds were fed a corn-soybean meal diet for 7 days. The experimental treatments included a corn soybean meal diet and 3 other treatments containing 1.5, 3.0 and 4.5% HW. five replicate groups of 15 Ross 308 broiler chicks were allocated to each dietary treatment. Data were analyzed in a completely randomized design. Results indicated that there were no significant differences in weight gains among different dietary treatments. Feed intake in the 4.5% treatment was significantly higher (p < 0.05) and 3% treatment had lower feed intake than the other treatments. The results indicated that feed conversion in the 3% HW treatment was lower in most of the period (p > 0.05). Results of carcass analysis showed no significant differences between treatments. Also, there were no significant differences between blood calcium and phosphorous among treatments. The 4.5 and 3.0% hatchery wastes treatments had the highest tibia ash (p < 0.05). Based on the result of this experiment, the utilization of hatchery wastes as much as 3% can increase tibia strength without having adverse effect on broilers performance.


Aortic regurgitation after closure of ventricular septal defect by transcatheter device: the long-term complication.
Ventricular septal defect is the most common type of CHD, and transcatheter ventricular septal defect closure has been shown to be an alternative to surgical closure with acceptable mortality and morbidity as well as encouraging results. Short-term and mid-term follow-ups have indicated the safety and efficacy of transcatheter closure, but long-term follow-up results were rare. In this report, we first found that aortic regurgitation occurred in patients 9-12 years following transcatheter closure and regurgitation were gradually increased. The findings indicate that the long-term outcome of transcatheter closure of ventricular septal defect may not be as satisfied as expected.


Facial Action Unit Detection using 3D Face Landmarks for Pain Detection.
Automatic detection of facial action units (AUs) has recently gained attention for its applications in facial expression analysis. However, using AUs in research can be challenging since they are typically manually annotated, which can be time-consuming, repetitive, and error-prone. Advancements in automated AU detection can greatly reduce the time required for this task and improve the reliability of annotations for downstream tasks, such as pain detection. In this study, we present an efficient method for detecting AUs using only 3D face landmarks. Using the detected AUs, we trained state-of-the-art deep learning models to detect pain, which validates the effectiveness of the AU detection model. Our study also establishes a new benchmark for pain detection on the BP4D+ dataset, demonstrating an 11.13% improvement in F1-score and a 3.09% improvement in accuracy using a Transformer model compared to existing studies. Our results show that utilizing only eight predicted AUs still achieves competitive results when compared to using all 34 ground-truth AUs.