Food labeling issues for severe food allergic patients.
Food allergy carries high importance and responsibility, affecting an estimated 220 million people worldwide. It is a frequent cause of food-induced anaphylaxis, a life-threatening condition requiring a toll of about one death per 50 million people a year worldwide. In order to help patients to identify allergenic foods and thus avoid anaphylactic reactions, 66 countries over the 5 continents require by law that allergenic ingredients must be declared when used in prepackaged foods. Unfortunately, the mandatory allergen list is not uniform, but varies among different countries. The widespread adoption of Precautionary Allergen Labeling (PAL) results in a proliferation of unregulated PALs with different informative statements. In this situation, the need of a scientific consensus on the definition of food allergy and the identification of a tolerable risk with routinely used detection assays, considering not only the eliciting dose but also the food source, is urgent. The aim of this manuscript is: 1) to draw a picture of the global situation in terms of PALs, and 2) to highlight new approaches that could aid in tackling the problem of regulating the labeling of allergens. These include the Voluntary Incidental Trace Allergen Labelling (VITAL) system, which intersects reference doses and labelling decisions, and a direct quantification of trace amounts of allergens at lower limit of detection (LOD) levels in the food itself through proteomics. We here highlight how, although with some limitations, the steady advances in proteomic approaches possess higher sensitivity than the recommended VITAL reference doses, allowing the identification of allergens at much lower LOD levels than VITAL. Considering that each assay used to detect allergen in food products carries method-specific issues, a more comprehensive and harmonized approach implementing both quantitative and qualitative methods could help overcoming the risk stratification approach and the overuse of PALs, offering promise as the field moves forward towards improving consumers' quality of life.


Potent and Selective Modulation of the RhlR Quorum Sensing Receptor by Using Non-native Ligands: An Emerging Target for Virulence Control in Pseudomonas aeruginosa.
Pseudomonas aeruginosa uses N-acylated L-homoserine lactone signals and a triumvirate of LuxR-type receptor proteins--LasR, RhlR, and QscR--for quorum sensing (QS). Each of these receptors can contribute to QS activation or repression and, thereby, the control of myriad virulence phenotypes in this pathogen. LasR has traditionally been considered to be at the top of the QS receptor hierarchy in P. aeruginosa; however, recent reports suggest that RhlR plays a more prominent role in infection than originally predicted, in some circumstances superseding that of LasR. Herein, we report the characterization of a set of synthetic, small-molecule agonists and antagonists of RhlR. Using E. coli reporter strains, we demonstrated that many of these compounds can selectively activate or inhibit RhlR instead of LasR and QscR. Moreover, several molecules maintain their activities in P. aeruginosa at concentrations analogous to native RhlR signal levels. These compounds represent useful chemical probes to study the role of RhlR in the complex QS circuitry of P. aeruginosa, its direct (and indirect) effects on virulence, and its overall merit as a target for anti-infective therapy.


Endothelium-dependent relaxation of rat aorta to a histamine H(3) agonist is reduced by inhibitors of nitric oxide synthase, guanylate cyclase and Na,K-ATPase.
The possible involvement of different effector systems (nitric oxide synthase, guanylate cyclase, beta-adrenergic and muscarinic cholinergic receptors, cyclooxygenase and lipoxygenase, and Na(+),K(+)-ATPase) was evaluated in a histamine H(3) receptor agonist-induced ((R)alpha-methylhistamine, (R)alpha-MeHA) endothelium-dependent rat aorta relaxation assay. (R)alpha-MeHA (0.1 nM - 0.01 mM) relaxed endothelium-dependent rat aorta, with a pD(2) value of 8.22 +/- 0.06, compared with a pD(2) value of 7.98 +/- 0.02 caused by histamine (50% and 70% relaxation, respectively). The effect of (R)alpha-MeHA (0.1 nM - 0.01 mM) was competitively antagonized by thioperamide (1, 10 and 30 nM) (pA(2) = 9.21 +/- 0.40; slope = 1.03 +/- 0.35) but it was unaffected by pyrilamine (100 nM), cimetidine (1 muM), atropine (10 muM), propranolol (1 muM), indomethacin (10 muM) or nordthydroguaiaretic acid (0.1 mM). Inhibitors of nitric oxide synthase, L-N(G)-monomethylarginine (L-NMMA, 10 muM) and N(G)-nitro-L-arginine methylester (L-NOARG, 10 muM) inhibited the relaxation effect of (R)alpha-MeHA, by approximately 52% and 70%, respectively). This inhibitory effect of L-NMMA was partially reversed by L-arginine (10 muM). Methylene blue (10 muM) and ouabain (10 muM) inhibited relaxation (R)alpha-MeHA-induced by approximately 50% and 90%, respectively. The products of cyclooxygenase and lipoxygenase are not involved in (R)alpha-MeHA-induced endothelium-dependent rat aorta relaxation nor are the muscarinic cholinergic and beta-adrenergic receptors. The results also suggest the involvement of NO synthase, guanylate cyclase and Na(+),K(+)-ATPase in (R)alpha-MeHA-induced endothelium-dependent rat aorta relaxation.


Pharmacokinetics of piperacillin-tazobactam in anuric intensive care patients during continuous venovenous hemodialysis.
The pharmacokinetics of piperacillin-tazobactam were investigated in eight anuric intensive care patients treated by continuous venovenous hemodialysis (CVVHD). The elimination half-life of piperacillin was 4.3 +/- 1.2 h, and that of tazobactam was 5.6 +/- 1.3 h. The contribution of CVVHD to the overall elimination was relevant (>25%) for both drugs.


Association of polycyclic aromatic hydrocarbon metabolite concentration in urine and occupational stress in underground coal miners in China: propensity score and bayesian kernel machine regression.
This study intends to examine the association of urinary monohydroxyl PAHs (OH-PAHs) concentration and occupational stress in coal miners. We sampled 671 underground coal miners from Datong, China, assessed their occupational stress using the Occupational Stress Inventory-Revised edition (OSI-R), and categorized them into the high stress miners and controls based on that. We determined urinary OH-PAHs concentration using ultrahigh performance liquid chromatography-tandem mass spectrometry, and analyzed its association with occupational stress using multiple linear regression, covariate balancing generalized propensity score (CBGPS), and Bayesian kernel machine regression (BKMR). The low molecular weight (LMW) OH-PAHs in quartile or homologue was significantly positively associated with Occupational Role Questionnaire (ORQ) and Personal Strain Questionnaire (PSQ) score, but was not associated with Personal Resources Questionnaire (PRQ) score. The OH-PAHs concentration was positively associated with ORQ and PSQ scores in coal miners, particularly the LMW OH-PAHs. Non-association was found in the OH-PAHs with PRQ score.


Immediate effects of 14 non MAOI antidepressants in rats with spontaneous petit mal-like seizures.
1. Wistar rats of a strain presenting spontaneous petit mal-like seizures were injected intraperitoneally with graded doses of 14 non-monoamine oxidase inhibitor antidepressants and the immediate effects on behavior and the EEG were recorded. 2. Amineptine and nomifensine, the two drugs interacting with dopaminergic neurotransmission, reduced the duration of spontaneous spike-wave discharges (SWD) and were thus potentially antiepileptic. 3. Trazodone increased SWD duration. 4. The antidepressants, imipramine-like (imipramine, chlorimipramine, desipramine, metapramine and amitriptyline) and non-imipraminic (minaprine, maprotiline, viloxazine, mianserin, fluvoxamine and indalpine), and the 3 noted above, had potentially convulsive effects.


Circadian regulation of mTORC1 signaling via Per2 dependent mechanism disrupts folliculogenesis and oocyte maturation in female mice.
mTOR (mammalian target of Rapamycin) is an important signaling pathway involved in several crucial ovarian functions including folliculogenesis and oocyte maturation. The circadian rhythm regulates multiple physiological processes and PER2 is one of the core circadian rhythm components. mTOR is regulated by the circadian clock and in turn, the rhythmic mTOR activities strengthen the clock function. Our current study aims to investigate a possible interconnection between the circadian clock and the mTORC1 signaling pathway in folliculogenesis and oocyte maturation. Here we demonstrate that the circadian system regulates mTORC1 signaling via Per2 dependent mechanism in the mouse ovary. To investigate the effect of constant light on ovarian and oocyte morphology, animals were housed 12:12 h L:D group in standard lightening conditions and the 12:12 h L:L group in constant light for one week. Food intake and body weight changes were measured. Ovarian morphology, follicle counting, and oocyte aging were evaluated. Afterward, western blot for mTOR, p-mTOR, p70S6K, p-p70S6K, PER2, and Caspase-3 protein levels was performed. The study demonstrated that circadian rhythm disruption caused an alteration in their food intake and decrease in primordial follicle numbers and an increase in the number of atretic follicles. It caused an increase in oxidative stress and a decrease in ZP3 expression in oocytes. Decreased protein levels of mTOR, p-mTOR, p70S6K, and PER2 were shown. The results showed that the circadian clock regulates mTORC1 through PER2 dependent mechanism and that decreased mTORC1 activity can contribute to premature aging of mouse ovary. In conclusion, these results suggest that the circadian clock may control ovarian aging by regulating mTOR signaling pathway through Per2 expression.


Treatment of infrapopliteal critical limb ischemia in 2013: the wound perfusion approach.
The primary goals of treatment for critical limb ischemia (CLI) are alleviation of ischemic rest pain, healing of arterial insufficiency ulcers, and improving quality of life. These goals are directed toward preventing limb loss and CLI-related mortality. Arterial revascularization serves as the foundation of a contemporary approach to promote amputation-free survival. Mounting evidence supports a wound-directed angiosome revascularization approach, increasingly achieved with endovascular techniques. Innovations in technology and wound-perfusion strategy have advanced patient care and are accelerating the pace of CLI treatment. The evolving angiosome revascularization approach has been augmented with a multidisciplinary wound care strategy that deserves particular emphasis. These state-of-the-art advances in CLI management are reported herein with considerations for the future treatment of CLI.


Rituximab in combination with adapted-dose of ifosfamide and etoposide as salvage treatment in elderly refractory/relapsed diffuse large B-cell lymphoma patients non-candidate for high dose therapy: a retrospective study.
We retrospectively reviewed for 72 relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) patients ineligible for autologous stem-cell transplantation (ASCT) treated between 2004 and 2017, efficacy and safety profile of rituximab (375 mg/m2) in combination with etoposide (300 mg/m2) and ifosfamide (1500 mg/m2) at 2, 3, or 4-week intervals. Median age was 79 years (range, 64-92). The median number of previous line was 1 (range 1-8). Patients received a median of six cycles (1-12). Fourteen patients (19%) presented partial and 14 complete responses (19%). Among the 369 cycles, nine patients developed febrile neutropenia (13%), 14 a grade 3-4 neutropenia (19%), 7 a grade 3-4 thrombocytopenia (10%) without grade 3-4 non-hematological toxicity. With a median follow up of 7.8 months, the median progression-free survival, overall survival, and duration of response were 4.4 months, 9.4 months, and 12 months, respectively. This regimen represents a therapeutic option in R/R DLBCL patients ineligible to ASCT.


Effects of Historical Recording Technology on Vibrato in Modern-Day Opera Singers.
Past literature indicates that vibrato measurements of singers objectively changed (i.e., vibrato rate decreased and vibrato extent increased) from 1900 to the present day; however, historical audio recording technology may distort acoustic measurements of the voice output signal, including vibrato. As such, the listener's perception of historical singing may be influenced by the limitations of historical technology. This study attempts to show how the wax cylinder phonograph system-the oldest form of mass-produced audio recording technology-alters the recorded voice output signal of modern-day singers and, thus, provides an objective lens through which to study the effect(s) of historical audio recording technology on vibrato measurements. Twenty professional Western opera singers sang a messa di voce on the vowel [a] and on the pitch C4 for male singers and C5 for female singers, three times into a flat-response omnidirectional microphone and onto an Edison Home Phonograph simultaneously. The middle 1-3 seconds (6-10 vibrato cycles) of each sample was analyzed for vibrato rate, vibrato extent, jitter (ddp), shimmer (dda), and fundamental frequency for each recording condition (wax cylinder phonograph or microphone). Steady-state and frequency-modulating sinewave test signals were also recorded under the multiple recording conditions. Results indicated no significant effect of recording condition on vibrato rate (mean [standard deviation], cylinder: 5.3 Hz [0.5], microphone: 5.3 Hz [0.5]) and no significant difference was found for mean fundamental frequency (cylinder: 389 Hz [137], microphone: 390 Hz [137]). A significant main effect of recording condition was found for vibrato extent (cylinder: ±103 cents [30], microphone: ±100 cents [31]). Additionally, mean jitter (ddp) (cylinder: 1.22% [1.09], microphone: 0.24% [0.12]) and mean shimmer (dda) (cylinder: 9.40% [4.90], microphone: 1.92% [0.94]) were significantly higher for the cylinder recording condition, indicating more cycle-to-cycle variability in the wax cylinder recorded signal. Analysis of test signals revealed similar patterns based on recording condition. This study validates past scholarly inquiry about vibrato measurements as extracted from digitized wax cylinder phonograph recordings by demonstrating that measured vibrato rate remains constant during both recording conditions. In other words, vibrato rate as measured from historical recordings can be viewed as an accurate representation of the historical singer being studied. Furthermore, it suggests that the value of prior vibrato extent measurements from these acoustic recordings may be slightly overestimated from the original voice output signals produced by singers near the beginning of the 20th century (i.e., a narrow vibrato extent might have been numerically smaller on average). Increased jitter and shimmer in the wax cylinder recording conditions may be indicative of nonlinearities in the phonograph recording or playback systems.


Gastric Carcinosarcoma and 18F-FDG PET/CT.
Gastric carcinosarcoma is a rare, malignant neoplasm that simultaneously comprises mixed epithelial and mesenchymal elements. In the present study, we report a case of gastric carcinosarcoma composed of rhabdomyosarcoma and adenocarcinoma on F-FDG PET/CT.


Intragenic compensation through the lens of deep mutational scanning.
A significant fraction of mutations in proteins are deleterious and result in adverse consequences for protein function, stability, or interaction with other molecules. Intragenic compensation is a specific case of positive epistasis when a neutral missense mutation cancels effect of a deleterious mutation in the same protein. Permissive compensatory mutations facilitate protein evolution, since without them all sequences would be extremely conserved. Understanding compensatory mechanisms is an important scientific challenge at the intersection of protein biophysics and evolution. In human genetics, intragenic compensatory interactions are important since they may result in variable penetrance of pathogenic mutations or fixation of pathogenic human alleles in orthologous proteins from related species. The latter phenomenon complicates computational and clinical inference of an allele's pathogenicity. Deep mutational scanning is a relatively new technique that enables experimental studies of functional effects of thousands of mutations in proteins. We review the important aspects of the field and discuss existing limitations of current datasets. We reviewed ten published DMS datasets with quantified functional effects of single and double mutations and described rates and patterns of intragenic compensation in eight of them. The online version contains supplementary material available at 10.1007/s12551-022-01005-w.


Effectiveness of Inactivated and mRNA COVID-19 Vaccines Against SARS-CoV-2 Infection, Severe Disease and Mortality in the Geriatric Population.
Older age (>60 years) has been identified as the main risk factor for COVID-19. In this study, we aimed to evaluate the efficacy of Pfizer-BioNTech and CoronaVac vaccines against COVID-19 infection, serious illness, and mortality in the geriatric population. We found that 2 doses of CoronaVac vaccine were ineffective in protecting against COVID-19 infection in people over 65 years of age, while the vaccine efficacy (VE) of the mRNA vaccine against COVID-19 was 80% (95% CI 70-87). The VE of full vaccination with BioNTech was 89% (95% CI 53-97) against hospitalization, 79% (95% CI 0-97) against death, and 79% (95% CI 0-97) against intensive care unit (ICU) admission. However, the VE of full vaccination with CoronaVac was 50% (95% CI 33-63) against hospitalization, 53% (95% CI 26-70) against ICU admission, and 56% (95% CI 30-73) against death. In conclusion, we found that the mRNA vaccine has higher efficacy against severe COVID-19 infection and mortality in the geriatric population than the inactivated vaccine. Booster doses of vaccines should be considered in increasing the effectiveness of inactivated vaccines. Given the potential of SARS-CoV-2 mutations evading vaccination protection and the risk of reduced immunity over time, regular monitoring of vaccine effectiveness in the real world is critical.


Distinct urban-rural gradients of air NO2 and SO2 concentrations in response to emission reductions during 2015-2022 in Beijing, China.
Nitrogen dioxide (NO2) and sulfur dioxide (SO2) are two major air pollutants in urban environment. Emission reduction policies have thus been implemented to improve urban air quality, especially in the metropolises. However, it remains unclear whether the air concentrations of NO2 and SO2 in and around large cities follow a same spatial pattern and how their characteristics change over time in response to the emission reductions. Using ground-based monitoring datasets of air NO2 and SO2 concentrations in Beijing, China, we tested the hypothesis of urban air pollutant islands and evaluated their seasonal and inter-annual variations during 2015-2022. The results showed that air NO2 concentrations increased significantly towards the urban core, being in line with the hypothesis of urban air pollutant island, while air SO2 concentrations showed no such spatial patterns. The urban air NO2 island varied seasonally, with larger radius and higher air NO2 concentrations in spring and winter. In response to the emission reduction, the annual mean radius of the urban air NO2 island showed a rapid decrease from 45.8 km to zero km during the study period. The annual mean air NO2 concentration at the urban core showed a linear decrease at a rate of 4.5 μg m-3 yr-1. In contrast, air SO2 concentration decreased nonlinearly over time and showed a legacy in comparison to the emission reduction. Our findings suggest different urban-rural gradients of air NO2 and SO2 concentrations and highlight their distinct responses to the regional reductions of anthropogenic emissions.


Derivation of hormone-responsive human endometrial organoids and stromal cells from cryopreserved biopsies.
The human endometrium is a dynamic tissue that undergoes cyclic changes in response to sex steroid hormones to provide a receptive status for embryo implantation. Disruptions in this behavior may lead to implantation failure and infertility; therefore, it is essential to develop an appropriate in vitro model to study endometrial changes in response to sex hormones. In this regard, the first choice would be human endometrial cells isolated from biopsies that could be used as monolayer cell sheets or to generate endometrial organoids. However, the need for fresh samples and short-time viability of harvested endometrial biopsy limits these approaches. In order to overcome these limitations, we sought to develop an efficient, simple, robust and reproducible method to cryopreserve human endometrial biopsies that could be stored and/or shipped frozen and later thawed to generate endometrial organoids and endometrial stromal cells (EnSCs). These cryopreserved biopsies could be thawed and used to generate simple endometrial organoids or organoids for co-culture with matched stromal cells that are functionally responsive to sex hormones as similar as the organoids generated from fresh biopsy. An optimal endometrial tissue cryopreservation method would allow the possibility for endometrial tissue biobanking to enable future organoid generation from both healthy tissues and pathological conditions, and open new venues for generate endometrial assembloids, consisting of epithelial organoids and primary stromal cells.


The core promoter: At the heart of gene expression.
The identities of different cells and tissues in multicellular organisms are determined by tightly controlled transcriptional programs that enable accurate gene expression. The mechanisms that regulate gene expression comprise diverse multiplayer molecular circuits of multiple dedicated components. The RNA polymerase II (Pol II) core promoter establishes the center of this spatiotemporally orchestrated molecular machine. Here, we discuss transcription initiation, diversity in core promoter composition, interactions of the basal transcription machinery with the core promoter, enhancer-promoter specificity, core promoter-preferential activation, enhancer RNAs, Pol II pausing, transcription termination, Pol II recycling and translation. We further discuss recent findings indicating that promoters and enhancers share similar features and may not substantially differ from each other, as previously assumed. Taken together, we review a broad spectrum of studies that highlight the importance of the core promoter and its pivotal role in the regulation of metazoan gene expression and suggest future research directions and challenges.


Urgent Liver Transplantation from Deceased Donor With a Calcified Hydatid Cyst: A Case Report.
Liver transplantation is the final treatment option for end-stage liver disease and acute liver failure, although availability of donor organs is a major limitation. The large gap between the growing list of patients awaiting liver transplantation and the scarcity of donor organs has fueled efforts to maximize the existing donor pool and identify new avenues. We treated a 13-year-old boy who had acute liver failure, due to Wilson's disease, with transplantation of a liver from a deceased liver donor with a calcified hydatid cyst. After 3 years of follow-up, liver function tests remained normal, hydatid cyst serology was negative, and no hydatid cyst or other problems were observed.


Preparation and characterization of stable aqueous higher-order fullerenes.
Stable aqueous suspensions of nC₆₀ and individual higher fullerenes, i.e. C₇₀, C₇₆ and C₈₄, are prepared by a calorimetric modification of a commonly used liquid-liquid extraction technique. The energy requirement for synthesis of higher fullerenes has been guided by molecular-scale interaction energy calculations. Solubilized fullerenes show crystalline behavior by exhibiting lattice fringes in high resolution transmission electron microscopy images. The fullerene colloidal suspensions thus prepared are stable with a narrow distribution of cluster radii (42.7 ± 0.8 nm, 46.0 ± 14.0 nm, 60 ± 3.2 nm and 56.3 ± 1.1 nm for nC₆₀, nC₇₀, nC₇₆ and nC₈₄, respectively) as measured by time-resolved dynamic light scattering. The ζ-potential values for all fullerene samples showed negative surface potentials with similar magnitude ( - 38.6 ± 5.8 mV, - 39.1 ± 4.2 mV, - 38.9 ± 5.8 mV and - 41.7 ± 5.1 mV for nC₆₀, nC₇₀, nC₇₆ and nC₈₄, respectively), which provide electrostatic stability to the colloidal clusters. This energy-based modified solubilization technique to produce stable aqueous fullerenes will likely aid in future studies focusing on better applicability, determination of colloidal properties, and understanding of environmental fate, transport and toxicity of higher-order fullerenes.


Integrative DNA methylation and gene expression analysis to assess the universality of the CpG island methylator phenotype.
The CpG island methylator phenotype (CIMP) was first characterized in colorectal cancer but since has been extensively studied in several other tumor types such as breast, bladder, lung, and gastric. CIMP is of clinical importance as it has been reported to be associated with prognosis or response to treatment. However, the identification of a universal molecular basis to define CIMP across tumors has remained elusive. We perform a genome-wide methylation analysis of over 2000 tumor samples from 5 cancer sites to assess the existence of a CIMP with common molecular basis across cancers. We then show that the CIMP phenotype is associated with specific gene expression variations. However, we do not find a common genetic signature in all tissues associated with CIMP. Our results suggest the existence of a universal epigenetic and transcriptomic signature that defines the CIMP across several tumor types but does not indicate the existence of a common genetic signature of CIMP.


Insulin and glucagon signaling in the central nervous system.
The prevalence of the obesity and diabetes epidemic has triggered tremendous research investigating the role of the central nervous system (CNS) in the regulation of food intake, body weight gain and glucose homeostasis. This invited review focuses on the role of two pancreatic hormones--insulin and glucagon--that trigger signaling pathways in the brain to regulate energy and glucose homeostasis. Unlike in the periphery, insulin and glucagon signaling in the CNS does not seem to have opposing metabolic effects, as both hormones exert a suppressive effect on food intake and weight gain. They signal through different pathways and alter different neuronal populations suggesting a complementary action of the two hormones in regulating feeding behavior. Similar to its systemic effect, insulin signaling in the brain lowers glucose production. However, the ability of glucagon signaling in the brain to regulate glucose production remains unknown. Future studies that aim to dissect insulin and glucagon signaling in the CNS that regulate energy and glucose homeostasis could unveil novel signaling molecules to lower body weight and glucose levels in obesity and diabetes.


Ways that nursing home nursing staff build resilience: a phenomenographic approach.
Resilience has been studied as an effective concept in nursing that acts as a protective factor which aids in overcoming difficult situations and related mental problems. With the recent increase in demand for nursing homes, nursing home nursing staff are facing a variety of stresses and psychological burdens. Improving resilience has been suggested as one way to deal with the difficulties, such as stress, exhaustion, and burnout, that nursing home nursing staff are experiencing. In order to provide successful education aimed at improving such resilience, it is very important to understand how to perceive experience from the learner's point of view. The study's aim is to identify the ways that nursing home nursing staff build resilience. This study used phenomenography, a methodology for exploring the relationship between subject and phenomenon. From January 15, 2022 to February 20, 2022, data collection was undertaken at three nursing homes located in the Republic of Korea. The data was collected through semi-structured interviews with 20 nursing staff members in NHs and a data analysis that strictly followed the 7-step analysis process of phenomenography. Eight categories were derived. The eight categories were then divided into two groups of four representing perception and strategy. Perception included four categories: 'grasping the situation', 'thinking about one's responsibility for the resident and personal values', 'considering one's strength' and 'thinking of an improved self'. Strategy included four categories: 'evaluation of oneself and one's environment', 'taking care of oneself', 'finding concrete ways to manage the problem' and 'self-development for growth'. Perception had three levels of awareness, valuing and assuring, while strategy had three levels of identifying, introspecting and concretizing. This study provides insight into how individual nursing staff build resilience, a complex and subjective concept. It provides a foundation for future resilience education of nursing home nursing staff and suggests future educational intervention development directions.


Intrinsic disorder and oligomerization of the hepatitis delta virus antigen.
The 195 amino acid basic protein (δAg) of hepatitis delta virus (HDV) is essential for replication of the HDV RNA genome. Numerous properties have been mapped to full-length δAg and attempts made to link these to secondary, tertiary and quaternary structures. Here, for the full-size δAg, extensive intrinsic disorder was predicted using PONDR-FIT, a meta-predictor of intrinsic disorder, and evidenced by circular dichroism measurements. Most δAg amino acids are in disordered configurations with no more than 30% adopting an α-helical structure. In addition, dynamic light scattering studies indicated that purified δAg assembled into structures of as large as dodecamers. Cross-linking followed by denaturing polyacrylamide gel electrophoresis revealed hexamers to octamers for this purified δAg and at least this size for δAg found in virus-like particles. Oligomers of purified δAg were resistant to elevated NaCl and urea concentrations, and bound without specificity to RNA and single- and double-stranded DNAs.


Identification of a variation in the IVSII of α2 gene and its frequency in the population of Guangxi.
During thalassemia screening, a previously unidentified α2 gene variation in α-globin gene cluster was isolated. This variation was distinct from other variations known to confer thalassemia as assessed by conventional thalassemia genotype analysis. Because the sample in the thalassemia screening was positive (MCV=83.6fL, MCH=26.1pg/cell, Hb=11.3g/dL), further analysis was required. MLPA (multiplex ligation-dependent probe amplification) and sequencing were used for analysis, and a qPCR system was designed for the frequency study. The MLPA result showed that there was a mutation or small fragment deletions between 34247 (160bp probe) and 34618 (196bp probe) in α-globin gene cluster (NG_000006.1). Through sequencing, this variation was identified as HBA2: c.301-24delGinsCTCGGCCC. The gene polymorphisms similar to HBA2:c.301-24delGinsCTCGGCCC are α121 and α212. Since α212 is unrelated to microcytosis, and the structure of HBA2: c.301-24delGinsCTCGGCCC is similar to α212, this change is more appropriately considered as a polymorphism. The allele frequency of HBA2: c.301-24delGinsCTCGGCCC is 0.184% in this region. There is a certain ratio for HBA2:c.301-24delGinsCTCGGCCC carriers among the Chinese population. The HBA2:c.301-24delGinsCTCGGCCC variant results in an abnormal result from MLPA analysis. Investigators performing thalassemia screening in Guangxi region should be aware of the HBA2:c.301-24delGinsCTCGGCCC variant to avoid misinterpretation of the MLPA results.


An unusual cause of acute abdomen-Gas-forming liver abscess due to Salmonella enteritidis.
Gas-forming pyogenic liver abscess (GFPLA) is considered to be a very severe form of PLA and carries a high mortality. Klebsiella pneumoniae is the most common pathogen responsible for the disease, whereas cases where Salmonella is cited as the cause are very uncommon. We report the first case of a 53-year-old lady suffering from GFPLA due to Salmonella, who was successfully treated with surgical drainage. To the best of our knowledge, this is the first case of GFPLA caused by Salmonella enteritidis to be reported in the English literature.


Comprehensive assessment of TP53 loss of function using multiple combinatorial mutagenesis libraries.
The diagnosis of somatic and germline TP53 mutations in human tumors or in individuals prone to various types of cancer has now reached the clinic. To increase the accuracy of the prediction of TP53 variant pathogenicity, we gathered functional data from three independent large-scale saturation mutagenesis screening studies with experimental data for more than 10,000 TP53 variants performed in different settings (yeast or mammalian) and with different readouts (transcription, growth arrest or apoptosis). Correlation analysis and multidimensional scaling showed excellent agreement between all these variables. Furthermore, we found that some missense mutations localized in TP53 exons led to impaired TP53 splicing as shown by an analysis of the TP53 expression data from the cancer genome atlas. With the increasing availability of genomic, transcriptomic and proteomic data, it is essential to employ both protein and RNA prediction to accurately define variant pathogenicity.


Localization of Coronary High-Intensity Signals on T1-Weighted MR Imaging: Relation to Plaque Morphology and Clinical Severity of Angina Pectoris.
This study sought to investigate the relationship between localization of high-intensity signals (HISs) on T1-weighted imaging (T1WI) with the noncontrast magnetic resonance technique and plaque morphology detected on optical coherence tomography, and the clinical severity of angina pectoris. Since the introduction of the T1WI noncontrast magnetic resonance technique for plaque imaging, some groups have reported that HISs in the coronary artery on T1WI are associated with a vulnerable morphology and future cardiac events. However, the association between the localization of HISs, such as coronary intrawall or intraluminal, and plaque morphology has not been investigated. One hundred lesions with either stable or unstable angina were included and divided into 3 groups according to the following criteria using T1WI. First, the plaques with the ratio between the signal intensities of coronary plaque and cardiac muscle ≤1.0 were classified as non-HISs (n = 39). Then, HISs with the ratio between the signal intensities of coronary plaque and cardiac muscle >1.0 were classified into 2 types by using cross-sectional T1WI. Those localized within the coronary wall when the lumen was identified were defined as intrawall HISs (n = 37), whereas those occupying the lumen when the lumen was not, or even if only partly, identified, were defined as intraluminal HISs (n = 24). Multivariate analysis revealed that intrawall HISs were associated with macrophage accumulation and the absence of calcification assessed by using optical coherence tomography. In contrast, thrombus and intimal vasculature were independent factors associated with intraluminal HISs. Furthermore, 50% of patients with intraluminal HISs experienced rest angina, such as Braunwald class II or III. This study shows that intrawall and intraluminal HISs on T1WI in patients with angina are related to the different types of vulnerable plaque morphology and the clinical severity.


Thalamic degeneration in MPTP-treated Parkinsonian monkeys: impact upon glutamatergic innervation of striatal cholinergic interneurons.
In both Parkinson's disease (PD) patients and MPTP-treated non-human primates, there is a profound neuronal degeneration of the intralaminar centromedian/parafascicular (CM/Pf) thalamic complex. Although this thalamic pathology has long been established in PD (and other neurodegenerative disorders), the impact of CM/Pf cell loss on the integrity of the thalamo-striatal glutamatergic system and its regulatory functions upon striatal neurons remain unknown. In the striatum, cholinergic interneurons (ChIs) are important constituents of the striatal microcircuitry and represent one of the main targets of CM/Pf-striatal projections. Using light and electron microscopy approaches, we have analyzed the potential impact of CM/Pf neuronal loss on the anatomy of the synaptic connections between thalamic terminals (vGluT2-positive) and ChIs neurons in the striatum of parkinsonian monkeys treated chronically with MPTP. The following conclusions can be drawn from our observations: (1) as reported in PD patients, and in our previous monkey study, CM/Pf neurons undergo profound degeneration in monkeys chronically treated with low doses of MPTP. (2) In the caudate (head and body) nucleus of parkinsonian monkeys, there is an increased density of ChIs. (3) Despite the robust loss of CM/Pf neurons, no significant change was found in the density of thalamostriatal (vGluT2-positive) terminals, and in the prevalence of vGluT2-positive terminals in contact with ChIs in parkinsonian monkeys. These findings provide new information about the state of thalamic innervation of the striatum in parkinsonian monkeys with CM/Pf degeneration, and bring up an additional level of intricacy to the consequences of thalamic pathology upon the functional microcircuitry of the thalamostriatal system in parkinsonism. Future studies are needed to assess the importance of CM/Pf neuronal loss, and its potential consequences on the neuroplastic changes induced in the synaptic organization of the thalamostriatal system, in the development of early cognitive impairments in PD.


[Study of arterial pressure levels at consultation in treated hypertensive Algerian patients].
Hypertension is responsible for 8.5 million deaths from stroke, ischemic heart disease and other vascular and kidney diseases. In Algeria, hypertension (HTN) is the most common chronic disease with an estimated prevalence of 23,6%. The PACT II study is a national, observational, descriptive, cross-sectional, multicenter and non-interventional study of therapeutic strategy, conducted in Algeria on hypertensive patients treated for at least 3 months, followed by 100 specialists or general practitioners. The primary objective is to describe the hypertension management in Algeria through the distribution of patients treated for HTN through predefined levels of arterial pressure (AP) reached under treatment. 2000 eligible patients were recruited in the study. 63.5% and 36.4% of patients were female and male respectively. The average age was 62.4 years ± 10.7. The most affected age group (65.2%) was between 55 to 75 years old. Most of the patients had an elevated blood pressure (BP) with 49.30 % at level III AP (130 - 139 mmHg of SBP or 80 - 89 mmHg of DBP), with 49.6% for diabetic patients and 48.8% for non-diabetic patients, then followed by 20.35% at the level IV AP (140 - 159 mmHg of SBP or 90 - 99 mmHg of DBP) with 21.4% for diabetic and 18.3% for non-diabetic patients. Also, 47.32% were at AP level III in patients with Renal failure. Regarding the achievement of the BP target, it was 17.4% for the overall population with 18,3% for diabetic's patients and only 12.64% for Renal failure patients. Additionally, the risk of cardiovascular disease (CVD) was at very high level for most patients, corresponding to 38,4 % of the overall study population. At last, PACT II study data were collected on analysis of blood pressure levels in the overall population and in cardiovascular risk (CVR) population groups such as diabetes (65%), sedentary lifestyle (53%), dyslipidemia (50%), obesity (44%), and renal failure (11.3%). PACT II has made it possible to update national data relating to hypertension in Algeria. It confirmed the low level of achievement of the BP target, even if the average arterial pressure level obtained was acceptable in 76% patients with a BP level which was lower than 140 mmHg for SBP and less than 90 mmHg for DBP. Many efforts must be made, according to WHO recommendations, to improve the management of hypertensive patients and BP control in Algeria.


β-Estradiol and ethinyl-estradiol contamination in the rivers of the Carpathian Basin.
17β-Estradiol (E2) and 17α-ethinyl estradiol (EE2), which are environmental estrogens, have been determined with LC-MS in freshwater. Their sensitive analysis needs derivatization and therefore is very hard to achieve in multiresidue screening. We analyzed samples from all the large and some small rivers (River Danube, Drava, Mur, Sava, Tisza, and Zala) of the Carpathian Basin and from Lake Balaton. Freshwater was extracted on solid phase and derivatized using dansyl chloride. Separation was performed on a Kinetex XB-C18 column. Detection was achieved with a benchtop orbitrap mass spectrometer using targeted MS analysis for quantification. Limits of quantification were 0.05 ng/L (MS1) and 0.1 ng/L (MS/MS) for E2, and 0.001 ng/L (MS1) and 0.2 ng/L (MS/MS) for EE2. River samples contained n.d.-5.2 ng/L E2 and n.d.-0.68 ng/L EE2. Average levels of E2 and EE2 were 0.61 and 0.084 ng/L, respectively, in rivers, water courses, and Lake Balaton together, but not counting city canal water. EE2 was less abundant, but it was still present in almost all of the samples. In beach water samples from Lake Balaton, we measured 0.076-0.233 E2 and n.d.-0.133 EE2. A relative high amount of EE2 was found in river Zala (0.68 ng/L) and in Hévíz-Páhoki canal (0.52 ng/L), which are both in the catchment area of Lake Balaton (Hungary).


A simplified assay of hemoglobin AIc in diabetic patients by use of isoelectric focusing and quantitative microdensitometry.
Isoelectric focusing (IEF) of human erythrocyte hemolystaes on polyacrylamide slab gels over a pH gradient of 6 to 8 provides sufficient resolution of hemoglobin AIc (HbAIc) from other hemoglobin components (AIa, AIb, AII, S, and F) to allow quantification by high-resolution microdensitometry. Twice-chromatographed HbAIc alone and in admixtures with normal and diabetic hemolysates were employed to verify the identification and quantification of the AIc component. Relative concentration was determined as a per cent of the total hemoglobin absorption at 556 nm on acid-fixed, unstained gels. A total of 60 patient samples were examined by IEF, and, for 35 samples, both column chromatography and IEF determination were obtained, revealing excellent correlation between these two methods.


Three-Dimensional Analysis and Surgical Planning in Craniomaxillofacial Surgery.
Three-dimensional (3D) analysis and planning are powerful tools in craniofacial and reconstructive surgery. The elements include 1) analysis, 2) planning, 3) virtual surgery, 4) 3D printouts of guides or implants, and 5) verification of actual to planned results. The purpose of this article is to review different applications of 3D planning in craniomaxillofacial surgery. Case examples involving 3D analysis and planning were reviewed. Common threads pertaining to all types of reconstruction are highlighted and contrasted with unique aspects specific to new applications in craniomaxillofacial surgery. Six examples of 3D planning are described: 1) cranial reconstruction, 2) craniosynostosis, 3) midface advancement, 4) mandibular distraction, 5) mandibular reconstruction, and 6) orthognathic surgery. Planning in craniomaxillofacial surgery is useful and has applicability across different procedures and reconstructions. Three-dimensional planning and virtual surgery enhance efficiency, accuracy, creativity, and reproducibility in craniomaxillofacial surgery.


Complication of a closed Colles-fracture: necrotising fasciitis with lethal outcome. A case report.
We report a case of a 77-year-old female patient who died 4 days after a closed colles-fracture of the right wrist because of secondary emerged necrotising fasciitis. At the time of visiting our emergency department, the patient reports about untypical pain and progressive swelling of the entire right arm 3 days following a fall onto the outstretched hand where she sustained a closed distal radius fracture. Within 6 h, the patient developed hypotension and fever leading to cardiac and respiratory failure. The emergent-induced diagnostic presented a severe septic situation in the laboratory examination of the blood samples, an apparent before unknown diabetes mellitus and an unknown bronchial carcinoma with part of post-stenosis pneumonia of the right lung. After initial CPR and stabilisation, the patient underwent an urgent and aggressive surgical debridement with fasciotomies of the muscle compartments of the entire right upper extremity. The microbiological investigation of the intraoperative taken specimens presented plentiful group-A-beta-haemolytic streptococcus. Despite a broad spectrum intravenous antibiotic therapy, intensive care support and a second look operation 12 h later with exarticulation of the right arm in the shoulder joint, the patient died of septic shock and multiorgan failure 34 h after admission.


Unhappy landings. Health care feels the fallout from Washington's 1997 balanced budget.
Health care is already feeling the fallout from the 1997 balanced budget pact. And the accord's $100 billion in Medicare cuts, spread over five years, are only beginning to take effect. H&HN looks at two especially hard-hit sectors: home health agencies and rural hospitals.


Single-port transumbilical laparoscopic-assisted adnexal surgery.
To evaluate the efficiency and feasibility of single-port access transumbilical laparoscopic-assisted surgery in patients with large (>8cm) adnexal tumors and to present our initial experience. Twenty-two patients with presumably benign adnexal tumors who have undergone single-port access transumbilical laparoscopic-assisted surgery were enrolled. The procedure was performed using the method of exteriorization and extracorporeal surgery of adnexal tumors outside the abdominal cavity under laparoscopic guidance with preservation of as much ovarian tissue as possible. In each case, a homemade single-port device was inserted into the abdomen through a 2-cm umbilical incision. The clinical characteristics and operative outcomes of these patients were reviewed. Twenty of 22 cases were completed successfully. The one failed case required an additional trocar for adequate adhesiolysis, and the other case needed intraperitoneal drainage. The median operating time was 50 minutes (range, 35 to 120), and the estimated blood loss was 38mL (range, 10 to 300). Cyst rupture occurred in 2 cases, but there were no major postoperative complications. Single-port access transumbilical laparoscopic-assisted surgery for benign and relatively large adnexal tumors is feasible and could be an alternative to convention open laparotomy or laparoscopic surgery.


Oscillometric Blood Pressure in Indian School Children: Simplified Percentile Tables and Charts.
Data on blood pressure recorded by oscillometric method is limited. To develop simplified tables and charts of blood pressure recorded by oscillometric method in children. Cross-sectional. Ballabhgarh, Haryana. Healthy school-children. Blood pressure measured by oscillometric method. The study group included 7,761 children (58.4% males) with mean (SD) age of 10.5 (2.8) years. Age and gender were used to create simplified percentile tables and charts, as height was seen to explain very little variability of either systolic or diastolic blood pressure. Formulae for SBP and DBP thresholds for hypertension were derived as [110 + 1.6 x age] and [79 + 0.7 x age], respectively, with 1 mm Hg to be added for females. 95th percentile values suggest simple levels indicating hypertension to be 120/80, 125/85 and 135/90 at ages of 5, 10 and 15 years, respectively. Simplified reference tables and charts, formulae for SBP and DBP, and simple convenient thresholds may be useful for rapid screening of hypertension using oscillometric method.


A quantitative study of the sintering and mechanical properties of hydroxyapatite/phosphate glass composites.
Previous work has shown that small additions of a phosphate glass (CaO-P2O5) can significantly enhance the sinterability and strength of hydroxyapatite. However, there are no quantitative phase analyses available for these materials which would provide indicators of biocompatibility and resorbability. Similarly, there is little information available about the mechanical properties, especially with high glass additions. In this study, the effects of sintering hydroxyapatite with phosphate glass additions of 2.5, 5, 10, 25, and 50 wt.% are quantified. Each composition was sintered over a range of temperatures, and quantitative phase analysis was carried out using XRD. In addition, the microstructures were studied using RLOM and SEM, and mechanical properties (Vickers hardness, KIC, and MOR) measured. These results may be used to indicate which compositions and processing conditions may provide materials suitable for use in hard tissue replacement. Composites containing up to 10 wt.% glass additions formed dense HA/TCP composite materials possessing flexural strength and fracture toughness values up to 200% those of pure HA. The HA/TCP ratio was strongly dependent on the percentage glass addition. Higher glass additions resulted in composites containing beta-TCP together with large amounts of alpha- or beta-calcium pyrophosphate, and having similar mechanical strengths to pure HA.


Fetal growth restriction: associated genetic etiology and pregnancy outcomes in a tertiary referral center.
The etiology of fetal growth restriction (FGR) is complex and currently, there is a paucity of research about the genetic etiology of fetal growth restriction. We investigated the genetic associations and pregnancy outcomes in cases of fetal growth restriction. A retrospective analysis of 210 pregnant women with fetal growth restriction was performed using karyotype analysis and single nucleotide polymorphism arrays (SNP-array). The differences in pathogenic copy number variation (CNV) detected by the two methods were compared. At the same time, the fetuses were divided into three groups: isolated FGR (n = 117), FGR with ultrasonographic soft markers (n = 48), and FGR with ultrasonographic structural anomalies (n = 45). Further, the differences in pathogenic copy number variations were compared among the groups. The total detection rate of pathogenic CNVs was 12.4% (26/210). Pathogenic copy number variation was detected in 14 cases (6.7%, 14/210) by karyotype analysis. Furthermore, 25 cases (11.9%, 25/210) with pathogenic CNVs were detected using the SNP-array evaluation method. The difference in the pathogenic CNV detection rate between the two methods was statistically significant. The result of the karyotype analysis and SNP-array evaluation was inconsistent for 13 cases with pathogenic CNV. The rate of detecting pathogenic CNVs in fetuses with isolated FGR, FGR combined with ultrasonographic soft markers, and FGR combined with ultrasonographic structural malformations was 6.0, 10.4, and 31.1%, respectively, with significant differences among the groups. During the follow-up, 35 pregnancies were terminated, two abortions occurred, and 13 cases were lost to follow-up. Of the 160 deliveries, nine fetuses had adverse pregnancy outcomes, and the remaining 151 had normal postnatal growth and developmental assessments. Early diagnosis and timely genomic testing for fetal growth restriction can aid in its perinatal prognosis and subsequent intervention.


Thought suppression, impaired regulation of urges, and Addiction-Stroop predict affect-modulated cue-reactivity among alcohol dependent adults.
Abstinent alcohol dependent individuals commonly employ thought suppression to cope with stress and intrusive cognitions about alcohol. This strategy may inadvertently bias attention towards alcohol-related stimuli while depleting neurocognitive resources needed to regulate urges, manifested as decreased heart rate variability (HRV) responsivity to alcohol cues. The present study tested the hypothesis that trait and state thought suppression, impaired regulation of urges, and alcohol attentional bias as measured by the Addiction-Stroop would have significant effects on the HRV responsivity of 58 adults in residential treatment for alcohol dependence (mean age=39.6 ± 9.4, 81% female) who participated in an affect-modulated cue-reactivity protocol. Regression analyses controlling for age, level of pre-treatment alcohol consumption, and baseline HRV indicated that higher levels of trait thought suppression, impaired regulation of alcohol urges, and attentional fixation on alcohol cues were associated with lower HRV responsivity during stress-primed alcohol cue-exposure. Moreover, there was a significant state × trait suppression interaction on HRV cue-responsivity, such that alcohol dependent persons reporting high levels of state and trait suppression exhibited less HRV during cue-exposure than persons reporting low levels of state and trait suppression. Results suggest that chronic thought suppression taxes regulatory resources reflected in reduced HRV responsivity, an effect that is particularly evident when high trait suppressors engage in intensive suppression of drinking-related thoughts under conditions of stress. Treatment approaches that offer effective alternatives to the maladaptive strategy of suppressing alcohol urges may be crucial for relapse prevention.


Surgery as an intervention for obesity. Results from the Swedish obese subjects study.
The prevalence of obesity is increasing dramatically all over the world, leading to suffering as well as high health care costs due to obesity-related co-morbidity. Long-term results from weight loss studies are hard to attain due to the difficulties in sustaining weight losses. Gastric surgery results in large and maintainable weight reductions. The Swedish obese subjects (SOS) study offers a unique possibility for investigating the effects of weight loss as compared with weight stability in obese subjects over a long period of time.


Reduced levels of sialic acid in the plasma membrane during hepatocellular proliferation.
When rats were infused with a solution containing triiodothyronine, amino acids, glucagon and heparin (solution A) the hepatocytes increased DNA synthesis and decreased plasma membrane sialic acid. In order to study whether the reduced levels of sialic acid in the plasma membrane were associated with hepatocyte proliferation, different mixtures of three components of solution A were infused into rats and the DNA synthetic activity as well as the sialic acid content measured. Results reported here show a correlation between DNA synthetic activity and sialic acid reduction suggesting that the decrease in the plasma membrane sialic acid can be a pre-replicative step associated to cell proliferation.


COVID-19 vaccination coverage and its cognitive determinants among older adults in Shanghai, China, during the COVID-19 epidemic.
This study aimed to examine the coverage of coronavirus disease 2019 (COVID-19) vaccination and its cognitive determinants among older adults. A cross-sectional study was conducted using a questionnaire to conduct a survey among 725 Chinese older adults aged 60 years and above in June 2022, 2 months after the mass COVID-19 outbreak in Shanghai, China. The questionnaire covered demographic characteristics, COVID-19 vaccination status, internal risk perception, knowledge, and attitude toward the efficacy and safety of COVID-19 vaccines. The vaccination rate was 78.3% among the surveyed individuals. Self-reported reasons for unwillingness to get vaccinated (multiple selections) were "concerns about acute exacerbation of chronic diseases after vaccination (57.3%)" and "concerns regarding vaccine side effects (41.4%)." Compared to the unvaccinated group, the vaccinated group tended to have a higher score in internal risk perception (t = 2.64, P < 0.05), better knowledge of COVID-19 vaccines (t = 5.84, P < 0.05), and a more positive attitude toward the efficacy and safety of COVID-19 vaccines (t = 7.92, P < 0.05). The path analysis showed that the cognitive effect on vaccination behavior is relatively large, followed by the internal risk perception, and then the attitude toward COVID-19 vaccines. The more knowledgeable the participants were about COVID-19 vaccines, the more likely they were to receive the COVID-19 vaccines. In the multivariate logistic regression, the increased coverage of COVID-19 vaccination was associated with reduced age (OR = 0.53 95% CI 0.43-0.66, P < 0.001), being a resident in other places than Shanghai (OR = 0.40, 95% CI 0.17-0.92, P < 0.05), a shorter time of lockdown (OR = 0.33, 95% CI 0.13-0.83, P < 0.05), a history of other vaccines (OR = 2.58, 95% CI 1.45-4.60, P < 0.01), a fewer number of chronic diseases (OR = 0.49, 95% CI 0.38-0.62, P < 0.001), better knowledge about COVID-19 vaccines (OR = 1.60, 95% CI 1.17-2.19, P < 0.01), and a positive attitude toward COVID-19 vaccines (OR = 9.22, 95% CI 4.69-18.09, P < 0.001). Acquiring accurate knowledge and developing a positive attitude toward COVID-19 vaccines are important factors associated with COVID-19 vaccination. Disseminating informed information on COVID-19 vaccines and ensuring efficacious communication regarding their efficacy and safety would enhance awareness about COVID-19 vaccination among older adults and consequently boost their vaccination coverage.


Using chemometric models to predict the biosorption of low levels of dysprosium by Euglena gracilis.
The critical rare earth element dysprosium (Dy) is integral for sustainable technologies. What is concerning is that Dy is in imminent short supply and no current replacements yet exist, coupled with increasing environmental Dy levels influenced by anthropogenic activities. This study applies chemometric methods such as response surface methodology and artificial neural networks to predict low Dy removal levels using the biosorbent Euglena gracilis. A three-factor Box-Behnken experimental design was conducted with initial concentration (1 to 100 µg L-1), contact time (30 to 180 min), and pH (3 to 8) as the three independent variables, and percentage removal and sorption capacity (q) as dependent variables. Using Dy percentage removal as response, for the worst and best conditions ranged from 0 to 92% respectively, with an average removal of 66 ± 4%. Using sorption capacity (q) as a different response variable, q varied from 0 to 93 µg/g with 27 ± 4 µg/g capacity as average. Maximum removal was 92% (q = 93 µg/g) was at pH 3, a contact time of 105 min and at a concentration of 100 µg/L. Using sorption capacity as the response variable for ANOVA, pH and metal concentrations were statistically significant factors, with lower pH and higher metal concentration having improved Dy removal, with a desirability near 1. Statistical tests such as analysis of variance, lack-of-fit, and coefficient of determination (R2) confirmed model validity. A 3-10-1 ANN network array was used to model experimental responses (q). RSM and ANN effectively modeled Dy biosorption. E. gracilis proved to be a cheap and effective biosorbent for Dy biosorption and has the potential to remediate acid mine drainage areas exhibiting low Dy concentrations.


Reconstruction of mandibular defects with metallic prostheses and microvascular jejunal autografts: an experimental study.
A study was undertaken to determine the adequacy of vascularised jejunum to provide stable mucosal cover over a non-biological mandibular substitute. Employing a canine model, composite intra-oral bone-mucosal defects were created and reconstructed with a metal plate covered by a microvascular jejunal patch. These were followed for six months and were assessed clinically, histologically and radiologically. Rapid mucosal healing occurred in all cases. The autografts conformed to the contour of the prosthesis and adequate tongue mobility was preserved. All mandibles remained stable throughout the follow-up period. Histologically, short villi covered the jejunal grafts to three months whilst at six months both normal and abnormal jejunal mucosal morphology was evident.


Molecular authentication of Cissampelos pareira L. var. hirsuta (Buch.-Ham. ex DC.) Forman, the genuine source plant of ayurvedic raw drug 'Patha', and its other source plants by ISSR markers.
Cissampelos pareira L. var. hirsuta (Buch.-Ham. ex DC.) Forman belongs to family Menispermaceae. The roots of this taxon are used in the treatment of various diseases like stomach pain, fever, skin disease, etc., in Ayurveda and is commonly known as Patha. Two other species, viz., Cyclea peltata (Lam.) Hook.f. & Thomson and Stephania japonica (Thunb.) Miers of the same family are being used as the source of this drug in various parts of India. This type of substitution or adulteration will ultimately affect the therapeutic efficacy of the medicines adversely. ISSR profiles of all the three taxa are generated and analyzed to assess the genetic relationships among these three species. The profiles of all the three species displayed a high level of polymorphism among them. ISSR markers developed can be used in authenticating and validating the exact species discrimination of the genuine raw drug of 'Patha' from its substitutes/adulterants to guarantee the quality and legitimacy of this drug in the market.


Economic Burden of Illness among Persons with Hemophilia B from HUGS Vb: Examining the Association of Severity and Treatment Regimens with Costs and Annual Bleed Rates.
To determine US societal burden of illness, including direct and indirect costs and annual bleed rate (ABR), for persons with hemophilia B (HB), a rare and debilitating genetic disorder, and to examine associations of hemophilia severity and treatment regimens with costs and ABR. From 2009 to 2014, the Hemophilia Utilization Group Studies Part Vb collected prospective data from 10 US hemophilia treatment centers. Participants with HB completed initial surveys on sociodemographic characteristics, clinical characteristics, and treatment patterns. During the 2-year follow-up, participants reported bleeding episodes, work absenteeism, and caregiver time quarterly. These data were used to calculate ABR and indirect costs. Direct costs were calculated using 1-year clinical chart records and 2-year dispensing records. Of the 148 participants, 112 with complete medical records and one or more follow-up survey were included. Total mean annual per-person costs were $85,852 (median $20,160) for mild/moderate HB, $198,733 (median $147,891) for severe HB, and $140,240 (median $63,617) for all participants without inhibitors (P < 0.0001). Mean ABR for participants with severe HB on prophylaxis (5.5 ± 7.9 bleeds/y) was almost half that of those treated episodically. Clotting factor and indirect costs accounted for 85% and 9% of total costs, respectively. Compared with episodic treatment, prophylaxis use was associated with 2.5-fold higher clotting factor costs (P < 0.01), low but significantly more missed parental workdays (P < 0.0001) and clinician (P < 0.001) or nursing visits (P < 0.0001), less part-time employment and unemployment, and lower hospitalizations costs (P = 0.17) and ABR (P < 0.0001). HB is associated with high economic burden, primarily because of clotting factor costs. Nevertheless, prophylaxis treatment leads to clinical benefits and may reduce other nonfactor costs.


Improved freedom from PSA failure with whole pelvic irradiation for high-risk prostate cancer.
To determine the impact of whole pelvic irradiation on the risk of PSA failure in prostate cancer patients, at high predicted risk for lymph node involvement, receiving definitive radiotherapy. Between October 1987 and December 1995, 506 patients with clinically localized prostate cancer were treated with definitive radiotherapy at UCSF and affiliated institutions. Treatment consisted of 4-field whole pelvic irradiation followed by a prostate-only boost, or prostate-only treatment (median follow-up was 35 months and 30 months, respectively). PSA failure was defined as: 1. a PSA value > or = 1 ng/ml; or 2. a PSA value that rose > or = 0.5 ng/ml in < or = 1 year posttreatment on two consecutive measurements, with the first rise defined as the time of failure. The calculated risk of lymph node positivity (%rLN+) was defined as 2/3(iPSA) + 10(GS-6), and high risk was defined as %rLN+ > or = 15%. Univariate and multivariate analyses were performed. A total of 201 high-risk patients were identified. High-risk patients who received whole pelvic irradiation had significantly improved freedom from PSA failure compared to those who received prostate-only treatment (median PFS = 34.3 months vs. 21.0 months; p = 0.0001). Potential confounding variables, including initial PSA, Gleason score, T stage, radiation dose, year of treatment, use of three-dimensional (3D) conformal techniques, and use of hormone therapy, did not account for the observed difference in time to PSA failure. Multivariate analysis revealed type of radiation treatment to be the most significant independent predictor of outcome. Whole pelvic radiotherapy significantly improves the PSA failure-free survival in patients with a high calculated risk of lymph node positivity.


Biodegradable Lubricant with High-Temperature and Ionic-Contamination Resistance: Deep Eutectic Solvent ChCl-PEG.
Drilling fluid lubricants guarantee safe and fast drilling. When drilling high-temperature or NaCl/CaCl2-containing formations, there is an urgent need to develop environmentally friendly lubricants that are resistant to high temperature and ionic contamination. In this study, a deep eutectic solvent (DES) ChCl-PEG lubricant for a water-based drilling fluid was designed and prepared. ChCl-PEG is a kind of biodegradable material with high thermal stability formed by hydrogen bonding between choline chloride (ChCl) and polyethylene glycol (PEG). Within 240 °C, ChCl-PEG significantly improved the lubricating properties of drilling fluids and mud cakes. The lubrication coefficient (K) was controlled within 0.2, and the reduction rate of the adhesion coefficient (Δf) was higher than 40%. The salt and calcium resistances of ChCl-PEG at high temperature (150 °C) are as high as 36% NaCl and 20% CaCl2. Under these conditions, ChCl-PEG maintains a low value of K: 0.097-0.157 (5-36% NaCl) and 0.145-0.162 (5-20% CaCl2), respectively. Also, it maintains higher values of Δf, which can reach up to 51.6% and 80%. The lubricating mechanism of ChCl-PEG can be summarized as the adsorption of ChCl and the formation of a large number of hydrated molecules.


Characterization of crystalline linear (1→3)-α-d-glucan synthesized in vitro.
We investigated the crystal structure and molecular arrangement of the linear (1→3)-α-d-glucan synthesized by glucosyltransferase GtfJ cloned from Streptococcus salivarius using sucrose as a substrate. The synthetic products had two morphologies: wavy fibril-like crystals as major and thin lamellae as minor products. Their structures were analyzed using electron microdiffraction, synchrotron X-ray powder diffraction, and solid-state 13C NMR spectroscopy. The fibrils and lamellae had the same allomorphic form but different molecular arrangements. The wet crystals were in a hydrated form, which converted into an anhydrous form with a significant decrease in crystallinity on drying. The hydrated and anhydrous forms had an extended-chain conformation with 2/1 helix, and the hydrated form was estimated to contain one water molecule per glucose residue. The long glucan chains were folded in the fibril crystals, while the short, extended chains were arranged perpendicular to the base plane of the lamellae.


Solvent Perturbation of Protein Structures - A Review Study with Lectins.
Use of organic molecules as co-solvent with water, the ubiquitous biological solvent, to perturb the structure of proteins is popular in the research area of protein structure and folding. These organic co-solvents are believed to somehow mimic the environment near the cell membrane. Apart from that they induce non-native states which can be present in the protein folding pathway or those states also may be representative of the off pathway structures leading to amyloid formation, responsible for various fatal diseases. In this review, we shall focus on organic co-solvent induced structure perturbation of various members of lectin family. Lectins are excellent model systems for protein folding study because of its wide occurrence, diverse structure and versatile biological functions. Lectins were mainly perturbed by two fluoroalcohols - 2,2,2- trifluoroethanol and 1,1,1,3,3,3-hexafluoroisopropanol whereas glycerol, ethylene glycol and polyethylene glycols were used in some cases. Overall, all native lectins were denatured by alcohols and most of the denatured lectins have predominant helical secondary structure. But characterization of the helical states and the transition pathway for various lectins revealed diverse result.


Protein intake distribution pattern does not affect anabolic response, lean body mass, muscle strength or function over 8 weeks in older adults: A randomized-controlled trial.
In our recent acute metabolic study, we found no differences in the anabolic response to differing patterns of dietary protein intake. To confirm this in a chronic study, we investigated the effects of protein distribution pattern on functional outcomes and protein kinetics in older adults over 8 weeks. To determine chronic effects of protein intake pattern at 1.1 g protein/kg/day in mixed meals on lean body mass (LBM), functional outcomes, whole body protein kinetics and muscle protein fractional synthesis rate (MPS) over 8-week respective dietary intervention, fourteen older subjects were randomly divided into either EVEN or UNVEN group. The UNEVEN group (n = 7) consumed the majority of dietary protein with dinner (UNEVEN, 15/20/65%; breakfast, lunch, dinner), while the EVEN group (n = 7) consumed dietary protein evenly throughout the day (EVEN: 33/33/33%). We found no significant differences in LBM, muscle strength, and other functional outcomes between EVEN and UNEVEN before and after 8-week intervention. Consistent with these functional outcomes, we did not find significant differences in the 20-h integrated whole body protein kinetics [net protein balance (NB), protein synthesis (PS), and breakdown (PB)] above basal states and MPS between EVEN and UNEVEN intake patterns. We conclude that over an 8-week intervention period, the protein intake distribution pattern in mixed meals does not play an important role in determining anabolic response, muscle strength, or functional outcomes. This trial is registered at https://ClinicalTrials.gov as NCT02787889.


Discovering Dynamic Plant Enzyme Complexes in Yeast for Kratom Alkaloid Pathway Identification.
Discovering natural product biosynthetic pathways of medicinal plants is challenging and laborious. Capturing the coregulation patterns of pathway enzymes, particularly transcriptomic regulation, has proven an effective method to accelerate pathway identification. In this study, we developed a yeast-based screening method to capture the protein-protein interactions (PPI) between plant enzymes, which is another useful pattern to complement the prevalent approach. Combining this method with plant multiomics analysis, we discovered four enzyme complexes and their organized pathways from kratom, an alkaloid-producing plant. The four pathway branches involved six enzymes, including a strictosidine synthase, a strictosidine β-D-glucosidase (MsSGD), and four medium-chain dehydrogenase/reductases (MsMDRs). PPI screening selected six MsMDRs interacting with MsSGD from 20 candidates predicted by multiomics analysis. Four of the six MsMDRs were then characterized as functional, indicating the high selectivity of the PPI screening method. This study highlights the opportunity of leveraging post-translational regulation features to discover novel plant natural product biosynthetic pathways.


Cognitive trajectories preluding the imminent onset of Alzheimer's disease dementia in individuals with normal cognition: results from the HELIAD cohort.
The cognitive trajectories of cognitively normal (CN) individuals rapidly progressing to Alzheimer's disease dementia (AD) have not been investigated. To explore the preclinical pattern of cognitive performance heralding the rapid progression from normal cognition to AD. The HELIAD cohort underwent comprehensive neuropsychological assessments (memory, language, attention, executive and visuo-perceptual functions) at baseline and after approximately 3-year intervals. The cognitive trajectories of those with normal cognition at baseline were explored according to the follow-up diagnosis using adjusted generalised estimating equations analyses. A total of 932 predominantly female (61%), older (72.9 ± 4.9), CN participants were followed for 3.09 (± 0.83) years. Among them, 761 individuals remained CN, 29 progressed to AD and 142 developed MCI (33 single-domain amnestic, 41 multidomain amnestic, 37 single-domain non-amnestic and 31 multidomain non-amnestic). Those progressing to AD were already performing worse than the healthy reference in every single cognitive domain at baseline. Cognitive deficits ranged between ~ 0.5SD (attention, executive function and language) and ~ 1.0SD (memory and visuo-perceptual skills). Throughout the 3-year follow-up, memory constantly exhibited the most prominent impairment compared to the remaining cognitive domains while executive function diminished in the most abrupt fashion (~ 0.19SD yearly) separating from the remaining three cognitive functions before the development of full-blown AD. Heterogeneous patterns of cognitive decline clearly differentiated those progressing to MCI from those rapidly converting to AD, as well. Poor performance in every cognitive domain may characterise cognitively normal individuals at high risk of fast progression to AD. Strict neuropsychological cut-offs fail to detect a considerable number of individuals at high risk of rapid progression to AD.


Impact of the Tumor Microenvironment for Esophageal Tumor Development-An Opportunity for Prevention?
Despite therapeutical advancements, and in contrast to other malignancies, esophageal adenocarcinoma (EAC) prognosis remains dismal while the incidence has markedly increased worldwide over the past decades. EAC is a malignancy of the distal esophageal squamous epithelium at the squamocolumnar junction with gastric cells expanding into the esophagus. Most EAC patients have a history of Barret's esophagus (BE), a metaplastic adaption to chronic reflux, initially causing an inflammatory microenvironment. Thus, the immune system is highly involved early on in disease development and progression. Normally, anti-tumor immunity could prevent carcinogenesis but in rare cases BE still progresses over a dysplastic intermediate state to EAC. The inflammatory milieu during the initial esophagitis phase changes to a tolerogenic immune environment in BE, and back to pro-inflammatory conditions in dysplasia and finally to an immune-suppressive tumor microenvironment in EAC. Consequently, there is a huge interest in understanding the underpinnings that lead to the inflammation driven stepwise progression of the disease. Since knowledge about the constellations of the various involved cells and signaling molecules is currently fragmentary, a comprehensive description of these changes is needed, allowing better preventative measures, diagnosis, and novel therapeutic targets.


Design, synthesis, and biological evaluation of a small molecule oral agonist of the glucagon-like-peptide-1 receptor.
An absolute or relative deficiency of pancreatic β-cells mass and functionality is a crucial pathological feature common to type 1 diabetes mellitus and type 2 diabetes mellitus. Glucagon-like-peptide-1 receptor (GLP1R) agonists have been the focus of considerable research attention for their ability to protect β-cell mass and augment insulin secretion with no risk of hypoglycemia. Presently commercially available GLP1R agonists are peptides that limit their use due to cost, stability, and mode of administration. To address this drawback, strategically designed distinct sets of small molecules were docked on GLP1R ectodomain and compared with previously known small molecule GLP1R agonists. One of the small molecule PK2 (6-((1-(4-nitrobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-6H-indolo[2,3-b]quinoxaline) displays stable binding with GLP1R ectodomain and induces GLP1R internalization and increasing cAMP levels. PK2 also increases insulin secretion in the INS-1 cells. The oral administration of PK2 protects against diabetes induced by multiple low-dose streptozotocin administration by lowering high blood glucose levels. Similar to GLP1R peptidic agonists, treatment of PK2 induces β-cell replication and attenuate β-cell apoptosis in STZ-treated mice. Mechanistically, this protection was associated with decreased thioredoxin-interacting protein expression, a potent inducer of diabetic β-cell apoptosis and dysfunction. Together, this report describes a small molecule, PK2, as an orally active nonpeptidic GLP1R agonist that has efficacy to preserve or restore functional β-cell mass.


Heart sarcolemmal Ca2+ transport in endotoxin shock: II. Mechanism of impairment in ATP-dependent Ca2+ transport.
The role of the phosphorylation and dephosphorylation of sarcolemma and that of the alteration of membrane lipids in the endotoxin-induced impairment of the ATP-dependent Ca2+ transport in canine cardiac sarcolemma were investigated. The results indicate that the ATP-dependent Ca2+ transport in canine cardiac sarcolemma was decreased by 30-35% 4 h after endotoxin administration. Phosphorylation of sarcolemma by the catalytic subunit of the cAMP-dependent protein kinase or calmodulin stimulated ATP-dependent Ca2+ transport in both groups, however, the phosphorylation-stimulated activities remained significantly lower in endotoxic animals. Dephosphorylation of sarcolemma decreased ATP-dependent Ca2+ transport in both groups, yet, the time required to reach maximal dephosphorylation was reduced from 120 to 90 min 4 h post-endotoxin. Analysis of sarcolemmal membranes reveals that phosphatidylcholine and phosphatidylethanolamine contents were decreased while their respective lysophosphatide levels were increased significantly after endotoxin injection. Digestion of control heart sarcolemma with phospholipase A2 inhibited Ca2+ transport and the inhibition was reversible by phosphatidylcholine. The inhibition caused by the in vivo administration of endotoxin was completely reversible by the addition of phosphatidylcholine. Based on these data, it is concluded that endotoxin administration impairs ATP-dependent Ca2+ transport in canine cardiac sarcolemma and that the impairment may be due to i) a defective phosphorylation of sarcolemma; ii) a reduced number of Ca2+ pumps; iii) an accelerated dephosphorylation of sarcolemma; and iv) an alteration in membrane phospholipid profile in response to phospholipase A activation.


Constructing an artificial boundary to regulate solid electrolyte interface formation and synergistically enhance stability of nano-Si anodes.
Low coulombic efficiency and poor cyclic stability are two common problems for silicon anodes. Therefore, it is of great significance to improve cycling performance and initial coulombic efficiency (ICE) via rational surface engineering on nano-Si anodes. Herein, a new nano-silicon anode is obtained by straightforward constructing a multifunctional polypyrrole protective layer on the surface of silicon nanoparticles, which is further used as the inner boundary of solid electrolyte interface (SEI) film. Specifically, the Li salt decomposition reaction between the electrolyte and silicon surface is effectively inhibited under the protection of the compact artificial boundary. The transfer of Li+ for forming the SEI film is selectively slower than that of lithiation/delithiation reaction. This further reduces the amount of SEI film, leading to a high ICE of 93.2% at 0.5 A g-1 for modified nano-Si anodes. In addition, the flexible SEI precursor combined with the high proportion of organic components in SEIs not only accommodates the volume change of nano-silicon, but also suppresses accumulation of "waste SEI", so the electrode can maintain a reversible capacity of 1153.2 mAh g-1 at 1 A g-1 after 500 cycles. This work provides important guidance for surface structural optimization of alloy-type anodes with high volume change.


A uterocervical anomaly (Uterus bicorpor bicollis) in a mare, and the manual disruption of early bilateral pregnancies.
A developmental anomaly, resulting from partial segmental aplasia of the Mullerian ducts, was present in a Clydesdale mare. She had complete double cervices and a divided uterine body. In this mare, bilateral pregnancies were destroyed in sequence by squeezing them per rectum 25 and 29 days after insemination.


Use of Microfluidic Capillary Electrophoresis for the Determination of Multi-Component Protein Adsorption Isotherms: Application to High-Throughput Analysis for Hydrophobic Interaction Chromatography.
Chromatography is a widely used separation process for purification of biopharmaceuticals that is able to obtain high purities and concentrations. The phenomena that occur during separation, mass transfer and adsorption are quite complex. To better understand these phenomena and their mechanisms, multi-component adsorption isotherms must be investigated. High-throughput methodologies are a very powerful tool to determine adsorption isotherms and they waste very small amounts of sample and chemicals, but the quantification of component concentrations is a real bottleneck in multi-component isotherm determination. The behavior of bovine serum albumin, Corynebacterium diphtheriae CRM197 protein and lysozyme, selected as model proteins in binary mixtures with hydrophobic resin, is investigated here. In this work we propose a new method for determining multi-component adsorption isotherms using high-throughput experiments with filter plates, by exploiting microfluidic capillary electrophoresis. The precision and accuracy of the microfluidic capillary electrophoresis platform were evaluated in order to assess the procedure; they were both found to be high and the procedure is thus reliable in determining adsorption isotherms for binary mixtures. Multi-component adsorption isotherms were determined with a totally high-throughput procedure that turned out to be a very fast and powerful tool. The same procedure can be applied to every kind of high-throughput screening.


Education and training evolution in urolithiasis: A perspective from European School of Urology.
With the worldwide increase in urolithiasis prevalence, the present study aimed to delineate and summarise recent evolutions in training for the management of urolithiasis. A PubMed search using the key words "simulation", "training", "ureteroscopy", "RIRS", "URS", "percutaneous nephrolithotomy", "PCNL", "virtual reality", "augmented reality", "artificial intelligence", "healthcare", "curriculum", and "assessment" was used to examine how education and training in urolithiasis have adapted over recent years. Focus was placed on the role of high- and low-fidelity simulation models, virtual reality and artificial intelligence, and standardised assessment and curriculum. This review supports the necessity to incorporate technology, simulation, and other skill enhancement training modalities into surgical training. However, these cannot solely replace mentored training with an experienced professional supervisor. Whilst technological and simulation advancements are likely to prove increasingly important in urolithiasis training, it is just as important for stratification of robust curricula with validated assessment. We also propose a pathway for future training. Endourology subspeciality training programmes have successfully incorporated simulation model-based training for skill acquisition, refinement, and improving operative outcomes. Success is achieved by maintaining a delicate balance between machine and in person mentor-based training. A trainee-centred model that follows the proposed curriculum could aid this balance for the future generation of trainees.


Phage Langmuir monolayers and Langmuir-Blodgett films.
Stable, insoluble Langmuir monolayer films composed of Staphylococcus aureus-specific lytic bacteriophage were formed at an air-water interface and characterized. The phage monolayer was very strong, withstanding a surface pressure of ∼40 mN/m at 20 °C. The surface pressure-area (Π-A) isotherm possessed a shoulder at ∼7 × 10(4)nm(2)/phage particle, attributed to a change in phage orientation at the air-water interface from horizontal to vertical capsid-down/tail-up orientation as surface pressure was increased. The Π-A-dependence was accurately described using the Volmer equation of state, assuming horizontal orientation to an air-water interface at low surface pressures with an excluded area per phage particle of 4.6 × 10(4)nm(2). At high pressures phage particles followed the space-filling densely packed disks model with a specific area of 8.5 × 10(3)nm(2)/phage particle. Lytic phage monolayers were transferred onto gold-coated silica substrates from the air-water interface at a constant surface pressure of 18 mN/m by Langmuir-Blodgett method, then dried and analyzed by scanning electron microscopy (SEM) and ellipsometry. Phage specific adsorption (Γ) in Langmuir-Blodgett (LB) films measured by SEM was consistent with that calculated independently from Π-A isotherms at the transfer surface pressure of 18 mN/m (Γ=23 phage particles/μm(2)). The 50 nm-thickness of phage monolayer measured by ellipsometer agreed well with the horizontal phage average size estimated by SEM. Surface properties of phage Langmuir monolayer compare well with other monolayers formed from nano- and micro-particles at the air-water interface and similar to that of classic amphiphiles 1,2-diphytanoyl-sn-glycero-3-phosphocholine (phospholipid) and stearic acid.


When Shall I Ask for a Second Opinion in Specialized Centers and How Can I Find Them? Do I Need a Medical Therapy in My Disease Course?
Penile cancer is an uncommon malignancy in the United States and most developed countries, with higher incidence in the developing nations of Africa, Asia, and South America. Standard treatment involves a urologist, medical oncologist, and radiation oncologist to deliver multimodal treatment in an integrated fashion. This article will discuss the patterns of specialty referral that are important for men affected by penile cancer. An electronic literature search using PubMed was conducted. Clinical experience also informed the article. Nurses and other health care providers caring for patients with penile cancer do not always have prior experience with this rare disease. Referral to a high-volume specialty center for multidisciplinary management is often appropriate. Additionally, evidence suggests that men affected by penile cancer experience a range of unmet supportive care needs involving their physical, psychological, and sexual well-being. Timely and appropriate specialty referrals are a means for helping patients maintain an acceptable quality of life. It is important that oncology nurses understand and anticipate the need for referrals to specialized centers for definitive treatment of locoregional penile cancer. Nurses are also positioned to facilitate specialty referrals and deliver complex supportive care interventions.


Teeth loss, teeth brushing and esophageal carcinoma: a systematic review and meta-analysis.
Esophageal carcinoma (EC) is a serious malignancy, and its epidemiologic etiology is not fully explained. We performed this review to investigate the association between teeth loss and teeth brushing and the risk of EC. A systematic search was conducted to identify all relevant studies. The Q test and I(2) statistic were used to examine between-study heterogeneity. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were considered by fixed or random effects models. Furthermore, we conducted subgroup analyses based on study design, the studies' geographic regions and case type of origin. Modified Egger linear regression test was used to estimate publication bias. Ten articles were included. Pooled analyses indicated that teeth loss was associated with an increased risk of EC for Asians (OR, 1.52; 95% CI: 1.30, 1.78), and high frequency of teeth brushing was associated with a lower incidence of EC (OR, 0.62; 95%CI: 0.43, 0.89). Subgroup analyses showed consistent results and no publication bias existed. Teeth loss and teeth brushing play potential roles in the progressing of EC. People should take care of their oral health in daily life. And large well-designed researches are needed to fully describe the association between teeth health and EC risk.


Spatio-temporal variations of black carbon concentrations in the Megacity Beijing.
The spatial and temporal distribution and the flux of black carbon (BC) concentration in Beijing were continuously investigated over a two-year period at five sites to highlight the relative influence of contributing sources. The results demonstrate firstly that there is significant spatio-temporal variability of BC in Beijing. Highest concentrations occurred during winter primarily due to stagnant meteorological conditions, and seasonal BC sources, such as coal combustion for heating purposes. Biomass burning was identified as a minor seasonal source during the summer months. BC also varied spatially with higher concentrations in the SE of Beijing and lower concentrations in the NW, due to the differing emission intensity of various local BC sources such as traffic and industry. Frequently, overnight BC concentrations were higher due to specific meteorological conditions, such as the lower urban mixing layer height and various anthropogenic activities, such as exclusive night-time heavy duty vehicle traffic in the inner-city.


Cholangiocarcinoma: A diagnostic dilemma on cytology.
Cholangiocarcinoma is a relatively rare form of adenocarcinoma which may resemble adenocarcinoma of pancreatobiliary origin or adenocarcinomas from many other sites in the body. As a result, its diagnosis relies mainly on clinical history and morphology. A 64-year-old male with cirrhosis and worsening liver failure underwent fine needle aspiration of a radiologically detected liver mass. Cytological material showed a monomorphic population of cells arranged singly and in clusters, reminiscent of a neuroendocrine tumour (NET). Cell block morphology added to the diagnostic dilemma by showing a delicate vasculature among the tumour cells. Immunohistochemistry on the cell block revealed that cells were positive for CK7 and CK19 and negative for synaptophysin and chromogranin, thereby pointing towards a pancreatobiliary origin for the tumour and excluding an NET. In the case of liver aspirates, even when encountering confusing morphological entities, it is imperative to keep in mind the possibility of a rare neoplasm such as cholangiocarcinoma. In the absence of core needle biopsy, cell block sections prepared from aspirated material can provide appreciable immunohistochemistry results to resolve the diagnostic dilemma.


Ultimobranchial body and parathyroid glands of the freshwater snake Natrix piscator in response to vitamin D3 administration.
Vitamin D3 (20 I.U./100 g body wt) was administered to the freshwater snake Natrix piscator for 15 days. Elevation of serum calcium and inorganic phosphate levels was observed after the treatment. The ultimobranchial body became active whereas the parathyroid glands exhibited reduced activity.


Multidrug resistance-associated protein 1 (MRP1) mediated vincristine resistance: effects of N-acetylcysteine and Buthionine sulfoximine.
Multidrug resistance mediated by the multidrug resistance-associated protein 1 (MRP1) decreases cellular drug accumulation. The exact mechanism of MRP1 involved multidrug resistance has not been clarified yet, though glutathione (GSH) is likely to have a role for the resistance to occur. N-acetylcysteine (NAC) is a pro-glutathione drug. DL-Buthionine (S,R)-sulfoximine (BSO) is an inhibitor of GSH synthesis. The aim of our study was to investigate the effect of NAC and BSO on MRP1-mediated vincristine resistance in Human Embryonic Kidney (HEK293) and its MRP1 transfected 293MRP cells. Human Embryonic Kidney (HEK293) cells were transfected with a plasmid encoding whole MRP1 gene. Both cells were incubated with vincristine in the presence or absence of NAC and/or BSO. The viability of both cells was determined under different incubation conditions. GSH, Glutathione S-Transferase (GST) and glutathione peroxidase (GPx) levels were measured in the cell extracts obtained from both cells incubated with different drugs. N-acetylcysteine increased the resistance of both cells against vincristine and BSO decreased NAC-enhanced MRP1-mediated vincristine resistance, indicating that induction of MRP1-mediated vincristine resistance depends on GSH. Vincristine decreased cellular GSH concentration and increased GPx activity. Glutathione S-Transferase activity was decreased by NAC. Our results demonstrate that NAC and BSO have opposite effects in MRP1 mediated vincristine resistance and BSO seems a promising chemotherapy improving agent in MRP1 overexpressing tumor cells.


Proposing a care practice bundle for neonatal encephalopathy during therapeutic hypothermia.
Neonates with neonatal encephalopathy (NE) often present with multi-organ dysfunction that requires multidisciplinary specialized management. Care of the neonate with NE is thus complex with interaction between the brain and various organ systems. Illness severity during the first days of birth, and not only during the initial hypoxia-ischemia event, is a significant predictor of adverse outcomes in neonates with NE treated with therapeutic hypothermia (TH). We thus propose a care practice bundle dedicated to support the injured neonatal brain that is based on the current best evidence for each organ system. The impact of using such bundle on outcomes in NE remains to be demonstrated.


Renal protein excretion after exercise in man.
Thirteen men were submitted to graded exhaustive cycle exercise to determine the kinetics of proteinuria in the recovery period. Venous blood samples were analysed for haematocrit, lactate, creatinine, total protein and albumin for 1 h following exercise. Urine samples were collected during a 3-h recovery period. Total protein, albumin, and creatinine levels were determined for these samples. Total protein and albumin urinary excretion increased to 581 and 315 micrograms min-1, respectively, at the end of the 1st h of recovery as compared to 42 and 15 micrograms.min-1 for resting values. Plasma volume returned to pre-exercise levels between 30 and 60 min after cessation of exercise, while urinary total protein and albumin content still remained above the resting values for the following 2 h. Both post-exercise urinary total protein and albumin excretion followed a logarithmic decline with the same half-life of 54 min, thus requiring about 4 h to regain resting values. The reduction of plasma volume and the degree of dehydration do not seem to be involved in the process. The present study indicates the delayed recovery of protein handling by the kidney, as compared with other biochemical parameters, and provides accurate information on the kinetics of post-exercise proteinuria.


Strain-controlled fatigue behaviors of porous PLA-based scaffolds by 3D-printing technology.
In the study, the low-cycle fatigue behaviors of 3D-printed poly lactic acid (PLA) scaffolds with 60% porosity and two kinds of geometrical pores were investigated under strain-controlled loading. The obtained Δεa-Nf curves were fitted by Coffin-Manson relation. The mechanical stability of the porous structure under cyclic loading was studied. Both kinds of specimens undergo the strain softening after the initial cyclic hardening. The scaffold with circular pore exhibits stable resistance to the fatigue damage which is desirable for bone repairing. Regarding to the accumulation of inelastic deformation, the triangular-scaffold is more sensitive to the cyclic load. The superior fatigue behaviors of the scaffold with circular pore is attributed to homogeneous distribution of the applied mechanical stress and diminishing stress concentration by the introduction of circular pore.


Failure of engineering artifacts: a life cycle approach.
Failure is a central notion both in ethics of engineering and in engineering practice. Engineers devote considerable resources to assure their products will not fail and considerable progress has been made in the development of tools and methods for understanding and avoiding failure. Engineering ethics, on the other hand, is concerned with the moral and social aspects related to the causes and consequences of technological failures. But what is meant by failure, and what does it mean that a failure has occurred? The subject of this paper is how engineers use and define this notion. Although a traditional definition of failure can be identified that is shared by a large part of the engineering community, the literature shows that engineers are willing to consider as failures also events and circumstance that are at odds with this traditional definition. These cases violate one or more of three assumptions made by the traditional approach to failure. An alternative approach, inspired by the notion of product life cycle, is proposed which dispenses with these assumptions. Besides being able to address the traditional cases of failure, it can deal successfully with the problematic cases. The adoption of a life cycle perspective allows the introduction of a clearer notion of failure and allows a classification of failure phenomena that takes into account the roles of stakeholders involved in the various stages of a product life cycle.