Role of a functional human gene polymorphism in stress responsivity and addictions.
Over the past decade, enormous progress has been made in both the technical approaches and the scientific information available for studying the human genome. Therefore, increasingly, scientists have begun to address not just single-gene disorders but complex disorders. The limiting factor in most of such studies remains appropriate, well-focused detailed phenotyping of the complex disorders under study, with careful ascertainment of subjects with the specific disorder, as well as healthy control subjects.


Bis(4-nitro-phen-yl) selenide.
In the title compound, C12H8N2O4Se, the Se atom is situated on a twofold rotational axis, so the asymmetric unit contains one half-mol-ecule. In the mol-ecule, the C-Se-C angle is 99.48 (13)°, the two benzene rings are inclined to each other at an angle of 63.8 (1)° and the nitro group is twisted by 15.9 (1)° from the attached benzene ring. In the crystal, mol-ecules are held together through weak C-H⋯O inter-actions, forming a three-dimensional network.


Domino coupling relay approach to polycyclic pyrrole-2-carboxylates.
CuBr2-catalyzed three-component coupling of N-benzylallylamine, ethyl glyoxalate, and terminal alkynes afforded glycine-tethered 1,6-enynes, which were further transformed into polycyclic pyrrole-2-carboxylates via novel cycloisomerization/Diels-Alder cycloaddition/dehydrogenation sequence under iridium-catalyzed conditions.


Clinical relevance of the use of Dentoxol® for oral mucositis induced by radiotherapy: A phase II clinical trial.
Severe oral mucositis associated with cancer therapy is a frequent complication that may affect a patient's systemic condition, resulting in interruption and/or prolongation of cancer therapy. Dentoxol® is a medical solution in the form of a mouthwash that has been shown to result in statistically significant improvement in the prevention of severe oral mucositis. However, knowing the measures of the clinical significance of this therapy is important for accurate decision-making. To describe the clinical impact of Dentoxol® use in severe oral mucositis. Clinical significance was measured using the results obtained in a randomized controlled clinical trial previously conducted by the same group of researchers. The measures of clinical significance evaluated were the absolute risk or incidence, relative risk, absolute risk reduction, relative risk reduction, number needed to treat, and odds ratio. The data obtained show that the impact of Dentoxol® on reducing the severity of oral mucositis has important clinical relevance. The results of this study justify the incorporation of Dentoxol® mouth rinse into clinical protocols as a complement to cancer therapy to prevent and/or treat oral mucositis secondary to radiotherapy.


SEM and XRD for removal of heavy metals from industrial wastewater and characterization of chicken eggshell.
Heavy metal toxicity due to industrial wastewater has been a threat to the environment for the past many decades, especially in developing countries. Electroplating Industry wastewater containing heavy metals can become a serious environmental pollutant if not treated appropriately. Present study investigated the removal of nickel and chromium ions from electroplating wastewater using calcined hen eggshells because of it high removal capability, little cost and easy approachability. Characterization of the adsorbent such as proximate analysis, surface charge, X-ray diffraction, and surface area was done prior to adsorption process. Batch adsorption experiment was performed to study the effect of different parameters such as adsorbent dose, contact time, temperature, and pH for adsorbent. Removal percentage of both heavy metals was checked by using calcined eggshell as adsorbent. Comparison was made between nickel and chromium to identify the most effective removal efficacy. It was concluded that utilization of natural waste was found suitable, easier, cost operative and environmental approachable for removal of heavy metals from industrial wastewater. RESEARCH HIGHLIGHTS: To use ecofriendly approach for the treatment of industrial wastewater. To used calcined eggshell as adsorbents for removing metal concentration from industrial wastewater. To find the metal removal potential of calcined eggshell under various environmental conditions like dosage, contact time, temperature, and pH. To checking the efficacy of calcined eggshell.


Information transfer via temporal convolution in nonlinear optics.
Nonlinear parametric processes involving ultrashort pulses are typically carried out in time domain, which mathematically corresponds to a convolution of their frequency spectra. In contrast, this spectral convolution changes into a multiplication operation when performing the nonlinear interaction in frequency domain. Here, we extend the scope of frequency-domain nonlinear optics by demonstrating its ability to perform a temporal convolution. Through this approach, nonlinear optical operations that are inaccessible in time domain can be realised: specific optical information can be coherently advanced by picoseconds within a pulse sequence-a newly generated second harmonic pulse carries the amplitude and phase information of two input pulses. This central pulse is isolated when using an input field consisting of two cross-polarized input pulses in combination with type-II second harmonic generation. The effects of nonlinear temporal convolution can be viewed from the aspect of signal processing and pulse shaping, where the nonlinear interaction in the parametric crystal plays the role of a dynamic linear optical filter-in contrast to conventional static filters-with a shaping mask instantaneously adapting to the laser field.


Analysis of the Risk Factors for C5 Nerve Palsy After Cervical Posterior Open-Door Laminoplasty for Patients with Cervical Spondylotic Myelopathy-From the Perspective of Cervical Sagittal Parameters.
This study was performed to explore the sagittal radiological parameters related to the occurrence of C5 nerve palsy after cervical posterior open-door laminoplasty for the patients with cervical spondylotic myelopathy. Sixty-two patients who underwent cervical posterior open-door laminoplasty were reviewed retrospectively from March 2017 to March 2022. The C2-7 Cobb angle, C2-7 sagittal vertex axis, thoracic inlet angle, neck tilt, T1 slope, and encroachment ratio of ossification were measured on X-rays. The enrolled patients were divided into C5 nerve palsy and control groups. Logistic regression was performed to analyze the potential risk factors for the occurrence of C5 nerve palsy. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to evaluate the significance of the results and the optimal diagnostic value. The results of logistic regression showed that only the T1 slope and encroachment ratio were variables that were responsible for C5 nerve palsy (P = 0.024; P = 0.04). The ROC curve analysis for the T1 slope showed that the cutoff value was 21.3° and the AUC was 0.796. The ROC curve analysis for the encroachment ratio revealed that the cutoff value was 0.21 and the AUC was 0.763. Both analyses demonstrated good diagnostic value for C5 nerve palsy. The preoperative T1 slope and encroachment ratio were variables that were risk factors for C5 nerve palsy in patients who underwent cervical posterior open-door laminoplasty.


The Relationship Between Pharyngeal Constriction and Post-swallow Residue.
Pharyngeal constriction has been proposed as a parameter that may distinguish functional from impaired swallows. We employed anatomically normalized pixel-based measures of pharyngeal area at maximum constriction, and the ratio of this measure to area at rest, and explored the association between these measures and post-swallow residue using the normalized residue ratio scale (NRRS). Videofluoroscopy data for 5 ml boluses of 22 % (w/v) liquid barium were analyzed from 20 healthy young adults and 40 patients with suspected neurogenic dysphagia. The frames of maximum pharyngeal constriction and post-swallow hyoid rest were extracted. Pixel-based measures of pharyngeal area were made using ImageJ and size-normalized using the squared C2-C4 vertebral distance as a reference scalar. Post-swallow residue and the areas of the vallecular and pyriform sinus spaces were measured on the hyoid rest frame to calculate the NRRSv and NRRSp. The dataset was divided into swallows with residue within or exceeding the upper confidence interval boundary seen in the healthy participants. Mixed model repeated measures ANOVAs were used to compare pharyngeal area (rest, constriction) and the pharyngeal constriction ratio, between individuals with and without residue. Measures of pharyngeal area at maximum constriction were significantly larger (i.e., less constricted, p = 0.000) in individuals with post-swallow residue in either the valleculae or the pyriform sinus. These results support the idea that interventions targeted toward improving pharyngeal constriction have the potential to be effective in reducing post-swallow residue.


CardioWest total artificial heart in a moribund adolescent with left ventricular thrombi.
Bridge to transplant is a well-known strategy to enable patients with congestive heart failure to live until transplant. A 15-year-old boy with Beckers' muscular dystrophy and cardiomyopathy was accepted for heart transplantation. He suffered a cardiac arrest and was placed on extracorporeal membrane oxygenator. A paracorporeal biventricular assist device and a total artificial heart were considered for bridge to transplant. A CardioWest total artificial heart was chosen because of the patient's size. Multiple left ventricular thrombi were identified at the time of the ventriculectomy. The patient did well with the total artificial heart was transplanted and discharged home. The unknown presence of significant left ventricular thrombi raises the question of outcome with a paracorporeal ventricular assist device.


Individualized prediction of survival benefits from perioperative chemoradiotherapy for patients with resectable gastric cancer.
The survival benefits of perioperative chemoradiotherapy (PCRT) and perioperative chemotherapy (PCT) for resectable gastric cancer (GC) patients remain unclear. This study aimed to compare the effects of PCRT and PCT in patients with resectable GC and develop a nomogram to evaluate the prognosis and disease risk of patients. A total of 6890 patients with stage IB-IIIC GC from 2010 to 2015 were retrieved from the Surveillance, Epidemiology and End Results (SEER) database. Univariate Cox proportional hazards regression analyses were performed to evaluate the prognostic value of involved variables. A new nomogram was constructed based on development cohort and validated by an external validation cohort. The clinical practicability and accuracy were assessed by concordance index (C-index), calibration plot, and receiver operating characteristic (ROC) curve. A better prognosis was obtained for patients with stage III GC treated with PCRT compared with those treated with PCT. Additionally, patients with grade III/IV, diffuse type GC, distal gastric cancer (DGC), tumor size >34 millimeters, or positive lymph nodes were more likely to benefit from PCRT. Multivariate analyses indicated that age, grade, tumor size, T stage, N stage, and comprehensive treatment were independent covariates. Excellent agreement of calibration plots and good discrimination power were obtained using the nomogram. The nomogram achieved a better net benefit than the 8th edition AJCC TNM staging. An online version was built based on the nomogram for convenient clinical use. The application of perioperative chemoradiotherapy should be determined according to the clinicopathological features of patients. Our nomogram provided a reliable tool for screening patients who were right for PCRT and evaluating individual survival benefits.


Parp-1 protects homologous recombination from interference by Ku and Ligase IV in vertebrate cells.
Parp-1 and Parp-2 are activated by DNA breaks and have been implicated in the repair of DNA single-strand breaks (SSB). Their involvement in double-strand break (DSB) repair mediated by homologous recombination (HR) or nonhomologous end joining (NHEJ) remains unclear. We addressed this question using chicken DT40 cells, which have the advantage of carrying only a PARP-1 gene but not a PARP-2 gene. We found that PARP-1(-/-) DT40 mutants show reduced levels of HR and are sensitive to various DSB-inducing genotoxic agents. Surprisingly, this phenotype was strictly dependent on the presence of Ku, a DSB-binding factor that mediates NHEJ. PARP-1/KU70 double mutants were proficient in the execution of HR and displayed elevated resistance to DSB-inducing drugs. Moreover, we found deletion of Ligase IV, another NHEJ gene, suppressed the camptothecin of PARP-1(-/-) cells. Our results suggest a new critical function for Parp in minimizing the suppressive effects of Ku and the NHEJ pathway on HR.


Swine-manure composts induce the enrichment of antibiotic-resistant bacteria but not antibiotic resistance genes in soils.
Composting is a common and effective strategy for reducing antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) from animal manure. However, it is unclear whether the advantages of composting for the control of ARGs and ARB can be further increased in land application. This study investigated the fate of ARB and ARGs after land application of swine-manure composts (SMCs) to three different soil types (red soil, loess and black soil). The results showed that although the SMCs caused an increase in the abundance of total ARGs in the soil in the short period, they significantly reduced (p < 0.01) the abundance of total ARGs after 82 days compared to the control. The decay rate of ARGs reflected by the half-life times (t1/2) varied by soil type, with red soil being the longest. The SMCs mainly introduced ermF, tetG and tetX into the soils, while these ARGs quickly declined to the control level. Notably, SMCs increased the number of ARB in the soils, especially for cefotaxime-resistant bacteria. Although SMCs only affected the microbiome significantly during the early stage (p < 0.05), it took a much longer time for the microbiome to recover compared to the control. Statistical analysis indicated that changes in the microbial community contributed more to the fate of ARGs during SMCs land application than other factors. Overall, it is proposed that the advantages of ARGs control in the composting process for swine manure can be further increased in land application, but it can still bring some risks in regard to ARB.


Decreased numbers of FoxP3-positive and TLR-2-positive cells in intestinal mucosa are associated with improvement in patients with active inflammatory bowel disease following selective leukocyte apheresis.
Impaired immunological tolerance to commensal enteric flora is considered one possible pathogenic mechanism of inflammatory bowel disease (IBD). Given that regulatory T cells and Toll-like receptor (TLR)-positive cells are key actors in mucosal immune regulation, we aimed to identify the dynamics of these actors in the intestinal mucosa in relation to clinical improvement following selective leukapheresis treatment. Ten patients with active IBD despite treatment with corticosteroids, immunomodulators, or anti-tumor necrosis factor therapy were assessed by immunohistochemical staining of colorectal mucosal biopsies obtained before and after five sessions (week 7) of granulocyte and monocyte adsorption apheresis (GCAP). The presence of FoxP3-positive regulatory T cells, macrophages, dendritic cells, and TLR-2 and-4 positive cells was determined in relation to short-(week 7) and long-term (week 52) clinical outcome data. Following GCAP, the number of FoxP3-(P = 0.012) and TLR-2 (P = 0.008)-positive cells significantly decreased in biopsies after 7 weeks, in parallel with both clinical improvement at week 7 and a longstanding response after 12 months. Downregulation of FoxP3 and TLR-2 cells in the colorectal mucosa mirrors both short-and long-term improvement in patients with active IBD responding to GCAP. This observation suggests a potential role of these cells in the pathogenesis of IBD and the induction of immunological tolerance in the mucosa.


Precocious retina development caused by receptor cell independent light effect.
In the retina of the mouth-brooding teleost Tilapia leucosticta, light causes and accelerated development of ganglion cells. This effect is presumably not mediated by receptor and interneuronal cells.


Tau Pathology Triggered by Spinal Cord Injury Can Play a Critical Role in the Neurotrauma Development.
Traumatic spinal cord injury (SCI) can result in substantial neurological impairment along with significant emotional and psychological distress. It is clear that there is profound neurodegeneration upon SCI, gradually spread to other spinal cord regions and brain areas. Despite extensive considerations, it remains uncertain how pathogenicity diffuses in the cord. It has been reported that tau protein abnormal hyperphosphorylation plays a central role in neurodegeneration triggered by traumatic brain injury (TBI). Tau is a microtubule-associated protein, heavily implicated in neurodegenerative diseases. Importantly, tau pathology spreads in a traumatic brain in a timely manner. In particular, we have recently demonstrated that phosphorylated tau at Thr231 exists in two distinct cis and trans conformations, in which that cis P-tau is extremely neurotoxic, has a prion nature, and spreads to various brain areas and cerebrospinal fluid (CSF) upon trauma. On the other hand, tau pathology, in particular hyperphosphorylation at Thr231, has been observed upon SCI. Taken these together, we conclude that cis pT231-tau may accumulate and spread in the spinal cord as well as CSF and diffuse tau pathology in the central nervous system (CNS). Moreover, antibody against cis P-tau can target intracellular cis P-tau and protect pathology spreading. Thus, considering cis P-tau as a driver of tau pathology and neurodegeneration upon SCI would open new windows toward understanding the disease development and early biomarkers. Furthermore, it would help us develop effective therapies for SCI patients.


Autoregulation and the CO2 responsiveness of cerebral blood flow after cardiopulmonary bypass.
Cerebral blood flow (CBF) was measured by 133Xe clearance to determine whether there were any residual effects of cardiopulmonary bypass (CPB) on the CBF response to changes in arterial PCO2 or blood pressure in the early (3-8 hr) post-CPB period. During CPB, the nine patients studied were managed according to alpha-stat, temperature uncorrected, pH management. The mean +/- SD increase in CBF resulting from an increase in PaCO2 (1.35 +/- 0.5 ml.100 g-1.min-1.mmHg-1 PaCO2) was within the normal range, indicating appropriate CBF response to a change in PaCO2. There were no significant differences in CBF, being 25.7 ml.100 g-1.min-1 at a mean arterial blood pressure of 70 mmHg and 26.5 ml.100 g-1.min-1 at 110 mmHg, demonstrating intact cerebral autoregulation over this pressure range. We conclude that cerebral autoregulation and CO2 responsiveness are preserved in the immediate postoperative period after CPB using alpha-stat pH management.


A series of asymmetrical phthalocyanines: synthesis and near infrared properties.
We report here the preparation of asymmetrical phthalocyanine dimers 1a-3a, which are endowed with novel charge transfer bands at 1,151-1,154 nm and strong NIR luminescences at 840-860 nm and 1,600-1,650 nm. Through H-bonding interaction, 1a-3a are inclined to self-assemble into hexrod nanotubes at the interface of CHCl₃ and CH₃H. Our results provide further insights into the interaction in molecular dimers, and suggest that 1a-3a have potential application in magnets and supramolecular architectures.


Laparoscopic-Assisted Endoscopic Retrograde Cholangiopancreatography (ERCP) for Bile Duct Stones After Roux-en-Y-Gastric Bypass: Single-Centre Experience.
Gallstones are common in bariatric patients due to obesity and rapid weight loss. Bile duct stones after Roux-en-Y gastric bypass (RYGB) pose a technical challenge. We present our experience in management of bile duct stones following RYGB using laparoscopic-assisted endoscopic retrograde cholangiopancreatography (LA-ERCP). Retrospective review of RYGB patients who had endoscopic intervention for bile duct stones between 2010 and 2019. We assessed demographic and clinical outcomes. There were 12 patients: 9 females, median age 64 years (range 34-73), median ASA score 3 (range 2-3), and median body mass index (BMI) 30 kg/m2 (range 24.4-46). Median time of presentation since RYGB was 5 years (range 6-96 months). Clinical presentations were biliary pain with deranged liver function tests (n = 8, 67%) and cholangitis (n = 4, 33%). Ten patients (83%) had cholecystectomy prior to presentation. LA-ERCP was performed in all 12 patients. It was successful in 10 patients (83%) of which 7 were performed as a primary intervention for bile duct stones and 3 were for residual stones following previous bile duct exploration. Two out of 12 LA-ERCPs (17%) were converted to open duct clearance. Median overall hospital stay was 2.5 days (range 1-10). One patient developed post-ERCP pancreatitis; one had chronic pain. There was no major complication or mortality. LA-ERCP is feasible for bile duct stones after RYGB and can clear the duct primarily or following previous surgical exploration. It also provides an opportunity to perform cholecystectomy and diagnostic laparoscopy.


Identification of a catalytic aspartyl residue of D-ribulose 5-phosphate 3-epimerase by site-directed mutagenesis.
Guided by comparative sequence considerations, we have examined the possibility of a catalytic role of Asp186 of D-ribulose 5-phosphate epimerase by site-directed mutagenesis of the recombinant spinach enzyme. Accordingly, D186A, D186N, and D186E mutants of the epimerase were constructed, purified, and characterized; as judged by their electrophoretic mobilities the mutants are properly assembled into octamers like the wild-type enzyme. Based on the extent of internal quenching of Trp fluorescence, the conformational integrity of the wild-type enzyme is preserved in the mutants. The wild-type kcat of 7.1 x 10(3) s-1 is lowered to 3.3 x 10(-4) s-1 in D186A, 0.13 s-1 in D186N, and 1.1 s-1 in D186E; as gauged by D186A, altogether lacking a functional side chain at position 186, the beta-carboxyl of Asp186 facilitates catalysis by >10(7)-fold. Relative to the wild-type enzyme, the Km for D-ribulose 5-phosphate is essentially unaltered with D186N and D186E but increased 10-fold with D186A. Apart from their impairments in epimerase activity, the mutants are unable to catalyze exchange between solvent protons and the C3 proton of substrates. This deficiency and the differential alterations of kinetic parameters among the mutants are consistent with Asp186 serving as an electrophile to facilitate alpha-proton abstraction. This study is the first to identify a catalytic group of the epimerase.


Combined detection of estrogen and tumor markers is an important reference factor in the diagnosis and prognosis of lung cancer.
The correlation between lung cancer tumor markers and sex differences in lung cancer remains a clinical problem that is worthy of further study. This study investigated the significance of the combined detection of 17β-estrogen (E2) and tumor markers in the diagnosis and prognosis of lung cancer. A total of 174 patients, including 117 patients with non-small-cell lung cancer (NSCLC) and 57 patients with benign pulmonary lesions (BPL), were enrolled. An enzyme-linked immunosorbent assay was used to detect the expression of E2, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) in patients with NSCLC and BPL to analyze the correlation between E2 and CEA, NSE or CYFRA21-1 expression, and its correlation with clinicopathological features and prognosis. The expression of tumor markers was then examined in different lung cancer cells (A549, H1795, H460, and SK-MES-1). The expression of tumor markers was detected by a real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. The expressions of p-p44/42 mitogen-activated protein kinase (MAPK) and phospho-AKT (p-AKT) were detected by Western blot analysis. The expression levels of E2, CEA, NSE, and CYFRA21-1 in patients with NSCLC were significantly higher than those in patients with BPL ( P < .05); E2 was positively correlated with tumor markers ( P < .01). Patients with a high expression of E2 and tumor markers showed a poor prognosis ( P < .05). RT-quantitative PCR and Western blot analysis showed that the expression levels of CEA, NSE, CYFRA21-1, p-p44/42 MAPK, and p-AKT in the E2 group were higher than those in the other groups ( P < .05). These studies indicate that the interaction of E2 and tumor markers can significantly improve the role of tumor markers in the diagnosis and prognosis of lung cancer.


Non-coding RNA and their potential role in cardiovascular diseases.
Cardiovascular diseases are the leading cause of mortality worldwide. The timely diagnosis of CVD is still an unmet challenge. Non-coding RNAs which were earlier considered to be "junk DNA" are now considered to play crucial role as potential transcriptional regulators and therapeutic targets for treatment of CVDs. A literature search has been performed on PubMed, SCOPUS where keywords such as "non- coding RNAs" and "coronary artery disease" and "miRNAs" and "Myocardial infarction" or "cardiovascular diseases" were used with no date restriction in writing this review article. This review focus on the role of non- coding RNAs in cardiovascular disease along with the database which can enhance the efficiency of experimental analysis of non-coding RNAs.


Nurses' experiences of ethical and legal issues in post-resuscitation care: A qualitative content analysis.
Cardiopulmonary resuscitation and subsequent care are subject to various ethical and legal issues. Few studies have addressed ethical and legal issues in post-resuscitation care. To explore nurses' experiences of ethical and legal issues in post-resuscitation care. This qualitative study adopted an exploratory descriptive qualitative design using conventional content analysis. In-depth, semi-structured interviews were conducted in three educational hospital centers in northwestern Iran. Using purposive sampling, 17 nurses participated. Data were analyzed by conventional content analysis. The study was approved by Research Ethics Committees at Tabriz University of Medical Sciences. Participation was voluntary and written informed consent was obtained. For each interview, the ethical principles including data confidentiality and social distance were respected. Five main categories emerged: Pressure to provide unprincipled care, unprofessional interactions, ignoring the patient, falsifying documents, and specific ethical challenges. Pressures in the post-resuscitation period can cause nurses to provide care that is not consistent with guidelines, and to avoid communicating with physicians, patients and their families. Patients can also be labeled negatively, with early judgments made about their condition. Medical records can be written in a way to indicate that all necessary care has been provided. Disclosure, withdrawing, and withholding of therapy were also specific important ethical challenges in the field of post-resuscitation care. There are many ethical and legal issues in post-resuscitation care. Developing evidence-based guidelines and training staff to provide ethical care can help to reduce these challenges.


Update on hand hygiene.
Recent developments related to hand hygiene include new test methods for evaluating hand hygiene products, improvements in alcohol-based hand rubs, novel methods of hand antisepsis, and new strategies and technologies for monitoring hand hygiene practices among health care personnel.


Rupture of a congenital diaphragmatic eventration in a child: report of a case.
Diaphragmatic rupture may be traumatic or may occur spontaneously. Spontaneous diaphragmatic rupture is a rare entity seen almost entirely in adults. We report here a case with spontaneous rupture of a congenital diaphragmatic evantration in a child.


Three-layer model for the control of epidemic infection over multiple social networks.
This paper presents a hierarchical approach for controlling the spread of an epidemic disease. The approach consists of a three-layer architecture where a set of two-layer multiple social networks is governed by a (third) top-layer consisting of an optimal control policy. Each of the two-layer social networks is modeled by a microscopic Markov chain. On top of all the two-layer networks is an optimal control policy that has been developed by using an underlying Markov Decision Process (MDP) model. Mathematical models pertaining to the top-level MDP as well as two-layer microscopic Markov chains have been presented. Practical implementation methodology using the proposed models has also been discussed along with a numerical example. The results in the numerical example illustrate the control of an epidemic using the optimal policy. Directions for further research and characterization of the optimal policy have also been discussed with the help of the same numerical example. An optimal approach for controlling the spread of an epidemic infection.The approach is able to model the uncertainties involved in the problem.The approach is able to cater for the underlying social network.


Hyaluronic acid family in bladder cancer: potential prognostic biomarkers and therapeutic targets.
Molecular markers of clinical outcome may aid in designing targeted treatments for bladder cancer. However, only a few bladder cancer biomarkers have been examined as therapeutic targets. Data from The Cancer Genome Atlas (TCGA) and bladder specimens were evaluated to determine the biomarker potential of the hyaluronic acid (HA) family of molecules - HA synthases, HA receptors and hyaluronidase. The therapeutic efficacy of 4-methylumbelliferone (4MU), a HA synthesis inhibitor, was evaluated in vitro and in xenograft models. In clinical specimens and TCGA data sets, HA synthases and hyaluronidase-1 levels significantly predicted metastasis and poor survival. 4-Methylumbelliferone inhibited proliferation and motility/invasion and induced apoptosis in bladder cancer cells. Oral administration of 4MU both prevented and inhibited tumour growth, without dose-related toxicity. Effects of 4MU were mediated through the inhibition of CD44/RHAMM and phosphatidylinositol 3-kinase/AKT axis, and of epithelial-mesenchymal transition determinants. These were attenuated by HA, suggesting that 4MU targets oncogenic HA signalling. In tumour specimens and the TCGA data set, HA family expression correlated positively with β-catenin, Twist and Snail expression, but negatively with E-cadherin expression. This study demonstrates that the HA family can be exploited for developing a biomarker-driven, targeted treatment for bladder cancer, and 4MU, a non-toxic oral HA synthesis inhibitor, is one such candidate.


[cDNA cloning and prokaryotic expression of human cholesteryl ester transfer protein and preparation of its antiserum].
To clone human cholesteryl ester transfer protein (CETP) cDNA, express and purify human CETP in E.coli and prepare CETP-specific rabbit antiserum. by RT-PCR method, the encoding sequence of human cholesteryl ester transfer protein (CETP) was cloned into pET-30b(+) vector. Then BL21 (DE3) of E.coli transformed with recombinant vector pET-CETP was induced to express CETP in high level by IPTG. The expressed protein was purified from SDS-polyacrylamide gel, and the antiserum against CETP was raised in rabbit. The titer and specificity of rabbit antiserum were evaluated by ELISA, Western blot and immunofluorescence assay. The results of SDS-PAGE showed that CETP was expressed in the form of inclusion bodies in BL21(DE3) and the best expression time was about 4 hours. The titer of the rabbit antiserum prepared with CETP purified from SDS-PAGE was 1:5. 12 x 10(5) and the antiserum reacted specifically with CETP expressed in BL21 (DE3) and COS7 cells. The preparation of the specific rabbit antiserum against CETP will be valuable for the study on the structure and function of human CETP.


Airway endoscopy in the diagnosis and treatment of bacterial tracheitis in children.
Children with bacterial tracheitis present with the symptoms of viral laryngotracheobronchitis or epiglottitis, but do not respond to appropriate therapy for these diseases and frequently develop acute respiratory decompensation. Since the treatment and outcome of bacterial tracheitis differ so much from those of viral laryngotracheobronchitis and epiglottitis, prompt and accurate diagnosis is essential. The aim of this study was to evaluate the significance of different diagnostic characteristics in a group of eleven patients and to compare the results to those recently reported in the pediatric and otorhinolaryngologic literature. The present study suggests that reliable predictive factors do not exist for bacterial tracheitis. No single clinical, radiological or laboratory feature was a reliable diagnostic predictor for bacterial tracheitis, nor was it any combination of these features. The only diagnostic procedure to distinguish bacterial tracheitis accurately and promptly from other forms of acute obstructive upper airway diseases was direct laryngo-tracheo-bronchoscopy. Following endoscopic removal of all tracheal secretions and pulmonary toilet, nasotracheal intubation provides sufficient airway maintenance and obviates the need for tracheostomy. Endoscopy is thus diagnostic and therapeutic at the same time. If bacterial tracheitis is suspected a direct laryngoscopy and rigid tracheobronchoscopy should be performed under general anesthesia, as prompt diagnosis and adequate treatment are essential to survival. The cultures of the purulent tracheal secretions frequently revealed Staphylococcus aureus in combination with various pathogens, particularly the involvement of Pseudomonas aeruginosa was noted in two patients. Our data imply a susceptibility of children with Down's syndrome or immunodeficiency to bacterial tracheitis.


[Angiographic abnormalities after punch-biopsy of the liver (author's transl)].
The authors report on 10 cases of complications during punch-biopsy of the liver, an arterio-portal fistula being the one most frequently encountered (8 out of 10 cases). The clinical condition improved in 9 cases out of 10. The authors stress the frequency of arterioportal fistula after punch-biopsy of the liver (60% it arteriography is carried out during the first week). They recall the benign character of these fistulae and their tendency towards spontaneous healing.


National Trends in Pediatric Facial Fractures: The Impact of Health Care Policy.
Traumatic injuries are significant sources of morbidity and mortality in the pediatric population. Using a national database, this study aims to characterize pediatric facial fracture management and the effect of health care policy changes on populations receiving treatment. A retrospective cohort study was performed using Healthcare Cost and Utilization Project Kids' Inpatient Database databases from 2000 to 2016. Pediatric patients admitted with a facial fracture diagnosis were included. Clinical outcomes include mortality, reduction of fracture during hospital stay, and open fracture reduction. The impact of the Affordable Care Act on patient demographics and management was assessed. Between 2000 and 2016, 82,414 patients were managed for facial fractures, 8.3 percent of whom were managed after implementation of the Affordable Care Act (n = 6841). Mean age was 15.2 years, and the male-to-female ratio was 2.9:1. Significant racial disparities were identified before the Affordable Care Act: African American and Native American patients had decreased odds of having facial fracture reduction during the initial hospital stay (OR, 0.84 and 0.86, respectively), and identifying as either Hispanic or Native American was associated with higher odds of mortality (OR, 1.4 or 2.4, respectively). Race was not contributory to patient mortality after the Affordable Care Act. Before Affordable Care Act implementation, patients receiving care with no charge (including charity care/charity research) had lower odds of having an open reduction or any reduction; insurance status was not contributory to management after the Affordable Care Act. Although the Affordable Care Act may have increased access to care for certain populations, race- and sex-associated differences in mortality rate and fracture management should be further investigated to ensure a national standard of equitable patient care.


Material damage diagnosis and characterization for turbine rotors using three-dimensional adaptive ultrasonic NDE data reconstruction techniques.
Damage diagnosis for turbine rotors plays an essential role in power plant management. Ultrasonic non-destructive examinations (NDEs) have increasingly been utilized as an effective tool to provide comprehensive information for damage diagnosis. This study presents a general methodology of damage diagnosis for turbine rotors using three-dimensional adaptive ultrasonic NDE data reconstruction techniques. Volume reconstruction algorithms and data fusion schemes are proposed to map raw ultrasonic NDE data back to the structural model of the object being examined. The reconstructed volume is used for automatic damage identification and quantification using region-growing algorithms and the method of distance-gain-size. Key reconstruction parameters are discussed and suggested based on industrial experiences. A software tool called AutoNDE Rotor is developed to automate the overall analysis workflow. Effectiveness of the proposed methods and AutoNDE Rotor are explored using realistic ultrasonic NDE data.


Integrative analyses of maternal plasma cell-free DNA nucleosome footprint differences reveal chromosomal aneuploidy fetuses gene expression profile.
Chromosomal aneuploidy is the most common birth defect. However, the developmental mechanism and gene expression profile of fetuses with chromosomal aneuploidy are relatively unknown, and the maternal immune changes induced by fetal aneuploidy remain unclear. The inability to obtain the placenta multiple times in real-time is a bottleneck in research on aneuploid pregnancies. Plasma cell-free DNA (cfDNA) carries the gene expression profile information of its source cells and may be used to evaluate the development of fetuses with aneuploidy and the immune changes induced in the mother owing to fetal aneuploidy. Here, we carried out whole-genome sequencing of the plasma cfDNA of 101 pregnant women carrying a fetus with trisomy (trisomy 21, n = 42; trisomy 18, n = 28; trisomy 13, n = 31) based on non-invasive prenatal testing (NIPT) screening and 140 normal pregnant women to identify differential genes according to the cfDNA nucleosome profile in the region around the transcription start sites (TSSs). The plasma cfDNA promoter profiles were found to differ between aneuploid and euploid pregnancies. A total of 158 genes with significant differences were identified, of which 43 genes were upregulated and 98 genes were downregulated. Functional enrichment and signaling pathway analysis were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases found that these signal pathways were mainly related to the coordination of developmental signals during embryonic development, the control of cell growth and development, regulation of neuronal survival, and immune regulation, such as the MAPK, Hippo, TGF-β, and Rap1 signaling pathways, which play important roles in the development of embryonic tissues and organs. Furthermore, based on the results of differential gene analysis, a total of 14 immune-related genes with significant differences from the ImmPort database were collected and analyzed. These significantly different immune genes were mainly associated with the maintenance of embryonic homeostasis and normal development. These results suggest that the distribution characteristics of cfDNA nucleosomes in maternal plasma can be used to reflect the status of fetal development and changes of the immune responses in trisomic pregnancies. Overall, our findings may provide research ideas for non-invasive detection of the physiological and pathological states of other diseases.


Ozonation of blood during extracorporeal circulation. II. Comparative analysis of several oxygenator-ozonators and selection of one type.
Exposure of human blood ex vivo to oxygen-ozone (O2-O3) using either dialysis exchangers or normal oxygenators gives rise to a number of problems, one of which linked to platelet activation, leads to rapid occlusion and no gas exchange. Semipermeable membranes were found unsuitable because, except for one, they were gas-transfer inefficient, allowed ultrafiltration and were more or less vulnerable to O3. Over the last three years we have examined several types of hydrophobic O3-resistant hollow fiber capillaries but, if the polypropylene surface is not properly coated, there is platelet aggregation and blood coagulation. These problems while far less relevant with O2 alone, become prohibitive in the presence of ozone. Recently new oxygenators have been prepared with special materials to make them more biocompatible and it has become possible to oxygenate and ozonate up to 5L of blood in about an hour, thus making the treatment of critical patients feasible.


Reconstructing the single-cell-level behavior of a toggle switch from population-level measurements.
Single-cell-level behaviors of cells are typically inferred from ensemble measurements. However, such inferences implicitly assume a biological version of ergodicity: the percentage of cells in a state is identical to the probability to find a cell in that state. While the ergodicity does not always hold, it has been rarely tested. Here, we reveal that the ergodicity does not necessarily hold even for simple toggle switches and that apparent stabilities of the switches are due to a balance between single-cell-level biased stabilities and growth rates differences. Therefore, verification of the ergodicity and reconstructing single-cell-level behaviors are crucial for understanding intracellular systems.


Comparison of multipoint linkage analyses for quantitative traits in the CEPH data: parametric LOD scores, variance components LOD scores, and Bayes factors.
We performed multipoint linkage analyses with multiple programs and models for several gene expression traits in the Centre d'Etude du Polymorphisme Humain families. All analyses provided consistent results for both peak location and shape. Variance-components (VC) analysis gave wider peaks and Bayes factors gave fewer peaks. Among programs from the MORGAN package, lm_multiple performed better than lm_markers, resulting in less Markov-chain Monte Carlo (MCMC) variability between runs, and the program lm_twoqtl provided higher LOD scores by also including either a polygenic component or an additional quantitative trait locus.


Germ-line transformation of the Australian sheep blowfly Lucilia cuprina.
The Australian sheep blowfly, Lucilia cuprina, is the most important economic insect pest for the sheep industries in Australia and New Zealand. piggyBac-mediated germ-line transformation of L. cuprina was achieved with a helper plasmid that had the Drosophila melanogaster hsp70 promoter controlling expression of the transposase and a piggyBac vector with an EGFP marker gene. Two transformant lines were obtained, at a frequency of approximately 1-2% per fertile G0. One of these lines has a single copy of the transgene, the other most likely has four copies. This is the first report of germ-line transformation of L. cuprina and is an important step towards the generation of engineered strains that would be suitable for male-only release eradication/suppression programmes.


Adverse events after coronary artery bypass grafting in patients with preoperative metabolic syndrome: A 10-year follow-up of the Veterans Affairs Database.
Data regarding 10-year survival and adverse cardiovascular events in patients with metabolic syndrome (MET) after coronary artery bypass grafting (CABG) is limited. We compared 10-year events rates for veterans undergoing isolated CABG (January 1, 2005, to December 31, 2014, follow-up October 31, 2019) stratified by presence of metabolic syndrome (MET+) versus without (MET-). A multivariable weighted Cox model was used to analyze all-cause mortality. Competing risk analysis was used to calculate cumulative event rates for congestive heart failure, myocardial infarction, and cerebrovascular events. The Fine-Gray subhazard model was used to determine adjusted association of MET with myocardial infarction and stroke. Congestive heart failure was modeled as a recurrent-event analysis. Nationally, 9615 adults (median age, 60 years; 98.9% men) underwent isolated coronary artery bypass grafting at 41 centers); among them, 3121 out of 9615 (32.5%) had MET. The prevalence of MET increased from (27.88% in 2005 to 34.02% in 2014; P = .02). MET+ group members were likely younger (median age, 63 vs 64 years; P < .01), White (72% vs 68%), and had more peripheral vascular disease (30% vs 28%; P = .04). Multivessel (72% vs 70%; P = .23) and multiarterial (4% vs 4%; P = .14) grafting was performed equally. With a median follow-up of 6.5 years, survival was similar (P = .26); however, MET was associated with higher risks for myocardial infarction (21% vs 16%; hazard ratio, 1.3; P < .01) and recurrent admissions for congestive heart failure. Patients with metabolic syndrome undergoing coronary artery bypass grafting have higher 10-year cardiovascular event rates.


Efficacy of glutamine-supplemented parenteral nutrition on short-term survival following allo-SCT: a randomized study.
Fifty-three patients with hematological malignancies who underwent Allo-SCT from HLA-identical siblings were randomly assigned to receive glutamine-enriched parenteral nutrition-PN (GlPN, n=27) or standard PN (PN, n=26), in isonitrogenous solutions. Deaths (D+100 and D+180), infections, acute GVHD, length of stay, time of neutropenia and intestinal permeability (IP) were studied. Ages, gender, diagnosis, disease status and treatment variables were equally distributed between groups. Survival on D+180 was increased in GlPN (74%) vs PN (46%), P=0.03 (log-rank), as on D+100 (P=0.05). Most deaths occurred before D+100, especially in PN (10/26, 39%) vs GlPN (4/27, 15%). GVHD was the most frequent cause of death (8/21, 38%), especially in PN (n=6, five before D+100). Other outcomes were not affected. IP was affected on admission, was not affected by glutamine enrichment, but consistently worsened throughout the study. Results showed that GlPN was efficacious in increasing short-term survival after Allo-SCT. Benefits of glutamine seem to be independent of mucosal protection, as IP was not affected by its use. A trend to a lower incidence of GVHD deaths may suggest an immunomodulatory role of glutamine.


Sustaining rural pharmacy workforce understanding key attributes for enhanced retention and recruitment.
To pilot the Pharmacist Community Apgar Questionnaire (PharmCAQ) and evaluate its usability and capacity to develop a greater understanding of the unique factors that impact the rural recruitment and retention of pharmacists. Cross-sectional design involving face-to-face, telephone or video conferencing interviews. Twelve rural communities across Tasmania and Western Victoria, Australia. Participants (n = 24) included pharmacists, a Director of Clinical Services, pharmacy practice managers and senior pharmacy assistants. Interviews enabled the completion of the PharmCAQ, which assigns quantitative values to 50 key factors to ascertain a community's strengths and challenges associated with recruitment and retention and their relative importance to the pharmacist workforce. The cumulative PharmCAQ scores indicated the tool was sensitive enough to differentiate high- and low-performing communities. Overall, the highest-rated factors considered most vital to pharmacist recruitment and retention were the reputation of the pharmacy, the ability of the pharmacist to be independent and autonomous, the loyalty of the community to the pharmacy, the level and stability of monetary compensation and the breadth of tasks available to a pharmacist. This study identified the strengths and challenges of participating communities and provided an insight into the shared factors to consider in recruiting and retaining pharmacists. Further, each community has unique strengths that can further be promoted in recruitment, flagging where limited resources are best used to address site specific challenges. This is more likely to ensure the matching of the right candidate with the right community.


Neuropsychiatric effects of tamoxifen: Challenges and opportunities.
Epidemiological, clinical, and basic research over the past thirty years have described the benefits of estrogen on cognition, mood, and brain health. Less is known about tamoxifen, a selective estrogen receptor modifier (SERM) commonly used in breast cancer which is able to cross the blood-brain barrier. In this article, we review the basic pharmacology of tamoxifenas well as its effects on cognition and mood. The literature reveals an overall impairing effect of tamoxifen on cognition in breast cancer patients, hinting at central antiestrogen activity. On the other hand, tamoxifen demonstrates promising effects in psychiatric disorders, like bipolar disorder, where its therapeutic action may be independent of interaction with estrogen receptors. Understanding the neuropsychiatric properties of SERMs like tamoxifen can guide future research to ameliorate unwanted side-effects and provide novel options for difficult to treat disorders.


Enriched Endogenous Omega-3 Polyunsaturated Fatty Acids Protect Cortical Neurons from Experimental Ischemic Injury.
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert therapeutic potential in a variety of neurological disorders, including ischemic stroke. However, the underlying mechanisms still lack investigation. Here, we report that cultured cortical neurons isolated from fat-1 mice with high endogenous n-3 PUFAs were tolerant to oxygen-glucose deprivation/reperfusion (OGD/R) injury. Fat-1 neurons exhibited significantly attenuated reactive oxygen species (ROS) activation induced by OGD/R injury, upregulated antiapoptotic proteins Bcl-2 and Bcl-xL, and reduced cleaved caspase-3. Exogenous administration of docosahexaenoic acid (DHA), a major component of the n-3 PUFA family, resulted in similar protective effects on cultured cortex neurons. We further verified the protective effects of n-3 PUFAs in vivo, using a mini ischemic model with a reproducible cortical infarct and manifest function deficits by occlusion of the distal branch of the middle cerebral artery with focused femtosecond laser pulses. The Fat-1 animals showed decreased ROS expression and higher level of glutathione in the injured brain, associated with improved functional recovery. We therefore provide evidence that n-3 PUFAs exert their protective effects against ischemic injury both in vitro and in vivo, partly through inhibiting ROS activation.


Isostatic ultra-high-pressure effects on supercooled melts in colloidal triglyceride dispersions.
Colloidal triglyceride dispersions can form metastable supercooled melts that need tedious tempering processes to be transformed into a crystalline state. We investigated the possibility of transforming the supercooled melts into crystals in a short time by treatment with isostatic high pressure. Nanosized supercooled melts of triglycerides in aqueous dispersions (prepared by high-pressure homogenization) were exposed to isostatic ultrahigh pressure for short periods to initialize crystallization processes. The dispersions were analyzed with different appropriate measuring methods such as differential scanning calorimetry, nuclear magnetic resonance, X-ray scattering, and electron paramagnetic resonance. The resulting particle sizes were estimated by photon correlation spectroscopy and transmission electron microscopy. The results of differential scanning calorimetry, X-ray, and nuclear magnetic resonance experiments show the induction of triglyceride particle crystallization by high-pressure treatment. Electron paramagnetic resonance spectroscopy shows that the triglyceride crystallization coincides with relocation of the lipophilic probe into a more polar environment. Transmission electron microscopy micrographs show the transformation of supercooled liquid particles into crystallized anisotropic particles. Crystal transformation in nanoscaled systems can be delayed for months, depending on the materials and the composite. It is shown that isostatic high-pressure treatment can be a valuable method to induce, accelerate, and control crystallization processes in specific colloidal triglyceride dispersions.


Comparison of different ovarian stimulation protocols for gamete intrafallopian transfer in patients with minimal and mild endometriosis.
Three different stimulation protocols were tested in patients affected by stage I and II endometriosis with no other causes of infertility, and scheduled for the gamete intrafallopian transfer technique. In two protocols a gonadotropin hormone-releasing hormone analog was used. The analog was started 6 months before stimulation in the former and along with the exogenous gonadotropin in the latter. Patients receiving only gonadotropin served as controls. Sixty patients were selected for this study; 55 reached laparoscopy. Whereas patients receiving either gonadotropin alone or simultaneous analog and gonadotropin had similar pregnancy rates, this was much higher in the patients undergoing a prolonged, medically induced hypoestrogenism. Prolonged analog pretreatment before ovarian stimulation may give better chances of success in endometriosis patients undergoing assisted reproduction techniques.


Trainees' perceptions of being allowed to fail in clinical training: A sense-making model.
Clinical supervisors allow trainees to fail during clinical situations when trainee learning outweighs concerns for patient safety. Trainees perceive failure as both educationally valuable and emotionally draining; however, the nuance of supervised failures has not been researched from the trainee perspective. This study explored trainees' awareness and their experience of failure and allowed failure to understand those events in-depth. We interviewed 15 postgraduate trainees from nine teaching sites in Europe and Canada. Participants were a purposive sample, representing 1-10 years of clinical training in various specialties. Consistent with constructivist grounded theory, data collection and analysis were iterative, supporting theoretical sampling to explore themes. Trainees reported that failure was a common, valuable, and emotional experience. They perceived that supervisors allowed failure, but they reported never having it explicitly confirmed or discussed. Therefore, trainees tried to make sense of these events on their own. If they interpreted a failure as allowed by the supervisor, trainees sought to ascertain supervisory intentions. They described situations where they judged supervisor's intentions to be constructive or destructive. Our results confirm that trainees perceive their failures as valuable learning opportunities. In the absence of explicit conversations with supervisors, trainees tried to make sense of failures themselves. When trainees judge that they have been allowed to fail, their interpretation of the event is coloured by their attribution of supervisor intentions. Perceived intentions might impact the educational benefit of the experience. In order to support trainees' sense-making, we suggest that supervisory conversations during and after failure events should use more explicit language to discuss failures and explain supervisory intentions.


Weight change and healthcare resource use in English patients with type 2 diabetes mellitus initiating a new diabetes medication class.
The aim of this study was to investigate the association between weight change and healthcare resource use (HCRU) and costs in English primary care patients with type 2 diabetes mellitus (T2DM) initiating treatment with a new diabetes medication class. Patients diagnosed with T2DM initiating a new diabetes medication class (first-line, switch or add-on treatment) were selected from Clinical Practice Research Datalink. Weight change (index date) was measured 6 months after initiating new treatment. HCRU was derived up to 1 year after index. Adjusted analyses evaluated the association between weight change and HCRU and costs (GBP, 2013 prices). Of 9031 patients, about half (n = 4901) experienced < 3% weight change (weight neutral); the proportions gaining or losing weight were similar. Compared with the weight neutral group, weight gain was associated with significantly increased total costs within a year (3.0-5.4% weight gain: £58.9; p = 0.01, ≥ 5.5% weight gain: £52.9; p = 0.04) and diabetes primary care costs (3.0-5.4% weight gain: £29.2; p < 0.001, ≥ 5.5% weight gain: £34.2; p < 0.001). This included increased rates of prescribing drugs for diabetes and, in ≥ 5.5% weight gain, increased primary care contacts. A ≥ 5.5% weight loss was associated with increased hospital admissions (odds ratio = 1.4; p < 0.0001) and total costs (£126.3; p < 0.001). Weight gain after initiating a new glucose-lowering medication is associated with increased prescribing and contact with primary care clinicians, with increased costs in primary care and total spending. This study supports that weight gain in diabetes is associated with increased healthcare costs.


Variability of the caprine whey protein genes and their association with milk yield, composition and renneting properties in the Sarda breed: 2. The BLG gene.
The variability of the promoter region and the 3'UTR (exon-7) of the BLG gene, encoding the β-lactoglobulin, was investigated by sequencing in 263 lactating Sarda goats in order to assess its association with milk traits. Milk traits included: milk yield, fat, total protein and lactose content, pH, daily fat and protein yield (DFPY), freezing point, milk energy, somatic cell count, total microbial mesophilic count, rennet coagulation time (RCT), curd firming rate (k20) and curd firmness (a30). A total of 7 polymorphic sites were detected and the sequence analysed was given accession number KM817769. Only three SNPs (c.-381C>T, c.-323C>T and c.*420C>A) had minor allele frequency higher than 0.05. The effects of farm, stage of lactation and the interaction farm × stage of lactation significantly influenced all the milk traits (P T and c.*420C>A (P T (P < 0.001). The c.-381TT homozygous goats showed lower pH, RCT and k20 than c.-381CT (P < 0.05). In conclusion the polymorphism of the goat BLG gene did not affect the total protein content of the Sarda goat milk, and only weakly influenced RCT and k20. On the other hand, an interesting effect on milk yields and DFPY emerged in two SNPs. This information might be useful in dairy goat breeding programs.


Differential role of vasoactive prostanoids in porcine and human isolated pulmonary arteries in response to endothelium-dependent relaxants.
The pig is increasingly being used in medical research, both as a model of the human cardiovascular system, and as a possible source of organs for xenotransplantation. However, little is known about the comparative functions of the vascular endothelium between porcine and human arteries. We have therefore compared the effects of two endothelium-dependent vasorelaxants, acetylcholine (ACh) and the Ca2+-ATPase inhibitor, cyclopiazonic acid (CPA) on the porcine and human isolated pulmonary artery using isometric tension recording. ACh and CPA produced endothelium-dependent relaxations of both the human and porcine pulmonary arteries. In the porcine pulmonary artery, the cyclo-oxygenase inhibitor, flurbiprofen had no effect on relaxations to ACh (Emax: control 67.8+/-8.8% versus 72.4+/-9.5% (n=11)) or CPA (Emax: control 79.6+/-5.0% versus 94.0+/-10.6% (n=7)). The nitric oxide synthase inhibitor, L-NAME converted relaxations to both ACh and CPA into contractile responses (maximum response: ACh 30.0+/-11.1% (n = 10); CPA 80.4+/-26.2% (n = 8) of U46619-induced tone). These contractile responses in the presence of L-NAME were abolished by flurbiprofen. In the human pulmonary artery, L-NAME and flurbiprofen partly attenuated relaxations to ACh (Emax: control: 45.1+/-12.1%; flurbiprofen: 33.4+/-13.5%; L-NAME: 10.1+/-7.2%) and CPA (Emax: control: 78.1+/-5.5%; flurbiprofen: 69.6+/-7.2%; L-NAME 37.9+/-10.7% of U46619-induced tone). These responses were abolished by the combination of both inhibitors. We have demonstrated that while the release of nitric oxide is important in responses to endothelium-dependent vasorelaxants in both human and porcine pulmonary arteries, in the human arteries, there is an important role for vasorelaxant prostanoids whilst in the porcine arteries, vasoconstrictor prostanoids are released.


Production of antiviral and migration inhibitory activities in the peritoneum of mice after inoculation with allogenic Ehrlich ascites tumor cells.
Peritoneal inoculation of Ehrlich ascites cells into mice stimulates the appearance of migration inhibitory factor (MIF) not only in the peritoneum but also in the circulation of mice. Whereas the MIF-activity in the peritoneum reached maximum at 6 days and disappeared within 17 days, the MIF-activity of sera reached maximum levels at about 11 days after intraperitoneal inoculation of tumor cells (10(6) of EAC per mouse). In addition, an antiviral activity of peritoneal exudates was observed in the early stage (24--72 h) of tumor challenge. The time-course of appearance of both MIF and AV-inhibitor are presented. A significant decrease of MIF-activity was noted when the tumor-inoculated mice were treated with ds-RNA, antithymocyte serum and cyclophosphamide, respectively. The appearance of antiviral activity in the peritoneum of tumor-inoculated mice seems to be macrophage-dependent. Although the antiviral factor meets several criteria of interferons, further studies are required for its characterization.


CYBA as a Potential Biomarker for Renal Cell Carcinoma: Evidence from an Integrated Genetic Analysis.
Oxidative stress plays an important role in various pathogenic processes, and disruption in the coordinated production of NADPH oxidase (NOX)-derived reactive oxygen species has been associated with carcinogenesis. However, little is known about whether genetic variants in NOX can contribute to the development of renal cell carcinoma (RCC). This study aimed to bridge this knowledge gap by analysing the association of 10 single-nucleotide polymorphisms in the phagocyte NOX genes, CYBA and CYBB, with RCC risk and tumour characteristics in 630 RCC patients and controls. Differential gene expression and patient prognosis analyses were performed using gene expression data obtained from public databases. Multivariate analysis and multiple testing corrections revealed the A allele of rs7195830 in CYBA to be a significant risk allele for RCC, compared to the G allele [odds ratio (OR)=1.70, 95% confidence interval (CI)=1.27-2.26, p<0.001]. A pooled analysis of 17 renal cancer gene expression datasets revealed a higher CYBA expression in RCC than in normal tissues. Moreover, high CYBA expression was associated with advanced tumour characteristics and worse patient prognosis. CYBA might play an oncogenic role in RCC and serve as a predictive indicator of patient prognosis.


Americans with Disabilities Act: Its Importance in Special Care Dentistry.
This article focuses on understanding the Americans with Disabilities Act and developmental disabilities for health care providers in special care dentistry. Essential to this awareness is a comprehension of statutory and regulatory requirements and how state disability acts can be more rigorous in application. Developmental disabilities are re-examined in the context of the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Understanding of intellectual disability, epilepsy, autism spectrum disorder, and cerebral palsy is necessary because the management of oral health considerations for special care patients has become ever more complex and indispensable.


Spermatozoa motility and fructolysis--comparative study of samples obtained by masturbation and with plastic collectors.
A comparative study was made of spermatozoa motility and fructolysis with semen normal donors incubated in glass flasks and plastic collectors at room temperature (22 degrees to 25 degrees C). With the results obtained we came to the conclusion that poliethylene plastic collectors of low density, polimero 0.921, thickeness 20 to 30 mu, do not affect motility of fructose consumption of semen from normal donors. This material showed similar conditions to those in glass flasks.


Active clearance of chest drainage catheters reduces retained blood.
Chest tubes are used to clear blood from around the heart and lungs after heart surgery, but they can be obstructed by a blood clot, leading to retained blood syndrome (RBS). We sought to examine the frequency of RBS and associated morbidity, and to determine the influence of a preventative active chest tube clearance (ATC) protocol on these outcomes. A multidisciplinary team developed a simple protocol to institute ATC to preventatively clear chest tubes of clot during the first 24 hours after heart surgery. An extensive educational in-service was performed before universal implementation (phase 1). We retrospectively compared data collected prospectively from 1849 patients before universal implementation (phase 0) with data from 256 patients collected prospectively after universal implementation (phase 2), and then used propensity matching for outcomes assessment. In propensity-matched patients, 19.9% of patients had interventions for RBS (phase 0). After the implementation of ATC (phase 2), the percent of patients with interventions for RBS was reduced to 11.3%, representing a 43% reduction in RBS (P = .0087). These patients had a 33% reduced incidence of postoperative atrial fibrillation from 30% (78 out of 256) in phase 0 to 20% (52 out of 256) in phase 2. (P = .013). ATC is associated with a reduced need for interventions for RBS and postoperative atrial fibrillation. Our findings underscore the importance of maintaining chest tube patency in the early hours after cardiac surgery.


Hypertensive disorders of pregnancy share common cfDNA methylation profiles.
Hypertensive disorders of pregnancy (HDP) contribute substantially to perinatal morbidity and mortality. Epigenetic changes point towards cardio-metabolic dysregulation for these vascular disorders. In early pregnancy, epigenetic changes using cell free DNA (cfDNA) are largely unexplored. We aimed to investigate these in HDP between 11 and 14 weeks of gestation by analysis of cfDNA methylation profiles in patients with hypertensive disorders. We identified patients without chronic hypertension but with subsequent development of preeclampsia (PE) (n = 11), with chronic hypertension (HT) but without PE development (n = 14), and lacking both PE and HT (n = 422). We matched patients according to PE risk factors into three groups (n = 5 each group): (1) PE: no HT but PE development, (2) HT: chronic hypertension but no PE and (3) Control: no PE or HT. We successfully optimized our cfDNA isolation process prior to whole genome bisulfite sequencing. Analysis of cfDNA methylation changes indicate a common predisposition in PE and HT groups, chiefly of maternal origin. Assessment of significant differentially methylated regions and annotated genes point towards a common cardiovascular predisposition in preeclampsia and hypertension groups in the first trimester. We postulate the pivotal role of the maternal cardiovascular system in HDP, which is already evident in the first trimester.


Cosmetic dermatology and physicians' ethical obligations: more than just hope in a jar.
Cosmetic dermatology provides new esthetic options for patients and expanded practice opportunities for physicians. Perhaps because of its recent inception, discussions of the ethical quandaries in the field are relatively new. Certainly, these dilemmas remain unresolved. This article aims to identify ethical obligations that practicing cosmetic dermatologists and the professional societies that regulate them should assume. Heightened attention to familiar duties and new attention to proposed responsibilities will enhance patient safety and choice. It will also ensure that dermatologists practice their craft in an ethically sound manner.


Development of a screening system for detection of somatic mutations. I. Enzyme immunoassay for detection of antibodies against specific hemoglobin determinants.
A solid-phase enzyme immunoassay for the detection of antibodies, specific for hemoglobin (Hb) is described. The application of glutaraldehyde resulted in a sensitive assay and allowed the use of urea, which is an important advantage if polypeptides not soluble in aqueous buffers are to be used. Mutation-carrying Hb chains can be purified, solubilized in urea and used in the immunoassay to monitor the purification and selection of antibodies specific for these variants. Specific antibodies are the main tools for the development of a hemoglobin-locus mutation system for detection of potentially mutagenic environmental agents. With erythrocytes as target cells, this system permits in vivo monitoring of subjects under exposure. Conventional antibody production, however, frequently turns out to be unsuccessful. The production of monoclonal antibodies has several advantages over conventional antibody production, but a sensitive antibody screening system is essential. Because of the sensitivity and the ease with which a large panel of antibody fractions against a vast panel of Hb antigens can be examined, the described immunoassay has potential value for the screening of hybridoma cultures.


Lethal effect of dehydroleucodine (DhL) on amphibian Bufo arenarum embryos.
The dehydroleucodine is a sesquiterpene lactone isolated from Artemisia douglasiana Besser which is used in popular medicine. Toxicity tests using embryos of amphibian have been widely used in order to predict toxic effects of different compounds. However, to our knowledge, there are not studies focussed on the toxic effects of dehydroleucodine on Bufo arenarum, which is an anuran widely distributed in South America. The effect of dehydroleucodine on the survival of embryos was evaluated in an acute test during the early life stage of B. arenarum embryos. Lethality and the degree of adverse effects were dehydroleucodine dose-dependent. Overall, amphibian early life stages appeared to be more susceptible to the embryotoxicity associated with exposure to dehydroleucodine, especially at concentration greater that 3mM. This increased susceptibility may result from the relatively high rate of cellular differentiation and morphogenesis that occurs at this early stage of development.


[Health and demographic status of unauthorized immigrants: the Albanian refugees landed in Italy (Apulia) in 1997].
This study is aimed at assessing the health care demand of the Albanian groups arrived in Italy (Apulia) in 1997 and accommodated in the Cassano and Palese refugee camps. The analysis is based on the forms filled in on their arrival and first aid registers. Albanian health and demographic official data were also analyzed. The most common health problems observed amongst refugee groups were slight illnesses (23.3%), respiratory tract infections (11.3%), gastroenteritis (9.9%). In the light of these data, the refugees' status does not appear to be critical, although there remains the need to carry out constant monitoring to prevent infectious diseases and improve the quality of social facilities.


Campylobacter pyloridis degrades mucin and undermines gastric mucosal integrity.
The role of Campylobacter pyloridis, a spiral bacteria associated with gastritis and peptic ulcers in weakening the mucus component of gastric mucosal barrier was investigated. The colonies of bacteria, cultured from antral mucosal biopsies of patients undergoing gastroscopy, were washed with saline, passed through sterilization filter and the filtrate was examined for protease and glycosylhydrolase activities. The obtained results revealed that the filtrate exhibited a strong proteolytic activity not only towards the typical protein substrates such as albumin but also towards gastric mucin. Optimum enzymatic activity for degradation of mucin was attained at pH 7.0 and the protease activity was found in a low m.w. (less than 50K) protein fraction. The filtrate showed little glycosylhydrolase activity and did not cause the hydrolysis of mucin carbohydrates. The data suggest that C pyloridis infection weakens the gastric mucosal defense by causing proteolytic degradation of mucin component of the protective mucus layer.


A comparison of pretreatment with a topical combination of nonivamide and nicoboxil and surgical delay in a random pattern skin flap model.
Delay procedures are intended to increase flap safety in otherwise risky flaps. In general they are of surgical nature, making an additional operation necessary. To overcome this drawback, non-surgical alternatives that may be as effective as the surgical procedure are constantly sought. We have previously shown an effective postoperative method to augment flap viability by topical application of a combination of nicoboxil and nonivamide. The goal of this study was to investigate whether this combination is also effective in inducing a delay effect in experimental skin flaps. Thirty male Wistar rats were randomised into three groups (n=10), and a standardised dorsal random pattern (6x2 cm) skin flap was raised on each animal. In rats of group 1, a surgical delay procedure was carried out 1 week prior to full flap harvest by incising the two longitudinal borders of the flap. In group 2 rats, the whole flap area was treated by the topical ointment once a day in order to induce a chemical delay effect for 7 days prior to flap harvest. In group 3 rats, the flap was harvested without any prior intervention and this group served as a control. Skin flap viability was assessed on postoperative day 7, and the extent of the viable skin flap area was compared between the three groups. The surgical delay procedure resulted in a significant increase in the viable area of the skin flaps compared to the chemical delay group and the control group. Additionally, there was a significant increase in skin flap viability between the chemical group and the control group (mean percentage of viable skin flap area in surgical delay group, 80.9+/-15.6; nonivamide/nicoboxil pre-treated group, 71.8+/-4.9; control group, 60.7+/-2.1; p<0.05). Although not as effective as the surgical delay procedure, the topical combination of nicoboxil and nonivamide proved to be of significant value in order to ameliorate ischemic necrosis in experimental skin flaps. Due to its ease and safety in application, this ointment may prove clinically useful in selected situations, especially when combined with an additional postoperative treatment.


Pharmacokinetics of and maintenance dose recommendations for vancomycin in severe pneumonia patients undergoing continuous venovenous hemofiltration with the combination of predilution and postdilution.
Therapeutic vancomycin levels are difficult to maintain in severe pneumonia patients who are receiving IV vancomycin therapy while on continuous venovenous hemofiltration (CVVH). The objective of this study was to determine the pharmacokinetics and maintenance dose recommendations of vancomycin in severe pneumonia patients receiving CVVH. A prospective study was conducted in the intensive care unit of a university hospital. Ten severe pneumonia patients receiving vancomycin and CVVH treatment were determined the initial and steady-state pharmacokinetics of vancomycin. CVVH was performed in mixed predilution and postdilution mode with a blood flow rate of 180 mL/min and an ultrafiltrate flow rate of 30-40 mL/kg/h. Group A received an initial dose of 500 mg only, whereas group B received 500 mg every 12 h until steady state is achieved. Serum and ultrafiltrate were collected over 12 h after infusion of vancomycin. After initial dosing, the mean sieving coefficient (SC) was 0.72 ± 0.02, and CVVH clearance (CLCVVH, 1.35 ± 0.03 L/h) constituted 60.55% ± 13.69% of total vancomycin clearance (CLtot, 2.36 ± 0.72 L/h). When steady state was reached, the SC of the patients was 0.71 ± 0.03, and the CLCVVH (1.34 ± 0.06 L/h) accounted for 66.96% ± 6.05% of the CLtot (2.03 ± 0.27 L/h). The recommended maintenance dose for vancomycin in severe pneumonia patients was 400-650 mg every 12 h, which was calculated based on CLtot, to achieve a trough concentration of 15-20 mg/L at steady state. Single administration or multiple administration does not affect SC and CLCVVH. Owing to therapeutic vancomycin levels is difficult to maintain in severe pneumonia patients who are receiving IV vancomycin therapy while on CVVH, close monitoring of serum trough concentrations is required.


A quantitative technique for growing human adult skeletal muscle in culture starting from mononucleated cells.
A quantitative and reproducible technique for establishing primary surface cultures from normal and diseased human muscle is described. Successful cultures were prepared from both fresh muscle and that stored up to 96 hr at 4 degrees C. The CPK activity of the muscle cells ranged between 0.5-3.0 micronmoles creatine per min per mg protein at 30 degrees C, thus indicating a high degree of differentiation. Spontaneous contractions were observed in 4 out of the 22 cultures established. Nerve cells were not required to achieve this level of differentiated function. No gross differences in plating efficiency, rate of myotube formation or CPK specific activity were found for the diseased muscle cells cultured so far. However, a 5--10-fold higher cell yield was obtained from muscles of patients with an inflammatory myopathy. The advantages of this technique for carrying out comparative studies on normal and dystrophic muscle cells are discussed.


[Adjuvant simultaneous mistletoe chemotherapy in breast cancer--influence on immunological parameters, quality of life and tolerability].
The objective of this feasibility study was to identify suitable surrogate parameters for a randomized confirmative trial with mistletoe treatment in patients with breast cancer. Tolerability,quality of life, hematological and immunological parameters were evaluated during postoperative chemotherapy. This prospective open 2-armed non-randomized study compared 33 patients with primary breast cancer during adjuvant chemotherapy (CMF or EC) and simultaneous treatment with Iscador M 5 mg spezial (IM spez) with 33 controls without mistletoe. Before and 14 days after chemotherapy hematology, lymphocyte subpopulations, stimulability of lymphozytes and quality of life(EORTC QLQ-C30, BR23) were assessed. Although there was a slight increase in thrombocytes within normal values (p =0.01), no clinically important laboratory parameter was favorable in the mistletoe group during the trial. There was no difference in immuno suppression due to chemotherapy. We found a lower frequency of nausea/vomiting and systemic therapy side effects (EORTC)during add-on-therapy with mistletoe (p = 0.02 each). Glucocorticoidco treatment in the mistletoe group was less frequent (p = 0.006), as well. In general, the add-on-therapy was well tolerated, taking into account that dose reduction was often necessary at the beginning of the chemotherapy because of large local reactions at the site of the injections. Therefore, blinding seems impossible if treatment with mistletoe and chemotherapy is started more or less simultaneously. Reductions in quality of life seem to be smaller during add-on-therapy with mistletoe. Laboratory parameters showed no difference compared to the control group. Quality of life and reduction of glucocorticoid cotreatment should be further evaluated.


[Effects of tumor necrosis factor-α on release of MMP-3, MMP-9, and interleukin-17 in mouse bone marrow-derived mast cells in vitro].
To investigate the effect of tumor necrosis factor-α (TNF-α) on the release of matrix metalloproteinase-3 (MMP-3), MMP-9, and interleukin-17 (IL-17) in cultured mouse bone marrow-derived mast cells (BMMCs) in vitro. Primarily cultured mouse BMMCs at 8 weeks were exposed PBS (control) or TNF-α at the concentrations of 2, 10, or 50 ng/mL for 12 or 24 h. Real-time PCR was performed to detect the mRNA expressions of MMP-3, MMP-9, and IL-17 in the exposed cells. A 12-hour exposure of the BMMCs to TNF-α caused significantly increased expressions of MMP-3, MMP-9, and IL-17 in a concentration-dependent manner (P<0.05). Prolonged exposures of the cells to 2 and 10 TNF-α for 24 h further increased MMP-3, MMP-9, and IL-17 mRNA expressions, but exposure to 50 ng/mL TNF-α for 24 h increased only MMP-3 and MMP-9 expressions but not IL-17 mRNA expression. TNF-α treatment of primarily cultured BMMCs can significantly increase the cellular expressions of MMP-3, MMP-9, and IL-17 mRNA in a time- and dose-dependent manner.


Domain interactions of H-2 class I antigens alter cytotoxic T-cell recognition sites.
H-2 class I antigens appear to direct the recognition of virus-infected and neoplastic transformed cells by cytotoxic T lymphocytes (CTLs). Here, to identify the regions of class I antigens involved in CTL recognition, four hybrid class I genes were constructed in which exons were exchanged between the H-2Kb and H-2Db genes. These class I genes were expressed in mouse L cells and recognition of the hybrid Kb/Db antigens by CTLs and monoclonal antibodies specific for either Kb or Db was investigated. The pattern of CTL and monoclonal antibody recognition obtained indicates three correlations between structure and function of class I antigens. First, most CTL recognition sites and alloantigenic determinants are located on domains 1 and 2 of the antigen molecule. Second, these CTL recognition sites and alloantigenic determinants are not influenced by interaction of domains 1 and 2 with polymorphic regions of domain 3. Third, in contrast, interaction between domains 1 and 2 alters these CTL recognition sites and alloantigenic determinants. The alteration of CTL recognition sites by interaction between domains 1 and 2 suggests that a CTL site may be formed by amino acids from both domains 1 and 2, or that the conformation of amino acids at a CTL site may be altered by interactions between domains 1 and 2. Through these two features, the conformation of CTL recognition sites on H-2 class I antigens may be sensitive to alteration by interaction of either domain 1 or 2 with viral antigens.


The role of activin type I receptors in activin A-induced growth arrest and apoptosis in mouse B-cell hybridoma cells.
Activins transduce their signals by binding to activin type I receptors and activin type II receptors, both of which contain a serine/threonine kinase domain. In this study, we established stable transfectants expressing two types of activin receptors, ActRI and ActRIB, to clarify the role of these receptors in activin signalling for growth inhibition in HS-72 mouse B-cell hybridoma cells. Over-expression of ActRI suppressed activin A-induced cell-cycle arrest in the G1 phase caused by inhibition of retinoblastoma protein phosphorylation through induction of p21CIP1/WAF1, a cyclin-dependent kinase inhibitor, and subsequent apoptosis. In contrast, HS-72 clones that over-expressed ActRIB significantly facilitated activin A-induced apoptosis. These results indicate that ActRI and ActRIB are distinct from each other and that the ActRI/ActRIB expression ratio could regulate cell-cycle arrest in the G1 phase and subsequent apoptosis in HS-72 cells induced by activin A.


Changes in plasma mass-spectral profile in course of treatment of non-small cell lung cancer patients with epidermal growth factor receptor tyrosine kinase inhibitors.
Our previous study showed that pretreatment serum or plasma Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry may predict clinical outcome of non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). In this study, plasma proteomic profiles of NSCLC patients were evaluated in the course of EGFR TKIs therapy. Plasma samples were collected at baseline, in the course of gefitinib therapy and at treatment withdrawal. Samples were analyzed by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Acquired spectra were classified by the VeriStrat test into "good" and "poor" profiles. The association between VeriStrat classification and progression-free survival (PFS) and overall survival (OS), and types of clinical progression, was analyzed. Plasma samples from 111 NSCLC patients treated with gefitinib were processed. VeriStrat "good" classification at baseline correlated with longer PFS (hazard ratio [HR], 0.54; 95% confidence interval, 0.35-0.83; p = 0.005) and OS (HR, 0.40; 95% confidence interval, 0.26-0.61; p < 0.0001), when compared with VeriStrat "poor." Multivariate analysis confirmed longer PFS (HR, 0.52; p = 0.025) and OS (HR, 0.44; p = 0.001) in patients classified as VeriStrat "good", when VeriStrat was considered as a time-dependent variable. About one-third of baseline "good" classifications had changed to "poor" at the time of treatment withdrawal; progression in these patients was associated with the development of new lesions. Our findings support the role of VeriStrat in the assistance in treatment selection of NSCLC patients for EGFR TKI therapy and its potential utility in treatment monitoring.


Dysregulated expression and functions of microRNA-330 in cancers: A potential therapeutic target.
As small non-coding RNAs, MicroRNAs (miRNAs) bind to the 3' untranslated region (3'-UTR) of mRNA targets to control gene transcription and translation. The gene of miR-330 has two miRNA products, including miR-330-3p and miR-330-5p, which exhibit anti-tumorigenesis and/or pro-tumorigenesis effects in many kinds of malignancies. In cancers, miR-330-3p and miR-330-5p aberrant expression can influence many malignancy-related processes such as cell proliferation, migration, invasion, apoptosis and epithelial-mesenchymal transition, as well as angiogenesis and responsiveness to treatment. In many cancer types (such as lung, prostate, gastric, breast, bladder, ovarian, colorectal, and pancreatic cancer, and osteosarcoma), miR-330-5p acts as an anti-tumor agent. These cancers have low levels of miR-330-5p that leads to the upregulation of the tumor promotor target genes leading to tumor progression. Here, overexpression of miR-330-5p using miRNA inducers can prevent tumor development. Dual roles of miR-330-5p have been also indicated in the thyroid, liver and cervical cancers. Moreover, miR-330-3p exhibits pro-tumorigenesis effects in lung cancer, pancreatic cancer, osteosarcoma, bladder cancer, and cervical cancer. Here, downregulation of miR-330-3p using miRNA inhibitors can prevent tumor development. Demonstrated in breast and liver cancers, miR-330-3p also has dual roles. Importantly, the activities of miR-330-3p and/or miR-330-5p are regulated by upstream regulators long non-coding RNAs (lncRNAs), including circular and linear lncRNAs. This review comprehensively explained miR-330-3p and miR-330-5p role in development of cancers, while highlighting their downstream target genes and upstream regulators as well as possible therapeutic strategies.


The effect on expiratory flow rate of maintaining bag compression during manual hyperinflation.
Operator performance during the expiratory phase of manual hyperinflation appears to vary between physiotherapists for Mapleson-B or C circuits. Some physiotherapists release the valve but maintain compression of the bag, whereas others release both the valve and the bag. The effect of this difference on peak expiratory flow rate (PEFR) has not been reported. The aim of this study was to document the effect of maintaining bag compression during expiration on PEFR and inspiratory to expiratory flow rate ratio (I:E). Six physiotherapists with experience using manual hyperinflation participated. A within-subjects repeated measures design was used. Subjects performed manual hyperinflation using a Mapleson-C circuit with 'rapid release', releasing the valve only, or releasing both the bag and the valve, during expiration in a test lung model. Inspiratory time was controlled using a metronome and flows were measured with a heated pneumotachometer. Maintaining bag compression significantly reduced PEFR (1.54 (0.08) vs 2.00 (0.07) l/sec, p = 0.008) and increased I:E flow rate ratio (0.65 (0.04) vs 0.50 (0.02), p = 0.02) for the Mapleson-C circuit at a 1.4 litre target volume. There were no significant differences for these measures between techniques when subjects emptied the bag. The effect needs to be confirmed in the clinical setting.


Targeting Estrogen Receptor Sites in Human Breast Cancer Cell Line T47D With Copper Conjugates of Nonsteriodal Anti-inflammatory Drug Derivatives: Antiproliferative Activity of Ketoprofen Derivative and its Copper Complex.
A square planar copper complex of derivatized NSAID drug (Ketoprofen thiosemicarbazone [3-benzoyl-alpha-methyl benzene acetic acid thiosemicarbazone]), is characterized by elemental analysis, spectroscopy, electrochemistry and magnetic susceptibility studies which exhibits dose-dependent and enhanced antiproliferative effects on human breast cancer cell line T47D rich in progesterone receptors.


Cardiac output and regional myocardial contraction in anorexia nervosa.
The study measured cardiac output and assessed regional myocardial contraction in 14 patients with anorexia nervosa, some of whom also had bulimia, and in 15 controls. The experimental and control groups were not significantly different in age or body surface area (p = greater than 0.05). To evaluate regional myocardial contraction, 12 of 14 anorexia nervosa-bulimia (ANB) patients were studied in the acute phase and once serially at a mean interval of 1.5 years by assessing the movement of each left ventricular wall segment toward the center of the ventricle as imaged in the precordial short axis. Cardiac output was measured in the ascending aorta by pulsed Doppler for control subjects and for 13 ANB patients. Regional myocardial contraction was normal for all controls, but eight of 14 ANB patients showed regional myocardial contraction abnormalities. Between studies, four of these eight demonstrated improved regional myocardial contraction, three remained unchanged, and one was worse. Mean cardiac output was markedly reduced in ANB patients (2.6 L/min) compared to controls (4.5 L/min) (p = less than 0.001). The low cardiac output in ANB patients was reflected as reduced mean ascending aortic velocity/second (18.5 cm/s) compared to a mean of 22.8 cm/s for controls (p = less than 0.02). Mean ascending aortic area was slightly smaller for ANP patients. Mean peak ascending aortic velocity was significantly lower in ANB patients than in controls (p = less than 0.02). Mitral valve prolapse was seen during at least one examination in seven of 14 ANB patients (0/15 controls) and disappeared in two of three patients following hydration.(ABSTRACT TRUNCATED AT 250 WORDS)


Cancer-related pain in older adults receiving palliative care: patient and family caregiver perspectives on the experience of pain.
Despite an emphasis on pain management in palliative care, pain continues to be a common problem for individuals with advanced cancer. Many of those affected are older due to the disproportionate incidence of cancer in this age group. There remains little understanding of how older patients and their family caregivers perceive patients' cancer-related pain, despite its significance for pain management in the home setting. To explore and describe the cancer pain perceptions and experiences of older adults with advanced cancer and their family caregivers. A qualitative descriptive approach was used to describe and interpret data collected from semistructured interviews with 18 patients (≥65 years of age) with advanced cancer receiving palliative care at home and their family caregivers. The main category 'Experiencing cancer pain' incorporated three themes. The theme 'Feeling cancer pain' included the sensory aspects of the pain, its origin and meanings attributed to the pain. A second theme, 'Reacting to cancer pain', included patients' and family caregivers' behavioural, cognitive (ie, attitudes, beliefs and control) and emotional responses to the pain. A third theme, 'Living with cancer pain' incorporated individual and social-relational changes that resulted from living with cancer pain. The findings provide an awareness of cancer pain experienced by older patients and their family caregivers within the wider context of ongoing relationships, increased patient morbidity and other losses common in the aged.


New trends in photobiology. The interaction of UVA radiation with cultured cells.
Recent work concerning the interaction of UVA radiation (320-380 nm) with cultured cells is reviewed with particular emphasis on the involvement of cellular oxidative stress in the biological effects of this radiation on eucaryotic cells. Possible chromophores are considered and their role in generation of various oxidant species including hydrogen peroxide, superoxide anion, singlet oxygen and hydroxyl radical. DNA and membranes are discussed as possible targets for the lethal action of long wavelength radiation. Four mechanisms of cellular defence are proposed: (1) DNA repair; (2) antioxidant enzymes; (3) endogenous free radical quenchers; (4) inducible protection.


A microcomputer-directed mass spectrometer as a compound-selective detector for gas chromatography.
Determination and quantitation by mass spectrometry can be difficult for compounds in complex biological mixtures where chromatographic interferences are frequently encountered. A gas chromatographic-mass spectrometric system is described which utilizes reverse spectral search and retention time screening to provide a high degree of compound specificity. Computer control of instrument operation, and of data acquisition, analysis and printout allows technologist operators to obtain highly reliable, precise quantitative results using relatively crude sample preparation procedures and short chromatographic times.


Frequent expression of PD-L1 in lymphocyte-rich hepatocellular carcinoma: A report of 4 cases.
Programmed death ligand 1 (PD-L1) is an immune checkpoint inhibitor. PD-L1 binds to its receptor programmed death receptor (PD-1) expressed by immune cells and plays a key role in regulating immune responses. Engagement of PD-L1 on cancer cells and PD-1 on immune cells avoid destruction of tumour cells by immune cells. Immunostaining with PD-L1 has been suggested as a biomarker predictive of antiPD-L1 immunotherapy. Lymphocyte-rich hepatocellular carcinoma (LrHCC) is a rare histological HCC subtype which is characterised by neoplastic epithelial cells intermixed with numerous immune cells. Here in we investigated immunohistochemical PD-L1 expression in 4 cases of LrHCC. Tumour proportion score (TPS) and immune cell score was recorded. Immunophenotypic characterization of the tumour and inflammatory cells was also done. Epstein-Barr encoding region (EBER) in situ hybridization (ISH) assay as performed in all four tumours. Expression of PD-L1 was demonstrated in tumour epithelial cells and immune cells in all four cases. Incomplete to membranous staining was demonstrated in the tumour cells. Tumour proportion score (TPS) was 1.2-20 %. Immune cells demonstrated membranous and cytoplasmic immunostaining. Immune cell score was ≥1 % to >10 %. PD-L1 expression in both tumour and immune cells suggests distinct immunogenic feature and potential role of antiPD-L1 therapies in cases with inoperable disease.


Discovery of novel arylthioacetic acid derivatives as 4-hydroxyphenylpyruvate dioxygenase inhibitors.
4-Hydroxyphenylpyruvate dioxygenase (HPPD) plays an important role in addressing the issue of plant protection research. In a continuing effort to discover novel HPPD inhibitors, we adopted a bioisosterism strategy to design a series of novel arylthioacetic acid scaffold based on the previously discovered aryloxyacetic acid scaffold. This study sheds new light on the discovery of novel HPPD inhibitors. The compounds A1-A30 and B1-B39 were prepared through an efficient synthetic route for in vitro and glasshouse experiments (herbicidal activities, herbicidal activity spectrum, and crop selectivity). Preliminary bioassay results reveal that these derivatives are promising Arabidopsis thaliana HPPD inhibitors, compounds A11 (Ki = 0.021 μmol L-1 ) and B20 (Ki = 0.022 μmol L-1 ), which exhibit similar activities to that of mesotrione (Ki = 0.020 μmol L-1 ). The glasshouse experiments data indicated that compounds B34 displayed excellent herbicidal activity, which was higher compared to that of mesotrione. Moreover, molecular simulation results show that the compounds B20, B34, and mesotrione shared similar interplay with surrounding residues, which led to a perfect interaction with the active site of Arabidopsis thaliana HPPD. Based on herbicidal results, compound B34 was selected for crop selectivity studies (corn injury ≤ 10%), indicating its potential for weed control in corn fields. These bioassay results showed that the compound B34 could be used as a possible lead compound for the development of HPPD inhibitors. © 2020 Society of Chemical Industry.


Two dental x-ray films compared for rater preference using endodontic views.
Four groups of patients were selected during various phases of endodontic therapy to receive two comparable radiographic exposures. One exposure was made with Kodak Ultraspeed dental x-ray film and the second exposure was made with Kodak Ektaspeed dental x-ray film. The films were coded and mounted in a side-by-side format to be judged by thirty raters. A double-blind clinical protocol was followed. Ultraspeed film was judged superior to Ektaspeed film in terms of contrast, image quality and rater satisfaction.