Structural and biophysical insights into the role of CD4 and CD8 in T cell activation.
T cell receptors (TCRs) recognize peptides presented by MHC molecules (pMHC) on an antigen-presenting cell (APC) to discriminate foreign from self-antigens and initiate adaptive immune responses. In addition, T cell activation generally requires binding of this same pMHC to a CD4 or CD8 co-receptor, resulting in assembly of a TCR-pMHC-CD4 or TCR-pMHC-CD8 complex and recruitment of Lck via its association with the co-receptor. Here we review structural and biophysical studies of CD4 and CD8 interactions with MHC molecules and TCR-pMHC complexes. Crystal structures have been determined of CD8αα and CD8αβ in complex with MHC class I, of CD4 bound to MHC class II, and of a complete TCR-pMHC-CD4 ternary complex. Additionally, the binding of these co-receptors to pMHC and TCR-pMHC ligands has been investigated both in solution and in situ at the T cell-APC interface. Together, these studies have provided key insights into the role of CD4 and CD8 in T cell activation, and into how these co-receptors focus TCR on MHC to guide TCR docking on pMHC during thymic T cell selection.


Extracellular presence of the lysosomal proteinase cathepsin B in rheumatoid synovium and its activity at neutral pH.
The presence of the lysosomal proteinases cathepsin B and cathepsin D at extracellular sites in rheumatoid synovium was demonstrated using the antibody capture technique. Unlike cathepsin D, the cysteine proteinase cathepsin B was commonly detected only at the edges of the synovial explants. Radioimmunoassay and enzyme activity assay of these proteinases demonstrated that both were released from rheumatoid synovial cells in comparable amounts. Since lysosomal cathepsin B is unstable and denatured at physiologic pH and the antibody used only recognizes inactivated enzyme, we believe the selective detection of cathepsin B at the edge of the synovium may be due to the proteinase maintaining a native conformation within the explant, where the pH may be low enough to permit this. By use of a fluorescent substrate in a sensitive, continuous enzyme assay, cathepsin B was shown to express significant activity at neutral and alkaline pH before being inactivated. This and earlier work from this laboratory indicate that cathepsin B secreted by rheumatoid synovial cells may possess extracellular activity in vivo and be involved in the degradation of connective tissue macromolecules.


Future shock. Proposed NFPA 99 wet location revision revives a bad idea.
NFPA 99 is one of the principal performance standards on electrical safety for healthcare facilities. However, a proposed change regarding what areas should be considered "wet locations" may have a big effect on the way hospitals equip their operating rooms. ECRI Institute thinks that this change is ill-advised--that it will cost hospitals money with no real benefit, and in some cases could actually increase risks.


[Mesenteric and omental cysts. Apropos of 2 cases].
Two cases of abdominal lymphatic cysts are described, one had an omental origin , and the other arose from jejunal mesentery. Both patients presented with non-specific abdominal pain, and a vague clinical picture. Diagnosis was made through echography findings, which were unmistakable .


Buccal Fat Pad in Primary and Secondary Cleft Palate Repair: A Systematic Review of the Literature.
To review the evidence supporting the use of buccal fat pad (BFP) in primary and secondary cleft palate repair and its short- and long- term clinical outcomes. Systematic review conducted by 2 independent reviewers following PRISMA guidelines. Articles were identified from three databases (Pubmed/Medline, Embase and Web of Science). Search terms included "cleft palate", "palatoplasty", "palate repair", "buccal fat pad". Use of BFP in primary and secondary cleft palatoplasty. Primary outcomes were immediate postoperative complications, postoperative fistula, and maxillary growth. Secondary outcomes were palatal length, speech, and donor site morbidity. Ninety-one reports were retrieved after excluding duplicates. Twenty-three studies were included (13 case series and 10 comparative studies). Overall level of evidence was low. Randomized and non-randomized studies had a high risk of bias. In primary palatoplasty, BFP was more frequently used filling lateral relaxing incisions(57.4%), or in the hard-soft palate junction and covering mucosal defects(30.1%). In these patients, post operative fistula incidence was 2.8%. Two studies found wider transverse maxillary dimensions after BFP use. No higher incidence of bleeding, infection, dehiscence, or flap necrosis was reported. In secondary palatoplasty, no recurrent fistulas were reported for patients undergoing BFP for fistula repair. BFP appears to be associated with a favorable impact in fistula prevention and management, as well as in transverse maxillary growth. However, there is a high heterogeneity among studies, high risk of bias and overall low quality of evidence. More high-quality research with long-term follow-up is warranted.


Dysthymia and mental handicap.
Two cases of dysthymia in mentally handicapped patients are described. The absence of publications on dysthymia in the mentally handicapped is noted. The importance of early diagnosis and treatment with advanced antidepressants and psychotherapy is emphasised.


Effects of Simulation on Nursing Student Stress: An Integrative Review.
The effects of stress on nursing students' health and learning is important to educators. The purpose of this review was to critically integrate the literature related to the stress that nursing students experience regarding high-fidelity simulation (HFS). Literature from multiple search engines and databases was systematically searched. Keywords and Boolean combinations included nursing students, simulation, stress, anxiety, and self-efficacy. Qualitative or quantitative studies published in English between 2010 and 2015 and studies including the effects of simulation on nursing student anxiety and stress were included. Seventeen studies were chosen. Overall, students reported either moderate or high stress associated with simulation, but they rated the HFS experience as a valuable learning tool. This review demonstrated student acceptance of simulation as a learning strategy. However, more high-quality studies are needed to investigate techniques that can be implemented to decrease the negative effects of simulation stress on nursing students. [J Nurs Educ. 2017;56(3):139-144.].


Toward the appropriate interpretation of Alphafold2.
In life science, protein is an essential building block for life forms and a crucial catalyst for metabolic reactions in organisms. The structures of protein depend on an infinity of amino acid residues' complex combinations determined by gene expression. Predicting protein folding structures has been a tedious problem in the past seven decades but, due to robust development of artificial intelligence, astonishing progress has been made. Alphafold2, whose key component is Evoformer, is a typical and successful example of such progress. This article attempts to not only isolate and dissect every detail of Evoformer, but also raise some ideas for potential improvement.


The Transcription of ZIP9 Is Associated With the Macrophage Polarization and the Pathogenesis of Hepatocellular Carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common digestive system cancers (DSCs) with a poor prognosis. Zinc-regulated transporter (ZRT)/iron-regulated transporter (IRT) like protein transporters (ZIPs) encode membrane transport proteins, which are responsible for the absorption of zinc and play important roles in the pathogenesis of various human cancers. Tumor-associated macrophages (TAMs) are important participants in the regulation of tumor microenvironment and the development of HCC. Individual role of each ZIP involved in hepatocarcinogenesis remains elusive. In this study, the transcription patterns of ZIPs in the DSCs were screened firstly through GEPIA2 database. Interestingly, the analysis of the DSCs data showed the distinct mRNA levels of ZIPs between DSCs tissues and healthy controls. Notably, the transcription levels of ZIP2, ZIP5, ZIP8, ZIP9 and ZIP14 were decreased significantly in the tissues of human liver cancer compared to paracarcinoma liver tissues. To further confirm the mRNA transcriptional changes of Zips in HCC, N-Nitrosodiethylamine (DEN) combined with carbon tetrachloride (CCl4) inducing mouse model of HCC were established. Consistently, the mRNA levels of Zip2, Zip9, and Zip14 in liver tissues of HCC induced mice were also decreased compared with the healthy controls. In addition, mouse peritoneal elucidated macrophages (PEMs)-derived M1/M2 macrophages in vitro, as well as human patients of HCC-derived TAMs, were used to examine the transcription levels of ZIPs. Our results showed that both Zip2 and Zip9 were up-regulated in M2-polarized macrophages. Zip2 transcript was also up-regulated M1-polarized macrophages, but Zip9 was slightly down-regulated. TAMs generated from human liver cancer tissues also displayed a decrease in ZIP9 transcription compared to paracarcinoma tissues. To further explore the role of Zip9 in M1/M2 polarization, the siRNA knockdown results revealed that Zip9, but not Zip2, could promote M2 macrophage polarization and impair M1 macrophage polarization. Mechanistically, Zip9 enhances phosphorylated STAT6 to promote M2 macrophage polarization but suppresses the phosphorylation of IκBα/β to inhibit M1 macrophage polarization. Together, our results indicate that ZIP9 may involve in macrophages polarity in HCC development and may be a potent new biomarker for the diagnosis of HCC.


The use of tumor registry data.
The End Results Group, sponsored by the National Cancer Institute, coordinates a national cooperative program for evaluating the results of cancer therapy. Three central tumor registries (in California, Connecticut and Massachusetts) plus nine individual hospital registries (in university hospitals) are participating in the program. During the period 1940-59, there was an encouraging increase in five-year survival rates among patients with carcinomas and sarcomas (solid tumors). Preliminary data for 1955-59 suggest that the upward trend is leveling off. A smaller absolute increase in five-year survival rates occurred among patients with lymphomas and leukemia. These increases in patient survival rates coincided with more frequent use of surgical operation for solid tumors and more frequent use of chemotherapy for lymphomas and leukemia.


The relationship between depressive symptoms, diabetes symptoms, and self-management among an urban, low-income Latino population.
To investigate the prevalence of depression symptoms among Latinos with diabetes following transition from hospital to home and the relationship of depressive symptoms to diabetes symptom severity and self-management activities. 203 Latino patients with diagnosed diabetes completed a survey assessing depressive symptoms (PHQ-9), diabetes symptom severity, and diabetes self-management activities (SDSCA). Characteristics and diabetes outcomes between patients with and without probable major depression were compared. Associations between PHQ-9 scores and diabetes outcomes were assessed. Multivariate regression models evaluated the relationship between depressive symptoms and diabetes outcomes and exercise after controlling for patient characteristics. 31.5% of participants indicated probable major depression (PHQ-9≥10). More severe diabetes symptoms and less reported exercise were associated with higher PHQ-9 scores. Regression models showed no relationship between self-management and depression. More severe diabetes symptoms were significantly associated with being female, married, and having probable major depression. Odds of exercising were reduced by 6% for every one-unit increase in PHQ-9 score. The prevalence of probable depressive symptoms is high in this population. Having depressive symptoms is an indicator of poorer diabetes symptoms. Screening for depressive symptoms may help identify individuals who need additional support with diabetes symptom and self-management.


Genetic correlations between two strains of Durocs and crossbreds from differing production environments for slaughter traits.
The aim of this study was to estimate the genetic correlations between 2 purebred Duroc pig populations (P1 and P2) and their terminal crossbreds [C1 = P1 x (Landrace x Large White) and C2 = P2 x (Landrace x Large White)] raised in different production environments. The traits analyzed were backfat (BF), muscle depth (MD), BW at slaughter (WGT), and weight per day of age (WDA). Data sets from P1, P2, C1, and C2 included 26,674, 8,266, 16,806, and 12,350 animals, respectively. Two-trait models (nucleus and commercial crossbreds) for each group included fixed (contemporary group, sex, weight, and age), random additive (animal for P1 and P2 and sire for C1 and C2), random litter, and random dam (C1 and C2 only) effects. Heritability estimates (+/-SE) for BF were 0.46 +/- 0.04, 0.38 +/- 0.02, 0.32 +/- 0.02, and 0.33 +/- 0.02 for P1, P2, C1, and C2, respectively. Heritability estimates for MD were 0.31 +/- 0.01, 0.23 +/- 0.02, 0.19 +/- 0.01, and 0.12 +/- 0.01 for P1, P2, C1, and C2, respectively. The estimates for WGT and WDA were 0.31 +/- 0.01, 0.21 +/- 0.02, 0.16 +/- 0.01, and 0.18 +/- 0.01 and 0.32 +/- 0.01, 0.22 +/- 0.02, 0.16 +/- 0.01, and 0.19 +/- 0.01, respectively. Genetic correlations between purebreds and crossbreds for BF were 0.83 +/- 0.09 (P1 x C1) and 0.89 +/- 0.05 (P2 x C2), for MD 0.78 +/- 0.05 (P1 x C1) and 0.80 +/- 0.08 (P2 x C2). For WGT and WDA, the correlations were 0.53 +/- 0.08 (P1 x C1), 0.80 +/- 0.10 (P2 x C2), and 0.60 +/- 0.07 (P1 x C1) and 0.79 +/- 0.09 (P2 x C2), respectively. (Co)variances in crossbreds were adjusted to a live BW scale. Compared with purebreds, the genetic variances in crossbreds were lower, and the residual variances were greater. Sire variances in crossbreds were approximately 20 to 30% of the animal variances in purebreds for BF and MD but were 13 to 25% for WGT and WDA. The efficiency of purebred selection on crossbreds, assessed by EBV prediction weights, ranged from 0.43 to 0.91 for line 1 and 0.70 to 0.92 for line 2. When nucleus and commercial environments differ substantially, the efficiency of selection varies by line and traits, and selection strategies that include crossbred data from typical production environments may therefore be desirable.


The effects of prenatal exposure to Ramadan on stature during childhood and adolescence: Evidence from the Indonesian Family Life Survey.
Many pregnant Muslim women fast during the Muslim holy month of Ramadan. A number of studies have reported negative life outcomes in adulthood for children who were prenatally exposed to Ramadan. However, other studies document minimal to no impact on neonatal indicators. Using data from the Indonesian Family Life Survey consisting of 45,246 observations of 21,723 children born to 9771 mothers, we contribute to the current discussion on prenatal exposure to Ramadan by examining the effects on stature (height-for-age Z-scores, weight-for-age Z-scores, and body-mass-index-for-age Z-scores: HAZ, WAZ, and BAZ, respectively) from early childhood to late adolescence (0-19 years of age). We introduce an objective mother's religiosity indicator to improve the intention-to-treat estimations. Children were classified into three groups based on their mother's religion-religiosity: religious Muslims, less-religious Muslims, and non-Muslims. Using cluster-robust mother fixed-effects, we found negative effects on stature for children born to religious Muslim mothers. The effects were age-dependent and timing-sensitive. For example, children born to religious Muslim mothers were shorter in late adolescence (15-19 years of age) compared to their unexposed siblings if they were prenatally exposed in the first trimester of pregnancy (HAZ difference = -0.105 SD; p-val. <0.05). Interestingly, we found positive effects on stature for exposed less-religious Muslim children that peak in early adolescence (10-14 years of age) and negative effects on stature for exposed non-Muslim children that occur only in early childhood (0-4 years of age). We nuance our discussion of health and socioeconomic factors to explain these surprising results.


On the density of states of circular graphene quantum dots.
We suggest a simple approach to calculate the local density of states that effectively applies to any structure created by an axially symmetric potential on a continuous graphene sheet such as circular graphene quantum dots or rings. Calculations performed for the graphene quantum dot studied in a recent scanning tunneling microscopy measurement (Gutierrez et al 2016 Nat. Phys. 12 1069-75) show an excellent experimental-theoretical agreement.


[Relationships between lipid peroxidation or cyclic nucleotides and motility in human asthenozoosperm and normosperm].
The relationships between sperm lipid peroxidation (LP) or cyclic nucleotides and sperm motility in normospermic and asthenozoospermic specimens were analyzed. Sperm motility was measured by the transmembrane migration method; LP was measured by thiobarbituric acid (TBA) method and the intracellular cAMP and cGMP contents was measured by radioimmunoassay in 20 fertile and 20 asthenozoospermic infertile human semen specimens. Results showed that in both fertile and infertile individual, there was a close negative correlation between sperm LP formation and motility (r = -0.76; P < 0.001 and r = -0.68; P < 0.001); there were significant positive correlations between intracellular cAMP (r = 0.64; P < 0.01 and r = 0.59; P < 0.01) or cGMP (r = 0.60; P < 0.01 and r = 0.55; P < 0.05) and sperm motility; and the correlation between LP and motility was the closest. These results suggest a causative role for LP in the aetiology of male infertility due to defective sperm motility, and confirmed that intra-cellular cyclic nucleotides likely also have influences on sperm motility.


A Fully Integrated Miniaturized Optical Biosensor for Fast and Multiplexing Plasmonic Detection of High- and Low-Molecular-Weight Analytes.
Optical biosensors based on plasmonic sensing schemes combine high sensitivity and selectivity with label-free detection. However, the use of bulky optical components is still hampering the possibility of obtaining miniaturized systems required for analysis in real settings. Here, a fully miniaturized optical biosensor prototype based on plasmonic detection is demonstrated, which enables fast and multiplex sensing of analytes with high- and low molecular weight (80 000 and 582 Da) as quality and safety parameters for milk: a protein (lactoferrin) and an antibiotic (streptomycin). The optical sensor is based on the smart integration of: i) miniaturized organic optoelectronic devices used as light-emitting and light-sensing elements and ii) a functionalized nanostructured plasmonic grating for highly sensitive and specific localized surface plasmon resonance (SPR) detection. The sensor provides quantitative and linear response reaching a limit of detection of 10-4 refractive index units once it is calibrated by standard solutions. Analyte-specific and rapid (15 min long) immunoassay-based detection is demonstrated for both targets. By using a custom algorithm based on principal-component analysis, a linear dose-response curve is constructed which correlates with a limit of detection (LOD) as low as 3.7 µg mL-1 for lactoferrin, thus assessing that the miniaturized optical biosensor is well-aligned with the chosen reference benchtop SPR method.


The role of the Fracture Liaison Service (FLS) in subsequent fracture prevention in the extreme elderly.
Several guidelines recommend a bone and fall-related osteoporosis risk assessment in all patients with fracture and age > 50 years. In practice, however, there is no consensus whether screening > 85 years is useful. To evaluate the subsequent fracture risk in all patient > 85 years, comparing the two populations of Fracture Liaison Service (FLS) attenders and non-attenders. All patients > 85 years that presented at the FLS with a non-vertebral fracture were included in the study during a 5-year period (September 2004 and December 2009). Excluded were pathologic fractures, death < 30 days, or patients on osteoporosis treatment. in patients that attended the FLS, assessment of bone mineral density and fall-risk factors were screened. In both the attenders and non-attenders groups, mortality and subsequent fracture rates were scored during a follow-up of 2 years. 282 patients fulfilled inclusion criteria for screening, of which 160 (57%) patients did not attend the FLS. 122 patients were screened for osteoporosis and fall-related risk of whom 72 were diagnosed with osteoporosis. Subsequent fracture risk in both groups was 19%. Medical treatment was started in 51 patients, of which 15 patients developed a subsequent fracture. Cox-regression analysis indicated a significantly lower mortality rate, but not a diminished subsequent fracture rate in the FLS screened population compared to the non-attenders. The advantage of a FLS in reducing subsequent fracture risk in patients > 85 years seems to be limited. In practice a large proportion of these patients are not screened.


Factors associated with a negative outcome of medication-overuse headache: a 3-year follow-up (the 'CARE' protocol).
To evaluate factors associated with a negative outcome in a 3-year follow-up of subjects diagnosed with medication-overuse headache (MOH) (revised-ICHD-II criteria). All consecutive patients entering the center's inpatient detoxification program were analyzed in a prospective, non-randomized fashion. All participants were assessed by a neurologist using an ad hoc patient record form. Personality was assessed using the Minnesota Multiphasic Personality Inventory (MMPI)-2, Chi-square test, one-way analysis of variance (ANOVA), and odds ratios (OR) were calculated as appropriate. One-hundred and fifty patients completed the follow-up (79.3% females, age 46.40 ± 11.31 years): 13 never stopped their drug overuse (A), 38 stopped their overuse, but relapsed at least once (B), and 99 stopped and never relapsed (C). The Group A patients differed from those in B + C as they were more frequently single (OR 0.134; P = 0.007) and unemployed (OR 3.273; P = 0.04), took a higher number of drug doses ( P < 0.001), and less frequently drank coffee (OR 3.273; P = 0.044). Personality profile: subjects in A scored higher than those in C on the following scales: Hypochondriasis ( P = 0.007), Depression ( P = 0.003), Paranoia ( P = 0.025), Fears ( P = 0.003), Obsessiveness ( P = 0.026), Bizarre Mentation ( P = 0.046), Social Discomfort ( P = 0.004), Negative Treatment Indicators ( P = 0.040), Repression ( P = 0.007), Overcontrolled Hostility ( P = 0.040), Addiction Admission ( P = 0.021), Social Responsibility ( P = 0.039), and Marital Distress ( P = 0.028). Disease outcome in MOH patients is influenced negatively by overuse severity and by specific psychological and socio-economic variables. Other possible modifier factors were voluptuary habits.


A Two-Phase Time Synchronization-Free Localization Algorithm for Underwater Sensor Networks.
Underwater Sensor Networks (UWSNs) can enable a broad range of applications such as resource monitoring, disaster prevention, and navigation-assistance. Sensor nodes location in UWSNs is an especially relevant topic. Global Positioning System (GPS) information is not suitable for use in UWSNs because of the underwater propagation problems. Hence, some localization algorithms based on the precise time synchronization between sensor nodes that have been proposed for UWSNs are not feasible. In this paper, we propose a localization algorithm called Two-Phase Time Synchronization-Free Localization Algorithm (TP-TSFLA). TP-TSFLA contains two phases, namely, range-based estimation phase and range-free evaluation phase. In the first phase, we address a time synchronization-free localization scheme based on the Particle Swarm Optimization (PSO) algorithm to obtain the coordinates of the unknown sensor nodes. In the second phase, we propose a Circle-based Range-Free Localization Algorithm (CRFLA) to locate the unlocalized sensor nodes which cannot obtain the location information through the first phase. In the second phase, sensor nodes which are localized in the first phase act as the new anchor nodes to help realize localization. Hence, in this algorithm, we use a small number of mobile beacons to help obtain the location information without any other anchor nodes. Besides, to improve the precision of the range-free method, an extension of CRFLA achieved by designing a coordinate adjustment scheme is updated. The simulation results show that TP-TSFLA can achieve a relative high localization ratio without time synchronization.


Orchestrating phonosurgery.
A thyroplasty implant (prosthesis) has been designed to accomplish medialization to restore/improve the voice in unilateral vocal cord paralysis. The perioperative nurse plays an essential role in ensuring success of laryngoplasty procedures by communicating with the surgeon and planning for the timely delivery of appropriate sizers, implants, and instrumentation. The surgical team will witness the success of the thyroplasty procedure when the patient phonates as various implant sizers are applied/implanted to achieve improvement of the voice.


Hematological and biochemical profiles and histopathological evaluation of experimental intoxication by sodium fluoroacetate in cats.
Sodium fluoroacetate (SFAC) is a potent rodenticide, largely used for rodent and domestic pest control. The toxic effects of SFAC are caused by fluoroacetate, a toxic metabolite, whose toxic action blocks the Krebs cycle and also induces the accumulation of citrate in the body, which is a serum calcium chelator. The most common clinical signs of this intoxication are the cardiac and neurological effects. However, the hematological, biochemical and histopathological findings occurring in intoxication are still unknown in different species. In the present study, 16 domestic cats were experimentally intoxicated with oral doses of fluoroacetate (0.45 mg/kg). The hematological and biochemical profiles and histopathological findings were made to look for auxiliary diagnosis methods in SFAC intoxications. The hematological profile showed transitory leucopenia and thrombocytopenia; in the biochemical profiles were detected hyperglycemia, increase of creatinequinase enzyme (CK) and creatinequinase cardiac isoenzyme (CK-MB), hypokalemia and hypophosfatemia. In the macroscopic and histopathological findings were observed lesions characteristic of degenerative and ischemic processes in heart, kidneys, liver, brain and lungs. These changes may be auxiliary to the diagnosis of intoxication by SFAC in cats, when associated with clinical signs described for the species. Thus, the complete blood count with platelet count, serum glucose, enzymes CK and CK-MB isoenzyme, as well as the electrolytes potassium and phosphorus, can facilitate the laboratory diagnosis during intoxication by SFAC, associated with the pathological findings in the case of death of the intoxicated animal.


Finding the time: an audit of the acute ward mealtime processes.
It has been found that many organisations still fail to meet the basic rights of those in their care, in terms of access to food, drink and support when they need it. In acknowledgment that food service in hospitals must be given a higher priority, and be recognised as an integral part of the patient's treatment and care, Irish hospitals must now have a system to evaluate the nutritional and hydrational care for patients admitted to hospital. The purpose of this audit was to examine the level of mealtime support available to patients during the main mealtime service in our hospital. As the audit highlighted the need to alter ward processes around the mealtime service, quality improvement initiatives were introduced. These initiatives had a positive impact, enabling ward staff to improve adequacy of mealtime support to patients, leading to better patient quality care at this time.


Interdisciplinary Shared Governance in Ambulatory Care: One Health System's Journey.
The implementation of shared governance structures in acute care has illustrated the positive relationship between shared decision making and nurse empowerment and positive nurse and patient outcomes. Little is known, however, about interdisciplinary shared governance, and even less is known about shared governance in ambulatory care. This article details one health system's experience with the implementation of an interdisciplinary shared governance structure in ambulatory care over a 4-year period. The authors report lessons learned, positive health system outcomes that resulted including improved communication, better preparedness for accreditation visits, improved assessment of fall risk, and a streamlined documentation system. Also discussed are mechanisms to enhance sustainability of the structure and discussion of future opportunities and challenges.


[The treatment of meniscal tear with bio-absorbable arrow--3 years follow-up].
The introduction of bio-absorbable materials has improved the ability to offer a simple fast and friendly solution to meniscal tears. The technique of meniscal suture with bio-absorbable arrows is associated with lower morbidity and complication rates. The clinical evaluation of treatment of meniscal tear by suture with bio-absorbable arrows. During the period 1997-2004, 14 patients underwent arthroscopic all-inside meniscus repair. The "Biofix" bio-absorbable arrows fixation technique was used. Fourteen patients were followed--11 males and 3 females. Their mean age was 23 years (range 16-34 years). Follow-up period was an average of 34 months (range 6-72 months). Sport injuries were the main cause of meniscal tear (60%). Other causes included: work accidents (20%) and military accidents (20%). All the tears were located in an area suitable for suture in the "red-red" or "red-white" zone. One patient had a tear of the lateral meniscus. Four patients had anterior cruciate ligament (ACL) tear. The mean length of the tear was 9.6 mm. Tears were fixed with 2.5 arrows in average. The clinical evaluation was by the Lysholm Score. Excellent results were reported in 10 patients, good in one patient, fair in 2 patients and poor in 1 patient. One patient suffered from a transient tender point on the medial joint line due to protruded arrow tip, one patient needed a menisectomy due to unresolved symptoms and one patient underwent ACL reconstruction. Meniscal suture with bio-absorbable arrows is an easy and reliable suture technique compared to the classical methods and it seems to have a lower complication rate. Further studies are needed to establish the quality of the repair and the associated morbidity.


Correlation of Inpatient Experience Survey Items and Domains With Overall Hospital Rating.
To determine which individual patient experience questions and domains were most correlated with overall inpatient hospital experience. Within 42 days of discharge, 27 639 patients completed a telephone survey based upon the Hospital-Consumer Assessment of Healthcare Systems and Processes instrument. Patients rated their overall experience on a scale of 0 (worst care) to 10 (best care). Correlation coefficients were calculated to assess the relationships between individual survey questions and domains with overall experience. Questions on provider coordination and nursing care were most correlated with overall experience. Hospital cleanliness, quietness, and discharge information questions showed poor correlation. Correlation with overall experience was strongest for the "communication with nurses" domain. Our individual question results are novel, while the domain-based findings replicate those of US-based providers, results which had not yet been reported in the Canadian context-one with universal health care coverage. Our results suggest that our large health care organization may attain initial inpatient experience improvements by focusing upon personnel-based initiatives, rather than physical attributes of our hospitals.


Microanalytical partition of rat-liver homogenates by poly(ethylene glycol)-dextran counter-current distribution.
1. The principal organelles from rat liver homogenates were fractionated by counter-current partition between solutions of dextran T50 and poly(ethylene glycol) 6000 in 0.25 M sucrose containing 10 mM sodium phosphate/phosphoric acid buffer, pH 7.4. 2. A small-volume (1.3-ml sample well)counter-current partition apparatus capable of 17 transfers, in which separation of the phases was enhanced by low-speed centrifugation, was used. 3. Variations in distribution of organelles was observed with increasing concentration of dextran and/or poly(ethylene glycol). At a constant polymer composition of 5.0% (w/w) dextran and 4.0% (w/w) poly(ethylene glycol), increasing concentrations of sodium chloride (2.5 mM, 5 mM and 10 mM) also altered the partition of the organelles. 4. Useful analytical resolution of the various organelles was achieved. In particular, separation of endoplasmic reticulum from plasma membrane components was obtained.


Stair-step tracheal repair: Surgical technique.
Typical surgical treatment for invasive thyroid carcinoma at the level of the cricoid substantially reduces surrounding cartilaginous support and risks damage to the recurrent laryngeal nerve (RLN). We present a novel tracheal reconstructive technique that minimizes this injury risk. A 72-year-old man with recurrent invasive thyroid carcinoma underwent cricotracheal resection and reconstruction using a stair-step approach. Diseased cartilage was removed by a left hemitracheal and hemicricoid resection. A portion of normal trachea was also resected on the contralateral right side, removing the third and fourth hemitracheal rings, to close the defect with a sliding tracheoplasty and avoid dissection near the right cricothyroid joint on the side of the functioning RLN. The trachea was elevated superiorly and reanastomosed to the cut margin of the cricoid. This novel stair-step approach to tracheal reconstruction offers reduced risk of injury to the contralateral RLN while still establishing a patent airway.


Development and mining of a volatile organic compound database.
Volatile organic compounds (VOCs) are small molecules that exhibit high vapor pressure under ambient conditions and have low boiling points. Although VOCs contribute only a small proportion of the total metabolites produced by living organisms, they play an important role in chemical ecology specifically in the biological interactions between organisms and ecosystems. VOCs are also important in the health care field as they are presently used as a biomarker to detect various human diseases. Information on VOCs is scattered in the literature until now; however, there is still no available database describing VOCs and their biological activities. To attain this purpose, we have developed KNApSAcK Metabolite Ecology Database, which contains the information on the relationships between VOCs and their emitting organisms. The KNApSAcK Metabolite Ecology is also linked with the KNApSAcK Core and KNApSAcK Metabolite Activity Database to provide further information on the metabolites and their biological activities. The VOC database can be accessed online.


A globally applicable "triple A" risk model for essential thrombocythemia based on Age, Absolute neutrophil count, and Absolute lymphocyte count.
We examined the individual prognostic contribution of absolute neutrophil (ANC), lymphocyte (ALC), and monocyte (AMC) counts, on overall (OS), leukemia-free (LFS), and myelofibrosis-free (MFFS) survival in essential thrombocythemia (ET). Informative cases (N = 598; median age 59 years; females 62%) were retrospectively accrued from a Mayo Clinic database: JAK2 59%, CALR 27%, triple-negative 11%, and MPL 3%; international prognostic scoring system for ET (IPSET) risk high 21%, intermediate 42%, and low 37%; 7% (37/515) had abnormal karyotype and 10% (21/205) adverse mutations (SF3B1/SRSF2/U2AF1/TP53). At median 8.4 years, 163 (27%) deaths, 71 (12%) fibrotic, and 20 (3%) leukemic transformations were recorded. Multivariable analysis resulted in HR (95% CI) of 16.5 (9.9-27.4) for age > 70 years, 3.7 (2.3-6.0) for age 50-70 years, 2.4 (1.7-3.3) for ANC ≥8 × 109 /L, and 1.9 (1.4-2.6) for ALC <1.7 × 109 /L. The corresponding HR-based scores were 4, 2, 1, and 1, resulting in an new 4-tiered AgeAncAlc (AAA; triple A) risk model: high (5-6 points; median survival 8 years; HR 30.1, 95% CI 17.6-54), intermediate-2 (4 points; median 13.5 years; HR 12.7, 95% CI 7.1-23.0), intermediate-1 (2-3 points; median 20.7 years; HR 3.8, 95% CI 2.3-6.4) and low (0-1 points; median 47 years). The AAA model (Akaike Information Criterion [AIC] 621) performed better than IPSET (AIC 647) and was subsequently validated by an external University of Florence ET cohort (N = 485). None of the AAA variables predicted LFS while ALC <1.7 × 109 /L was associated with inferior MFFS (p = .01). Adverse mutations (p < .01) and karyotype (p < .01) displayed additional prognostic value without disqualifying the prognostic integrity of the AAA model. This study proposes a simple and globally applicable survival model for ET, which can be used as a platform for further molecular refinement. This study also suggests a potential role for immune-related biomarkers, as a prognostic tool in myeloproliferative neoplasms.


Detection of protein secondary structures via the discrete wavelet transform.
We subject the primary sequence of proteins gathered from the Structural Classification of Proteins (SCOP) database to a discrete wavelet transform (DWT) analysis to search for predictors of secondary structures. We use proteins with both alpha helices and beta sheets (the A/B , A+B databases from SCOP). The amino acids composing the protein are converted to their hydrophobicity values using three hydrophobicity scales. Results prove to be independent of the scale used. Using a DWT multiresolution decomposition, each protein is coarse grained, in effect, creating snapshots of each protein at multiple scales. For each protein, a control data set is formed by generating random realizations that remove the positional informational in the sequence but still contain the same amino acid frequencies. Regions of salient hydrophobicity in the protein sequence are identified by comparing the transforms of the original sequence with those of the control set, at each resolution. We find significant matching between regions of salient hydrophobicity and the locations of secondary structure along the amino acid chains. We calculate the sensitivity, specificity, and Matthews correlation to quantify the agreement between the wavelet detected structures and the real protein. In addition we are able to distinguish between the morphologically different subsets, A/B and A+B. We also construct a correlation function based on the DWT that correlates quasilocalized structures at lengths in wavelet space. Through a similar comparison to the control data sets, features in this space-scale correlation are identified that show correspondence to the typical lengths of the secondary structures.


Evaluation of the eyebrow position after aponeurosis advancement.
Patients often develop eyebrow drooping after blepharoplasty or ptosis repair. After aponeurosis advancement was performed in 53 patients (100 eyelids) with blepharoptosis, the eyebrow heights at the medial canthus, center of the pupil, and lateral canthus were measured using scanned photographs obtained preoperatively and 3 months postoperatively. In the 100 eyelids subjected to aponeurosis advancement, the eyebrow position was lowered at the medial canthus in 81 eyelids (81%), at the center of the pupil in 84 eyelids (84%), and at the lateral canthus in 80 eyelids (80%). The mean distance of eyebrow drooping in the 100 eyelids was 2.80 mm at the medial canthus, 2.87 mm at the center of the pupil, and 2.50 mm at the lateral canthus. The preoperative margin reflex distance (MRD) was significantly associated with the distance of eyebrow drooping at the medial canthus, the center of the pupil, and the lateral canthus in the 100 eyelids, but the postoperative MRD was not significantly associated with these parameters in the 100 eyelids. In conclusion, eyebrow drooping developed after aponeurosis advancement in most cases, and the distance of eyebrow drooping was associated with the severity of blepharoptosis.


Coherent reflection without traveling waves: on the origin of long-latency otoacoustic emissions in lizards.
Lizard ears produce otoacoustic emissions with characteristics often strikingly reminiscent of those measured in mammals. The similarity of their emissions is surprising, given that lizards and mammals manifest major differences in aspects of inner ear morphology and function believed to be relevant to emission generation. For example, lizards such as the gecko evidently lack traveling waves along their basilar membrane. Despite the absence of traveling waves, the phase-gradient delays of gecko stimulus-frequency otoacoustic emissions (SFOAEs) are comparable to those measured in many mammals. This paper describes a model of emission generation inspired by the gecko inner ear. The model consists of an array of coupled harmonic oscillators whose effective damping manifests a small degree of irregularity. Model delays increase with the assumed sharpness of tuning, reflecting the build-up time associated with mechanical resonance. When tuning bandwidths are chosen to match those of gecko auditory-nerve fibers, the model reproduces the major features of gecko SFOAEs, including their spectral structure and the magnitude and frequency dependence of their phase-gradient delays. The same model with appropriately modified parameters reproduces the features of SFOAEs in alligator lizards. Analysis of the model demonstrates that the basic mechanisms operating in the model are similar to those of the coherent-reflection model developed to describe mammalian emissions. These results support the notion that SFOAE delays provide a noninvasive measure of the sharpness of cochlear tuning.


Changes in protein profiles of guinea pig sclera during development of form deprivation myopia and recovery.
To investigate changes in protein profiles of posterior sclera in guinea pigs during development of form deprivation myopia and recovery. Three groups of guinea pigs (developing form deprivation myopia, recovering from the myopia and normal control) were evaluated for protein profiles of the posterior sclera using two-dimensional gel electrophoresis. Protein spots with a different intensity of at least threefold among the 3 groups were further identified with mass spectrometry. Key proteins associated with ocular growth (crystallins) were examined at mRNA levels using RT-PCR. Moderate myopia was induced at 7 weeks of monocular deprivation and then more gradually recovered toward the previous refractive status 4 days after re-exposure of the eye to normal visual conditions. The profile of all protein spots at the posterior sclera was similar for both the deprived and the recovery eyes but distinct between either of the 2 experimental eyes and the normal control eyes. Twenty-six and 33 protein spots were differentially expressed in the deprived and the recovery eyes, respectively, compared to the normal control eyes. In contrast, the number of proteins differentially expressed between the deprived and the recovery eyes was only 5. Among the different subtypes of crystallins, βB2-crystallin was down-regulated and βA4-crystallin was upregulated in the deprived eyes at both protein and mRNA levels compared to the normal control eyes. The trend of expression for βA3/A1-crystallin was also similar at both mRNA and protein levels for the deprived eyes. However, αA-crystallin mRNA in the recovery eyes was upregulated while αA-crystallin itself was down-regulated. A similar inconsistency in expression of βA3/A1-, βA4-, and βB2-crystallins between the protein and mRNA levels also occurred in the recovery eyes. Proteomic analysis provides a useful survey of the number of proteins whose levels change during form deprivation myopia and the subsequent recovery. In particular, the crystallins changed during the development of form deprivation myopia and recovery. The changes in crystallin protein levels were consistent with that in mRNA levels during the development stage of form-deprivation myopia (FDM). However, the changes of most crystallin protein levels were mismatched with mRNA levels during the recovery stage.


Incidence and clinical impact of coronary stent fracture after sirolimus-eluting stent implantation.
Stent fracture is one of the possible causes of restenosis after sirolimus-eluting stents (SES) implantation. The aim of our study was to evaluate the prevalence and clinical impact of coronary stent fracture after SES implantation. From our prospective institutional database, 280 patients were treated solely with SES from August 2004 to June 2005. Among the 280 patients, 256 patients with a total of 307 lesions underwent follow-up angiography on an average of 240 days after the procedure. Stent fractures were observed in eight (2.6%) lesions. Of the eight lesions with stent fracture, five were located in the right coronary artery (RCA), two in the saphenous vein (SV) graft, and one in the left anterior descending coronary artery. The stent fractures were all in the locations that served as hinges during vessel movement in the cardiac contraction cycle. Seven of the eight stent fractures were adjacent to the edge of previously implanted or overlapped stent. Significant multivariate predictors of stent fracture were SV graft location (Odds ratio 35.88; 95% confidence interval 2.73-471.6, P = 0.006), implanted stent length (Odds ratio 1.04; 95% confidence interval 1.01-1.07, P = 0.02), and RCA location (Odds ratio 10.00; 95% confidence interval 1.11-89.67, P = 0.04). In-stent binary restenosis rate was 37.5% and target lesion repeat revascularization rate was 50.0% in patients with stent fracture. Stent fracture was likely to be affected by mechanical stress provoked by rigid structures and hinge points. Stent fracture might be associated with the high incidence of target lesion revascularization.


TEM observations of Au and Ir particles supported on CeO2.
Au/CeO2 and Ir/CeO2 catalysts were observed by a transmission electron microscope in order to investigate the nano-structures of Au and Ir particles and CeO2 grains and the interface structure between metallic particles and CeO2. An annular dark field scanning transmission electron microscope (ADF-STEM) and an energy dispersive X-ray spectroscopy (EDS) revealed that the metallic particles smaller than 2 nm in diameter are highly dispersed on CeO2 supports in both catalysts. For model samples of larger CeO2 particles with flat facets of low-index surfaces, high resolution transmission electron microscopy observations of Au/CeO2 and Ir/CeO2 interfaces were made and the epitaxial relationship between Au and CeO2, (111)[110]Au//(111)[110]CeO2 has been found for the first time.


Dietary polyunsaturated fatty acids increase survival and decrease bacterial load during septic Staphylococcus aureus infection and improve neutrophil function in mice.
Severe infection, including sepsis, is an increasing clinical problem that causes prolonged morbidity and substantial mortality. At present, antibiotics are essentially the only pharmacological treatment for sepsis. The incidence of resistance to antibiotics is increasing; therefore, it is critical to find new therapies for sepsis. Staphylococcus aureus is a major cause of septic mortality. Neutrophils play an important role in the defense against bacterial infections. We have shown that a diet with high levels of dietary saturated fatty acids decreases survival in septic mice, but the mechanisms behind this remain elusive. The aim of the present study was to investigate how the differences in dietary fat composition affect survival and bacterial load after experimental septic infection and neutrophil function in uninfected mice. We found that, after S. aureus infection, mice fed a polyunsaturated high-fat diet (HFD-P) for 8 weeks had increased survival and decreased bacterial load during sepsis compared with mice fed a saturated high-fat diet (HFD-S), similar to mice fed a low-fat diet (LFD). Uninfected mice fed HFD-P had a higher frequency of neutrophils in bone marrow than mice fed HFD-S. In addition, mice fed HFD-P had a higher frequency of neutrophils recruited to the site of inflammation in response to peritoneal injection of thioglycolate than mice fed HFD-S. Differences between the proportion of dietary protein and carbohydrate did not affect septic survival at all. In conclusion, polyunsaturated dietary fat increased both survival and efficiency of bacterial clearance during septic S. aureus infection. Moreover, this diet increased the frequency and chemotaxis of neutrophils, key components of the immune response to S. aureus infections.


Lipid metabolism during lactation: a review of adipose tissue-liver interactions and the development of fatty liver.
Fatty acids are the major source of energy for most tissues during periods of negative energy balance; however, fatty acids can, in some circumstances, have pathological effects. Fatty acids are stored as triacylglycerols (TAG), mostly in the various adipose tissue depots of the body. However, if blood unesterified fatty acid (NEFA) levels are elevated for prolonged periods, as may occur during lactation or obesity, TAG can accumulate in other tissues including liver and muscle cells (myocytes), and this can have pathological consequences such as the development of ketosis (Grummer, 1993; Drackley et al. 2001) or type 2 diabetes (Boden & Shulman, 2002; McGarry, 2002).


Deep sclerectomy with collagen implant: medium term results.
To study prospectively the success rate and complications of deep sclerectomy with collagen implant (DSCI), a new non-penetrating filtration procedure. Non-randomised prospective trial involving consecutive patients. 100 eyes of 100 patients with medically uncontrolled primary and secondary open angle glaucoma. A superficial scleral flap was raised and a deep sclerectomy was performed in the scleral bed. Schlemm's canal was opened and dissection of the cornea was performed up to Descemet's membrane, at which point aqueous percolated through the remaining trabeculo-Descemet's membrane. A collagen implant was sutured radially in the scleral bed. Visual acuity, intraocular pressure (IOP) measurements, and slit lamp examinations were performed before surgery and after surgery at 1 and 7 days, and 1, 3, 6, 9, 12, 18, 24, 30, and 36 months. The mean follow up period was 17.8 (SD 8.7) months. The mean preoperative IOP was 27.8 (8.6) mm Hg; the mean postoperative IOP was 5.7 (4.0) at day 1, 11.2 (4.6) at month 1, 14.0 (3.5) at month 12, and 13.0 (3.8) at month 36. Complete success rate, defined as an IOP lower than 21 mm Hg without medication, was 44.6% at 36 months. Qualified success rate, defined as an IOP lower than 21 mm Hg with medication, was 97.7% at 36 months. Early postoperative complications included hyphaema in seven patients, would leak in 10 patients, and subtle choroidal detachment in 11 patients. Goniopuncture was performed in 41 of the patients, and 5-fluorouracil injections were made in 23 patients; cataract progression occurred in seven patients. When comparing the different types of open angle glaucoma, no difference was found in terms of reduction in IOP, number of patients requiring antiglaucoma medications, or success rate. Deep sclerectomy with collagen implant appears to provide reasonable control of IOP at medium term follow up, with few immediate postoperative complications.


Epigallocatechin-3-gallate augments the therapeutic effects of benzo[a]pyrene-mediated lung carcinogenesis.
Our previous study found curcumin and vitamin E to have protective effects against benzo[a]pyrene (BaP) exposure in human normal lung epithelial BEAS-2B cells. The first objective of this study was to determine whether epigallocatechin-3-gallate (EGCG) elicited the same response. Co-treatment with 5 µM BaP and 20 µM EGCG in BEAS-2B promoted a significant reduction in cell viability and greater G2/M cell cycle arrest, induction of ROS, and reductions in BaP-induced CYP1A1/CYP1B1/COMT, EGFR, p-Akt (Ser473), p-p53 (Thr55), and survivin mRNA/protein expression, as well as an increase in p-p53 (Ser15). Based on these findings, the second objective was to extend the investigation by developing a novel BaP-transformed BEAS-2B cell line, BEAS-2BBaP , to examine the effects of EGCG when co-administered with gefitinib, an EGFR tyrosine kinase inhibitor. Cell colony formation assay demonstrated in vitro tumorigenic potential of BEAS-2BBaP , which had an overexpression of EGFR. Viability testing revealed gefitinib co-treatment with EGCG resulted in more cell death compared with gefitinib alone. Co-treated cells had greater reductions in gefitinib-induced CYP1A1/CYB1B1, EGFR, cyclin D1, p-Akt (Ser473), and survivin mRNA/protein expression, as well as an increase in p-p53 (Ser15). Therefore, EGCG was found to promote greater cytotoxicity to BEAS-2B co-treated with BaP and BEAS-2BBaP upon gefitinib co-treatment through regulating metabolism enzymes and signaling pathways involving EGFR and p53. These findings suggest that EGCG did not act as a protective compound in BEAS-2B after acute BaP exposure, but has the potential to be a useful adjuvant chemotherapeutic compound when coupled with gefitinib for chemosensitization. © 2017 BioFactors, 43(4):529-539, 2017.


Development of a Label-Free Electrochemical Aptasensor for the Detection of Tau381 and its Preliminary Application in AD and Non-AD Patients' Sera.
The electrochemical aptamer sensor has been designed for detecting tau381, a critical biomarker of Alzheimer's disease in human serum. The aptasensor is obtained by immobilizing the aptamer on a carboxyl graphene/thionin/gold nanoparticle modified glassy-carbon electrode. As a probe and bridge molecule, thionin connected carboxyl graphene and gold nanoparticles, and gave the electrical signal. Under optimal conditions, the increment of differential pulse voltammetry signal increased linearly with the logarithm of tau381 concentration in the range from 1.0 pM to 100 pM, and limit of detection was 0.70 pM. The aptasensor reliability was evaluated by determining its selectivity, reproducibility, stability, detection limit, and recovery. Performance analysis of the tau381 aptasensor in 10 patients' serum samples showed that the aptasensor could screen patients with and without Alzheimer's disease. The proposed aptasensor has potential for use in clinically diagnosing Alzheimer's disease in the early stage.


Epidemiological drivers of transmissibility and severity of SARS-CoV-2 in England.
As the SARS-CoV-2 pandemic progressed, distinct variants emerged and dominated in England. These variants, Wildtype, Alpha, Delta, and Omicron were characterized by variations in transmissibility and severity. We used a robust mathematical model and Bayesian inference framework to analyse epidemiological surveillance data from England. We quantified the impact of non-pharmaceutical interventions (NPIs), therapeutics, and vaccination on virus transmission and severity. Each successive variant had a higher intrinsic transmissibility. Omicron (BA.1) had the highest basic reproduction number at 8.3 (95% credible interval (CrI) 7.7-8.8). Varying levels of NPIs were crucial in controlling virus transmission until population immunity accumulated. Immune escape properties of Omicron decreased effective levels of immunity in the population by a third. Furthermore, in contrast to previous studies, we found Alpha had the highest basic infection fatality ratio (2.9%, 95% CrI 2.7-3.2), followed by Delta (2.2%, 95% CrI 2.0-2.4), Wildtype (1.2%, 95% CrI 1.1-1.2), and Omicron (0.7%, 95% CrI 0.6-0.8). Our findings highlight the importance of continued surveillance. Long-term strategies for monitoring and maintaining effective immunity against SARS-CoV-2 are critical to inform the role of NPIs to effectively manage future variants with potentially higher intrinsic transmissibility and severe outcomes.


Pharmacological validation of a translational model of cocaine use disorder: Effects of d-amphetamine maintenance on choice between intravenous cocaine and a nondrug alternative in humans and rhesus monkeys.
Drug self-administration procedures are the gold standard for laboratory research to study mechanisms of drug use disorders and evaluate candidate medications. However, preclinical-to-clinical translation has been hampered by a lack of coordination. To address this limitation, we previously developed homologous intravenous (IV) cocaine choice self-administration procedures in rhesus monkeys and humans, and then demonstrated their functional equivalence. The present studies sought to determine the sensitivity of these procedures to d-amphetamine maintenance. Three (N = 3) rhesus monkeys with histories of cocaine self-administration and 16 (N = 16) humans with cocaine use disorder completed the studies. Monkeys were maintained on IV d-amphetamine (0, 0.019, 0.037 and 0.074 mg/kg/h), and then completed 7 sessions during each condition in which they completed 9 choice trials to receive 0.14 mg/kg/injection IV cocaine (corresponding to 10 mg/70 kg in humans) or 10 food pellets under independent, concurrent progressive-ratio schedules. Humans were maintained on oral extended release d-amphetamine (0, 30 and 60 mg/day, corresponding to the lowest 3 doses in monkeys) and participated in 12 sessions in which they chose money ($6.00) or IV cocaine (0, 3, 10 and 30 mg/70 kg). Blood samples were taken to compare d-amphetamine plasma levels across species. In monkeys and humans, d-amphetamine reduced the number of cocaine choices and produced comparable blood levels at equivalent daily doses. d-Amphetamine had similar efficacy, though lower potency, at reducing choice for an equivalent cocaine dose in monkeys relative to humans. These coordinated studies support the utility of these procedures as a translational model for cocaine use disorder. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Methadone Concentrations in Exhaled Breath Condensate, Serum and Urine of Patients Under Maintenance Treatment.
Drug abuse is a serious problem causing health, economical and psycho-social negative outcomes. Methadone is commonly used drug for management of drug addiction. Exhaled breath condensate (EBC) is a promising non-invasive biological sample which attracted more attention in recent years. This work aimed to extend the applicability of a developed preconcentration - liquid chromatographic method for analysis of methadone in serum and urine samples. Drug concentrations in EBC, serum and urine are also investigated for dose-concentration and their inter-correlations. Biological samples were collected from 53 patients receiving methadone and the concentrations were determined using a validated analytical method after a pre-concentration step. Methadone measured in all samples and there are correlations between administered dose of methadone and its serum and urine concentrations. A weak correlation is observed between dose and EBC concentration. Wider variations in EBC concentrations of methadone could be justified concerning a number of affecting parameters such as relative humidity of the collection area and further investigations are required for standardization of EBC as a non-invasive biological sample to be used in clinical practice.


Evaluation of postoperative blood coagulation changes in elderly patients undergoing major surgery.
18 elderly patients submitted to major surgery for malignancies or other disease were studied to assess the relationship between changes of blood coagulation factors and inhibitors in the early post-operative period and the appearance of lower limb deep vein thrombosis. A decrease in serum antithrombin III (AT III) Protein C antigen (PC: Ag) and Plasminogen activity (PLG) levels from the second to the fourth postoperative day, together with a simultaneous increase in serum fibrinogen (FG) and von Willebrand Factor (vWF:Ag) antigen levels was observed. In 8 patients, PC:Ag levels dropped below the limit considered at risk to develop DVT (less than 60 U/dl). A patient with the lowest PC:Ag levels had deep vein thrombosis From the analysis of data it was concluded that in the postoperative period, blood coagulation changes occur in elderly patients, predisposing to the risk of deep vein thrombosis.


Extension of pulmonary adenocarcinoma into the left atrium.
A 62-year-old man presented with pulmonary adenocarcinoma that penetrated through the pulmonary vein into the left atrium. The tumor in the left atrium was removed via a right lower lobectomy under cardiopulmonary bypass. In selected cases, radical removal of a tumor in patients without mediastinal lymph node involvement may improve the prognosis. The use of cardiopulmonary bypass extends the possibilities of radical tumor removal.


Transposon insertional mutagenesis in mice identifies human breast cancer susceptibility genes and signatures for stratification.
Robust prognostic gene signatures and therapeutic targets are difficult to derive from expression profiling because of the significant heterogeneity within breast cancer (BC) subtypes. Here, we performed forward genetic screening in mice using Sleeping Beauty transposon mutagenesis to identify candidate BC driver genes in an unbiased manner, using a stabilized N-terminal truncated β-catenin gene as a sensitizer. We identified 134 mouse susceptibility genes from 129 common insertion sites within 34 mammary tumors. Of these, 126 genes were orthologous to protein-coding genes in the human genome (hereafter, human BC susceptibility genes, hBCSGs), 70% of which are previously reported cancer-associated genes, and ∼16% are known BC suppressor genes. Network analysis revealed a gene hub consisting of E1A binding protein P300 (EP300), CD44 molecule (CD44), neurofibromin (NF1) and phosphatase and tensin homolog (PTEN), which are linked to a significant number of mutated hBCSGs. From our survival prediction analysis of the expression of human BC genes in 2,333 BC cases, we isolated a six-gene-pair classifier that stratifies BC patients with high confidence into prognostically distinct low-, moderate-, and high-risk subgroups. Furthermore, we proposed prognostic classifiers identifying three basal and three claudin-low tumor subgroups. Intriguingly, our hBCSGs are mostly unrelated to cell cycle/mitosis genes and are distinct from the prognostic signatures currently used for stratifying BC patients. Our findings illustrate the strength and validity of integrating functional mutagenesis screens in mice with human cancer transcriptomic data to identify highly prognostic BC subtyping biomarkers.


Sex differences in the genome-wide DNA methylation pattern and impact on gene expression, microRNA levels and insulin secretion in human pancreatic islets.
Epigenetic factors regulate tissue-specific expression and X-chromosome inactivation. Previous studies have identified epigenetic differences between sexes in some human tissues. However, it is unclear whether epigenetic modifications contribute to sex-specific differences in insulin secretion and metabolism. Here, we investigate the impact of sex on the genome-wide DNA methylation pattern in human pancreatic islets from 53 males and 34 females, and relate the methylome to changes in expression and insulin secretion. Glucose-stimulated insulin secretion is higher in female versus male islets. Genome-wide DNA methylation data in human islets clusters based on sex. While the chromosome-wide DNA methylation level on the X-chromosome is higher in female versus male islets, the autosomes do not display a global methylation difference between sexes. Methylation of 8,140 individual X-chromosome sites and 470 autosomal sites shows sex-specific differences in human islets. These include sites in/near AR, DUSP9, HNF4A, BCL11A and CDKN2B. 61 X-chromosome genes and 18 autosomal genes display sex-specific differences in both DNA methylation and expression. These include NKAP, SPESP1 and APLN, which exhibited lower expression in females. Functional analyses demonstrate that methylation of NKAP and SPESP1 promoters in vitro suppresses their transcriptional activity. Silencing of Nkap or Apln in clonal beta-cells results in increased insulin secretion. Differential methylation between sexes is associated with altered levels of microRNAs miR-660 and miR-532 and related target genes. Chromosome-wide and gene-specific sex differences in DNA methylation associate with altered expression and insulin secretion in human islets. Our data demonstrate that epigenetics contribute to sex-specific metabolic phenotypes.


Optimization and characterization of biosurfactant production from kitchen waste oil using Pseudomonas aeruginosa.
Kitchen waste oil (KWO) from catering industries or households was used as a low-cost carbon source for producing biosurfactants by self-isolated Pseudomonas aeruginosa. Fermentation performance with KWO was superior to those with four other carbon sources, with higher optical density (OD600) of 2.33 and lower interfacial tension of 0.57 mN/m. Culture conditions for biosurfactant production were optimized, with optimal pH of 8.0 and nitrogen source concentration of 2.0 g/L, respectively. The results of infrared spectroscopy and liquid chromatography-mass spectrometry (LC-MS) showed that the biosurfactant was a mixture of six rhamnolipid congeners, among which Rha-Rha-C10-C10 and Rha-C10-C10 were the main components, with mass fraction of approximately 34.20 and 50.86%, respectively. The critical micelle concentration (CMC) obtained was 55.87 mg/L. In addition, the rhamnolipids exhibited excellent tolerance to temperature (20-100 °C), pH (6.0-12.0), and salinity (2-20%; w/v) in a wide range, thereby showing good stability to extreme environmental conditions. The rhamnolipids positively affected oil removal from oil sludge and KWO-contaminated cotton cloth, with removal rate of 34.13 and of 30.92%, respectively. Our results demonstrated that biosurfactant production from KWO was promising, with advantages of good performance, low cost and environmental safety.


A Low-Cost Data Acquisition System for Automobile Dynamics Applications.
This project addresses the need for the implementation of low-cost acquisition technology in the field of vehicle engineering: the design, development, manufacture, and verification of a low-cost Arduino-based data acquisition platform to be used in <80 Hz data acquisition in vehicle dynamics, using low-cost accelerometers. In addition to this, a comparative study is carried out of professional vibration acquisition technologies and low-cost systems, obtaining optimum results for low- and medium-frequency operations with an error of 2.19% on road tests. It is therefore concluded that these technologies are applicable to the automobile industry, thereby allowing the project costs to be reduced and thus facilitating access to this kind of research that requires limited resources.


Effects of enrichment with salicylate on bacterial selection and PAH mineralization in a microbial community from a bioreactor treating contaminated soil.
We investigated enrichment with salicylate as a method to stimulate the degradation of polycyclic aromatic hydrocarbons (PAHs) by a microbial communityfrom a bioreactortreating PAH-contaminated soil. DNA-based stable isotope probing (SIP) was used to compare the effect of alternate methods of salicylate addition (spike vs slow, continuous addition) on the diversity of the enriched microbial community. After identification of salicylate degraders by SIP, real-time quantitative PCR (qPCR) primers were developed to quantify the abundances of three groups containing salicylate-utilizing organisms in the bioreactor community before and after enrichment. The different methods of salicylate addition were found to select for different microbial communities. Two groups containing salicylate-degrading bacteria increased in abundance substantially after enrichment by continuous addition of salicylate but did not increase in abundance in response to the spike addition, whereas a third group increased in abundance in response to both methods of salicylate addition. The initial rate of naphthalene mineralization increased significantly after enrichment by spike addition of salicylate, but neither phenanthrene nor benzo[a] pyrene mineralization rates were enhanced. Continuous addition of salicylate did not enhance the mineralization rate for any of the PAHs. These results suggest that enrichment with salicylate can select for naphthalene-degrading bacteria, but does not select for organisms responsible for degrading PAHs of higher molecular weight. Differences in microbial selection observed in this study that resulted from different rates of carbon source addition also have implications for the design of SIP experiments with water-soluble carbon sources.


[The translation of knowledge in the ambit of international cooperation: the experience of Fiocruz in introducing health technologies to Haiti].
To investigate the debate about South-South cooperation, we conducted an analysis of a course on the Management of Physical and Technological Resources in Health given in Haiti as part of a partnership between Fiocruz and the Brazilian and Haitian ministries of health with the aim of enabling the functioning of the units built by Brazil, contributing to the sustainability of the tripartite cooperation project. The course format - designing interventions to overcome real problems identified by the students - resulted in the development of eight intervention pre-projects geared towards overcoming management problems at the reference community hospitals built by Brazil in Haiti.


Social relationships in adolescence and heavy episodic drinking from youth to midlife in Finland and Sweden - examining the role of individual, contextual and temporal factors.
Applying the Process-Person-Context-Time (PPCT) model of the bioecological theory, this study considers whether proximal processes between the individual and the microsystem (social relationships within family, peer group and school) during adolescence are associated with heavy episodic drinking (HED), from youth to midlife, and whether the macro level context (country) plays a role in these associations. Participants of two prospective cohort studies from Finland and Sweden, recruited in 1983/1981 at age 16 (n = 2194/1080), were followed-up until their forties using postal questionnaires. Logistic regression analysis was used to examine associations between social relationships at age 16 and HED (at least monthly intoxication or having six or more units of alcohol in one occasion) at ages 22/21, 32/30 and 42/43. Additive interactions between microsystem settings, as well as between settings and country, were also considered. Consistent with the PPCT model, we found individual, contextual and temporal aspects to be associated with drinking habits. Higher levels of poor family relationships were associated with an increased likelihood of HED (ages 22/21 and 32/30) in both Finnish women and men and Swedish men. Higher levels of peer contact were associated with an increased likelihood of HED in both Finnish women (ages 32 and 42) and men (ages 22 and 32), and Swedish men (age 21). In contrast with the other groups, poorer relationships with classmates were associated with an increased likelihood of HED (age 30) for Swedish women only. For women, the combined effect of having both daily peer contact and living in Finland for HED at age 42/43 was statistically distinguishable from a pure additive effect. Micro and to a lesser extent macro level contexts are associated with heavy episodic drinking well into adulthood. The most relevant processes in the adolescent microsystem occur in family and peer settings. However, long-lasting protective or risk-raising effects between different settings and later HED were not found. Promoting good relationships across different contexts during adolescence may reduce the incidence of HED in adulthood.


Dental caries experience among secondary school children in the Vardar region of the Republic of Macedonia.
The aim of this study was to assess the dental caries in 15-year-old children attending regular public secondary schools in Veles. The study has been carried out during 2013 on adolescents aged 15.01(± 0.42).In this cross-sectional study, the secondary school children from first grades (N = 127) have been selected from 2 Secondary Schools in Veles. The dental status of the participants was evaluated on the basis of the 1997 World Health Organization caries diagnostic criteria for Decayed, Missing or Filled Teeth (DMFT) by 2 calibrated examiners. P value ≤ 0.05 was considered statistically significant. The total number of children in the exercise was 127, consisting of 59 (46.46%) female and 68 (53.54.2%) male. The mean DMFT was 4.9768, with standard deviation (SD) of 3.5084 and 95% confidence interval (CI) of 4.3603-5.5925. Significant Caries (SiC) index was 8.9302. The prevalence of caries-free children was 9.45%. The percentage of untreated caries or the ration of D/DMFT was 0.5601 (56.01%). The present study provides some evidence of relatively high caries prevalence and severity in comparison with the Western European countries. It is necessary to dedicate more attention to the oral health of children and adolescents in our country.


[Accumulation of industrial radionuclides by the Yenisei River aquatic plants in the area affected by the activity of the mining and chemical plant].
The aim of the paper is to investigate accumulation of artificial radionuclides by the Yenisei River aquatic plants collected in the area affected by the activity of the Mining-and-Chemical Combine (Zheleznogorsk) from 1997 to 2000. The samples of aquatic plants were of four species: Potamogeton lucens, Fontinalis antipyretica, Elodea canadensis, and Ceratophyllum demersum. The gamma-spectrometric analysis of the samples of aquatic plants for artificial radionuclides revealed a wide spectrum of long-half-life and short-half-life radionuclides. Radionuclides of activation origin were found in the aquatic plants taken both near the Combine and 200 km down of it. The data obtained suggest that the cooling water of the operating reactor is still being released into the Yenisei. The radiochemical analysis of aquatic plants revealed strontium and plutonium isotopes. Among the aquatic plants, the highest concentration factors for the principal radionuclides were recorded in Fontinalis antipyretica (water moss).


High-order-harmonic generation and superradiance in a seeded free-electron laser.
Higher order harmonic generation in a free-electron laser amplifier operating in the superradiant regime [R. H. Dicke, Phys. Rev. 93, 99 (1954).] has been observed. Superradiance has been induced by seeding a single-pass amplifier with the second harmonic of a Ti:sapphire laser, generated in a β-Barium borate crystal, at seed intensities comparable to the free-electron laser saturation intensity. Pulse energy and spectral distributions of the harmonics up to the 11th order have been measured and compared with simulations.


Protamine-containing insulin allergy and renal dysfunction in a patient with type 2 diabetes.
An 87-year-old woman with type 2 diabetes noticed a red itchy rash at the insulin injection sites 3 weeks after initiation of premixed insulin therapy. Laboratory data at that time showed marked eosinophilia and progression of renal dysfunction. Insulin treatment was discontinued, and antidiabetic oral drugs were used, as well as intravenous injection of dexamethasone. Her skin lesions disappeared, and both eosinophilia and renal dysfunction gradually improved. The results of skin prick tests and measurement of specific immunoglobulin E antibodies suggested that the insulin allergy was caused by protamine. Although cases of insulin allergy associated with renal dysfunction are rare, we must be aware, especially for elderly patients with poor renal function in the first application of insulin.


Viroporin-mediated calcium-activated autophagy.
Autophagy is a cellular response activated by many pathogens, but the mechanism of activation is largely unknown. Recently we showed for the first time that rotavirus initiates the autophagy pathway through a calcium-mediated mechanism. Expression of the rotavirus-encoded NSP4, a pore-forming protein (viroporin), elicits the release of endoplasmic reticulum (ER) lumenal calcium into the cytoplasm of the infected cell. The increased cytoplasmic calcium activates a calcium signaling pathway involving calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) and 5' adenosine monophosphate-activated protein kinase (AMPK) to trigger autophagy. Rotavirus further manipulates autophagy membrane trafficking to transport viral ER-associated proteins to viroplasms, sites of viral genome replication and immature particle assembly. Transport of viral proteins to viroplasms is required for assembly of infectious virus. Thus, NSP4, a multifunctional viral protein known to regulate infectious particle assembly, also modulates membrane trafficking by orchestrating the activation of autophagy to benefit viral replication.


Charging effect of aluminum nitride thin films containing Al nanocrystals.
In this work, the Al-rich AIN thin film is deposited on Si substrate by radio frequency (RF) sputtering to form a metal-insulator-semiconductor (MIS) structure. Al nanocrystals (nc-Al) are formed and embedded in the AIN thin film. Charge trapping/detrapping in the nc-Al leads to a shift in the flat-band voltage (VFB) of the MIS structure. The charge storage ability of the AIN thin films containing Al nanocrystals provides the possibility of memory applications. On the other hand, charge trapping in nc-Al reduces the current conduction because of the breaking of some tunneling paths due to Coulomb blockade effect and the current conduction evolves with a trend towards one-dimensional transport.


Remission of post-transplant focal segmental glomerulosclerosis with angiotensin receptor blockers.
Recurrence of focal segmental glomerulosclerosis (FSGS) is common after kidney transplantation. Plasmapheresis (PP) is considered to be the most effective treatment; however, results are variable and relapse is common after stopping plasmapheresis. Here, we report an unusual case of recurrent FSGS, who achieved complete remission with angiotensin receptor blocker therapy.


Growth curve model analysis for quality of life data.
There is increasing interest in measuring health related quality of life in cancer clinical trials. Most quality of life data are measured repeatedly over a fixed time schedule to capture changes and to reflect relative advantages of study treatments. A multivariate repeated measures model is usually used to analyse this type of data. However, one of the difficulties of this analysis is that quality of life may be affected by the occurrence of some critical events experienced by patients. We may separate a patient's lifetime during study into different 'health states'. The duration of these health states may vary among patients, and may relate to the efficacy of the study treatment. In some cases quality of life data may be missing due to one of the many different types of missing data mechanisms specific for a health state. It is reasonable to assume that the missing data mechanism for a treatment arm is homogeneous within a defined health state, and to control for the potential confounding effect to appropriately assess the impact of treatment on the quality of life. In this paper, we propose a growth curve model conditional on a time-dependent variable of defined health states in order to assess the overall treatment effect while taking into account occurrences of missing data and measurements from irregular visits. A specific contrast can be drawn within the overall model for testing a specific hypothesis without relying on the analysis of subgroups of patients based on a smaller number of repeated measurements. Quality of life data from a recently completed small-cell lung cancer randomized trial are used to illustrate this method.


Natural Products as Promising Therapeutics for Treatment of Influenza Disease.
The influenza virus represents a permanent global health threat because it circulates not only within but also between numerous host populations, thereby frequently causing unexpected outbreaks in animals and humans with a generally unpredictable course of disease and epidemiology. Conventional influenza therapy is directed against the viral neuraminidase protein, which promotes virus release from infected cells, and the viral ion channel M2, which facilitates viral uncoating. However, these drugs, albeit effective, have a major drawback: their targets are of a highly variable sequence. As a consequence, the virus can readily acquire resistance by mutating the drug targets. Indeed, most seasonal A/H1N1 viruses and the 2009 H1N1 virus are resistant to M2 inhibitors, and a significant proportion of the seasonal A/H1N1 viruses are resistant to the neuraminidase inhibitor oseltamivir. Development of new effective drugs for treatment of disease during the regular influenza seasons and the possible influenza pandemic represents an important goal. The results presented here point out natural products as a promising source of low toxic and widely accessible drug candidates for treatment of the influenza disease. Natural products combined with new therapeutic targets and drug repurposing techniques, which accelerate development of new drugs, serve as an important platform for development of new influenza therapeutics.


Cuffless Hypertension Detection using Swarm Support Vector Machine Utilizing Photoplethysmogram and Electrocardiogram.
Hypertension is associated with severe complications, and its detection is important to provide early information about a hypertension event, which is essential to prevent further complications. This study aimed to investigate a strategy for hypertension detection without a cuff using parameters of bioelectric signals, i.e., Electrocardiogram (ECG), Photoplethysmogram (PPG,) and an algorithm of Swarm-based Support Vector Machine (SSVM). This experimental study was conducted to develop a hypertension detection system. ECG and PPG bioelectrical records were collected from the Medical Information Mart for Intensive Care (MIMIC) from normal and hypertension participants and processed to find the parameters, used for the inputs of SSVM and comprised Pulse Arrival Time (PAT) and the characteristics of PPG signal derivatives. The SSVM was n Support Vector Machine (SVM) algorithm optimized using particle swarm optimization with Quantum Delta-potential-well (QDPSO). The SSVMs with different inputs were investigated to find the optimal detection performance. The proposed strategy was performed at 96% in terms of F1-score, accuracy, sensitivity, and specificity with better performance than the other methods tested and methods and also could develop a cuff-free hypertension monitoring system. Hypertension using SSVM, ECG, and PPG parameters is acceptably performed. The hypertension detection had lower performance utilizing only PPG than both ECG and PPG.


Collection and characterization of grapevine genetic resources (Vitis vinifera) in the Holy Land, towards the renewal of ancient winemaking practices.
The importance and extent of wine consumption in all life aspects at the Holy Land is well documented. The Muslim influence in this region led to the abandonment of winemaking practices, and possible loss of indigenous wine varieties. Here we present a country wide collection of the local grapevine population including wild and cultivated forms, and its characterization by genetic, ampelographic and enological methods. The ampelographic analysis shows clear differences between Sativa and Sylvestris groups in flower, leaf and cluster parameters, and that most Sativa belong to proles orientalis. Genetic population analysis was conducted by analyzing 22 common SSR markers, determining first the unique genotypes, and internally assessing the population's structure, showing the existence of two distinct Sativa and Sylvestris populations, and a third mixed one. Likewise, the relationship between the Israeli grapevine population and grapevine populations in Europe and parts of Asia was investigated, showing that the Israeli Sativa and Sylvestris populations cluster closely together, suggesting a common genetic source. Lastly, the enological characteristics of selected Sativa and Sylvestris genotypes are presented, demonstrating their potential for quality wine production. This research significantly contributes toward the re-establishment of indigenous and traditional local grapevine varieties into the modern international wine industry.


Bifacial and Semitransparent Sb2 (S,Se)3 Solar Cells for Single-Junction and Tandem Photovoltaic Applications.
Thin-film solar cells are expected to play a significant role in the space industry, building integrated photovoltaic (BIPV), indoor applications, and tandem solar cells, where bifaciality and semitransparency are highly desired. Sb2 (S,Se)3 has emerged as a promising new photovoltaic (PV) material for its high absorption coefficient, tunable bandgap, and nontoxic and earth-abundant constituents. However, high-efficiency Sb2 (S,Se)3 solar cells exclusively employ monofacial architectures, leaving a considerable gap toward large-scale application in aforementioned fields. Here, a bifacial and semitransparent Sb2 (S,Se)3 solar cell and its extended application in tandem solar cells are reported. The transparent conductive oxides (TCOs) and the ultrathin inner n-i-p structure provide high long-wavelength transmittance. Despite the MnS/ITO Schottky junction, power conversion efficiencies (PCEs) of 7.41% and 6.36% are achieved with front and rear illumination, respectively, contributing to a great bifaciality of 0.86. Consequently, the reported device gains great enhancement in PV performance by exploiting albedo of surroundings and shows exceptional capability in absorbing tilt incident light. Moreover, an Sb2 (S,Se)3 /Si tandem solar cell with a PCE of 11.66% is achieved in preliminary trials. These exciting findings imply that bifacial and semitransparent Sb2 (S,Se)3 solar cells possess tremendous potential in practical applications based on their unique characteristics.


The integration of a telemental health service into rural primary medical care.
Mental health care shortages in rural areas have resulted in the majority of services being offered through primary medical care settings. The authors argue that a paradigm shift must occur so that those in need of mental health care have reasonable, timely access to these services. Changes proposed include integrating mental health services into primary medical care settings, moving away from the traditional view of mental health care services (one therapist, one hour, and one client), and increasing the consultative role of psychologists and other mental health care providers in primary medical care. Characteristics of mental health providers that facilitate effective integration into primary medical care are presented. The results of a needs assessment survey and an example of a telemental health project are described. This project involved brief consultations with patients and their physicians from a shared care model using a broadband internet telecommunications link between a rural clinic and mental health service providers in an urban area.


Development and Characterization of Nanoembedded Microparticles for Pulmonary Delivery of Antitubercular Drugs against Experimental Tuberculosis.
The foremost objective of the present research study was to develop and evaluate the potential of rifampicin (RIF) and isoniazid (INH) loaded spray dried nanoembedded microparticles against experimental tuberculosis (TB). In this study, RIF-INH loaded various formulations (chitosan, guar gum, mannan, and guar gum coated chitosan) were prepared by spray drying and characterized on the basis of in vitro as well as in vivo studies. Results showed that guar gum spray dried particles showed uniform size distribution with smooth surface as compare to mannan formulations. Guar gum batches exhibited excellent flow ability attributed to their optimum moisture content and uniform size distribution. The drug release showed the biphasic pattern of release, i.e., initial burst followed by a sustained release pattern. The preferential uptake of guar gum coated formulations suggested the presence and selective uptake capability of mannose moiety to the specific cell surface of macrophages. In vivo lung distribution study showed that guar gum coated chitosan (GCNP) batches demonstrated prolonged residence at the target site and thereby improve the therapeutic utility of drug with a significant reduction in systemic toxicity. Optimized drug loaded GCNP formulation has resulted in almost 5-fold reduction of the number of bacilli as compared to control group. Histopathology study also demonstrated that none of the treated groups show any evidence of lung tissue abnormality. Hence, GCNPs could be a promising carrier for selective delivery of antitubercular drugs to alveolar macrophages with the interception of minimal side effects, for efficient management of TB.


Obesity accelerates mouse mammary tumor growth in the absence of ovarian hormones.
Obesity increases incidence and mortality of breast cancer in postmenopausal women. Mechanisms underlying this association are poorly understood. Suitable animal models are needed to elucidate potential mechanisms for this association. To determine the effects of obesity on mammary tumor growth, nonovariectomized and ovariectomized C57BL/6 mice of various body weights (lean, overweight, and obese) were implanted subcutaneously with mammary tumor cells from syngeneic Wnt-1 transgenic mice. In mice, the lean phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status. Ovariectomy delayed Wnt-1 tumor growth consistent with the known hormone responsiveness of these tumors. However, obesity accelerated tumor growth in ovariectomized but not in nonovariectomized animals. Diet-induced obesity in a syngeneic mouse model of breast cancer enhanced tumor growth, specifically in the absence of ovarian hormones. These results support epidemiological evidence that obesity is associated with increased breast cancer incidence and mortality in postmenopausal but not premenopausal women. In contrast, maintaining a lean body weight phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status.


Delineating reclamation zones for site-specific reclamation of saline-sodic soils in Dushak, Turkmenistan.
Soil salinization is the widespread problem seriously affecting the agricultural sustainability and causing income losses in arid regions. The major objective of the study was to quantify and map the spatial variability of soil salinity and sodicity. Determining salinity and sodicity variability in different soil layers was the second objective. Finally, proposing an approach for delineating different salinity and sodicity zones was the third objective. The study was carried out in 871.1 ha farmland in Southeast of Dushak town of Ahal Province, Turkmenistan. Soil properties, including electrical conductivity (EC), soil reaction (pH), sodium adsorption ratio (SAR), calcium carbonate and particle size distribution (clay, silt and sand fractions) in 0-30, 30-60, 60-90 and 90-120 cm soil layers were recorded. The EC values in different soil layers indicated serious soil salinization problem in the study area. The mean EC values in 0-90 cm depth were high (8 dS m-1), classifying the soils as moderate to strongly saline. Spatial dependence calculated by the nugget to sill ratio indicated a strong spatial autocorrelation. The elevation was the primary factor affecting spatial variation of soil salinity in the study area. The reclamation of the field can be planned based on three distinct areas, i.e., high (≥12 dS m-1), moderate (12-8 dS m-1) and low (<8 dS m-1) EC values. The spatial trend analyses of SAR values revealed similar patterns for EC and pH; both of which gradually decreased from north to the south-west. The amount of water needed to leach down the salts from 60 cm of soil profile is between 56.4-150.0 ton ha-1 and the average leaching water was 89.8 tons ha-1. The application of leaching water based on the amount of average leaching water will result in higher or lower leaching water application to most locations and the efficiency of the reclamation efforts will be low. Similar results were recorded for sulfur, sulfuric acid and gypsum requirements to remediate sodicity. The results concluded that the best management strategy in planning land development and reclamation schemes for saline and sodic soils require accurate information about the spatial distribution of salinity and sodicity across the target area.


Coronoid hyperplasia. A case report.
Coronoid hyperplasia is a rare condition which is macroscopically characterized by an increase in the dimensions of the coronoid process resulting from an abnormal bony elongation of histologically normal bone. Unilateral cases are more frequent than bilateral ones and can recognize a number of etiological factors, such as exostoses, osteochondroma, traumatic events, inflammatory reactions, neoplasia and manifestations secondary to other pathologies. Etiopathogenesis of bilateral forms has not yet been clarified: in the literature hints to both developmental and endocrine abnormalities are present, and a familiar pattern of inheritance has been evidenced. The poor specificity of signs and symptoms associated with coronoid hyperplasia, which are similar to those of other more frequent forms of temporomandibular disorders, present some problems of differential diagnosis. An accurate assessment must be based on a clinical and anamnestical approach aiming at the identification of pathognomonic clinical symptoms. Considering its limits (such as the possible presence of artefacts and image distortions), orthopantomography has a poor diagnostic usefulness. In this case, magnetic resonance (MR) allowed to evaluate disk-condyle relationship, but it could be also useful to evaluate post-operative complications. In the case of coronoid hyperplasia, the computed tomography (CT) is fundamental for a correct differential diagnosis. CT also allows surgical planning due to its accuracy to detect coronoid process volume and morphology. The present case report is an example of the need for a correct differential diagnosis between the different types of temporomandibular disorders, and it also lends support to the importance of requesting modern imaging techniques during the diagnostic process of the rare or complex cases.


Molecular cloning of polymorphic markers on RLGS gel using the spot target cloning method.
A new method for target cloning of DNA fragments corresponding to spots on the two-dimensional restriction landmark genomic scanning (RLGS) profile has been developed (targeted spot cloning). We used a Not I restriction trapper to select target DNA fragments from Not I, Eco RV double digests of genomic DNA. The use of the restriction trapper substantially reduces the background clones that are established from the direct recovery of RLGS spot DNA from the two-dimensional gels. Genomic DNA clones were isolated in this study as mouse genome markers for 58 spot loci that were previously characterized using RLGS spot mapping. This method provides a powerful tool for isolating DNA clones after their identification by RLGS system.


Fat absorption after longitudinal pancreaticojejunostomy.
This study was undertaken to determine whether fat absorption is improved following longitudinal pancreaticojejunostomy. Ten consecutive patients with chronic pancreatitis underwent measurement of fat absorption (fecal fat, 14C-labeled phenylacetic dipalmitate oil absorption test) before and after operation. Fecal fat increased in 8 of 10 patients following side-to-side pancreaticojejunostomy. However, the average postoperative fecal fat increase of 4.3 gm was of no clinical significance. The observed mild postoperative decline in fat absorption was confirmed by the 14C-labeled phenylacetic dipalmitate test. An improvement in postoperative fat absorption following side-to-side pancreaticojejunostomy Roux-en-Y should not be expected. The primary indication for this procedure for patients with chronic pancreatitis continues to be intractable pain.


Development of a high-efficiency laminated dye-sensitized solar cell with a condenser lens.
Dye-sensitized solar cells have slightly lower photoelectric efficiency than silicon solar cells. Researchers have investigated various ways to address this problem. In this paper, we found that the optimized separation between the condenser lens and the cells was 8 mm. The cell efficiency increased from 2.5% to 8.3% compared to two isolated cells without a lens. If the efficiency of the basic cell can be increased sufficiently, it should be possible to commercialize the product.


Charge distribution in a Kondo-correlated quantum dot.
We report on direct measurement of charge and its distribution in a Kondo correlated quantum dot (QD). A noninvasive potential-sensitive detector, in proximity with a QD, reveals that, although the conductance of the QD is significantly enhanced as it enters the Kondo regime, the average charge remains unaffected. This demonstrates the separation between spin and charge degrees of freedom. We find, however, under certain conditions, an abrupt redistribution of charge in the QD, taking place with an onset of Kondo correlation. This suggests a correlation between the spin and charge degrees of freedom.