Functional Reach Test, Single-Leg Stance Test, and Tinetti Performance-Oriented Mobility Assessment for the Prediction of Falls in Older Adults: A Systematic Review.
The authors sought to systematically review the existing literature on the falls-related diagnostic test properties of the Functional Reach Test (FRT), single-leg stance test (SLST), and Tinetti Performance-Oriented Mobility Assessment (POMA) in older adults across settings and patient populations. The PubMed, EMBASE, and CINAHL databases were searched (inception-July 2020). Inclusion criteria were participants aged 60 years or more, prospectively recorded falls, and the reporting of falls-related predictive validity. Manuscripts not published in English were excluded. Methodological quality of reporting was assessed using the Tooth Scale. Of 1071 studies reviewed, 21 met the inclusion criteria (12 POMA, 8 FRT, 6 SLST). Seven studies (58.3%) used a modified version of the POMA, and 3 (37.5%) used a modified FRT. For the outcome of any fall, the respective ranges of sensitivity and specificity were 0.076 to 0.615 and 0.695 to 0.97 for the POMA, 0.27 to 0.70 and 0.52 to 0.83 for the modified POMA, 0.73 and 0.88 for the FRT, 0.47 to 0.682 and 0.59 to 0.788 for the modified FRT, and 0.51 and 0.61 for the SLST in community-dwelling older adults. For the SLST, the sensitivity and specificity for recurrent falls in the community-dwelling setting were 0.33 and 0.712, respectively. All the clinical tests of balance demonstrated an overall low diagnostic accuracy and a consistent inability to correctly identify fallers. None of these tests individually are able to predict future falls in older adults. Future research should develop a better understanding of the role that clinical tests of balance play in the comprehensive assessment of falls risk in older adults. Neither the FRT, SLST, nor POMA alone shows consistent evidence of being able to correctly identify fallers across fall types, settings, or older adult subpopulations. These clinical tests of balance cannot substitute a comprehensive falls risk assessment and thus should be incorporated in practice solely to identify and track balance impairment in older adults.


The Yeast Nucleosome Atlas (YNA) database: an integrative gene mining platform for studying chromatin structure and its regulation in yeast.
Histone modification and remodeling play crucial roles in regulating gene transcription. These post-translational modifications of histones function in a combinatorial fashion and can be recognized by specific histone-binding proteins, thus regulating gene transcription. Therefore, understanding the combinatorial patterns of the histone code is vital to understanding the associated biological processes. However, most of the datasets regarding histone modification and chromatin regulation are scattered across various studies, and no comprehensive search and query tool has yet been made available to retrieve genes bearing specific histone modification patterns and regulatory proteins. For this reason, we developed the Yeast Nucleosome Atlas database, or the YNA database, which integrates the available experimental data on nucleosome occupancy, histone modifications, the binding occupancy of regulatory proteins, and gene expression data, and provides the genome-wide gene miner to retrieve genes with a specific combination of these chromatin-related datasets. Moreover, the biological significance analyzer, which analyzes the enrichments of histone modifications, binding occupancy, transcription rate, and functionality of the retrieved genes, was constructed to help researchers to gain insight into the correlation among chromatin regulation and transcription. Compared to previously established genome browsing databases, YNA provides a powerful gene mining and retrieval interface, and is an investigation tool that can assist users to generate testable hypotheses for studying chromatin regulation during transcription. YNA is available online at http://cosbi3.ee.ncku.edu.tw/yna/.


Alcohol and tobacco use and the diseases treated in general practice.
To characterize the use of alcohol and tobacco and correlate both to the diseases of outpatients in a general practice outpatient clinic. The ASSIST (Alcohol, Smoking and Substance Involvement Screening Test) questionnaire was answered by 300 randomly chosen subjects assigned to different groups according to the diseases being treated at the Outpatient General and Teaching Clinic of the Department of Internal Medicine, Hospital das Clínicas of the University of São Paulo's School of Medicine (HC-FMUSP, in the Portuguese acronym), São Paulo, Brazil. The consumption of tobacco and alcohol was characterized and its correlation with the groups of diseases being treated was calculated using Chi-square and Pearson test statistics. Compared to alcohol, tobacco use was more prevalent, more intense and showed more health-, social-, legal- and financial-related damage. Tobacco smoking presented a positive significant (p<0.0001) correlation with respiratory diseases. According to the questionnaire's criteria, few alcohol users would be referred to clinical interventions in comparison to smokers. Respiratory diseases and tobacco use were well correlated based on the ASSIST questionnaire. The preventive value of the questionnaire was more evident in relation to tobacco than alcohol consumption.


[Caerulein-induced contraction of the ileal longitudinal smooth muscle isolated from various animal species].
An effect of caerulein was studied on a contractile response of the ileal longitudinal smooth muscle isolated from seven animal species, monkey, dog, rabbit, guinea-pig, rat, vole and mouse. In isotonic recording, caerulein induced a contraction in the muscle isolated from all animal species. Sensitivities of ileal strips to caerulein in the contractile response was divided into three groups. That is, a high sensitive group; dog and guinea-pig, a middle sensitive group; rabbit and vole, a low sensitive group; monkey, rat and mouse. In another series of experiment, effect of several antagonists was examined on the caerulein-induced contraction in ileal muscle of dog, rabbit or guinea-pig. TTX inhibited the contractions in all the ilea. As the contraction was inhibited by atropine and scopolamine in dog ileum but not in rabbit one, the contraction may be due to an excitation of the cholinergic neuron or an excitation of non-cholinergic excitatory neuron, respectively. On the other hand, it is supposed that the contraction in guinea-pig ileum is involved to both the neurons because the contraction was inhibited partially by scopolamine and not by atropine. In conclusion, the ilea isolated from seven animal species showed species differences in sensitivity to caerulein in contractile response, and caerulein seems induces the contractions involving to different nervous systems in dog, rabbit or guinea-pig ileum, respectively.


Triamcinolone acetonide and hexacetonide intra-articular treatment of symmetrical joints in juvenile idiopathic arthritis: a double-blind trial.
Pharmacokinetic studies have shown that the biological effect of triamcinolone acetonide (TA) is equivalent to that of triamcinolone hexacetonide (TH), if used at double the dosage. In this study we compared the efficacy of intra-articular TA at a dose twice that of TH in symmetrically involved joints, in children with juvenile idiopathic arthritis (JIA). Children with active arthritis and a similar degree of inflammation in two symmetrical joints were enrolled in the study. The symmetry was assessed by both clinical examination and synovial fluid analysis. The dose given was 1 mg/kg up to 40 mg of TH or 2.0 mg/kg up to 80 mg of TA. The identity of injected compound was blinded to the patient and to the physician. Thirty-seven patients, 30 female, seven male, with JIA, entered the study. A total of 86 joints were injected. Twenty-one (53.8%) of the joints injected with TA relapsed first compared with only six (15.4%) of the joints injected with TH. In three (7.7%) relapse occurred simultaneously. Nine (23%) were still in remission after 24-month follow-up. The percentage of joints with lasting remission was higher with TH than with TA (80 vs 47.5% after 12 months and 63.6 vs 32.4% after 24 months, respectively; log rank test P = 0.003). Even when TA is given at higher doses, TH is more effective and should be considered the drug of choice for intra-articular treatment of JIA.


Glycine/glycine N-methyltransferase/sarcosine axis mediates benzene-induced hematotoxicity.
Benzene, an important and widely used industrial chemical, is the cause of different types of blood disorders. However, the mechanisms of benzene-induced hematotoxicity are still unclear. This study aimed to explore the effects of benzene on metabolism, especially in amino acid metabolism, in human peripheral blood B lymphocyte cells (AHH-1 cells) treated with 1,4-benzoquinone (1,4-BQ) and in benzene-exposed population based on the un-targeted and targeted metabolomics platforms. The results showed that 1,4-BQ disturbed the metabolic activity, such as arginine biosynthesis, citrate cycle, glycine, serine, and threonine metabolism pathways, and significantly upregulated the ratio of sarcosine/glycine in vitro. Meanwhile, the targeted metabolomics further showed that the ratio of sarcosine/glycine was also increased in the benzene exposure population. Notably, the expression of glycine N-methyltransferase (GNMT), an enzyme catalyzing the transformation of glycine to sarcosine, was upregulated both in 1,4-BQ treated AHH-1 cells and benzene-exposed workers. These results imply that the glycine/GNMT/sarcosine axis was involved in benzene-induced hematotoxicity. Such evidence will help to develop a better understanding of the underlying mechanism of benzene-induced hematotoxicity at the level of amino acid metabolism.


5-Aminoimidazole-4-carboxamide ribotide transformylase-IMP cyclohydrolase from human CCRF-CEM leukemia cells: purification, pH dependence, and inhibitors.
The bifunctional enzyme 5-aminoimidazole-4-carboxamide ribotide (AICAR) transformylase-IMP cyclohydrolase has been purified 780-fold to apparent homogeneity from human CCRF-CEM leukemia cells, completed with chromatography on Affi-Gel Blue followed by AICAR-Sepharose 4B. Using a sensitive radioassay, IMP cyclohydrolase has a Ks value for 5-formamidoimidazole-4-carboxamide ribotide (FAICAR) at pH 7.4 of 0.87 +/- 0.11 microM. The following purine nucleotide derivatives were potent competitive inhibitors of IMP cyclohydrolase: 2-mercaptoinosine 5'-monophosphate (Ki = 0.094 +/- 0.024 microM), xanthosine 5'-monophosphate (Ki = 0.12 +/- 0.01 microM), 2-fluoroadenine arabinoside 5'-monophosphate (Ki = 0.16 +/- 0.02 microM), 6-mercaptopurine riboside 5'-monophosphate (Ki = 0.20 +/- 0.02 microM), adenosine N1-oxide 5'-monophosphate (Ki = 0.28 +/- 0.03 microM), and N6-(carboxymethyl)adenosine 5'-monophosphate (Ki = 1.7 +/- 0.42 microM). The pH dependencies of Vmax and Vmax/Ks values for IMP cyclohydrolase are consistent with a single ionizable amino acid residue (pKa = 7.57 +/- 0.09) of the enzyme which must be unprotonated for catalysis to occur and a residue (pKa = 7.57 +/- 0.14) which must be unprotonated for FAICAR to bind. The pKa values of 5.81 +/- 0.03 and 9.41 +/- 0.04 determined for FAICAR indicate that ionization of the substrate does not contribute significantly to the pH effects observed. Chemical modification of IMP cyclohydrolase provides evidence for arginine and cysteine residues at the active site, and roles for these residues in the mechanism of catalysis are proposed.


Theoretical clues to the mechanism of dioxygen formation at the oxygen-evolving complex of photosystem II.
The mechanism of the generation of dioxygen at the oxygen-evolving complex (OEC) of photosystem II (PSII), a crucial step in photosynthesis, is still under debate. The simplest unit present in the OEC that can produce O2 is a dinuclear oxo-bridge manganese complex within the tetranuclear Mn4 cluster. In this paper we report a theoretical study of the model complexes [Mn2(mu-O)2(NH3)6(H2O)2]n+ (n = 2-5), for which density functional calculations have been carried out for several electronic configurations. The molecular orbital picture deduced from the calculations indicates that one-electron oxidation of the Mn2IV,IV/(O2-)2 complex (n = 4) mostly affects the oxygen atoms, thus ruling out the existence of a MnV oxidation state in this context, while the incipient formation of an O-O bond in the O2(3-) transient species evolves exothermally toward the dissociation of dioxygen and a Mn2II,III couple. These results identify the electronic features that could be needed to enable an intramolecular mechanism of oxygen-oxygen bond formation to exist at the OEC during photosynthesis.


[Chronic renal disease in diabetic and prediabetic subjects: a community-based study in Shanghai].
The aim of the present study was to assess the prevalence and risk factors of chronic renal disease in hyperglycemic population of Shanghai Caoyang Community. Microalbuminuria was determined by measuring urinary albumin-to-creatinine ratio (ACR) and glomerular filtration rate (GFR) was estimated from fasting serum creatinine. A total of 406 Shanghai Chinese, with the average age of 67.5 +/- 13.8 years (244 with diabetes mellitus and 162 with impaired glucose regulation) from the established hyperglycemic cohort were included. (1) The prevalence of microalbuminuria was 20.9% and 10.5% in the subjects with diabetes and impaired glucose regulation (IGR); (2) The prevalence of a cGFR >or= 60 and < 90, >or= 30 and < 60, < 30 mlxmin(-1)x(1.73 m(2))(-1) were 41.6%, 37.0%, 1.2% respectively in the patients with diabetes, and 34.2%, 47.2%, 1.9% in the patients with IGR. Impaired renal function was 38.2% and 49.1% respectively in the subjects with diabetes and IGR; (3) The prevalence of microalbuminuria was significantly higher in the diabetic patients with hypertension, central obesity, dyslipidemia, history of cardiovascular disease or selinity. Systolic blood pressure, waist circumstance, fasting plasma glucose and history of cardiovascular disease were all independently associated with hyperglycemic microalbuminuria; (4) cGFR was diminished with increased age and the impaired renal function was more frequent in the patients with hypertension (48.5%). There was a significant positive correlation between a diminished cGFR and increasing levels of ACR after the patients with macroalbuminuria were deleted and adjusted age. Serum creatinine, age and systolic blood pressure were independently associated with diabetic cGFR < 60 ml/min/1.73 m(2). The high prevalence of microalbuminuria and impaired renal function in the hyperglycemic population of Caoyang Community underlines the need for cost-effective programs for the detection of chronic renal disease, and approaches to screen it in the hyperglycemic patients should incorporate assessment of GFR in addition to monitoring urine albumin excretion.


Protein-losing enteropathy in ulcerative colitis.
Protein-losing enteropathy (PLE) is a debilitating potential complication of ulcerative colitis (UC). We report a case of PLE in a 26-year-old male patient with UC. The patient lost 50 pounds in the setting of a UC flare and was found to have an albumin level of 1.2 g/dl. Although the patient's UC was clinically controlled with steroids, the weight loss and hypoalbuminemia persisted with the patient's course complicated by development of deep vein thrombosis and pulmonary embolism. The diagnosis of PLE was confirmed with measurement of stool alpha-1-antitrypsin clearance. The patient's condition significantly improved following procto-colectomy.


The intertwining of structure and function: proposed helix-swapping of the SH2 domain of Grb7, a regulatory protein implicated in cancer progression and inflammation.
Grb7 is a multidomain intracellular signaling protein that links activated tyrosine kinases with downstream signaling targets. Best known for its regulatory role in cell migration and tumor metastasis, Grb7 also regulates inflammation by coupling NF-kappaB-inducing kinase with erbB/EGFR family receptors. The "adaptor" role of Grb7 in these processes depends upon binding to membrane-associated tyrosine kinases through its C-terminal SH2 domain. The Grb7-SH2 domain shares structural and functional similarity with the SH2 domain of Grb2, a constituent of the MAP kinase pathway. Both domains show unusual affinity for cyclic (beta-turn) ligands. The Grb2-SH2 domain also shows distinctive self-association behavior, forming intertwined ("swapped") dimers. While Grb7 and its SH2 domain are each known to dimerize, the mechanisms and functional significance of this self-association are incompletely understood. Additional residues in the Grb7-SH2 domain effectively lengthen its "EF loop" and render the domain a good candidate for swapped dimerization, through exchange of a C-terminal helix. We propose the existence of a swapped dimeric form of the Grb7-SH2 domain and offer a structural model derived through novel application of nuclear magnetic resonance-derived restraints.


Decreased osmotic fragility of red blood cells of Eimeria adenoeides-infected turkeys.
The osmotic fragility of red blood cells (RBC) from Eimeria adenoeides-infected turkey poults was compared with that of RBC from control and water-deprived poults. At different hypotonic NaCl concentrations, lysis of RBC from infected poults was 10 to 35% less on day 4 postinoculation (PI) and 50 to 65% less on day 7 PI than that of controls. Red blood cells of poults deprived of water for 3 days were also resistant to lysis; the percent lysis was roughly the same as that of RBC from infected poults at day 7 PI. Incubating control RBC in plasma from infected poults, in extracts of infected ceca, or at different pH levels did not increase their resistance to lysis, suggesting that neither a stabilizing factor in the plasma that had rapid effect on the RBC nor a transient shift in blood pH was involved. Mean RBC size differed little among infected, water-deprived, and control poults (14.0-14.2 X 8.0-8.1 X 3.8 microns). However, although 3.5% of RBC population of control and water-deprived poults were immature (mid to late polychromatic erythrocytes), only 0.4% of the RBC of infected poults were immature. The data suggest that reduced water intake as well as other factors may be involved in the decreased osmotic fragility of RBC from poults infected with E. adenoeides.


Efficacy of a modified transvaginal ultrasound-guided fresh embryo transfer procedure.
To present a modified transvaginal ultrasound (TVUS) guided embryo transfer (ET) procedure and analyze its efficacy in comparison with conventional transabdominal ultrasound (TAUS) guided ET in an unselected population of Brazilian women. This retrospective observational case-control study involved 447 fresh ET cycles, 221 guided by TVUS (Group 1), conducted between June 2016 and February 2019, and 226 by TAUS (Group 2), conducted between July 2012 and December 2015. Pregnancy rate was the main endpoint. Groups were compared using the Z test at a level of significance of 95% (p≤0.05). Patient age ranged from 21 and 48 years; mean age was 37.7 years in Group 1 and 38 years in Group 2. Overall, patients that underwent TVUS-guided fresh ET demonstrated significantly higher pregnancy rates than their counterparts that underwent TAUS-guided fresh ET (p=0.0107). TVUS-guided fresh ET also yielded significantly higher pregnancy rates in the subgroups of women aged 36-39 years (p=0.0037) and ≥ 40 years (p=0.0025). However, no significant pregnancy rate difference was observed in women aged ≤ 35 years (p=0.0905). The results suggested that TVUS-guided fresh ET was at least as effective as TAUS-guided fresh ET in the studied sample. Pending further prospective studies to better ascertain the effect of TVUS-guided ET, the technique presented deserves consideration since it can offer better visualization, more comfort to patients, and requires only one operator, without negatively affecting pregnancy results.


Dermoscopic features of melanocytic nevi in seven different anatomical locations in patients with atypical nevi syndrome.
Dermoscopic screening facilitates early detection of melanoma and is recommended in patients with multiple or atypical nevi. To investigate whether dermoscopic features of acquired melanocytic nevi differ between six body sites (neck, axilla, pectoral area, shoulders, buttocks, legs) and the trunk. One hundred six patients with atypical nevi syndrome from a Digital Dermoscopy Unit were evaluated for the presence of nevi in each of seven body sites, and nevi representative of each region were selected as the predominant nevi. Dermoscopic features of 684 melanocytic nevi located in seven different body sites were analyzed. Globular and globular-homogeneous pattern nevi showed a cephalad distribution. Nevi at the neck, axilla, shoulders, and pectoral area showed a higher proportion of globular and globular-homogeneous patterns than other locations (p < .001). Comma vessels were also more frequent on the neck, axillary area, and shoulders (p < .001). A reticular pattern was more frequent on caudal areas (legs, buttocks and lower back, and abdomen; p < .001). Dermoscopic differences were found in different body areas. This information should be considered in the evaluation of lesions in patients with atypical nevus syndrome.


Scaphocephaly: aesthetic and psychosocial considerations.
A series of 48 children with scaphocephaly has been reviewed. 44 had synostosis of the sagittal suture alone, and four had additional involvement of other sutures. Although six children showed significant developmental delay, with eventual mental retardation in five cases, it does not appear that this is caused by mechanical constriction of the brain. In the majority of cases, scaphocephaly appears to be a benign variant in cranial development. Operation by linear craniectomy was performed for cosmetic reasons in 14 cases, and in general the results were good. Operation was not performed in the other 34 cases, including 15 seen in infancy, and review of these has shown a high incidence of anxiety among parents and children. Therefore there is an acceptable case for cosmetic correction of severe scaphocephaly in infancy.


Localized delivery of DNA to the cells by viral collagen-loaded silica colloidal crystals.
Low-molecular-weight colloidal crystals with enhanced biocompatibility and ordered porous structure are used in drug-delivery systems. The objective of our study is to demonstrate the use of silica nanoscale colloid particles for localized recombinant DNA release. The colloids were coated with collagen-containing viral vector constructs of lentiviral green fluorescent protein (GFP), and solidified at 37 degrees C. The colloid-collagen-viral vector platform (CCP) was transferred to cell monolayer cultures of human lung fibroblasts. Results show specific infection of cells directly beneath the platform, as evidenced by positive GFP in their cytoplasm, while neighboring cells show no cytoplasmic GFP The infection of specific cells is probably due to the gradual release of viral particles from the collagen matrix by cell-secreted collagenase, which avoids overdosing the cells with viral particles, resulting from the cytopathic effect often seen with high-titer viral infection. Cells infected with the lentiviral-GFP or lentivirus alone, not incorporated into the colloid-collagen device, show caspase 3-associated apoptotic cell death. This suggests that colloidal crystal-coated collagen may be used as a powerful platform to deliver genes of choice to localized subgroups of specific cells of interest. This specificity in the delivery mode is beneficial for functional studies of gene-directed impact on a particular cell population of interest in a heterogeneous cell culture.


High-resolution, non-invasive animal tracking and reconstruction of local environment in aquatic ecosystems.
Acquiring high resolution quantitative behavioural data underwater often involves installation of costly infrastructure, or capture and manipulation of animals. Aquatic movement ecology can therefore be limited in taxonomic range and ecological coverage. Here we present a novel deep-learning based, multi-individual tracking approach, which incorporates Structure-from-Motion in order to determine the 3D location, body position and the visual environment of every recorded individual. The application is based on low-cost cameras and does not require the animals to be confined, manipulated, or handled in any way. Using this approach, single individuals, small heterospecific groups and schools of fish were tracked in freshwater and marine environments of varying complexity. Positional tracking errors as low as 1.09 ± 0.47 cm (RSME) in underwater areas up to 500 m2 were recorded. This cost-effective and open-source framework allows the analysis of animal behaviour in aquatic systems at an unprecedented resolution. Implementing this versatile approach, quantitative behavioural analysis can be employed in a wide range of natural contexts, vastly expanding our potential for examining non-model systems and species.


Impulsive ecological control of a stage-structured pest management system.
The dynamics of a stage-structured pest management system is studied by means of autonomous piecewise linear systems with impulses governed by state feedback control. The sufficient conditions of existence and stability of periodic solutions are obtained by means of the sequence convergence rule and the analogue of the Poincare criterion. The attractive region of periodic solutions is investigated theoretically by qualitative analysis. The bifurcation diagrams of periodic solutions are obtained by using the Poincare map, as well as the chaotic solution generated via a cascade of period-doubling bifurcations. The superiority of the state feedback control strategy is also discussed.


Clinical biocompatibility of a neutral peritoneal dialysis solution with minimal glucose-degradation products--a 1-year randomized control trial.
Chronic utilization of a bio-incompatible peritoneal dialysis (PD) solution with acidic pH and a high content of glucose degradation product (GDP) has been implicated as a contributing cause of peritoneal failure. We compared a newly formulated solution of neutral pH and low levels of GDP to a standard PD solution. Fifty new PD patients were randomized to a conventional lactate-buffered fluid (control) and a pH neutral, lactate-buffered, low GDP solution (balance). Patients were followed for 12 months. Serum samples were assayed for C-reactive protein (CRP). PD effluent was collected and assayed for cancer antigen-125 (CA125) and hyaluronan (HA). Clinical end points were the residual renal function and dialysis adequacy indices. After 52 weeks of treatment, PD fluid CA125 rose from 2.45 +/- 0.96 to 14.30 +/- 2.17 U/ml (P < 0.001), and HA declined from 2.26 +/- 0.60 to 1.45 +/- 0.32 mug/ml (P = 0.07) in the balance group. The balance group had a higher PD fluid CA-125 (14.30 +/- 2.17 vs 7.36 +/- 2.23 U/ml, P = 0.007), lower HA (1.45 +/- 0.32 vs 2.55 +/- 0.32 mug/ml, P = 0.007), and lower serum CRP level (1.77 +/- 0.42 vs 7.73 +/- 2.42 mg/l, P = 0.026) than the control group at 52 weeks. There was no difference in dialysis adequacy indices, ultrafiltration volume, urine output, residual renal function, peritonitis rate or need of hospitalization in 1 year. As compared to conventional PD solution, the use of balance, a neutral pH, low GDP solution resulted in a superior profile of PDE mesothelial cell marker and a lower degree of systemic inflammation, and the difference was maintained for 1 year. It remains to be determined whether these effects could result in better long-term clinical outcome.


Effects of body position on intracranial and cerebral perfusion pressures in isoflurane-anesthetized horses.
Inhalant anesthetics may interfere with normal cerebrovascular autoregulation. It was, therefore, hypothesized that intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in isoflurane-anesthetized horses would be especially sensitive to body and head position because of the potential for large hydrostatic gradients between the brain and heart in this species. Anesthesia was induced and maintained in six clinically healthy, unmedicated geldings with 1.57% isoflurane in O(2); mechanical ventilation was used to maintain normocapnia. ICP was measured by using a subarachnoid strain-gauge transducer. Blood gases and carotid arterial, right atrial, and airway pressures were also measured. Five body positions were studied in semirandomized order: dorsal recumbency (DR) with head down (HD), DR with head level (HL), lateral recumbency (LR), sternal recumbency (SR) with HL, and SR with head up (HU). Data were analyzed by using paired t-tests. ICP and CPP values, respectively, are as follows (means +/- SD): 36 +/- 4 and 55 +/- 18 mmHg (DR-HD); 34 +/- 6 and 51 +/- 32 mmHg (DR-HL); 24 +/- 5 and 48 +/- 4 mmHg (LR); 19 +/- 11 and 87 +/- 12 mmHg (SR-HL); and -14 +/- 7 and 71 +/- 10 mmHg (SR-HU). Significant differences were found among all positions, except for SR-HL vs. LR. Significant increases in CPP were observed only in sternal positions. In conclusion, ICP in isoflurane-anesthetized horses changes inversely with the brain-to-heart hydrostatic gradient. DR may also cause increases in ICP, irrespective of head position.


Four-dimensional space groups for pedestrians: composite structures.
Higher-dimensional crystals have been studied for the last thirty years. However, most practicing chemists, materials scientists, and crystallographers continue to eschew the use of higher-dimensional crystallography in their work. Yet it has become increasingly clear in recent years that the number of higher-dimensional systems continues to grow from hundreds to as many as a thousand different compounds. Part of the problem has to do with the somewhat opaque language that has developed over the past decades to describe higher-dimensional systems. This language, while well-suited to the specialist, is too sophisticated for the neophyte wishing to enter the field, and as such can be an impediment. This Focus Review hopes to address this issue. The goal of this article is to show the regular chemist or materials scientist that knowledge of regular 3D crystallography is all that is really necessary to understand 4D crystal systems. To this end, we have couched higher-dimensional composite structures in the language of ordinary 3D crystals. In particular, we developed the principle of complementarity, which allows one to identify correctly 4D space groups solely from examination of the two 3D components that make up a typical 4D composite structure.


Beyond 'clinical'?: four-dimensional medical education.
Medical education is in crisis. Undergraduates experience an excessive burden of information, develop attitudes to learning that are based on passive acquisition of knowledge than on curiosity and exploration, and suffer from progressive disenchantment with medicine. There is also a serious problem of providing adequate clinical experience for medical students at existing teaching sites, largely because of reduction in bed numbers, increased patient throughput and clinical specialization. This problem was identified over a decade ago in London but has not been solved by the merger of medical schools. A recent survey in one London teaching hospital showed underemployment of students and limited patient contact. A review of clinical clerkships in an Australian medical school revealed that one-third of teachers were perceived as unconcerned, discouraging, derogatory or hostile, and only one-half were rated as effective educators. One consequence has been the development of a wide-ranging debate on changing medical education. Traditionalists have diminishing room for manoeuvre in defence of existing educational practices, as cautious bodies like the General Medical Council (GMC) opt for fundamental reform.


Leukocyte count and risk of thrombosis in patients undergoing haematopoietic stem cell transplantation or intensive chemotherapy.
Elevated white blood cell count has recently been established as an independent risk factor for thromboembolic events in patients with myeloproliferative syndromes. Thrombotic events occur frequently in patients with haematological malignancies undergoing intensive cytoreductive treatment. We evaluated retrospectively the association of leukocyte counts and thrombosis in three cohorts of 100 patients each undergoing autologous or allogeneic haematopoietic stem cell transplantation or chemotherapy, respectively. A total of 26 thromboembolic events were recorded, 10 in recipients of allogeneic transplants, five in autografted patients, and 11 in the chemotherapy group. Fifteen events were central venous catheter related. Non-catheter related thrombotic events were pulmonary embolism (N=5), hepatic veno-occlusive disease (N=2), deep-vein thrombosis (N=1), stroke (N=1), ovarian vein thrombosis (N=1), and left ventricular thrombosis (N=1). Hazard rates showed two peaks, a first during cytoreduction in all groups, and a second after engraftment in transplanted patients. Time-dependent multivariable Cox analysis confirmed an association of leukocytosis with development of thrombosis (hazard ratio for leukocyte count > 11G/l: 9.73, 95% confidence interval 1.98-47.9, p=0.005). The risk associated with leukocytosis was independent from C-reactive protein level. Thrombocyte count and type of treatment (allogeneic vs. autologous transplantation vs. chemotherapy) had no significant influence on thrombosis development. In three cohorts of patients undergoing intensive cytoreductive treatment for haematological malignancy, leukocyte count was strongly associated with development of thrombotic complications.


Synthesis, structure, and spectroscopy of phenylacetylenylene rods incorporating meso-substituted dipyrrin ligands.
The synthesis, structure, and spectroscopic characterization of a series of phenylacetylenylene rodlike molecules containing dipyrromethene (dipyrrin) ligands are described. The combination of the phenylacetylenylene groups with the porphyrinogenic dipyrrin moieties results in a rich absorption spectroscopy for these compounds, although the fluorescence of the phenylacetylenylene moiety is quenched by presence of the dipyrrin chelator. The Cu(2+) and Fe(3+) complexes of these ligands have been prepared and three of these compounds have been structurally characterized by using single-crystal X-ray diffraction. Unlike other octahedral metal-dipyrrin complexes described to date, one of the iron complexes demonstrates ideal threefold symmetry in the solid-state. The elongated structure and high symmetry of these complexes suggests the use of these meso-substituted phenylacetylenylene ligands as an interesting class of extended, branched molecules for the construction of supramolecular architectures.


Nosocomial postoperative tetanus infection.
In light of the fact that tetanus spores are present throughout the environment, this article presents a case of nosocomial postoperative tetanus. A review of the immunization schedule is included to familiarize the surgeon with the active and passive methods of immunization. The authors recognize that tetanus infections are uncommon in our society, but all doctors should become aware of the appropriate treatment program as presented in this article.


Development of a ligase detection reaction/CGE method using a LIF dual-channel detection system for direct identification of allelic composition of mutated DNA in a mixed population of excess wild-type DNA.
We developed an inexpensive LIF dual-channel detection system and applied it to a ligase detection reaction (LDR)/CGE method to identify the allelic composition of low-abundance point mutations in a large excess of wild-type DNA in a single reaction with a high degree of certainty. Ligation was performed in a tube with a nonlabeled common primer and multiplex discriminating primers, each labeled with a different standard fluorophore. The discriminating primers were directed against three mutant variations in codon 12 of the K-ras oncogene that have a high diagnostic value for colorectal cancer. LDR products generated from a particular K-ras mutation through successful ligation events were separated from remaining discriminating primers by CGE, followed by LIF detection using the new system, which consists of two photomultiplier tubes, each with a unique optical filter. Each fluorophore label conjugated to the corresponding LDR product produced a distinct fluorescence signal intensity ratio from the two detection channels, allowing spectral discrimination of the three labels. The ability of this system to detect point mutations in a wild-type sequence-dominated population, and to disclose their allelic composition, was thus demonstrated successfully.


RET fusion in advanced non-small-cell lung cancer and response to cabozantinib: A case report.
Lung cancer is a series of gene-driven disease. EGFR, ALK, and ROS1 are 3 major driver genes that play an important role in lung cancer development and precision management. Additionally, rare genetic alterations continue to be discovered and may become novel targets for therapy. The RET gene is one of such rare genetic alteration of non-small cell lung cancer (NSCLC). In this report, we present a RET-positive case that benefited from cabozantinib treatment. A 50-year-old male patient was diagnosed with lung adenocarcinoma 2 years ago, at that time he received palliative surgery of pulmonary carcinoma and completed 4 cycles of chemotherapy with gemcitabine and cisplatin. Six months later, he was hospitalized in our cancer center due to the disease recurrence, presenting with pleural metastasis. Gene alteration was examined using the intraoperative specimen by PCR method, and KIF5B/RET gene fusion was detected. Therefore, the patient was diagnosed with late-stage lung adenocarcinoma with RET gene mutation. The patient received treatment with cabozantinib from June 2017. Cabozantinib was administered (140 mg orally, once daily) for approximate 9 months, and his disease achieved stable disease (SD). During that period, there were no severe adverse events (AE), except for a grade II rash (CTCAE 4.0). We found that the RET fusion gene is a novel driver molecular of lung adenocarcinoma in patients without common mutations in such genes as EGFR, ALK, and ROS1. This case report supports a rationale for the treatment of lung adenocarcinoma patients with a RET fusion and provides alternative treatment options for these types of NSCLC patients.


Managing everyday ethics in assisted living: a research-based case analysis for the classroom.
This paper presents a complex, but realistic, picture of the lived experience in assisted living (AL), and provokes thoughtful reflection about the operational and ethical challenges faced in the delivery of care to an increasingly frail population in a typical AL facility. Developed from the findings of a two-year qualitative research project, the case represents a composite of selected data collected at five AL facilities that participated in the study. Students will participate in individual and small group exercises that challenge them to identify everyday ethical concerns in AL, and to suggest ways that management can address these issues. The case is suitable for cross-disciplinary use, and can be effectively applied in the fields of management, health care administration, sociology, gerontology, social work, and nursing, either on the graduate or undergraduate level. It is especially well suited to courses that incorporate the topics of long-term care, senior housing, or ethics.


Chromium speciation and fractionation in ground and surface waters in the vicinity of chromite ore processing residue disposal sites.
Chromium concentrations of up to 91 mg l(-1) were found by ICP-OES for ground water from nine boreholes at four landfill sites in an area of S.E. Glasgow/S. Lanarkshire where high-lime chromite ore processing residue (COPR) from a local chemical works had been deposited from 1830 to 1968. Surface water concentrations of up to 6.7 mg l(-1) in a local tributary stream fell to 0.11 mg l(-1) in the River Clyde. Two independent techniques of complexation/colorimetry and speciated isotope dilution mass spectrometry (SIDMS) showed that Cr was predominantly (>90%) in hexavalent form (CrVI) as CrO4(2-), as anticipated at the high pH (7.5-12.5) of the sites. Some differences between the implied and directly determined concentrations of dissolved CrIII, however, appeared related to the total organic carbon (TOC) content. This was most significant for the ground water from one borehole that had the highest TOC concentration of 300 mg l(-1) and at which < 3% of Cr was in the form of CrVI. Subsequent ultrafiltration produced significant decreases in Cr concentration with decreasing size fractions, e.g. <0.45 microm, < 100 kDa, <30 kDa and < 1 kDa by the tangential-flow method. As this appeared related more to concentrations of humic substances than of TOC per se, horizontal bed gel electrophoresis of freeze-dried ultrafilter retentates was carried out to further characterise the CrIII-organic complex. This showed for the main Cr-containing fraction, 100 kDa-0.45 microm, that the Cr was associated with a dark brown band characteristic of organic (humic) matter. Comparison of gel electrophoresis and FTIR results for ultrafilter retentates of ground water from this borehole with those for a borehole at another site where CrVI predominated suggested the influence of carboxylate groups, both in reducing CrVI and in forming soluble CrIII-humic complexes. The implications of this for remediation strategies (especially those based on the addition of organic matter) designed to reduce highly mobile and carcinogenic Cr(VI)O4(2-) to the much less harmful CrIII as insoluble Cr(OH)3 are discussed.


Reactive angioendotheliomatosis: a study of 15 cases demonstrating a wide clinicopathologic spectrum.
Reactive angioendotheliomatosis (RAE) is a rare condition characterized by cutaneous vascular proliferation that usually occurs in patients with diverse types of coexistent systemic disease. Although intravascular proliferation of endothelial cells has been considered to be the key histologic feature in RAE, other patterns of vascular proliferation have also been described. We reviewed the clinicopathologic features in 15 cases of RAE. The study group comprised eight males and seven females with an age range of 47-88 years (median 65 years). Eleven patients had coexistent systemic disease: renal disease (six patients, including three post renal transplantation); valvular cardiac disease (two patients); one patient each had alcoholic cirrhosis, glioblastoma multiforme (on chemotherapy), and rheumatoid arthritis/polymyalgia rheumatica. Six patients were iatrogenically immunosuppressed at the onset of the skin lesions. The clinical appearance included multiple erythematous macules, plaques, tumors, and ulcerated lesions, with a wide distribution but a propensity to involve limbs. Lesions had been present for 1 month to 4 years (median 4 months). Lesions resolved in four cases, improved in two cases, remained static in one case, and progressed in four cases. Two cases were recent and follow-up was not available in two other cases. Three patients died of their coexistent systemic disease with resolution, improvement, and progression of lesions, respectively. All lesions were characterized histologically by a proliferation of capillaries in the dermis, with variably diffuse (seven cases), lobular (six cases), or mixed lobular and diffuse patterns (two cases). There was marked intercase and intracase heterogeneity in histologic features. Common features included fibrin microthrombi (nine cases), reactive (fasciitis-like) dermal alterations (seven cases), and foci of epithelioid endothelium (four cases). Four of 10 cases tested showed positive immunohistochemical staining for HHV-8 latent nuclear antigen in lesional endothelial cell nuclei. This study suggests that RAE has a broader clinicopathologic spectrum than previously described. The pathogenesis of this rare disorder is unknown, but it is likely that immunologic factors play a role.


Two-dimensional liquid chromatography coupled with mass spectrometry for the analysis of Lobelia chinensis Lour. using an ESI/APCI multimode ion source.
A comprehensive approach for the separation and identification of components in a traditional Chinese medicine Lobelia chinensis Lour. was developed using 2D-HPLC coupled with an online photodiode array (PDA) detector and a mass spectrometer. The extract of L. chinensis Lour. was separated on a CN column in the first-dimensional HPLC, and then each of the collected fractions was further separated on an ODS column followed by an online PDA detector. After separation in the two different chromatographic modes, the eluents were delivered to a quadrupole mass spectrometer equipped with a multimode ion source of an ESI and an atmospheric pressure chemical ionization (ESI/APCI). At least 536 components in L. chinensis Lour. extract were detected and 6 of them were identified as apigenin 7-O-rutinoside, luteolin, lobetyolinin, lobetyolin, diosmin, and linarin, respectively, according to their UV spectrum and mass spectrum. The results demonstrated the powerful resolution, high peak capacity, as well as the identification capability of the 2D-HPLC combined with PDA and ESI/APCI-MS for the analyses of complex samples.


Feasibility, acceptability, and cost of referring surgical patients for postdischarge cessation support from a quitline.
The aim of the study was to assess the feasibility, acceptability, and cost of referral of smoking patients to a proactive quitline service for postdischarge cessation support. Participants were recruited from the preoperative clinic of an Australian hospital. Data were collected from project records and a telephone interview with participants 6 months after attending the preoperative clinic. The study found that 64% of the 67 participants accepted an offer of referral to the quitline by preoperative clinic staff. Some 74% of patients referred to the quitline were contacted by the quitline after discharge. Smokers contacted by the quitline and clinic staff referring patients to the quitline generally responded favorably on items assessing the acceptability of the quitline service and the process of referral to the quitline. Referral to the quitline service cost less than US$2 per patient. Referral of patients to a quitline is feasible, was generally considered acceptable by surgical patients and staff, and was inexpensive.


Sharing the Same Reality, Healthy Relations Between Colleagues at Work: A Meta-Synthesis.
Good relations are important at work, leading to well-being among coworkers. Since the latest research in nursing is mostly about bullying, and lateral violence, it was important to study what healthy relations mean. The aim was to identify and synthesize qualitative studies that describe healthy relations, creating health and well-being between colleagues at work. A meta-synthesis approach, inspired by Sherwood's steps of analysis, was chosen for this study. Ten articles from three continents, comprising 230 participants, were included. Two themes were identified as follows: (a) creating a mutual bond on a personal level and a permissive atmosphere through the human warmth; and (b) sharing togetherness in a greater whole, offering unconditional help and devoting themselves to taking care of each other. An overarching metaphor implicating the home/homeness was abstracted from the two themes: "Healthy relations between colleagues at work constitute the community as a common world, containing feelings of being at home, implying acting in an expression of the ethos and dignity, a culture created that makes the ideal form of healthy relations visible." Nurses find their meaning when they work in a permissive environment, and when they are allowed to be themselves. Such meaning can be found through their engagement with one another, by offering each other unconditional help. Good relationships lead to a place they call their home, where there is trust and friendship.


Anti-Markovnikov Hydrofunctionalization of Alkenes: Use of a Benzyl Group as a Traceless Redox-Active Hydrogen Donor.
A protocol for the anti-Markovnikov hydrofunctionalization of alkenes has been developed by the use of a benzyl group as a traceless redox-active hydrogen donor. Under copper catalysis and in the presence of CF3 - or N3 -containing hypervalent iodine reagents, a series of homoallylic alcohol derivatives were hydrofunctionalized regioselectivity. A similar principle was also applied to the hydrofunctionalization of alkenols.


The business of palliative medicine--Part 3: The development of a palliative medicine program in an academic medical center.
Palliative medicine is the total continuing care of patients with cancer. Most resources for cancer care focus on curative attempts while often ignoring the symptoms created by the disease and its treatment. Attempts at curative treatment of the malignancy must be coupled with pain and symptom relief psychosocial and spiritual care, and support for the patient and family extending from the time of diagnosis through the bereavement period. To accomplish this important goal, we must establish comprehensive palliative medicine programs in cancer centers throughout the world. These programs must include education, research, and patient care and must work through an interdisciplinary team. The Cleveland Clinic Foundation palliative medicine program (PMP) is composed of a primary inpatient service, consult service, outpatient clinic, hospice homecare, and cancer homecare services. In this article, we describe the structure and development of the program and suggest future avenues for growth.


Improved ultrastructure of the desmosome-intermediate filament complex in MCF-7 breast cancer cells.
We report on the application of variations to the traditional TEM processing methods, which provide improved clarity of the desmosome-cytoskeleton complex of MCF-7 human breast cancer cells. A more comprehensive understanding of the ultrastructure is presented, which in the past has been demonstrated in diagrammatic form based on numerous electron micrographs. Ultrastructural analysis shows that intermediate filament bundles do not terminate at the desmosome structure, but instead are continuous into the cytoplasm. Furthermore only a minor proportion of individual filaments are in actual contact with the desmosome plaque. Intermediate filaments were also observed throughout the cytoplasm and to the surface of the nuclear membrane. Extraction protocols allowed clear identification of other cellular features such as nuclear pores, which are approximately 80-85 nm in diameter, and were best viewed in sections cut tangentially to the nuclear surface.


Arterial Spin-Labeling Improves Detection of Intracranial Dural Arteriovenous Fistulas with MRI.
Intracranial dural arteriovenous fistulas carry a risk of substantial neurologic complications but can be difficult to detect on structural MR imaging and TOF-MRA. The purpose of this study was to assess the accuracy and added value of 3D pseudocontinuous arterial spin-labeling MR imaging for the detection of these lesions. This retrospective study included 39 patients with a dural arteriovenous fistula and 117 controls who had undergone both DSA and MR imaging with pseudocontinuous arterial spin-labeling. Two neuroradiologists blinded to the DSA results independently assessed MR imaging with and without pseudocontinuous arterial spin-labeling. They recorded specific signs, including venous arterial spin-labeling signal, and the likelihood of a dural arteriovenous fistula using a 5-point Likert scale. Logistic regression and receiver operating characteristic analyses were performed to determine the accuracy of specific signs and the added value of pseudocontinuous arterial spin-labeling. Interobserver agreement was determined by using κ statistics. Identification of the venous arterial spin-labeling signal had a high sensitivity (94%) and specificity (88%) for the presence a dural arteriovenous fistula. Receiver operating characteristic analysis showed significant improvement in diagnostic performance with the addition of pseudocontinuous arterial spin-labeling in comparison with structural MR imaging (Δarea under the receiver operating characteristic curve = 0.179) and a trend toward significant improvement in comparison with structural MR imaging with time-of-flight MRA (Δarea under the receiver operating characteristic curve = 0.043). Interobserver agreement for the presence of a dural arteriovenous fistula improved substantially and was almost perfect with the addition of pseudocontinuous arterial spin-labeling (κ = 0.92). Venous arterial spin-labeling signal has high sensitivity and specificity for the presence of a dural arteriovenous fistula, and the addition of pseudocontinuous arterial spin-labeling increases confidence in the diagnosis of this entity on MR imaging.


Operant conditioning and the orbitofrontal cortex in schizophrenic patients: unexpected evidence for intact functioning.
Neuroimaging and neuropsychological studies have consistently implicated dorsolateral prefrontal cortex as abnormal in schizophrenia. However, other areas of frontal cortex have received far less attention. In particular, few studies have examined orbital frontal regions with other than olfactory tests. In the present study we wished to assess the functional capability of orbital frontal cortex using a test developed by Bechara et al. (1994) that assesses a subject's capacity to acquire a preference through reward and punishment, using a gambling task that involved gains and losses of play money. Thirty normal subjects and 12 patients with schizophrenia (three undifferentiated, eight paranoid, one schizoaffective) comprised the sample in the present study. We found that patients with schizophrenia exhibited a pattern of findings similar to that of normals and dissimilar to that of patients with known orbital frontal damage. In our study, both normal subjects and schizophrenic patients chose most frequently from decks of cards in which there were frequent rewards and infrequent penalties, as might be expected on the basis of operant conditioning literature. We also found that performance on this task was not correlated with tests of working memory or long-term memory, suggesting that the development of a preference may occur implicitly. Our findings also argue against a general deficit in schizophrenia, as performance on the gambling task appeared relatively uncompromised.


From Sticky to Slippery: Self-Functionalizing Lubricants for In Situ Fabrication of Liquid-Infused Surfaces.
Liquid-infused surfaces offer a versatile approach to create self-cleaning coatings. In such coatings, a thin film of a fluid lubricant homogeneously coats the substrate and thus prevents direct contact with a second, contaminating liquid. For stable repellency, the interfacial energies need to be controlled to ensure that the lubricant is not replaced by the contaminating liquid. Here, we introduce the concept of self-functionalizing lubricants. Functional molecular species that chemically match the lubricant but possess selective anchor groups are dissolved in the lubricant and self-adhere to the surface, forming the required surface chemistry in situ from within the applied lubricant layer. To add flexibility to the self-functionalizing concept, the substrate is first primed with a thin polydopamine base layer, which can be deposited to nearly any substrate material from aqueous solutions and retains reactivity toward electron-donating groups such as amines. The temporal progression of the in situ functionalization is investigated by ellipsometry and quartz crystal microbalance and correlated to macroscopic changes in contact angle and contact angle hysteresis. The flexibility of the approach is underlined by creating repellent coatings with various substrate/lubricant combinations. The prepared liquid-infused surfaces significantly reduce cement adhesion and provide easy-to-clean systems under real-world conditions on shoe soles.


Protein and siRNA delivery by transportan and transportan 10 into colorectal cancer cell lines.
Cell penetrating peptides (CPPs) have the ability to translocate through cell membranes with high efficiency and therefore can introduce biological agents with pharmaceutical properties into the cell. Transportan (TP) and its shorter analog transportan 10 (TP10) are among the best studied CPPs, however, their effects on viability of and cargo introduction into colorectal cancer (CRC) cells have yet not been investigated. The aim of our study was to evaluate the cytotoxic effects of TP and TP10 on representative CRC lines and the efficiency of protein (streptavidin) and siRNA cargo delivery by TP-biotinylated derivatives (TP-biot). HT29 (early stage CRC model) and HCT116 (metastatic CRC model) cell lines were incubated with TP, TP10, TP-biot1, TP-biot13 and TP10-biot1. The effects of studied CPPs on cell viability and cell cycle were assessed by MTT and annexin V assays. The uptake of streptavidin-FITC complex into cells was determined by flow cytometry and fluorescence microscopy, with the inhibition of cellular vesicle trafficking by brefeldin A. The efficiency of siRNA for SASH1 gene delivery was measured by quantitative PCR (qPCR). Since up to 10 µM concentrations of each CPP showed no significant cytotoxic effect, the concentrations of 0.5-5 µM were used for further analyses. Within this concentration range none of the studied CPPs affected cell viability and cell cycle. The efficient and endocytosis-independent introduction of streptavidin-FITC complex into cells was observed for TP10-biot1 and TP-biot1 with the cytoplasmic location of the fluorescent cargo; decreased SASH1 mRNA level was noticed with the use of siRNA and analyzed CPPs. We conclude that TP, TP10 and their biotinylated derivatives can be used as efficient delivery vehicles of small and large cargoes into CRC cells.


Seroprevalence of Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV) In District Vehari, Pakistan.
The aim of the study was to evaluate the prevalence of hepatitis C virus (HCV) and hepatitis B virus (HBV) in district Vehari, Pakistan; and to highlight the alarming situation of HCV. This survey was conducted in the district from June to August 2018. A total of 697 (72.99%) cases out of 955, were found to be infected with hepatitis viruses, among which, 681 (71.3%) were infected with HCV and 16 (1.68%) with HBV. HCV was found more prevalent in females while more cases of HBV were reported in males. Overall age ranged from 31 to 60 years, with females from 51-60 years; infected with HCV and HBV in male with age range 19-30 years infected with HBV. The situation of the seroprevalence of HCV is alarming and the authorities in Pakistan should take extensive measures for the elimination of the hepatitis viruses from Pakistan. Key Words: Seroprevalence, Hepatitis C virus, Hepatitis B virus, Pakistan.


Type 1 allergy-induced endolymphatic hydrops and the suppressive effect of leukotriene receptor antagonist.
To investigate allergic endolymphatic hydrops (EH) and the effect of leukotriene receptor antagonist (LTRA). Experiment 1: Thirty-six guinea pigs were actively sensitized with DNP-ascaris twice and were provoked with DNP-bovine serum albumin 1 week after the second sensitization. Alterations in the inner ear were investigated histologically at 1, 12, 24, and 36 hours after the provocation, and changes of the endolymphatic space were quantitatively assessed. The animals in the control group received no sensitization but only distilled water. Experiment 2: Twenty-four guinea pigs were actively sensitized and provoked in the same manner. Animals received oral administration of LTRA 1 hour before the provocation. Alterations in the inner ear were investigated as same manner as in Experiment 1. Experiment 3: Eleven of 19 guinea pigs were actively sensitized and provoked in the same manner. Eight animals in the control group received distilled water. One hour after these procedures, the changes in p-AVP levels were investigated. Experiment 1: EH was observed 12, 24, and 36 hours after the last sensitization. In these groups, their cross-sectional areas of the scala media were significantly larger than that of the control group. Degranulation of mast cells was observed in the endolymphatic sac. Experiment 2: In animal groups with LTRA, EH was not observed at all. Experiment 3: P-AVP levels were significantly elevated in animals with the sensitization. The sensitization with DNP-Ascaris produced allergic EH and elevation of p-AVP, and allergic EH was inhibited by LTRA.


Experimental renal failure in the rat modulates cardiac Na,K-ATPase alpha 2 mRNA but not protein.
The decreased abundance and enzymatic activity of myocardial Na,K-ATPase have been recognized previously to occur in chronic uremia. However, the activity of the cardiac sodium pump as defined by the uptake of 86Rb is normal. The discrepancies between these findings may have resulted from the inability to distinguish between the different Na,K-ATPase isoforms now known to exist in cardiac muscle. To investigate this question, steady-state levels of Na,K-ATPase alpha and beta mRNA isoforms, alpha 1, alpha 2, and beta 1 protein, and specific high-affinity binding of [3H]ouabain were quantitated in cardiac muscle from uremic and pair-fed, sham-operated control rats. Steady-state levels of alpha 2 and beta 2 mRNA were significantly decreased (percentage of control levels: alpha 2, 48 +/- 10; beta 2, 74 +/- 9; N = 10; P < 0.025) in chronic renal failure without any change in alpha 1, alpha 3, or beta 1 expression. The number of high-affinity [3H]ouabain-binding sites and Na,K-ATPase alpha 1, alpha 2, and beta 1 subunits was not different from control. In acute renal failure, alpha 2 and beta 2 mRNA levels also were significantly decreased (percentage of control levels: alpha 2, 24 +/- 5; beta 2, 44 +/- 8; N = 6; P < 0.001), but there was no change in the level of alpha 3 or beta 1 mRNA, the number of high-affinity [3H]ouabain-binding sites, or the level of Na,K-ATPase alpha 2 and beta 1 subunits.(ABSTRACT TRUNCATED AT 250 WORDS)


Protease production by species of Entomophthora.
Ten insect-pathogenic species of Entomophthora showed wide variation in their ability to produce alkaline protease in surface culture. E. coronata, the most active producer, was selected for studies in submerged culture together with E. virulenta. All media tested appeared suitable for mycelial growth of these two organisms, but a liver medium was superior for the production of protease. The effect of the constituents of the liver medium upon yield was investigated. The lag between growth and the production of protease was 24 to 40 hr, and only very small amounts of protease were obtained from sonically treated mycelium. The pH values during growth rose from ranges of 4.5 to 7.5 in the initial medium to 7.2 to 7.9, and did not affect the final yields. The optimal temperature for the production of protease by E. coronata was 24 to 32 C, and good growth was observed at temperatures as low as 16 C. The process with E. coronata was scaled up to fermentors without a decrease in yield; 5 enzyme units/liter were obtained after approximately 33 hr. This corresponds to a maximal productivity of 0.45 enzyme unit per liter per hr during the protease-producing phase. The process was insensitive to changes in aeration rate. The liver in the medium was replaced by various agricultural by-products, meat scrap, rapeseed oil meal, cottonseed nutrients, milk powder, and meat hydrolysate, with approximately the same or higher yields of protease.


Altered adenosine 2A and dopamine D2 receptor availability in the 6-hydroxydopamine-treated rats with and without levodopa-induced dyskinesia.
Several lines of evidence imply alterations in adenosine signaling in Parkinson's disease (PD). Here, we investigated cerebral changes in adenosine 2A receptor (A2AR) availability in 6-hydroxydopamine (6-OHDA)-lesioned rats with and without levodopa-induced dyskinesia (LID) using positron-emission tomography (PET) with [11C]preladenant. In parallel dopamine type 2 receptor (D2R) imaging with [11C]raclopride PET and behavioral tests for motor and cognitive function were performed. Parametric A2AR and D2R binding potential (BPND) images were reconstructed using reference tissue models with midbrain and cerebellum as reference tissue, respectively. All images were anatomically standardized to Paxinos space and analyzed using volume-of-interest (VOI) and voxel-based approaches. The behavioral alternations were assessed with the open field test, Y-maze, novel object recognition test, cylinder test, and abnormal involuntary movement (AIM) score. In total, 28 female Wistar rats were included. On the behavioral level, 6-OHDA-lesioned rats showed asymmetry in forepaw use and deficits in spatial memory and explorative behavior as compared to the sham-operated animals. 15-Days of levodopa (L-DOPA) treatment induced dyskinesia but did not alleviate motor deficits in PD rats. Intranigral 6-OHDA injection significantly increased D2R binding in the lesioned striatum (BPND: 2.69 ± 0.40 6-OHDA vs. 2.31 ± 0.18 sham, + 16.6%; p = 0.03), whereas L-DOPA treatment did not affect the D2R binding in the ipsilateral striatum of the PD rats. In addition, intranigral 6-OHDA injection tended to decrease the A2AR availability in the lesioned striatum. The decrease became significant when data were normalized to the non-affected side (BPND: 4.32 ± 0.41 6-OHDA vs. 4.58 ± 0.89 sham; NS, ratio: 0.94 ± 0.03 6-OHDA vs. 1.00 ± 0.02 sham; - 6.1%; p = 0.01). L-DOPA treatment significantly increased A2AR binding in the affected striatum (BPND: 6.02 ± 0.91 L-DOPA vs. 4.90 ± 0.76 saline; + 23.4%; p = 0.02). In PD rats with LID, positive correlations were found between D2R and A2AR BPND values in the ipsilateral striatum (r = 0.88, ppeak = 8.56.10-4 uncorr), and between AIM score and the D2R BPND in the contralateral striatum (r = 0.98; ppeak = 9.55.10-5 uncorr). A2AR availability changed in drug-naïve and in L-DOPA-treated PD rats. The observed correlations of striatal D2R availability with A2AR availability and with AIM score may provide new knowledge on striatal physiology and new possibilities to further unravel the functions of these targets in the pathophysiology of PD.


Neuroprogression and Immune Activation in Major Depressive Disorder.
Traditionally, the neurobiology of major depressive disorder (MDD) has been largely considered from the perspective of the state of major depressive episodes (MDE) versus being in remission, but the current accumulation of disease markers, largely acquired cross-sectionally, is strongly suggestive of neuroprogressive aspects of MDD. This chapter focuses on the changes in disease markers involved in the reorganization of the nervous system in MDD, including the translocator protein (TSPO; an index of microglial activation), glial fibrillary acidic protein (GFAP; an index of astroglial activation), [11C]harmine (a marker of monoamine oxidase A; MAO-A), and several other indices (metabotropic glutamate receptor 5 [mGluR5], excitatory amino acid transporters, and magnetic resonance imaging spectroscopy measurements) of glutamate dysregulation. These are markers of processes involved in immune activation, oxidative stress, and chronic glucocorticoid exposure. Positron emission tomography studies of the TSPO distribution volume, a marker of microglial activation, provide strong evidence for microglial activation throughout the gray matter of the brain during MDE of MDD. In postmortem studies, GFAP reductions in the orbitofrontal cortex, anterior cingulate cortex, and hippocampus indicate a deficit in reactive astroglia. Elevated MAO-A levels are present throughout the gray matter of the brain, including affect-modulating brain regions, starting in high-risk states for MDE such as the early postpartum period, perimenopause, heavy cigarette smoking, heavy alcohol intake, and prior to MDE recurrence. Evidence is accumulating for glutamate dysregulation, with some findings of reduced glutamate transporter density in the orbitofrontal cortex, and decreased mGluR5 density. Collectively, these changes suggest an imbalance in the immune system with increased microglial activation and decreased astroglial activation, continued elevations of the MAO-A level, and, likely, the development of extracellular glutamate dysregulation. Many of these imbalances involve processes implicated in increased oxidative stress, apoptosis, and neurodegeneration. Future studies are required to assess potential therapeutics targeting these processes to ameliorate progression of MDD.


Betamax: towards optimal sampling strategies for high-throughput screens.
Sample size is a critical component in the design of any high-throughput genetic screening approach. Sample size determination from assumptions or limited data at the planning stages, though standard practice, may at times be unreliable because of the difficulty of a priori modeling of effect sizes and variance. Methods to update the sample size estimate during the course of the study could improve statistical power. In this article, we introduce an approach to estimate the power and update it continuously during the screen. We use this estimate to decide where to sample next to achieve maximum overall statistical power. Finally, in simulations, we demonstrate significant gains in study recall over the naive strategy of equal sample sizes while maintaining the same total number of samples.


Highly Chemoselective Transamidation of Unactivated Tertiary Amides by Electrophilic N-C(O) Activation by Amide-to-Acyl Iodide Re-routing.
The challenging transamidation of unactivated tertiary amides has been accomplished via cooperative acid/iodide catalysis. Most crucially, the method provides a novel manifold to re-route the reactivity of unactivated N,N-dialkyl amides through reactive acyl iodide intermediates, thus reverting the classical order of reactivity of carboxylic acid derivatives. This method provides a direct route to amide-to-amide bond interconversion with excellent chemoselectivity using equivalent amounts of amines. The combination of acid and iodide has been identified as the essential factor to activate the amide C-N bond through electrophilic catalytic activation, enabling the production of new desired transamidated products with wide substrate scope of both unactivated amides and amines, including late-stage functionalization of complex APIs (>80 examples). We anticipate that this powerful activation mode of unactivated amide bonds will find broad-ranging applications in chemical synthesis.


Expression of receptors for VEGFs on normal human thyroid follicular cells and their role in follicle formation.
Human thyroid follicular cells in culture expressed the mRNAs for the receptors for vascular endothelial growth factors (VEGFRs). The relative expression was neuropilin1 = neuropilin2 = VEGFR2 > VEGFR1 > VEGFR3. Western blotting for VEGFR2 showed labeling of proteins ~200-230 kDa. Clonal follicular thyroid cell lines (FRTL5 and FTC133) also expressed mRNAs for the VEGFR1 and 2 obviating concerns of endothelial cell contamination. In the primary cultures, TSH, which is essential for expression of differentiated function, reduced VEGFR2 mRNA levels by 60%. Immunostaining for VEGFRs and neuropilin2 (NRP2), showed expression on the plasma membrane but with the exception of neuropilin1 (NRP1), all VEGFRs were also found in the cytoplasm and nucleus. Antibody specific for phosphotyrosine 1214 in VEGFR2 showed that the receptor was phosphorylated in the primary cultures and the cell lines. When VEGFR signaling was blocked with a specific inhibitor, follicle formation in the primary cultures was enhanced suggesting that VEGFR activation was detrimental to follicle formation. Immunostaining of sections of normal thyroids and various pathologies showed staining for VEGFR2 and pVEGFR2. We conclude that normal thyroid follicular cell express VEGFRs. For VEGFR2 its subcellular localization suggests functions additional to that of a cell surface receptor and a role in follicular integrity.


The functional impact of rare variation across the regulatory cascade.
Each human genome has tens of thousands of rare genetic variants; however, identifying impactful rare variants remains a major challenge. We demonstrate how use of personal multi-omics can enable identification of impactful rare variants by using the Multi-Ethnic Study of Atherosclerosis, which included several hundred individuals, with whole-genome sequencing, transcriptomes, methylomes, and proteomes collected across two time points, 10 years apart. We evaluated each multi-omics phenotype's ability to separately and jointly inform functional rare variation. By combining expression and protein data, we observed rare stop variants 62 times and rare frameshift variants 216 times as frequently as controls, compared to 13-27 times as frequently for expression or protein effects alone. We extended a Bayesian hierarchical model, "Watershed," to prioritize specific rare variants underlying multi-omics signals across the regulatory cascade. With this approach, we identified rare variants that exhibited large effect sizes on multiple complex traits including height, schizophrenia, and Alzheimer's disease.


A Comparison between Triphenylmethyl and Triphenylsilyl Spirobifluorenyl Hosts: Synthesis, Photophysics and Performance in Phosphorescent Organic Light-Emitting Diodes.
This study presents the synthesis and characterization of two spirobifluorenyl derivatives substituted with either triphenylmethyl (SB-C) or triphenylsilyl (SB-Si) moieties for use as host materials in phosphorescent organic light-emitting diodes (PHOLED). Both molecules have similar high triplet energies and large energy gaps. Blue Ir(tpz)3 and green Ir(ppy)3 phosphorescent devices were fabricated using these materials as hosts. Surprisingly, SB-Si demonstrated superior charge-transporting ability compared to SB-C, despite having similar energies for their valence orbitals. In particular, SB-Si proved to be a highly effective host for both blue and green devices, resulting in maximum efficiencies of 12.6% for the Ir(tpz)3 device and 9.6% for the Ir(ppy)3 device. These results highlight the benefits of appending the triphenylsilyl moiety onto host materials and underscore the importance of considering the morphology of hosts in the design of efficient PHOLEDs.


[Gene polymorphism of tumor necrosis factor-alpha receptor II in 196 site and premature births in Chinese Han Population].
To investigate the relationship between tumor necrosis factor receptor II (TNFR II) gene 196T/G polymorphism and preterm labor in Han population in Chengdu. Samples were collected from 96 subjects in corresponding period, 46 preterm labor pregnant women (we collected partial placental tissues of preterm labor, 21 cases of infectious group with chorioamnionitis, 25 cases of noninfectious group without chorioamnionitis), and 50 normal labor pregnant women. The DNA was extracted from each sample by using Chelex-100 method, then PCR-RFLP was performed to determine the TNFR II 196 gene polymorphism. 1) TNFR II 196 genotype frequencies of 196M/M (TT), 196M/R (TG) + 196R/R (GG) were 71.7%, 21.7%+ 6.5% and 80.0%, 20.0%+0.0% in preterm labor and normal control group respectively. Allele frequencies of R (G), M (T) were 17.4%, 82.6% and 10.0%, 90.0%, respectively. There were no significant difference in frequencies of genotype and allele in TNFR II 196 gene polymorphism between two groups (P > 0.05, P > 0.05, respectively). 2) Close correlation was observed between the different genotypes and the chorioamnionitis (chi2 = 11.088, P < 0.05). The odds ratio (OR) for TG+GG genotype was 12.65, 95% CI 2.359, 67.848, with more than 12.65 times probability of chorioamnionitis than that of TT genotype group. Polymorphism in 196 site of TNFR II gene was not crucial in preterm labor genesis, TG (GG) genotype may contribute to susceptibility to chorioamnionitis in the process of preterm labor in Chinese Han population.


ADAPTATION TO FINE-GRAINED ENVIRONMENTAL VARIATION: AN ANALYSIS OF WITHIN-INDIVIDUAL LEAF VARIATION IN AN ANNUAL PLANT.
Recent studies of evolution in heterogeneous environments have concentrated on the role of coarse-grained environmental variation. Here I explore the potential for a modular organism to adapt to fine-grained environmental variation through within-individual variation among modules. I describe the pattern of variation among leaves of single individuals and report results of initial analyses of genetic variation for within-individual variability in leaf traits and of genetic correlations that could influence the rate of further evolution of within-individual variation of these traits. Plants from 24 paternal half-sib families were raised in growth chambers, and five traits were measured for two leaves produced by each plant. Four of the five traits differed significantly between sampling times. Genetic analyses revealed significant additive genetic variation for within-individual variation in several traits. Estimates of family mean correlations between traits expressed at different times suggest few relationships that would be expected to impede response to selection for changes in the pattern of within-individual variation in leaf traits. These results support the possibility that within-individual variation could evolve as an adaptive response to fine-grained environmental variation and suggest a need for further investigation to improve understanding of evolution in heterogeneous environments.


Chido and Rogers antigenic determinant on the fourth component of human complement.
The blood group substances Chido (Cha) and Rogers (Rga) represent two electrophoretic variants of human C4. Based on the observation that anti-Cha and anti-Rga antisera agglutinated human red blood cells prepared in sucrose-activated autologous serum (LIS cells) at 37 degrees C, it has been assumed that the Cha and Rga antigenic determinants reside in the C4d fragment of C4. Here, we present evidence indicating that C4d is not present on those cells. In order to identify structurally the C4 fragments deposited, LIS cells were prepared at 37 degrees C and 4 degrees C in autologous serum to which 125I-C4 was added. Membranes of LIS cells were solubilized and analyzed by SDS-PAGE in 5 to 15% gradient gels followed by autoradiography. C4d was not deposited on LIS cells prepared at 37 degrees C, whereas C4c (beta, gamma, alpha 3 alpha 4) was. Cells prepared at 4 degrees C carried C4d (alpha 2) and C4c. Anti-Cha and anti-Rga antisera agglutinated both cell types, although C4d was not present on the cells prepared at 37 degrees C. Purified C4, C4c, C4d, and alpha-, beta- and gamma-chains of C4, as well as alpha 3 and alpha 4, were used to neutralize these antisera. C4 and the alpha-chain C4d and alpha 4 fragment of C4c, but neither the alpha 3 fragment nor the beta- or gamma-chains, were capable of neutralizing anti-Cha and anti-Rga antisera. These results strongly suggest that C4d and alpha 4 share an antigenic determinant, both of which are recognized by anti-Cha and anti-Rga antisera.


Effects and Mechanisms of Vitamin C Post-Conditioning on Platelet Activation after Hypoxia/Reoxygenation.
Platelet activation occurs upon ischemia/reperfusion and is related to the generation of reactive oxygen species (ROS) during this process. Vitamin C (VC) is a powerful antioxidant. VC scavenges ROS, reduces platelet activation, and attenuates reperfusion injury. However, the effects of VC on platelets undergoing hypoxia/reoxygenation (H/R) remain unclear. Herein, we evaluated the effects of VC on platelets in vitro following H/R and the related mechanisms. Fresh platelets were collected from 67 volunteers at the Blood Center of Hebei Province. Platelets were diluted with saline to a concentration of 2.00 × 1011/L. Aggregation and the curve slope were evaluated within 4 h with a whole-blood impedance analyzer. To determine the optimal experimental time, platelets were treated with hypoxia or reoxygenation for different times, and impedance aggregometry was carried out by measuring changes in electrical impedance induced by arachidonic acid (0.5 mM) and adenosine diphosphate (10 µM), thereby establishing the H/R model. Three antioxidants (VC, melatonin, and probucol) were used to treat platelets after H/R, and impedance aggregometry was used to determine their effects on platelet aggregation. The influence of VC on apoptosis-related indicators was detected. ROS and the mitochondrial membrane potential were observed by inverted fluorescence microscopy and flow cytometry, respectively. Related protein levels were detected by Western blotting. ROS scavengers inhibited platelet activation and aggregation in a concentration-dependent manner. VC post-conditioning scavenged ROS, downregulated cytochrome C, Bax, and caspase-9 proteins, and upregulated Bcl-2 protein. These effects collectively blocked platelet apoptosis and inhibited platelet aggregation. VC inhibited platelet aggregation by blocking apoptosis. Thus, VC may have applications in the treatment of platelet-related diseases.


Peripheral pulmonary artery aneurysm presenting as a solitary pulmonary nodule.
We report the case of a 63-year-old female patient who was evaluated due to a solitary pulmonary nodule. The final diagnosis was a solitary peripheral pulmonary artery saccular aneurysm. The patient was submitted to a pulmonary lobectomy with excellent recovery. Peripheral pulmonary artery aneurysms that arise from segmental or intrapulmonary branches are extremely rare, and their management is still controversial.


Epstein-Barr virus reactivation in renal transplant recipients.
Renal transplant recipients at Tygerberg Hospital were investigated to determine the importance of Epstein-Barr virus (EBV) as a pathogen in these patients. All 106 patients investigated were shown to have EBV antibodies before transplantation and most had serological evidence of reactivation of the infection after transplantation. A mild clinical illness was present in a few patients concomitant with EBV reactivation, which may suggest that this virus has a role in the morbidity of some renal transplant recipients. Lymphoblastoid cell lines were established from 11 renal transplant recipients; 5 of these cell lines were shown to be virus producers and 1 is thought to have unique properties.


Crystallization of Covalent Organic Frameworks for Gas Storage Applications.
Covalent organic frameworks (COFs) have emerged as a new class of crystalline porous materials prepared by integrating organic molecular building blocks into predetermined network structures entirely through strong covalent bonds. The consequently encountered "crystallization problem" has been conquered by dynamic covalent chemistry in syntheses and reticular chemistry in materials design. In this contribution, we have reviewed the progress in the crystallization of COF materials and their hydrogen, methane and carbon dioxide gas storage properties for clean energy applications.


Healthy Aging Promotion through Neuroscientific Information-Based Strategies.
To ensure the well-being of a rapidly growing elderly population, it is fundamental to find strategies to foster healthy brain aging. With this intention, we designed a program of scientific-based lectures aimed at dissemination by established neuroscientists about brain function, brain plasticity and how lifestyle influences the brain. We also carried out a pilot study on the impact of the lectures on attendees. The objective was to provide information to elderly people in order to encourage them to identify unhealthy and healthy daily habits, and more importantly, to promote behavioral changes towards healthy brain aging. Here we report on our experience. In order to determine the impact of the lectures in the daily routine of the attendees, we asked them to fill out questionnaires. Preliminary results indicate that neuroscientific information-based strategies can be a useful method to have a positive impact on the lives of elderly, increase their awareness on how to improve brain function and promote positive lifestyle modifications. Furthermore, based on self-reported data, we also found that through this strategy it is possible to promote behavioral changes related to nutrition, sleep, and realization of physical and cognitively stimulating activities. Finally, based on the results obtained, the importance of promoting self-efficacy and the empowerment of the older populations is highlighted.


Patterns of liver injury in COVID-19 - a German case series.
Reports of liver injury in patients with novel coronavirus disease 2019 (COVID-19) are emerging from China and the USA. A wide variety of liver function test abnormalities and few cases of severe liver failure have been reported. No data on the hepatic phenotype from Europe are available at current. We report a case series of 44 consecutive patients hospitalized for COVID-19 in Germany. At the time of admission, aspartate aminotransferase greater than the upper limit of normal was present in 70%, while alanine aminotransferase was elevated in 15.8%. Markers of cholestatic liver injury were altered only in a minority of patients. During hospitalization, 31% and 22% experienced increasing aspartate aminotransferase and alanine aminotransferase, respectively, when transaminases were normal at admission. Severe liver injury defined by 3×> upper limit of normal was observed in 9.1% over a mean time of 10.5 days. Importantly, patients exhibited cytotoxicity including lactate dehydrogenase and creatinine kinase elevations, but no signs of relevant liver function impairment. In summary, in a case series of hospitalized patients in Germany, cytotoxicity in the absence of severe liver dysfunction at admission and only few cases suggestive of severe liver injury during hospital were observed.


Physical activity levels and energy intake according to the presence of metabolic syndrome among single-household elderly in Korea: Korean National Health and Nutrition Examination Survey 2016-2018.
Exercise and dietary and nutritional intake affect the risk and prevalence of metabolic syndrome (MetS) in elderly people, effects that may differ according to sex in elderly single households (ESH). This study aimed to analyze the differences in physical activity (PA) levels and energy intake according to sex and prevalence of MetS among elderly people in Korea to investigate the relationships between these factors. Data from 893 elderly individuals (aged >65 years) were obtained from the Korean National Health and Nutrition Examination Survey (2016-2018). We analyzed PA levels (occupational and recreational PA and place movement) and energy intake (EI; total, carbohydrate, protein, and fat), and found that there were sex differences in both according to the presence or absence of MetS in ESH. Among both males and females, the MetS group had a significantly lower recreational moderate PA than the non-MetS group. However, total PA in males was significantly higher in the non-MetS than in the MetS group, but there was no significant difference in females. Furthermore, the EI of females did not differ in the presence or absence of MetS, except for fat intake, and in the nutritional intake of ESH in males, no difference was found in the presence or absence of MetS. We also found that in Odd ratio, "active" was associated with lowering high waist circumference (OR = 0.40, 95%CI = 0.21-0.76), and "very active" was associated with lower MetS occurrence (OR = 0.51, 95%CI = 0.33-0.81) and low high-density lipoprotein cholesterol (HDL-C) (OR = 0.55, 95%CI = 0.37-0.83). Therefore, in the MetS group of ESH, there was a significant correlation of the MetS component in PA rather than EI. Male ESH require interventions that increase PA, while female ESH require nutrition interventions that increase and balance PA. Therefore, a new program is needed that promotes continuous interest and healthy lifestyles in consideration of the characteristics of ESH.


Opioid-mediated suppression of cultured peripheral blood mononuclear cell respiratory burst activity.
Opiate addiction and stress have been associated with altered immune responses. In this study, we evaluated the influence of morphine and the stress responsive opioid peptide beta-endorphin (beta-END) on O-2 and H2O2 production by cultured human peripheral blood mononuclear cells. Exposure of these cells during 48 hr of culture to morphine and beta-END at pharmacologically (10(-8) M) and physiologically (10(-12) M) relevant concentrations, respectively, markedly suppressed peripheral blood mononuclear cell O-2 and H2O2 release in response to the respiratory burst stimuli opsonized zymosan and phorbol myristate acetate. Both opioids also induced a minimal, but statistically significant, increase in resting O-2 and H2O2 generation. The modulatory effects of morphine and beta-END on peripheral blood mononuclear cell oxygen metabolism appeared to involve a classical opioid receptor, because opioid activity was blocked by naloxone and was not observed with N-acetylated-beta-END. Using purified lymphocyte and monocyte preparations, we determined that although opioids directly increase monocyte-resting oxygen metabolism, lymphocytes are the primary target cell in opioid-mediated suppression of monocyte respiratory burst activity. The release of a suppressive product from opioid-triggered lymphocytes was inhibited by cyclosporine. Based on the results of this study, we propose that opioid-mediated suppression of mononuclear phagocyte respiratory burst activity is another factor to be considered in the immunodeficiency of opiate addiction and stress.


Left colon gangrene after acute inferior mesenteric artery occlusion.
We report here an experience with five patients, aged 58 to 70, suffering gangrene of the left colon after spontaneous inferior mesenteric artery occlusion. All cases were the result of arteriosclerosis; in two, small aortic aneurysms were present and might have been responsible for emboli to the inferior mesenteric artery. The dead bowel was resected in all patients; three patients survived. No primary anastomoses were done and they are not recommended. Because ligation of the patent inferior mesenteric artery has been done so often without ill effects during aortic surgery, the collateral circulation to the left colon can be considered excellent. Gangrene is therefore rare and requires major interference with collateral circulation by emboli or arteriosclerotic occlusion. The clinical symptoms and signs may be confusing.


Endothelial GABBR2 Regulates Post-ischemic Angiogenesis by Inhibiting the Glycolysis Pathway.
Purpose: Angiogenesis post-ischemia plays an essential role in preventing ischemic damage to tissue by improving the blood recovery. Determining the regulatory mechanism of ischemic angiogenesis, therefore, could provide effective therapeutics for ischemic injury. Materials and Methods: The RNA sequencing (RNA-seq) database was used to predict the association of gamma-aminobutyric acid type B receptor subunit 2 (GABBR2) with endothelial-specific expression. The role of GABBR2 in angiogenesis was verified in vitro by downregulating GABBR2 in human umbilical vein endothelial cells (HUVECs) with lentiviral vectors. Besides, the in vivo effect of GABBR2 on the blood recovery of an ischemic hindlimb was demonstrated by establishing a hindlimb ischemia model in normal and GABBR2 adenoviral vector-infected mice. Then, the mobilization of endothelial progenitor cells (EPCs) in peripheral blood post-ischemia was determined by flow cytometry. Finally, the XF analyzer and Western blot were used to determine the effect of GABBR2 on endothelial metabolism. Results: The RNA-seq results indicated a strong association between GABBR2 and endothelial revascularization, and the upregulation of GABBR2 was detected in both hypoxia-treated HUVECs and ischemic mouse hindlimb. Hypoxia treatment for 6 h increased the proliferation, migration, and tube formation of HUVECs, which were inhibited by GABBR2 knockdown. Additionally, GABBR2 downregulation significantly decreased the blood flow recovery of mouse ischemic hindlimb. The expressions of the EPC markers CD34+ and CD133+ significantly decreased in the peripheral blood in hindlimb post-ischemia. Mechanically, glycolysis-dominated metabolism of HUVECs was compromised by GABBR2 knockdown. Evidences of the decreased expressions of HKII, PFKFB3, and PKM1 also supported the compromised glycolysis induced by GABBR2 downregulation. Conclusion: Our study demonstrated that GABBR2 regulated angiogenesis post-ischemia by inhibiting the glycolysis pathway.


Polymorphism in 5' untranslated region of heat-shock protein 70 gene as marker of post-partum anoestrus in Murrah buffaloes.
The enormous production potential of buffaloes has never been accomplished due to various reproductive insufficiencies. Among them, post-partum anoestrus, a multifactorial disorder, is predominant but any genetic association is yet to be established. This study focused to identify novel polymorphisms in heat-shock protein 70 (HSP70) gene and its possible association with post-partum anoestrus in Murrah buffaloes. A 579-bp fragment from 5' untranslated region of HSP70 gene was amplified by polymerase chain reaction from blood genomic DNA of 614 animals maintained under similar management conditions. In phase-I experiment, custom sequencing and restriction enzyme (RE) digestion of the amplified fragment were performed in 40 buffaloes with similar post-partum oestrous conditions over previous consecutive three or more gestations-20 animals each showing post-partum anoestrus (>120 days after parturition) and normal cyclicity (<65 days after parturition). While in phase-II experiment, herd screening by RE analysis was performed in remaining 574 animals. Four transversions at T-75G, C+31G, T+38G and C+97A and three transition mutations at T-153C, T+33C and A+44G positions were observed. Polymorphism at T+38G site revealed significant (p < .05) variation, where homozygous G was present only in post-partum anoestrous animals while nucleotide T was present randomly in both groups of phase-I animals whereas phase-II experiments revealed homozygous G in 55 animals. Regression analysis in relation to average post-partum interval against genotypic frequencies at T+38G also depicted significant association. HSP70 gene polymorphism at T+38G position can therefore be used as genetic marker for excluding probable post-partum anoestrous buffaloes from herd for breeding programmes.


Translation, Cross-Cultural Adaptation, and Psychometric Validation of the Chinese/Mandarin Cardiac Rehabilitation Barriers Scale (CRBS-C/M).
Cardiovascular diseases are among the leading causes of morbidity in China and around the world. Cardiac rehabilitation (CR) effectively mitigates this burden; however, utilization is low. CR barriers in China have not been well characterized; this study sought to translate, cross-culturally adapt, and psychometrically validate the CR Barriers Scale in Chinese/Mandarin (CRBS-C/M). Independent translations of the 21-item CRBS were conducted by two bilingual health professionals, followed by back-translation. A Delphi process was undertaken with five experts to consider the semantics and cross-cultural relevance of the items. Following finalization, 380 cardiac patients from 11 hospitals in Shanghai were administered a validation survey including the translated CRBS. Following exploratory and confirmatory factor analysis, internal consistency was assessed. Validity was tested through assessing the association of the CRBS-C/M with the CR Information Awareness Questionnaire. Items were refined and finalized. Factor analysis of CRBS-C/M (Kaiser Meyer Olkin = 0.867, Bartlett's test p < 0.001) revealed five factors: perceived CR need, external logistical factors, time conflicts, program and health system-level factors, and comorbidities/lack of vitality; Cronbach's alpha (α) of the subscales ranged from 0.67 to 0.82. The mean total CRBS score was significantly lower in patients who participated in CR compared with those who did not, demonstrating criterion validity (2.35 ± 0.71 vs. 3.08 ± 0.55; p < 0.001). Construct validity was supported by the significant associations between total CRBS scores and CR awareness, sex, living situation, city size, income, diagnosis/procedure, disease severity, and several risk factors (all p < 0.05). CRBS-C/M is reliable and valid, so barriers can be identified and mitigated in Mandarin-speaking patients.


Implementation of a modified birdcage resonator for 19F/1H MRI at low fields (0.14 T).
Fluorine-19 nuclear magnetic resonance of perfluorinated blood substitute materials provides a method for determination of oxygen tension (pO2) in vivo. Use of a double resonant 19F/1H radio frequency coil allows convenient correlation between the high resolution anatomic presentation of proton images and the fluorine distribution. However, quantitative 19F measurements require an RF coil with good H1 field homogeneity over the image volume and a high quality factor (Q) to minimize errors caused by the low signal-to-noise levels available in in vivo imaging and image nonuniformities introduced by the large chemical shift of fluorocarbons. The birdcage coil design provides a high Q structure with optimum H1 field uniformity and fill factor. However, at low resonance frequencies, the inherently low inductance of the birdcage geometry requires the use of a large number of chip capacitors giving rise to unwieldy coil fabrication and increased cost. This communication describes a modification to the birdcage design that reduces the chip capacitor requirement by at least a factor of 4 for a given dimension, yet retains the essential characteristics of the birdcage design. The modified structure was tuned for double resonance at 5.7/6.0 MHz for 19F/1H magnetic resonance imaging at 0.14 T. For a coil with a length to diameter ratio of 1.67, an H1 uniformity of +/- 2% for the 19F resonance was obtained over a cylindrical region with radius approximately 0.6r (r = radius of coil) and length approximately 1.8r within the coil.