Magnetic resonance imaging for preoperative diagnosis in third molar surgery: a systematic review.
In recent years, magnetic resonance imaging (MRI) has made great strides through various technical improvements and new sequences, which have made it one of the most promising and leading imaging techniques in the head and neck region. As modern imaging techniques in dentistry aim to reduce radiation exposure, this systematic review evaluated the possibilities, advantages, and disadvantages of advanced imaging diagnostics using dental MRI and its evidence for clinical indications and limitations relevant to mandibular third molar (MTM) surgery. Two reviewers performed multiple database searches (PubMed MEDLINE, EMBASE, Biosis, and Cochrane databases) following the PICOS search strategy using medical subject headings (MeSH) terms, keywords, and their combinations. Ten studies were included in this systematic review. By providing high spatial resolution and excellent soft tissue contrast, black bone MRI sequences such as 3D Double Echo Steady State (DESS) and 3D Short Tau Inversion Recovery (STIR) imaging protocols have the potential to become a valuable alternative to cone-beam computed tomography (CBCT) in future dental clinical routines. Overall, radiation-free MRI represents another step toward personalized dentistry and improved decision-making that avoids ineffectiveness and minimizes risks in oral surgery by taking into account additional patient-side factors such as comorbidity, anatomical norm variations, and imaging biomarkers.


Effect of multiple injections of beta-glucan on non-specific immune response and disease resistance in Labeo rohita fingerlings.
The purpose of this study was to determine if multiple injections of different dosages of beta-glucan derived from barley would enhance the immune response and disease resistance against infections due to opportunistic pathogens Aeromonas hydrophila and Edwardsiella tarda in Labeo rohita fingerlings. Hence, four different dosages of beta-glucan suspension in phosphate-buffered saline at the rate of 0, 5, 10, 15 mg kg(-1) body weight of fish were injected intraperitoneally to the fingerlings of Labeo rohita at two-week intervals for four times. After every two-week interval different serum biochemical, haematological and immunological parameters of fish were evaluated. At the end of immunostimulation trial of 56 days, fish were divided into four subgroups under each major treatment group for challenge through i.p injection and bath immersion with two pathogens, A. hydrophila and E. tarda. The mortality (%) and agglutinating antibody titre was recoded on 28th day post challenge. Most of the immune parameters such as leucocyte count, phagocytic ratio, phagocytic index, lysozyme activity, complement activity, serum bactericidal activity were significantly (P < 0.05) enhanced on 42 days after three i.p injections of 10 mg of beta-glucan kg(-1) body wt. Challenge study indicated least mortality in the group of fishes injected with medium dose of 10 mg of beta-glucan kg(-1) body wt. four times. Multiple injections of beta-glucan might have maintained the activation of phagocytic cells for a long period which in turn would lead to long-term protection in fishes. Thus, injections of 10 mg of beta-glucan kg(-1) body wt. for three times can be advocated to enhance the immune response of fish species under aquaculture.


Targeting epigenetic regulators for treating diabetic nephropathy.
Diabetes is accompanied by the worsening of kidney functions. The reasons for kidney dysfunction mainly include high blood pressure (BP), high blood sugar levels, and genetic makeup. Vascular complications are the leading cause of the end-stage renal disorder (ESRD) and death of diabetic patients. Epigenetics has emerged as a new area to explain the inheritance of non-mendelian conditions like diabetic kidney diseases. Aberrant post-translational histone modifications (PTHMs), DNA methylation (DNAme), and miRNA constitute major epigenetic mechanisms that progress diabetic nephropathy (DN). Increased blood sugar levels alter PTHMs, DNAme, and miRNA in kidney cells results in aberrant gene expression that causes fibrosis, accumulation of extracellular matrix (ECM), increase in reactive oxygen species (ROS), and renal injuries. Histone acetylation (HAc) and histone deacetylation (HDAC) are the most studied epigenetic modifications with implications in the occurrence of kidney disorders. miRNAs induced by hyperglycemia in renal cells are also responsible for ECM accumulation and dysfunction of the glomerulus. In this review, we highlight the role of epigenetic modifications in DN progression and current strategies employed to ameliorate DN.


The tale of a modern animal plague: tracing the evolutionary history and determining the time-scale for foot and mouth disease virus.
Despite significant advances made in the understanding of its epidemiology, foot and mouth disease virus (FMDV) is among the most unexpected agricultural devastating plagues. While the disease manifests itself as seven immunologically distinct strains their origin, population dynamics, migration patterns and divergence times remain unknown. Herein we have assembled a comprehensive data set of gene sequences representing the global diversity of the disease and inferred the time-scale and evolutionary history for FMDV. Serotype-specific rates of evolution and divergence times were estimated using a Bayesian coalescent framework. We report that an ancient precursor FMDV gave rise to two major diversification events spanning a relatively short interval of time. This radiation event is estimated to have taken place towards the end of the 17th and the beginning of the 18th century giving us the present circulating Euro-Asiatic and South African viral strains. Furthermore our results hint that Europe acted as a possible hub for the disease from where it successfully dispersed elsewhere via exploration and trading routes.


Racial Differences in the Effectiveness of Internet-Delivered Mental Health Care.
Computerized cognitive behavioral therapy (cCBT) can improve mental health outcomes in White populations; however, it is unknown whether racial and ethnic minority populations receive clinical benefits from cCBT. To study race differences in the impact of cCBT use on mental health outcomes among White and African American primary care patients. Secondary analysis of a three-arm randomized controlled clinical trial. Primary care physicians (PCPs) referred 2,884 patients aged 18-75; 954 met eligibility criteria (including elevated mood and/or anxiety symptoms indicated as a score ≥ 10 on Patient Health Questionnaire or Generalized Anxiety Disorder scale); 704 were randomized in 3:3:1 ratio to receive either (1) the cCBT program (cCBT-only), (2) cCBT plus access to an Internet Support Group (cCBT+ISG), or (3) their PCP's usual care (UC). After exclusions, this study analyzed 689 patients: 590 receiving cCBT, in the combined cCBT-only and cCBT+ISG groups (91 African American, 499 White), and 99 receiving UC (22 African American, 77 White). We used the Beating the Blues cCBT program that consisted of eight 50-min Internet-delivered interactive sessions and "homework" assignments to complete between weekly sessions. College graduate-level care coaches provided six months of remote support. After prior analyses demonstrated no effect of the ISG program, we combined the cCBT-only and cCBT+ISG groups (cCBT) to compare to UC at 6-month follow-up. Controlling for sociodemographic factors, baseline symptoms, and treatment arm, we examined race differences for impact of cCBT versus UC on the mental health-related quality-of-life (Short-form 12 Health Survey), and Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety, and depression. Compared to UC, cCBT had no effect on quality of life (d = 0.10; p = 0.40), depression (d = - 0.19; p = 0.10), or anxiety (d = - 0.16; p = 0.18) for Whites. However, for African American patients, cCBT was associated with significant 6-month decrease in depression (d = - 0.47, p < 0.01) and anxiety scores (d = - 0.54, p < 0.01). cCBT may be an efficient and scalable first step to eliminating disparities in mental health care. Clinicaltrials.gov Identifier: NCT01482806. https://www.clinicaltrials.gov/ct2/show/NCT01482806?term=rollman&rank=4.


Prospective evaluation of ultrasound and colour duplex imaging for the assessment of surgical resectability of pancreatic tumours.
This study was performed to evaluate colour duplex imaging (CDI) for the assessment of resectability of pancreatic tumours (PTs). From October 1998 to December 2001, 182 patients consecutively having surgery for a PT were enrolled in this prospective study. Extension of the tumour to large blood vessels and retroperitoneum, the detection of liver metastases, enlarged lymph nodes and peritoneal carcinomatosis were defined as criteria for assessment. The patients were grouped into three classes of resectability: US-TU 1 = resectable/potentially curable, US-TU 2 = questionably resectable/curable, and US-TU 3 = non-resectable/not curable. CDI was performed by five different examiners. Results were compared with intra-operative findings. Using CDI, we classified 85 (46.7%) tumours as resectable, 64 (35.2%) as non-resectable, and 33 (18.1%) as questionably resectable. Overall, 46.2% ( n=84) were found to be resectable, and 53.8% ( n=98) to be non-resectable, intra-operatively. A correlation between CDI classification and intra-operative findings was found in 138 of 149 cases (92.6%) (sensitivity 88.4%, specificity 96.3%). With regard to the complete oncological status (local extension, metastases, lymph-node staging and peritoneal carcinomatosis), a sensitivity of 77.2% and specificity of 95.7% were found. Non-correlated findings were likely attributed to missing small liver metastases, peritoneal carcinomatosis without ascites, and on difficulties in the assessment of enlarged lymph nodes concerning tumour infiltration. The use of CDI in evaluation of PTs may provide valuable pre-operative assessment of surgical resectability and may be performed in the clinical setting.


Adaptation of cultured mammalian neurons to a hypotonic environment with age-related response.
The response of neurons to osmolal concentration changes has not been well-documented compared to erythrocytes, urinary bladder and epithelial cells. The effects of a hypotonic solution on morphology and electrophysiological functions in cultured dissociated neurons can be precisely studied. From the analysis of video pictures from Nomarski optics, diameters of the cells were seen to increase and then recover to the initial values after the application of a hypotonic solution. The rate of increase of cell size in fetal neurons was 4-5 times faster than in mature neurons. This age-related transient response was accompanied by a change of resting potential and membrane resistance. This transient depolarization and decrease of the resistance corresponded to morphological changes. However, the amplitude of an action potential scarcely changed during the cell membrane expansion. It is plausible that increased membrane tension caused by the membrane expansion might facilitate the opening of the channel. The cell membrane expansion might also increase ionic permeability through the membrane. This may reduce a swollen cell volume to the initial one by diluting their intracellular solute concentration. After this adaptation the cultured neurons were able to survive for a long time and extend processes in the hypotonic environment.


Increase Risk of Dementia in Patients With Sudden Hearing Loss: A Population-Based Cohort Study With 7-Year Follow-Up in Taiwan.
To investigate the prevalence and risk of subsequent dementia in subjects with sudden hearing loss during a 7-year follow-up period through comparisons with cohorts matched by sex, age group, and year of index date. A retrospective matched-cohort study. The Longitudinal Health Insurance Database 2000 (LHID2000) in Taiwan. This study included a total of 11,148 subjects, including 1,858 in the study group and 9,290 in the comparison cohort group. None. We analyzed the differences in sociodemographic characteristics and comorbidities between subjects with sudden hearing loss and the comparison cohort group. Then, we estimated the risk of dementia and also plotted the survival outcomes to evaluate differences in dementia-free survival rates between the two groups. The dementia incidence rates per 1000 person-years were 20.45 and 8.15 for the subjects with sudden hearing loss and comparison cohorts, respectively. When we adjusted for the subjects' characteristics, the hazard ratio for dementia was 1.69 (95% confidence interval [CI] = 1.06-2.68, p < 0.01) for subjects with sudden hearing loss compared with comparison cohorts during the follow-up period, and subjects with sudden hearing loss had lower 7-year dementia-free survival rates compared with comparison cohorts by using a log-rank test. Furthermore, male subjects with sudden hearing loss had a higher risk of dementia (adjusted hazard ratio [HR] = 2.11) than did the male comparison cohorts. This study revealed a relationship between sudden hearing loss and dementia in an Asian country. The risk of dementia was higher among patients with sudden hearing loss compared with matched cohorts during the 7-year follow-up period.


Left hemicolectomy and low anterior resection in colorectal cancer patients: Knight-griffen vs. transanal purse-string suture anastomosis with no-coil placement.
Colorectal cancer (CRC) is considered one of the most frequent neoplasms of the digestive tract with a high mortality rate. Left hemicolectomy (LC) and low anterior resection (LAR) with minimally invasive laparoscopic and robotic approaches or with the open technique are the gold standard curative treatment. Seventy-seven patients diagnosed with CRC were recruited between September 2017 and September 2021. All patients underwent a preoperative staging with a full-body CT scan. The goal of this study was to compare both types of surgeries, LC-LAR LS with Knight-Griffen colorectal anastomosis and LC-LAR open with Trans-Anal Purse-String Suture Anastomosis (the TAPSSA group), by positioning a No-Coil transanal tube (SapiMed Spa, Alessandria, Italy), in terms of postoperative complications such as prolonged postoperative ileus (PPOI), anastomotic leak (AL), postoperative ileus (POI), and hospital stay. The patients were divided into two groups: the first with 39 patients who underwent LC and LAR in LS with Knight-Griffen anastomosis (Knight-Griffen group) and the second with 38 patients who underwent LC and LAR by the open technique with the TAPSSA group. Only one patient who underwent the open technique suffered AL. POI was 3.76 ± 1.7 days in the TAPSSA group and 3.07 ± 1.3 days in the Knight-Griffen group. There were no statistically significant differences in terms of AL and POI between the two different groups. The important point that preliminarily emerged from this retrospective study was that the two different techniques showed similarities in terms of AL and POI, and therefore, all the advantages reported in the previous studies pertaining to No-Coil also hold good in this study regardless of the surgical technique used. However, randomized controlled trials are needed to confirm these findings.


Selecting useful groups of features in a connectionist framework.
Suppose for a given classification or function approximation (FA) problem data are collected using l sensors. From the output of the ith sensor, ni features are extracted, thereby generating p = sigma li = 1 ni features, so for the task we have X subset Rp as input data along with their corresponding outputs or class labels Y subset Rc. Here, we propose two connectionist schemes that can simultaneously select the useful sensors and learn the relation between X and Y. One scheme is based on the radial basis function (RBF) network and the other uses the multilayered perceptron (MLP) network. Both schemes are shown to possess the universal approximation property. Simulations show that the methods can detect the bad/derogatory groups of features online and can eliminate the effect of these bad features while doing the FA or classification task.


Enhancing Enneagram Therapy with Contemporary Research on the Conscious and Unconscious Mind.
The Enneagram is a personality framework with ancient philosophical underpinnings and cross cultural roots. It outlines nine different pathways of growth for nine different personalities. In recent years, it has started to gain traction in the peer reviewed level of research. Since the Enneagram has a conceptual versatility in addressing various levels and dimensions of the human psyche, it can both contribute and benefit from cross pollinating its insights with the latest scientific research on how the human mind works. One area of research that has the potential for this type of symbiotic partnership with the Enneagram is the study of the interaction between the conscious and unconscious mind. There is rich potential for the multi-leveled integration of contemporary findings on how the conscious and unconscious mind mutually interact with one another along with insights into personality structures from the Enneagram. These integrative insights have clinical implications and create possible directions for future research.


Differences in metabolic network modulation between capsulotomy and deep-brain stimulation for refractory obsessive-compulsive disorder.
Around 7%-10% of patients with obsessive-compulsive disorder (OCD) are refractory to first-line treatment. Neurosurgical approaches are available such as capsulotomy or deep-brain stimulation (DBS). There is strong evidence for central involvement of the corticostriatopallidothalamocortical (CSPTC) circuit in OCD, but the exact mechanism through which these interventions lead to clinical improvement and potential differences in network modulation are not fully understood. In total, 13 capsulotomy patients (aged 29-59 y, 10 men and 3 women) and 16 DBS patients (aged 25-56 y, 6 men and 10 women) were prospectively included. (18)F-FDG PET was performed before and after capsulotomy and before and after DBS in both stimulation-on and stimulation-off conditions. Presurgical scans were compared with scans of healthy volunteers using SPM8 and global scaling, and metabolic changes after DBS were compared with changes after capsulotomy. Correlations with clinical improvements were investigated using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Hamilton Depression Rating Scale (HAM-D). Both groups had similar pretreatment clinical morbidity as assessed by Y-BOCS and the Hamilton Depression Rating Scale. Preoperative superior frontal and supplementary motor cortex hypometabolism was common to both patient groups, and the subgenual anterior cingulate, occipital cortex (cuneus), and posterior cerebellum were relatively hypermetabolic. Postoperative metabolic decreases were common to both interventions in the anterior cingulate and the prefrontal and orbitofrontal cortices. Compared with DBS, capsulotomy resulted in more intense metabolic changes, with additional significant decreases in the mediodorsal thalamus, caudate nucleus, and cerebellum as well as increases in the precuneus and the fusiform and lingual gyrus. The stimulation-off condition of DBS patients showed no significant differences from the preoperative state. Improvement in Y-BOCS scores correlated with metabolic changes in the occipital cortex. Baseline metabolism in the subgenual anterior cingulate and superior temporal cortices were related to postoperative improvement of depressive symptoms. Capsulotomy and DBS lead to similar clinical improvement and similar metabolic network changes in the CSPTC circuit, with a prominent role for the subgenual anterior cingulate and other core structures of the CSPTC. However, metabolic changes are more pronounced and extended in capsulotomy than in DBS. Furthermore, cortical regions outside the CSPTC may also play an important role in OCD symptomatology.


Levels and distributions of phospholipids and cholesterol in the plasma membrane of neuroblastoma cells.
Murine neuroblastoma cells (clone N-2A) grown in suspension (spinner cells) or attached on a plastic surface (monolayer cells) were used in studies of the phospholipid and cholesterol composition of whole cells, primary plasma membranes, plasma membranes internalized during phagocytosis of polystyrene latex beads, mitochondria and microsomes. Monolayer cells contained higher concentrations of total phospholipid, phosphatidylserine and phosphatidylcholine, and lower concentration of phosphatidylethanolamine than spinner cells. The cholesterol levels and the relative proportions of the various phospholipids were similar in both cell types except phosphatidylethanolamine and sphingomyelin whose proportions were lower in monolayer cells. The primary plasma membranes of the two cell types differed significantly in the relative proportions of all phospholipids, except sphingomyelin, and the phospholipid to protein and the cholesterol to protein ratios were all higher in the membranes of spinner cells. In contrast to these results, all the phospholipid to protein and the cholesterol to protein ratios of the internalized plasma membranes were higher in monolayer than in spinner cells, and the proportions of all phospholipids, except phosphatidylethanolamine, were similar in both cell types. The membrane distributions of individual phospholipids and cholesterol were inferred from comparison of the phospholipid and cholesterol compositions of primary plasma membranes and plasma membranes internalized during phagocytosis of polystyrene beads. The results are consistent with a non-random distribution of most phospholipids in both spinner and monolayer cells, but the patterns of these distributions were different in the two cell types. With regard to cholesterol the results are compatible with a random or a heterogeneous distribution. All the phospholipid to protein ratios of the mitochondrial fraction of both cell types were lower than those of the plasma membranes. However, these ratios of the microsomal fraction were higher than those of the plasma membranes of monolayer cells, whereas they were comparable, with a few exceptions, to those of spinner cell membranes. The cholesterol to phospholipid molar ratios of plasma membranes were 6.4 and 4.3 fold greater than those of the mitochondrial and microsomal fractions, respectively.


Peculiarities of Biofilms Formation by Campylobacter Bacteria in Mixed Populations with Other Microbial Contaminants of Food Products.
Peculiarities of biofilms formation by Campylobacter bacteria in mixed populations with other microbial contaminants was studied by real-time impedance spectroscopy on an automated xCelligence real time cell analyzer (RTCA). This method is based on measuring the medium resistance in special plates (E-plates) with interdigitated microelectrodes. Coculturing of campylobacter with coliform bacteria is accompanied by film formation; the intensity of this process varies depending on the type of the test cultures and the nature of their interaction in mixed populations. Film formation by C. jejuni during co-culturing with enterobacteria is maximum during the first hours and depends on the presence of stress factors in the environment. The biomatrix film was synthesized by 3 times more intensively in the presence of oxygen than in microaerobic conditions, and also by 1.7-4.3 times more active in the mixed culture with Enterobacter cloacae, E. coli, and K. pneumoniae. During co-culturing of campylobacter with salmonella, no enhanced film formation by the tested strains was observed. Unlike members of the genus Enterobacter intensively producing exopolysaccharides, pathogenic member of Enterobacteriaceae, salmonella, demonstrated weak capacity to form film matrix. The study of film formation by Campylobacter allows more accurate assessment of the effectiveness of sanitary bactericidal treatment of food industry facilities, predict the appearance of biofilms and the intensity of their formation depending son the nature of the antimicrobial effect and the used means.


Absorbance or organization into ankylosis: a microarray analysis of haemarthrosis in a sheep model of temporomandibular joint trauma.
Traumatic haemarthrosis was hypothesized to be the etiology of temporomandibular (TMJ) ankylosis. Here, taking haematoma absorbance as a control, we aimed to reveal the molecular mechanisms involved in haematoma organizing into ankylosis using transcriptome microarray profiles. Disk removal was performed to building haematoma absorbance (HA) in one side of TMJ, while removal of disk and articular fibrous layers was performed to induced TMJ ankylosis through haematoma organization (HO) in the contralateral side in a sheep model. Haematoma tissues harvested at days 1, 4 and 7 postoperatively were examined by histology, and analyzed by Affymetrix OviGene-1_0-ST microarrays. The DAVID were recruited to perform the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis for the different expression genes (DEGs). The DEGs were also typed into protein-protein interaction (PPI) networks to get the interaction data. Six significant genes screened from PPI analysis, were confirmed by real-time PCR. We found 268, 223 and 17 DEGs at least twofold at days 1, 4 and 7, respectively. At day 1, genes promoting collagen ossification (POSTN, BGN, LUM, SPARC), cell proliferation (TGF-β), and osteogenic differentiation of mesenchymal stem cells (BMP-2) were up-regulated in the HO side. At day 4, several genes involved in angiogenesis (KDR, FIT1, TEK) shower higher expression in the HO side. While HA was characterized by a continuous immune and inflammatory reaction. Our results provide a comprehensive understanding of the role of haematoma in the onset and progress of TMJ ankylosis. The study will contribute to explaining why few injured TMJs ankylose and most do not from the molecular level.


The influence of patients' hopes of receiving a prescription on doctors' perceptions and the decision to prescribe: a questionnaire survey.
To measure patients' expectations of receiving prescriptions and general practitioners' perceptions of these expectations and to determine the factors most closely associated with the decision to prescribe. Questionnaires were completed by patients waiting to see their general practitioners, and by their doctors immediately after the consultations. Four non-fundholding groups practices in southeast London. 544 unselected patients consulting 15 general practitioners. Doctor's perceptions of patients' expectations; doctors' decisions to prescribe. 67% (354/526) of patients hoped for a prescription; doctors perceived that 56% (305/542) of patients wanted prescriptions; and doctors wrote prescriptions in 59% (321/543) of consultations. Despite the close agreement between patients' hopes and doctors' perceptions, 25% (89/353) of patients hoped for a prescription but did not receive one. In 22% (68/313) of consultations in which prescriptions were written, they were not strictly indicated on purely medical grounds, and in only 66% (202/306) of consultations in which prescriptions were written were they both indicated and hoped for. Doctors' perceptions of patients' expectations were the strongest predictor of the decision to prescribe, but the final regression model also included patients' hopes and ethnic group, and the doctor's feeling of being pressurised. In an area of low prescribing and high expectations the decision to prescribe was closely related to actual and perceived expectations, but the latter was the more significant influence.


Polymorphic solidification of Linezolid confined in electrospun PCL fibers for controlled release in topical applications.
Poly(ϵ-caprolactone) (PCL) membranes loaded with Linezolid, chemically N-[[(5S)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (empirical formula C16H20FN3O4) have been prepared by electrospinning technique, at different Linezolid concentrations (0.5, 1, 2.5 and 5%, w/w). Structural characterization, morphological analysis and the study of the mechanical properties have been performed on loaded membranes and compared with neat PCL membranes. Linezolid embedded in the membranes is prevalently amorphous, with a low crystallinity showing a different polymorphic form respect to the usual Form I and Form II. The release kinetics of the drug were studied by spectrophotometric analysis (UV-vis). It allowed to discriminate between Linezolid molecules on the surface and encapsulated into the fibers. The antibacterial activity of the electrospun membranes was effective to inhibit Staphylococcus aureus. The properties of the loaded membranes and their capability for local delivery of the antibiotic make them good candidates as drug release devices for topical use.


Quantitative trait loci determining autogeny and body size in the Asian tiger mosquito (Aedes albopictus).
The majority of mosquito species require a blood meal to stimulate vitellogenesis and subsequent oviposition (anautogeny), but some autogenous individuals complete their first ovarian cycle without a blood meal. Autogeny may be facultative or obligatory. In this study, we selected for an autogenous strain in the Asian tiger mosquito Aedes albopictus and examined an F(1) intercross population for quantitative trait loci (QTL) determining the autogeny trait as well as wing length as a proxy for body size. Using composite interval mapping, we identified four QTL for each trait and observed considerable overlap in genome positions between each QTL for autogeny (follicle size) and wing length. Most QTL were minor in magnitude, individually explaining <10% of the phenotypic variation. Alleles from the autogenous parent generally showed a dominance or overdominance effect on both phenotypes. Strong genetic and phenotypic correlations indicate that autogeny and wing length are determined by up to four clusters of tightly linked genes or the potential pleiotropic effects of single genes. Although females from the autogenous strain produced approximately fivefold more eggs following a blood meal than through autogeny, we suggest that the maintenance of alleles for autogeny in natural populations is likely due to balancing selection. Autogeny should be favored under conditions of limited host availability for blood feeding or increased defensive behavior by the host and adequate larval nutrition. Correlation between autogeny and body size may reflect an increased ability for larger females to accumulate sufficient nutrient reserves to support oogenesis without the requirement for a blood meal.


Association between comprehensive geriatric assessment and short-term outcomes among older adult patients with stroke: A nationwide retrospective cohort study using propensity score and instrumental variable methods.
Comprehensive geriatric assessment (CGA) is a multidimensional and multidisciplinary method to identify geriatric conditions among older patients. The aim of the present study was to examine the associations between CGA and short-term outcomes among older adult inpatients with stroke. The study was a nationwide, retrospective cohort study. We used the Diagnosis Procedure Combination database, a national Japanese inpatient database, to identify older adult stroke patients from 2014 to 2017. The associations between CGA and in-hospital mortality, length of hospital stay, readmission rate, rehabilitation intervention, and introduction of home health care were evaluated using propensity score matching and instrumental variable analysis. We identified 338,720 patients, 21·3% of whom received CGA. A propensity score-matched analysis of 53,861 pairs showed that in-hospital mortality was significantly lower in the CGA group than in the non-CGA group (3·6% vs. 4·1%, p < 0·001). The rate of long-term hospitalization (> 60 days) was significantly lower in the CGA group than in the non-CGA group (8·7% vs. 10·1%, p < 0·001), and the rates of rehabilitation intervention (30·3% vs. 24·9%, p < 0·001) and home health care (8·3% vs. 7·6%, p = 0·001) were both higher in the CGA group than in the non-CGA group. Instrumental variable analysis showed similar results. CGA was significantly associated with the examined short-term outcomes. These findings from Japan, one of the most aged countries worldwide, highlight the possible benefits of CGA for short-term outcomes and can be of use for health policy in other international contexts. This work was supported by grants from the Ministry of Health, Labour and Welfare, Japan (19AA2007 and H30-Policy-Designated-004) and the Ministry of Education, Culture, Sports, Science and Technology, Japan (17H04141).


Poly(ADP-ribose)polymerases are involved in microhomology mediated back-up non-homologous end joining in Arabidopsis thaliana.
Besides the KU-dependent classical non-homologous end-joining (C-NHEJ) pathway, an alternative NHEJ pathway first identified in mammalian systems, which is often called the back-up NHEJ (B-NHEJ) pathway, was also found in plants. In mammalian systems PARP was found to be one of the essential components in B-NHEJ. Here we investigated whether PARP1 and PARP2 were also involved in B-NHEJ in Arabidopsis. To this end Arabidopsis parp1, parp2 and parp1parp2 (p1p2) mutants were isolated and functionally characterized. The p1p2 double mutant was crossed with the C-NHEJ ku80 mutant resulting in the parp1parp2ku80 (p1p2k80) triple mutant. As expected, because of their role in single strand break repair (SSBR) and base excision repair (BER), the p1p2 and p1p2k80 mutants were shown to be sensitive to treatment with the DNA damaging agent MMS. End-joining assays in cell-free leaf protein extracts of the different mutants using linear DNA substrates with different ends reflecting a variety of double strand breaks were performed. The results showed that compatible 5'-overhangs were accurately joined in all mutants, that KU80 protected the ends preventing the formation of large deletions and that PARP proteins were involved in microhomology mediated end joining (MMEJ), one of the characteristics of B-NHEJ.


AMPK increases expression of ATM through transcriptional factor Sp1 and induces radioresistance under severe hypoxia in glioblastoma cell lines.
We have previously reported that severe hypoxia increases expression and activity of the DNA damage sensor ATM by activation of the key energy sensor AMPK. Here, to elucidate molecular mechanisms underlying increased expression and activity of ATM by AMPK under severe hypoxia, we investigated roles of transcriptional factors Sp1 and FoxO3a using human glioblastoma cell lines T98G and A172. Severe hypoxia increased expression of ATM, AMPKα and Sp1 but not that of FoxO3a. Knockdown of AMPKα suppressed expression of ATM and Sp1 and suppressed cellular radioresistance under severe hypoxia without affecting cell cycle distribution. Knockdown of Sp1 suppressed expression of ATM. These results suggest that increased expression and activity of AMPK under severe hypoxia induce cellular radioresistance through AMPK/Sp1/ATM pathway.


Multiscale modeling of hemolysis during microfiltration.
In this paper, we propose a multiscale numerical algorithm to simulate the hemolytic release of hemoglobin (Hb) from red blood cells (RBCs) flowing through sieves containing micropores with mean diameters smaller than RBCs. Analyzing the RBC damage in microfiltration is important in the sense that it can quantify the sensitivity of human erythrocytes to mechanical hemolysis while they undergo high shear rate and high deformation. Here, the numerical simulations are carried out via lattice Boltzmann method and spring connected network (SN) coupled by an immersed boundary method. To predict the RBC sublytic damage, a sub-cellular damage model derived from molecular dynamic simulations is incorporated in the cellular solver. In the proposed algorithm, the local RBC strain distribution calculated by the cellular solver is used to obtain the pore radius on the RBC membrane. Index of hemolysis (IH) is calculated by resorting to the resulting pore radius and solving a diffusion equation considering the effects of steric hinderance and increased hydrodynamic drag due to the size of the hemoglobin molecule. It should be mentioned that current computational hemolysis models usually utilize empirical fitting of the released free hemoglobin (Hb) in plasma from damaged RBCs. These empirical correlations contain ad hoc parameters that depend on specific device and operating conditions, thus cannot be used to predict hemolysis under different conditions. In contrast to the available hemolysis model, the proposed algorithm does not have any empirical parameters. Therefore, it can predict the IH in microfilter with different sieve pore sizes and filtration pressures. Also, in contrast to empirical correlations in which the Hb release is related to shear stress and exposure time without considering the physical processes, the proposed model links flow-induced deformation of the RBC membrane to membrane permeabilization and hemoglobin release. In this paper, the cellular solver is validated by simulating optical tweezers experiment, shear flow experiment as well as an experiment to measure RBC deformability in a very narrow microchannel. Moreover, the shape of a single RBC at the rupture moment is compared with corresponding experimental data. Finally, to validate the damage model, the results obtained from our parametric study on the role of filtration pressure and sieve pore size in Hb release are compared with experimental data. Numerical results are in good agreement with experimental data. Similar to the corresponding experiment, the numerical results confirm that hemolysis increases with increasing the filtration pressure and reduction in pore size on the sieve. While in experiment, the RBC pore size cannot be measured, the numerical results can quantify the RBC pore size. The numerical results show that at the sieve pore size of 2.2 μm above 25 cm Hg, RBC pore size is above 75 nm and RBCs experience rupture. More importantly, the results demonstrate that the proposed approach is independent from the operating conditions and it can estimate the hemolysis in a wide range of filtration pressure and sieve pore size with reasonable accuracy.


Left ventricular assist device deactivation following cardiac recovery and pump thrombosis.
Left ventricular assist devices (LVADs) have become an increasingly important component of the management of severe heart failure not only as bridge therapy to eventual orthotopic heart transplantation, but also as destination therapy. Timely diagnosis and management of device complications are of vital importance. Rarely, LVAD placement can result in cardiac recovery that may necessitate device removal. While there are reports of minimally invasive LVAD deactivation, there are currently no guidelines for device extraction or deactivation in the setting of cardiac recovery. This is a case of both cardiac recovery and pump thrombosis following LVAD implantation, managed with device inactivation and driveline excision.


The design of an energy plant and artificial intelligence-based optimization for pasteurization with the least amount of carbon emissions based on animal waste.
It has been known for a very long time that chemical energy may be converted into electrical energy by using biomass, considered a renewable energy source. In the study that is being presented here, an explanation and a presentation are offered on a one-of-a-kind hybrid system that generates dependable power and cooling by harnessing the chemical energy of biomass. An anaerobic digester takes in organic material and converts it into biomass by using the high-energy content of cow manure as fuel. The Rankin cycle is the primary engine that drives the system that produces energy, and its combustion-based byproducts are routed to an ammonia absorption refrigeration system in order to provide sufficient cooling for the process of pasteurizing and drying the milk. It is expected that solar panels might contribute to the production of sufficient amounts of power for necessary activities. The technical and financial facets of the system are both being investigated at the moment. In addition, the optimal working conditions are determined by employing a forward-thinking multi-objective optimization strategy. This method simultaneously raises the operational effectiveness to the greatest extent that is practically possible while simultaneously lowering both expenses and emissions. The findings indicate that under ideal conditions, the levelized cost of the product (LCOP), efficiency, and emission of the system are, respectively, 0.087 $/kWh, 38.2%, and 0.249 kg/kWh. The digester and the combustion chamber both have very high exergy destruction rates, with the digester having the highest rate and the combustion chamber having the second-highest rate among all of the system's components. This assertion is supported by every one of these components.


L-374,087, an efficacious, orally bioavailable, pyridinone acetamide thrombin inhibitor.
Replacement of the amidinopiperidine P1 group of 3-benzylsulfonylamino-6-methyl-2-pyridinone acetamide thrombin inhibitor L-373,890 (2) with a mildly basic 5-linked 2-amino-6-methylpyridine results in an equipotent compound L-374,087 (5, Ki = 0.5 nM). Compound 5 is highly selective for thrombin over trypsin, is efficacious in the rat ferric chloride model of arterial thrombosis and is orally bioavailable in dogs and cynomolgus monkeys. The structural basis for the critical importance of both methyl groups in 5 was confirmed by X-ray crystallography.


Development of an in vitro model to study hepatitis C virus effects on hepatocellular lipotoxicity and lipid metabolism.
Hepatic steatosis is common in patients infected with hepatitis C virus (HCV). Particularly in patients infected with non-genotype 3 HCV, hepatic steatosis is closely related to factors of the metabolic syndrome such as hyperlipidemia. However, the molecular mechanisms involved in this "metabolic" steatosis in non-3 genotype HCV infections are not well understood. Here, we aimed to develop an in vitro model to study the effect of genotype 1 HCV infection on hepatic lipotoxicity and lipid metabolism. Cellular lipid accumulation was induced in Huh-7 hepatoma cells transfected with HCV genotype 1b replicon (HCV+) by incubation with increasing doses of palmitic acid (C16:0) or oleic acid (C18:1 n-9) complexed to albumin mimicking hyperlipidemic conditions. Mock transfected hepatoma cells (HCV-) were used as controls. Incubation with oleic acid concentrations as high as 0.5 mM did not induce toxic effects in HCV+ or HCV- cells. In contrast, incubation with palmitic acid caused dose-dependently cytotoxic effects which were more pronounced in HCV+ compared to HCV- cells. Further analysis with subtoxic palmitic and oleic acid concentrations revealed a higher uptake of fatty acids and intracellular triglyceride accumulation in HCV+ compared to HCV- cells. Carnitine palmitoyltransferase I (CPT1) expression, indicative of mitochondrial beta-oxidation, was markedly stimulated by lipid exposure in HCV+ but not in HCV- cells. Furthermore, heme oxygenase 1 (HMOX1) expression levels increased in FA stimulated cells, and this increase was significantly higher in HCV+ compared to HCV- cells. In contrast, expression of the key enzymes of hepatic de novo lipogenesis fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD-1) was significantly reduced upon oleate exposure in HCV- but not in HCV+ cells. In summary, our newly developed cell culture model revealed effects of HCV genotype 1b infection on metabolic susceptibility to lipid accumulation and toxicity particularly to saturated lipids. These results may indicate that HCV (genotype 1b) infected individuals with hyperlipidemia may benefit from dietary or pharmacological intervention.


Intramedullary spinal cord metastasis arising from papillary thyroid carcinoma: A case report and review of literature.
Intramedullary spinal cord metastases (IMSCM) are typically drop lesions from intracranial metastases and are a rare manifestation of systemic malignancy (8.5% of central nervous system metastases). They arise from primaries such as the lungs, breast, kidney, melanoma, or lymphoma. On the other hand, they arise very rarely from papillary thyroid carcinoma (PTC), even though it is the most common type of primary thyroid malignancy. A 54-year-old male presented with pain in the lower back along with tingling, numbness, and weakness in the bilateral lower limbs. This was associated with urine incontinence for 1½ months. In the previous month, he developed a left-sided solitary thyroid nodule. Fine needle aspiration cytology and ultrasonography were suggestive of metastasis. Furthermore, the thoracolumbar magnetic resonance imaging showed T1-hypo and T2-hyper-intense D11-D12 level intramedullary lesion, with intense enhancement, which was consistent with an intramedullary lesion involving the conus. At surgery, a firm, brownish yellow, friable, vascular tumour was removed en toto. Upon discharge, the patient was neurologically intact except for residual bladder incontinence. In an extensive literature review (pubmed), IMSCM metastasis from PTC primary is confirmed as a rarity and this may be the fourth documented case. Moreover, this may be the first report of a case of PTC metastatic neurological deterioration "even before the treatment of the primary was undertaken." Early diagnosis and microsurgical resection can result in improvement of neurological deficits and in the quality of life of patients with IMSCM.


Transgenes and gene suppression: telling us something new?
Transgenes provide unique opportunities to assess the relationship between genotype and phenotype in an organism. In most cases, introduction and subsequent expression of a transgene will increase (with a sense RNA) or decrease (with an antisense RNA) the steady-state level of a specific gene product. However, a number of surprising observations have been made in the course of many transgenic studies. We develop a hypothesis that suggests that many examples of endogenous gene suppression by either antisense or sense transcripts are mediated by the same cellular mechanism.


Prediction of the morbidity and mortality rates of COVID-19 in Egypt using non-extensive statistics.
Non-extenstive statistics play a significant role in studying the dynamic behaviour of COVID-19 to assist epidemiological scientists to take appropriate decisions about pandemic planning. Generic non-extensive and modified-Tsallis statistics are used to analyze and predict the morbidity and mortality rates in future. The cumulative number of confirmed infection and death in Egypt at interval from 4 March 2020 till 12 April 2022 are analyzed using both non-extensive statistics. Also, the cumulative confirmed data of infection by gender, death by gender, and death by age in Egypt at interval from 4 March 2020 till 29 June 2021 are fitted using both statistics. The best fit parameters are estimated. Also, we study the dependence of the estimated fit parameters on the people gender and age. Using modified-Tsallis statistic, the predictions of the morbidity rate in female is more than the one in male while the mortality rate in male is greater than the one in female. But, within generic non-extensive statistic we notice that the gender has no effect on the rate of infections and deaths in Egypt. Then, we propose expressions for the dependence of the fitted parameters on the age. We conclude that the obtained fit parameters depend mostly on the age and on the type of the statistical approach applied and the mortality risk increased with people aged above 45 years. We predict - using modified-Tsallis - that the rate of infection and death in Egypt will begin to decrease till stopping during the first quarter of 2025.


Autoimmune diabetes mellitus after COVID-19 vaccination in adult population: a systematic review of case reports.
Autoimmune/type 1 diabetes mellitus (T1DM) is a recently described rare occurrence following the administration of adjuvants such as coronavirus disease 2019 (COVID-19) vaccines. This systematic review aimed to review all available literature on the potential association between COVID-19 vaccines and T1DM. The Directory of Open Access Journals, MEDLINE, Google Scholar, and Scopus were systematically searched for all published studies from inception to July 2022. Articles reporting T1DM development within 8 weeks of administration of COVID-19 vaccine were included. Two reviewers independently performed the risk of bias assessment following the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports. Eight eligible studies were retrieved, comprising 12 patients diagnosed with T1DM after being vaccinated with a COVID-19 vaccine. Six patients (50%) reported T1DM after receiving the second dose. Five patients (41.7%) presented with diabetic ketoacidosis, of which four presented within the first eight days after vaccination. Five patients (41.7%) had genetic susceptibility, with RNA binding motif protein 45 (RBM45/DRB1) and major histocompatibility complex, class II, DQ beta 1 (HLA-DQB1) mutations being prominent. In this review, we have shown a small number of new-onset diabetes cases coincidently occurring soon after the COVID-19 vaccine, especially in those with genetic susceptibility. Despite being older, these patients had a similar phenotype to T1DM. While there might be a causal relationship between COVID-19 vaccines and T1DM development, this should not influence decisions regarding vaccination since the overall benefit outweighs the risk. Further larger prospective trials are needed to assess causal relationship and to clarify the potential roles of COVID-19 vaccine-derived antigens in autoimmune disease development. PROSPERO-CRD42022342093.


Presence of organochlorine pesticides in breast milk samples from Colombian women.
The presence of organochlorine pesticides (OCPs) in biological and environmental samples has been studied for decades in many countries. Nonetheless, studies in Latin American countries like Colombia have been scarce. Determining the presence of OCPs in breast milk will be of relevance to assess exposures, potential health risks, and for surveillance among Latin American populations. Thirty-two breast-feeding mothers were selected to voluntarily participate in the study. Breast milk samples were analyzed for 10 OCPs (α-, β-, γ-, δ-HCH, Heptachlor, α-, γ-Chlordane, 4,4' DDT, 4,4' DDE, 4,4' DDD). Milk samples were analyzed using liquid-liquid extraction, followed by sulfuric acid clean-up, and quantified using GC/μECD. Results were confirmed by GC/MS. OCPs concentrations were normalized using fat content. In all but one sample, 4,4' DDE was quantified in concentrations ranging between<17 and 14948 ng g(-1) (ng of OCP per g of lipids), with a mean value of 203 ng g(-1). One woman had 4,4' DDE concentrations that were orders of magnitude above the average concentrations observed worldwide. Concentrations of 4,4' DDE in a second breast milk sample collected in a different time period of lactation from a sub-group of 13 women from the original participants, showed no statistically significant difference with the concentrations found in the first sample. Based on the results obtained from the Persistent Organic Pollutants Global Monitoring Plan report of 2009 of the Stockholm Convention, Colombia ranks fourth from bottom to top in terms of 4,4' DDE average concentrations.


Cartilage-hair hypoplasia gene assigned to chromosome 9 by linkage analysis.
Cartilage-hair hypoplasia (CHH) is an autosomal recessive skeletal dysplasia of unknown pathogenesis leading to short-limbed stature. Associated features include hypoplasia of hair, abnormal cellular immunity, deficient erythrogenesis, increased risk of malignancies, Hirschsprung disease, and Diamond-Blackfan type hypoplastic anaemia. We mapped the CHH gene by linkage analysis with 5 markers to chromosome 9. Multipoint linkage analysis gives a lod score of 9.94 for a location between D9S43 and D9S50. Based on strong linkage disequilibrium the closest marker, D9S50, is likely to be less than 1 cM from the gene. No heterogeneity was observed in 14 Finnish families, nor was there evidence of reduced penetrance. These results provide a starting point for the eventual cloning and characterization of the CHH gene.


Risk factors for the infection with Brachyspira hyodysenteriae in pig herds.
Swine dysentery (SD), caused by infection with Brachyspira hyodysenteriae, is a serious disease in pig production worldwide. Quantitative risk factors triggering the occurrence of infection are unknown. The present case-control study aimed at identifying major risk factors related to presence of B. hyodysenteriae in pig herds. Twenty case herds and 60 randomly selected control herds with a minimum herd size of '10 sows/ 80 fattening pigs' were examined by means of a questionnaire-based interview and a herd examination. Herds with previous eradication of SD were excluded. Logistic regression models revealed that the 'positive/suspicious SD status of source herds', the regular application of treatment, purchasing more than 4 batches/ year, contact to foxes, diagnostics performed during last 12 months, liquid feeding systems, rats on farm, and >250 fatting places were associated with higher chances of a herd to be infected. On the contrary, having different sources of grower pigs within one batch, the presence of raptor birds and the presence of martens in the region were associated with fewer chances of being infected. The final multivariable logistic regression model identified purchasing more than 4 batches/ year (OR = 7.5, 95 % CI 1.8-54.3) and contact to foxes (OR = 5.9; 97.5 % CI 1.2-34.6) as the two main risk factors in our study. 'More than 4 batches/ year' implies continuous herd management supporting persistence of B. hyodysenteriae in an infected herd, but also increased number of purchases each increasing the risk of B. hyodysenteriae introduction by carrier pigs or transport vehicles. Foxes might be infected with B. hyodysenteriae by feeding on positive piglets and rodents. Besides, 'contact to foxes' might represent a lack in biosecurity. In conclusion, the risk factors detected underline the importance of biosecurity in SD prevention and control.


Macrophage Sprouty4 deficiency diminishes sepsis-induced acute lung injury in mice.
Inflammation and oxidative stress play critical roles in sepsis-induced acute lung injury (ALI). Sprout4 (Spry4) is involved in regulating inflammation and tissue injury; however, its role and mechanism in sepsis-induced ALI remain elusive. Macrophage-specific Spry4 knockout (Spry4MKO), transgenic (Spry4MTG) mice and matched control littermates were generated and exposed to cecum ligation and puncture (CLP) surgery to establish bacterial sepsis-induced ALI. Bone marrow-derived macrophages (BMDMs) from Spry4MKO or Spry4MTG mice were isolated and subjected to lipopolysaccharide (LPS) stimulation to further validate the role of Spry4 in vitro. To verify the necessity of AMP-activated protein kinase (AMPK), Spry4 and AMPK double knockout mice and compound C were used in vivo and in vitro. BMDMs were treated with STO-609 to inhibit calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2). We found that macrophage Spry4 was increased in CLP mice and positively correlated with sepsis-induced ALI. Macrophage Spry4 deficiency prevented, while macrophage Spry4 overexpression exacerbated sepsis-induced inflammation, oxidative stress and ALI in mice and BMDMs. Mechanistic studies revealed that macrophage Spry4 deficiency alleviated sepsis-induced ALI through activating CaMKK2/AMPK pathway. Our study identify macrophage Spry4 as a promising predictive and therapeutic target of sepsis-induced ALI.


Predation risk increases in estuarine bivalves stressed by low salinity.
Salinity drops in estuaries after heavy rains are expected to increase in frequency and intensity over the next decades, with physiological and ecological consequences for the inhabitant organisms. It was investigated whether low salinity stress increases predation risk on three relevant commercial bivalves in Europe. In laboratory, juveniles of Venerupis corrugata, Cerastoderma edule, and the introduced Ruditapes philippinarum were subjected to low salinities (5, 10 and control 35) during two consecutive days and, afterwards, exposed to one of two common predators in the shellfish beds: the shore crab Carcinus maenas and the gastropod Bolinus brandaris, a non-indigenous species present in some Galician shellfish beds. Two types of choice experiment were done: one offering each predator one prey species previously exposed to one of the three salinities, and the other offering each predator the three prey species at the same time, previously exposed to one of the three salinities. Consumption of both predators and predatory behaviour of C. maenas (handling time, rejections, consumption rate) were measured. Predation rates and foraging behaviour differed, with B. brandaris being more generalist than C. maenas. Still, both predators consumed significantly more stressed (salinity 5 and 10) than non-stressed prey. The overall consumption of the native species C. edule and V. corrugata was greater than that of R. philippinarum, likely due to their vulnerability to low salinity and physical traits (e.g., thinner shell, valve gape). Increasing precipitations can alter salinity gradients in shellfish beds, and thus affect the population dynamics of harvested bivalves via predator-prey interactions. The online version contains supplementary material available at 10.1007/s00227-021-03942-8.


Synthesis and evaluation of a novel series of phosphodiesterase IV inhibitors. A potential treatment for asthma.
The synthesis and pharmacological profile of a novel series of potent and selective phosphodiesterase type IV (PDE IV) inhibitors is described.


Microtubules and desmin filaments during the onset of heart growth in the rat.
Microtubules and intermediate desmin filaments were visualized in rat cardiomyocytes during the onset of heart growth by double immunolabelling of isolated myocytes, with specific antibodies raised against tubulin and desmin. Heart growth was stimulated either by mechanical overloading induced by aortic stenosis, or by injection of thyroxine into hypothyroid rats. In both experimental models, alterations in the microtubule pattern were observed soon after stimulation of growth whereas desmin filament organization remained unchanged. Microtubules were redistributed in arrays parallel to the long axis of the myocytes and were more numerous around the nuclei. Microtubules therefore appeared to be involved in the cellular events occurring during stimulated heart growth irrespective of the nature of the stimulus.


Expression of late viral functions in SV40-infected rat-monkey somatic cell hybrids.
Somatic cell hybrids between a rat hepatoma cell line and an SV40-transformed African green monkey kidney cell line (T22 TK-) have been isolated and their response to infection by SV40 virus characterized. The parental rat cells are nonpermissive to productive infection by SV40, while the parental monkey cells, which are T-antigen positive and capsid antigen negative, are permissive to productive infection. Hybrid clones, which had segregated monkey chromosomes, were infected with SV40 virus, and some clones were found to be negative for SV40 capsid antigen production while other clones were positive. Capsid antigen-positive clones production while other clones were positive. Capsid antigen-positive clones produced little or no form I SV40 DNA, no infectious virus, and were not capable of rescuing SV40 from SV40-transformed mouse cells. Such hybrids, which produce late viral proteins in the absence of mature progeny viral DNA may be useful in the study of control of SV40 RNA transcription.


Seat belt use law enforcement and publicity in Elmira, New York: a reminder campaign.
A three-week belt use law publicity and enforcement campaign in Elmira, New York, in November 1985, increased use from 49 per cent to 77 per cent; four months later belt use was 66 per cent. A reminder program, in April 1986, increased belt use to 80 per cent; use declined to 69 per cent four months later and to 60 per cent eight months later. Throughout these periods, belt use in Glens Falls, a comparison community, remained stable at just over 40 per cent.


[Pelvic floor and anal incontinence. Conservative therapy].
Conservative treatment of fecal incontinence and obstructive defecation can be treated by many conservative treatment modalities. This article presents the options of medication therapy, spincter exercises, electric stimulation, transcutaneous tibial nerve stimulation, anal irrigation and injection of bulking agents. These methods are presented with reference to the currently available literature but the evidence-based data level for all methods is low. For minor disorders of anorectal function these conservative methods can lead to an improvement of anorectal function and should be individually adapted.


Improving the Manufacturability of Cohesive and Poorly Compactable API for Direct Compression of Mini-tablets at High Drug Loading via Particle Engineering.
To utilize a particle engineering strategy to improve the manufacturability of a cohesive and poorly compactable API at high drug loading for direct compression of mini-tablets. A high-shear mixer was used for wet milling during the API manufacturing process to obtain target particle size distributions. The targeted particles were characterized and formulated into blends by mixing with excipients. The formulated blends were compressed directly into mini-tablets using a compaction simulator. The tablet hardness, weight variation, and friability of the mini-tablets were characterized and compared with mini-tablets prepared with hammer milled APIs. Compared to the hammer milled APIs, the wet milled APIs, had smoother surface, narrower particle size distributions and demonstrated a better flow properties. Moreover, the mini-tablets produced with the wet milled APIs exhibited better weight uniformity, robust tablet mechanical strength and ultimately better friability. In addition, unlike the hammer milled process, the wet milling process is controllable and easy to scale up. This study successfully implemented API particle engineering through a high shear wet milling process to produce particles suitable for robust drug product manufacturing.


[Sepsis therapy: present guidelines and their application].
Severe sepsis and septic shock have an increasing incidence and unchanged high mortality. Early diagnosis is necessary to slow the progression of organ dysfunction and improve outcome. Early administration of broad-spectrum antimicrobial therapy, early and aggressive hemodynamic therapy, and surgical source control are the most promising therapeutic approaches. Norepinephrine is the first choice as a vasopressor. Starches for volume resuscitation, intensive insulin therapy (aiming at 80-110 mg/dl), and low-dose hydrocortisone are not recommended outside randomized trials. Recombinant activated protein C is one choice for certain patients. The German Sepsis Competence Network (SepNet) is currently investigating other open questions.


Blockade of the antinociceptive effect of spinally administered kyotorphin by naltrindole in mice.
We investigated the role of spinal opioid receptors in the antinociceptive effect of kyotorphin (Tyr-Arg, KTP) by using an in vivo mice tail-pinch test and an in vitro opioid receptor binding assays. Intrathecal administration of KTP produced a dose-dependent antinociceptive effect with an ED(50) value of 24 microg/mouse. This antinociception, which was reversed by the KTP antagonist Leu-Arg, was completely blocked by naltrindole but not by naloxonazine, beta-funaltrexamine, or nor-binaltorphimine. The results from the binding study in vitro indicated that KTP bound to spinal KTP receptors but not to any opioid receptors in the mouse spinal cord. These results suggest that KTP-induced antinociception is mediated by binding to KTP receptors followed by an indirect activation of the delta-opioid receptors in the spinal cord.


Studies on brain lesion by administration of monosodium L-glutamate to mice. I. Brain lesions in infant mice caused by administration of monosodium L-glutamate.
Light-microscopic examination was performed on the brain lesions induced by monosodium L-glutamate (MSG) in neonatal and infant mice of ICR strain. Lesions characterized as cytoplasmic balooning, chromatin clumping, pyknosis and karyorrhexis of neurons were recognized in the arcuate nucleus (AN), subfornical organ, preoptic area, area postrema and cerebral cortex. The most vulnerable region was the AN in which the region near the root of the median eminence was easily damaged. The changes in the AN were severest in 7-day-old mice, but only slight in 20-day-old mice. Thresholds of inducing AN lesions in 10-day-old mice after intraperitoneal injection and force-tube feeding were 0.4 and 0.7-0.8 g/kg body weight, respectively. The threshold of retinal changes was about 2.5-fold that of AN in force-tube feeding. In neonatal mice injected daily with 4 g MSG/kg body weight, the neurons of the AN disappeared almost completely by the 4th day of intraperitoneal administration.


Machine learning to identify and understand key factors for provider-patient discussions about smoking.
We sought to identify key determinants of the likelihood of provider-patient discussions about smoking and to understand the effects of these determinants. We used data on 3666 self-reported current smokers who talked to a health professional within a year of the time the survey was conducted using the 2017 National Health Interview Survey. We included wide-ranging information on 43 potential covariates across four domains, demographic and socio-economic status, behavior, health status and healthcare utilization. We exploited a principled nonparametric permutation based approach using Bayesian machine learning to identify and rank important determinants of discussions about smoking between health providers and patients. In the order of importance, frequency of doctor office visits, intensity of cigarette use, length of smoking history, chronic obstructive pulmonary disease, emphysema, marital status were major determinants of disparities in provider-patient discussions about smoking. There was a distinct interaction between intensity of cigarette use and length of smoking history. Our analysis may provide some insights into strategies for promoting discussions on smoking and facilitating smoking cessation. Health care resource usage, smoking intensity and duration and smoking-related conditions were key drivers. The "usual suspects", age, gender, race and ethnicity were less important, and gender, in particular, had little effect.


Parathyroid adenoma in patient with prostatic carcinoma and hypercalcemia.
A sixty-seven-year-old white man with prostatic carcinoma was noted to be hypercalcemic and was subsequently found to have a parathyroid adenoma. Review of the literature revealed only 13 prior cases of hypercalcemia in patients with prostate malignancy. In none of those recorded cases was a parathyroid abnormality found, although a complete evaluation was not made in most of the patients. Because of the infrequent occurrence of hypercalcemia and prostatic carcinoma, it is suggested that patients with both disorders be evaluated for causes of hypercalcemia other than those generally associated with malignancy.


Distinct development and functions of resident and recruited liver Kupffer cells/macrophages.
Although mouse liver F4/80(+) Kupffer cells consist of cytokine-producing CD11b(+) cells and phagocytic CD68(+) cells, an undefined CD11b(-) CD68(-) subset (30%) also exists. We herein demonstrate a more fundamental classification by adding CD32 (FcγRII), which covers most liver F4/80(+) cells and the distinct functions of them. Among the F4/80(+) cells, 50%, 40%, and 30% of cells were CD32(+), CD68(+), and CD11b(+), respectively, and one-half of the CD68(+) cells coexpressed CD32. CD68(+) and CD32(+) cells, but not CD11b(+) cells, expressed a phagocytosis-related CRIg. Gy (6) irradiation depleted liver CD11b(+) cells and those in the spleen, bone marrow, and peripheral blood but not liver CD32/CD68(+) cells. Transfer of bone marrow cells into the irradiated mice reconstituted liver CD11b(+) cells. Conversely, clodronate pretreatment depleted only liver CD32/CD68(+) cells but not liver CD11b(+) cells and peripheral blood or spleen CD11b(+) monocytes/macrophages. Moreover, the CD32(+) cells might be precursors of CD68(+) cells, as a large proportion of CD32(+) cells expressed the c-kit (CD117), and CD34 and CD32(+) cells acquired CD68 immediately after bacteria administration. CD32/CD68(+) cells, but not CD11b(+) cells, expressed resident macrophage-specific MerTK and CD64 (FcγRI). Challenge with Staphylococcus aureus or liver metastatic EL-4 tumor cells indicated that the CD68(+) subset is engaged in systemic bactericidal activity, whereas the CD11b(+) subset is pivotal for liver antitumor immunity. Human liver CD14(+) Kupffer cells could also be classified into three similar subsets. These results suggest that liver CD68(+) Kupffer cells and CD11b(+) Kupffer cells/macrophages are developmentally and functionally distinct subsets.


In vitro assessment of environmental stress of persistent organic pollutants on the Indo-Pacific humpback dolphin.
Persistent organic pollutants (POPs) are detected ubiquitously and are linked to range of adverse health effects. The Indo-Pacific humpback dolphin inhabited the Pearl River Estuary (PRE), China, where high concentrations of POPs have been reported. This study evaluated the threats posed by POPs in the environment to the dolphin using an in vitro system. We selected BNF(β-naphthoflavone) and four POPs (DDTs (dichlorodiphenyltrichloroethanes), CHLs(chlorides), HCHs(hexachlorocyclohexanes) and HCB(hexachlorobenzene)) which had been accumulated in the dolphin with high concentrations to treat the cultured skin fibroblast cells (ScSF cells) of the dolphin, and investigated the expression patterns of the ecological stress biomarkers CYP1A1, AHR and HSP70 in the cell line. The results showed that CYP1A1 was up-regulated after being exposed to different concentrations of BNF, DDTs and HCHs. CHLs, HCHs and HCB promoted AHR expression. HSP70 expression was increased by high concentrations of BNF and DDTs. Moreover, comet assay experiments revealed that DDTs produced higher degree of DNA damage to ScSF cells than other POPs, implying that the Indo-Pacific humpback dolphin in the PRE has been threatened by POPs accumulated in the body, especially by DDTs. Our results provided important information to assess the risk of the Indo-Pacific humpback dolphin raised by environmental POPs in vivo.


Psychodynamic Leadership Approach and Leader-Member Exchange (LMX): A Psychiatric Perspective on Two Leadership Theories and Implications for Training Future Psychiatrist Leaders.
An increased emphasis in recent years on psychiatrists as healthcare leaders has not only drawn attention to the skills they can bring to this role but has also raised questions about how to best train and prepare them to assume leadership responsibilities. Such training should not be conducted in isolation from, and oblivious to, the wide-ranging expertise in human behaviour and relationships that psychiatrists can bring to the leadership arena. The aim of this theoretical paper is to draw attention to how psychiatrists can use their existing knowledge and skill set to inform their understanding of leadership theory and practice. In particular, the Psychodynamic Leadership Approach and Leader-Member Exchange theory are compared and contrasted to illustrate this point. The former represents a less well-known approach to leadership theory and practice whereas the latter is a widely familiar, conventional theory that is regularly taught in leadership courses. Both are underpinned by their emphasis on leader-follower relationships-and human relationships more broadly-and are intuitively appealing to psychiatrists endeavouring to understand aspects of organisational behaviour in the healthcare settings in which they work and lead. The application of these theories to assist reflection on and understanding of professional and personal leadership behaviours through leadership-oriented Balint-style groups and 360-degree appraisal is proposed. It is hoped that this paper will serve to stimulate thought and discussion about how leadership training for future psychiatrists can be tailored to better harness their existing competencies, thereby developing richer formative learning experiences and, ultimately, achieving superior leadership outcomes.


Bioassays: The best alternative for conventional methods in detection of Legionella pneumophila.
Fastidious bacteria are group of bacteria that not only grow slowly but also have complex nutritional needs. In this review, recent progress made on development of biosensing strategies towards quantification of Legionella pneumophila as fastidious bacteria in microbiology was investigated. In coincidence with medical bacteriology, it is the most widely used bio-monitoring, biosensors based on DNA and antibody. Also, all of legionella pneumophila genosensors and immunosensors that developed in recent years were collected analyzed. This review is meant to provide an overview of the various types of bioassays have been developed for determination of Legionella Legionella, along with significant advances over the last several years in related technologies. In addition, this review described: i) Most frequently applied principles in bioassay/biosensing of Legionellaii) The aspects of fabrication in the perspective of bioassay/biosensing applications iii) The potential of various electrochemical and optical bioassay/biosensing for the determination of Legionella and the circumvention of the most serious problem in immunosensing/immunoassay was discussed. iv) Some of bioassay/biosensing has been discussed with and without labels. v) We also summarize the latest developments in the applications of bioassay/biosensing methods for detection of Legionella. vi) The development trends of optical and electrochemical based bioassay/biosensing are also introduced.


Amorphous-to-crystalline transformation of sucrose.
The transformation of amorphous sugar in the form of lyophilized spheres into crystalline sucrose was studied. The lyophilisate, when exposed to moist atmospheres, picks up moisture to a constant weight. The amount of moisture addition is a function of relative humidity of the atmosphere and temperature. The loose "lyophilisate structure" collapses to form a denser amorphous phase ("hydrated amorphate"). After a lag time which varies with relative humidity of the atmosphere and temperature, the hydrated amorphate loses moisture (weight) and, in the process, forms crystalline sucrose. The phase nature of the hydrated amorphate is equivalent to an aqueous solution that is supersaturated with respect to crystalline sucrose. A model was developed for the lag time which accounts for the experimental results.


Coordinate induction of electrophoretic variants of juvenile hormone esterase.
Major and minor electrophoretic variants of juvenile hormone esterase (JHE) were found in the hemolymph of last instar larvae of Trichoplusia ni, both before and after metamorphic commitment. The average ratios of activity of the two major forms were similar during both last stadium peaks in activity. Immunological analysis showed that the hemolymph concentration of JHE during this stadium paralleled the level of enzymatic activity, and no putative higher molecular weight, inactive forms were detected. Immunological analysis provided the first evidence of relatedness of major and minor forms. After hormonal stimulation, the concentration of the two major forms increased concomitantly and by a similar proportion, suggesting that charge variation, at least for these two major forms, is not a point of hormonal or developmental regulation of JHE.


Size dependence of cell cycle parameters for lung metastases from B16 melanoma.
Data presented show that the cell cycle time of the lung metastases from a B16 melanoma tumor growing in the foot pad of C57 BL/6J mice increases as the size of the metastases increases. This increased cell phase durations of the small metastases being closer to those of the primary tumor. The growth fractions of the primary tumor and of the lung metastases of different sizes are analyzed.


It is not all about mating: Attractiveness predicts partner value across multiple relationship domains.
An account of the "beauty premium" based only on mating motivations overlooks adaptationist models of social valuation that have broader explanatory power. We suggest a broader approach based on evolved preferences for attractive partners in multiple cooperative domains (not just mating), which accounts for many observations of attractiveness-based preferential treatment more comfortably than does the target article's mating-specific account.


The effect of gravity on the ligaments of the medial malleolus and its pronating effect on the tarsus.
The strethcing effect of the force of gravity on the ligamentous system of the medial malleolus and the tarsus is described, based on biomechanical calculations. Attention is called to the necessity of the complete healing of the injuries of the ligaments and to the prevention of the valgus tendency of the tarsus.


The Effect of Large-scale Health Coverage Expansions in Wealthy Nations on Society-Wide Healthcare Utilization.
Most analysts project that a reform like Medicare-for-All that lowers financial barriers to care would cause a surge in the utilization of services, raising costs despite stable or even reduced prices. However, the finite supply of physicians and hospital beds could constrain such utilization increases. We reviewed the effects of 13 universal coverage expansions in capitalist nations on physician and hospital utilization, beginning with New Zealand's 1938 Social Security Act up through the 2010 Affordable Care Act in the USA. Almost all coverage expansions had either a small (i.e., < 10%) or no effect on society-wide utilization. However, coverage expansions often redistributed care-increasing use among newly covered groups while producing small, offsetting reductions among those already covered. We conclude that in wealthy nations, large-scale coverage expansions need not cause overall utilization to surge if provider supply is controlled. However, such reforms could redirect care towards patients who most need it.


Contralateral hydrothorax following subclavian catheter replacement using a guidewire.
Replacement of central venous catheters over a guidewire is now practiced throughout the United States. Although potential mechanical complications of this technique have been mentioned in the literature, few such complications have been documented. We report a patient who suffered a fatal contralateral hydrothorax following replacement of a central venous catheter using the guidewire technique.


Optimization of synchrotron based ion beam therapy facilities for treatment time reduction, options and the MedAustron development roadmap.
A faster treatment reduces the risk of intra-fraction movement of organs, offers a more comfortable treatment to the patient, allows to treat lesion of larger volumes in a reasonable time and most of all expands the capacity of the facility. This work presents possible machine upgrades for synchrotron based ion beam therapy centers to shorten the irradiation time. The expected delivery times for each scenario are simulated for the study case of proton beams of MedAustron. The second part of the work focuses on the MedAustron development roadmap, where recently increase of ring fillings and delivered intensities were implemented for proton treatments achieving an average irradiation time of ~50% since start of operation.


Exploring time-scales of closed-loop decoder adaptation in brain-machine interfaces.
Performing closed-loop modifications of a brain-machine interface (BMI) decoder is a technique that shows great promise for improving performance. We compare two algorithms for implementing adaptations that update decoder parameters on different time-scales (discrete batches vs. online), and present experimental results of a non-human primate performing a standard center-out BMI task. To ensure that our experimental training models are representative of a broad range of paralyzed patients, our decoders were initially trained using neural activity recorded during subject observation of cursor movement. We find that both closed-loop adaptation algorithms can be used to boost BMI performance from 20-30% to 80%, yielding movement kinematics similar to natural arm movements. Based on insights derived from the performance of each algorithm, we propose that a hybrid of batch and online decoder adaptation may be the best approach.


The Enduring Association between Education and Mortality: The Role of Widening and Narrowing Disparities.
This paper examines how educational disparities in mortality emerge, grow, decline, and disappear across causes of death in the United States and how these change contribute to the enduring association of education and mortality over time. Focusing on adults age 40-64, we first examine the extent to which disparities in all-cause mortality by education persisted from 1989-2007. We then test the "fundamental cause" prediction that mortality disparities persist, in part, by shifting to new health outcomes over time, most importantly for those causes of death that have increasing mortality rates. To test this hypothesis, we focus in depth on the period from 1999-2007, when all causes of death were coded to the same classification system. The results indicate (a) both substantial widening and narrowing of mortality disparities across causes of death, (b) almost all causes of death that had increasing mortality rates also had widening disparities by education, and (c) the total disparity by education in all-cause mortality would be about 25% smaller today were it not for newly widened or emergent disparities since 1999. These results point to the theoretical and policy importance of identifying the social forces that cause health disparities to widen over time.


Alzheimer changes are common in aged drivers killed in single car crashes and at intersections.
With increasing age, diseases affecting the cognitive functions are more frequent. These diseases may increase the risk for fatal car crashes. We analyzed the frequency of neuropathological alterations characteristic of Alzheimer's disease (i.e. neuritic and diffuse plaques, and neurofibrillary tangles) in two association areas of the brain, parietal and frontal cerebral cortex, from 98 fatally injured aged drivers. In the age groups of 65-75 and over 75 years of age, 50% and 72% of the drivers, respectively, had neuritic plaques in either parietal and/or frontal cortex. In 14% of all killed drivers the number of neuritic plaques reached the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) age-related histologic score C, which indicates the diagnosis of Alzheimer's disease (AD), and an additional 33% had score B, which suggests the diagnosis of AD. Neuropathological AD changes were most common in the brains of drivers killed in single vehicle crashes, followed by multivehicle crashes at intersections and least common in multivehicle crashes elsewhere, but the differences did not reach statistical significance. In a great majority (80-85%) of cases the killed aged driver was the guilty party of the crash. The results imply, that incipient AD may contribute to fatal crashes of aged drivers, and therefore the forensic autopsy of these victims should include neuropathological examination.


Elemental analysis of renal slices by proton-induced X-ray emission.
We optimized proton-induced X-ray emission (PIXE) for tissue analysis in a toxicity-disposition study. We used cultured rabbit renal slices as the biological system to demonstrate the use of PIXE analysis. The renal slices were exposed to HgCl2, CdCl2, K2Cr2O7, or NaAsO2 alone or in a mixture. The PIXE analysis provides information on concentrations of elements above atomic number 11, and it is the only analytical technique that can determine 20-30 elements nondestructively in a single, small sample (approximately 5 mg) with detection limits of 1-5 ppm (dry weight). The renal slices are thin targets that yield X-ray emission spectra with low backgrounds and high elemental sensitivities. The nondestructive nature of PIXE and the ability to simultaneously measure uptake of multiple metals and endogenous elements are unique to this methodology.


Molecular players regulating the jasmonate signalling network.
Many plant developmental and stress responses require the coordinated interaction of the jasmonate and other signalling pathways, such as those for ethylene, salicylic acid and abscisic acid. Recent research in Arabidopsis has uncovered several key players that regulate crosstalk between these signalling pathways and that shed light on the molecular mechanisms modulating this coordinated interaction. Genes that are involved in the regulation of protein stability through the ubiquitin-proteasome pathway (COI1, AXR1 and SGT1b), signalling proteins (MPK4) and transcription factors (AtMYC2, ERF1, NPR1 and WRKY70) form a regulatory network that allows the plant to fine-tune specific responses to different stimuli.


A possible role of xanthine oxidase in producing oxidative stress in the heart of chronically ethanol treated rats.
Examination of hearts and livers of rats fed ethanol for 25-30 weeks showed significant increases in catalase and glutathione peroxidase activity. Further examination revealed that the xanthine dehydrogenase/oxidase activity ratio in both tissues were decreased, suggesting that an interconversion of the dehydrogenase into oxidase might have occurred. Such an interconversion would be expected to enhance the formation of superoxide anions during acetaldehyde metabolism by xanthine oxidase. Since a role of oxidative or free radical damage in the etiology of ethanol-induced liver pathology is becoming increasingly apparent, the observation that the biochemical changes in the heart and liver are comparable suggests that oxidative damage is involved in alcoholic pathology of the heart as well as liver.


Persistent dizziness and nausea in patients receiving postoperative epidural pain control after living donor liver transplantation: case reports.
Dizziness and nausea are frequent problems among patients receiving patient-controlled epidural analgesia (PCEA) after major surgery. It is important to consider the various etiologies that might cause these adverse events, especially among patients who have undergone massive hepatic resection for living donor liver transplantation (LDLT). We have described 2 LDLT cases with persistent dizziness and nausea postoperatively despite several adjustments in PCEA management. Their symptoms were quickly relieved after suspension of PCEA medication. Our 2 cases of LDLT represented a unique setting for this type of complication.


Fibronectin on the surface of human lymphocytes.
Fibronectin was detected by immunofluorescence technique on the surface of one part of separated normal peripheral blood lymphocytes by using FITC-conjugated anti-human fibronectin antibodies. Approximately one-fifth of isolated B cells and 7% of O cells contained surface-bound fibronectin but T cells failed to stain. There were no detectable free receptors for fibronectin on the surface of lymphocytes of different subsets as it was studied with FITC-labelled purified fibronectin. The percent of B and O cells bearing surface bound fibronectin was markedly decreased in patients with acute and chronic lymphocytic leukemias.


Multifactorial effects of gluconic acid pretreatment of waste straws on enzymatic hydrolysis performance.
The chemical compositions of lignin, hemicellulose and cellulose are so far unascertained to various lignocellulose in respect to effect of cellulose enzymatic hydrolysis. The novel and environment-friendly gluconic acid (GA) pretreatment technology showed impressive results on the enzymatic hydrolysis of cellulose in various agricultural straws. However, only few of the main reasons or critical issues pertaining to this reaction are known. Therefore, the novel GA pretreatment was carried out to remove hemicellulose from the three representative waste straws under different conditions. Next, for the enzymatic hydrolysis of the residual cellulose fraction in the pretreated straws, some mathematical correlations have been investigated between enzyme accessibility, hemicellulose removal rate, and cellulose crystallinity index. Both linear and nonlinear models were compared using five-parameter logic curve, four-parameter logic curve, and Deming regression. Hemicellulose removal was logically ascribed to be the trigger for cellulose saccharification efficiency during GA pretreatment of these waste straws.


Patient education.
The 120 studies included in this review were grouped in relation to five categories of variables basic to a theory of instruction in patient education. Findings in the studies related to the characteristics of the patient as learner support the following variables as significant for a theory of instruction: demographic characteristics including age, race, duration and type of illness, educational level, and family preparedness. Selected psychological variables are significant as they interact with teaching approaches. Given only two studies in which the characteristics of the nurse as teacher were the main variables, no inferences for a theory of instruction could be drawn. However, the findings from those studies combined with results from studies in which characteristics of the nurse were secondary variables support the importance of this category of variables. The educational preparation, motivation, values, and job description of the nurse implementing patient teaching appear to be significant variables for a theory of instruction. Investigators explored a wide range of teaching strategies in the studies of patient teaching. The setting for teaching, group and individual teaching, and a variety of instructional strategies all prove promising at the operational level. The instructional strategies were too diverse to allow analysis at a level of abstraction beyond the operational. Findings in this review also support characteristics of the health care setting as an important category of variables for a theory of instruction. The organizational structure, a quality assurance framework, and valuing patient teaching appear to be significant variables. Patient education research provides a rich data source for future developments in theory, practice, and research. The effectiveness of patient education as a nursing intervention is clearly established. Furthermore, positive learning outcomes are associated with a broad range of teaching strategies, content areas, and patient populations. Systematic explorations of the characteristics of the patient as learner, the nurse as teacher, and the health care setting as a learning environment are still necessary for developing a theory of instruction for patient education. Future researchers should attend to phenomena unique to patient education rather than to duplicating general educational research. Instead of the investigator-driven research approach that characterizes research to date, replication should be encouraged. Future research should be designed to link theory and research and thereby contribute to the further development of a theory of instruction in patient education.


Antibiotic A 19009. Structural investigation and synthesis.
The structure of fermentation product A 19009 was reinvestigated by 13C and 1H NMR spectroscopy and established by independent synthesis to be N2-L-alanyl-N3-fumaramoyl-L-2,3-diaminopropanoic acid (2), i.e. a structure isomeric with the originally proposed structure 1. In contrast to 1 which also was synthesized, 2 has a very low activity against Trichomonas vaginalis.


Encapsulation of vasoactive intestinal peptide into liposomes: effects on vasodilation in vivo.
The purpose of this study was to determine whether encapsulation of vasoactive intestinal peptide (VIP) into liposomes potentiated its vasorelaxant effects in vivo. Using intravital microscopy, we measured the diameter of second-order arterioles (53 +/- 1 microns) in the hamster cheek pouch before, during and after suffusion of VIP, liposomes and VIP encapsulated into liposomes for 7 min. We found that VIP (0.05, 0.1 & 1.0 nmol) induced significant, time- and concentration-dependent vasodilation (9 +/- 1%, 13 +/- 3% and 14 +/- 1% increase from baseline values, respectively; mean +/- SEM; n = 12; p < 0.05). Arteriolar diameter returned to baseline values within 1-4 min after suffusion was stopped. These effects were significantly potentiated when VIP (0.05, 0.1 & 1.0 nmol) was encapsulated into liposomes (26 +/- 6%, 38 +/- 7% and 34 +/- 3% increase from baseline values, respectively; n = 12; p < 0.05). In addition, arteriolar diameter returned to baseline values 5-13 min after suffusion was stopped. Suffusion of liposomes alone had no significant effects on arteriolar diameter (n = 12; p > 0.5). We conclude that encapsulation of VIP into liposomes potentiates and prolongs of its vasorelaxant effects in the peripheral microcirculation in vivo.


Impact of extent of antral resection on surgical outcomes of sleeve gastrectomy for morbid obesity (a prospective randomized study).
Laparoscopic sleeve gastrectomy (LSG) is a surgical technique that treats morbid obesity. Consecutive patients with morbid obesity treated by LSG at our department were evaluated. Patients enrolled in the study were randomized into group I (LSG begins the division 2 cm from the pylorus) and group II (LSG begins the division 6 cm from the pylorus). The primary outcome measure was the percent of excess weight loss (% EWL); secondary outcomes included postoperative morbidity and mortality and improvement of comorbidity. One hundred five patients (79 (75.2 %) were females) were randomized into two groups of (GI) 52 patients and (GII) 53 patients. In group I, the mean % EWL was 51.8 ± 13.9, 63.8 ± 16.1 and 71.8 ± 12; however, in group II, the mean % EWL was 38.3 ± 10.9, 51.9 ± 13.6 and 61 ± 11.1 at 6, 12, and 24 months, respectively (P = 0.0001, 0.0001, 0.003). There was weight regain after 2 years in five patients in group II and only one patient in group I (P = 0.09). There was no significant difference between both group as regards gastric leakage, vomiting or GER. There was significant improvement in comorbidity after LSG in both groups, but no significant difference between them. Hospital mortality occurred in group II in one case as a result of gastric leakage. LSG is a safe and effective procedure with good short-term outcome. Increasing the size of the resected antrum is associated with better weight loss without increasing the rate of complications significantly.


In vitro development of one-cell embryos from outbred mice: influence of culture medium composition.
One-cell embryos from outbred mice (CF1, CD-1, and Dub:ICR) were cultured in various modifications of egg culture medium (ECM). The best development was observed in medium in which inorganic salts of modified T6 medium (mT6) replaced those of ECM. In this modification (TE), 66% of one-cell CF1 embryos developed into blastocysts, compared to 46 and 43% for ECM and mT6, respectively. Moreover, the cell numbers of blastocysts developing in TE (7.49 +/- 3.3) were higher than the cell numbers of those developing in ECM (55.1 +/- 2.4). The culture requirements of embryos varied between different stocks of mice: Fewer CF1 embryos developed to the blastocyst stage than either Dub:ICR embryos (90%) or CD-1 embryos (84%). Lowering the osmolarity of the medium from 300 to 280 mOSM, increasing the concentration of KC1 from 1.42 to 25 mM, or omitting lactate from the medium during Day 1 of culture did not further improve development of embryos, in contrast to previous reports. However, the time at which embryos were transferred to outgrowth medium influenced their postblastocyst development. The best development was observed when embryos were transferred on Day 4 of culture at the late morula-early blastocyst stage.


An objective measure of hyperactivity aspects with compressed webcam video.
Objective measures of physical activity are currently not considered in clinical guidelines for the assessment of hyperactivity in the context of Attention-Deficit/Hyperactivity Disorder (ADHD) due to low and inconsistent associations between clinical ratings, missing age-related norm data and high technical requirements. This pilot study introduces a new objective measure for physical activity using compressed webcam video footage, which should be less affected by age-related variables. A pre-test established a preliminary standard procedure for testing a clinical sample of 39 children aged 6-16 years (21 with a clinical ADHD diagnosis, 18 without). Subjects were filmed for 6 min while solving a standardized cognitive performance task. Our webcam video-based video-activity score was compared with respect to two independent video-based movement ratings by students, ratings of Inattentiveness, Hyperactivity and Impulsivity by clinicians (DCL-ADHS) giving a clinical diagnosis of ADHD and parents (FBB-ADHD) and physical features (age, weight, height, BMI) using mean scores, correlations and multiple regression. Our video-activity score showed a high agreement (r = 0.81) with video-based movement ratings, but also considerable associations with age-related physical attributes. After controlling for age-related confounders, the video-activity score showed not the expected association with clinicians' or parents' hyperactivity ratings. Our preliminary conclusion is that our video-activity score assesses physical activity but not specific information related to hyperactivity. The general problem of defining and assessing hyperactivity with objective criteria remains.