Preoperative poor coronary collateral circulation can predict the development of atrial fibrillation after coronary artery bypass graft surgery.
Coronary collateral circulation (CCC) helps to protect and preserve myocardium from episodes of ischemia, and reduce angina symptoms, arrhythmia, and cardiovascular events. Atrial fibrillation (AF) is the most frequent form of arrhythmia after coronary artery bypass graft (CABG) surgery. The aim of this study was to investigate the association between CCC and the development of AF in patients undergoing CABG surgery. A total of 165 patients (mean age 63±10 years, 74% men, 26% women) who were undergoing CABG surgery at our department were enrolled into this study. Patients were categorized into two groups according to preoperative CCC using the Rentrop method. Of the patients, 79 had poor CCC and 89 had good CCC. The AF incidence rate in the poor collateral group was significantly higher than that in the good collateral group [37 (49%) vs. 12 (14%), P<0.001]. In univariate analysis, age, left atrium size, and poor CCC grade were associated with AF after CABG surgery. Multivariate analysis showed that only poor CCC grade (odds ratio: 11.500; 95% confidence interval 3.977-33.253, P<0.001) was an independent predictor of the development of AF after adjustment of other potential confounders in patients undergoing CABG surgery. The present study showed that preoperative poor CCC is a powerful predictor of the development of AF after CABG surgery.


Psychological predictors of memory decline in a racially and ethnically diverse longitudinal sample of older adults in the United States.
In the United States, racial and ethnic disparities in memory dysfunction and Alzheimer disease are evident even after accounting for many risk factors. Psychological factors, such as psychological well-being, perceived control, depressive symptoms, and negative affect, may influence memory dysfunction, and associations may differ by race and ethnicity. This study examined whether psychological factors are differentially associated with episodic memory trajectories across racial and ethnic groups in the United States. The National Health and Aging Trends Study (NHATS), is a US-representative, longitudinal study of Medicare-eligible adults 65+ years old. Analyses of 5 years of data, included a total of 9411 participants without dementia at baseline. Adjusting for relevant covariates, a linear mixed model estimated the associations between psychological predictors and a composite of immediate and delayed trials from a word list memory test. More depressive symptoms (B = -0.02), lower psychological well-being (B = 0.03), and lower perceived control (B = 0.05) were independently associated with lower initial memory. Depressive symptoms were associated with faster rate of memory decline (B = -0.01). Black (B = -0.34) and Hispanic (B = -0.28) participants evidenced lower initial memory level than whites, but only Hispanic (B = -0.04) participants evidenced faster memory decline than whites. There were no significant interactions between the psychological variables and race and ethnicity. Results extend previous studies showing racial and ethnic disparities in episodic memory trajectories, and the longitudinal effects of depressive symptoms on episodic memory in US samples. Epidemiological studies of cognitive aging should incorporate more psychological factors clarify cognitive decline and disparities.


Phase I dose escalation and pharmacokinetic evaluation of two different schedules of LY2334737, an oral gemcitabine prodrug, in patients with advanced solid tumors.
This Phase-I-study aimed to determine the recommended Phase-II-dosing-schedule of LY2334737, an oral gemcitabine prodrug, in patients with advanced/metastatic solid tumors. Pharmacokinetics, cytokeratin-18 (CK18) levels, genetic polymorphisms, and antitumor activity were additionally evaluated. Patients received escalating doses of LY2334737 either every other day for 21 days (d) followed by 7 days-drug-free period (QoD-arm) or once daily for 7 days every other week (QD-arm). The 28 days-cycles were repeated until disease progression or unacceptable toxicity. Standard 3 + 3 dose-escalation was succeeded by a dose-confirmation phase (12 additional patients to be enrolled on the maximum tolerated dose [MTD]). Forty-one patients received QoD- (40-100 mg) and 32 QD-dosing (40-90 mg). On QoD, 3/9 patients experienced dose-limiting toxicities (DLTs) on the 100 mg dose (2 × G3 diarrhea, 1 × G3 transaminase increase); 1 additional DLT (G3 diarrhea) occurred during dose confirmation at 90 mg (12 patients). On QD, 1 patient each experienced DLTs on 60 mg (G3 transaminase increase) and 80 mg (G3 prolonged QTcF-interval); 2/7 patients had 3 DLTs on the 90 mg dose (diarrhea, edema, liver-failure; all G3). The MTD was established at 90 mg for the QoD-arm. Seven patients on QoD and 4 on QD achieved SD (no CR + PR). Pharmacokinetics showed a dose-proportional increase in exposure of LY2334737 and dFdC without accumulation after repeated dosing. Significant increases in CK18 levels were observed. Genetic polymorphism of the cytidine deaminase gene (rs818202) could be associated with ≥ G3 hepatotoxicity. Both schedules displayed linear pharmacokinetics and acceptable safety profiles. The recommended dose and schedule of LY2334737 for subsequent Phase-II-studies is 90 mg given QoD for 21 day.


Sleep disordered breathing in the elderly.
Sleep-disordered breathing, especially obstructive sleep apnea (OSA), has a high prevalence among the elderly, where it may present with atypical symptoms. Untreated OSA can reduce quality of life and have adverse health consequences. Effective treatment is available, so all physicians treating the elderly should be aware of the clinical presentation, diagnostic methods, and treatment options for OSA.


A fusca gene homologue in mammalian tissues: Developmental regulation in the rat testes.
By differential screening of a rat pineal cDNA library we identified earlier a novel transcript having a 57% nucleotide homology and a 45% amino acid identity with a plant fusca-gene (fus6) to which a corresponding human sequence (gps1) has recently been reported. Expression of this mammalian fusca homologue (mfh) was seen in a variety of mammalian tissues, including kidney, pineal and retina, but it was particularly strong in the testes. Northern blot analysis demonstrated that the rat testicular mfh message increases markedly from day 28 onwards. Additionally, by in situ hybridization, mfh was localized primarily to the seminiferous tubules with a stage-dependent distribution pattern, a result which was confirmed by immunohistochemistry with antibodies raised against a synthetic MFH oligopeptide. Western blotting also revealed strong signals of the expected molecular weight in testicular extracts from several species. In view of its homology to fus6, a plant gene known to be involved in repressing photomorphogenesis in darkness, the conservation of mfh in mammals suggests a potential function for MFH in signaling pathways involved in the regulation of mammalian differentiation and development.


Blood pressure during oestrogen/progestogen substitution therapy in healthy post-menopausal women.
In order to explore the long-term effect of hormone (17 beta-oestradiol) substitution therapy on blood pressure in healthy post-menopausal women, we reviewed the data from five long-term (1-2 yr), double-blind, placebo-controlled studies carried out in our department over the last decade. Three of the studies related to early post-menopausal women (mean age 50 in all three cases) and two involved later post-menopausal women (mean ages 64 and 70, respectively). The systolic blood pressure values during hormonal substitution therapy showed no change in relation to those recorded during placebo administration, whereas the diastolic blood pressure fell slightly in all five studies. However, in that based on the oldest subjects, the results were not statistically significant. It was therefore concluded that hormone substitution therapy with 17 beta-oestradiol has no adverse effect on blood pressure, and may even have a beneficial action.


Visual impairment and circadian rhythm disorders.
Many aspects of human physiology and behavior are dominated by 24-hour circadian rhythms that have a major impact on our health and well-being, including the sleep-wake cycle, alertness and performance patterns, and many daily hormone profiles. These rhythms are spontaneously generated by an internal "pacemaker" in the hypothalamus, and daily light exposure to the eyes is required to keep these circadian rhythms synchronized both internally and with the external environment. Sighted individuals take this daily synchronization process for granted, although they experience some of the consequences of circadian desynchrony when "jetlagged" or working night shifts. Most blind people with no perception of light, however, experience continual circadian desynchrony through a failure of light information to reach the hypothalamic circadian clock, resulting in cyclical episodes of poor sleep and daytime dysfunction. Daily melatonin administration, which provides a replacement synchronizing daily "time cue, " is a promising therapeutic strategy, although optimal treatment dose and timing remain to be determined.


MiR-195 inhibits the proliferation of human cervical cancer cells by directly targeting cyclin D1.
MicroRNAs are important regulators of multiple cellular processes, and aberrant miRNA expression has been observed in human cervical cancer (CC). The present study was to evaluate the level of miR-195 and cyclin D1 in CC tissues and cells. We further investigated the molecular mechanisms of miR-195 and cyclin D1 in CC cell lines HeLa and SiHa. Here, we found that miR-195 expression was down-regulated in CC tissues, and HeLa and SiHa cells (all p < 0.001). By contrast, cyclin D1 was up-regulated. Furthermore, the expression of miR-195 was inversely proportional to that of cyclin D1 mRNA or protein (p = 0.013, p = 0.015, respectively). In vitro studies demonstrated that the overexpression of miR-195 played a suppressor role in the proliferation of HeLa and SiHa cells and promoted cell apoptosis. Luciferase reporter assays confirmed that miR-195 binding to the 3'-UTR regions of cyclin D1 inhibited the expression of cyclin D1 in HeLa and SiHa cells. However, the inhibitor of miR-195 promoted the expression of cyclin D1 and cell proliferation. In conclusion, our data suggest that miR-195 may have the potential role in treatment of CC patients, as well as miR-195 is a novel regulator of invasiveness and tumorigenicity in CC cells by targeting cyclin D1. MiR-195/cyclin D1 pathway may be a useful therapeutic agent in CC patients.


Epidermal growth factor receptor as a predictor of tumor downstaging in locally advanced rectal cancer patients treated with preoperative chemoradiotherapy.
To examine retrospectively whether levels of epidermal growth factor receptor (EGFR) expression can predict tumor downstaging after preoperative chemoradiotherapy in patients with locally advanced rectal cancer. A total of 183 patients with rectal cancer (cT3-T4 or N+) were enrolled in this study. Preoperative chemoradiotherapy consisted of 50.4 Gy of pelvic radiation with concurrent 5-fluorouracil and leucovorin bolus intravenous chemotherapy in 94 patients or oral capecitabine and leucovorin in 89 patients. EGFR expression in pretreatment paraffin-embedded tumor biopsy specimens was assessed by immunohistochemistry. EGFR expression was determined from the intensity and extent of staining. Tumor downstaging was defined as a reduction of at least one T-stage level. Tumor downstaging occurred in 97 patients (53%), and the tumors showed a pathologic complete response in 27 patients (15%). Positive EGFR expression was observed in 140 (76%) of 183 patients. EGFR expression levels were low in 113 patients (62%) and high in 70 patients (38%). On logistic regression analysis, the significant predictive factor for increased tumor downstaging was a low level of EGFR expression and preoperative chemotherapy using oral capecitabine (odds ratio, 0.437; p = 0.012 vs. odds ratio, 3.235; p < 0.001, respectively). A high level of EGFR expression may be a significant predictive molecular marker for decreased tumor downstaging after preoperative chemoradiotherapy in locally advanced rectal cancer.


Therapeutic Effects of Exercise Training On Selected Cardio-Pulmonary Parameters and Body Composition of Nigerians with Chronic Heart Failure (A Preliminary Study).
The use of exercise training in the management of individuals with chronic heart failure has not been widely accepted by health care providers especially in Sub-Saharan Africa because of the possibility that the failing hearts may have a negative response to the increased workload and stress of exercise. The study aimed to evaluate the effects of exercise training (ET) on selected cardio-respiratory and body composition variables of Nigerians with chronic heart failure (CHF). Thirty two Nigerians with CHF (male - 17), aged 30 to 71 years, mean age 54.2 ± 1.9 years and New York Heart Association Functional Class (NYHA) II-III recruited from Cardiology Clinic of Lagos University Teaching Hospital Nigeria participated in the study. They were randomized into exercise (EG) and control groups (CG). Exercise group performed 12-weeks of aerobic and resistance training for 60 minutes, three sessions per week. Selected cardio-respiratory and body composition variables were measured pre and post intervention in both groups. Data was analyzed using SPSS-17 package. Level of significance was set at 0.05. There was no significant difference in the measured variables between the groups at baseline (p > 0.05). Significant improvement was seen in EG in all the measured variables except the systolic (p = 0.29) and diastolic blood pressure (p = 0.45). No adverse effect was observed during the exercise training. No significant improvement was observed in the control group (p > 0.05). Exercise training may improve cardiorespiratory and body composition variables in patients with chronic heart failure.


Sleep medicine in Europe: 50 years of evolution.
The evolution of sleep medicine in Europe over the past 50 years https://bit.ly/3AVexV8.


2,5-Hexanedione alters microtubule assembly. II. Enhanced polymerization of crosslinked tubulin.
The toxic syndrome resulting from in vivo exposure to n-hexane or n-hexane derivatives may, in part, be a manifestation of altered tubulin and microtubule properties. The effect of in vitro gamma-diketone derivatization was first studied using purified bovine brain tubulin and the results were then verified in tubulins purified from target organs of an experimental species. Microtubule assembly and structure were modified after in vitro incubation with 2,5-hexanedione (2,5-HD) as follows: 2,5-HD derivatization of purified tubulin resulted in an alteration in microtubule assembly kinetics, most prominently a decrease in the length of the nucleation phase, the alteration in assembly kinetics was accompanied by the formation of a covalently crosslinked tubulin dimer, mixing experiments which combined different proportions of control and treated tubulin showed that only a small amount of derivatized tubulin need be present to induce altered assembly properties, and as a result of the more rapid nucleation phase, a greater number of nucleating seeds produced more numerous and shorter assembled polymers. In vitro incubation with the 2,5-HD congener 3,4-dimethyl-2,5-hexanedione produced similar alterations in microtubule assembly. Thus, both the kinetics of tubulin polymerization and the morphology of the final assembly product were modified by in vitro gamma-diketone incubation.


Isolated cardiac metastasis in a patient with neuroendocrine carcinoma of pancreas discovered on ⁶⁸Ga-DOTANOC PET/CT.
We present an interesting image that demonstrates utility of (68)Ga-DOTANOC PET/CT for demonstrating rare metastatic sites of neuroendocrime tumor.


Cell signaling during development of Dictyostelium.
Continuous communication between cells is necessary for development of any multicellular organism and depends on the recognition of secreted signals. A wide range of molecules including proteins, peptides, amino acids, nucleic acids, steroids and polylketides are used as intercellular signals in plants and animals. They are also used for communication in the social ameba Dictyostelium discoideum when the solitary cells aggregate to form multicellular structures. Many of the signals are recognized by surface receptors that are seven-transmembrane proteins coupled to trimeric G proteins, which pass the signal on to components within the cytoplasm. Dictyostelium cells have to judge when sufficient cell density has been reached to warrant transition from growth to differentiation. They have to recognize when exogenous nutrients become limiting, and then synchronously initiate development. A few hours later they signal each other with pulses of cAMP that regulate gene expression as well as direct chemotactic aggregation. They then have to recognize kinship and only continue developing when they are surrounded by close kin. Thereafter, the cells diverge into two specialized cell types, prespore and prestalk cells, that continue to signal each other in complex ways to form well proportioned fruiting bodies. In this way they can proceed through the stages of a dependent sequence in an orderly manner without cells being left out or directed down the wrong path.


Comparison of hybrid endovascular and open surgical repair for proximal aortic arch diseases.
To compare the outcomes of hybrid endovascular and open surgical repair for proximal aortic arch diseases. A total of 55 consecutive patients with aortic arch aneurysm or aortic dissection involving any of zone 0 to 1 (39 male, age 63.4 ± 14.3 years) underwent a hybrid endovascular repair (n=35) or open surgical repair (n=20) from 2006 to 2014 were analyzed retrospectively. Perioperative and late outcomes were compared. Baseline characteristics were similar between the two groups, except age and EuroSCORE II, which were higher in the hybrid group. Perioperative mortality or stroke was not significantly different between the two groups, however, tended to be lower in the hybrid repair group than in the open repair group (11.4% vs. 30.0%, p=0.144). Incidences of other morbidities did not differ. During follow-up, over-all survival was similar between the hybrid and the open repair was similar (87.3% vs. 79.7% at 1 year and 83.8% vs. 72.4% at 3 years; p=0.319). However, reintervention-free survival was significantly lower for hybrid repair compared with open repair (83.8% vs. 100% at 1 year and 65.7% vs. 100% at 3 years; p=0.022). Hybrid repair of proximal aortic disease showed comparable perioperative and late outcomes compared with open surgical repair despite a higher reintervention rate during follow-up. Therefore, hybrid repair may be considered as an acceptable treatment alternative to surgery especially in patients at high surgical risk.


An educational intervention to enhance nurse leaders' perceptions of patient safety culture.
To design a training intervention and then test its effect on nurse leaders' perceptions of patient safety culture. Three hundred and fifty-six nurses in clinical leadership roles (nurse managers and educators/CNSs) in two Canadian multi-site teaching hospitals (study and control). A prospective evaluation of a patient safety training intervention using a quasi-experimental untreated control group design with pretest and posttest. Nurses in clinical leadership roles in the study group were invited to participate in two patient safety workshops over a 6-month period. Individuals in the study and control groups completed surveys measuring patient safety culture and leadership for improvement prior to training and 4 months following the second workshop. Individual nurse clinical leaders were the unit of analysis. Exploratory factor analysis of the safety culture items was conducted; repeated-measures analysis of variance and paired t-tests were used to evaluate the effect of the training intervention on perceived safety culture (three factors). Hierarchical regression analyses looked at the influence of demographics, leadership for improvement, and the training intervention on nurse leaders' perceptions of safety culture. A statistically significant improvement in one of three safety culture measures was shown for the study group (p<.001) and a significant decline was seen on one of the safety culture measures for the control group (p<.05). Leadership support for improvement was found to explain significant amounts of variance in all three patient safety culture measures; workshop attendance explained significant amounts of variance in one of the three safety culture measures. The total R(2) for the three full hierarchical regression models ranged from 0.338 and 0.554. Sensitively delivered training initiatives for nurse leaders can help to foster a safety culture. Organizational leadership support for improvement is, however, also critical for fostering a culture of safety. Together, training interventions and leadership support may have the most significant impact on patient safety culture.


Contrastive domain adaptation with consistency match for automated pneumonia diagnosis.
Pneumonia can be difficult to diagnose since its symptoms are too variable, and the radiographic signs are often very similar to those seen in other illnesses such as a cold or influenza. Deep neural networks have shown promising performance in automated pneumonia diagnosis using chest X-ray radiography, allowing mass screening and early intervention to reduce the severe cases and death toll. However, they usually require many well-labelled chest X-ray images for training to achieve high diagnostic accuracy. To reduce the need for training data and annotation resources, we propose a novel method called Contrastive Domain Adaptation with Consistency Match (CDACM). It transfers the knowledge from different but relevant datasets to the unlabelled small-size target dataset and improves the semantic quality of the learnt representations. Specifically, we design a conditional domain adversarial network to exploit discriminative information conveyed in the predictions to mitigate the domain gap between the source and target datasets. Furthermore, due to the small scale of the target dataset, we construct a feature cloud for each target sample and leverage contrastive learning to extract more discriminative features. Lastly, we propose adaptive feature cloud expansion to push the decision boundary to a low-density area. Unlike most existing transfer learning methods that aim only to mitigate the domain gap, our method instead simultaneously considers the domain gap and the data deficiency problem of the target dataset. The conditional domain adaptation and the feature cloud generation of our method are learning jointly to extract discriminative features in an end-to-end manner. Besides, the adaptive feature cloud expansion improves the model's generalisation ability in the target domain. Extensive experiments on pneumonia and COVID-19 diagnosis tasks demonstrate that our method outperforms several state-of-the-art unsupervised domain adaptation approaches, which verifies the effectiveness of CDACM for automated pneumonia diagnosis using chest X-ray imaging.


Human protein requirements: obligatory urinary and faecal nitrogen losses and the factorial estimation of protein needs of Nigerian male adults.
1. The present study was designed to use the factorial approach to estimate protein requirements of Nigerian male adults by measuring obligatory nitrogen losses via urine, faeces and sweat when N intake was very low and energy intake adequate. 2. Eight adult men from Osegere village near Ibadan and seven medical students from the University of Ibadan, who volunteered to participate as subjects in the study, were given a low-protein diet (based on staple foods habitually consumed by subjects) for 10 d. Mean daily total protein intake was 4.68 g while that of energy was 0.2 MJ/kg body-weight. After an initial 5 d adaptation period, 24 h urine and faces were collected in marked containers for five consecutive days for N determination. N losses from the skin were also determined in the village adults. 3. Mean daily urinary, faecal and sweat N losses (mg N/kg body-weight) were 45.88 (SD4.84), 21.79 (SD4.19), and 7.46 (SD1.71) from the village adults. The corresponding urinary and faecal N losses from the university students were 43.45 (SD2.28) and 18.32 (SD4.66) (sweat N loss not measured). Thus the total daily obligatory N losses (per kg body-weight) from the village adults and university students were 75.13 and 69.23 mg N respectively (assuming a sweat N loss of 7.46 mg for the university students). After adjusting for requirement and making a 30% allowance for individual variability, the safe level of protein intake was calculated to be 0.78 and 0.73 g protein/kg body-weight for the village men and university students respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


The association of cerebrospinal fluid pressure with optic nerve head and macular vessel density.
The present study aims to investigate the effect of temporary cerebrospinal fluid pressure (CSFP) reduction on optic nerve head (ONH) and macular vessel density (VD) using optical coherence tomography angiography. Forty-four eyes of 44 adults with diagnostic lumbar puncture and CSFP reduction were recruited. Thirty-two eyes of 32 healthy volunteers were controls. ONH and macular VD images were evaluated differences between baseline and after CSFP reduction. The results showed that the mean CSFP decreased from (11.6±2.1) mmHg to (8.2±3.4) mmHg (P<0.001). VD in the macular regions decreased significantly after CSFP reduction in the study group (all P<0.05). The control group showed no significant changes in macular VD (all P>0.05). In the study group, decreased VD in the macular parainferior region was associated with CSFP reduction (R2=0.192, P=0.003), the reduction of macular VD in parafoveal (R2=0.098, P=0.018), parainferior (R2=0.104, P=0.021), parasuperior (R2=0.059, P=0.058), paranasal (R2=0.057, P=0.042), paratemporal (R2=0.079, P=0.026) was associated with mean ocular perfusion pressure decrease following CSFP reduction. ONH vessel density did not differ after CSFP reduction (all P>0.05). In conclusion, macular vessel density decreased in association with CSFP reduction. Retinal vessel density in the macular region is more sensitive than that in peripapillary region after CSFP reduction.


Management of Childhood-onset Craniopharyngioma in Italy: A Multicenter, 7-Year Follow-up Study of 145 Patients.
Nationwide data on children diagnosed with craniopharyngioma (CP) are not available in Italy. This work aimed to identify patients' characteristics, type of surgical approach, complications and recurrences, number of pituitary deficits, and number of patients starting growth hormone (GH) treatment. A retrospective multicenter collection took place of 145 patients aged 0 to 18 years who underwent surgery for CP between 2000 and 2018, and followed up in 17 Italian centers of pediatric endocrinology. Age at diagnosis was 8.4 ± 4.1 years. Duration of symptoms was 10.8 ± 12.5 months and headache was most frequent (54%), followed by impaired growth (48%) and visual disturbances (44%). Most lesions were suprasellar (85%), and histology was adamantinomatous in all cases but two. Surgical approach was transcranial (TC) in 67.5% of cases and transsphenoidal (TS) in 31.%. The TC approach was prevalent in all age groups. Postsurgery complications occurred in 53% of cases, with water-electrolyte disturbances most frequent. Radiotherapy was used in 39% of cases. All patients but one presented with at least one hormone pituitary deficiency, with thyrotropin deficiency most frequent (98.3%), followed by adrenocorticotropin (96.8%), arginine vasopressin (91.1%), and GH (77.4%). Body mass index (BMI) significantly increased over time. A hypothalamic disturbance was present in 55% of cases. GH therapy was started during follow-up in 112 patients at a mean age of 10.6 years, and 54 developed a recurrence or regrowth of the residual lesion. CP is often diagnosed late in Italy, with TC more frequent than the TS surgical approach. Postsurgery complications were not rare, and hypopituitarism developed almost in all cases. BMI shows a tendency to increase overtime.


Food intake and temperature response to injections of catecholamines into the lateral ventricle of the turkey brain.
The effects of dopamine, norepinephrine, and epinephrine on food intake, water intake, and colonic body temperature (Tc) were investigated in adult Medium White turkey hens. Solutions containing dopamine, L-norepinephrine, or L-epinephrine were prepared in concentrations of 0, 33, and 67 micrograms/10 microliters in artificial cerebrospinal fluid and injected into the lateral cerebral ventricles. Dopamine, norepinephrine, and epinephrine significantly decreased Tc. Food intake was significantly decreased by norepinephrine and epinephrine whereas dopamine had no effect. These results suggest that brain catecholamines are involved in the neural control of food intake and body temperature of turkeys.


Inflammatory epidermolysis bullosa acquisita with coexistent IgA antibodies to plectin.
We present a case of inflammatory epidermolysis bullosa acquisita (EBA) with IgA antibodies to plectin. Analysis of lesional skin biopsies by electron microscopy revealed the split level to be in the sublamina densa zone, corresponding to the diagnosis of EBA. Direct immunofluorescence of perilesional skin demonstrated u-serrated depositions of IgG and IgA that under immunoelectron microscopy were shown to be located in the sublamina densa. In contrast, indirect immunofluorescence on salt-split skin revealed circulating IgA antibodies that stained the roof rather than the floor of the blister. Immunoblotting showed these serum antibodies to be directed to the cytoplasmic hemidesmosomal antigen plectin. The antiplectin specificity of these antibodies was confirmed by 'knockout' immunofluorescence analysis; the serum IgA did not bind to skin sections of a patient with plectin-deficient epidermolysis bullosa. To our knowledge, this case demonstrates for the first time the existence of IgA antibodies against plectin.


Glaucoma in siblings with Morquio syndrome.
Two cases of association between the Morquio Syndrome and glaucoma in one family are described. Possible role of Mucopolysaccharides acting in the anterior chamber angle is discussed.


Evaluation of diurnal and postural intracranial pressure employing telemetric monitoring in idiopathic intracranial hypertension.
Intracranial pressure (ICP) has been thought to vary diurnally. This study evaluates diurnal ICP measurements and quantifies changes in ICP occurring with changes in body posture in active idiopathic intracranial hypertension (IIH). This prospective observational study utilized telemetric ICP monitoring in people with active IIH. Participants had the Raumedic p-Tel ICP intraparenchymal device (Raumedic, Hembrechts, Germany) surgically inserted. Changes in ICP in the supine position were evaluated. Then, the ICP was measured in the standing, sitting, supine, left lateral decubitus positions and with coughing and bending. Ultimately, changes in ICP over the course of 24 h were recorded. ISRCTN registration number 12678718. 15 women were included, mean (standard deviation) age 29.5 (9.5) years, body mass index 38.1 (6.2) kg/m2, and baseline mean ICP of 21.2 (4.8) mmHg (equivalent to 28.8 (6.5) cmCSF). Mean ICP rose with the duration in the supine position 1.2 (3.3) mmHg over 5-minutes (p = 0.175), 3.5 (2.8) mmHg over 30-minutes (p = 0.0002) and by a further 2.1 (2.2) mmHg over 3 h (p = 0.042). Mean ICP decreased by 51% when moving from the supine position to standing (21.2 (4.8) mmHg to 10.3 (3.7) mmHg respectively, p = 0.0001). Mean ICP increased by 13% moving from supine to the left lateral decubitus position (21.2 (4.8) mmHg to 24.0 (3.8) mmHg, p = 0.028). There was no significant difference in ICP measurements at any point during the daytime, or between 5-minute standing or supine recordings and prolonged ambulatory daytime and end of night supine recordings respectively. ICP, following an initial drop, increased progressively in conjunction with lying supine position from 23:00 h to 07:00 h by 34% (5.2 (1.9) mmHg, p = 0.026). This analysis demonstrated that ICP does not appear to have a diurnal variation in IIH, but varies by position and duration in the supine position. ICP rose at night whilst the patient was continuously supine. Furthermore, brief standing and supine ICP measures in the day predicted daytime prolonged ambulatory measures and end of night peak ICP respectively. This knowledge gives reassurance that ICP can be accurately measured and compared at any time of day in an ambulant IIH patient. These are useful findings to inform clinical measurements and in the interpretation of ICP analyses in IIH. ISTCRN (12678718).


APE1 promotes radiation resistance against radiation-induced pyroptosis by inhibiting the STING pathway in lung adenocarcinoma.
Mammalian apurinic/apyrimidinic endonuclease 1 (APE1, APEX1) is a multifunctional enzyme that maintains cellular homeostasis. It is involved in the base excision repair (BER) pathway and plays a key role in radiation-induced DNA damage response. However, the relationship between APE1-driven radiation resistance and pyroptosis in lung adenocarcinoma (LUAD) cells and the underlying molecular mechanisms remain unclear. We found that APE1 was significantly upregulated in LUAD tissues compared to para-carcinoma tissues and promoted the proliferation and invasion of LUAD cells in vitro and in vivo. Mechanistically, APE1 inhibited pyroptosis by inactivating the interferon gene stimulator (STING) pathway via direct interaction with AIM2 and DDX41, as detected by RNA-seq and co-immunoprecipitation. APE1 protects LUAD cells against radiation-induced damage and induces radio-resistance by targeting the STING pathway. It can induce pyroptosis and is negatively regulated by interactions with AIM2 and DDX41. Therefore, APE1 inhibitors should be considered to enhance the radiosensitivity of LUAD cells and improve patient prognosis and therapeutic outcomes. Thus, APE1 play a role in the tumor immune microenvironment and in tumor immunotherapy.


Molecular cloning of alpha-amylase gene from Bacillus amyloliquefaciens and its expression in B. subtilis.
The gene coding for alpha-amylase from Bacillus amyloliquefaciens was isolated by direct shotgun cloning using B. subtilis as a host. The genome of B. amyloliquefaciens was partially digested with the restriction endonuclease MboI and 2- to 5-kb fragments were isolated and joined to plasmid pUB110. Competent B. subtilis amylase-negative cells were transformed with the hybrid plasmids and kanamycin-resistant transformants were screened for the production of alpha-amylase. One of the transformants producing high amounts of alpha-amylase was characterized further. The alpha-amylase gene was shown to be present in a 2.3-kb insert. The alpha-amylase production of the transformed B. subtilis could be prevented by inserting lambda DNA fragments into unique sites of EcoRI, HindIII and KpnI in the insert. Foreign DNA inserted into a unique ClaI site failed to affect the alpha-amylase production. The amount of alpha-amylase activity produced by this transformed B. subtilis was about 2500-fold higher than that for the wild-type B. subtilis Marburg strain, and about 5 times higher than the activity produced by the donor B. amyloliquefaciens strain. Virtually all of the alpha-amylase was secreted into the culture medium. The secreted alpha-amylase was shown to be indistinguishable from that of B. amyloliquefaciens as based on immunological and biochemical criteria.


5-HT(1B) receptor knockout mice show no adaptive changes in 5-HT(1A) receptor function as measured telemetrically on body temperature and heart rate responses.
Two presynaptic receptors play an important role in the regulation of serotonergic neurotransmission, i.e., the 5-HT(1A) and 5-HT(1B) receptor. The present study focuses on putative adaptive changes in the 5-HT(1A) receptor system in mice that lack 5-HT(1B) receptors (5-HT(1B) KO). 5-HT(1A) receptor sensitivity was assessed in vivo in two models of presynaptic 5-HT(1A) receptor activity: agonist-induced hypothermia and prevention of stress-induced hyperthermia. The effects of 5-HT(1A) receptor activation by flesinoxan (0.1-3.0 mg/kg s.c.) were determined telemetrically on body temperature and heart rate in 5-HT(1B) KO and wild-type (WT) mice. Flesinoxan induced hypothermia dose-dependently without affecting heart rate and prevented stress-induced hyperthermia and tachycardia equipotently in both genotypes. Specificity of these responses was confirmed by blockade with the selective 5-HT(1A) receptor antagonist WAY100635 (1.0 mg/kg s.c.). The importance of continuous sampling in freely moving subjects to improve appropriate characterization of mutants is discussed. 5-HT(1B) KO mice showed no shift in 5-HT(1A) receptor sensitivity compared to WT mice. This study found no indications for adaptive changes in presynaptic 5-HT(1A) receptor function in 5-HT(1B) KO mice as measured telemetrically on body temperature and heart rate responses.


Evaluating suspected fetal anemia with Doppler ultrasound.
To evaluate Doppler studies of the fetal middle cerebral artery to predict fetal or neonatal anemia. The perinatal database at one institution was searched for all patients evaluated for suspected fetal anemia. Middle cerebral artery peak velocity measurements just prior to cordocentesis or the last measurement prior to delivery was used for analysis. The primary outcome data analyzed were fetal or neonatal hematocrit at the time of the cordocentesis or delivery. During the study period there were 36 patients who met the inclusion criterion. There was a significant correlation between middle cerebral artery peak velocity and fetal or neonatal hematocrit. Peak flow velocity in the middle cerebral artery is an accurate, noninvasive clinically useful method of evaluating suspected fetal anemia.


Optimization of antimicrobial peptides for the application against biocorrosive bacteria.
Microbiologically influenced corrosion is a common problem in the industrial field due to the deterioration of metals in the presence of various microorganisms, in particular sulfate-reducing bacteria (SRB) and sulfur-oxidizing bacteria (SOB). A common method to reduce microbiologically influenced corrosion is the application of biocides. The limited number of suitable biocides and the resulting development of resistance, high dosage, and high application rate hinder an effective application. An environmentally friendly alternative could be the application of antimicrobial peptides (AMP), which have already been established in the field of medical devices for a while. Here, the successful treatment of different AMPs against 3 SRB and 1 SOB was demonstrated. The peptide L5K5W was favored due to its broad activity, high stability, and simple structure resulting in low synthesis costs. An alanine scan showed that substitution of leucine with tryptophan increased the activity of this peptide twofold compared to the original peptide against D. vulgaris, the main representative of SRB. Additional optimization of this modified peptide through changes in amino acid composition and lipidations significantly increased the effectiveness, finally resulting in a minimum inhibitory concentration (MIC) of 15.63 μg/mL against Desulfovibrio vulgaris. Even against the marine SRB Desulfovibrio indonesiensis with a required salt concentration of min. 2%, an activity of the peptides can be observed (MIC: 31.25 μg/mL). The peptides also remained stable and active for 7 days in the supernatant of the bacterial culture. KEY POINTS: • Antimicrobial peptides provide an alternative to combat biocorrosive bacteria. • Optimization of the peptide sequence leads to a significant increase in activity. • The investigated peptides exhibit high stability, both in the medium and in the bacterial supernatant.


Single-cell RNA sequencing analysis revealed malignant ductal cell heterogeneity and prognosis signatures in pancreatic cancer.
Pancreatic cancer (PAC) remains one of the most lethal malignant neoplasms, which is diagnosed at an advanced stage and thus lose the chance for curative resection. Here, we further probed PAC with a comprehensive multi-omics approach. Using single-cell RNA sequencing, we provided an integrated analysis of ductal cell subpopulations over the Leiden algorithm to identify two mian subcluster: S100A6 + cells and FXYD2 + cells. The gene set enrichment analysis results show that the two subtypes focused on different pathways related to tumor development. Furthermore, we integrated bulk and single-cell RNA sequencing datasets to generate and validate the prognostic signatures of the overall survival (OS) in PAC patients and S100A6 + cells were significantly enriched in high-risk groups which had a poor prognosis. Collectively, this research expands our understanding of ductal cell and provides a new reliable prognosis signature in PAC.


Pathological findings in retina and visual pathways associated to natural Scrapie in sheep.
This work represents a comprehensive pathological description of the retina and visual pathways in naturally affected Scrapie sheep. Twenty naturally affected Scrapie sheep and 6 matched controls were used. Eyes, optic nerves and brain from each animal were fixed and histologically processed using hematoxylin-eosin, followed by immunohistochemical staining for prion protein (PrPsc) and glial fibrillar acidic protein (GFAP). Retinal histopathological changes were observed in only 7 clinically affected animals and mainly consisted of loss of outer limitant layer definition, outer plexiform layer atrophy, disorganization and loss of nuclei in both nuclear layers, and Müller glia hypertrophy. PrPsc was detected in the retina of 19 of the 20 sheep and characterized by a disseminated granular deposit across layers and intraneuronally in ganglion cells. The inner plexiform and the ganglion cell layers were the structures most severely affected by PrPsc deposits. PrPsc exhibited a tendency to spread from these two layers to the others. A marked increase in the number and intensity of GFAP-expressing Müller cells was observed in the clinical stage, especially at the terminal stage of the disease. Spongiosis and PrPsc were detected within the visual pathways at the preclinical stage, their values increasing during the course of the disease but varying between the areas examined. PrPsc was detected in only 3 optic nerves. The results suggest that the presence of PrPsc in the retina correlates with disease progression during the preclinical and clinical stages, perhaps using the inner plexiform layer as a first entry site and diffusing from the brain using a centrifugal model.


Broflanilide: A meta-diamide insecticide with a novel mode of action.
Broflanilide is a meta-diamide [3-benzamido-N-(4-(perfluoropropan-2-yl)phenyl)benzamide] that exhibits high larvicidal activity against Spodoptera litura. It has been suggested that broflanilide is metabolized to desmethyl-broflanilide and that it acts as a noncompetitive resistant-to-dieldrin (RDL) γ-aminobutyric acid (GABA) receptor antagonist. The binding site of desmethyl-broflanilide was demonstrated to be distinct from that of conventional noncompetitive antagonists such as fipronil. It has been proposed that the site of action for desmethyl-broflanilide is close to G336 in the M3 region of the Drosophila RDL GABA receptor. However, although the site of action for desmethyl-broflanilide appears to overlap with that of macrocyclic lactones, different modes of actions have been demonstrated for desmethyl-broflanilide and the macrocyclic lactones. The mechanisms underlying the high selectivity of meta-diamides are also discussed in this review. Broflanilide is expected to become a prominent insecticide because it is effective against pests with resistance to cyclodienes and fipronil.


Comparison of lead complications with polyurethane tined, silicone rubber tined, and wedge tip leads: clinical experience with 822 ventricular endocardial lads.
Lead-related complications have been prospectively studied for 602 unipolar tined endocardial ventricular pacemaker leads implanted over a five-year period. No differences were noted in overall complication rates between 238 polyurethane insulated leads (4.2%) and 364 silicone rubber insulated leads (3.6%). Comparing the total series of 602 tined leads to a retrospective survey of 220 wedge tip leads, a marked reduction in dislodgements (0.3% vs. 7.7%, P less than 0.001) and reoperations (2.0% vs 15.0%, P less than 0.001) was found using tined leads. We conclude that tined ventricular leads are far superior to wedge tip leads with respect to lead complications.


"Mobile Health" for the Management of Spondyloarthritis and Its Application in China.
Spondyloarthritis (SpA) is a group of inflammatory diseases characterized by inflammation in the spine, peripheral joints, and entheses that usually start at the prime of one's life and lead to impaired physical function and reduced quality of life. Ankylosing spondylitis (AS) is prototype of SpA. This article reviews the opportunities and challenges of using mobile health (mHealth) in managing SpA, and report some of our experiences using a mHealth solution for management of SpA patients and performing related research in China. The recent rapid development of mobile communications and the common use of intelligent electronic devices have led to the increasing application of mHealth for chronic disease management by healthcare providers and patients alike. This is a promising new technology that can help mitigate limitations in time and space for patient management, promote easier communication between patients and their healthcare providers, reduce medical expenses, and optimize medical services. We have developed a smartphone-based mHealth SpA management system (SpAMS) that also helps the patients to monitor, manage, and share information on their disease with their physician at regular intervals. There is a shift from a paternalistic model of healthcare to more personalized healthcare in which disease management is conducted by the patient together with their healthcare providers. The increasing utility of mHealth is expected to benefit disease management, promote patient-doctor communication, reduce medical expenses, and optimize medical services.


Conformational Kinetics in Chiral Poly(diphenylacetylene)s: A Dynamic P/M Memory Effect.
Dynamic P/M (plus/minus) helical memory in chiral dissymmetric poly(diphenylacetylene)s (PDPA) is shown using a PDPA that bears the benzamide of (L)-alanine methyl ester as pendant. For a single chiral polymer, it is possible to obtain either P or M helical structures in a specific solvent without the presence of any chiral external stimuli. To do that, it is necessary to combine the conformational control at the pendant group with a high steric hindrance at the backbone. In this case, by thermal annealing in low-polar solvents, an anti-conformer is stabilized at the pendant which commands a P helix in the PDPA. Next, solvent removal followed by addition of a polar solvent such as dimethyl sulfoxide (DMSO), results in the kinetic conformationally trapped P helix. However, in this medium, the preferred handedness and the thermodynamic macromolecular helix for poly-(L)-1 is M. This process also occurs in the opposite way. Electronic circular dichroism (ECD) and circularly polarized luminescence (CPL) studies show that the dynamic memory effect is present both in ground and excited states.


[An analysis of the development and the choice of the future direction of cryogenic medical apparatus].
The paper analyses the available medical cryoequipment and provides strong evidence for using the microchoke circuits for the equipment. Moreover, it recommends to employ thermoelectric cooling for promising developments of medical cryoequipment constructions.


Toxicological risks on the human health of populations living around the Mediterranean Sea linked to the invasion of non-indigenous marine species from the Red Sea: A review.
The Mediterranean region is, by far, a prime travel destination, having hosted more than 330 million tourists in 2016, mostly for seaside holidays. A greatly increased influx of thermophilic Red Sea species, introduced through the Suez Canal in a process referred to as Lessepsian invasion (in honor of Ferdinand de Lesseps who instigated the building of the Suez Canal), have raised awareness among scientists, medical personnel, and the public, of health risks caused by some venomous and poisonous marine species. The main species of concern are the poisonous Lagocephalus sceleratus, and the venomous Plotosus lineatus, Siganus luridus, Siganus rivulatus, Pterois miles, Synancea verrucosa, Rhopilema nomadica, Macrorhynchia philippina and Diadema setosum. Recognizing that the main factors that drive the introduction and dispersal of Red Sea biota in the Mediterranean, i.e., Suez Canal enlargements and warming seawater, are set to increase, and international tourist arrivals are forecasted to increase as well, to 500 million in 2030, an increase in intoxications and envenomations by alien marine species is to be expected and prepared for.


Towards More Personalized Surgical Indications for Thoracic Aortic Dilatation: Are We There Yet?
Thoracic aortic aneurysms remain an important cause of death in the general population. The key to improving patient prognosis with thoracic aortic dilatation lies in early identification and tailored management strategies. Advances in the understanding of the molecular mechanisms of aneurysm formation, the natural history of disease, and clinical risk factors have led to significant improvements in patient management and overall outcomes. In the past decade, identification of the genetic basis of disease, together with wider availability of molecular testing, ushered in a new era for a tailored approach to the management of patients with thoracic aortic aneurysms. In this viewpoint, we explore these various iterative steps and future challenges.


Factors affecting relapse of type 2 diabetes after bariatric surgery in Sweden 2007-2015: a registry-based cohort study.
Although a large proportion of patients with type 2 diabetes (T2DM) who have undergone metabolic surgery experience initial remission some patients later suffer from relapse. While several factors associated with T2D remission are known, less is known about factors that may influence relapse. To identify possible risk factors for T2D relapse in patients who initially experienced remission. Nationwide, registry-based study. We conducted a nationwide registry-based retrospective cohort study including all adult patients with T2D and body mass index ≥35 kg/m2 who received primary metabolic surgery with Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) in Sweden between 2007 and 2015. Patients who achieved complete diabetes remission 2 years after surgery was identified and analyzed. Main outcome measure was postoperative relapse of T2D, defined as reintroduction of diabetes medication. In total, 2090 patients in complete remission at 2 years after surgery were followed for a median of 5.9 years (interquartile range [IQR] 4.3-7.2 years) after surgery. The cumulative T2D relapse rate was 20.1%. Duration of diabetes (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.05-1.14; P < .001), preoperative glycosylated hemoglobin A1C (HbA1C) level (HR, 1.01; 95% CI, 1.00-1.02; P = .013), and preoperative insulin treatment (HR, 2.67; 95% CI, 1.84-3.90; P < .001) were associated with higher rates for relapse, while postoperative weight loss (HR, .93; 95% CI, .91-.96; P < .001), and male sex (HR, .65; 95% CI, .46-.91; P = .012) were associated with lower rates. Longer duration of T2D, higher preoperative HbA1C level, less postoperative weight loss, female sex, and insulin treatment prior to surgery are risk factors for T2D relapse after initial remission.


The application of resilience assessment grid in healthcare: A scoping review.
The Resilience Assessment Grid (RAG) has attracted increasing interest in recent healthcare discourse as an instrument to understand and measure the resilience performance of socio-technical systems. Despite its growing popularity in healthcare, its applicability and utility remain unclear. This scoping review aims to understand the practical application of RAG method and its outcomes in healthcare. We followed the Arksey and O'Malley, and the Levac and colleagues' framework for scoping reviews and the PRISMA-ScR Checklist. We conducted searches of three electronic databases [Medline, Embase and Web of Science] in May 2021. Supplementary searches included Google Scholar, web and citation searches, and hand searches of the nine seminal edited books on Resilience Engineering and Resilient Health Care. All English language, empirical studies of RAG application in the healthcare setting were included. Open Science Framework [Registration-DOI. 10.17605/OSF.IO/GTCZ3]. Twelve studies met the inclusion criteria. Diversities were found across study designs and methodologies. Qualitative designs and literature reviews were most frequently used to develop the RAG and applied it in practice. Eight of the studies had qualitative designs, three studies had mixed-methods designs and one study had a quantitative design. All studies reported that the RAG was very helpful for understanding how frontline healthcare professionals manage the complexity of everyday work. While the studies gained insights from applying the RAG to analyze organizational resilience and identify areas for improvement, it was unclear how suggestions were implemented and how they contributed to quality improvement. The RAG is a promising tool to manage some of the current and future challenges of the healthcare system. To realise the potential benefits of the RAG, it is important that we move beyond the development phase of the RAG tool and use it to guide implementation and management of quality initiatives.


Pulmonary infection by Mycobacterium gordonae in an immunocompromised patient.
Mycobacterium gordonae, a scotochromogenic organism, is considered a saprophyte and isolation of this organism in sputum cultures is not generally considered clinically significant. We report the case of 70-yr-old man with Hodgkin's disease and pulmonary infection caused by Mycobacterium gordonae. The clinical and radiographic findings in this case and the course are outlined. Mycobacterium gordonae isolated from patients with debilitating diseases should not automatically be rejected as a contaminant.


Detection and chemical profiling of medicine counterfeits by Raman spectroscopy and chemometrics.
Raman spectroscopy combined with chemometrics has recently become a widespread technique for the analysis of pharmaceutical solid forms. The application presented in this paper is the investigation of counterfeit medicines. This increasingly serious issue involves networks that are an integral part of industrialized organized crime. Efficient analytical tools are consequently required to fight against it. Quick and reliable authentication means are needed to allow the deployment of measures from the company and the authorities. For this purpose a method in two steps has been implemented here. The first step enables the identification of pharmaceutical tablets and capsules and the detection of their counterfeits. A nonlinear classification method, the Support Vector Machines (SVM), is computed together with a correlation with the database and the detection of Active Pharmaceutical Ingredient (API) peaks in the suspect product. If a counterfeit is detected, the second step allows its chemical profiling among former counterfeits in a forensic intelligence perspective. For this second step a classification based on Principal Component Analysis (PCA) and correlation distance measurements is applied to the Raman spectra of the counterfeits.


Milk feeding and xylazine treatment induce increased antroduodenal motility in young cattle with opposite effects on duodenal digesta flow rate.
Antroduodenal myoelectrical activity and duodenal digesta flow rate in young cattle were assessed by implanted nichrome wire electrodes and reentrant duodenal cannulation with interposed flow-meter. In addition, a small glass electrode was inserted through a duodenal cannula to continuously measure the pH of duodenal contents. When eating only hay ad libitum, the duodenal myoelectrical activity showed the usual migrating myoelectrical complex (MMC) pattern. Duodenal contents pH rose sharply at the end of a period of repetitive spike activity (RSA), or phase III, from pH less than 2 to greater than 5 and remained high through most of the subsequent period of no spike activity (NSA), or phase I, during which there was no antral spiking and no flow of duodenal contents. Feeding milk (pH 6.5) caused a marked increase in antroduodenal spike activity and intraduodenal flow rate, with a concomitant rapid rise in duodenal contents pH from 1.8 +/- 0.3 (SEM) to 5.0 +/- 0.2 which then slowly declined over the next few hours. Within 5 min after the administration of the alpha 2-adrenergic agonist xylazine (25 and 50 micrograms/kg intramuscular), there was a significant increase (P less than 0.05) in antroduodenal spike frequency and a concomitant marked drop in intraduodenal flow rate with a sustained low pH of intraduodenal contents. The results suggest that: (1) continuous measurement of proximal duodenal pH adds a useful dimension to documenting relationships between antroduodenal myoelectrical activity and duodenal digesta flow rate; and (2) increased spike activity in the antroduodenal region does not necessarily indicate an increased duodenal flow rate is occurring.


Serum lipoprotein(a) levels and diabetic nephropathy among Japanese patients with type 2 diabetes mellitus.
We aimed to evaluate the association between serum lipoprotein(a) [Lp(a)] levels and diabetic nephropathy among Japanese patients with type 2 diabetes mellitus. This study included 581 patients with type 2 diabetes mellitus. Serum Lp(a) levels were divided into four groups; the cut-off points were at the 30th, 60th, and 90th percentile values on the basis of the distribution for all subjects. Diabetic nephropathy was defined as present when the urinary albumin-creatinine ratio was ≥33.9mg/mmol creatinine and/or the estimated glomerular filtration rate was <30ml/min/1.72m(2). Adjustment was made for age, sex, body mass index, hemoglobin A1c, duration of diabetes mellitus, current drinking, current smoking, hypertension, dyslipidemia, coronary heart disease, and stroke. Higher serum Lp(a) levels were significantly associated with a higher prevalence of diabetic nephropathy: the adjusted odds ratios (95% confidence intervals) for diabetic nephropathy in relation to serum Lp(a) levels of ≤6, 7-15, 16-38, and ≥39mg/dl were 1.00 (reference), 2.74 (1.08-7.00), 3.31 (1.28-8.54), and 4.80 (1.57-14.60), respectively (P for trend=0.004). The results suggest that serum Lp(a) levels may be positively associated with diabetic nephropathy among Japanese patients with type 2 diabetes mellitus.


Metal ion binding to calmodulin: NMR and fluorescence studies.
Calmodulin is an important second messenger protein which is involved in a large variety of cellular pathways. Calmodulin is sensitive to fluctuations in the intracellular Ca2+ levels and is activated by the binding of four Ca2+ ions. In spite of the important role it plays in signal transduction pathways, it shows a surprisingly broad specificity for binding metal ions. Using 15N-Gly biosynthetically-labelled calmodulin, we have studied the binding of different metal ions to calmodulin, including K+, Na+, Ca2+, Mg2+, Zn2+, Cd2+, Pb2+, Hg2+, Sr2+, La3+ and Lu3+, by 1H,15N HMQC NMR experiments. The effects of these ions on the substrate-binding ability of calmodulin have also been studied by fluorescence spectroscopy of the single tryptophan residue in a 22-residue synthetic peptide encompassing the skeletal muscle myosin light chain kinase calmodulin-binding domain. Most of these metal ions can activate a calmodulin target enzyme to some extent, though they bind to calmodulin in a different manner. Mg2+, which is of direct physiological interest, has a distinct site-preference for calmodulin, as it shows the highest affinity for site I in the N-terminal domain, while the C-terminal sites III and IV are the high affinity binding sites for Ca2+ (as well as for Cd2+). At a high concentration of Mg2+ and a low concentration of Ca2+, calmodulin can bind Mg2+ in its N-terminal lobe while the C-terminal domain is occupied by Ca2+; this species could exist in resting cells in which the Mg2+ level significantly exceeds that of Ca2+. Moreover, our data suggest that the toxicity of Pb(2+)--which, like Sr2+, binds with an equal and high affinity to all four sites--may be related to its capacity to tightly bind and improperly activate calmodulin.


[Effect of pravastatin on hypercholesterolemia associated with proteinuria].
Hyperlipidemia associated to nephrotic syndrome has been involved in the deterioration of the renal function in these patients. The reduction in the synthesis of cholesterol with pravastatin, an hydrophilic inhibitor of such synthesis, may improve both the dyslipemia, the renal function and the proteinuria. We conducted a controlled open randomized study in 16 patients with proteinuria greater than 2 g/day, creatinine clearance greater than 0.5 ml/s (30 ml/min) and hypercholesterolemia with LDL cholesterol greater than 4.9 mmol/l (190 mg/dl) distributed in two groups. One of these groups received hypolipemiant dietetic treatment and 20-40 mg of pravastatin and the other group, only the dietetic treatment. The patients receiving pravastatin showed a 27% decrease in total plasmatic cholesterol, compared to a 6.7% in the control group (p < 0.01). This decrease was more evident in the LDL cholesterol fraction (44 vs 9%; p < 0.01). No significant modifications were observed in the HDL cholesterol fraction, triglycerides, renal function or proteinuria. Neither clinical nor enzymatiz adverse effects from hepatic or muscular origin were observed.


Meat and cancer: meat as a component of a healthy diet.
Based on epidemiological studies it is assumed that meat, especially red meat, enhances risk for cancer, particularly of the colon, breast and prostate. Meat and meat products are important sources of protein, some micronutrients and fat. High fat intake has been blamed for correlation with different diseases, including cancer. Meat protein is reported to contribute to cancer formation. However, meat, including liver, is not only composed of fat and protein, it contains essential nutrients which appear exclusively in meat (vitamin A, vitamin B12) and micronutrients for which meat is the major source because of either high concentrations or better bioavailability (folate, selenium, zinc). In particular, vitamin A, folate and selenium are reported to be cancer-preventive, with respect to colon, breast and prostate cancer. Taken together, meat consists of a few, not clearly defined cancer-promoting and a lot of cancer-protecting factors. The latter can be optimized by a diet containing fruit and vegetables, which contain hundreds of more or less proven bioactive constituents, many of them showing antioxidative and anticarcinogenic effects in vitro.


Efficacy of an imidacloprid/flumethrin collar against fleas and ticks on cats.
The objectives of the studies listed here were to ascertain the therapeutic and sustained efficacy of 10% imidacloprid (w/w) and 4.5% flumethrin (w/w) incorporated in a slow-release matrix collar, against laboratory-infestations of fleas and ticks on cats. Efficacy was evaluated against the flea Ctenocephalides felis felis, and the ticks Ixodes ricinus, Amblyomma americanum and Rhipicephalus turanicus. The number of studies was so large that only a general overview can be presented in this abstract. Preventive efficacy was evaluated by infesting groups of cats (n = 8-10) with C. felis felis and/or I. ricinus, A. americanum or R. turanicus at monthly intervals at least, for a period of up to 8 months. Efficacy against fleas was evaluated 24 to 48 h after treatment and 24 h after infestation, and against ticks at 6 h (repellent) or 48 h (acaricidal) after infestation. Efficacy against flea larvae was evaluated over a period of 8 months by incubating viable flea eggs on blanket samples after cat contact. In all cases efficacy was calculated by comparison with untreated negative control groups. Efficacy against fleas (24 h) generally exceeded 95% until study termination. In vitro efficacy against flea larvae exceeded 92% until Day 90 and then declined to 67% at the conclusion of the study on Day 230.Sustained acaricidal (48 h) efficacy over a period of eight months was consistently 100% against I. ricinus from Day 2 after treatment, 100% against A. americanum, except for 98.5% and 97.7% at two time-points, and between 94% and 100% against R. turanicus.From Day 2 until 8 months after treatment the repellent (6 h), efficacy was consistently 100% against I. ricinus, and between 54.8% and 85.4% against R. turanicus. The rapid insecticidal and acaricidal properties of the medicated collars against newly- acquired infestations of fleas and ticks and their sustained high levels of preventive efficacy have been clearly demonstrated. Taking into account the seasonality of fleas and ticks, the collars have the potential to prevent the transmission of vector-borne diseases and other conditions directly associated with infestation throughout the season of parasite abundance.


Admission to acute care hospitals for adolescent substance abuse: a national descriptive analysis.
Use of alcohol and illicit drugs by adolescents remains a problem in the U.S. Case identification and early treatment can occur within a broad variety of healthcare and non-healthcare settings, including acute care hospitals. The objective of this study is to describe the extent and nature of adolescent admissions to the acute inpatient setting for substance abuse (SA). We use the Agency for Healthcare Research and Quality (AHRQ) 2000 Healthcare Cost and Utilization Project Kids Inpatient Database (HCUP-KID) which includes over 2.5 million admissions for youth age 20 and under to 2,784 hospitals in 27 states in the year 2000. Specifically, this analysis estimates national number of admissions, mean total charges, and mean lengths of stay for adolescents between the ages of 12 and 17 admitted to an acute care hospital for the following diagnostic categories from the AHRQ's Clinical Classifications Software categories: "alcohol-related mental disorders" and "substance-related mental disorders". Frequency and percentage of total admissions were calculated for demographic variables of age, gender and income and for hospital characteristic variables of urban/rural designation and children's hospital designation. SA admissions represented 1.25 percent of adolescent admissions to acute care hospitals. Nearly 90 percent of the admission occurred in non-Children's hospitals. Most were for drug dependence (38%) or non-dependent use of alcohol or drugs (35%). Costs were highest for drug dependence admissions. Nearly half of admissions had comorbid mental health diagnoses. Higher rates of admission were seen in boys, in older adolescents, and in "self-pay" patients. Alcohol and drug rehabilitation/detoxification, alone or in combination with psychological and psychiatric evaluation and therapy, was documented for 38 percent of admissions. Over 50 percent of cases had no documentation of treatment specific to substance use behavior. General acute care hospitals have a significant and important opportunity to recognize, treat, and refer adolescents with substance abuse problems. These results suggest that inpatient facilities should develop and implement policies and processes to ensure that adolescent substance abusers admitted to their institutions receive appropriate care during the admission and appropriate referral to community care resources.


Effect of esmolol on fluid therapy in normovolemia and hypovolemia.
beta-Adrenergic agonists can enhance vascular volume expansion after a fluid bolus. The present study addresses how the beta-adrenergic antagonist esmolol influences volume expansion and fluid balance during normovolemia (series 1) and hypovolemia (series 2). Sheep were instrumented, and the spleen was removed. For series 1, continuous infusion of 50 to 100 microg.kg(-1).min(-1) esmolol (n = 6) or control (no drug; n = 6) was begun 30 min before administration of a 24-mL kg(-1) 20-min bolus of 0.9% NaCl. For series 2, anesthetized sheep were infused with 50 to 100 microg.kg(-1).min(-1) esmolol (n = 6) or control (no drug; n = 6) 30 min before a-20 mL kg(-1) hemorrhage. Fluid resuscitation (0.9% NaCl) was begun 30 min after hemorrhage. The 24-mL kg(-1) 20-min bolus was followed by titrated fluid therapy. Hemoglobin, fluid in, and urinary output were used to calculate changes in plasma volume (DeltaPV), extravascular volume (DeltaEVV = fluid in - urinary output - DeltaPV), volume expansion efficiency (VEE = fluid in / DeltaPV), and fluid distribution ratio (DeltaPV/DeltaEVV). Hemodynamics for both series were similar with the exception of heart rate. In series 1, peak DeltaPV was 9.1 +/- 1.0 mL kg(-1) in control and 3.7 +/- 1.0 mL kg(-1) at study end. Esmolol resulted in a lower peak DeltaPV (6.4 +/- 2.0 mL kg(-1)) and a negative DeltaPV (-0.4 +/- 0.6 mL kg(-1)) at study's end. Urinary output was lower, and EVV was greater with esmolol. In series 2, esmolol increased fluid requirements (67 +/- 7 mL kg(-1)) compared with control (54 +/- 5 mL kg(-1)). Esmolol reduced DeltaPV/DeltaEVV. These data suggest that esmolol impairs the vascular retention of fluid and may increase the amount of volume support during fluid resuscitation.


Biologic tumor behavior in pilocytic astrocytomas.
The aim is to describe the behavior of pilocytic astrocytoma (PAs) and its effects on patient prognosis by using flow cytometric, immunohistochemical and cytogenetic methods. We also aim to find out whether there is any difference between differently localized tumors by the above mentioned analyses. We studied DNA index, expression of p53, p16, pRb, MMAC/PTEN1, VEGF, MIB-1 index and chromosomal anomalies which can be detected by array comparative genomic hybridization (CGH) technique. We analyzed the association of the results of these studies with clinical prognosis and tumor localization. We included 53 patients (18 cerebellar, 20 chiasmatic/hypothalamic and 15 hemispheric). Samples were studied from paraffin embedded tumors. We found that PAs are mostly diploid and ploidy pattern does not affect the prognosis. The expression of p53, p16, pRb, MMAC/PTEN1 and VEGF was not significantly different between different localizations and could not predict the prognosis. Frequently seen copy number aberrations (CNAs) are: amplification in 1p36.33, 2p11.2, 9p11.2, 9q12, 16p11.2, 19q13.12-q13.2, Xp22.2-p21.3, Xp11.3-p11.22, Xq11.1-q12, Xq13.1, Xq21.1-q21.31, Xq22.3, Xq26.3 and homozygous deletion in 2p11.2, 8p23.1, 16p12.3. Among them, 2p11.2 amp, 9p11.2 amp and 1p36.21 hom del were correlated with prognosis. Moreover, we found a significant correlation between 16p11.2 amp and tumor localization. Differently localized PAs have different properties which make them behave with different biological aggressiveness. PAs demonstrate a significant amount of CNAs that can be detected by a high-resolution study. However, tumor suppressor genes p53, p16, pRb, MMAC/PTEN1 and expression patterns do not play a significant role in PAs.


Protein kinases in brown adipose tissue of developing rats. I. GTP as nucleotide substrate for histone phosphorylation.
100 000 times g soluble extracts from interscapular brown adipose tissue catalyzed the transfer of the terminal phosphoryl group from GTP to histone. Maximal velocity was achieved only with both cyclic AMP and ATP present. The cyclic AMP dose-response curve was the same as for the ATP-utilizing enzyme, with maximum stimulation at 0.5 muM. ATP (1--100muM) increased the rate of histone phosphorylation with GTP as the radioactive substrate. Higher concentrations had a dilution effect similar to that of GTP on the ATP-utilizing enzyme. Similar effects were observed with ADP and AMP. The apparent Km values for histone were the same with both GTP and ATP as nucleotide substrates. The effects of pH, purified beef muscle kinase inhibitor and of NaCl were also the same. Maximum velocities of histone phosphorylation from ATP and those from GTP were almost the same in brown fat of all age groups testes, Separated on histone-Sepharose, the GTP-utilizing activity was absolutely dependent on the re-addition of the ATP-utilizing enzyme (a linear relationship with a slope of approx. 0.95). An extremely active nucleotide phosphotransferase activity was found in the same subcellular fraction. The rate of equilibration of the gamma-32-P between GTP and ATP could account for all the histone phosphorylation with [gamma-32-P] GTP. It is concluded that, in spite of the presence of nucleotide phosphotransferase and ATP-protein kinase activities, a direct transfer from GTP to a protein substrate cannot be excluded. Also, histone may not be the natural protein acceptor for GTP-linked phosphorylation.


Short communication: Prevalence and risk factors of subclinical mastitis as determined by the California Mastitis Test in water buffaloes (Bubalis bubalis) in Nueva Ecija, Philippines.
A retrospective analysis using records of lactating Bulgarian Murrah buffaloes subjected to the California Mastitis Test in a herd in Nueva Ecija, Philippines was done to determine the prevalence of subclinical mastitis (SCM) and to identify risk factors that may influence its occurrence and recurrence. Results showed that SCM prevalence was 42.76%, whereas its recurrence was 75.03%. Age and lactation length influenced the occurrence of SCM. In contrast to the conclusions for dairy cows, younger buffalo cows were more susceptible compared with those at least 6 yr old. Dams younger than 3 yr have a 76% probability, whereas those age 3 yr have an 82% probability of having SCM.


A comparative study on autologous bone grafting combined with or without posterior interosseous nerve neurectomy for scaphoid nonunion treatment.
Scaphoid nonunion (SN) is a challenging state after scaphoid fracture. The posterior interosseous nerve neurectomy (PINN) is often performed adjunctively with scaphoid reconstruction using autologous bone grafts. However, it remains unclear whether PINN has a prophylactic or therapeutic value, and thus it results superior to patients with SN without PINN. A retrospective study was performed to evaluate patients with SN who were treated with autologous bone grafts with (cohort 1) or without PINN (cohort 2) between 1996 and 2010. Clinical outcomes, Mayo-wrist score, quality of life by Short Form (SF)-36 questionnaire, and analysis of risk factors were included. A total of 151 patients with SN met the inclusion criteria, and 48 were lost in follow-up. The mean follow-up was 71.3 ± 39.0 months. Out of the remaining 103 patients, the union rate was without a statistical difference (P = 0.847) between cohorts 1 and 2. Functional results and the Mayo score were comparable in patients with bone union between both cohorts (P > 0.05). The results of wrist-pain measurements, including visual pain scales and wrist tenderness, were found to be similar (P > 0.05). Additionally, there was no significant difference in the quality of life. The comparative study on autologous bone grafts for scaphoid reconstruction revealed comparable results for both patients with and without PINN independent from the choice of bone graft. We anticipate a prophylactic value of PINN due to a potential injury or an irritation during dissection of the wrist capsule. Further research on PIN, its sensory characteristics, and its impact on wrist function is required.


Transcriptional responses in Japanese medaka (Oryzias latipes) exposed to binary mixtures of an estrogen and anti-estrogens.
Determining ecotoxicological risks of exposure to mixtures of endocrine disrupting chemicals (EDCs) remains a daunting challenge in environmental toxicology. Recently, some studies have illustrated that transcriptional profiling of genes offers the potential to identify the chemical causation of effects that are induced by exposure to complex mixtures. In the present study, the transcriptional responses of a set of genes involved in the hypothalamic-pituitary-gonadal (HPG, or HPG[L]-liver) axis of Japanese medaka (Oryzias latipes) were systematically examined after treatment with a combination of an estrogen (17α-ethinylestradiol [EE2], 20 ng/L) and two model anti-estrogens, the aromatase inhibitor (AI) letrozole (LET) and the selective estrogen-receptor modulator (SERM) tamoxifen (TAM), at three concentrations (30, 100 and 300 μg/L) for 72 h. The data presented demonstrate that although gene transcription analyses increase our mechanistic understanding of the modes of action (MOAs) of EDCs, the characteristic of most genes altered by a certain single chemical exposure may not be useful for diagnostic chemical causation in a mixture exposure situation. For example, the induction of one vitellogenin gene (VTG1) transcription caused by EE2 in male fish was effectively blocked after exposure to a combination of EE2 and LET but not EE2 and TAM. Moreover, the responses in gene transcription to coexposure were elicited partially in a nonmonotonic concentration-dependent manner. Therefore, the application of transcriptional profiling of genes for screening complex environmental samples should be further evaluated until biomarker gene responses are robust and sensitive enough to properly assess the complex interactions.


Microbial fixation of nitrogen in presence of sodium tungstate.
The effect of sodium tungstate in the culture media of three different species of Azotobacter, isolated from Allahabad soil, was studied. It was observed that the presence of tungstate in the culture media of bacterial sample A2 and A3 decreased the fixation of nitrogen, except in the bacterial sample A1.


Immortalized mouse articular cartilage cell lines retain chondrocyte phenotype and respond to both anabolic factor BMP-2 and pro-inflammatory factor IL-1.
Articular cartilage chondrocytes help in the maintenance of tissue homeostasis and function of the articular joint. Study of primary chondrocytes in culture provides information closely related to in vivo functions of these cells. Limitations in the primary culture of chondrocytes have lead to the development of cells lines that serve as good surrogate models for the study of chondrocyte biology. In this study, we report the establishment and characterization of chondrocyte cell lines, MM-Sv/HP and MM-Sv/HP-2 from mouse articular cartilage. Cells were isolated from mouse femoral head articular cartilage, immortalized and maintained in culture through numerous passages. The morphology of the cells was from fibroblastic to polygonal in nature. Gene expression studies using quantitative PCR (Q-PCR) were performed on cells in monolayer culture and cells embedded in a three-dimensional alginate matrix. Stimulation of cells in monolayer culture with anabolic factor, BMP-2, resulted in increased gene expression of the extracellular matrix molecules, aggrecan and type II collagen and their regulator transcription factor, Sox9. Treatment by pro-inflammatory IL-1 resulted in increased gene expression of catabolic effectors including Aggrecanases (ADAMTS4, ADAMTS5), MMP-13 and nitric oxide synthase (Nos2). Cells in alginate treated with BMP-2 resulted in increased synthesis of proteoglycan which was released into the conditioned media on IL-1 stimulation. Western analysis of conditioned media showed the presence of Aggrecanase-cleaved aggrecan fragments. In summary, MM-Sv/HP and MM-Sv/HP-2 show preservation of important characteristics of articular chondrocytes as examined under multiple culture conditions and would provide a useful reagent in the study of chondrocyte biology.


[Polysynaptic effects in neurons of the cervical portion of the cat spinal cord induced by activation of long propriospinal pathways].
Effects evoked in cervical moto- and interneurons by stimulation of lateral (LF) and ventral (VF) funicles at low thoracic level were studied in anaesthetized cats; degeneration of descending supraspinal fibres was provided by preliminary cord sections. LF and (or) VF stimulation evoked PSPs (usually mixed) in 57 of 90 studied motoneurons. Monosynaptic EPSPs were "primary" actions in 9 motoneurons while poly(di)-synaptic EPSPs or IPSPs--in the rest. Intensity of excitatory synaptic action on motoneurons of proximal muscles was substantially higher than on "distal" ones. LF and VF stimulation excited interneurons localized in the ventral quadrant and had no action on interneurons situated more dorsally. The effects studied are suggested to be mainly a result of activation of long proporiospinal fibres ascending via LF and VF to the cervical enlargement; certain part of reactions is supposed to be transmitted via collaterals of descending propriospinal fibres to the cervical neurons.


Glycolysis and oxidtion enzyme activity in rat brain during insulin-induced hypoglycemia against the background of alloxan-induced diabetes mellitus.
Insulin-induced hypoglycemic coma in animals with alloxan diabetes was observed at a higher basal glucose level in the blood compared to healthy animals. It was associated with inhibition of glycolysis and glycogenolysis and decreased activities of succinate dehydrogenase and glutamate dehydrogenase in the cerebral hemispheres and brainstem.


Seasonal patterns of CO2 and water vapor exchange of the tall and short height forms of Spartina alterniflora Loisel in a Georgia salt marsh.
Seasonal patterns of the responses of net photosynthesis, transpiration, leaf diffusive conductance, water-use efficiency and respiration to temperature, light and CO2 concentration were determined on intact plants of the short and tall height forms of Spartina alterniflora. The studies were conducted on in situ plants in an undisturbed marsh community on Sapelo Island, Ga. Net photosynthesis of the tall form at full sunlight was significantly higher than the short form except during the winter months. Tall S. alterniflora did not light saturate during any season, whereas the short form tended to saturate during all seasons except the summer. The temperature optima of photosynthesis of both forms were similar and showed acclimation to prevailing seasonal temperatures. Leaf conductances to water vapor decreased with increasing temperature and were significantly different between the height forms only at higher temperatures. Dark respiration was relatively low at seasonal temperatures, but increased with temperature. Dark respiration and the respiratory Q10 of the short form tended to be slightly higher than those of the tall form during all seasons. Transpiration rates and water-use efficiency of the tall form were generally higher than the short form.The seasonal response patterns showed intrinsic differences in the capacities of the height forms to metabolize CO2 and respond to prevailing environmental parameters. Analyses of the components of the CO2 diffusion pathway suggested that metabolic or internal components were more important than stomatal factors in determining the photosynthetic patterns of the short height form. It is suggested that the observed differences in the physiological responses of the height forms of the C4 species are due to micro-habitat differences between the low and high marsh. Higher salinity, lower nitrogen availability and other soil factors may limit the CO2 and water vapor exchange capacity of the short form compared to the tall.


Effects of gossypol acetate on pituitary-adrenal axis in male albino rats.
Histopathological effects of gossypol acetate (GA) on pituitary-adrenal axis in male Wistar rats were investigated. Sexually mature rats of proven fertility were administered orally with 10 and 25 mg/kg for 4 and 5 weeks, respectively. In both experimental groups, corticotrophs (ACTH cells) of anterior pituitary showed progressive regression. At the 10 mg low-dose treatment for 4 weeks, no significant changes were observed in all the zones of the adrenal gland, while at the same dose for 5 weeks of treatment, cells of zona glomerulosa showed hypertrophy and degranulation as compared to that of control. Cells of zona fasciculata and reticularis showed no significant changes. In the medulla, the thickly granulated cells were degranulated and reduced in number. At the 25 mg treatment, the cells of the zona fasciculata showed hypertrophy and degranulation. The possible mechanism of action of GA is discussed.


Combining exercise with cognitive training and vitamin D3 to improve functional brain connectivity (FBC) in older adults with mild cognitive impairment (MCI). Results from the SYNERGIC trial.
Changes in functional brain connectivity (FBC) may indicate how lifestyle modifications can prevent the progression to dementia; FBC identifies areas that are spatially separate but temporally synchronized in their activation and is altered in those with mild cognitive impairment (MCI), a prodromal state between healthy cognitive aging and dementia. Participants with MCI were randomly assigned to one of five study arms. Three times per week for 20-weeks, participants performed 30-min of (control) cognitive training, followed by 60-min of (control) physical exercise. Additionally, a vitamin D3 (10,000 IU/pill) or a placebo capsule was ingested three times per week for 20-weeks. Using the CONN toolbox, we measured FBC change (Post-Pre) across four statistical models that collapsed for and/or included some or all study arms. We conducted Pearson correlations between FBC change and changes in physical and cognitive functioning. Our sample included 120 participants (mean age: 73.89 ± 6.50). Compared to the pure control, physical exercise (model one; p-False Discovery Rate (FDR) < 0.01 & < 0.05) with cognitive training (model two; p-FDR = < 0.001), and all three interventions combined (model four; p-FDR = < 0.01) demonstrated an increase in FBC between regions of the Default-Mode Network (i.e., hippocampus and angular gyrus). After controlling for false discovery rate, there were no significant correlations between change in connectivity and change in cognitive or physical function. Physical exercise alone appears to be as efficacious as combined interventional strategies in altering FBC, but implications for behavioral outcomes remain unclear.


Breaking the waves: improved detection of copy number variation from microarray-based comparative genomic hybridization.
Large-scale high throughput studies using microarray technology have established that copy number variation (CNV) throughout the genome is more frequent than previously thought. Such variation is known to play an important role in the presence and development of phenotypes such as HIV-1 infection and Alzheimer's disease. However, methods for analyzing the complex data produced and identifying regions of CNV are still being refined. We describe the presence of a genome-wide technical artifact, spatial autocorrelation or 'wave', which occurs in a large dataset used to determine the location of CNV across the genome. By removing this artifact we are able to obtain both a more biologically meaningful clustering of the data and an increase in the number of CNVs identified by current calling methods without a major increase in the number of false positives detected. Moreover, removing this artifact is critical for the development of a novel model-based CNV calling algorithm - CNVmix - that uses cross-sample information to identify regions of the genome where CNVs occur. For regions of CNV that are identified by both CNVmix and current methods, we demonstrate that CNVmix is better able to categorize samples into groups that represent copy number gains or losses. Removing artifactual 'waves' (which appear to be a general feature of array comparative genomic hybridization (aCGH) datasets) and using cross-sample information when identifying CNVs enables more biological information to be extracted from aCGH experiments designed to investigate copy number variation in normal individuals.


[A telephone hotline as an easily accessible service for questions on schizophrenia].
Public relations activities of the German Research Network on Schizophrenia (GRNS) have shown that there is a demand for more information about schizophrenia disorder. This confirms international research findings that relatives of schizophrenia patients are particularly in need of information and support. In response, the GRNS has maintained a telephone hotline since 2001. The hotline is manned by clinical experts, psychiatrists, or psychologists once a week. The telephone calls are documented in a systematic manner. From 2001 to 2003, 3,909 calls were registered. This volume exceeds the limit of the hotline's resources. The telephone hotline is mainly used by relatives of psychotic patients. Most questions relate to the symptoms of schizophrenia and pharmaceutical treatment. The need for emotional support is also a high motivational factor for dialing the hotline number. The telephone hotline seems to be a worthwhile addition to the already existing crisis telephones and should be maintained even after public funding of the network expires.


New quantitative trait loci that regulate wound healing in an intercross progeny from DBA/1J and 129 x 1/SvJ inbred strains of mice.
Wound healing/regeneration mouse models are few, and studies performed have mainly utilized crosses between MRL/MPJ (a good healer) and SJL/J (a poor healer) or MRL/lpr (a good healer) and C57BL/6J (a poor healer). Wound healing is a complex trait with many genes involved in the expression of the phenotype. Based on data from previous studies that common and additional quantitative trait loci (QTL) were identified using different crosses of inbred strains of mice for various complex traits, we hypothesized that a new cross would identify common and additional QTL, unique modes of inheritance, and interacting loci, which are responsible for variation in susceptibility to fast wound healing. In this study, we crossed DBA/1J (DBA, a good healer) and 129/SvJ (129, a poor healer) and performed a genome-wide scan using 492 (DBA x 129) F2 mice and 98 markers to identify QTL that regulate wound healing/regeneration. Four QTL on chromosomes 1, 4, 12, and 18 were identified which contributed toward wound healing in F2 mice and accounted for 17.1% of the phenotypic variation in ear punch healing. Surprisingly, locus interactions contributed to 55.7% of the phenotype variation in ear punch healing. In conclusion, we have identified novel QTL and shown that minor interacting loci contribute significantly to wound healing in DBA x 129 mice cross.


Association of miR-146a polymorphism rs2910164 and type 2 diabetes risk: a meta-analysis.
Circulating miR-146a is aberrantly expressed in patients with type 2 diabetes (T2D), probably resulting from gene polymorphisms. However, the role of polymorphism rs2910164 in T2D pathogenesis remains controversial. Thus, we designed a meta-analysis to investigate the association between rs2910164 and T2D. PubMed and Embase were searched for eligible papers in English published through September 2, 2019. Random or fixed effect models were used to determine risk estimates according to heterogeneities. Four studies, involving 2,069 patients and 1,950 controls, were included. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size. The pooled ORs and 95% CIs were 1.501 (0.887-2.541), 1.102 (0.931-1.304), 1.276 (0.900-1.811), 1.204 (0.878-1.652), 1.238 (0.880-1.740), and 1.350 (0.904-2.016) under the homozygote, heterozygote (CG vs. GG and CC vs. CG), dominant, allele, and recessive models, respectively. Heterogeneity was detected in most genetic models, with subgroup analyses performed by ethnicity, genotyping method, and disease duration. The co-dominant model was determined to be the most appropriate genetic model. Our findings suggested that polymorphism rs2910164 is not correlated with T2D susceptibility. However, the results should be interpreted with caution because of confounding factors.


Competition for gradient-free tuning of large language models: approaches, results, current challenges and future directions.
This perspective presents a brief overview of the background of Gradient-free tuning for large language models competition, the championship scheme, as well as the challenges and future directions.


Isoelectric focusing in a multicompartment electrolyzer with zwitterionic membranes, exemplified by purification of glucoamylase.
A highly purified preparation of glucoamylase G1 from Aspergillus niger was found, by isoelectric focusing in immobilized pH gradients, to contain a major form with a pI of 3.50 and a number of minor, more acidic and more basic contaminants. The major isoform was purified to homogeneity by recycling isoelectric focusing in a multicompartment electrolyzer, by confining this form in between two zwitterionic membranes, with pI 3.49 at the anodic side and pI 3.52 at the cathodic side. Recoveries were high (90%) and, notwithstanding the rather low operational pH, the electrosmotic flow was minimal and no protein precipitation occurred up to concentrations of 2.5 mg/ml (at the isoelectric point). The forms resolved in an analytical focusing gel were subjected to two types of in situ enzyme detections, by the glucose oxidase peroxidase (GOP) test and by the starch-iodine test. By both criteria all resolved zones exhibited enzyme activity, the GOP assay, however, following more closely the Coomassie blue stained protein profile. By computer modelling, it is shown that it is impossible to obtain linear pH gradients at such low pH values (pH 2.5-4.5 intervals) when the mixture has a low buffering power (beta = 2.0 mequiv.l-1 pH-1). When the beta power was gradually raised (beta = 4, beta = 6, beta = 8) the pH gradient became progressively linear until, in a recipe with beta = 10 mequiv.l-1 pH-1 full linearity of the pH gradient could be obtained. This is shown to be due to the substantial buffering power of bulk water in the pH 2.5-3.5 region.


A novel videoendoscopy system by using autofluorescence and reflectance imaging for diagnosis of esophagogastric cancers.
Image quality of the prior autofluorescence (AF) imaging systems, including the fiber-optic endoscope, was not feasible for general clinical use. The use of AF image alone resulted in low specificity. The objective of the study was to evaluate the resolution and the sensitivity of the novel videoendoscopy system by using AF and reflectance imaging (AFI) in the diagnosis of early esophagogastric cancers. This was a case series study. The setting was a pretreatment examination at a cancer center. Five patients with superficial esophageal cancers (SEC) and 21 patients with 22 early gastric cancers (EGC) were included in the study. The extent of the tumors was diagnosed by white light (WL), AF and chromoendoscopic observations. The main outcome measurement was the diagnostic accuracy of each observation in relation to the histologic mapping as a criterion standard. Two of 5 SECs (40%) were correctly diagnosed in the WL image and all (100%) in the AF image as purple or magenta color in a green background. EGCs in atrophic mucosa were observed as purple or magenta areas in a green background, while diffuse-type EGCs in fundic mucosa were observed as green areas in a purple background. Of the 22 EGCs, diagnostic accuracy of WL, AF, and chromoendoscopic observations were 36%: 95% CI [16%, 56%], 68%: 95% CI [49%, 88%], and 91%: 95% CI [79%, 100%], respectively. AFI could reveal flat or isochromatic extensions that were not detected in the WL images. The limitations of the study were ulcerations or inflammation that caused overdiagnosis in the AF observation. The resolution of the AFI at present is limited, but the image quality was acceptable. The current system of AFI does not equal to chromoendoscopy in sensitivity but has an advantage over standard WL videoendoscopy.


[Chronic pancreatitis; surgical therapy (author's transl)].
41 patients suffering from chronic pancreatitis underwent surgery from 1965 to May 1978. Mortality rate was 4,8%. Drainage operations and resections are the methods of choice today.