Association between cerebral small vessel diseases and mild parkinsonian signs in the elderly with vascular risk factors.
The aim of this study was to examine the association between mild parkinsonian signs (MPS), cerebral small-vessel disease (SVD), and total SVD burden in patients with vascular risk factors. We performed a cross-sectional study among 268 patients with vascular risk factors but without parkinsonism or dementia (71.0 ± 7.8 years, 63% male). MPS was evaluated via Unified Parkinson's Disease Rating Scale Part III. Brain MRI was used to determine SVD (cerebral microbleeds [CMBs], lacunar infarctions [LIs], and white matter hyperintensities [WMH]). The presence of each SVD feature was indicated by the total SVD score. Logistic regression analyses were performed adjusting for age, sex, history of stroke, hypertension, diabetes mellitus, and dyslipidemia. In a multivariate analysis, we found that the presence of CMBs, deep CMBs, mixed (in the basal ganglia and thalamus) LIs, periventricular hyperintensities (PVH), and deep WMH (DWMH), and total SVD score were significantly associated with MPS, whereas strictly lobar CMBs and other LIs (in strictly basal ganglia or strictly thalamus) were not. We also found a significant association between mixed LIs, PVH, DWMH and total SVD score and gait/balance function, between PVH and rigidity, and between mixed LIs and bradykinesia. Among elderly participants (≥73years), the association of total SVD score, deep CMBs, mixed LIs, and PVH, with MPS remained significant. Our results provide additional evidence that SVD including CMBs, and especially total SVD burden, might be a surrogate marker for MPS and support the contribution of hypertensive microangiopathy as the underlying etiology.


Insulinoma: only in adults?-case reports and literature review.
Insulinomas first presenting as refractory seizure disorders are well documented in adulthood but rarely found in children. Only a few cases of childhood insulinoma have been reported so far. We report on two adolescents with hyperinsulinaemic hypoglycaemia, initially misdiagnosed as epilepsy and migraine accompagnée, and compare those to other cases published. Localization of insulinoma was challenging and, in one patient, angiography with selective arterial calcium stimulation and hepatic venous sampling in addition to CT and MRI was necessary. In these patients, long-term recovery was achieved by laparoscopic distal pancreatic resection in one and by conventional enucleation in the pancreatic head in the second patient. In contrast to adults, macrosomy and a decrease in school performance were the main symptoms and, during fasting, impaired cognitive function occurred after a relatively short period and at a higher glucose threshold or lower insulin/glucose ratio, respectively. Neuroglycopenic signs may be attributed to behaviour abnormalities or seizure disorders but in children and adolescents may already be caused by insulinoma. In these cases, timely diagnosis as well as tumour resection ensure long-term cure.


Locomotor Stimulant and Rewarding Effects of Inhaling Methamphetamine, MDPV, and Mephedrone via Electronic Cigarette-Type Technology.
Although inhaled exposure to drugs is a prevalent route of administration for human substance abusers, preclinical models that incorporate inhaled exposure to psychomotor stimulants are not commonly available. Using a novel method that incorporates electronic cigarette-type technology to facilitate inhalation, male Wistar rats were exposed to vaporized methamphetamine (MA), 3,4-methylenedioxypyrovalerone (MDPV), and mephedrone (4-methylmethcathinone) in propylene glycol vehicle using concentrations ranging from 12.5 to 200 mg/ml. Rats exhibited increases in spontaneous locomotor activity, measured by implanted radiotelemetry, following exposure to methamphetamine (12.5 and 100 mg/ml), MDPV (25, 50, and 100 mg/ml), and mephedrone (200 mg/ml). Locomotor effects were blocked by pretreatment with the dopamine D1-like receptor antagonist SCH23390 (10 μg/kg, intraperitoneal (i.p.)). MA and MDPV vapor inhalation also altered activity on a running wheel in a biphasic manner. An additional group of rats was trained on a discrete trial intracranial self-stimulation (ICSS) procedure interpreted to assess brain reward status. ICSS-trained rats that received vaporized MA, MDPV, or mephedrone exhibited a significant reduction in threshold of ICSS reward compared with vehicle. The effect of vapor inhalation of the stimulants was found comparable to the locomotor and ICSS threshold-reducing effects of i.p. injection of mephedrone (5.0 mg/kg), MA (0.5-1.0 mg/kg), or MDPV (0.5-1.0 mg/kg). These data provide robust validation of e-cigarette-type technology as a model for inhaled delivery of vaporized psychostimulants. Finally, these studies demonstrate the potential for human use of e-cigarettes to facilitate covert use of a range of psychoactive stimulants. Thus, these devices pose health risks beyond their intended application for the delivery of nicotine.


Characterization of atherosclerotic plaques by laser speckle imaging.
A method capable of determining atherosclerotic plaque composition and measuring plaque viscoelasticity can provide valuable insight into intrinsic features associated with plaque rupture and can enable the identification of high-risk lesions. In this article, we describe a new optical technique, laser speckle imaging (LSI), that measures an index of plaque viscoelasticity. We evaluate the potential of LSI for characterizing atherosclerotic plaque. Time-varying helium-neon laser speckle images were acquired from 118 aortic plaque specimens from 14 human cadavers under static and deforming conditions (0 to 200 microm/s). Temporal fluctuations in the speckle patterns were quantified by exponential fitting of the normalized cross-correlation of sequential frames in each image series of speckle patterns to obtain the exponential decay time constant, tau. The decorrelation time constants of thin-cap fibroatheromas (TCFA) (tau=47.5+/-19.2 ms) were significantly lower than those of other atherosclerotic lesions (P<0.001), and the sensitivity and specificity of the LSI technique for identifying TCFAs were >90%. Speckle decorrelation time constants demonstrated strong correlation with histological measurements of plaque collagen (R=0.73, P<0.0001), fibrous cap thickness (R=0.87, P<0.0001), and necrotic core area (R=-0.81, P<0.0001). Under deforming conditions (10 to 200 microm/s), tau correlated well with cap thickness in necrotic core fibroatheromas (P>0.05). The measurement of speckle decorrelation time constant from laser speckle images provides an index of plaque viscoelasticity and facilitates the characterization of plaque type. Our results demonstrate that LSI is a highly sensitive technique for characterizing plaque and identifying thin-cap fibroatheromas.


Nukbone® promotes proliferation and osteoblastic differentiation of mesenchymal stem cells from human amniotic membrane.
Bovine bone matrix Nukbone® (NKB) is an osseous tissue-engineering biomaterial that retains its mineral and organic phases and its natural bone topography and has been used as a xenoimplant for bone regeneration in clinics. There are not studies regarding its influence of the NKB in the behavior of cells during the repairing processes. The aim of this research is to demonstrate that NKB has an osteoinductive effect in human mesenchymal stem cells from amniotic membrane (AM-hMSCs). Results indicated that NKB favors the AM-hMSCs adhesion and proliferation up to 7 days in culture as shown by the scanning electron microscopy and proliferation measures using an alamarBlue assay. Furthermore, as demonstrated by reverse transcriptase polymerase chain reaction, it was detected that two gene expression markers of osteoblastic differentiation: the core binding factor and osteocalcin were higher for AM-hMSCs co-cultured with NKB in comparison with cultivated cells in absence of the biomaterial. As the results indicate, NKB possess the capability for inducing successfully the osteoblastic differentiation of AM-hMSC, so that, NKB is an excellent xenoimplant option for repairing bone tissue defects.


Benefit of dosimetry distribution for patients with multiple brain metastases from non-small cell lung cancer by a Cyberknife stereotactic radiosurgery (SRS) system.
In order to obtain a high dose conformal index of tumor and steep dose fall-off in healthy tissues for brain metastasis stereotactic radiosurgery (SRS), the aim of this study was to investigate SRS planning optimization by comparing one multiple-lesions plan (MLP) with multiple single-lesion plans (SLPs) for patients with multiple brain metastases using the Cyberknife (CK) system. Fifty non-small cell lung cancer (NSCLC) patients (28 males and 22 females) with 2-4 brain metastases, inter-tumour distances less than 3 cm, were retrospectively replanned with the original prescription dose (12-32 Gy) in the original fractions (1-3). Two different clinical CK SRS plans (SLPs and MLP) were generated for the same patients with the same collimator and prescription isodose line (62-68%) by the CK Multiplan System. Both SLPs and MLP were able to achieve > 95% PTV volume covered prescription dose and met the Timmerman 2011 organs at risk (brainstem, optic nerve and pituitary) constraints. Compared with those in the SLPs, the maximum dose (Dmax) and mean dose (Dmean) of brainstem in the MLP were reduced 0.22-3.13% (2.62%) and 2.71-12.56% (5.57%), respectively, all P < 0.05. Meanwhile, the volumes of the whole brain minus the tumors that received a single dose equivalent of 8-16 Gy (V8Gy-V16Gy) were effectively reduced in the MLP. The treatment time parameters, the total number of beams and monitor units, of the MLP were reduced by 3.31 and 1.47% (P < 0.05), respectively. Although there were a few differences in the conformity index (CI) and homogeneity index (HI) between the two treatment plans, the differences were not statistically significant (P = 2.94 and 1.08 > 0.05). One multiple-lesions plan for brain metastases could achieve higher precision in the target and lower doses in healthy tissue while shortening the treatment time and improving the treatment efficiency over multiple single-lesion plans.


Comparison of short term results of single injection of autologous blood and steroid injection in tennis elbow: a prospective study.
It has been recently reported that local injection of autologous blood in tennis elbow offers a significant benefit by virtue of various growth factors contained therein. The objective of our study was assessment of efficacy of autologous blood injection versus local corticosteroid injection in the treatment of tennis elbow. A single blinded, prospective parallel group trial was undertaken. 50 consecutive patients of untreated lateral epicondylitis were enrolled. Randomisation was done on alternate basis and two groups were constituted, first one receiving steroid injection and second one injection of autologous blood. Both groups were evaluated at 2 and 6 weeks for pain relief and stage of disease. Baseline evaluation showed no difference between the two groups (chi square test, P > 0.05). Between group analysis at 2 weeks showed no difference in pain relief and Nirschl stage (unpaired t test, P > 0.05). Evaluation at 6 weeks demonstrated a significant decrease in pain levels and stage of disease in blood group (unpaired t test, p < 0.05). Autologous blood injection was more effective than steroid injection in the short term follow up in tennis elbow.


In vivo modulation of iNOS pathway in hepatocellular carcinoma by Nigella sativa.
Nitric oxide (NO) and inducible nitric oxide synthase enzyme (iNOS) have been implicated in various tumors. Hepatocellular carcinoma is a highly aggressive form of solid tumor. The lack of effective therapy necessitates the introduction of novel therapeutic strategies to counter this disease. Nigella sativa (NS) has been shown to have specific health benefits. The aim of this study was to investigate the in vivo modulation of the iNOS pathway by NS ethanolic extract (NSEE) and the implications of this effect as an antitumor therapeutic approach against diethylnitrosamine (DENA)-induced hepatocarcinogenesis. Rats were divided into four groups, normal control, NSEE control, cancer control, and NSEE-DENA groups. The diagnosis of cancer was based on alpha-fetoprotein (AFP) levels and histological variations. Serum NO, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels and serum iNOS activity were measured. Liver iNOS expression was investigated by reverse transcriptase (RT)-PCR and western blot assays. Serum AFP, NO, TNF-α, and IL-6 levels and iNOS enzyme activity were significantly increased in rats treated with DENA. Significant up-regulation of liver iNOS mRNA and protein expression was also observed. Subsequent treatment with NSEE significantly reversed these effects and improved the histopathological changes in malignant liver tissue which appeared after treatment with DENA, without any toxic effect when given alone. These results provide evidence that attenuation of the iNOS pathway and suppression of the inflammatory response mediated by TNF-α, and IL-6 could be implicated in the antitumor effect of NSEE. As such, our findings hold great promise for the utilization of NS as an effective natural therapeutic agent in the treatment of hepatocarcinogenesis.


Up-regulation of 5-HT2 serotonin receptor: a possible mechanism of transformed migraine.
Transformation of episodic migraine to chronic daily headache (so called transformed migraine) is now a well recognized phenomenon. Although several factors, i.e. analgesic overuse, increasing age, psychiatric disorders are reported to play some roles in this transformation, the precise cascade is still unclear. Further suppression of an already abnormal antinociceptive system with up-regulation of post-synaptic receptors is one of the possible explanation. In order to understand the mechanism underlying this condition, 5-HT2 serotonin receptors on platelets were assayed by the radioligand binding technique. Six transformed migraine patients (67.67 +/- 1.52 years) and seven healthy controls (72.86 +/- 1.82 years) were studied. [3H]-spiperone and ketanserin were used to determine the specific binding. We found a significant increase (P < 0.05) in the maximal receptor numbers (Bmax) on platelet membrane of the migraine patients when compared to the controls (64.31 +/- 11.06 and 39.96 +/- 5.42 fmol/mg protein, respectively), whereas the dissociation equilibrium constant (KD) values remained unchanged (3.63 +/- 0.78 nM and 2.84 +/- 0.48 nM for the migraine patients and controls, respectively). The up-regulation of serotonin receptors found in this study provided further support to the "serotonergic hypofunction" theory of migraine pathogenesis and may explain the unusual loss of episodicity seen in the transformed migraine patients.


Complete genome sequence of keunjorong mosaic virus, a potyvirus from Cynanchum wilfordii.
We have determined the complete genome sequence of keunjorong mosaic virus (KjMV). The KjMV genome is composed of 9,611 nucleotides, excluding the 3'-terminal poly(A) tail. It contains two open reading frames (ORFs), with the large one encoding a polyprotein of 3,070 amino acids and the small overlapping ORF encoding a PIPO protein of 81 amino acids. The KjMV genome shared the highest nucleotide sequence identity (57.5 %) with pepper mottle virus and freesia mosaic virus, two members of the genus Potyvirus. Based on the phylogenetic relatedness to known potyviruses, KjMV appears to be a member of a new species in the genus Potyvirus.


Expression of the ubiquitin variant ubR48 decreases proteolytic activity in Arabidopsis and induces cell death.
The ubiquitin-proteasome pathway is the major route for protein degradation in eukaryotes. We show here that this pathway can be inhibited in Arabidopsis thaliana by expression of a ubiquitin variant that contains Arg instead of Lys at position 48 (ubR48). A major consequence of ubR48 expression is the induction of cell death. Cell death induction coincides with the appearance of reactive oxygen intermediates, but is independent of salicylic acid. We found changes in expression of some defense-related genes, but these changes are apparently insufficient to cause alterations in the response to a bacterial pathogen. Expression of ubR48 from an inducible gene allowed investigation of kinetic parameters of cell death induction. In the absence of additional stress factors, slow death processes dominate if the transgene is induced in seedlings older than 2 weeks. The inducible gene also allowed isolation of suppressor mutants. Expression of ubR48 may cause changes similar to inhibition of the proteasome, which also induces various forms of cell death. Thus, ubR48 is a tool to manipulate protein turnover and to probe cell death programs in plants.


The efferent vestibular system in the cat: a horseradish peroxidase and fluorescent retrograde tracers study.
Neurons of the efferent vestibular system were investigated in the cat using retrograde axonal transport of horseradish peroxidase and fluorescent retrograde double labelling techniques. The number of efferent neurons was clearly higher than previously reported. A three dimensional reconstruction of the location of these neurons showed that they constitute a single group and did not give evidence of an eventual specialization based on neuron subpopulations. However, a study of cross-sectional areas of the horseradish peroxidase-labelled efferent neurons detected that the ipsilateral population contained a larger number of small neurons than the contralateral one. Double labelling by means of either 4',6-diamidino-2- phenylindol 2HCl in combination with horseradish peroxidase or Fast Blue in combination with Nuclear Yellow showed that 20% of efferent neurons project to both labyrinths. Such a high percentage raises the question of the role of these double-projecting cells and the specificity of their branching on vestibular receptors. This study expands previous work in the cat demonstrating that a much greater number of efferent neurons exists than had hitherto been assumed, among them 20% have both crossed and uncrossed projections.


Necrotizing enterocolitis and C-KIT.
In the gut, C-KIT is important for immune system homeostasis, and C-KIT+ cells are known to increase during inflammation. Recently the authors identified that spontaneous intestinal mucosal erosion develops in C-KIT-depleted W/Wv mice after day 14 of life at a high frequency, whereas genotypically normal litter mates do not. The authors hypothesized that a lack of C-KIT may be implicated in the development of necrotizing enterocolitis (NEC). Bowel specimens were taken during surgery or postmortem from nine cases of NEC (mean gestational age, 32.0 weeks), six age-matched cases of enteritis, and 10 age-matched controls. Specimens were formalin fixed, paraffin embedded, and labeled with antibody to C-KIT. The number of C-KIT+ cells from five random fields per specimen were compared under light microscopy (200x). Results were expressed as the mean +/- SD and compared using the analysis of variance (ANOVA) test. In enteritis, the number of C-KIT+ cells in the lamina propria and submucosa was significantly higher than in controls (P<.01) indicative of their involvement in inflammation. However, in NEC, the number of C-KIT+ cells in the lamina propria and submucosa was significantly lower than in controls (P<.05) despite histological evidence of inflammation. A lack of C-KIT+ cells may exert a causal influence on the development of NEC.


Social adjustment does not predict depressive relapse during continuation fluoxetine therapy.
The purpose of this study was to assess the relationship between social adjustment and the risk of depressive relapse during continuation antidepressant treatment. The Social Adjustment Scale-Self Report Version (SAS-SR) was used to assess a broad range of social functioning before and after acute treatment in 41 outpatients with unipolar depression who responded to fluoxetine and then continued on this antidepressant. No differences were detected between those who relapsed and those who stayed well with regard to pre- and posttreatment SAS-SR total or subscale scores. These data suggest that social functioning does not affect the risk of relapse while depressed patients are taking fluoxetine continuation treatment.


Head injury prediction capability of the HIC, HIP, SIMon and ULP criteria.
The objective of the present study is to synthesize and investigate using the same set of sixty-one real-world accidents the human head injury prediction capability of the head injury criterion (HIC) and the head impact power (HIP) based criterion as well as the injury mechanisms related criteria provided by the simulated injury monitor (SIMon) and the Louis Pasteur University (ULP) finite element head models. Each accident has been classified according to whether neurological injuries, subdural haematoma and skull fractures were reported. Furthermore, the accidents were reconstructed experimentally or numerically in order to provide loading conditions such as acceleration fields of the head or initial head impact conditions. Finally, thanks to this large statistical population of head trauma cases, injury risk curves were computed and the corresponding regression quality estimators permitted to check the correlation of the injury criteria with the injury occurrences. As different kinds of accidents were used, i.e. footballer, motorcyclist and pedestrian cases, the case-independency could also be checked. As a result, FE head modeling provides essential information on the intracranial mechanical behavior and, therefore, better injury criteria can be computed. It is clearly shown that moderate and severe neurological injuries can only be distinguished with a criterion that is computed using intracranial variables and not with the sole global head acceleration.


Probing tumor phenotypes using stable and regulated synthetic microRNA precursors.
RNA interference is a powerful method for suppressing gene expression in mammalian cells. Stable knock-down can be achieved by continuous expression of synthetic short hairpin RNAs, typically from RNA polymerase III promoters. But primary microRNA transcripts, which are endogenous triggers of RNA interference, are normally synthesized by RNA polymerase II. Here we show that RNA polymerase II promoters expressing rationally designed primary microRNA-based short hairpin RNAs produce potent, stable and regulatable gene knock-down in cultured cells and in animals, even when present at a single copy in the genome. Most notably, by tightly regulating Trp53 knock-down using tetracycline-based systems, we show that cultured mouse fibroblasts can be switched between proliferative and senescent states and that tumors induced by Trp53 suppression and cooperating oncogenes regress upon re-expression of Trp53. In practice, this primary microRNA-based short hairpin RNA vector system is markedly similar to cDNA overexpression systems and is a powerful tool for studying gene function in cells and animals.


Two-year follow-up of a randomised controlled trial to assess the sustainability of a school intervention to improve the implementation of a school-based nutrition policy.
School-based nutrition policies can have a positive effect on the school food environment. The primary aim of this study was to assess the primary school adherence to a mandatory state-wide healthy canteen policy 12 months after an effective multi-strategic implementation intervention concluded. Primary schools were randomised to (a) a 12-14 months multi-strategic intervention or (b) no-intervention (control). The intervention aimed to improve implementation of a state-wide canteen policy by encouraging schools to remove unhealthy food and beverages (classified as ''red'' or ''banned'') from canteen menus and replace with healthy items (classified as ''green''). No implementation support was provided to either group by the research team between the 12 and 24 months data collection period. Seventy schools participated, of which 56 schools were assessed at 24-month follow-up. Intervention schools were less likely to have a menu which contained ''red/banned'' items at 24-month follow-up (RR = 2.28; 95% CI: 1.18-4.40; P = 0.01). Intervention schools, however, were not more likely than controls to have a menu which contained >50% ''green'' items at 24-month follow-up (RR = 1.29; 95% CI: 0.98-1.70; P = 0.10). Intervention schools were more likely to adhere to both policy components (no red/banned items and >50% green items on the menu) than control schools (RR = 2.61; 95% CI: 1.29-5.29; P = 0.006). Among intervention schools that were fully adherent to the policy following implementation support (12-month post baseline), all were also adherent at the 24-month follow-up. The intervention was effective in achieving long-term school adherence to a state-wide canteen policy at 24-month follow-up. SO WHAT?: The findings suggest that sustained improvements in implementation of school nutrition policies is possible following a period (12 months) of comprehensive implementation support.


Specificity of steroid binding to testicular microsomal cytochrome P-450. Relation of steroid structure to type-I spectral responses after correction for hydrophobic association with the membrane.
On the basis of the concept that steroids accumulate in the lipid phase of endoplasmic reticulum membranes and approach the active sites of steroidogenic cytochromes P-450 from a hydrophobic environment, we describe a procedure that allows calculation of spectral dissociation constants Ks for steroid interaction with testicular microsomal cytochrome P-450 after correction for hydrophobic association of ligand with the membrane. Maximal type-I spectral responses, apparent Ks, and partition into microsomal lipids were determined for 36 steroids, and corrected Ks values were derived from these primary data. Partition coefficients range from 60 to 62,000, and corrected Ks range from 60 microM to 25 mM steroid concentration in the lipid phase. Full spectral properties depend on a side-chain (1-3 carbon atoms) at the C17-position which may be hydrophobic or may bear a 20-oxo or 20 beta-hydroxy, but not a 20 alpha-hydroxy group. Binding constants are especially sensitive towards modifications of ring A structure (aromatization or 5 beta-, but not 5 alpha-reduction) and of the side-chain length. Androgens, with the exception of those bearing a 17 beta-acetoxy or 17 beta-propionyloxy group, are poorly accommodated by this cytochrome P-450.


Are all calories created equal? Emerging issues in weight management.
The global prevalence of overweight and obesity is growing. Correction of the problem through dietary intervention has been disappointing and has prompted research into variations of diet composition or pattern to promote negative energy balance. Limited research suggests that selected approaches, such as low-carbohydrate diets, augment weight loss and offer an advantage over conventional low-fat diets. This has led to the hypothesis that although in theoretical terms a calorie is a calorie, in practice this is not the case. Support for such views and plausible mechanisms exist. Although any advantage may augment weight management, reported discrepancies between theoretical and observed effects are small. Thus, energy-restricted diets should be based primarily on energy intake and expenditure.


The perception of healthcare quality of elderly in the city of Bari, South Italy.
In recent decades in Italy, as in all the industrialized nations, the proportion of elderly subjects in the total population is constantly on the increase. However the increased life expectancy is not always paralleled by a true improvement in the quality of life. In this context, it is essential to analyze elderly real health needs and the responses to these needs, especially in terms of healthcare, that the territorial services are perceived to offer. In the period from June to September 2006 we selected randomly one General Practitioner (GP) for each district of the Bari Municipal Area and, form each GP, we randomly chose 25 patients over 65 years old (YO). We conducted phone interviews using a standard data collection questionnaire and, for each of the recruited subjects, the GP filled a data collection sheet. Although the mean age (73.6 years) of the population under study was quite high, the general state of health was judged good both by the G P- and by their elderly patients (>75%).Notably, the great majority of elderly patients considered the healthcare they receive to be satisfactory (>60%): in particular, the GP was the true point of reference for this slice of the population for strictly medical problems as well as for advice. On the contrary, the patients attributed little value to social services, which were poorly known and scarcely used (8.5%). Public hospital facilities played a central role in second level healthcare in more than 30% of cases; private facilities covered by public health insurance were also very important. As possible solutions to the problem of loneliness, 36.6% of the patients declared that they approved of nursing homes. Decision makers need to create services supporting the key role played by General Practitioners, who are well aware that their assistance is not sufficient to satisfy the health needs of the elderly.


Trypanosoma congolense: host responses following tsetse transmitted infection of Kilifi isolates in goats.
East African x Galla goats, when infected with Trypanosoma congolense isolates from the Kilifi area of Kenya by Glossina morsitans centralis, did not develop the characteristic chancre reaction at the bite sites, whereas bites of tsetse infected with the cloned T. congolense IL.1180 from Serengeti, Tanzania, resulted in chancres in the same goats. Histological changes could not be observed in skin biopsies collected 8 or 9 days after infection with Kilifi isolates. However, all goats became parasitemic about 10 days after challenge. It is concluded that the absence of chancre development is a characteristic feature of T. congolense parasites from Kilifi. The isoenzyme analysis of clones of two T. congolense Kilifi isolates and the T. congolense clone IL.1180 indicated that they belong to different zymodemes. Neutralizing antibodies to homologous metacyclic variable antigen types were detected in six out of seven (86%) of the sera from goats infected with a clone or stock of a T. congolense Kilifi isolate, 20 days after infection. Goats primed by tsetse transmitted infection with a stock or clone of T. congolense from Kilifi and treated with Berenil were, in three out of eight cases (37%), not immune to homologous challenge. It is suggested that the reduced immune response to metacyclic variable antigen types could be a result of the absence of cellular infiltration, i.e., chancre development in the skin at the tsetse bite site. It is concluded that the use of the chancre reaction as a marker for serodeme analysis of recently isolated stocks of T. congolense from Kilifi was not feasible.


Validation of "the patient evaluation of emotional care during hospitalisation" questionnaire in intensive care unit patients.
To validate the "Patient Evaluation of Emotional Care During Hospitalization" (PEECH) questionnaire, which assesses hospitalised patients' emotional experiences, in patients admitted to the intensive care unit (ICU). Prospective study. The PEECH consists of three sections and four sub-scales: "level of security", "level of knowing", "level of personal value", and "level of connection". The questionnaire was completed by 253 hospitalised patients. Expert judgement was used to analyse the content validity and factor analysis was performed to confirm construct validity. Cronbach's alpha was used to measure the internal consistency of the four sub-scales. In the confirmatory factor analysis of the four sub-scales, the weights of all questions were found to be significant (>1). The internal consistency of the PEECH questionnaire was 0.86 (Cronbach's alpha) and the homogeneity index was high (>0.50). The PEECH questionnaire is a valid and reliable tool to evaluate the perception of emotional care in ICU patients. The information gathered can help provide more comprehensive care for patients in the ICU and in other hospitalised patients.


Effect of enzyme pretreatment on dehulling, cooking time and protein content of pigeon pea (variety BDN2).
This study was carried out to investigate the effect of enzymatic pretreatment at different enzyme concentration, incubation time, incubation temperature and tempering water pH on the hulling efficiency, cooking quality and protein content of pigeon pea (variety BDN2). Response surface methodology based on a four-factor, five-level, central composite design was employed to study the effect of the independent variables and optimize processing conditions. A quadratic model satisfactorily described the hulling efficiency, cooking time and protein content with high value for the coefficient of determination R2 (0.95, 0.92 and 0.97 respectively). It predicted a maximum hulling efficiency of 84.35%, minimum cooking time 13.06 min and maximum protein content 22.60% at enzyme concentration, and 31.34 mg/100 g dry matter, incubation time, 8.72 h, incubation temperature, 43.47 °C and tempering water, pH 5.99. Results were also compared with hulling efficiency, cooking time and protein content obtained with traditional oil pretreated method 78.30%, 14.30 min and 18.53% respectively. It revealed that hulling efficiency and protein content of enzyme pretreated pigeon pea could be increased 2.44% and 6.77% respectively, whereas cooking time could be reduced 1.50 min compared to the oil pretreated method.


AMPK: An Energy-Sensing Pathway with Multiple Inputs and Outputs.
AMP-activated protein kinase (AMPK) is a key regulator of energy balance expressed ubiquitously in eukaryotic cells. Here we review the canonical adenine nucleotide-dependent mechanism that activates AMPK when cellular energy status is compromised, as well as other, noncanonical activation mechanisms. Once activated, AMPK acts to restore energy homeostasis by promoting catabolic pathways, resulting in ATP generation, and inhibiting anabolic pathways that consume ATP. We also review the various hypothesis-driven and unbiased approaches that have been used to identify AMPK substrates and have revealed substrates involved in both metabolic and non-metabolic processes. We particularly focus on methods for identifying the AMPK target recognition motif and how it can be used to predict new substrates.


Two further cases of acute myeloid leukemia with trisomy 4.
Two cases of acute myeloid leukemia (FAB M1 and M2) with trisomy 4 are described. Morphologic abnormalities were confined to the granulocytic monocytic lineage with no evidence of erythroid or megakaryocytic involvement. One of the cases, who also had trisomy 13, presented initially with skin infiltration without bone marrow involvement.


Cardiac sodium/calcium exchanger preconditioning promotes anti-arrhythmic and cardioprotective effects through mitochondrial calcium-activated potassium channel.
Reverse-mode of the Na(+)/Ca(2+) exchanger (NCX) stimulation provides cardioprotective effects for the ischemic/reperfused heart during ischemic preconditioning (IP). This study was designed to test the hypothesis that pretreatment with an inhibitor of cardiac delayed-rectifying K(+) channel (IKr), E4031, increases reverse-mode of NCX activity, and triggers preconditioning against infarct size (IS) and arrhythmias caused by ischemia/reperfusion injury through mitoKCa channels. In the isolated perfused rat heart, myocardial ischemia/reperfusion injury was created by occlusion of the left anterior descending coronary artery for 30 min followed by 120 min reperfusion. Two cycles of coronary occlusion for 5 min and reperfusion were performed, or pretreatment with E4031 or sevoflurane (Sevo) before the 30 min occlusion with the reversed-mode of NCX inhibitor (KB-R7943) or not. E4031 or Sevo preconditioning not only markedly decreased IS but also reduced arrhythmias, which was significantly blunted by KB-R7943. Furthermore, these effects of E4031 preconditioning on IS and arrhythmias were abolished by inhibition of the mitoKCa channels. Similarly, pretreatment with NS1619, an opener of the mitoKCa channels, for 10 min before occlusion reduced both the infarct size and arrhythmias caused by ischemia/reperfusion. However, these effects weren't affected by blockade of the NCX with KB-R7943. Taken together, these preliminary results conclude that pretreatment with E4031 reduces infarct size and produces anti-arrhythmic effect via stimulating the reverse-mode NCX, and that the mitoKCa channels mediate the protective effects.


Mitral annular reconstruction with anterior leaflet flip-over in concomitant surgery for mitral regurgitation associated with extensive posterior annular calcification and hypertrophic obstructive cardiomyopathy.
We describe a case of severely calcified posterior mitral annulus associated with grade IV mitral regurgitation in addition to significant hypertrophic obstructive cardiomyopathy. A 70-year-old woman underwent successfully annular reconstruction with anterior mitral leaflet flip-over and mitral valve replacement with a bileaflet mechanical prosthesis combined with left ventricular septal myectomy. This technique can serve not only to cover the debrided posterior annulus, but also to eliminate left ventricular outflow tract obstruction and to keep left ventricular function by virtue of not severing ventricular-annular continuity.


Analysis of povidone iodine, chlorhexidine acetate and polyhexamethylene biguanide as wound disinfectants: in vitro cytotoxicity and antibacterial activity.
Even though disinfectants are commonly used in clinical practice and daily life, there are few studies on their antibacterial ability and cytotoxicity, which are closely related to the safety and effectiveness of their use. To provide a basis for the use of disinfectants, the cytotoxicity and antibacterial activity of three most commonly used disinfectants, povidone-iodine, chlorhexidine acetate and polyhexamethylene biguanide (PHMB), were investigated. A CCK-8 assay was used to measure the activities of human fibroblasts (HF) and keratinocytes (HaCat), the two most important cells in wound healing, following their exposure to disinfectants. The effects of different times and concentrations were included. The antibacterial activity of disinfectants against Staphylococcus aureus, Acinetobacter baumannii, Klebsiella pneumoniae was reflected by their minimum inhibitory concentration and minimum bactericidal concentration. All three disinfectants showed strong cytotoxicity in direct contact with HF and HaCat cells. Cytotoxicity increased with increasing exposure time and concentration. S. aureus, A. baumannii and K. pneumoniae comprised 70%, 55% and 85% of the strains sensitive to povidone iodine; 50%, 45% and 80% of the strains sensitive to chlorhexidine acetate; and 60%, 45% and 80% of the strains sensitive to PHMB, respectively. All three disinfectants were cytotoxic; therefore, it is necessary to pay attention to the use time and concentration in the clinical setting. All three disinfectants were cytotoxic, with povidone-iodine being the most cytotoxic even at low concentrations. PHMB had better antibacterial efficacy against S. aureus and is suitable for the treatment of shallow wounds primarily. All three tested bacteria were significantly more sensitive to PHMB than to the other disinfectants.


Social and communication difficulties and obsessive-compulsive disorder.
The relationship between pervasive developmental disorder (PDD) and obsessive-compulsive disorder (OCD) has not been extensively studied despite having some phenomenological features in common. Abnormal social and communication behaviors (pragmatic behaviors) are key components of PDD and are also part of the broader autism phenotype (BAP). In this study we sought to establish if there is any association between the presence of abnormal pragmatic behaviors and OCD and whether this association delineates a familial subtype of OCD. As part of the Johns Hopkins OCD Family Study, 80 OCD case probands were recruited and matched with 73 control probands. Probands and their first-degree relatives were interviewed using the Schedule for Affective Disorders and Schizophrenia-Lifetime Anxiety and other diagnostic instruments. A Pragmatic Rating Scale (PRS) to assess pragmatic behaviors was completed by the examiner. The PRS was completed on 395 subjects, of which 3% (n = 11) achieved a score of greater than 6. The prevalence of high PRS scores was significantly greater amongst case probands and relatives (5%) compared to control probands and relatives (0.5%, p = 0.011). In case relatives the prevalence of OCD was significantly higher in those relatives who had a family member with a high PRS score (p < 0.001). The presence of social and communication difficulties in members of OCD case families appears to identify a familial subtype of OCD that may be related to PDD and/or BAP. This study was limited to using the PRS to identify pragmatic behaviors in subjects with OCD.


Stimulation of adrenal DNA synthesis in cadmium-treated male rats.
Cadmium chloride (CdCl2) at a dose of 1 mg/kg body wt was injected into male rats of the Wistar strain, weighing 250 g on the average, twice a day (12-hr intervals) for 7 consecutive days. DNA and RNA contents and [3H]-thymidine and [3H]-uridine incorporation into the acid-insoluble fraction significantly increased in the adrenals or rats treated with Cd for 2 and 7 consecutive days. Adrenal protein content and weight also significantly increased. These results indicate that continued treatment with Cd stimulates DNA and RNA synthesis in the adrenal cortex, which in turn results in the increase of the total protein contents of the adrenal gland and subsequently in the enlargement of the gland. Serum adrenocorticotrophin (ACTH) and insulin levels in Cd-treated rats were not higher than control levels, suggesting that the stimulation of DNA synthesis in the adrenals of Cd-treated rats is due to factor(s) other than serum ACTH and insulin. Treatment with Cd inhibited DNA synthesis in cultured adrenocortical cells at concentrations of 10(-4) to 10(-8) M, suggesting that Cd does not directly stimulate DNA synthesis in the adrenal gland in vivo. Although the adrenal gland became enlarged, the total adrenal corticosterone content decreased significantly. The decrease of total adrenal corticosterone content may be due to the fall in serum ACTH level of Cd-treated rats.


Prone position and pressure control inverse ratio ventilation in H1N1 patients with severe acute respiratory distress syndrome.
To observe the 28 and 90 days mortality associated with prone position and assist control-pressure control (with inverse ratio) ventilation (ACPC-IRV). All patients who were admitted to our medical Intensive Care Unit (ICU) who are positive for H1N1 viral infection with severe acute respiratory distress syndrome (ARDS) and requiring invasive mechanical ventilation in prone position were included in our prospective observational study. Six patients who are positive for H1N1 required invasive ventilation in prone position. These patients were planned to ventilate in prone for 16 h and in supine for 8 h daily until P/F ratio >150 with FiO2 of 0.6 or less and positive end-expiratory pressure <10 cm of H2 O. At admission, among these six patients the mean tidal volume generated was about 376.6 ml which was in the range of 6-8 ml/kg predicted body weight. The mean lung injury score was 3.79, mean PaO2 /FiO2 ratio was 52.66 and mean oxygenation index was 29.83. The mean duration of ventilation was 9.4 days (225.6 h). The ICU length of stay was 11.16 days. There was no mortality at 28 and 90 days. Early prone combined with ACPC-IRV in H1N1 patients having severe ARDS can be used as a rescue therapy and it should be confirmed by large observational studies.


Surface histamine receptors in rat peritoneal mast cells. Separation of receptor-bearing cells via binding to a histamine-protein conjugate, Cell-ect.
The Seragen Cell-ect Total Histamine KitTM was used to separate histamine receptor-bearing rat peritoneal mast cells from cells lacking these receptors. It was found that approximately 75% of the peritoneal mast cell population carried cell surface histamine receptors. The results further suggest that the mast cell histamine receptors present are mainly of an H1-type, as judged by the capacity of a specific H1-antagonist to reduce the histamine receptor-dependent cell adhesion. Moreover, an H1-agonist is less efficient in this respect and an H2-antagonist does not affect the cell adhesion at all. A possible functional role for these receptors, however, remains to be clarified.


Associations between pituitary-thyroid hormones and depressive symptoms in individuals with anorexia nervosa before and after weight-recovery.
There is sound evidence that the hypothalamic-pituitary-thyroid axis plays a role in mood regulation. Alterations in this axis, particularly low triiodothyronine syndrome, are a common neuroendocrine adaptation to semi-starvation in patients with anorexia nervosa (AN), who also frequently suffer from co-existing depressive symptoms. We therefore aimed to investigate the associations between pituitary-thyroid function and psychopathology, in particular depressive symptoms, at different stages of AN using a combined cross-sectional and longitudinal study design. Pituitary-thyroid status (FT3, free triiodothyronine; FT4, free thyroxine; conversion ratio FT3/FT4; TSH, thyroid-stimulating hormone) was assessed in 77 young acutely underweight females with AN (acAN) and in 55 long-term weight-recovered individuals with former AN (recAN) in a cross-sectional comparison to 122 healthy controls (HC). Further, pituitary-thyroid status of 48 acAN was reassessed after short-term weight-restoration. We performed correlation analyses of pituitary-thyroid parameters with self-reported measures of psychopathology. AcAN showed significantly lower FT3, FT4, FT3/FT4 ratio, and TSH levels compared to HC. Pituitary-thyroid alterations were partly reversed after short-term weight-restoration. RecAN still had lower FT3 concentrations than HC. Lower FT3 concentrations and FT3/FT4 ratios were associated with more severe depressive symptoms in acAN, occurring prominently in cases of manifest low triiodothyronine syndrome. Longitudinally increasing FT3/FT4 ratios (change scores) were inversely correlated with depressive and general psychiatric symptoms after short-term weight-restoration. Our results suggest a potential modulation of the severity of depressive symptoms by temporarily decreased FT3 concentrations and inhibited thyroid hormone conversion (FT3/FT4 ratios) in acutely underweight AN. Associations between conversion ratios FT3/FT4 and psychopathology seem to persist across short-term weight-restoration. The findings of our study might have relevant clinical implications, ranging from thyroid monitoring to experimental low-dose thyroid hormone supplementation in certain patients with AN showing severe psychiatric impairment and overt thyroid hormone alterations.


Pulmonary physiology in the postoperative period.
After upper abdominal or thoracic surgery, loss of lung volume, manifested most importantly by reduced FRC, and abnormal gas exchange, manifested by postoperative reduction in PaO2, are the rule rather than the exception. These physiologic alterations in lung function occur in the absence of superimposed complications such as pneumonia and/or lobar atelectasis; the usual physiologic alterations do, in fact, predispose to pulmonary complications (approximate 20 per cent incidence) which, when present, further compromise lung function. The mechanisms of postoperative impairment in lung function are multiple, interactive, and at the present, incompletely understood. An attempt to summarize the more important causes of impaired postoperative lung function is shown in Figure 6.


[Diagnosis of pulmonary tuberculosis using Ziehl-Neelsen stain and polymerase chain reaction].
Definitive diagnosis of unclear pulmonary lesions is mainly based on morphological methods. In addition to a neoplasm, inflammatory reactions, in particular tuberculosis (TB), have to be considered in most cases. Therefore, the aim of this work was to determine whether established methods used in general pathology can be efficiently used with cytological material. An established polymerase chain reaction (PCR) protocol for the detection of Mycobacterium tuberculosis complex (Mtc) DNA in fixed specimens was conducted on fixed material available as an assay for liquid-based cytology (LBC). CytoLyt®-fixed material of 45 patients with clinically suspected TB or other mycobacteriosis were selected and were initially tested cytologically. In cases of absent tumor cells, PCR for detection of Mtc DNA and Ziehl-Neelsen stain (ZN) were performed. In 9 patients (20 %), Mtc DNA was found by PCR. The following methods were used to obtain material: catheter biopsy (5), needle biopsy (2), transbronchial needle aspiration (1), and bronchoalveolar lavage (1). Cytologically an inflammatory reaction was observed in all cases. In 2 patients, a history of TB, in 2 further cases either silicosis or a posttransplant situation was known. In cases with a positive PCR, 7 patients (78 %) were positive in ZN and 3 patients (33.3 %) in TB culture (15.5 % vs. 6.7 % of the total cohort); however, the material used for investigation was not always from identical sources, respectively. In 36 out of 45 patients, both PCR and ZN were negative for the detection of Mtc DNA. The material intended for LBC can be used for detection of TB with ZN and Mtc PCR.


Dental pathology of the California sea lion (Zalophus californianus).
Skulls from 1,085 California sea lions (Zalophus californianus) were examined macroscopically according to defined criteria. The museum specimens, 61.8% male and 37.3% female, were acquired from strandings and varied in age from juvenile to adult. The majority of teeth were available for examination (95.7%); 3.8% of teeth were artefactually absent, 0.4% deemed absent due to acquired tooth loss and 0.1% were congenitally absent. Acquired tooth loss was associated significantly with sex (P = 0.004) with males having more tooth loss than females and total ante-mortem tooth loss was associated significantly with age (P <0.0001) with adults having more tooth loss than young adults and juveniles. Eleven teeth were malformed and 81 teeth were observed to have two roots. Supernumerary teeth (usually maxillary molar teeth) were associated with 1.3% of teeth, some specimens demonstrating up to four supernumerary teeth. Thirteen persistent deciduous teeth were identified. A total of 713 specimens showed attrition or abrasion, with 42.4% of teeth affected. A significant association was detected between sex and incidence of abrasion and age and the incidence of abrasion (P <0.0001 for both associations). Males showed more abrasion than females and adults showed more abrasion than young adults or juveniles. Two hundred and sixteen fractured teeth were observed, with root fractures being most prevalent. Fractures were associated significantly with sex and with age (P <0.0001 for each association). Males had more fractures than females and adults had more fractures than young adults and juveniles. Bony changes consistent with periodontitis were found, affecting 19.4% of teeth. Males were shown to have more periodontitis than females and adults were shown to have more periodontitis than young adults and juveniles. Sixty-three periapical lesions were noted.


Chemoinformatics-driven classification of Angiosperms using sulfur-containing compounds and machine learning algorithm.
Phytochemicals or secondary metabolites are low molecular weight organic compounds with little function in plant growth and development. Nevertheless, the metabolite diversity govern not only the phenetics of an organism but may also inform the evolutionary pattern and adaptation of green plants to the changing environment. Plant chemoinformatics analyzes the chemical system of natural products using computational tools and robust mathematical algorithms. It has been a powerful approach for species-level differentiation and is widely employed for species classifications and reinforcement of previous classifications. This study attempts to classify Angiosperms using plant sulfur-containing compound (SCC) or sulphated compound information. The SCC dataset of 692 plant species were collected from the comprehensive species-metabolite relationship family (KNApSAck) database. The structural similarity score of metabolite pairs under all possible combinations (plant species-metabolite) were determined and metabolite pairs with a Tanimoto coefficient value > 0.85 were selected for clustering using machine learning algorithm. Metabolite clustering showed association between the similar structural metabolite clusters and metabolite content among the plant species. Phylogenetic tree construction of Angiosperms displayed three major clades, of which, clade 1 and clade 2 represented the eudicots only, and clade 3, a mixture of both eudicots and monocots. The SCC-based construction of Angiosperm phylogeny is a subset of the existing monocot-dicot classification. The majority of eudicots present in clade 1 and 2 were represented by glucosinolate compounds. These clades with SCC may have been a mixture of ancestral species whilst the combinatorial presence of monocot-dicot in clade 3 suggests sulphated-chemical structure diversification in the event of adaptation during evolutionary change. Sulphated chemoinformatics informs classification of Angiosperms via machine learning technique.


Phytoextraction potential of two Rumex acetosa L. accessions collected from metalliferous and non-metalliferous sites: effect of fertilization.
Metal tolerance and phytoextraction potential of two common sorrel (Rumex acetosa L.) accessions, collected from a Pb/Zn contaminated site (CS, Lanestosa) and an uncontaminated site (UCS, Larrauri), were studied in fertilized and non-fertilized pots prepared by combining soil samples from both sites in different proportions (i.e., 0%, 33%, 66% and 100% of Lanestosa contaminated soil). The original metalliferous mine soil contained 20480, 4950 and 14 mg kg(-1) of Zn, Pb and Cd, respectively. The microcosm experiment was carried out for two months under greenhouse controlled conditions. It was found that fertilization increased mean plant biomass of both accessions as well as their tolerance. However, only the CS accession survived all treatments even though its biomass decreased proportionally according to the percentage of contaminated mine soil present in the pots. This metallicolous accession would be useful for the revegetation and phytostabilization of mine soils. Due to its high concentration and bioavailability in the contaminated soil, the highest values of metal phytoextracted corresponded to Zn. The CS accession was capable of efficiently phytoextracting metal from the 100% mine soil, indeed reaching very promising phytoextraction rates in the fertilized pots (6.8 mg plant(-1) month(-1)), similar to the ones obtained with hyperaccumulator plants. It was concluded that fertilization is certainly worth being considered for phytoextraction and revegetation with native plants from metalliferous soils.


Predictors of Emergency Room Visits After Ambulatory Breast Cancer Surgery in the Medicare Population.
Emergency department (ED) overuse is a large contributor to healthcare spending in the USA. We examined the rate of and risk factors for ED visits following outpatient breast cancer surgery. Using linked data from the Surveillance, Epidemiology, and End Results (SEER) program and Medicare, we identified women who underwent curative breast cancer surgery between 2003 and 2015. Our outcome of interest was ED visits within 30 days of surgery. Multivariate regression was used to evaluate the odds of ED visit while controlling for clinical and socioeconomic variables. Secondary analyses assessed admission from the ED as well as costs. Of the 78,060 included patients, 5.1% returned to the ED, of which only 29.8% required hospital admission. Rate of ED visits increased with patient age. A higher percentage of Black patients returned to the ED compared with white patients (7.0% versus 5.0%, p < 0.001). Patients with higher income were less likely to visit the ED compared with those with lower income (OR 0.76, p < 0.001). Predictors of ED visits included: being unmarried (OR 1.18, p < 0.001), having stage 2 (OR 1.20, p < 0.001) or stage 3 cancer (OR 1.38, p < 0.001), and those with Charlson comorbidity score of 1 (OR 1.39, p < 0.001) or ≥ 2 (OR 2.29, p < 0.001). While a substantial number of patients return to the ED following outpatient breast surgery, most do not require hospital admission, which indicates that a large proportion of these visits could have been avoided. We identified several clinical and socioeconomic predictors of postoperative ED visits, which will aid in the development of patient risk profiling tools.


The Kinase Activity of Drosophila BubR1 Is Required for Insulin Signaling-Dependent Stem Cell Maintenance.
As a core component of the mitotic checkpoint complex, BubR1 has a modular organization of molecular functions, with KEN box and other motifs at the N terminus inhibiting the anaphase-promoting complex/cyclosome, and a kinase domain at the C terminus, whose function remains unsettled, especially at organismal levels. We generate knock-in BubR1 mutations in the Drosophila genome to separately disrupt the KEN box and the kinase domain. All of the mutants are homozygously viable and fertile and show no defects in mitotic progression. The mutants without kinase activity have an increased lifespan and phenotypic changes associated with attenuated insulin signaling, including reduced InR on the cell membrane, weakened PI3K and AKT activity, and elevated expression of dFoxO targets. The BubR1 kinase-dead mutants have a reduced cap cell number in female germaria, which can be rescued by expressing a constitutively active InR. We conclude that one major physiological role of BubR1 kinase in Drosophila is to modulate insulin signaling.


Inflammation is associated with a reduced number of pro-angiogenic Tie-2 monocytes and endothelial progenitor cells in patients with critical limb ischemia.
Inflammation is the driving force in atherosclerosis. One central strategy in the treatment for PAD is the promotion of angiogenesis. Here, pro-angiogenic Tie-2-expressing monocytes (TEM) and endothelial progenitor cells (EPC) play a crucial role. Critical limb ischemia (CLI) is characterized by a severe, chronic inflammatory response; thus, progression of the disease might be related to the deleterious effects of inflammation on pro-angiogenic cells. Forty-five patients with intermittent claudication (IC) [three groups: Rutherford (R)-1, -2, or -3; each n = 15], 20 patients with CLI [n = 20; Rutherford 4 (15 %), 5 (40 %), and 6 (45 %)], and 20 healthy controls were included in the study. Analysis of TEM and EPC was performed from whole blood by flow cytometry. Treatment for IC patients was conservative, and CLI patients underwent surgical revascularization. Follow-up was performed after mean of 7.1 months. In comparison with healthy controls, we found increased proportions of TEM and EPC in dependence of the severity of PAD, with the highest level in patients with severe claudication (R3) (p < 0.01). In contrast, for patients with CLI, we found a significantly reduced expression of both TEM and EPC in comparison with healthy controls (p < 0.05) or IC patients (R-1, R-2, and R-3) (all p < 0.001). At follow-up, TEM and EPC in CLI patients increased significantly (both p < 0.001). Serum levels of fibrinogen and CRP were significantly increased in CLI patients (all p < 0.001), but decreased at follow-up (all p < 0.05). TEM and EPC proportions correlated inversely with levels of fibrinogen [(TEM: r = −0.266; p < 0.01) (EPC: r = −0.297; p < 0.001)], CRP (TEM: r = −0.283; p < 0.01) (EPC: r = −0.260; p < 0.01). We found a strong association of diverse inflammatory markers with a reduced proportion of pro-angiogenic TEM or EPC in patients with CLI, giving rise to the speculation that a severe chronic inflammation might lead to deleterious effects on TEM and EPC, possibly interfering with angiogenesis, thus promoting an aggravation of the disease.


Simultaneous acquisition of PAR and PAIN spectra.
We present a scheme that allows the simultaneous detection of PAR and PAIN correlation spectra in a single two-dimensional experiment. For both spectra, we obtain almost the same signal-to-noise ratio as if a PAR or PAIN spectrum is recorded separately, which in turn implies that one of the spectra may be considered additional information for free. The experiment is based on the observation that in a PAIN experiment, the PAR condition is always also fulfilled. The performance is demonstrated experimentally using uniformly (13)C,(15)N-labeled samples of N-f-MLF-OH and ubiquitin.


Experience with 407 transvenous, finned pacing leads with a sintered porous-surfaced electrode.
Experience with 407 transvenous ventricular finned pacing leads with a sintered porous-surfaced electrode is reported. A low complication rate was encountered: 97% of patients were free from lead-related complications. Four patients (1%) required re-operation: two for lead displacement, one for failure to sense spontaneous ventricular activity and one for exit block. A further patient developed exit block which resolved spontaneously. The vast majority of patients had low chronic stimulation thresholds; for example at six months after implantation, the mean threshold for a group of pacemakers with a pulse duration of 0.5 ms was 1.4 +/- 0.7 V and for another group with a pulse duration of 0.8 ms it was 1.9 +/- 0.7 mA. However, six patients developed a transient high stimulation threshold during the month after implantation, and a high threshold developed in another patient at five months and persisted. Mean acute stimulation and sensing thresholds were satisfactory: 0.7 +/- 0.2 V at 0.5 ms pulse duration and 7.6 +/- 2.4 mV, respectively.


[New elements in behavior therapy of a case of dog phobia in an adolescent patient with Down's syndrome. A critical study of the method].
A review of the actual literature shows, that we have no reports of successful behavioral methods for the treatment of mentally retarded children with phobias. This study suggests a new way for treating a dog-phobia of a seventeen year old boy with Downsyndrom, using a special form of flooding by including the Premack-principle. Problems of desensitization and other special effects during therapy of these patients are discussed.


Scanning electron microscopy of a bacterial infection of the human nasal mucosa.
Scanning electron micrographs of a bacterial infection of the human nasal mucosa indicate that the surface attachment of bacteria to epithelial cells is of significance for their pathogeneity in the airways. It is suggested that further scanning electron microscopic studies of natural and experimental infected human nasal mucosa can give valuable information about the initial interaction between micro-organisms and host cell and add to our understanding of airways infections.


[Mindfulness based cognitive therapy (MBCT) in patients with obsessive-compulsive disorder--an adaptation of the original program].
Mindfulness-based cognitive Therapy (MBCT) has shown to be effective in the relapse prevention and treatment of several psychiatric disorders. However, MBCT has not yet been applied in OCD (Obsessive-compulsive Disorder). This article proposes an adaptation of the eight-session group program for patients with residual symptoms after cognitive behavioural treatment (CBT) with exposure. It has proven feasible and was considered helpful by patients within the framework of a pilot study 1. Apart from an overview of the modified manual, OCD-specific elements are presented in detail and illustrated on the base of work sheets. The manual indicates that MBCT could be a useful supplement to CBT and is well applicable to the therapeutic needs of patients with OCD.


MicroRNA target detection and analysis for genes related to breast cancer using MDLcompress.
We describe initial results of miRNA sequence analysis with the optimal symbol compression ratio (OSCR) algorithm and recast this grammar inference algorithm as an improved minimum description length (MDL) learning tool: MDLcompress. We apply this tool to explore the relationship between miRNAs, single nucleotide polymorphisms (SNPs), and breast cancer. Our new algorithm outperforms other grammar-based coding methods, such as DNA Sequitur, while retaining a two-part code that highlights biologically significant phrases. The deep recursion of MDLcompress, together with its explicit two-part coding, enables it to identify biologically meaningful sequence without needlessly restrictive priors. The ability to quantify cost in bits for phrases in the MDL model allows prediction of regions where SNPs may have the most impact on biological activity. MDLcompress improves on our previous algorithm in execution time through an innovative data structure, and in specificity of motif detection (compression) through improved heuristics. An MDLcompress analysis of 144 over expressed genes from the breast cancer cell line BT474 has identified novel motifs, including potential microRNA (miRNA) binding sites that are candidates for experimental validation.


Musculoskeletal Pain and Vitamin D Deficiency in Children: A Pilot Follow-up Study of Vitamin D Therapy in Musculoskeletal/Orthopedic Conditions.
The prevalence of vitamin D deficiency in pediatric populations is high. In the present study we analyzed associations between vitamin D therapy and pain, mobility, fatigue, and daily functioning in children with musculoskeletal/orthopedic conditions suffering from chronic and recurrent pain, but also diagnosed with vitamin D deficiency. Children with different musculoskeletal/orthopedic conditions and vitamin D deficiency were prescribed to receive vitamin D over 6 months. Thirty-five children (18 males; age 10.48 ± 3.87 years) completed a 6-month follow-up. Self- and parent/proxy rating scales were used to evaluate pain, movement, fatigue, and daily functioning. At a six-month follow-up assessment involving child- and parent-reported scores, worst pain intensity significantly decreased (p ≤ 0.03) after vitamin D therapy, as well as functioning problems related to pain (p ≤ 0.01). The children reported better movement and balance with less fatigue. The parents reported better functioning in everyday activities of their children. This pilot study showed that vitamin D therapy possibly reduces pain intensity and improves mobility and daily functioning in children with musculoskeletal/orthopedic disorders, chronic recurrent pain, and vitamin D deficiency. Further follow-up and randomized studies are required in order to assess the validity of clinical recommendations.


Sudden death in acrogeria Gottron type.
In this paper, we describe the case of a 29-year-old Caucasian male who was reported dead in his home. In 2010, a diagnosis of acrogeria, Gottron type was obtained by genetic analysis of a COL3A1 gene mutation. External examination showed typical characteristics of acrogeria, Gottron type. Autopsy showed a full-thickness laceration in the inferior vena cava wall, which caused hemorrhage and death. Samples of inferior vena cava were processed by Masson trichrome staining, which revealed a reduction in vessel wall thickness and a decrease in the amount of elastic fibers. An antibody reaction with BCL-2 was intensely positive. Our case is extremely rare in the medical field and in the world of scientific literature, both because the patient had a variant of acrogeria, Gottron type and because of the cause of death, which is not typical of Ehlers-Danlos syndrome. To the best of our knowledge, this very rare event has not previously been reported in the international scientific literature.


Docetaxel: in gastric cancer.
Docetaxel is a taxane analogue that inhibits microtubule disassembly and, in cultured gastric cancer cells, induces apoptosis-associated binding activity of the transcription factor activating protein-1, and activates the proapoptotic genes BCL2L1 and BAX. In patients with metastatic or locally advanced/recurrent gastric or gastro-oesophageal junction adenocarcinoma, the median time to tumour progression was significantly prolonged with 3-week cycles of intravenous (IV) docetaxel plus cisplatin and fluorouracil (5-fluorouracil) compared with 4-week cycles of IV cisplatin plus IV fluorouracil (5.6 vs 3.7 months) in a large (n = 445), randomised, multicentre, phase III trial. Furthermore, recipients of this triple regimen experienced a significantly longer median overall survival time, a higher overall response rate and delayed deterioration in health-related quality of life than those receiving cisplatin plus fluorouracil. These data are supported by two large (n > 100), randomised, phase II studies in patients with metastatic or locally advanced/recurrent gastric or gastro-oesophageal junction cancer. In general, combination therapy with docetaxel, cisplatin and fluorouracil was relatively well tolerated given the nature of chemotherapy in patients with metastatic or locally advanced/recurrent gastric or gastro-oesophageal adenocarcinoma


Effect of relative GGBS/fly contents and alkaline solution concentration on compressive strength development of geopolymer mortars subjected to sulfuric acid.
The effect of submerging geopolymer mortar samples in highly acidic solution for 7-, 28-, and 90-days on stability of mass and the development of compressive strength development was assessed experimentally. The mortar binder consisted of GGBS or blends of GGBS and fly ash activated using combinations of NaOH and Na2SiO3 solutions, and samples were cured in room temperature. It was found that maintaining mortar samples continuously under sulfuric acid doesn't cause reduction compressive strength or mass from one age to the other, up to 90 days. While decalcification, delaumination, and formation of calcium salts due to sulfate attack may have affected mass and strength, submerging samples under water supported formation of geopolymerization products C-A-S-H and N-A-S-H, and consequently increased the mass and compressive strength of cubic mortar samples with fly ash + GGBS blended binder. The resistance of mortar to sulfuric acid remained consistent when mortars were prepared using GGBS:fly ash ratio of 3:1, equal amounts of GGBS and fly ash, and GGBS as sole binder. When geopolymer mortar samples made with each of the three binders was left exposed to air after casting, compressive strength increased from 7- to 28-days after casting, but at 90-days, all mortar samples experienced decrease in compressive strength relative to the 28-day values. The relatively high content of GGBS (≥ 50%) and absence of curing water in relatively dry conditions caused shrinkage cracking and decrease in compressive strength.


Baricitinib improves symptoms in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: patient-reported outcomes from two randomized monotherapy phase III trials.
Itch, skin pain, and sleep disturbance are burdensome symptoms in atopic dermatitis (AD) that negatively influence a patient's quality of life (QoL). To evaluate the impact of baricitinib on patient-reported outcomes (PROs) in adult patients with moderate-to-severe AD, and explore the association between improvement in key signs and symptoms of AD with improvements in QoL and patient's assessment of disease severity. Data were analyzed from two phase III monotherapy trials (BREEZE-AD1/BREEZE-AD2) in which patients were randomized 2:1:1:1 to once-daily placebo, baricitinib 1-mg, 2-mg, or 4-mg for 16 weeks and assessed using PRO measures. At week 16, baricitinib 4-mg and 2-mg significantly reduced itch severity (Itch Numeric Rating Scale (NRS) (BREEZE-AD1: percent change from baseline -36.6% and -29.4% vs. placebo (-12.0%), p≤.001 and p≤.05; BREEZE-AD2: -47.2% and -46.9% vs. placebo (-16.6%), p≤.001). Baricitinib significantly reduced SCORing AD (SCORAD) pruritus (4-mg in BREEZE-AD1 and 2-mg in BREEZE-AD2) and Patient Oriented Eczema Measure (POEM) itch (both doses). Improvements in skin pain severity and sleep disturbance were also observed. Improvements in AD symptoms showed higher correlations with patients' assessment of AD severity and QoL than improvements in skin inflammation. Baricitinib significantly improved symptoms in patients with moderate-to-severe AD. NCT03334396 (BREEZE-AD1) and NCT03334422 (BREEZE-AD2).


Substance abuse prevention program for children and adolescents in a community-based clinic.
This paper describes a community-based substance abuse prevention program utilizing a cognitive-behavioral curriculum to children and adolescents affected by a substance use disorder in a parent or caretaker.


Deoxycholic acid as a molecular scaffold for tyrosyl-DNA phosphodiesterase 1 inhibition: A synthesis, structure-activity relationship and molecular modeling study.
Para-Bromoanilides of deoxycholic acid with various functional groups on the steroid scaffold were designed as promising tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibitors. Tdp1 is a DNA repair enzyme, involved in removing DNA damage caused by topoisomerase I poisons; an important class of anticancer drugs. Thus, reducing the activity of Tdp1 can increase the efficacy of anticancer drugs in current use. Inhibitory activity in the low micromolar and submicromolar concentrations was observed with 3,12-dimethoxy para-bromoanilide 17 being the most active with an IC50 value of 0.27 μM. The activity of N-methyl para-bromoanilides was 3-4.8 times lower than of the corresponding para-bromoanilides. Increased potency of the ligands was seen with higher molecular weight and log P values. The ligands were evaluated for their cytotoxic potential in a panel of tumor cell lines; all were nontoxic to the A549 pulmonary adenocarcinoma cell line. However, derivatives containing a hydroxyl group at the 12th position were more toxic than their 12-hydroxyl group counterparts (acetoxy-, oxo- and methoxy- group) against HCT-116 human colon and HepG2 hepatocellular carcinomas. In addition, an N-methyl substitution led to an increase in toxicity for the HCT-116 and HepG2 cell lines. The excellent activity as well as low cytotoxicity, derivative 17 can be considered as a lead compound for further development.


Development and evaluation of spectral classification algorithms for fluorescence guided laser angioplasty.
Laser angioplasty, or the ablation of atherosclerotic plaque using laser energy, has tremendous potential to expand the scope of nonsurgical treatment of obstructive vascular disease. Clinical laser angioplasty, however, has been hindered by an unacceptable risk of vessel perforation. Laser-induced fluorescence spectroscopy can discriminate atherosclerotic from normal artery and may therefore be capable of guiding selective plaque ablation. To assess the feasibility of utilizing spectral information to discriminate arterial tissue type, several classification algorithms were developed and evaluated. Arterial fluorescence spectra from 350 to 700 nm were obtained from 100 human aortic specimens. Seven spectral classification algorithms were developed with the following techniques: multivariate linear regression, stepwise multivariate linear regression, principal components analysis, decision plane analysis, Bayes decision theory, principal peak ratio, and spectral width. The classification ability of each algorithm was evaluated by its application to the training set and to a validation set containing 82 additional spectra. All seven spectral classification algorithms prospectively classified atherosclerotic and normal aorta with an accuracy greater than 80 percent (range: 82-96 percent). Laser angioplasty systems incorporating spectral classification algorithms may therefore be capable of detection and selective ablation of atherosclerotic plaque.


Gorham-Stout disease of the mandible: case report and review of literature of a rare type of osteolysis.
Gorham-Stout disease (GSD) is a rare form of osteolysis, the aetiology and pathogenesis of which remains controversial to this date. Although more than 200 cases of GSD have been reported so far, this disease continues to go undiagnosed in the initial stages owing to its varied clinical presentations and rarity. Through this case report of GSD in a 3-year-old boy, we discuss the slow progression of the disease over a period of 13 years. The literature review is also done with an emphasis on the role of an oral and maxillofacial radiologist in understanding the disease at its incipient stage.


GLP1R inhibits the progression of endometrial carcinoma through activation of cAMP/PKA pathway.
This study strived to explore the role and mechanism of glucagon-like peptide-1 receptor (GLP1R) in endometrial carcinoma (EC). In detail, after transfection of GLP1R overexpression vector and small interfering RNA targeting PKA, the mRNA expressions of GLP1R and PKA in EC cells (Ishikawa and RL95-2) were quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The cell biological behaviors, including proliferation, migration, invasion, and apoptosis, were detected using 5-ethynyl-2'-deoxyuridine (EdU), wound healing, transwell, and flow cytometry assays, respectively. The cyclic adenosine monophosphate (cAMP) content and related protein expressions (GLP1R, p-PKA, and PKA) were determined by enzyme-linked immunosorbent assay (ELISA) and western blot. The effects of GLP1R and PKA on tumorigenesis were evaluated by measuring the tumor volume and weight of mice bearing EC. According to the results, GLP1R expression was downregulated in EC tissues and cells, and there was a positive correlation between GLP1R and PKA expressions. Upregulation of GLP1R promoted apoptosis and activated the cAMP/PKA signaling pathway in EC cells, while hindering the EC cell proliferation, invasion, migration, and the growth of tumor in mice. However, these effects were blunted by downregulation of PKA, which also accelerated the progression of EC in vitro and in vivo via inhibiting the activation of cAMP/PKA signaling pathway. Collectively, upregulation of GLP1R impeded EC progression via inducing the activation of cAMP/PKA signaling pathway, which may be a potential treatment for EC.


[Impact of foot reconstruction surgery on the daily life of patients with cerebrovascular accident sequelae].
The equinovarus deformity of the foot and digital scrolling is very common among people with sequelae from cerebrovascular accidents. The aim of this study was focused on changes produced by surgical correction of the deformity in terms of comfort, balance, independence and ability to move freely within the context of the daily life of the patient. The data was evaluated using a retrospective survey and a prospective analysis of gait habits using a recording walking device (WalkinSense(®)) before and after surgery. All the 15 patients enrolled in the study were submitted to similar surgical procedures of lengthening and tendon transfers. The use of technical aids to correct the deformity and to aid in walking, as well as painful calluses and difficulties with the shoes and walking on uneven surfaces, decreased significantly. Quantitative analysis of the gait showed that after surgery the patient started to move with smaller steps, although with a higher cadence. Gait analysis also revealed a decrease in the amount of gait segments and speed. The results showed a positive development in terms of indicators of comfort, balance, independence and self-image through surgery. However the new way of walking seems to be more tiring for the patients, which could justify a decrease in the number of gait segments and speed.


Homecare, technology, and the management of respiratory disease.
Taking care of ventilator-dependent patients in the home is demanding and complex. The difficulties that families face can be reduced by provision of homecare services that are the result of the collaborative work of a variety of health care disciplines. These difficulties cannot be eliminated, however. Sensitive care requires that the nursing case manager be aware of signs that indicate the costs are exceeding the families' ability and plan to meet their needs and the needs of the patients.


Small and potentially resectable focal pancreatic lesions noted on CT/MRI scans in nonjaundiced patients: likelihood of neoplasia and utility of EUS.
Management of small and potentially resectable "mass" lesions encountered on CT/MRI scans in patients without obstructive jaundice (ObJ) is rather empirical since there is scant data on likelihood of neoplasm to formulate treatment strategies. We evaluated (1) the prevalence of neoplasm and (2) performance characteristics of EUS-FNA for diagnosing neoplasm in above-mentioned subset of patients. This is a retrospective analysis of 232 patients (without ObJ) with a focal pancreatic lesion, ≤ 25 mm and potentially resectable on CT/MRI who underwent EUS-FNA from 2002 to 2009. Seventy-five patients (32.3%, 95% CI 26.6, 38.6) were finally diagnosed to have a neoplasm. Four of 92 (4.3%) lesions ≤ 15 mm, 13 of 57(22.8%) lesions 16-20 mm, and 35 of 83 (42.1%) lesions 21-25 mm had an adenocarcinoma. Larger lesion size, older patient age, and h/o recent weight loss significantly increased the likelihood of adenocarcinoma. EUS-FNA had 98.2% overall accuracy and 98.1% NPV with no significant differences based on lesion size. In nonjaundiced patient with a potentially resectable pancreatic lesion ≤25 mm in size noted on CT/MRI scanning, EUS-FNA can provide useful adjunctive information to optimize the use of surgery and can potentially obviate the need for "wait and watch approach" with repeat imaging in their clinical management.


Weighing Antitumor Immunity against Life-threatening Myocarditis from Immune-Checkpoint Inhibitors.
In this issue of Cancer Discovery, Salem and colleagues report a combination therapy for immune-checkpoint inhibitor (ICI) myocarditis using high-dose glucocorticoids, abatacept, and the JAK inhibitor ruxolitinib. The apparent efficacy of their strategy and an accompanying animal model provide further evidence for common immune mechanisms underlying ICI toxicities. See related article by Salem et al., p. 1100 (2).


Risk factors for hospital-acquired influenza A and patient characteristics: a matched case-control study.
While hospital-acquired influenza A results in an additional cost burden and considerable mortality in patients, its risk factors are unknown. We aimed to describe the characteristics of patients vulnerable to hospital-acquired influenza A and to identify its risk factors to assist clinicians control hospital-acquired infections and reduce the burden of treatment. A case-control study was conducted among hospitalized patients aged ≥18 years at a tertiary level teaching hospital during the 2018-2019 influenza A season. Patient data were retrieved from hospital-based electronic medical records. Hospital-acquired influenza A was defined as a case of influenza A diagnosed 7 days or more after admission, in a patient with no evidence of influenza A infection on admission. The controls without influenza A were selected among patients exposed to the same setting and time period. We identified risk factors using conditional logistic regression and described the characteristics of hospital-acquired influenza A by comparing the clinical data of infected patients and the controls. Of the 412 hospitalized patients with influenza A from all the departments in the study hospital, 93 (22.6%) cases were classified as hospital-acquired. The most common comorbidities of the 93 cases were hypertension (41.9%), coronary heart disease (21.5%), and cerebrovascular disease (20.4%). Before the onset of hospital-acquired influenza A, patients presented more lymphocytopenia (51.6% vs 35.5%, P = 0.027), hypoalbuminemia (78.5% vs 57.0%, P = 0.002), and pleural effusion (26.9% vs 9.7%, P = 0.002) than the matched controls. Infected patients also had longer hospital stays (18 days vs 14 days, P = 0.002), and higher mortality rates (10.8% vs 2.2%, P = 0.017) than the matched controls. Lymphocytopenia (odds ratio [OR]: 3.11; 95% confidence interval [CI]: 1.24-7.80; P = 0.016), hypoalbuminemia (OR: 2.24; 95% CI: 1.10-4.57; P = 0.027), and pleural effusion (OR: 3.09; 95% CI: 1.26-7.58; P = 0.014) were independently associated with hospital-acquired influenza A. Lymphocytopenia, hypoalbuminemia and pleural effusion are independent risk factors that can help identify patients at high risk of hospital-acquired influenza A, which can extend hospital stay and is associated with a high mortality.


Identification of a tetrasialylated monofucosylated tetraantennary N-linked carbohydrate chain in human platelet glycocalicin.
Glycocalicin (140 kDa), the main constituent of the glycoprotein Ib alpha-chain (150 kDa) of the human platelet membrane, contains 4 putative N-glycosylation sites. For the structural analysis of the N-glycosidic carbohydrate chains of glycocalicin, the glycoprotein has been subjected to the hydrazinolysis procedure. The acidic carbohydrate chains obtained were fractionated by ion-exchange chromatography on DEAE-Sephadex A-25, and subsequently analyzed by sugar analysis, anion-exchange chromatography on Mono Q HR 5/5 and 500 MHz 1H-NMR spectroscopy. A novel tetrasialylated monofucosylated tetraantennary chain was identified in the glycoprotein. It could also be deduced that in all structures the alpha 2----6-linked NeuAc is attached exclusively at the Gal beta 1----2Man alpha 1----3 antenna, whereas the other antennae can be terminated with alpha 2----3-linked NeuAc. As minor constituents sialylated N-linked carbohydrate chains with a terminal Fuc alpha 1----2Gal beta 1----sequence were detected.


Robust Prediction of Non-home Discharge After Thoracolumbar Spine Surgery With Ensemble Machine Learning and Validation on a Nationwide Cohort.
Delays in postoperative referrals to rehabilitation or skilled nursing facilities contribute toward extended hospital stays. Facilitating more efficient referrals through accurate preoperative prediction algorithms has the potential to reduce unnecessary economic burden and minimize risk of hospital-acquired complications. We develop a robust machine learning algorithm to predict non-home discharge after thoracolumbar spine surgery that generalizes to unseen populations and identifies markers for prediction. Retrospective electronic health records were obtained from our single-center data warehouse (SCDW) to identify patients undergoing thoracolumbar spine surgeries between 2008 and 2019 for algorithm development and internal validation. The National Inpatient Sample (NIS) database was queried to identify thoracolumbar surgeries between 2009 and 2017 for out-of-sample validation. Ensemble decision trees were constructed for prediction and area under the receiver operating characteristic curve (AUROC) was used to assess performance. Shapley additive explanations values were derived to identify drivers of non-home discharge for interpretation of algorithm predictions. A total of 5224 cases of thoracolumbar spine surgeries were isolated from the SCDW and 492,312 cases were identified from NIS. The model achieved an AUROC of 0.81 (standard deviation [SD] = 0.01) on the SCDW test set and 0.77 (SD = 0.01) on the nationwide NIS data set, thereby demonstrating robust prediction of non-home discharge across all diverse patient cohorts. Age, total Elixhauser comorbidities, Medicare insurance, weighted Elixhauser score, and female sex were among the most important predictors of non-home discharge. Machine learning algorithms reliably predict non-home discharge after thoracolumbar spine surgery across single-center and national cohorts and identify preoperative features of importance that elucidate algorithm decision-making.


Clinical observation on effect of triptolide tablet in treating patients with psoriasis vulgaris.
To investigate the effects of triptolide tablet in the treatment of patients with psoriasis vulgaris. By an open clinical study of 103 patients with psoriasis vulgaris. Psoriasis area severity index (PASI) was measured and recorded before and after treatment for efficacy evaluation. Of the 103 patients, markedly effective was got in 41 (39.7%), improved in 37 (35.8%) and ineffective in 25 (24.5%), the total effective rate being 75.7%, and the adverse reaction was shown only in few patients with decreased WBC during the treatment period. Triptolide tablet is effective for the treatment of psoriasis vulgaris during the one-year follow-up.


Olfactory identification in elderly Greek people in relation to memory and attention measures.
The University of Pennsylvania Smell Identification Test (UPSIT) and the Cross-Cultural Smell Identification Test (CC-SIT) were administered to nondemented Greek participants ranging in age from 49 to 88 years together with tests of verbal memory from the Wechsler Memory Scale-3rd Edition (WMS-III). The test scores of the sample administered the CC-SIT were compared with the test scores of the 12 analogous UPSIT items of the sample administered the UPSIT. The percent of individuals correctly identifying each of the odorants of the UPSIT and CC-SIT is reported, together with means and standard deviations (S.D.) of the total smell scores. UPSIT performance in both the full test and the 12 analogous items was associated with WMS-III Logical Memory I performance after accounting for the effects of age, education and gender. CC-SIT performance was associated with gender, score on the Beck Depression Inventory-II and Logical Memory I performance. The study shows that olfactory identification is associated with verbal memory in nondemented individuals after accounting for demographic variables.


Partial purification and characterization of phospholipid N-methyltransferases from murine thymocyte microsomes.
Significant amounts of phospholipid N-methyltransferase activity in murine thymocytes were found to be distributed on the plasma membrane. The enzyme activity had an optimum pH of 9. The presence of divalent cations, Mg2+ (10 mM) or Ca2+ (1 mM), and EGTA separately in the assay had only a small effect on the enzyme activity. However, addition of both 10 mM Mg2+ and 1 mM Ca2+ increased the enzyme activity. The presence of two enzymes for each conversion of phosphatidylethanolamine (PE) to phosphatidylmonomethylethanolamine (PME) and PME to phosphatidylcholine (PC) was suggested by the result of the determination of the incorporated radioactivity into PME, phosphatidyldimethylethanolamine (PDE) and PC; the apparent Km values for S-adenosyl-L-methionine were 20 and 400-500 microM for the conversion of PE to PME and for the conversion of PME to PC they were 5 microM and 40 microM. S-Adenosyl-L-homocysteine (AdoHcy), a known inhibitor of enzymatic methylation, competitively inhibited [14C]methyl incorporation into total lipid. The apparent Ki value for AdoHcy was 44.7 microM. Two phospholipid N-methyltransferases were partially purified by extraction with sodium deoxycholate, gel filtration on Sephadex G-75, and affinity column chromatography on AdoHcy-Sepharose. One enzyme, mainly catalyzing the formation of PME, was purified approximately 1548-fold and the other catalyzing the formation of PDE and PC, was purified approximately 629- to 703-fold. However, the former still contained a little activity for PDE and PC formation and the latter contained a little activity for PME formation. In these partially purified phospholipid N-methyltransferase preparations, little contaminating protein O-carboxylmethyltransferase activity was observed; however, significant PC-phospholipase A2 activity was detected. This result may suggest that phospholipid N-methyltransferases associate with phospholipase A2 in the thymocyte plasma membrane.


The role of the circle of Willis in internal carotid artery stenosis and anatomical variations: a computational study based on a patient-specific three-dimensional model.
The aim of this study is to provide better insights into the cerebral perfusion patterns and collateral mechanism of the circle of Willis (CoW) under anatomical and pathological variations. In the current study, a patient-specific three-dimensional computational model of the CoW was reconstructed based on the computed tomography (CT) images. The Carreau model was applied to simulate the non-Newtonian property of blood. Flow distributions in five common anatomical variations coexisting with different degrees of stenosis in the right internal carotid artery (RICA) were investigated to obtain detailed flow information. With the development of stenosis in unilateral internal carotid artery (ICA), the cerebral blood supply decreased when the degree of stenosis increased. The blood supply of the ipsilateral middle cerebral artery (MCA) was most affected by the stenosis of ICA. The anterior communicating artery (ACoA) and ipsilateral posterior communicating artery (PCoA) functioned as the important collateral circulation channels when unilateral stenosis occurred. The blood flow of the anterior circulation and the total cerebral blood flow (CBF) reached to the minimum in the configuration of the contralateral proximal anterior cerebral artery (A1) absence coexisting with unilateral ICA stenosis. Communicating arteries provided important collateral channels in the complete CoW when stenosis in unilateral ICA occurred. The cross-flow in the ACoA is a sensitive indicator of the morphological change of the ICA. The collateral function of the PCoA on the affected side will not be fully activated until a severe stenosis occurred in unilateral ICA. The absence of unilateral A1 coexisting with the stenosis in the contralateral ICA could be the most dangerous configuration in terms of the total cerebral blood supply. The findings of this study would enhance the understanding of the collateral mechanism of the CoW under different anatomical variations.


Application of a Clinical Whole-Transcriptome Assay for Staging and Prognosis of Prostate Cancer Diagnosed in Needle Core Biopsy Specimens.
Molecular and genomic analysis of microscopic quantities of tumor from formalin-fixed, paraffin-embedded biopsy specimens has many unique challenges. Herein, we evaluated the feasibility of obtaining transcriptome-wide RNA expression to measure prognostic classifiers in diagnostic prostate needle core biopsy specimens. One-hundred fifty-eight samples from diagnostic needle core biopsy specimens (BX) and radical prostatectomies (RPs) were collected from 33 patients at three hospitals; each patient provided up to six tumor and benign samples. Genome-wide transcriptomic profiles were generated using Affymetrix Human Exon arrays for comparison of gene expression alterations and prognostic signatures between the BX and RP samples. A sufficient amount of RNA (>100 ng) was obtained from all RP specimens (n = 77) and from 72 of 81 of BX specimens. Of transcriptomic features detected in RP, 95% were detectable in BX tissues and demonstrated a high correlation (r = 0.96). Likewise, an expression signature pattern validated on RPs (Decipher prognostic test) showed correlation between BX and RP (r = 0.70). Of matched BX and RP pairs, 25% showed discordant molecular subtypes. Genome-wide exon arrays yielded data of comparable quality from biopsy and RP tissues. The high concordance of tumor-associated gene expression changes between BX and RP samples provides evidence for the adequate performance of the assay platform with samples from prostate needle biopsy specimens with limited tumor volume.


Kinetic analysis, size profiling, and bioenergetic association of DNA released by selected cell lines in vitro.
Although circulating DNA (cirDNA) analysis shows great promise as a screening tool for a wide range of pathologies, numerous stumbling blocks hinder the rapid translation of research to clinical practice. This is related directly to the inherent complexity of the in vivo setting, wherein the influence of complex systems of interconnected cellular responses and putative DNA sources creates a seemingly arbitrary representation of the quantitative and qualitative properties of the cirDNA in the blood of any individual. Therefore, to evaluate the potential of in vitro cell cultures to circumvent the difficulties encountered in in vivo investigations, the purpose of this work was to elucidate the characteristics of the DNA released [cell-free DNA (cfDNA)] by eight different cell lines. This revealed three different forms of cfDNA release patterns and the presence of nucleosomal fragments as well as actively released forms of DNA, which are not only consistently observed in every tested cell line, but also in plasma samples. Correlations between cfDNA release and cellular origin, growth rate, and cancer status were also investigated by screening and comparing bioenergetics flux parameters. These results show statistically significant correlations between cfDNA levels and glycolysis, while no correlations between cfDNA levels and oxidative phosphorylation were observed. Furthermore, several correlations between growth rate, cancer status, and dependency on aerobic glycolysis were observed. Cell cultures can, therefore, successfully serve as closed-circuit models to either replace or be used in conjunction with biofluid samples, which will enable sharper focus on specific cell types or DNA origins.