Esophageal Adenocarcinoma-Derived Extracellular Vesicle MicroRNAs Induce a Neoplastic Phenotype in Gastric Organoids.
There have been no reports describing the effects of cancer cell-derived extracellular vesicles (EVs) on three-dimensional organoids. In this study, we delineated the proneoplastic effects of esophageal adenocarcinoma (EAC)-derived EVs on gastric organoids (gastroids) and elucidated molecular mechanisms underlying these effects. EVs were identified using PKH-67 staining. Morphologic changes, Ki-67 immunochemistry, cell viability, growth rates, and expression levels of miR-25 and miR-210, as well as of their target mRNAs, were determined in gastroids co-cultured with EAC-derived extracellular vesicles (c-EVs). C-EVs were efficiently taken up by gastroids. Notably, c-EV-treated gastroids were more crowded, compact, and multilayered and contained smaller lumens than did those cultured in organoid medium alone or in EAC-conditioned medium that had been depleted of EVs. Moreover, c-EV-treated gastroids manifested increased proliferation and cellular viability relative to medium-only or EV-depleted controls. Expression levels of miR-25 and miR-210 were significantly higher, and those of PTEN and AIFM3 significantly lower, in c-EV-treated versus medium-only or EV-depleted control groups. Inhibitors of miR-25 and miR-210 reversed the increased cell proliferation induced by c-exosomes in co-cultured gastroids by lowering miR-25 and miR-210 levels. In conclusion, we have constructed a novel model system featuring the co-culture of c-EVs with three-dimensional gastroids. Using this model, we discovered that cancer-derived EVs induce a neoplastic phenotype in gastroids. These changes are due, at least in part, to EV transfer of miR-25 and miR-210.


A Randomized Placebo-Controlled Trial of Omega-3 and Sertraline in Depressed Patients With or at Risk for Coronary Heart Disease.
Studies of depressed psychiatric patients have suggested that antidepressant efficacy can be increased by adding eicosapentaenoic acid (EPA), one of the omega-3 fatty acids found in fish oils. The purpose of this study was to determine whether the addition of EPA improves the response to sertraline in depressed patients with or at high risk for coronary heart disease (CHD). Between May 2014 and June 2018, 144 patients with DSM-5 major depressive disorder seen at the Washington University School of Medicine with or at high risk for CHD were randomized to receive either 50 mg/d of sertraline and 2 g/d of EPA or 50 mg/d of sertraline and corn oil placebo capsules for 10 weeks. The Beck Depression Inventory II (BDI-II) was the primary outcome measure. After 10 weeks of treatment, there were no differences between the arms on the mean baseline-adjusted BDI-II (placebo, 10.3; EPA, 12.1; P = .22), the 17-item Hamilton Depression Rating Scale (placebo, 7.2; EPA, 8.0; P = .40), or the 10-week remission rate (BDI-II score ≤ 8: placebo, 50.6%; EPA, 46.7%; odds ratio = 0.85; 95% CI, 0.43 to 1.68; P = .63). Augmentation of sertraline with 2 g/d of EPA for 10 weeks did not result in greater improvement in depressive symptoms compared to sertraline and corn oil placebo in patients with major depressive disorder and CHD or CHD risk factors. Identifying the characteristics of cardiac patients whose depression may benefit from omega-3 and clarifying the pathways linking omega-3 to improvement in depression symptoms are important directions for future research. ClinicalTrials.gov identifier: NCT02021669; FDA IND registration number: 121107.


Viscoelastic properties of waxy and nonwaxy rice flours, their fat and protein-free starch, and the microstructure of their cooked kernels.
Physicochemistry and structural studies of two types of japonica rice, low amylose Calmochi-101 (CM101) and intermediate amylose M-202 (M202), were conducted to determine similarities and differences between the rices perhaps attributable to amylose content differences. The rheological behavior of the gelation and pasting processes of flours and starches was determined with high accuracy and precision using a controlled stress rheometer. Fat and protein, although minor constituents of milled rice, were shown to have significant effects on the physicochemical and pasting properties of starches and flours. Removal of protein and lipids with aqueous alkaline or detergent solutions caused lower pasting temperatures and higher overall viscosity in both starches, compared with their respective flours. There was less viscosity difference between M202 flour and its starch when isolated by enzymatic hydrolysis of protein. The protease did not reduce internally bound lipids, suggesting that fats help to determine pasting properties of rice flours and their respective starches. Structural integrity differences in individual granules of waxy and nonwaxy rice flours, starches, and whole raw, soaked, and cooked milled grain were revealed by fracture analysis and scanning electron microscopy. Calmochi 101 and M202 did not differ in weight-averaged molar mass (Mw) and root-mean-square radii (Rz) between flours and starches, as determined by high-performance size exclusion chromatography (HPSEC) and multiple-angle laser light scattering (MALLS) (Park, I.; Ibanez, A. M.; Shoemaker, C. F. Starch 2007, 59, 69-77).


Increased survival of dopaminergic neurons in striatal grafts of fetal ventral mesencephalic cells exposed to neurotrophin-3 or glial cell line-derived neurotrophic factor.
The transplantation of fetal mesencephalic cell suspensions into the brain striatal system is an emerging treatment for Parkinson's disease. However, one objection to this procedure is the relatively poor survival of implanted cells. The ability of neurotrophic factors to regulate developmental neuron survival and differentiation suggests they could be used to enhance the success of cerebral grafts. We studied the effects of neurotrophin-3 (NT-3) or glial cell line-derived neurotrophic factor (GDNF) on the survival of dopaminergic neurons from rat fetal ventral mesencephalic cells (FMCs) implanted into the rat striatum. Two conditions were tested: (a) incubation of FMCs in media containing NT-3 and GDNF, prior to grafting, and (b) co-grafting of FMCs with cells engineered to overexpress high levels of NT-3 or GDNF. One week after grafting into the rat striatum, the survival of TH+ neurons was significantly increased by pretreatment of ventral mesencephalic cells with NT-3 or GDNF. Similarly, co-graft of ventral mesencephalic cells with NT-3- or GDNF-overexpressing cells, but not the mock-transfected control cell line, increased the survival of graft-derived dopaminergic neurons. Interestingly, we also found that co-grafting of GDNF-overexpressing cells was less effective than NT-3 at improving the survival of fetal dopaminergic neurons in the grafts, and that only GDNF induced intense TH immunostaining in fibers and nerve endings of the host tissue surrounding the implant. Thus, our results suggest that NT-3, by strongly enhancing survival, and GDNF, by promoting both survival and sprouting, may improve the efficiency of fetal transplants in the treatment of Parkinson's disease.


Perinatal HIV Infection and Exposure and Their Association With Dental Caries in Nigerian Children.
Although HIV infection is associated with well-known oral pathologies, there remains a dearth of comparative studies aimed at determining the association between HIV infection/exposure and early childhood caries. This is a cross-sectional study using a convenience sample of 3 groups of children receiving care at a tertiary care hospital in Nigeria. The groups include HIV infected (HI), HIV exposed but uninfected and HIV-unexposed and -uninfected children 6 through 72 months of age. Medical records were reviewed, and caregivers were interviewed for sociodemographic, maternal and birth factors as well as early feeding and dietary information. Oral examinations were performed by trained dentist examiners. Of 335 children enrolled, 33 (9.9%) presented with caries. In an adjusted analysis, compared with HIV-unexposed and -uninfected children, HI children had significantly greater odds of having caries (odds ratio = 2.58; 95% confidence interval: 1.04-6.40; P = 0.04), but there was no statistically significant difference in HIV exposed but uninfected children (odds ratio = 2.01; 95% confidence interval: 0.56-7.23; P = 0.28). Factors significantly associated with higher caries prevalence include low CD4 counts and percentage, older age, longer duration of breastfeeding and spontaneous membrane rupture during delivery. Caries was more prevalent in HI children. These findings support the need to target HI children for oral health prevention and treatment services particularly in Nigeria and other developing countries.


Reducing estrogen synthesis in developing boars increases testis size and total sperm production.
The abundant production of testicular estrogens and the presence of both ESR1 and ESR2 within boar testes are consistent with a role for estrogen in testicular development and/or function in this species. This study was aimed at determining the role of endogenous estrogen in the regulation of testicular development and function, including the effects on testis weight, histology, sperm production (detergent-resistant spermatid numbers), Sertoli cell numbers, and Leydig cell volume in the boar. Twenty-eight littermate pairs of boars were assigned to groups as follows: 1 boar from each pair was assigned to the control group (vehicle) and the other was assigned to treatment and received 0.1 mg/kg body weight of an aromatase enzyme inhibitor (letrozole) orally each week beginning at 1 week of age until castration at 2, 3, 4, 5, 6, 7, or 8 months of age. Testes were weighed and testicular parenchyma was recovered for determination of histology and detergent-resistant spermatid numbers, and for determination of Sertoli cell number and Leydig cell volume by staining for GATA-4 and 17-alpha hydroxylase/17-20 lyase respectively. Testes of aromatase-inhibited boars initially exhibited delayed lumen formation, lower testicular weight, fewer detergent-resistant spermatids, and fewer Sertoli cells, but by 7 to 8 months, these boars had recovered and had larger testes, more detergent-resistant spermatids per testis, and more Sertoli cells. Total Leydig cell volume increased in proportion to testis size. Reducing endogenous estrogen is consistent with a delay in testicular maturation/puberty that allows for a longer window for the proliferation of Sertoli cells and maturation of Leydig cells, resulting in larger testes and higher spermatid production.


Infants with flow limitation at 4 weeks: outcome at 6 and 11 years.
Within a longitudinal study of lung function in 243 infants, we identified a group of 23 individuals with flow limitation in tidal expiration. In infancy, flow-limited children have reduced lung function and increased airway responsiveness (AR), and at 2 years of age they are diagnosed with asthma more frequently. We hypothesized that these observations would persist throughout childhood. Data from ages 3 to 11 years were analyzed. Only at 4 years of age did the flow-limited group have increased wheeze compared with other cohort members (odds ratio, 4.25; 95% confidence interval [CI], 1.11 to 16.2; p = 0.04; n = 114). At 6 years of age, 117 cohort members were seen. The flow-limited group (n = 14) had greater AR (p = 0.009) and reduced mean FEV(1) (131 ml; 95% CI, 16 to 246; p = 0.03) and FEF(25-75) (0.28 L/second; 95% CI, 0.05 to 0.52; p = 0.02). At 11 years of age, 183 children were seen and the flow-limited group (n = 18) had greater AR (p = 0.02) and a trend toward reduced mean FEF(25-75) (0.24 L/second; 95% CI, -0.02 to 0.49; p = 0.08). Atopy and parental asthma were not increased in the flow-limited group. We suggest that the physiologic abnormality that causes flow limitation in early infancy may identify an at-risk group, different from asthma, who have reduced lung function and increased airway responsiveness in later life.


Amygdala abnormalities in first-degree relatives of individuals with schizophrenia unmasked by benzodiazepine challenge.
Impaired emotion processing in schizophrenia predicts broader social dysfunction and has been related to negative symptom severity and amygdala dysfunction. Pharmacological modulation of emotion-processing deficits and related neural abnormalities may provide useful phenotypes for pathophysiological investigation. We used an acute benzodiazepine challenge to identify and modulate potential emotion-processing abnormalities in 20 unaffected first-degree relatives of individuals with schizophrenia, compared to 25 control subjects without a family history of psychosis. An oral 1 mg dose of the short-acting anxiolytic benzodiazepine alprazolam was administered in a balanced crossover placebo-controlled double-blind design, preceding identical 3 T fMRI sessions approximately 1 week apart. Primary outcomes included fMRI activity in amygdala and related regions during two facial emotion-processing tasks: emotion identification and emotion memory. Family members exhibited abnormally strong alprazolam-induced reduction in amygdala and hippocampus activation during emotion identification, compared to equal reduction in both groups for the emotion memory task. GABAergic modulation with alprazolam produced differential responses in family members vs. controls, perhaps by unmasking underlying amygdalar and/or GABAergic abnormalities. Such pharmacological fMRI paradigms could prove useful for developing drugs targeting specific neural circuits to treat or prevent schizophrenia.


Enemas with mesalazine increase the tissue contents of mucins in the colonic mucosa devoid of fecal stream.
To evaluate the inflammatory reaction and measure the content of mucins, in the colonic mucosa without fecal stream submit to intervention with mesalazine. Twenty-four rats were submitted to a left colostomy and a distal mucous fistula and divided into two groups according to euthanasia to be performed two or four weeks. Each group was divided into two subgroups according daily application of enemas containing saline or mesalazine at 1.0 g/kg/day. Colitis was diagnosed by histological analysis and the inflammatory reaction by validated score. Acidic mucins and neutral mucins were determined with the alcian-blue and periodic acid of Schiff techniques, respectively. Sulfomucin and sialomucin were identified by high iron diamine-alcian blue technique. The tissue contents of mucins were quantified by computer-assisted image analysis. Mann-Whitney test was used to analyze the results establishing the level of significance of 5%. Enemas with mesalazine in colonic segments without fecal stream decreased the inflammation score and increased the tissue content of all subtypes of mucins. The increase of tissue content of neutral, acid and sulfomucin was related to the time of intervention. Mesalazine enemas reduce the inflammatory process and preserve the content of mucins in colonic mucosa devoid of fecal stream.


Potential of a commercially available water acidification product for reducing Campylobacter in broilers prior to slaughter.
1. This study investigated the potential of a commercially available acidified water treatment (PWT) for reducing the number of Campylobacter in vitro and other bacteria in the gut of live broilers. 2. In vitro tests indicated that PWT was highly effective for reducing Campylobacter jejuni and Campylobacter coli at the recommended concentration in water, reducing populations by greater than 7 log10 CFU/ml after 24 h exposure. The decrease in the number of Salmonella serovar Enteritidis and Escherichia coli was not significant. 3. Addition of PWT to the broiler drinking water for the first 7 d, 2 d before and 2 d after each feed change and at feed withdrawal prior to slaughter or only after feed withdrawal had no effect on the number of Campylobacter in caecal samples on farm before thinning and depopulation compared to untreated controls. 4. Although PWT was effective for reducing Campylobacter in water, the results suggest that it does not reduce the number of Campylobacter in the caeca of broilers prior to slaughter under the conditions used in the study.


Melatonin as a Therapy for Preterm Brain Injury: What Is the Evidence?
Despite significant improvements in survival following preterm birth in recent years, the neurodevelopmental burden of prematurity, with its long-term cognitive and behavioral consequences, remains a significant challenge in neonatology. Neuroprotective treatment options to improve neurodevelopmental outcomes in preterm infants are therefore urgently needed. Alleviating inflammatory and oxidative stress (OS), melatonin might modify important triggers of preterm brain injury, a complex combination of destructive and developmental abnormalities termed encephalopathy of prematurity (EoP). Preliminary data also suggests that melatonin has a direct neurotrophic impact, emphasizing its therapeutic potential with a favorable safety profile in the preterm setting. The current review outlines the most important pathomechanisms underlying preterm brain injury and correlates them with melatonin's neuroprotective potential, while underlining significant pharmacokinetic/pharmacodynamic uncertainties that need to be addressed in future studies.


Focal Nodular Hyperplasia in children presenting as acute Cholecystitis.
In this case report, a female child of 10 years old presented with pain epigastrium and with sonographic features of acute cholecystitis. Later on, the focal mass in the liver was diagnosed by Magnetic Resonance Imaging (MRI) examination and proved by the biopsy as focal nodular hyperplasia (FNH), a benign focal response of the liver and a hepatic mass. Although focal nodular hyperplasia is rare mass in children however, Computed Tomography (CT) scan / Magnetic Resonance Imaging (MRI) examination are essential for the diagnosis and can obviate the need for the biopsy and unnecessary surgery.


Brief reports: A distinct DNA methylation signature defines breast cancer stem cells and predicts cancer outcome.
Self-renewal and differentiation are two epigenetic programs that regulate stem cells fate. Dysregulation of these two programs leads to the development of cancer stem cells (CSCs). Recent evidence suggests that CSCs are relatively resistant to conventional therapies and responsible for metastasis formation. Deciphering these processes will help understand oncogenesis and allow the development of new targeted therapies. Here, we have used a whole genome promoter microarray to establish the DNA methylation portraits of breast cancer stem cells (bCSCs) and non-bCSCs. A total of 68 differentially methylated regions (DMRs) were more hypomethylated in bCSCs than in non-bCSCs. Using a differentiation assay we demonstrated that DMRs are rapidly hypermethylated within the first 6 hours following induction of CSC differentiation whereas the cells reached the steady-state within 6 days, suggesting that these DMRs are linked to early CSC epigenetic regulation. These DMRs were significantly enriched in genes coding for TGF-β signaling-related proteins. Interestingly, DMRs hypomethylation was correlated to an overexpression of TGF-β signaling genes in a series of 109 breast tumors. Moreover, patients with tumors harboring the bCSC DMRs signature had a worse prognosis than those with non-bCSC DMRs signature. Our results show that bCSCs have a distinct DNA methylation landscape with TGF-β signaling as a key epigenetic regulator of bCSCs differentiation.


The evolution of species recognition in competitive and mating contexts: the relative efficacy of alternative mechanisms of character displacement.
Sympatric divergence in traits affecting species recognition can result from selection against cross-species mating (reproductive character displacement, RCD) or interspecific aggression (agonistic character displacement, ACD). When the same traits are used for species recognition in both contexts, empirically disentangling the relative contributions of RCD and ACD to observed character shifts may be impossible. Here, we develop a theoretical framework for partitioning the effects of these processes. We show that when both mate and competitor recognition depend on the same trait, RCD sets the pace of character shifts. Moreover, RCD can cause divergence in competitor recognition, but ACD cannot cause divergence in mate recognition. This asymmetry arises because males with divergent recognition traits may avoid needless interspecific conflicts, but suffer reduced attractiveness to conspecific females. Therefore, the key empirical issue is whether the same or different traits are used for mate recognition and competitor recognition.


[Effect of afobazole on brain-ischemia-induced anxiety in rats].
The ability of afobazole, a selective anxiolytic to prevent the brain local ischemia-induced anxiety has been studied in experiments on rats. It is established that middle cerebral artery occlusion (MCAO) is accompanied by the development of anxiety, the degree of which increases with the duration of occlusion. Afobazole in a doze of 1 mg/kg administrated during 6 days after MCAO prevents the development of anxiety. The effect is manifested by positive changes in the parameters describing the behavior of animals in elevated plus maze test. No tolerance to the drug is developed during continuous afobazole injection within 12 days after MCAO. The experimental data indicate that the well-known anxiolytic action of afobazole is also well pronounced under the conditions of a local cerebrtal ischemia.


Concurrent Use of Cannabis and Alcohol: Neuropsychiatric Effect Consequences.
Concurrent use of cannabis and alcohol is frequent. According different studies, the prevalence is among 20-34% depending on different samples studied. In contrast with the wide evidence available about neuropsychiatric effects associated to the use of cannabis or alcohol separately, there are few studies of the neuropsychiatric effects of their combination. Our aim was to review the literature regarding this topic. We performed a search in MEDLINE and from 114 potentially eligible studies, 27 were selected. Most of them studied the relation between cannabis and alcohol, and with them combined to other substances of abuse, but only a few considered their concurrent effect among mental disorders (ADHD, bipolar disorder) and neuropsychological performance. More research in the neuropsychiatric effects of the concomitant use of cannabis and alcohol is needed.


Slide preparation method to preserve three-dimensional chromatin architecture of testicular germ cells.
During testicular germ cell differentiation, the structure of nuclear chromatin dynamically changes. The following describes a method designed to preserve the three-dimensional chromatin arrangement of testicular germ cells found in mice; this method has been termed as the three-dimensional (3D) slide method. In this method, testicular tubules are directly treated with a permeabilization step that removes cytoplasmic material, followed by a fixation step that fixes nuclear materials. Tubules are then dissociated, the cell suspension is cytospun, and cells adhere to slides. This method improves sensitivity towards detection of subnuclear structures and is applicable for immunofluorescence, DNA, and RNA fluorescence in situ hybridization (FISH) and the combination of these detection methods. As an example of a possible application of the 3D slide method, a Cot-1 RNA FISH is shown to detect nascent RNAs. The 3D slide method will facilitate the detailed examination of spatial relationships between chromatin structure, DNA, and RNA during testicular germ cell differentiation.


The conventional versus automated measurement of blood pressure in the office (CAMBO) trial: masked hypertension sub-study.
To determine the prevalence of masked hypertension [normal office blood pressure (BP) with high awake ambulatory BP] using automated office BP (AOBP) or conventional manual office BP (MOBP) measurement in routine clinical practice. The prevalence of masked hypertension was evaluated on three consecutive visits during a median 6 months period in patients with systolic hypertension randomized to management with AOBP (n = 140) or continued conventional MOBP (n = 112) in routine primary care practice. AOBP was recorded using the automated BpTRU device with the patient resting alone in a quiet examining room. All patients underwent 24-h ambulatory BP monitoring. The prevalence of masked hypertension on any one of three visits calculated using only SBP varied between 12 and 17% in the AOBP group compared with 19 and 22 % in the MOBP group. Masked hypertension was present on both of the first two visits in 7 and 12% and on all three visits in 6 and 7% of AOBP and MOBP patients, respectively. The prevalence for masked hypertension based upon both SBP and DBP was similar being 11-15% for AOBP and 19-20% for MOBP patients on single visits, but decreased to 6 and 10% when readings from the first two visits were used and to 4 and 6% when all three visits were used for the AOBP and MOBP groups, respectively. The prevalence of masked hypertension is lower with AOBP compared with MOBP. The number of patients with masked hypertension decreases if the criteria for having this condition need to be met on multiple visits.


Contrast encoding in retinal bipolar cells: current vs. voltage.
To investigate the influence of voltage-sensitive conductances in shaping light-evoked responses of retinal bipolar cells, whole-cell recordings were made in the slice preparation of the tiger salamander, Ambystoma tigrinum. To study contrast encoding, the retina was stimulated with 0.5-s steps of negative and positive contrasts of variable magnitude. In the main, responses recorded under voltage- and current-clamp modes were remarkably similar. In general agreement with past results in the intact retina, the contrast/response curves were relatively steep for small contrasts, thus showing high contrast gain; the dynamic range was narrow, and responses tended to saturate at relatively small contrasts. For ON and OFF cells, linear regression analysis showed that the current response accounted for 83-93% of the variance of the voltage response. Analysis of specific parameters of the contrast/response curve showed that contrast gain was marginally higher for voltage than current in three of four cases, while no significant differences were found for half-maximal contrast (C50), dynamic range, or contrast dominance. In sum, the overall similarity between current and voltage responses indicates that voltage-sensitive conductances do not play a major role in determining the shape of the bipolar cell's contrast response in the light-adapted retina. The salient characteristics of the contrast response of bipolars apparently arise between the level of the cone voltage response and the postsynaptic current of bipolar cells, via the transformation between cone voltage and transmitter release and/or via the interaction between the neurotransmitter glutamate and its postsynaptic receptors on bipolar cells.


Alterations in Rat Hippocampal Glutamatergic System Properties after Prolonged Febrile Seizures.
Febrile seizures during early childhood may result in central nervous system developmental disorders. However, the specific mechanisms behind the impact of febrile seizures on the developing brain are not well understood. To address this gap in knowledge, we employed a hyperthermic model of febrile seizures in 10-day-old rats and tracked their development over two months. Our objective was to determine the degree to which the properties of the hippocampal glutamatergic system are modified. We analyzed whether pyramidal glutamatergic neurons in the hippocampus die after febrile seizures. Our findings indicate that there is a reduction in the number of neurons in various regions of the hippocampus in the first two days after seizures. The CA1 field showed the greatest susceptibility, and the reduction in the number of neurons in post-FS rats in this area appeared to be long-lasting. Electrophysiological studies indicate that febrile seizures cause a reduction in glutamatergic transmission, leading to decreased local field potential amplitude. This impairment could be attributable to diminished glutamate release probability as evidenced by decreases in the frequency of miniature excitatory postsynaptic currents and increases in the paired-pulse ratio of synaptic responses. We also found higher threshold current causing hind limb extension in the maximal electroshock seizure threshold test of rats 2 months after febrile seizures compared to the control animals. Our research suggests that febrile seizures can impair glutamatergic transmission, which may protect against future seizures.


[Roles of protease-activated receptor-1 in thrombin-induced brain injury and neurogenesis in rats].
To investigate the roles of protease-activated receptors (PARs) in thrombin-induced brain injury and neurogenesis in rats. Ninety male SD rats were randomly assigned to receive intra-hippocampus injection of NS, thrombin or specific agonists of 3 protease-activated receptors (PAR-1, PAR-3 and PAR-4), respectively. At 1,3 and 7 d after injection, the area of the hippocampus was determined with HE staining, the density and morphology of astrocyte were detected with GFAP staining, degenerated neurons were detected with Fluoro-Jade C staining, and the neurogenesis was examined with DCX staining. Compared to NS injection, the area of the hippocampus significantly increased at 1-3 d and decreased at 7 d after the injection of thrombin and PAR-1 agonist (P<0.05). In addition, injection of thrombin and PAR-1 agonist significantly increased the density of astrocyte and Fluoro-Jade C positive cells at 1-7 d after injection (P<0.05), and significantly increased the density of DCX positive cells at 3-7 d after injection(P<0.05). The injection of PAR-3 agonist and PAR-4 agonist had no affect on the area of the hippocampus, the density of astrocyte, Fluoro-Jade C positive cells and DCX positive cells. The activation of protease-activated receptor-1 may be related to the thrombin-induced brain injury and neurogenesis in rat hippocampus.


Italian norms for the Freedman version of the Clock Drawing Test.
The Clock Drawing Test (CDT) is a valid screening tool for the evaluation of cognitive decline. This study aimed to compute standardized norms for the Freedman version of the CDT in a population of 248 healthy Italian individuals aged from 20 to 89 years. The effects of age, education, and gender on performance were assessed. Three conditions were administered: free-drawn clock (FD), which required participants to draw the contour, numbers, hands, and center of the clock; predrawn clock (PD), in which numbers, hands, and center had to be included in a predrawn contour; examiner-drawn clock (ED), in which only hands and center had to be inserted in a template including a predrawn contour and numbers. Scores for each of the single conditions and a total score were calculated. Age had no effect on the FD condition, whereas a significant effect of age was found for the PD and ED conditions and the total score. Gender and education had no influence on any of the scores. Correction grids, cutoffs, and equivalent scores were computed. Standardized norms for the Freedman version of the CDT were collected in a large sample of healthy individuals. No adjustments were required for scores on the free-drawn condition, whereas raw scores on the predrawn and examiner-drawn conditions and the total score needed adjustments to account for age effects. The availability of standardized norms for this version of the CDT could increase the use of this comprehensive tool in the detection of dementia.


Initial clinical experience with the modified Zenith "Pro-Form" TX2 thoracic endograft.
To assess the safety and efficacy of thoracic aortic endovascular repair (TEVAR) with the newly introduced Zenith TX2 thoracic stent-graft with Pro-Form. From March 2009 to present, the Zenith TX2 with Pro-Form was used to treat 27 patients (23 men; median age 65 years, range 22-77) suffering from descending thoracic aortic disease: 20 degenerative aneurysms, 3 chronic type B dissections, 2 type I endoleaks following previous endograft repair, 1 aortic ulcer, and 1 traumatic isthmic rupture. According to Ishimaru's classification, the distribution of the proximal landing zone was zone 0 in 4 cases, zone 1 in 2 cases, zone 2 in 9 cases, zone 3 in 7 cases, and zone 4 in 5 cases. One aneurysm distally involved the thoracoabdominal aorta. An acutely angulated (<90 degrees ) proximal landing zone was found in 9 patients. The device was safely and effectively deployed in all cases, with no problems during sheath retrieval. The postoperative course was free from major complications in all cases, and there was no perioperative mortality. Postoperative morbidity included respiratory failure in 1 case, transient acute renal failure in 3 cases, and post-implantation syndrome in 2 cases. Postoperative computed tomography at 1 and 6 months confirmed 100% clinical success with the absence of device-related complications. No type I endoleak was documented. The proximal sealing stent fitted well with the aortic profile in all cases except one, in which malapposition was seen in a severely angulated aorta at 6-month follow-up. Based on this preliminary experience, the TX2 thoracic stent-graft with Pro-Form can be safely and effectively deployed to satisfactorily repair thoracic aortic pathology, including lesions in the arch. Stent-graft conformance to the aorta was excellent even in cases with unfavorable anatomy. These encouraging results will need to be confirmed in larger series with larger follow-up.


Current and future utilization of services from medical oncologists.
There is limited information on the current use of oncologists and projections of future need. This analysis assesses current utilization patterns and projects the number of people with cancer and their use of oncologists' services through 2020. Data from the Surveillance, Epidemiology, and End Results cancer registries and Medicare physician claims were used to estimate oncologists' services from 1998 to 2003. We estimated the portion of patients with cancer who saw an oncologist, the mean number of visits, and the clinical setting where care was provided. Care was divided into initial, continuing, and last-year-of-life phases. Projections for future number of patients with cancer and visits were calculated by applying incidence and prevalence rates derived from Surveillance, Epidemiology, and End Results data to census population projections through 2020. The percentage of patients who saw an oncologist was 47% during the initial-care phase, 36% during the continuing-care phase, and 70% in the last year of life. The number of visits varied by age, sex, cancer site, and phase. The total number of cancer patients in the United States is projected to increase 55%, from 11.8 million in 2005 to 18.2 million in 2020. Total oncology visits are projected to increase from 38 million in 2005 to 57 million in 2020. Utilization of oncologists' services will increase appreciably between 2005 and 2020; this will be driven predominantly by an increase in survivors of cancer and by the aging of the population. The United States may face an acute shortage of medical oncologists if efforts are not taken to meet this growing need.


Upregulation of clusterin in prostate and DNA damage in spermatozoa from bisphenol A-treated rats and formation of DNA adducts in cultured human prostatic cells.
Among endocrine disruptors, the xenoestrogen bisphenol A (BPA) deserves particular attention due to widespread human exposure. Besides hormonal effects, BPA has been suspected to be involved in breast and prostate carcinogenesis, which share similar estrogen-related mechanisms. We previously demonstrated that administration of BPA to female mice results in the formation of DNA adducts and proteome alterations in the mammary tissue. Here, we evaluated the ability of BPA, given with drinking water, to induce a variety of biomarker alterations in male Sprague-Dawley rats. In addition, we investigated the formation of DNA adducts in human prostate cell lines. In BPA-treated rats, no DNA damage occurred in surrogate cells including peripheral blood lymphocytes and bone marrow erythrocytes, where no increase of single-strand DNA breaks was detectable by comet assay and the frequency of micronucleated cells was unaffected by BPA. Liver cells were positive at transferase dUTP nick end labeling assay, which detects both single-strand and double-strand breaks and early stage apoptosis. BPA upregulated clusterin expression in atrophic prostate epithelial cells and induced lipid peroxidation and DNA fragmentation in spermatozoa. Significant levels of DNA adducts were formed in prostate cell lines treated either with high-dose BPA for 24 h or low-dose BPA for 2 months. The BPA-related increase of DNA adducts was more pronounced in PNT1a nontumorigenic epithelial cells than in PC3 metastatic carcinoma cells. On the whole, these experimental findings support mechanistically the hypothesis that BPA may play a role in prostate carcinogenesis and may, potentially, affect the quality of sperm.


Congenital Spinal Cysts: An Update and Review of the Literature.
Congenital spinal cysts are rare and encompass a wide variety of diseases including arachnoid, enterogenous, teratomatous, neurenteric, foregut, bronchogenic, epithelial, ependymal, dermoid, and epidermoid cysts. Here, we elucidate the epidemiology, pathology, pathogenesis, and diagnostic findings of the most common congenital spinal cysts, followed by a discussion of their presentation and treatment options. Differentiating the cause of each lesion is crucial for targeted clinical and surgical management for the patient. Our review describes how arachnoid cysts can be observed, fenestrated, percutaneously drained, or shunted; however, the primary goal for neurenteric, dermoid, and epidermoid cysts is removal. Further, we discuss how patient presentation is dependent on the rate of growth and location of compression on the spinal cord and nerve roots. However, although many of these lesions are discovered incidentally on imaging, the spectrum of possible symptoms include pain, weakness, ataxia, bladder incontinence, and progressive or acute neurologic deficits. We present and review the histology and imaging of a variety of cysts and discuss how although the goal of treatment is resection, the risks of surgery must be considered against the benefits of complete resection in each case.


A report on the detection of placental acid phosphatase variants from Andhra Pradesh, South India.
850 placental extracts were screened to detect the placental acid phosphatase variants among a few population groups of Andhra Pradesh, South India. Two new electrophoretic patterns were encountered, one among the Brahmins and the other among the Muslims.


[Opioid peptides in the dynamics of "physiological" and "pathological" stress].
Clinical studies showed that short-term "physiological" stress (bicycle ergometry) did not cause increase of the blood plasma enkephalin content. Moderate-term (60-minute) stress, according to O. Desiderato, causes a rise of the blood enkephalin level in rats. It is supposed that such a reaction of the opioid system is characteristic of borderline conditions between normal and pathological states in stress. Severe "pathological" stress (myocardial infarction, experimental coronary occlusion, 6-hour stress after O. Desiderato) in rats led to a decrease of the concentration of enkephalins in the blood and disorders of their secretion and storage in the adrenals. It is suggested that changes of the activity of the opioid system are a predictor of the transition of a "physiological" stress to a "pathological" stress.


Functional Outcomes After Isolated and Combined Posterior Cruciate Ligament Reconstruction in a Military Population.
The rates of return to full activity, persistent disability, complications, and surgical revisions after operative management of posterior cruciate ligament (PCL) tears in a physically active population have not been reported. To evaluate the clinical outcomes of active military patients with symptomatic PCL tears who underwent surgical reconstruction and compare outcomes between isolated PCL and multiligament injuries. Cohort study; Level of evidence, 3. Individuals undergoing surgical reconstruction of the PCL (Current Procedural Terminology code 29889) were isolated from the Military Health System Management Analysis and Reporting Tool between fiscal years 2005 and 2010. Demographic variables and rates of postoperative complications, activity limitations, rates of revision surgery, physical disability ratings, and ultimate medical discharge were recorded from the electronic medical record and US Army Physical Disability Agency database. A total of 182 patients underwent 193 surgeries, including 118 isolated PCL reconstructions and 75 multiligament knee reconstructions, with an average follow-up of 19.5 months. There were 174 primary procedures and 19 revision reconstructions. The mean ± SD patient age was 28.4 ± 7.2 years, with males comprising 96.2% of patients. The overall surgical complication rate was 12.4%, with a significantly higher rate in multiligament knee reconstructions compared with isolated PCL reconstructions (18.7% vs 8.5%; P = .045). Overall, 35.1% of patients were discharged from military service due to disability. Rates of discharge were significantly higher in those undergoing surgery at lower volume institutions (those that performed <2 PCL reconstructions per year during the study period) than those at higher volume institutions (41.1% vs 26%; P = .040). The overall revision rate was 10.9%, with no significant difference between the isolated PCL and multiligament knee reconstructions. Of the 103 patients with primary isolated PCL reconstructions, 35% underwent medical discharge for persistent knee complaints, and 12.6% required revision PCL reconstruction. The overall failure rate for primary isolated PCL reconstructions, which includes both revision surgery and knee-related medical discharge from military service, was 42.7%. In a physically active, military population, nearly one-third of patients were unable to return to previous level of military function, and 12.6% required revision at short-term follow-up due to persistent instability. Perioperative complication rates were significantly higher among patients with multiligament knee reconstructions.


Intra- and extracellular distribution of an endogenous lectin during erythropoiesis.
An endogenous beta-galactoside-specific lectin has previously been isolated from rabbit bone marrow. The quantification of extracted lectin now indicates that approximately 75% of the lectin is intracellular in marrow. Indirect immunofluorescence studies show the extracellular lectin is associated with the erythroblast cell surface and is also found in some acellular areas of the marrow stroma. At enucleation, lectin surrounds the extruded nucleus while some residual lectin is observed in the cytoplasm of circulating reticulocytes and erythrocytes.


Apoptosis pattern and alterations of expression of apoptosis-related factors of supporting cells in Kölliker's organ in vivo in early stage after birth in rats.
Kölliker's organ is a temporary but indispensable structure in the development of the cochlea. Supporting cells (SCs) within it release adenosine 5'-triphosphate (ATP), which may play a crucial role in cochlear development before the onset of hearing. To reveal the apoptosis of Kölliker's organ in new-born rats, we studied the morphological changes and expression of apoptosis-related factors during early postnatal development. We found SCs in Kölliker's organ decreased in number and changed in appearance along the cochlea apex-to-base gradient, and the expression of caspase-3, caspase-8, caspase-9 and bcl-2 in Kölliker's organ of the cochlea fluctuated along the course of postnatal development, with an expression peak at postnatal day 3. This study demonstrates a time-dependent degeneration of Kölliker's organ during postnatal cochlea development, which might be triggered by endogenous factors.


Modulation by the BK accessory β4 subunit of phosphorylation-dependent changes in excitability of dentate gyrus granule neurons.
Large-conductance voltage- and calcium-activated potassium (BK) channels are large-conductance calcium- and voltage-activated potassium channels critical for neuronal excitability. Some neurons express so called fast-gated, type I BK channels. Other neurons express BK channels assembled with the accessory β4 subunit conferring slow gating of type II BK channels. However, it is not clear how protein phosphorylation modulates these two distinct BK channel types. Using β4-knockout mice, we compared fast- or slow-gated BK channels in response to changes in phosphorylation status of hippocampus dentate gyrus granule neurons. We utilized the selective PP2A/PP4 phosphatase inhibitor Fostriecin to study changes in action potential shape and firing properties of the neurons. In β4-knockout neurons, Fostriecin increases BK current, speeds up BK channel activation and reduces action potential amplitudes. Fostriecin increases spiking during early components of an action potential train. In contrast, inhibition of BK channels through β4 in wild-type neurons or by the BK channel inhibitor Paxilline opposes Fostriecin effects. Voltage clamp recordings of neurons reveal that Fostriecin increases both calcium and BK currents. However, Fostriecin does not activate BK α channels in transfected HEK293 cells lacking calcium channels. In summary, these results suggest that fast-gating, type I BK channels lacking β4 can increase neuronal excitability in response to reduced phosphatase activity and activation of calcium channels. By opposing BK channel activation, the β4 subunit plays an important role in moderating firing frequency regardless of changes in phosphorylation status.


CT Colonographic Screening of Patients With a Family History of Colorectal Cancer: Comparison With Adults at Average Risk and Implications for Guidelines.
The purposes of this study were to compare rates of lesion detection at CT colonographic (CTC) screening of adults without symptoms who had and who did not have a family history of colorectal cancer according to American Cancer Society guidelines and to consider the clinical implications. Over 134 months, consecutively registered CTC cohorts of adults without symptoms who had (n = 156; 88 [56.4%] women; 68 [43.6%] men; mean age, 56.3 years) and who did not have (n = 8857; 4757 [53.7%] women; 4100 [46.3%] men; mean age, 56.6 years) an American Cancer Society-defined family history of colorectal cancer (first-degree relative with diagnosis before age 60 years or two first-degree relatives with diagnosis at any age) were compared for relevant colorectal findings. For the family history versus no family history cohorts, the frequency of all nondiminutive polyps (≥ 6 mm) reported at CTC was 23.7% versus 15.5% (p = 0.007); small polyps (6-9 mm), 13.5% versus 9.1% (p = 0.068); and large polyps (≥ 10 mm), 10.2% versus 6.5% (p = 0.068). The rate of referral for colonoscopy was greater for the family history cohort (16.0% vs 10.5%; p = 0.035). However, the frequencies of proven advanced adenoma (4.5% vs 3.2%; p = 0.357), nonadvanced adenoma (5.1% vs 2.6%; p = 0.070), and cancer (0.0% vs 0.4%; p = 0.999) were not significantly increased. The difference in positive rates between the two cohorts (11.5% vs 4.3%; p < 0.001) was primarily due to nonneoplastic findings of no colorectal cancer relevance, such as small hyperplastic polyps, diverticular disease, and false-positive CTC findings. Although the overall CTC-positive and colonoscopy referral rates were higher in the family history cohort, the clinically relevant frequencies of advanced neoplasia and cancer were not sufficiently increased to preclude CTC screening. These findings support the use of CTC as a front-line screening option in adults with a family history of colorectal cancer.


gcpA (stm1987) is critical for cellulose production and biofilm formation on polystyrene surface by Salmonella enterica serovar Weltevreden in both high and low nutrient medium.
Biofilm formation by Salmonella is a serious concern in the food-processing industry and the persistence of the organism in biofilms becomes a constant source of contamination. Since there is zero tolerance for Salmonella in foods, it is important to understand the mechanism of biofilm formation and to prevent the formation. Therefore, this study aimed at investigating the biofilm-forming ability of seafood isolates of Salmonella enterica serovar Weltevreden (S. Weltevreden) under two different nutrient conditions (normal strength trypticase soy broth (TSB) and 1:100 diluted TSB). The role of cellulose production in biofilm formation and in the expression of multicellular behavior (rough, dark, red morphotype: rdar) was investigated. Fourteen isolates of seafood associated S. Weltevreden were studied for biofilm production in polystyrene microtitre plates. Only one (SW49) of 14 was a strong biofilm former on polystyrene template and was able to produce biofilm in both undiluted TSB and 1:100 diluted TSB at 24h. All others produced moderate or weak biofilms which was higher in 1:100 diluted TSB compared to undiluted medium. All the isolates except one were positive by PCR for the three genes, gcpA (stm1987), adrA (yaiC) and csgD. Gene expression of gcpA, adrA and csgD was studied by real-time PCR with the one strong (SW49) and one representative weak (SW30) biofilm former. In SW49 at 24h of incubation, the expression of gcpA from biofilm cells was 33 and 36 times higher than from planktonic cells grown in TSB and diluted TSB respectively and at 72h the expression from biofilm cells was 57 and 61 times higher than that from planktonic cells. Quantification of gene expression did not reveal any significant difference in the expression of csgD and adrA gene. Deletion of gcpA in SW49 resulted in its inability to produce cellulose and consequent inability to bind calcoflour, inability to form rdar colony on Congo Red-agar plates and failure to produce biofilm on polystyrene substrate. The data indicated that, in case of S. Weltevreden, gcpA is critical for activating cellulose synthesis and biofilm formation both in undiluted and diluted TSB. The results of this study suggest the existence of an alternative biofilm regulatory pathway in S. Weltevreden. Role of adrA in cellulose production in nutrient rich medium is known but role of gepA in the above phenomenon is proved in this study. An understanding of the genes involved would help in looking at strategies of repression of the gene to control formation of biofilm.


Variability in excess deaths across countries with different vulnerability during 2020-2023.
Excess deaths provide total impact estimates of major crises, such as the COVID-19 pandemic. We evaluated excess death trajectories across countries with accurate death registration and population age structure data and assessed relationships with vulnerability indicators. Using the Human Mortality Database on 34 countries, excess deaths were calculated for 2020-2023 (to week 29, 2023) using 2017-2019 as reference, with adjustment for 5 age strata. Countries were divided into less and more vulnerable; the latter had per capita nominal GDP < $30,000, Gini > 0.35 for income inequality and/or at least ≥2.5% of their population living in poverty. Excess deaths (as proportion of expected deaths, p%) were inversely correlated with per capita GDP (r = -0.60), correlated with proportion living in poverty (r = 0.66), and modestly correlated with income inequality (r = 0.45). Incidence rate ratio for deaths was 1.062 (95% CI, 1.038-1.087) in more versus less vulnerable countries. Excess deaths started deviating in the two groups after the first wave. Between-country heterogeneity diminished gradually within each group. Less vulnerable countries had mean p% = -0.8% and 0.4% in 0-64 and >65-y-old strata. More vulnerable countries had mean p% = 7.0% and 7.2%, respectively. Lower death rates were seen in children of age 0-14 y during 2020-2023 versus prepandemic years. While the pandemic hit some countries earlier than others, country vulnerability dominated eventually the cumulative impact. Half the analyzed countries witnessed no substantial excess deaths versus prepandemic levels, while the others suffered major death tolls.


An update on the pathophysiology of complex regional pain syndrome.
Complex regional pain syndrome (CRPS) is a neuropathic pain disorder with significant autonomic features. Few treatments have proven effective, in part, because of a historically poor understanding of the mechanisms underlying the disorder. CRPS research largely conducted during the past decade has substantially increased knowledge regarding its pathophysiologic mechanisms, indicating that they are multifactorial. Both peripheral and central nervous system mechanisms are involved. These include peripheral and central sensitization, inflammation, altered sympathetic and catecholaminergic function, altered somatosensory representation in the brain, genetic factors, and psychophysiologic interactions. Relative contributions of the mechanisms underlying CRPS may differ across patients and even within a patient over time, particularly in the transition from "warm CRPS" (acute) to "cold CRPS" (chronic). Enhanced knowledge regarding the pathophysiology of CRPS increases the possibility of eventually achieving the goal of mechanism-based CRPS diagnosis and treatment.


A new reportable disease is born: Taiwan Centers for Disease Control's response to emerging Zika virus infection.
Zika virus infection, usually a mild disease transmitted through the bite of Aedes mosquitos, has been reported to be possibly associated with microcephaly and neurologic complications. Taiwan's first imported case of Zika virus infection was found through fever screening at airport entry in January 2016. No virus was isolated from patient's blood taken during acute illness; however, PCR products showed that the virus was of Asian lineage closely related to virus from Cambodia. To prevent Zika virus from spreading in Taiwan, the Taiwan Centers for Disease Control has strengthened efforts in quarantine and surveillance, increased Zika virus infection diagnostic capacity, implemented healthcare system preparedness plans, and enhanced vector control program through community mobilization and education. Besides the first imported case, no additional cases of Zika virus infection have been identified. Furthermore, no significant increase in the number of microcephaly or Guillain- Barré Syndrome has been observed in Taiwan. To date, there have been no autochthonous transmissions of Zika virus infection.


Identification and quantitation of the components of polyvalent inactivated influenza virus vaccines by immunodiffusion.
One of the basic problems in the standardization of inactivated polyvalent influenza virus vaccines has been the determination of the relative potency of the individual strain components. The chicken cell agglutination test measures reliably the total hemagglutinin content of these vaccines. With immunodiffusion techniques, it is now possible to quantitate each strain component of polyvalent vaccines. Routine application of these techniques would serve as an interim procedure to assess antigenic potency of individual strain components of commercial vaccines until improved tests are developed.


Statins but not fibrates are associated with a reduced risk of venous thromboembolism: a hospital-based case-control study.
Previous studies of selected patients have suggested a reduction in the risk of venous thromboembolism with the use of statins. The objective of this study is to evaluate the influence of statin use on the risk of venous thromboembolic (VTE) events. The study is a case-control study (EDITH: Etude des Déterminants et Interactions de la Thrombose Veineuse), designed to investigate the genetic and environmental risk factors of VTE. A total of 377 patients consecutively hospitalized in the Brest University Hospital for a documented VTE event, between May 2000 and May 2002, and 377 age- and sex-matched controls were studied. Statin use was associated with a 58% decreased risk of VTE [odds ratio (OR) 0.42; 95% confidence interval (CI) 0.23-0.76; P = 0.002]. Adjustment for age, gender, coronary heart disease, atherosclerothrombotic disease or current use of aspirin did not alter the result. Neither fibrates (OR 1.38; 95% CI 0.76-2.52; P = 0.26), nor thienopyridines (OR 1.07; 95% CI 0.48-2.41; P = 0.85) were associated with a reduced risk of VTE. Aspirin use tended to decrease the risk of VTE, but this result was not significant (OR, 0.66; 95% CI, 0.42-1.05). The use of statins is associated with a significant reduction in the risk of VTE, irrespective of age, gender, and past history of atherosclerothrombotic disease, as well as the use of aspirin. This possible protective effect of statins warrants further investigations.


Optimizing functional outcome endpoints for stroke recovery studies.
Novel therapeutic intervention that aims to enhance the endogenous recovery potential of the brain during the subacute phase of stroke has produced promising results. The paradigm shift in treatment approaches presents new challenges to preclinical and clinical researchers alike, especially in the functional endpoints domain. Shortcomings of the "neuroprotection" era of stroke research are yet to be fully addressed. Proportional recovery observed in clinics, and potentially in animal models, requires a thorough reevaluation of the methods used to assess recovery. To this end, this review aims to give a detailed evaluation of functional outcome measures used in clinics and preclinical studies. Impairments observed in clinics and animal models will be discussed from a functional testing perspective. Approaches needed to bridge the gap between clinical and preclinical research, along with potential means to measure the moving target recovery, will be discussed. Concepts such as true recovery of function and compensation and methods that are suitable for distinguishing the two are examined. Often-neglected outcomes of stroke, such as emotional disturbances, are discussed to draw attention to the need for further research in this area.


The Effects of Running Compared with Functional High-Intensity Interval Training on Body Composition and Aerobic Fitness in Female University Students.
High-intensity interval running (HIIT-R) and high-intensity functional training (HIFT) are two forms of HIIT exercise that are commonly used. The purpose of this study was to determine the effects of HIFT on aerobic capacity and body composition when compared to HIIT-R in females. Twenty healthy, untrained female university students (age 20.5 ± 0.7 year) were randomly assigned to a 12-week HIIT-R or HIFT intervention. The HIIT-R group involved a 30 s maximal shuttle run with a 30 s recovery period, whereas the HIFT involved multiple functional exercises with a 2:1 work-active recovery ratio. Body composition, VO2max, and muscle performance were measured before and post intervention. As a result, HIIT-R and HIIT-F stimulated similar improvements in VO2max (17.1% ± 5.6% and 12.7% ± 6.7%, respectively, p > 0.05). Only the HIIT-F group revealed significant improvements in muscle performance (sit-ups, 16.5% ± 3.1%, standing broad jump 5.1% ± 2.2%, p < 0.05). Body fat percentage decreased (17.1% ± 7.4% and 12.6% ± 5.1%, respectively, p < 0.05) in both HIIT-R and HIIT-F with no between-group differences. We concluded that HIFT was equally effective in promoting body composition and aerobic fitness compared to HIIT-R. HIFT resulted in improved muscle performance, whereas the HIIT-R protocol demonstrated no gains.


Improvement in Strain Concordance between Two Major Vendors after the Strain Standardization Initiative.
Disagreement of strain measurements among different vendors has provided an obstacle to the clinical use of strain. A joint standardization task force between professional societies and industry was initiated to reduce intervendor variability of strain. Although feedback from this process has been used in software upgrades, little is known about the effects of efforts to improve conformity. The aim of this study was to assess whether intervendor agreement for global longitudinal strain (GLS) has improved after standardization initiatives. Eighty-two subjects (mean age, 52 ± 21 years; 55% men) prospectively underwent two sequential examinations using two most common ultrasound systems (Vivid E9 and iE33). GLS was calculated using proprietary software (EchoPAC-PC BT12 [E12] and BT13 [E13] vs QLAB version 8.0 [Q8], QLAB version 9.0 [Q9], and QLAB version 10.0 [Q10]). Agreements in GLS were evaluated with Bland-Altman plots. Coefficients of variation (CVs) were compared using the Friedman test and compared with CVs of left ventricular volumes and ejection fraction (LVEF). Median GLS using E12 was -19.2% (interquartile range [IQR], -15.2% to -23.2%), compared with -19.3% (IQR, -14.9% to -23.7%) for E13, -15.7% (IQR, -11.4% to -20%) for Q8, -19% (IQR, -15.7% to -22.3%) for Q9, and -18.7% (IQR, -15.7% to -21.7%) for Q10. The CVs of prestandardization GLS (12 ± 8% [E12/Q8] and 14 ± 8 [E13/Q8]) were significantly larger than that of LVEF (5 ± 5) (P < .001). Since standardization, the CVs of GLS have shown improvement (6 ± 4 [E12/Q9], 7 ± 4 [E12/Q10], 6 ± 4 [E13/Q9], and 7 ± 4 [E13/Q10]) and are similar to those of LVEF. Subsequent to the joint standardization task force, there has been improvement in between-vendor concordance in GLS between two leading ultrasound manufactures, the variability of which is now analogous to that of LVEF. The removal of concerns about measurement variability should allow wider use of GLS.


Design and fabrication of magnetically functionalized flexible micropillar arrays for rapid and controllable microfluidic mixing.
Magnetically functionalized PDMS-based micropillar arrays have been successfully designed, fabricated and implanted for controllable microfluidic mixing. The arrangement of PDMS micropillar arrays inside the microchannel can be flexibly controlled by an external magnetic field. As a consequence, the flow fields inside the microchannel can be regulated at will via magnetic activation conveniently. When a microchannel is implanted with such micropillar arrays, two microstreams can be mixed easily and controllably upon the simple application of an on/off magnetic signal. Mixing efficiencies based on micropillar arrays with different densities were investigated and compared. It was found that micropillar arrays with higher density (i.e. smaller pillar pitch) would render better mixing performance. Our microfluidic system is capable of generating highly reproducible results within many cycles of mixing/non-mixing conversion. We believe that the simple mixing-triggering method together with rapid and controllable mixing control will be extraordinarily valuable for various biological or chemical applications in the future.


The Applicability of a High-Intensity Functional Exercise Program Among Older People With Dementia Living in Nursing Homes.
Exercise programs for people with dementia need to be optimized. We therefore evaluated the applicability of a high-intensity functional exercise program among people with dementia in nursing homes with regard to attendance, achieved exercise intensity, adverse events, a focus on dementia type, and whether symptoms of dementia or other medical conditions common in this population were associated with program applicability. The Umeå Dementia and Exercise study, a cluster-randomized controlled trial set in 16 nursing homes in Umeå, Sweden. Ninety-three people with dementia (mean [SD] Mini-Mental State Examination score of 15.4 [3.4]) were randomized to the exercise intervention. Thirty-four participants had Alzheimer's disease (AD) and 59 non-Alzheimer's dementia (non-AD). High-Intensity Functional Exercise (HIFE) program was conducted in groups of 3 to 8 participants. Two physiotherapists led 5 sessions (45 minutes each) per fortnight for 4 months (total 40 sessions). Median attendance rate was 82.5%. Lower limb strength exercises were performed at high or medium intensity at a median interquartile range of 94.7% (77.8%-100%) of attended sessions. Participants with non-AD performed more sessions with high intensity in strength exercises than participants with AD (median interquartile range, 53.8% [25.7%-80%] vs 34.9% [2.02%-62.9%]; P = .035). Balance exercises were performed at high intensity at a median interquartile range of 75% (33.3%-88.6%). Adverse events (all minor and temporary, mostly musculoskeletal) occurred during the exercise sessions in 16% of attended sessions. Low motivation was the most common barrier for attendance. Buildup period, low motivation, and pain were common barriers for achieving high intensity in balance and strength exercises, and fear was a barrier in balance exercises. Of medical conditions, only behavioral and psychological symptoms of dementia, including apathy, were negatively associated with applicability. A group-based, supervised, and individualized high-intensity functional exercise program seems to be applicable with regard to attendance, achieved intensity, and adverse events during the exercise sessions, in people with mild to moderate dementia in nursing homes. Effective strategies to enhance motivation to participate in exercise, as well as prevention and treatment of pain and behavioral and psychological symptoms of dementia, are important when promoting exercise participation in this population.


Krüppel-like factor 4 is involved in functional differentiation of testicular Sertoli cells.
Krüppel-like factor 4 (KLF4) is a pleiotropic zinc finger transcription factor that regulates genes being involved in differentiation and cell-cycle control. Knockout studies revealed a critical function for KLF4 in the terminal differentiation of many epithelial cells. In testicular Sertoli cells, Klf4 is strongly inducible by the glycoprotein follicle stimulating hormone (FSH). Because KLF4 is essential for postnatal survival in mice, we deleted Klf4 specifically in Sertoli cells using the Cre/loxP system. Importantly, around postnatal day 18, a critical period of terminal Sertoli cell differentiation, mutant seminiferous tubules exhibited a disorganized germinal epithelium and delayed lumen formation. The ultrastructural finding of highly vacuolized Sertoli cell cytoplasm and the identification of differentially expressed genes, which are known to play roles during vesicle transport and fusion or for maintenance of the differentiated cell state, suggest impaired apical secretion of the Sertoli cell. Interestingly, a high proportion of all identified genes was localized in a small subregion of chromosome 7, suggesting coordinated regulation. Intriguingly, adult mutant mice are fertile and show normal testicular morphology, although the testosterone levels are decreased. In summary, KLF4 plays a significant role for proper and timely Sertoli cell differentiation in pubertal mice.


Utility of mammaglobin immunohistochemistry as a proxy marker for the ETV6-NTRK3 translocation in the diagnosis of salivary mammary analogue secretory carcinoma.
Mammary analogue secretory carcinoma is a recently described salivary gland neoplasm defined by ETV6-NTRK3 gene fusion. Mammary analogue secretory carcinoma's morphology is not entirely specific and overlaps with other salivary gland tumors. Documenting ETV6 rearrangement is confirmatory, but most laboratories are not equipped to perform this test. As mammary analogue secretory carcinomas are positive for mammaglobin, immunohistochemistry could potentially replace molecular testing as a confirmatory test, but the specificity of mammaglobin has not been evaluated across a large and diverse group of salivary gland tumors. One hundred thirty-one salivary gland neoplasms were evaluated by routine microscopy, mammaglobin immunohistochemistry, and ETV6 break-apart fluorescent in situ hybridization. The cases included 15 mammary analogue secretory carcinomas, 44 adenoid cystic carcinomas, 33 pleomorphic adenomas, 18 mucoepidermoid carcinomas, 10 acinic cell carcinomas, 4 adenocarcinomas not otherwise specified, 3 polymorphous low-grade adenocarcinomas, 3 salivary duct carcinomas, and 1 low-grade cribriform cystadenocarcinoma. All 15 mammary analogue secretory carcinomas harbored the ETV6 translocation and were strongly mammaglobin positive. None of the 116 other tumors carried the ETV6 translocation; however, mammaglobin staining was present in 1 (100%) of 1 low-grade cribriform cystadenocarcinoma, 2 (67%) of 3 polymorphous low-grade adenocarcinomas, 2 (67%) of 3 salivary duct carcinomas, 2 (11%) of 18 mucoepidermoid carcinomas, and 2 (6%) of 33 pleomorphic adenomas. Mammaglobin is highly sensitive for mammary analogue secretory carcinoma, but immunostaining can occur in a variety of tumors that do not harbor the ETV6 translocation. Strategic use of mammaglobin immunostaining has a role in the differential diagnosis of salivary gland neoplasms, but it should not be indiscriminately used as a confirmatory test for mammary analogue secretory carcinoma.


[Downs cephalometric analysis between juveniles of She and Han nationality in Lishui area of Zhejiang province].
To investigate the clinical normal values of juveniles with normal occlusions of She and Han nationality in Lishui area of Zhejiang province, and compare the craniofacial characteristics between She and Han nationality. Two hundred juveniles of She nationality and 200 juveniles of Han nationality with normal occlusion were recruited. Lateral cephalometric radiographs were taken, and Downs cephalometric analysis was performed. The data were compared using paired samples t test with SPSS 12.0 software package. There was no significant difference between males and females in the values of juveniles of both She and Han nationality. Compared to the male and female juveniles of Han nationality, MP-FH and U1-L1 of the She juveniles increased (P<0.05), while convexity decreased significantly (P<0.05). In addition, L1-MP of She female juveniles decreased significantly in comparison to that of Han female juveniles (P<0.05). There was no significant difference in other values between She and Han nationality. Compared to Han juveniles, She juveniles present an orthognathous and long face with vertical growth pattern. Sex differences are not apparent in juveniles of both She and Han nationality.


Validating a new methodology for optical probe design and image registration in fNIRS studies.
Functional near-infrared spectroscopy (fNIRS) is an imaging technique that relies on the principle of shining near-infrared light through tissue to detect changes in hemodynamic activation. An important methodological issue encountered is the creation of optimized probe geometry for fNIRS recordings. Here, across three experiments, we describe and validate a processing pipeline designed to create an optimized, yet scalable probe geometry based on selected regions of interest (ROIs) from the functional magnetic resonance imaging (fMRI) literature. In experiment 1, we created a probe geometry optimized to record changes in activation from target ROIs important for visual working memory. Positions of the sources and detectors of the probe geometry on an adult head were digitized using a motion sensor and projected onto a generic adult atlas and a segmented head obtained from the subject's MRI scan. In experiment 2, the same probe geometry was scaled down to fit a child's head and later digitized and projected onto the generic adult atlas and a segmented volume obtained from the child's MRI scan. Using visualization tools and by quantifying the amount of intersection between target ROIs and channels, we show that out of 21 ROIs, 17 and 19 ROIs intersected with fNIRS channels from the adult and child probe geometries, respectively. Further, both the adult atlas and adult subject-specific MRI approaches yielded similar results and can be used interchangeably. However, results suggest that segmented heads obtained from MRI scans be used for registering children's data. Finally, in experiment 3, we further validated our processing pipeline by creating a different probe geometry designed to record from target ROIs involved in language and motor processing.


Geometric graphs from data to aid classification tasks with Graph Convolutional Networks.
Traditional classification tasks learn to assign samples to given classes based solely on sample features. This paradigm is evolving to include other sources of information, such as known relations between samples. Here, we show that, even if additional relational information is not available in the dataset, one can improve classification by constructing geometric graphs from the features themselves, and using them within a Graph Convolutional Network. The improvement in classification accuracy is maximized by graphs that capture sample similarity with relatively low edge density. We show that such feature-derived graphs increase the alignment of the data to the ground truth while improving class separation. We also demonstrate that the graphs can be made more efficient using spectral sparsification, which reduces the number of edges while still improving classification performance. We illustrate our findings using synthetic and real-world datasets from various scientific domains.


Quantum theoretical study of cleavage of the glycosidic bond of 2'-deoxyadenosine: base excision-repair mechanism of DNA by MutY.
The enzyme adenine DNA glycosylase, also called MutY, is known to catalyze base excision repair by removal of adenine from the abnormal 2'-deoxyadenosine:8-oxo-2'-deoxyguanosine pair in DNA. The active site of the enzyme was considered to consist of a glutamic acid residue along with two water molecules. The relevant reaction mechanism involving different barrier energies was studied theoretically. Molecular geometries of the various molecules and complexes involved in the reaction, e.g., the reactant, intermediate, and product complexes as well as transition states, were optimized employing density functional theory at the B3LYP/6-31G(d,p) level in the gas phase. It was followed by single-point energy calculations at the B3LYP/AUG-cc-pVDZ, BHandHLYP/AUG-cc-pVDZ, and MP2/AUG-cc-pVDZ levels in the gas phase. Single-point energy calculations were also carried out at the B3LYP/AUG-cc-pVDZ and BHandHLYP/AUG-cc-pVDZ levels in aqueous media as well as in the solvents chlorobenzene and dichloroethane. For the solvation calculations, the integral equation formalism of the polarizable continuum model (IEF-PCM) was employed. It is found that glutamic acid along with two water molecules would effectively cleave the glycosidic bond of adenosine by a new two-step reaction mechanism proposed here which is different from the three-step mechanism proposed by other authors earlier regarding the working mechanism of MutY.


Determining the accuracy of an eye tracking system for laser refractive surgery.
Patient eye and head movements during laser refractive surgery may result in errors between the surgical beam position and the desired location for optimum correction. This, in turn, may lead to reduced postoperative vision, including increased higher order aberrations of the eye. Active eye tracking systems are often incorporated into laser delivery systems, which aim to reduce the effect of patient eye movement. In this study, the accuracy of an eye tracking system designed for laser refractive surgery was determined. An enucleated porcine eye was attached to a scanning device and the movement measured using the eye tracking system. The recorded position is compared to the preprogrammed position of the scanning device. The system demonstrated an accuracy of 0.06 m for an intact cornea and 0.1 mm for a cornea with a thin flap removed. This compares to an average decentration of ablation of 0.4 mm for patients relying on passive fixation, as measured by previous clinical trials. implementation of this eye tracker would lead to improved alignment between the laser and eye during laser refractive surgery.


Managing oncology research protocols.
Oncology research protocol management is important for the effective execution of clinical trials with oncology patients. Clinical trials explore investigational drug safety, efficacy, and effectiveness. Investigational drugs have not received approval for widespread use and marketing by the Food and Drug Administration (FDA). The National Cancer Institute (NCI) has several branches concerned with investigational drug procurement, distribution, and recordkeeping of investigational cancer chemotherapy agents. Before an investigational drug is approved by the FDA for marketing in the United States, it must undergo several phases of pre-clinical and clinical trials. The Institutional Review Board (IRB) must review and approve clinical trials to ensure that studies meet legal, ethical, and scientific standards. The principal investigator (PI) takes responsibility for the clinical trial. Informed consent must be obtained from subjects before they may participate in clinical trials. The informed consent form is reviewed by the IRB. The investigational drug storage, accountability, ordering, distribution, and drug information dissemination process is improved with a pharmacy-coordinated investigational drug service.


Comparison of symmetrical prism adaptation to asymmetrical prism adaptation in those with normal binocular vision.
This study sought to determine whether symmetrical compared to asymmetrical horizontal prisms (base-out or base-in) evoked different rates of phoria adaptation. Sixteen young adults with normal binocular vision participated in a symmetrical phoria adaptation experiment using a 3Δ base-out or 3Δ base-in binocular prism flipper and an asymmetrical phoria adaptation experiment using a 6Δ base-out or 6Δ base-in monocular wedge prism. The experiments were randomized and counterbalanced to reduce the influence of the prism stimulation order. Asymmetrical base-out prism adaptation was significantly faster than symmetrical prism adaptation for subjects with normal binocular vision. Asymmetrical phoria adaptation with base-in prism was not significantly different from symmetrical phoria adaptation implying that there are directional asymmetries (convergent versus divergent eye movements) in the slow fusional component of vergence. Data suggest that a potential interaction between the version system and the slow fusional vergence system may exist. Results have clinical relevance because patients with convergence or divergence insufficiency/excess may potentially show more pronounced differences between symmetrical and asymmetrical phoria adaptation compared to binocularly normal controls. These differences might also be relevant to clinical measurements such as vergence fusional range, which can be measured symmetrically (with Risley prisms in a phoroptor) or asymmetrically (with prism bar).


Nutritional indexes of clients in a maternity and infant care project. I. The target population.
The Detroit Maternity and Infant Care Project (DMICP) is funded under Title V of the Social Security Act. Records of 198 pregnant women and their infants seen by a project nutritionist in fiscal 1971-72 were studied. The women were predominantly young (below twenty years of age), black, and not enrolled in school. Most were pregnant for the first time. About a third were overweight. Mean scores on the APGAR scale for the infants at birth were high (7 to 10). More than half of these young mothers brought their infants to the project center for check-ups six to ten times during the first year.


Bartonella bovis Bermond et al. sp. nov. and Bartonella capreoli sp. nov., isolated from European ruminants.
Two novel species of Bartonella isolated from European ruminants are described. Bartonella capreoli sp. nov. was isolated from the blood of roe-deer (Capreolus capreolus) captured in Chizé, France. The type strain is IBS 193T (= CIP 106691T = CCUG 43827T). It is distinct from another European ruminant isolate that originated from a cow from a French herd of 430 dairy cattle. The latter isolate belongs to a novel species named Bartonella bovis Bermond et al. sp. nov. The type strain is strain 91-4T (= CIP 106692T = CCUG 43828T). The two bacteria appeared as small, fastidious, aerobic, oxidase-negative, gram-negative rods. Their biochemical properties were similar to those of members of the genus Bartonella. The sequences of the 16S rRNA and citrate synthase genes obtained from the two type strains were highly related to sequences of the different Bartonella species. Hybridization values when testing type strains of recognized Bartonella species, obtained with the nuclease/trichloroacetic acid method, support the creation of two novel species.


Factors influencing participation in an Ebola vaccine trial among front-line workers in Guinea.
Alongside the clinical aspects of the immunogenicity and safety trial of an Ebola vaccine deployed among front-line workers, a qualitative study was conducted to describe motivations behind individuals' decisions to participate - or not to participate - in the study. In July and August 2015, focus group discussions and semi-structured individual interviews were conducted in Conakry, Guinea. Individuals were eligible for the qualitative study if they met the inclusion criteria of the immunogenicity and safety study irrespective of their participation. Surveys were also conducted among several institution and department heads of staff included in the study as well as vaccine trial staff members. Discussion and interview transcripts were analyzed using content thematic analysis. Interviews and focus groups were conducted among 110 persons, of whom about two-thirds (67%) participated in the vaccine trial. There was at least one group interview conducted at each participating trial site, along with numerous formal and informal interviews and conversations through the enrollment period. Participants were often motivated by a desire to save and protect themselves and others, contribute to scientific progress, or lead by example. Non-participants expressed concerns regarding the risk and costs of participation, particularly the fear of unknown side effects following vaccination, and distrust or fear of stigmatization. Despite the unique nature of the 2014-2015 Ebola outbreak, front-line workers employed much of the same logic when choosing to participate as in other clinical trials in similar settings. Special consideration should be given to addressing perceived inequity, misunderstanding, and mistrust among the target populations in future trials. Clinical trial registry number: This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193.


Retinoic acid co-treatment aggravates severity of dioxin-induced skin lesions in hairless mice via induction of inflammatory response.
Exposure to toxic halogenated polyaromatic hydrocarbons, of which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent, induces diverse skin pathologies in humans, including chloracne, hyperkeratosis, hamartomas, etc. While the toxic effects of TCDD have been extensively studied, effective approaches to their treatment are still lacking. Retinoids are commonly used in therapy of acneiform skin diseases. In vitro, retinoids elicit antagonistic effects on keratinocyte differentiation and proliferation, as compared to TCDD, suggesting their potential in treatment of TCDD-induced skin lesions. Nevertheless, the modulation of TCDD activity in skin by retinoids in vivo was never reported. We have used N-TERT keratinocyte cell line and hairless (hr) mice to determine if retinoic acid (RA) can lessen or reverse TCDD-induced effects in vitro and in vivo. RA co-treatment suppressed TCDD-induced changes in the expression of differentiation-associated genes and N-TERT keratinocyte viability in vitro. However, in hairless mice (in vivo), RA/TCDD co-treatment produced more severe effects, than treatment with either of the two compounds individually. RA/TCDD co-application to mouse skin strongly stimulated keratinocyte proliferation, resulting in dramatic epidermal hyperplasia. It has also led to massive immune cell infiltration into the dermis, and increased mRNA expression of inflammation markers, including IL1β, IL6 and S100A7. Thus, retinoids not only appeared ineffective in treatment of TCDD-induced skin lesions in hairless mice, but also resulted in their exaggeration. These in vivo results question previous cell culture-based claims that RA may reduce TCDD-induced skin effects and caution against the reliance on in vitro data in TCDD toxicology research.


[Second solid tumors in childhood. Review based on three cases].
As children with cancer survive longer, the incidence of second malignant neoplasms has increased considerably. We describe here three cases of second solid tumors after 12, 8 and 2 years of initial diagnosis of cancer: one osteosarcoma of left maxilla in a previously treated child with bilateral retinoblastoma, a temporal astrocytoma associated with acute lymphoblastic leukemia and a glioblastoma multiforme in a girl with neurofibromatosis de Von Recklinghausen, after Non Hodgkin lymphoma, respectively. We review the literature about the influence of genetic, immunologic and therapeutic factors involved in the appearance of these second tumors.


Mapping determinants of variation in energy metabolism, respiration and flight in Drosophila.
We employed quantitative trait locus (QTL) mapping to dissect the genetic architecture of a hierarchy of functionally related physiological traits, including metabolic enzyme activity, metabolite storage, metabolic rate, and free-flight performance in recombinant inbred lines of Drosophila melanogaster. We identified QTL underlying variation in glycogen synthase, hexokinase, phosphoglucomutase, and trehalase activity. In each case variation mapped away from the enzyme-encoding loci, indicating that trans-acting regions of the genome are important sources of variation within the metabolic network. Individual QTL associated with variation in metabolic rate and flight performance explained between 9 and 35% of the phenotypic variance. Bayesian QTL analysis identified epistatic effects underlying variation in flight velocity, metabolic rate, glycogen content, and several metabolic enzyme activities. A region on the third chromosome was associated with expression of the glucose-6-phosphate branchpoint enzymes and with metabolic rate and flight performance. These genomic regions are of special interest as they may coordinately regulate components of energy metabolism with effects on whole-organism physiological performance. The complex biochemical network is encoded by an equally complex network of interacting genetic elements with potentially pleiotropic effects. This has important consequences for the evolution of performance traits that depend upon these metabolic networks.


Outcome of psychiatric intervention in factitious illness by proxy (Munchausen's syndrome by proxy).
To determine the outcome for children after psychiatric intervention in cases of factitious illness by proxy. All 17 children from 16 families, selected for admission to the Park Hospital Oxford family unit 1992-96 were followed up after a mean of 27 months. Information was obtained on the children and their carers from general practitioners, social workers or both; 13 of the children and carers were interviewed. All patients were at the severe end of the abuse spectrum; 12 involving direct induction of illness, 1 tampering with samples to mimic illness, and 4 fabrication of symptoms. The biological mother was the abuser in all cases. Four children and their parents had been initially admitted for assessment, and 13 for treatment to decide whether family reunification was viable. The 4 assessments clarified diagnosis, enabling improved care plans to be made. Of the 13 treatment cases, 10 were reunited with parents after a mean of 71/2 weeks' admission, whereas 3 were discharged to out of home care. There was a further episode of induced illness in 1 of the reunited children. Although some mothers had continuing mental health difficulties, only 1 of the other reunited cases had appreciable parent-child relationship difficulties (not requiring referral to psychiatric services). The children did well in their development, growth, and adjustment. Family reunification is feasible for certain cases, but long term follow up is necessary to ensure the child's safety and to identify deterioration in parent's mental health. The outcome for reunited children compared well with reported untreated cases.


Geographical Variations and Factors Associated with Childhood Diarrhea in Tanzania: A National Population Based Survey 2015-16.
Diarrhea remains the leading cause of morbidity and mortality among under 5 children in low- and middle-income countries. In Tanzania, diarrhea remains one of the major public health problems. This study aimed to investigate spatial variations and the factors correlated with diarrhea in under five children. This is a secondary data analysis using data from the population-based cross section Tanzanian Demographic and Health Survey 2015-16 data. Spatial analysis was done using the Bernoulli model from SaTScan™ software, and a generalized linear mixed model was used to identify the factors associated with childhood diarrhea. The overall reported prevalence of childhood diarrhea for the under five children in Tanzania was 12.1% (95%CI 11.3%-12.9%). The SaTScan spatial statics analysis revealed that diarrhea in children was not random. The odds of diarrhea were 7.35 times higher (AOR= 7.35; 95%CI: 5.29, 10.22) among children in the 6-11 months age group compared to children within the 48-59 months of age. As mother's age increased, the risk of diarrhea for the under five children decreased whereas the highest risk of diarrhea was observed in the two rich income brackets richer (AOR=1.70, 95%CI=1.30, 2.22), and richest (AOR= 1.05, 95%CI=1, 1.09). The odds of diarrhea were 1.25 times higher (AOR=1.25, 95%CI=1.06, 1.46) among children with unsafe stool disposal compared to those with safe disposal. The socio-demographic factors associated with diarrhea among children were mother's age in years, current age of the child, wealth index and child stool disposal.


[Valeriana officinalis and Crataegus oxyacantha: toxicity from repeated administration and pharmacologic investigations].
The aim of this work is to study the toxicity of Valeriana officinalis and Crataegus oxyacantha after reiterated administrations. The study has been carried on the rat which received 300 and 600 mg/kg/24 h of the drugs for 30 days. During the period of the treatment, animals weight and blood pressure have been measured. On the end of the treatment the animals have been sacrificed. The principal organs have been weighed and in blood samples collected hematological and biochemical parameters have been determined. This work is concerned by pharmacological properties which are related to the two plants. The influence of the drugs on the behaviour, the pain, the intestinal peristalsis and strychnine convulsions are reported.


Two mitochondrial lineages in Korean freshwater Corbicula (Corbiculidae: bivalvia).
The Korean freshwater Corbicula was surveyed genetically by sequencing 614-bp homologous fragment of mitochondrial cytochrome oxidase I subunit. Among a total of 127 individuals collected from 12 Korean freshwater localities we found only two COI haplotypes and these differed by a total of 9 base substitutions. Although the sequence divergence between the two haplotypes is moderate (p = 1.47%), placing the two mitotypic sequences in the context of Asian mtDNA phylogeny reveals that Korean freshwater Corbicula is comprised of two independent freshwater mitochondrial lineages. These results are in serious disagreement with the long-standing conclusions of earlier conchology-based taxonomic work on Korean Corbicula in which a number of species names (a minimum of 10 nominal species) have been used. This indicates that morphological characteristics alone are poor criteria for species-level identification in this group. In addition, our COI dataset shows that there is an extremely low level of genetic variation in Korean freshwater populations, suggesting that these populations have passed through a severe population bottleneck that greatly reduced their genetic variability. Our data also provide new information on the biogeographic distribution of Korean freshwater Corbicula. When haplotypic frequencies were compared, it was evident that the two Korean freshwater mitochondrial lineages have achieved very different distribution ranges: the predominant lineage (FWKR1) is widely distributed in Korean freshwater systems, whereas the minor lineage (FWKR2) is restricted to a relatively narrow range.


The impact of pretrial publicity on mock juror and jury verdicts: A meta-analysis.
We updated and extended a meta-analysis on pretrial publicity (PTP) conducted by Steblay et al. (1999) by reexamining the effect of negative (antidefendant) PTP on individual (juror) and deliberating group (jury) verdicts and the effect of positive (pro-defendant) PTP on individual verdicts. We hypothesized that exposure to negative PTP would increase guilty verdicts from both jurors and juries, whereas exposure to positive PTP would decrease guilty verdicts. We predicted that the relationship between negative PTP and juror verdicts would vary according to methodological and theoretical variables. For methodological variables, we hypothesized that published studies, community-member participants, and crime-related comparison conditions would have a stronger PTP effect. For theoretical variables related to the story model, source monitoring bias, and predecisional distortion, we predicted that the effect of PTP would be stronger with more serious crimes, longer time delays, greater amounts of PTP, and more-severe PTP. We analyzed 77 unique effect sizes extracted from 27 published and 18 unpublished reports based on 11,240 individual participants. Negative PTP increased juror guilty verdicts (r = .16) and jury verdicts (r = .35), whereas positive PTP decreased guilty verdicts (r = -.21). Moderator analyses revealed that negative PTP's effect on juror verdicts was stronger for published studies, student participants, and unrelated crime or no additional information control groups. Additionally, the biasing effect of negative PTP was stronger for nonviolent crimes, trial delays of less than 1 week, PTP presented in one article with multiple facts, and moderate-severity PTP. PTP has a modest biasing effect when it favors or disfavors the defendant. Nonetheless, the impact of negative PTP on individuals varies according to studies' methodological variables and variables theoretically related to the mechanism underlying PTP's biasing effect. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Synergistic activation of innate immunity by double-stranded RNA and CpG DNA promotes enhanced antitumor activity.
Double-stranded RNA (dsRNA) and unmethylated CpG sequences in DNA are pathogen-associated molecular patterns of viruses and bacteria that activate innate immunity. To examine whether dsRNA and CpG DNA could combine to provide enhanced stimulation of innate immune cells, murine macrophages were stimulated with poly-rI:rC (pIC), a dsRNA analog, and CpG-containing oligodeoxynucleotides (CpG-ODN). Combined treatments demonstrated synergy in nitric oxide, interleukin (IL)-12, tumor necrosis factor alpha, and IL-6 production. Studies using neutralizing antibodies for type I interferons (IFNs), IFN-alpha and IFN-beta, indicated that nitric oxide synthase synergism is mediated by paracrine/autocrine effects of IFN-beta. In contrast, enhanced cytokine production occurred independent of type I IFN and was maintained in macrophages from IFN-alpha/beta receptor knockout mice. Cotransfection of human Toll-like receptors 3 and 9 (receptors for dsRNA and CpG DNA, respectively) into 293T cells supported synergistic activation of an IL-8 promoter reporter construct by pIC, indicating interaction of the signaling pathways in driving the synergy response. In vivo stimulation of mice with pIC and CpG-ODN demonstrated synergy for serum IL-6 and IL-12p40 levels that correlated with an enhanced antitumor effect against established B16-F10 experimental pulmonary metastases. Treatment of tumor-bearing mice with pIC and CpG-ODN in combination resulted in enhanced nitric oxide synthase expression in lung tissue and enhanced up-regulation of class I major histocompatibility complex on splenic dendritic cells relative to treatments with either agent alone. In conclusion, the combined detection of viral pathogen-associated molecular patterns, i.e., dsRNA and CpG DNA, may mimic definitive viral recognition, resulting in an enhanced innate immune response that could be used for tumor vaccination or immunotherapy.