Lumbar Spinal Surgery in Patients With Parkinson Disease: A Multicenter Retrospective Study.
A multicenter, retrospective study. To identify the factors that affect surgery-related complications and to clarify the surgical strategy for treating lumbar disorders in Parkinson disease (PD). Previous studies have reported a high complication rate for spinal surgery in patients with PD. Because of the limited number of studies, there are no guidelines for spinal surgery for PD patients. We retrospectively reviewed the records for 67 PD patients who underwent lumbar spinal surgery. The patients were divided into 3 groups: 12 patients underwent laminectomy (Laminectomy), 24 underwent fusion surgery (Fusion) for lumbar canal stenosis, and 31 underwent corrective surgery for spinal deformity (Deformity). We assessed surgery-related complications in each group. The Cox proportional hazards model was used to identify the factors that predicted surgical failure. The percentages of patients who experienced failure of the initial surgery were 33.3% in the Laminectomy group, 45.8% in the Fusion group, and 67.7% in the Deformity group. The rates of implant failure were high in the Fusion and Deformity groups (33.3% and 38.7%, respectively). The Deformity group had a high rate of postoperative fracture (41.9%). These complications occurred at the most caudal site within a year after surgery and resulted in progression of kyphotic deformity. Multivariate analysis revealed that preoperative lumbar lordosis angle (LL) (per -1 degree) was associated with a failure of the initial surgery (hazard ratio, 1.024; 95% confidence interval, 1.008-1.04; P=0.003). We have demonstrated that a small preoperative LL increases the risk for failure of the initial surgery. Attaining and maintaining the proper lumbar lordosis with rigid fixation may be necessary in PD patients with a small preoperative LL.


Passive immunization protects the mouse eye from damage after herpes simplex virus infection by limiting spread of virus in the nervous system.
Mice were treated with serum containing antibodies to herpes simplex virus type 1 (HSV-1) or normal serum, 1 day before inoculation on the cornea with HSV-1 strain McKrae. As expected, without passive immunization, mice developed high levels of serum neutralizing antibody. By contrast, in passively immunized animals, such antibody became undetectable by 29 days after inoculation of serum, in spite of the virus infection. There was no difference between passively immunized mice and those given normal serum in the duration of shedding of virus in tears and the duration and severity of corneal epithelial disease. However, non-immunized mice had a high incidence of mortality and developed disease of the iris, corneal stroma and lids, and their corneas became opaque and vascularized. In non-immunized animals, the timing of isolation of virus from nervous tissues and the sequence of appearance of virus antigens in ocular tissues indicate that the disease of deeper eye tissue was caused by virus spreading from the nervous system back to the eye. Restriction of such spread in passively immunized animals seems the likely explanation for their protection from death and severe ocular damage. Despite this restricted spread, passively immunized animals had a high incidence of latent infection in the ophthalmic part of the trigeminal ganglion. However, in comparison with mice given normal serum, there was a far lower incidence of such infection in the other two parts of this ganglion and in the superior cervical ganglion. Since passively immunized animals have a high incidence of latent infection in the ophthalmic part of the trigeminal ganglion and their eyes are normal, they will prove useful in studies involving induction of recurrent disease.


Trends in out-of-hospital deaths due to coronary heart disease in Sweden (1991 to 2006).
Case fatality associated with a first coronary event is often underestimated when only those who survive to reach a hospital are considered. Few studies have examined long-term trends in case fatality associated with a major coronary event that occurs out of the hospital. Record linkage documented all case subjects 35 to 84 years of age in Sweden during 1991 to 2006 with a first major coronary event (out-of-hospital coronary death or hospitalization for acute myocardial infarction). Of the 384 597 cases identified, 111 319 (28.9%) died out of the hospital, and another 36 552 (9.5%) died in the hospital or within 28 days of hospitalization. From 1991 to 2006, out-of hospital deaths as a proportion of all major coronary events declined from 30.5% to 25.6% (adjusted mean annual decrease 2.2%, 95% confidence interval 2.1% to 2.4%), however, with a larger decline in 28-day case fatality in hospitalized cases (adjusted mean annual decrease 5.8%, 95% confidence interval 5.5% to 6.0%). As a result of the faster decline in in-hospital deaths, the relative contribution of out-of-hospital deaths to overall case fatality increased, particularly among younger individuals (eg, among those 35 to 54 years of age, no more than 10.8% of all deaths occurred in hospitalized cases during 2003-2006). Although female sex (odds ratio 0.85, 95% confidence interval 0.83 to 0.87) and older age (odds ratio 0.972, 95% confidence interval 0.971 to 0.974 per year) were associated with lower risk for initial out-of-hospital death, each successive calendar year was associated with increased risk (odds ratio 1.041, 95% confidence interval 1.038 to 1.044). The great majority of all fatal coronary events occur outside the hospital, and this proportion is increasing, particularly among younger individuals.


Ostomy or intestinal anastomosis in cases of peritonitis.
Twenty-six patients showing peritonitis due to nontraumatic acute abdomen were submitted to ostomy. Mean age was 51 years (range 25-83), being 13 males and 13 females. Bowel obstruction (BO) was the most frequent cause of peritonitis (11 cases), followed by intestinal perforation (IP) (8 cases), acute mesenteric infarction (AMI) (5 cases), and acute abdomen of inflammatory/infectious origin (AAIO) (2 cases). Brook's ileostomy was performed on 65% of the patients. Jejunostomy was performed only in 4 patients, leading to a bad evolution. Overall mortality was 54%. Primary ostomy or anastomosis in cases of peritonitis constitute a highly controversial theme. Indications and problems involving the intestinal exteriorization in emergency surgery urgency are herein discussed.


Pax3- and Pax7-mediated Dbx1 regulation orchestrates the patterning of intermediate spinal interneurons.
Transcription factors are key orchestrators of the emergence of neuronal diversity within the developing spinal cord. As such, the two paralogous proteins Pax3 and Pax7 regulate the specification of progenitor cells within the intermediate neural tube, by defining a neat segregation between those fated to form motor circuits and those involved in the integration of sensory inputs. To attain insights into the molecular means by which they control this process, we have performed detailed phenotypic analyses of the intermediate spinal interneurons (IN), namely the dI6, V0D, V0VCG and V1 populations in compound null mutants for Pax3 and Pax7. This has revealed that the levels of Pax3/7 proteins determine both the dorso-ventral extent and the number of cells produced in each subpopulation; with increasing levels leading to the dorsalisation of their fate. Furthermore, thanks to the examination of mutants in which Pax3 transcriptional activity is skewed either towards repression or activation, we demonstrate that this cell diversification process is mainly dictated by Pax3/7 ability to repress gene expression. Consistently, we show that Pax3 and Pax7 inhibit the expression of Dbx1 and of its repressor Prdm12, fate determinants of the V0 and V1 interneurons, respectively. Notably, we provide evidence for the activity of several cis-regulatory modules of Dbx1 to be sensitive to Pax3 and Pax7 transcriptional activity levels. Altogether, our study provides insights into how the redundancy within a TF family, together with discrete dynamics of expression profiles of each member, are exploited to generate cellular diversity. Furthermore, our data supports the model whereby cell fate choices in the neural tube do not rely on binary decisions but rather on inhibition of multiple alternative fates.


Aplysia californica neurons R3-R14: primary structure of the myoactive histidine-rich basic peptide and peptide I.
The R3-R14 neurons of the marine mollusc Aplysia are neuroendocrine cells that express a gene encoding peptides I, II and histidine-rich basic peptide (HRBP), a myoactive peptide that excites Aplysia heart and enhances gut motility in vitro. Peptide II has been chemically characterized (35), but the complete primary structures of peptide I and HRBP have not been established by amino acid sequence analysis. HRBP, peptide I, and the prohormone (proHRBP) were therefore purified from acid extracts of Aplysia californica neural tissue using sequential gel filtration and reverse-phase high-performance liquid chromatography and chemically characterized. Amino acid sequence analysis demonstrated that HRBP was a 43-residue peptide whose sequence was: less than Glu-Val-Ala-Gln-Met-His-Val-Trp-Arg-Ala-Val-Asn-His-Asp-Arg-Asn-His-Gly- Thr-Gly - Ser-Gly-Arg-His-Gly-Arg-Phe-Leu-Ile-Arg-Asn-Arg-Tyr-Arg-Tyr-Gly-Gly-Gly- His-Leu - Ser-Asp-Ala-COOH. Compositional and sequence analyses of peptide I and proHRBP demonstrated that peptide I was a 26-residue peptide with the following sequence: NH2-Glu-Glu-Val-Phe-Asp-Asp-Thr-Asp-Val-Gly-Asp-Glu-Leu-Thr-Asn-Ala- Leu-Glu-Ser-Val-Leu-Thr-Asp-Phe-Lys-Asp-COOH. These results demonstrated that the pro-HRBP sequence predicted by nucleotide sequence analysis of a cDNA clone (24) was in fact synthesized in R3-R14 neurons. Hydrophilicity and hydrophobicity profiles of preproHRBP, combined with charge distribution profiles and predictive secondary structural analysis, showed that cleavage at dibasic sequences was strongly associated with peaks of hydrophilicity in alpha-helical regions of the preprohormone.


Social communication intervention effects vary by dependent variable type in preschoolers with autism spectrum disorders.
Individuals with autism spectrum disorders (ASDs) have difficulty communicating in ways that are primarily for initiating and maintaining social relatedness (i.e., social communication). We hypothesized that the way researchers measured social communication would affect whether treatment effects were found. Using a best evidence review method, we found that treatments were shown to improve social communication outcomes approximately 54% of the time. The probability that a treatment affected social communication varied greatly depending on whether social communication was directly targeted (63%) or not (39%). Finally, the probability that a treatment affected social communication also varied greatly depending on whether social communication as measured in (a) contexts very similar to treatment sessions (82%) or (b) contexts that differed from treatment on at least setting, materials, and communication partner (33%). This paper also provides several methodological contributions.


Airway remodelling in the pathogenesis of asthma.
The inflammatory and remodelling processes that underlie asthma result from a highly complex interaction between various cell types. Apart from inflammatory cells, such as eosinophils, activated T cells, mast cells and macrophages, structural tissue cells such as epithelial cells, fibroblasts and smooth muscle cells can also play an important effector role through the release of a variety of mediators, cytokines and chemokines. This results in an acute inflammatory response that is characterized by vascular leakage, mucus hypersecretion, epithelial shedding and widespread airway narrowing. At the same time, through the release of mediators, cytokines, chemokines and growth factors, epithelial and mesenchymal cells cause persistence of the inflammatory infiltrate and induce structural changes in the airway wall, such as increased thickness of the basement membrane, increased collagen deposition, changes in bronchial microcirculation, and smooth muscle hypertrophy and hyperplasia. The end result of airway inflammation and remodelling is an increased thickness of the airway wall, leading to a reduced baseline airway calibre and exaggerated airway narrowing.


Occupational exposure to natural UV radiation and premature skin ageing.
The skin is the part of the human body most vulnerable to ultraviolet (UV) radiation. The spectrum of the negative effects of UV radiation on the skin ranges from acute erythema to carcinogenesis. Between these extreme conditions, there are other common skin lesions, e.g., photoageing. The aim of this study was to assess the skin for signs of photoageing in a group of 52 men occupationally exposed to natural UV radiation. There were 2 types of examinations: an examination of skin condition (moisture, elasticity, sebum, porosity, smoothness, discolourations and wrinkles) with a device for diagnosing the skin, and a dermatological examination. The results of both examinations revealed a higher percentage of skin characteristics typical for photoageing in outdoor workers compared to the general population.


Passive Exoskeleton-Assisted Gait Shows a Unique Interlimb Coordination Signature Without Restricting Regular Walking.
Exoskeleton assistive devices have been developed as a potential approach to solve gait deficits like paretic propulsion and reduced speed. However, it is unclear how these devices affect inter-limb coordination. The duration and the synchrony of gait coordination was assessed during passive exoskeleton-assisted walking in healthy young individuals. It was hypothesized that inter-limb coordination would be reduced in comparison to normal walking without assistance, thus demonstrating gait with exoskeleton to be more explorative and flexible. Eighteen participants were divided into two groups (EXO: n = 9; NO EXO: n = 9) and performed a 5-min walking trial at a preferred walking speed after a familiarization trial. The duration of inter-limb coordination was examined using cross-recurrence quantification analysis and the synchrony was measured using cross sample entropy. There were no significant differences in spatiotemporal measurements between the two groups. However, in comparison to the no exoskeleton group, there was a reduction in the duration of coordination (mean diagonal length: p < 0.01) and the synchrony of coordination (entropy value: p < 0.05) in the exoskeleton group. These results indicate that exoskeletal-assisted gait is characterized by reduced inter-limb coordination possibly for allowing gait patterns to be more explorative and flexible. This is important in rehabilitation of patients who suffer from coordination deficits.


[Clinical characteristics and prognosis of 28 cases of infant acute lymphoblastic leukemia].
Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.


High-throughput immunophenotypic characterization of bone marrow- and cord blood-derived mesenchymal stromal cells reveals common and differentially expressed markers: identification of angiotensin-converting enzyme (CD143) as a marker differentially expressed between adult and perinatal tissue sources.
Mesenchymal stromal cells (MSC) are a heterogeneous population of multipotent progenitors used in the clinic because of their immunomodulatory properties and their ability to differentiate into multiple mesodermal lineages. Although bone marrow (BM) remains the most common MSC source, cord blood (CB) can be collected noninvasively and without major ethical concerns. Comparative studies comprehensively characterizing the MSC phenotype across several tissue sources are still lacking. This study provides a 246-antigen immunophenotypic analysis of BM- and CB-derived MSC aimed at identifying common and strongly expressed MSC markers as well as the existence of discriminating markers between the two sources. BM-MSC (n = 4) were expanded and analyzed as bulk (n = 6) or single clones isolated from the bulk culture (n = 3). CB-MSC (n = 6) were isolated and expanded as single clones in 5/6 samples. The BM-MSC and CB-MSC phenotype was investigated by flow cytometry using a panel of 246 monoclonal antibodies. To define the markers common to both sources, those showing the smallest variation between samples (coefficient of variation of log2 fold increase ≤ 0.5, n = 59) were selected for unsupervised hierarchical cluster analysis (HCL). Differentially expressed markers were identified by directly comparing the expression of all 246 antigens between BM-MSC and CB-MSC. Based on HCL, 18 markers clustered as strongly expressed in BM-MSC and CB-MSC, including alpha-smooth muscle antigen (SMA), beta-2-microglobulin, CD105, CD13, CD140b, CD147, CD151, CD276, CD29, CD44, CD47, CD59, CD73, CD81, CD90, CD98, HLA-ABC, and vimentin. All except CD140b and alpha-SMA were suitable for the specific identification of ex-vivo expanded MSC. Notably, only angiotensin-converting enzyme (CD143) was exclusively expressed on BM-MSC. CD143 expression was tested on 10 additional BM-MSC and CB-MSC and on 10 umbilical cord- and adipose tissue-derived MSC samples, confirming that its expression is restricted to adult sources. This is the first study that has comprehensively compared the phenotype of BM-MSC and CB-MSC. We have identified markers that could complement the minimal panel proposed for the in-vitro MSC definition, being shared and strongly expressed by BM- and CB-derived MSC. We have also identified CD143 as a marker exclusively expressed on MSC derived from adult tissue sources. Further studies will elucidate the biological role of CD143 and its potential association with tissue-specific MSC features.


Post-exposure passive immunisation for preventing rubella and congenital rubella syndrome.
Control of rubella is desired because infection in early pregnancy can result in miscarriage, foetal death or congenital abnormality. Primary studies examining the effectiveness of immunoglobulins for post-exposure prophylaxis of rubella have small sample sizes and varying results. National public health recommendations suggest a degree of effectiveness. To assess the effectiveness of intramuscular injection or intravenous infusion of polyclonal immunoglobulins of human sera or plasma origin for preventing rubella and congenital rubella syndrome when administered to exposed susceptible people before the onset of disease. We searched CENTRAL (2014, Issue 7), MEDLINE (1946 to August week 2, 2014), EMBASE (1974 to August 2014), CINAHL (1981 to August 2014), LILACS (1982 to August 2014) and Web of Science (1955 to August 2014). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry on 16 October 2014. We searched the reference lists of relevant retrieved reviews and studies and identified national public health guidelines. For the outcome 'preventing cases of rubella', we included randomised controlled trials (RCTs) and quasi-RCTs. We found several studies addressing this outcome where the design was a controlled clinical trial (CCT) (with exposure to rubella virus controlled by the investigators) but the method of allocation of participants to groups was not reported. We found an alternative report of one of these studies that indicated participants were assigned to groups randomly. We therefore included such studies as meeting criteria for RCTs or quasi-RCTs and undertook sensitivity analyses. For the outcomes, 'congenital rubella infection' and 'congenital rubella syndrome', we included RCTs, quasi-RCTs and prospective controlled (cohort) studies. Participants were necessarily susceptible and exposed to rubella. Polyclonal immunoglobulins derived from human sera or plasma must have been administered intramuscularly or intravenously as the only intervention in at least one group. We used the standard methodological procedures expected by The Cochrane Collaboration. We included 12 studies (430 participants) in the review: seven RCTs and five CCTs where it was not clear whether participants were randomly allocated to groups. We did not include any unpublished studies. Participants included children and adults of both sexes. Only one study included pregnant women. All studies were conducted in high-income countries.The quality of the 11 studies in the initial meta-analysis was moderate, although we classified no study as having a low risk of bias on all criteria.We included 11 studies in the initial meta-analysis of gamma-globulin (concentrated polyclonal immunoglobulins) versus control (saline or no treatment) for rubella cases. The result favoured the intervention group (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.45 to 0.83) but was heterogenous (Chi² test = 36.59, df = 10 (P value < 0.0001); I² statistic = 73%). Heterogeneity was explained by subgrouping studies according to the estimated volume of gamma-globulin administered per pound of bodyweight and then removing those studies where the intervention was administered more than five days after participant exposure to rubella (post hoc analysis). The test of subgroup differences demonstrated heterogeneity between subgroups according to our protocol definition (P value < 0.1; I² statistic > 60%) and there appeared to be greater effectiveness of the intervention when a greater volume of gamma-globulin was administered ('0.027 to 0.037 ml/lb' RR 1.60 (95% CI 0.57 to 4.52); '0.1 to 0.15 ml/lb' RR 0.53 (95% CI 0.29 to 0.99); '0.2 to 0.5 ml/lb' RR 0.20 (95% CI 0.04 to 1.00)).None of the studies reported the outcome 'congenital rubella infection'. One included study reported on congenital rubella syndrome, with no cases among participants who were fewer than nine weeks pregnant at enrolment and who were randomised to one of two gamma-globulin groups ('high' or 'low' rubella titre). However, the study did not report how congenital rubella syndrome was measured and did not report the length of follow-up according to intervention group. This study did not include a non-treatment group.No included study measured adverse events. Compared to no treatment, polyclonal immunoglobulins seem to be of benefit for preventing rubella. The available evidence suggests that this intervention may be of benefit up to five days after exposure, and that effectiveness is dependent on dose. Considering the attack rate for rubella cases in the control group of the highest volume gamma-globulin subgroup (333 per 1000), the absolute risk reduction (calculated from the RR) for this volume of gamma-globulin was 266 (95% CI 0 to 320) and the number needed to treat to benefit is four (95% CI 3 to incalculable).The included studies did not measure rubella-specific antibodies in the immunoglobulin products used in a standard way and thus estimation of the dose of rubella-specific antibodies in international units administered was not possible. As the concentration of rubella-specific antibodies in today's polyclonal immunoglobulin products may vary from those products used in the studies in the review, the volume required per pound of bodyweight to produce similar results may also vary.There is insufficient evidence to make direct conclusions about the effectiveness of polyclonal immunoglobulins for preventing congenital rubella syndrome. This is an area requiring further research.


The complete genome sequence of the thermophilic bacterium Laceyella sacchari FBKL4.010 reveals the basis for tetramethylpyrazine biosynthesis in Moutai-flavor Daqu.
The genus Laceyella consists of a thermophilic filamentous bacteria. The pure isolate of Laceyella sacchari FBKL4.010 was isolated from Moutai-flavor Daqu, Guizhou Province, China. In this study, the whole genome was sequenced and analyzed. The complete genome consists of one 3,374,379-bp circular chromosome with 3,145 coding sequences (CDSs), seven clustered regularly interspaced short palindromic repeat (CRISPR) regions of 12 CRISPRs. Moreover, we identified that the genome contains genes encoding key enzymes such as proteases, peptidases, and acetolactate synthase (ALS) of the tetramethylpyrazine metabolic pathway. Metabolic pathways relevant to tetramethylpyrazine synthesis were also reconstructed based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) PATHWAY database. Annotation and syntenic analyses using antiSMASH 4.0 also revealed the presence of two gene clusters in this strain that differ from known tetramethylpyrazine synthesis clusters, with one encoding amino acid dehydrogenase (ADH) and the other encoding transaminase in tetramethylpyrazine metabolism. The results of this study provide flavor and genomic references for further research on the flavor-producing functions of strain FBKL4.010 in the Moutai liquor-making process.


Psychosocial outcomes of dyadic arts interventions for people with a dementia and their informal caregivers: A systematic review.
Dementia is a neurodegenerative syndrome that can lead to profound psychological and social challenges for people with dementia and their informal caregivers. Previous research has found positive effects of arts-based interventions for people with dementia and caregivers that have been dyadic in nature and the present article sought to review these findings. A systematic literature review was conducted to investigate psychosocial outcomes of dyadic arts interventions. PsychINFO, Medline, Web of Science and ASSIA databases (from journal inception to March 2020) were searched as well as Google Scholar and reference lists of relevant studies were searched. Interventions were delivered to people with dementia and their caregivers in community-based settings across five countries. Thirteen peer-reviewed journal articles met the criteria for inclusion in this review, six focusing on performing arts and seven on visual arts. The findings suggested that choral singing and visual arts interventions may have positive effects on psychosocial outcomes for both people with dementia and their informal caregivers. Improved well-being, quality of life, mood, enhanced identity and decreased social isolation were found in some studies. Importantly, across all studies, participants reported enjoying arts activities. This is the first review to systematically assess dyadic arts activities in a dementia context. These activities offer enjoyable and engaging experiences for many person with dementia and caregivers and were generally found to have positive results but mostly small sample size, lack of control groups and different outcome measures made comparisons challenging. Future research recommendations include further theoretical development, identifying key intervention components, and specifying relevant and measurable theoretically informed outcomes within dyadic interventions for this population.


The Natural Product N-Palmitoyl-l-leucine Selectively Inhibits Late Assembly of Human Spliceosomes.
The spliceosome is a dynamic complex of five structural RNAs and dozens of proteins, which assemble together to remove introns from nascent eukaryotic gene transcripts in a process called splicing. Small molecules that target different components of the spliceosome represent valuable research tools to investigate this complicated macromolecular machine. However, the current collection of spliceosome inhibitors is very limited. To expand the toolkit we used a high-throughput in vitro splicing assay to screen a collection of pre-fractions of natural compounds derived from marine bacteria for splicing inhibition. Further fractionation of initial hits generated individual peaks of splicing inhibitors that interfere with different stages of spliceosome assembly. With additional characterization of individual peaks, we identified N-palmitoyl-l-leucine as a new splicing inhibitor that blocks a late stage of spliceosome assembly. Structure-activity relationship analysis of the compound revealed that length of carbon chain is important for activity in splicing, as well as for effects on the cytological profile of cells in culture. Together these results demonstrate that our combination of in vitro splicing analysis with complex natural product libraries is a powerful strategy for identifying new small molecule tools with which to probe different aspects of spliceosome assembly and function.


[The biological role of carnosine in excitable tissues].
The authors summarize the data about characters of histidine-containing dipeptides (HCD) carnosine and homocarnosine in excitable tissues. The value of their antiradical, pH-buffer and metal-chelating characters is presented. The authors analyze data on participation of some cell membrane receptors in biological effects of HCD. These results were used earlier as the evidence of mediator function of carnosine in centre nerve system, though later it was not supported experimentally. It is considered now that the biological role of HCD in tissue is connected with the neutralization of superfluous protons, metal ions of changeable valence and free radical compounds, so called general buffer action. The result of this action is the normalization of cell metabolism and the protection of membrane of excitable cells against negative environmental influences.


COPD Assessment Test (CAT) is a Valid and Simple Tool to Measure the Impact of Bronchiectasis on Affected Patients.
The COPD assessment test (CAT) is a short questionnaire developed to help patients and clinicians to assess the impact of symptoms in routine clinical practice. We aimed to validate and to test the reproducibility of CAT in patients with bronchiectasis and correlate with the severity of dyspnea, aerobic and functional capacity, and physical activity in daily life. This is a cross-sectional study, patients with bronchiectasis underwent spirometry, cardiopulmonary exercise test (CPET), incremental shuttle walk test (ISWT), Saint George`s Respiratory Questionnaire (SGRQ), and received pedometer. CAT was applied twice (CAT-1 and CAT-2, 7 to 10 days apart). The severity of bronchiectasis was assessed by E-FACED and bronchiectasis severity index (BSI). A total of 100 patients were evaluated (48 ± 14 years, 59 women, FVC: 67 ± 22% pred, FEV1: 52 ± 25% pred). According to CAT, 14% patients presented low, 40% medium, 32% high, and 14% very high impact. The higher the CAT, the worse the severity of bronchiectasis, dyspnea, quality of life, performance on the CPET, and smaller the distance walked (DW) on the ISWT and number of steps (NS) per day. There was significant correlation between CAT and SGRQ, E-FACED, BSI, NS, ISWT, oxygen uptake, and workload at CPET. CAT-1 and CAT-2 presented similar values: 21 (13-26) and 19 (13-26), respectively. The CAT is a valid and reproducible instrument in patients with bronchiectasis presenting good correlation with clinical, functional, and quality of life measurements. This easy-to-use, easy-to-understand, quick, and useful tool may play an important role to assess the impact of bronchiectasis on both daily medical practice and clinical trial settings.


Culture and gender influence self-construal in mother-preschooler reminiscing.
The present study examined how culture and gender influence the self-construal of mothers and their four-year-olds during dyadic reminiscing. Participants were 21 Thai (11 girls, 10 boys) and 21 American (10 girls, 11 boys) mother-child dyads. Thai dyads exhibited a more interdependent self-construal, whereas American dyads exhibited a more independent self-construal, as measured by personal and group pronoun usage and discussions of behavioral expectations, thoughts and feelings, and personal attributes. Girls and boys differed in the extent to which their self-construal was defined in relation to others in their social groups, for example girls mentioned teachers and classmates more than boys. Culture and gender also interacted in influencing self-construal, with Thai girls (but not boys) mentioning family members more than American counterparts. These findings suggest that the development of children's self-construal, particularly the extent to which children are socialized to view and express themselves independently of others or interdependently with others, differs depending on culture and gender. This work contributes to our understanding of the relationship between autobiographical memory and self during the formative years. Starting as early as preschool, our social environment influences the way we remember our experiences, which in turn shapes our self-construal.


Anti-bacterial properties of calcium hydroxide in combination with silver, copper, zinc oxide or magnesium oxide.
Prevention of bacterial growth among root canal treatment sessions is a prerequisite for successful root canal treatment. The most common way to achieve this is to use calcium hydroxide in the treatment sessions. Some studies have shown calcium hydroxide inefficiency in this field. The aim of this study was to investigate and compare the effects of silver, copper, zinc oxide and magnesium oxide nanoparticles on the inhibitory effects of calcium hydroxide based on Enterococcus faecalis species. Enterococcus faecalis bacteria having 0.5 McFarland concentration were prepared. Plates containing BHI agar medium were prepared. In each plate, four wells were created and the plate was cultured using a sterile swab. Afterwards, calcium hydroxide composition of 1% and 2% concentration from silver, copper, zinc oxide and magnesium oxide nanoparticles were prepared separately, as well as the combination of calcium hydroxide with 1% silver in combination with 1% of copper, zinc oxide and magnesium oxide nanoparticles, which were then transferred to the wells. After 24 hours of incubation, the inhibition zone diameter was measured. Data were analyzed by Mann-Withney test. At 1% concentration, only the combination of copper nanoparticles with calcium hydroxide could significantly create an inhibition zone larger than calcium hydroxide alone (P value <0.5). At 2% concentration, the combination of copper nanoparticles with calcium hydroxide, and the combination of silver nanoparticles with calcium hydroxide, were significantly higher than calcium hydroxide alone (P value <0.5). The calcium hydroxide composition containing 1% silver nanoparticles in combination with 1% copper, zinc oxide and magnesium oxide nanoparticles significantly increased the growth inhibition zone more than calcium hydroxide alone. (P Value <0.5). Copper nanoparticles showed the best antibacterial properties among silver, copper, magnesium oxide and zinc oxide nanoparticles in combination with calcium hydroxide. Also, the combination of 1% of nanoparticles with each other increases antibacterial properties.


The Er:YAG vaginal laser for management of women with genitourinary syndrome of menopause (GSM).
The purpose of our study was to investigate the effects of vulvovaginal erbium laser on the genitourinary syndrome of menopause (GSM) and sexual function of postmenopausal women. We conducted a retrospective study of sixty-four postmenopausal women with GSM, and these patients were scheduled for three times of vulvovaginal erbium laser treatment. A baseline and post-treatment vaginal status was assessed by measuring vaginal pH, patients' subjective vulvovaginal atrophy (VVA) symptoms, which included dryness, dyspareunia, itching, and burning. The urinary response to treatment was assessed using ICIQ-SF, UDI-6, IIQ-7, OABSS, and POPDI-6. Sexual function was evaluated using the Female Sexual Function Index (FSFI) before and after vulvovaginal laser therapy. Patient follow-ups were scheduled for 12 months after treatment. A total of sixty-four patients were enrolled in the study. We observed the significant improvement in the percentage of negative symptoms (dryness/dyspareunia/itching/burning) and in lower urinary tracts symptoms evaluated with ICIQ-SF, UDI-6, IIQ-7, OABSS, and POPDI-6 (P < 0.05). Patients' overall satisfaction regarding their sexual life, assessed via Female Sexual Function Index (FSFI), showed significant improvement in its six domains of sexual function (P < 0.05). The pH level of vaginal secretions significantly decreased. No long-term complications were found post-treatment. The Er:YAG vaginal laser procedure is associated with a significant improvement in GSM and sexual function of postmenopausal women. Our result demonstrates that it can be a safe and efficacious treatment for patients with GSM without any serious adverse effects up to 1-year post-treatment. The long-term effects of using vulvovaginal laser in the treatment of GSM should be investigated.


A new ATP-sensitive K+ channel-independent mechanism is involved in glucose-excited neurons of mouse arcuate nucleus.
Glucose is known to modify electrical activity of neurons in different hypothalamic areas such as the arcuate nucleus (ARC) or the ventromedian nucleus. In these structures, it has been demonstrated that glucose-induced excitation of neurons involves ATP-sensitive K(+) (K(ATP)) channel closure. The aim of the present study was to determine whether ARC neurons were able to detect high extracellular glucose concentrations and which mechanisms were involved in this detection by using whole-cell and cell-attached patch-clamp techniques in acute mouse brain slices. An increase from 5 to 20 mmol/l glucose stimulated 19% and inhibited 9% of ARC neurons. Because of the high-glucose concentrations used, we called these neurons high-glucose-excited (HGE) and high-glucose-inhibited (HGI) neurons, respectively. Glucose-induced depolarization of HGE neurons was not abolished by tetrodotoxin treatment and was correlated with an increase of membrane conductance that reversed at approximately 20 mV. Experiments with diazoxide, pinacidil, or tolbutamide showed that K(ATP) channels were present and functional in most of the ARC neurons but were mostly closed at 5 mmol/l glucose. Moreover, HGE neurons were also present in ARC of Kir6.2 null mice. These results suggested that ARC neurons have the ability to sense higher glucose concentrations than 5 mmol/l through a new K(ATP) channel-independent mechanism.


[Radiologic changes of the hand and wrist in young children with hypotrophy and perinatal encephalopathy].
Disordered growth of the bones by length was found in infants with chronic disorders of nutrition and perinatal encephalopathy. Roentgenogrammetry helped make a more objective assessment of bone changes as against visual methods. The authors distinguish the x-ray characteristics most typical of such patients.


Ancyronyx lianlabangorum sp. nov., a new spider riffle beetle from Sarawak, and new distribution records for A. pulcherrimus Kodada, Jäch & Čiampor based on DNA barcodes (Coleoptera, Elmidae).
Ancyronyx lianlabangorum sp. nov. (Coleoptera, Elmidae), a new spider riffle beetle from the Kelabit Highlands (Sarawak, northern Borneo), is described. Illustrations of the habitus and diagnostic characters of the new species and the similar, polymorphic A. pulcherrimus Kodada et al. are presented. Differences to closely related species, based on COI nucleotide sequences and morphological characters, are discussed. Ancyronyx pulcherrimus is here recorded from Sarawak for the first time, based on DNA barcoding.


The role of tryptophan residues in Escherichia coli arginyl-tRNA synthetase.
The effect of N-bromosuccinimide (NBS) on the activity of Escherichia coli arginyl-tRNA synthetase (ArgRS) was studied. The results showed that only one tryptophan residue was easy of access to the reagent and was closely related to enzyme activity. When all the five tryptophan residues in ArgRS were changed via site-directed mutagenesis singly into Ala, the aminoacylation activity of the Trp162 mutated enzyme decreased seriously, while the other four mutant enzymes retained almost the same activity as the native one. The oxidation of the five mutant enzymes with NBS demonstrated that only the mutation of Trp162 resulted in the loss of sensitivity to the reagent. These results strongly suggest that Trp162 is more accessible to NBS and is related to enzyme activity. Furthermore, the far-UV CD spectroscopy of the mutant enzyme ArgRS162WA showed little change in its secondary structure. Finally, studies on the kinetics of the mutant enzyme ArgRS162WA in aminoacylation reaction showed that the reduction in activity could be attributed to the decrease in the values of kcat and kcat/Km for arginine. The thermodynamic calculation indicates that this mutation causes a decrease of the binding energy by 2.7 kJ/mol. Our data suggest that Trp162 is involved in the binding of arginine and in the transition state stabilization.


A weakness in process technology.
Although the United States seems to be neither behind when it comes to research and development on new products or the willingness of its consumers to buy new products, the evidence clearly shows that it is behind when it comes to process technologies. Often Americans, even when a correction is made for wage differences, cannot produce goods at the price or quality levels achieved abroad. There is no one overriding reason for this lag in process technologies. An undereducated and trained labor force, too little savings and investment, a failure to see production as a central task, and a number of other factors have all contributed to the problem.


Hyperproinsulinemia of type II diabetes is not present before the development of hyperglycemia.
To examine proinsulin and insulin levels in first-degree relatives of patients with non-insulin-dependent diabetes mellitus (NIDDM). Comparison of insulin and proinsulin responses to an oral glucose tolerance test in four groups of individuals: 1) 31 patients with newly diagnosed NIDDM treated with diet alone, 2) 34 first-degree relatives of NIDDM patients with impaired glucose tolerance (IGT), 3) 26 relatives with normal glucose tolerance (NGT), and 4) 30 subjects without a family history of diabetes. Both fasting and post-glucose levels of proinsulin were elevated in patients with diabetes, but not in the relatives with IGT or NGT. Levels of true insulin were highest in the diabetic group, followed by the subjects with IGT, and were lowest among relatives with NGT. Proinsulin levels correlated with glucose levels, suggesting that hyperglycemia is the main stimulus for increased proinsulin secretion. First-degree relatives of NIDDM patients, who have a high risk of developing diabetes, do not exhibit elevated levels of fasting or glucose-stimulated proinsulin as long as their fasting glucose levels remain normal.


A gel partition model for organic desorption from a pond sediment.
Adsorption at the water-sediment interface has been correlated with the organic carbon content of natural sediment samples and with water-octanol partitioning equilibria. In deriving a new model for sorption in sediment, it is assumed that adsorption is due to humin-kerogen polymers associated with the clay component in the sediment. The model includes solubility parameter theory applied to solute-gel-liquid interactions and a theory of the liquid-polymer interactions that control gel swelling. Partially swollen gels are expected to exhibit impeded diffusion. These concepts are able to explain observations of limited desorption of certain organic compounds from natural sediments and soil minerals. Experiments were performed in which extractive solvents flowed through a liquid chromatographic column packed with dried estuarine and pond sediment samples and the effluent was analyzed for a test lipophilic compound, di(2-ethylhexyl) phthalate. The model predicts that the maximum desorption rate and the maximum extent of gel swelling should coincide and, conversely, that the desorption rate should be diffusion-limited if the polymer gel is only partially swollen. The conditions for maximum desorption and for diffusion-limited desorption were both observed experimentally.


Can (and should) the venous tone be monitored at the bedside?
Most of our blood volume is contained in the venous compartment. The so-called 'compliant veins' are an adjustable blood reservoir, which is playing a paramount role in maintaining haemodynamic stability. The purpose of this study is to review what is known about this blood reservoir and how we can use this information to assess the cardiovascular state of critically ill patients. The mean systemic filling pressure (Pmsf) is the pivot pressure of the circulation, and a quantitative index of intravascular volume. The Pmsf can be measured at the bedside by three methods described in critically ill patients. The Pmsf can be modified by the fluid therapy and vasoactive medications. The Pmsf along with other haemodynamic variables can provide valuable information to correctly understand the cardiovascular status of critically ill patients and better manage the fluid therapy and cardiovascular support. Future studies using the Pmsf will show its usefulness for fluid administration.


EMP3 overexpression is associated with oligodendroglial tumors retaining chromosome arms 1p and 19q.
The epithelial membrane protein 3 (EMP3) gene located on chromosome 19q13 has been implicated as a candidate tumor suppressor gene (TSG) in neuroblastomas and gliomas. The aim of this study was to investigate whether EMP3 is involved in oligodendroglial tumors (OTs), which frequently carry combined chromosomes 1p and 19q deletion. We first investigated the transcript level of EMP3 in a cohort of 57 OTs by quantitative real-time RT-PCR. Our results showed that 10 (18%) tumors had reduced EMP3 expression level compared to normal brains. Six of these tumors carried chromosome 19q13 deletion but no statistical correlation was found between the 2 parameters. Intriguingly, a similar proportion (11 of 57, 19%) of tumors displayed EMP3 overexpression, with 8 of them having transcript level >10-fold higher than normal brain. All 11 OTs retained chromosomes 1p36 and 19q13, and a significant association was found between EMP3 overexpression and balanced chromosomes 1p36 and 19q13 (p = 0.004). The methylation status of EMP3 was evaluated by bisulfite sequencing in 29 OTs with diverse expression levels. All tumors except 3 showed aberrant methylation of EMP3 and no correlation was observed between transcript level and methylation status, suggesting that methylation alone does not mediate transcriptional down-regulation of EMP3 in OTs. In conclusion, our study demonstrates that EMP3 overexpression is involved in OTs retaining chromosomes 1p and 19q and does not support EMP3 as the target TSG on chromosome 19q13 in OTs.


A Multivariate Genome-Wide Association Study of Wing Shape in Drosophila melanogaster.
Due to the complexity of genotype-phenotype relationships, simultaneous analyses of genomic associations with multiple traits will be more powerful and informative than a series of univariate analyses. However, in most cases, studies of genotype-phenotype relationships have been analyzed only one trait at a time. Here, we report the results of a fully integrated multivariate genome-wide association analysis of the shape of the Drosophila melanogaster wing in the Drosophila Genetic Reference Panel. Genotypic effects on wing shape were highly correlated between two different laboratories. We found 2396 significant SNPs using a 5% false discovery rate cutoff in the multivariate analyses, but just four significant SNPs in univariate analyses of scores on the first 20 principal component axes. One quarter of these initially significant SNPs retain their effects in regularized models that take into account population structure and linkage disequilibrium. A key advantage of multivariate analysis is that the direction of the estimated phenotypic effect is much more informative than a univariate one. We exploit this fact to show that the effects of knockdowns of genes implicated in the initial screen were on average more similar than expected under a null model. A subset of SNP effects were replicable in an unrelated panel of inbred lines. Association studies that take a phenomic approach, considering many traits simultaneously, are an important complement to the power of genomics.


The prevalence of metabolic syndrome in Chinese postmenopausal women and the optimum body composition indices to predict it.
The aim of this study was to determine the prevalence of metabolic syndrome (MetS) in Chinese postmenopausal women and explore the optimum body composition indices to predict MetS. Participants were independent, community-dwelling women. Recruitment occurred through advertisements in newspapers and flyers posted in the local community. A total of 181 postmenopausal women were recruited. Their parameters were measured, including body height, weight, waist circumference (WC), hip circumference, sagittal abdominal diameter, blood pressure, follicle-stimulating hormone, luteinizing hormone, estradiol, triglyceride, high-density lipoprotein cholesterol, fasting plasma glucose, and body fat (BF; %). Logistic regression analyses were applied for correlation between stated variables. Optimization of body composition indices to predict MetS in postmenopausal women was analyzed with the area under the curve of the receiver. The prevalence of MetS in postmenopausal women was 33.7%. The risk factors of MetS in postmenopausal women were age, family history of metabolic disorders (obesity, hypertension, hyperlipemia, and diabetes mellitus), body composition indices (body mass index [BMI], WC, waist-to-hip ratio, sagittal abdominal diameter, and BF), and metabolic indices (systolic and diastolic blood pressure, fasting plasma glucose, and triglyceride; odds ratio > 1, P < 0.05), and the protective factor is high-density lipoprotein cholesterol (odds ratio = 0.114, P < 0.05). All body composition indices in our study had a positive correlation with number of MetS factors. The body composition indices in our study showed a positive correlation with each other (P < 0.001). BMI and WC were highly correlated with BF (r > 0.900, P < 0.001). Through receiver operating characteristic curve analysis, it was determined that body composition indices (WC, 80.75 cm; BF, 36.695%; sagittal abdominal diameter, 18.35 cm; or BMI, 24.835 kg/m) could be used to predict MetS. The prevalence of MetS in Chinese postmenopausal women is 33.7%. Body composition indices (WC > or = 80.75 cm, BF > or = 36.695%, sagittal abdominal diameter > or = 18.35 cm, or BMI > or = 24.835 kg/m) were discovered to predict MetS.


Hematopoietic growth factors in lung cancer.
Most patients affected by lung cancer are treated with chemotherapy, and hence are at risk of myelosuppression. Hematopoietic growth factors have a relevant role in this setting, as they can improve quality of life, reduce the rate of chemotherapy-induced complications and allow the administration of full-dose chemotherapy. Most data of hematologic growth factors in lung cancer come from dated publications or large trials involving different malignancies, thus limiting specific information for lung neoplasms. Nonetheless, most studies consistently identified myeloid growth factors as effective on specific end-points such as the duration and severity of neutropenia, or complications such as hospitalizations and febrile neutropenia; on the other hand, erythropoiesis-stimulating agents (ESAs) consistently improved anemia-specific end-points including hemoglobin values, transfusions rate and fatigue, although some specific safety issues characterized this drug class. The most recent international guidelines address these characteristics and include the main indications for hematologic growth factors in solid neoplasms, including lung cancer. Myeloid growth factors and ESAs have a relevant role in selected patients undergoing chemotherapy for nonsmall cell lung cancer and small cell lung cancer. Notably, a comprehensive risk-benefit assessment is required in the specific case of ESAs.


Curricular Quality Improvement in Midwifery: Simulating Unexpected Perinatal Loss.
Caring for families experiencing perinatal loss is a fundamental component of midwifery practice, but little attention is paid to perinatal palliative care in midwifery curricula. Lack of educational preparation and self-care resources negatively impacts midwifery students and health care teams caring for families experiencing stillbirth. A private, urban university conducted a curricular quality improvement project to integrate perinatal palliative care into the midwifery curriculum using a high-fidelity, branching simulation pedagogy. Simulation objectives were developed from curricular gap analyses and the Core Competencies for Basic Midwifery Practice. Development of the Unexpected Perinatal Loss Simulation was guided by the International Nursing Association for Clinical Simulation and Learning Outcomes and Objectives and Design Standards. The Unexpected Perinatal Loss Simulation was revised based on qualitative data from student focus groups and expert content validation. Qualitative data yielded 4 key domains: presimulation, simulation skills, prior experience/personal reflections, and recommendations. Simulation procedures and scenario content were revised, after which 8 expert clinicians in the fields of midwifery, palliative care, and psychiatry validated the scenario content using the Lynn method. Two items did not meet the content validity index (CVI) threshold of 0.78, necessitating review by stakeholders; however, the overall scenario CVI threshold was met (0.82). Through this project, faculty integrated perinatal palliative care into the midwifery program using a novel approach of high-fidelity, branching simulation, structured debriefing, and an introductory self-care skills workshop. Potential clinical impact includes skillful perinatal palliative care with effective communication skills to mitigate how families experience and remember a traumatic loss and facilitate the grieving process. Students voiced insights into how they would process loss and seek support to mitigate their own grief as future midwives.


Developmental trajectories of reading development and impairment from ages 3 to 8 years in Chinese children.
Early prediction of reading disabilities in Chinese is important for early remediation efforts. In this 6-year longitudinal study, we investigated the early cognitive predictors of reading skill in a statistically representative sample of Chinese children from Beijing. Two hundred sixty-one (261) native Chinese children were administered seven language-related skills over three years between the ages of 3 and 6 years. Performances on these skills were then examined in relation to subsequent word reading accuracy and fluency. Individual differences in developmental profiles across tasks were then estimated using growth mixture modeling. Four developmental trajectories were classified - the typical (control), catch-up (with low initial cognitive performances but adequate subsequent reading), literacy-related-cognitive-delay (with difficulties in morphological awareness, phonological awareness, and speeded naming and subsequent word recognition), and language-delay (relatively low across all tasks) groups. Findings suggest that the combination of phonological awareness, rapid naming and morphological awareness are essential in the early prediction of later reading difficulties in Chinese children.


Microbiota-Related Changes in Unconjugated Fecal Bile Acids Are Associated With Naturally Occurring, Insulin-Dependent Diabetes Mellitus in Dogs.
Diabetes mellitus (DM) in humans has recently been associated with altered intestinal microbiota. The consequences of intestinal dysbiosis, such as increased intestinal permeability and altered microbial metabolites, are suspected to contribute to the host inflammatory state and peripheral insulin resistance. Human diabetics have been shown to have changes in bile acid (BA) metabolism which may be detrimental to glycemic control. The purpose of this study was to examine BA metabolism in dogs with naturally-occurring, insulin-dependent DM and to relate these findings to changes in the intestinal microbiota. A prospective observational study of adult dogs with a clinical diagnosis of DM (n = 10) and healthy controls (HC, n = 10) was performed. The fecal microbiota were analyzed by 16S rRNA gene next-generation (Illumina) sequencing. Concentrations of fecal unconjugated BA (fUBA) were measured using gas chromatography and mass spectrometry. Analysis of bacterial communities showed no significant difference for any of the alpha-diversity measures between DM vs. HC dogs. Principal coordinate analysis based on unweighted Unifrac distance metric failed to show significant clustering between dog groups (ANOSIMUnweighted: R = 0.084; p = 0.114). However, linear discriminate analysis effects size (LEfSe) detected differentially abundant bacterial taxa (α = 0.01, LDA score >2.0) on various phylogenetic levels. While Enterobacteriaceae was overrepresented in dogs with DM, the proportions of Erysipelotrichia, Mogibacteriaceae, and Anaeroplasmataceae were increased in HC dogs. Dogs with DM had increased concentration of total primary fUBA compared to HC dogs (p = 0.028). The concentrations of cholic acid and the cholic acid percentage of the total fUBA were increased (p = 0.028 and p = 0.035, respectively) in the feces of DM dogs relative to HC dogs. The levels of lithocholic acid (both absolute value and percentage of the total fUBA) were decreased (p = 0.043 and p < 0.01, respectively) in DM dogs vs. HC dogs. Results indicate that dogs with DM have both intestinal dysbiosis and associated fUBA alterations. The pattern of dysbiosis and altered BA composition is similar to that seen in humans with Type 2 DM. The dog represents a novel large animal model for advancing translational medicine research efforts (e.g., investigating pathogenesis and therapeutics) in DM affecting humans.


Computed tomography and chymopapain chemonucleolysis: preliminary findings.
Ten lumbar disk levels in nine patients were examined by computed tomography (CT) before and 6 weeks after chymopapain chemonucleolysis of herniated nucleus pulposus (HNP). Patient selection for chemonucleolysis was partly based on CT scans demonstrating morphologic HNP criteria favoring a successful treatment outcome. Posttreatment CT scans disclosed a measurable HNP size decrease of 1-3 mm at nine of 10 levels studied as well as an increase in HNP attenuation at many levels. CT findings correlated closely with objective clinical parameters used to assess treatment outcomes.


Melatonin enters the cerebrospinal fluid through the pineal recess.
The pineal recess (PR), a third ventricle (IIIV) evagination penetrating into the pineal gland, could constitute a site of melatonin passage to the cerebrospinal fluid (CSF) and explain the high concentrations of melatonin in this fluid. To test this hypothesis, we characterized melatonin distribution in the IIIV of sheep by CSF collection in the ventral part of IIIV (vIIIV) and in PR. At 30 microl/min collection rate, melatonin concentrations were much higher in PR than in vIIIV (19,934 +/- 6,388 vs. 178 +/- 70 pg/ml, mean +/- SEM, respectively, P < 0.005), and they increased in vIIIV when CSF collection stopped in the PR (P < 0.05). At 6 microl/min, levels increased to 1,682 +/- 585 pg/ml in vIIIV and were not influenced by CSF collection in the PR. This concentration difference between sites and the influence of PR collection on vIIIV levels suggest that melatonin reaches the PR and then diffuses to the IIIV. To confirm the role of PR, we demonstrated that its surgical sealing off decreased IIIV melatonin levels (1,020 +/- 305 pg/ml, compared with 5,984 +/- 1,706 and 6,917 +/- 1,601 pg/ml in shams or animals with a failed sealing off, respectively, P < 0.01) without changes in blood levels. Therefore, this study identified the localization of the main site of penetration of melatonin into the CSF, the pineal recess.


Routine bone marrow biopsy is not necessary in the staging of patients with classical Hodgkin lymphoma in the 18F-fluoro-2-deoxyglucose positron emission tomography era.
Accurate staging of classical Hodgkin lymphoma (CHL) directs treatment intensity. Functional imaging can detect marrow/bone involvement making the role of bone marrow biopsy (BMB) unclear. We assessed current UK practice in CHL staging by questionnaire and retrospectively analyzed patients staged at a single center with BMB and (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). From 34 questionnaire responses 50% used FDG-PET/CT routinely. BMB was employed in 97% with advanced-stage and 30% of patients with limited-stage disease (70% of those not using routine FDG-PET/CT). Ten out of 50 patients were BM+, all of which were identified by FDG-PET/CT (PET+). Conventional BMB changed management in 2% of cases. There were no clinically significant FDG-PET/CT false positives. Conventional routine BMB staging in CHL is extremely insensitive. FDG-PET/CT can rule out marrow/bone involvement in CHL. In the FDG-PET/CT staging era BMB should be targeted to a minority of patients with FDG-PET/CT + bone/marrow uptake and only when management would be altered by the result.


Miniaturized plate readers for low-cost, high-throughput phenotypic screening.
We present a miniaturized plate reader for measuring optical density in 96-well plates. Our standalone reader fits in most incubators, environmental chambers, or biological containment suites, allowing users to leverage their existing laboratory infrastructure. The device contains no moving parts, allowing an entire 96-well plate to be read several times per second. We demonstrate how the fast sampling rate allows our reader to detect small changes in optical density, even when the device is placed in a shaking incubator. A wireless communication module allows remote monitoring of multiple devices in real time. These features allow easy assembly of multiple readers to create a scalable, accurate solution for high-throughput phenotypic screening.


Health Care Use and Health Behaviors Among Young Adults With History of Parental Incarceration.
To determine if longitudinal associations exist between parental incarceration (PI) and health care use or health behaviors among a national sample of young adults. We used the National Longitudinal Survey of Adolescent to Adult Health to examine associations between history of mother incarceration (MI) and father incarceration (FI), health care use, and 3 dimensions of health behaviors (eg, general health behaviors, substance use, and other risky behaviors) (N = 13 084). Multivariable logistic regression models accounted for individual, family, and geographic factors and generated adjusted odds ratios (aORs). Over 10% of the sample had a history of PI before the age of 18. History of MI and FI were both associated with forgone health care (aOR = 1.65 [95% confidence interval (CI), 1.20-2.27], aOR = 1.22 [95% CI, 1.02-1.47], respectively), prescription drug abuse (MI aOR = 1.61 [95% CI, 1.02-2.55], FI aOR = 1.46 [95% CI, 1.20-1.79]), and 10 or more lifetime sexual partners (MI aOR = 1.55 [95% CI, 1.08-2.22], FI aOR = 1.19 [95% CI, 1.01-1.41]). MI was associated with higher likelihood of emergency department use (aOR = 2.36 [95% CI, 1.51-3.68]), and FI was associated with illicit injection drug use (aOR = 2.54 [95% CI, 1.27-5.12]). The effects of incarceration extend beyond incarcerated individuals. PI histories are associated with lower health care use and unhealthy behaviors in young adulthood. By addressing barriers to health care and health-harming behaviors, health care providers and policy makers may reduce health disparities among this population.


Axial compression in femoral neck osteotomies. A biomechanic study in human cadaver hips.
The risk of applying compression to a sliding-screw-plate osteosynthesis in the treatment of femoral neck fractures was evaluated in an experimental study of 40 femoral neck osteotomies. Ten pairs of bones from autopsied women between 70 years and 79 years of age were compared to 10 pairs of bones from autopsied women of more than 80 years of age. The compression was applied intermittently but measured continuously. The results showed a diphasic curve. When the maximum axial compression force was reached, any attempt to apply further compression resulted in a rapid fall in pressure at the site of the osteotomy. The median of the maximum axial compression force was 971 N, ranging from 275 N to 1756N. The maximum axial compression forces were significantly lower in bones from women of more than 80 years of age compared to bones from women in the seventh decade. The clinical implication of the study is that compression of femoral neck fractures by a sliding-screw-plate system may be hazardous in patients with brittle bone, e.g. women over 80 years of age.


Deviation from the matching law reflects an optimal strategy involving learning over multiple timescales.
Behavior deviating from our normative expectations often appears irrational. For example, even though behavior following the so-called matching law can maximize reward in a stationary foraging task, actual behavior commonly deviates from matching. Such behavioral deviations are interpreted as a failure of the subject; however, here we instead suggest that they reflect an adaptive strategy, suitable for uncertain, non-stationary environments. To prove it, we analyzed the behavior of primates that perform a dynamic foraging task. In such nonstationary environment, learning on both fast and slow timescales is beneficial: fast learning allows the animal to react to sudden changes, at the price of large fluctuations (variance) in the estimates of task relevant variables. Slow learning reduces the fluctuations but costs a bias that causes systematic behavioral deviations. Our behavioral analysis shows that the animals solved this bias-variance tradeoff by combining learning on both fast and slow timescales, suggesting that learning on multiple timescales can be a biologically plausible mechanism for optimizing decisions under uncertainty.


Noninvasive evaluation of malignancy of brain tumors with proton MR spectroscopy.
To test clinical proton MR spectroscopy as a noninvasive method for predicting tumor malignancy. Water-suppressed single-voxel point resolved spectroscopy in the frontal white matter of 17 healthy volunteers and 25 patients with brain tumors yielded spectra with peaks of N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine/phosphocreatine (Cre), and lactate. These peak intensities were semiquantitated as a ratio to that of the external reference. The validity of the semiquantitation was first evaluated through phantom and volunteer experiments. The variation in measurements of the designated region in the volunteers was less than 10%. Normal ranges of NAA/reference, Cho/reference, and Cre/reference were 3.59 +/- 0.68, 1.96 +/- 0.66, and 1.53 +/- 0.64 (mean +/- SD), respectively. In 17 gliomas, the Cho/reference value in high-grade gliomas was significantly higher than in low-grade gliomas. Levels of NAA/reference were also significantly different in low-grade and high-grade malignancy. In eight meningiomas (four newly diagnosed and four recurrent), the level of Cho/reference was significantly higher in recurrent meningiomas than in normal white matter or in newly diagnosed meningiomas. Higher grades of brain tumors in this study were associated with higher Cho/reference and lower NAA/reference values. These results suggest that clinical proton MR spectroscopy may help predict tumor malignancy.


Non-culture diagnosis and serogroup determination of meningococcal B and C infection by a sialyltransferase (siaD) PCR ELISA.
Rapid, non-culture, serogroup determination of meningococcal infection is important in contact management where vaccination may be possible. The impending availability of polysaccharide-protein conjugate vaccines for serogroup C disease requires maximal case ascertainment, with serogroup determination, at a time when the number of culture confirmed meningococcal infections is decreasing. A polymerase chain reaction assay (PCR), based on a restriction fragment length polymorphism (RFLP) in the meningococcal serogroup B and C sialytransferase (siaD) gene, was developed to combine the non-culture diagnosis of meningococcal infection from CSF, whole blood and serum with serogroup (B and C) identification. The PCR assay was adapted to an ELISA format incorporating hybridization with serogroup-specific B and C oligonucleotide probes. Specificity for CSFs was 100% and sensitivities were respectively 81, 63 and 30% for CSFs, whole blood and sera. The serogroup-specific PCR ELISA is a significant addition to currently available tests for non-culture diagnosis of meningococcal infection and outbreak investigation.


Current Status of Mycotoxin Contamination of Food Commodities in Zimbabwe.
Agricultural products, especially cereal grains, serve as staple foods in sub-Saharan Africa. However, climatic conditions in this region can lead to contamination of these commodities by moulds, with subsequent production of mycotoxins posing health risks to both humans and animals. There is limited documentation on the occurrence of mycotoxins in sub-Saharan African countries, leading to the exposure of their populations to a wide variety of mycotoxins through consumption of contaminated foods. This review aims at highlighting the current status of mycotoxin contamination of food products in Zimbabwe and recommended strategies of reducing this problem. Zimbabwe is one of the African countries with very little information with regards to mycotoxin contamination of its food commodities, both on the market and at household levels. Even though evidence of multitoxin occurrence in some food commodities such as maize and other staple foods exist, available published research focuses only on Aspergillus and Fusarium mycotoxins, namely aflatoxins, deoxynivalenol (DON), trichothecenes, fumonisins, and zearalenone (ZEA). Occurrence of mycotoxins in the food chain has been mainly associated with poor agricultural practices. Analysis of mycotoxins has been done mainly using chromatographic and immunological methods. Zimbabwe has adopted European standards, but the legislation is quite flexible, with testing for mycotoxin contamination in food commodities being done voluntarily or upon request. Therefore, the country needs to tighten its legislation as well as adopt stricter standards that will improve the food safety and security of the masses.


Interlaboratory variability of rotational chair test results. Interlaboratory Rotational Chair Study Group.
Test-retest reliability of rotational chair testing for a single facility has previously been examined by others. The actual data analysis methods, however, have received far less attention. The variety of both hardware and software currently used theoretically may affect the results for a given subject tested at different facilities. The purposes of this study were, first, to quantify the amount of variability in the analysis of identical raw data files at multiple rotational chair testing facilities by using automated analysis; second, to evaluate the effect of operator intervention on the analysis; and third, to identify possible sources of variability. Raw data were collected from 10 normal subjects at 0.05 Hz and 0.5 Hz (50 degrees per second peak velocity). Diskettes containing raw electro-oculogram data files were then distributed to eight participating laboratories for analysis by two methods: (1) using automated analysis algorithms and (2) using the same algorithms but allowing operator intervention into the analysis. Response parameters calculated were gain and phase (re: velocity). The SD of gain values per subject for automated analysis ranged from 0.01 to 0.32 gain units and of phase values from 0.4 to 13.7 degrees. For analysis with operator intervention, the SD of gain values ranged from 0.02 to 0.10 gain units and of phase values from 0.4 to 4.4 degrees. The difference between automated analysis and analysis with operator intervention was significant for gain calculations (p < 0.02) but not for phase calculations (p > 0.05). This study demonstrates significant variability in automated analysis of rotational chair raw data for gain and phase.(ABSTRACT TRUNCATED AT 250 WORDS)


Revealing the presence of tryptamine new psychoactive substances using fused "neutral loss" spectra derived from DART high-resolution mass spectra.
A data fusion approach for the rapid extraction of core scaffold information that can be used to facilitate structure determination for new psychoactive substance (NPS) tryptamines is described. The method involves the screening of DART-HRMS data of new tryptamines against a partial least squares-discriminant analysis (PLS-DA) model that predicts the core tryptamine structure class into which the compound can be grouped. The PLS-DA prediction model was created and trained using neutral loss spectra derived from collision-induced dissociation (CID) DART mass spectral analysis of 50 tryptamine structures acquired at 60 V and 90 V, in which the sample groups were revealed by hierarchical clustering analysis (HCA). HCA of the fused neutral loss data clustered the 50 tryptamines into 10 groups based on the identities of the neutral fragments lost during fragmentation. "Leave-one-structure-out" validation of the PLS-DA model gave 100% accuracy, precision, sensitivity, and specificity. For external validation, the ability of the model to classify four compounds that were unfamiliar to it was tested, and the model was found to correctly predict the skeletal framework in each case. The results show proof of concept for how this approach can aide in the identification of new emerging psychoactive compounds.


Using imputed genotype data in the joint score tests for genetic association and gene-environment interactions in case-control studies.
Genome-wide association studies (GWAS) are now routinely imputed for untyped single nucleotide polymorphisms (SNPs) based on various powerful statistical algorithms for imputation trained on reference datasets. The use of predicted allele counts for imputed SNPs as the dosage variable is known to produce valid score test for genetic association. In this paper, we investigate how to best handle imputed SNPs in various modern complex tests for genetic associations incorporating gene-environment interactions. We focus on case-control association studies where inference for an underlying logistic regression model can be performed using alternative methods that rely on varying degree on an assumption of gene-environment independence in the underlying population. As increasingly large-scale GWAS are being performed through consortia effort where it is preferable to share only summary-level information across studies, we also describe simple mechanisms for implementing score tests based on standard meta-analysis of "one-step" maximum-likelihood estimates across studies. Applications of the methods in simulation studies and a dataset from GWAS of lung cancer illustrate ability of the proposed methods to maintain type-I error rates for the underlying testing procedures. For analysis of imputed SNPs, similar to typed SNPs, the retrospective methods can lead to considerable efficiency gain for modeling of gene-environment interactions under the assumption of gene-environment independence. Methods are made available for public use through CGEN R software package.


Colonic cancer during pregnancy: case report and review of the literature.
Colonic cancer during pregnancy is rare. Herein we describe a case of adenocarcinoma of the transverse colon in a 29-year-old pregnant patient. Early diagnosis is difficult because the initial symptoms of colorectal cancer, such as abdominal pain, nausea and vomiting, constipation, and abdominal distention, are often attributed to a normal pregnancy. Management of colonic cancer during pregnancy depends on gestational age and operability of the tumor. Medical and surgical management considerations are discussed.


Nanophotonic computational design.
In contrast to designing nanophotonic devices by tuning a handful of device parameters, we have developed a computational method which utilizes the full parameter space to design linear nanophotonic devices. We show that our method may indeed be capable of designing any linear nanophotonic device by demonstrating designed structures which are fully three-dimensional and multi-modal, exhibit novel functionality, have very compact footprints, exhibit high efficiency, and are manufacturable. In addition, we also demonstrate the ability to produce structures which are strongly robust to wavelength and temperature shift, as well as fabrication error. Critically, we show that our method does not require the user to be a nanophotonic expert or to perform any manual tuning. Instead, we are able to design devices solely based on the user's desired performance specification for the device.


Genetic regulation of dihydropyridine-sensitive calcium channels in brain may determine susceptibility to physical dependence on alcohol.
Experiments utilising rodents in vivo and cultures of adrenal cells in vitro have suggested that genetic regulation of dihydropyridine-sensitive calcium channels may be involved in dependence on alcohol. Selection of mouse lines for either a very severe ethanol-withdrawal syndrome (withdrawal seizure prone) or a very mild syndrome (withdrawal seizure resistant), has produced lines which differ very markedly in these characteristics. In these experiments, mice bred selectively for these symptoms for 26 generations, were compared for the severity of withdrawal from alcohol after inhalation of ethanol (plus injections of pyrazole) for 3 days. A proportion of animals from each line was killed before withdrawal and membranes from whole brain were analysed by radioligand binding for binding sites for [3H] nitrendipine. Mice which were withdrawal seizure prone showed a markedly greater severity of the ethanol-withdrawal syndrome, and also showed a significantly greater up-regulation of binding sites for [3H]nitrendipine with no significant difference in binding affinity. The results suggest a relationship between genetic susceptibility to dependence on alcohol and genetic regulation of neuronal calcium channels in brain.


[Perioperative thromboprophylaxis--for the immobilisation period, potential extension beyond hospitalisation].
Antithrombotic prophylaxis of venous thromboembolism after surgery, usually by means of subcutaneous administration of(low-molecular-weight) heparin, drastically reduces the incidence of postoperative thrombosis and pulmonary embolism. Therefore, this intervention is advocated in various national and international guidelines. A questionnaire-based study in this issue shows that 99% of surgeons in the Netherlands strictly adhere to these guidelines. Interestingly, the duration of thromboprophylaxis is much less clear and is usually restricted to the duration of hospitalisation. In view of the increasing number of surgical procedures in short-stay or even outpatient settings, it is possible that extended prophylaxis for perioperative thrombosis should be considered, particularly in patients with risk factors for thrombosis, such as the presence of malignant disease.


Inhibitory effect of ferulic acid on macrophage inflammatory protein-2 production in a murine macrophage cell line, RAW264.7.
We investigated time-related productions of certain cytokines in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, a murine macrophage cell line, by enzyme-linked immunosorbent assay. Macrophage inflammatory protein-2 (MIP-2) levels became detectable after 2 h and markedly increased over the first 8 h. Thereafter, this level remained at the same level between 10 and 16 h, and then increased again until 24 h, showing a tendency of biphasic pattern. Tumour necrosis factor (TNF)-alpha was detectable at 2 h and then increased sharply until 6 h at which it attained its peak. A low but recognizable level of interleukin (IL)-1alpha/beta was also detectable. When the inhibitory effect of ferulic acid (FA), an active component of the Rhizoma of Cimicifuga sp. used frequently as anti-inflammatory drug in Japanese Oriental medicines, was compared with that of dexamethasone (DX) on MIP-2 and TNF-alpha productions in response to LPS, both FA and DX could reduce the production of these cytokines in a dose-dependent manner. Concerning TNF-alpha, however, the inhibitory effect of FA was very weak compared with that of DX. In addition, FA as well as DX reduced MIP-2 production induced by TNF-alpha. These data suggest that MIP-2 might be induced by a direct effect of LPS and in part indirect one via initial induction of other cytokines such as TNF-alpha, leading a tendency of biphasic pattern. Comparing DX, FA is considered to be a novel and unique drug inhibiting MIP-2 production more selectively.


Schisandra chinensis regulates drug metabolizing enzymes and drug transporters via activation of Nrf2-mediated signaling pathway.
Drug metabolizing enzymes (DMEs) and drug transporters are regulated via epigenetic, transcriptional, posttranscriptional, and translational and posttranslational modifications. Phase I and II DMEs and drug transporters play an important role in the disposition and detoxification of a large number of endogenous and exogenous compounds. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a critical regulator of a variety of important cytoprotective genes that are involved in disposition and detoxification of xenobiotics. Schisandra chinensis (SC) is a commonly used traditional Chinese herbal medicine that has been primarily used to protect the liver because of its potent antioxidative and anti-inflammatory activities. SC can modulate some DMEs and drug transporters, but the underlying mechanisms are unclear. In this study, we aimed to explore the role of Nrf2 in the regulatory effect of SC extract (SCE) on selected DMEs and drug transporters in human hepatocellular liver carcinoma cell line (HepG2) cells. The results showed that SCE, schisandrin A, and schisandrin B significantly increased the expression of Nicotinamide Adenine Dinucleotide Phosphate-oxidase or:quinone oxidoreductase 1, heme oxygenase-1, glutamate-cysteine ligase, and glutathione S-transferase A4 at both transcriptional and posttranscriptional levels. Incubation of HepG2 cells with SCE resulted in a significant increase in the intracellular level of glutathione and total glutathione S-transferase content. SCE significantly elevated the messenger ribonucleic acid and protein levels of P-glycoprotein and multidrug resistance-associated protein 2 and 4, whereas the expression of organic anion transporting peptide 1A2 and 1B1 was significantly downregulated by SCE. Knockdown of Nrf2 by small interfering ribonucleic acid attenuated the regulatory effect of SCE on these DMEs and drug transporters. SCE significantly upregulated Nrf2 and promoted the translocation of Nrf2 from cytoplasm to the nuclei. Additionally, SCE significantly suppressed the expression of cytosolic Kelch-like ECH-associated protein 1 (the repressor of Nrf2) and remarkably increased Nrf2 stability in HepG2 cells. Taken together, our findings suggest that the hepatoprotective effects of SCE may be partially ascribed to the modulation of DMEs and drug transporters via Nrf2-mediated signaling pathway. SCE may alter the pharmacokinetics of other coadministered drugs that are substrates of these DMEs and transporters and thus cause unfavorable herb-drug interactions.


Clinical manifestations of new versus recrudescent malaria infections following anti-malarial drug treatment.
Distinguishing new from recrudescent infections in post-treatment episodes of malaria is standard in anti-malarial drug efficacy trials. New infections are not considered malaria treatment failures and as a result, the prevention of subsequent episodes of malaria infection is not reported as a study outcome. However, in moderate and high transmission settings, new infections are common and the ability of a short-acting medication to cure an initial infection may be outweighed by its inability to prevent the next imminent infection. The clinical benefit of preventing new infections has never been compared to that of curing the initial infection. Children enrolled in a sulphadoxine-pyrimethamine efficacy study in Blantyre, Malawi from 1998-2004 were prospectively evaluated. Six neutral microsatellites were used to classify new and recrudescent infections in children aged less than 10 years with recurrent malaria infections. Children from the study who did not experience recurrent parasitaemia comprised the baseline group. The odds of fever and anaemia, the rate of haemoglobin recovery and time to recurrence were compared among the groups. Fever and anemia were more common among children with parasitaemia compared to those who remained infection-free throughout the study period. When comparing recrudescent vs. new infections, the incidence of fever was not statistically different. However, children with recrudescent infections had a less robust haematological recovery and also experienced recurrence sooner than those whose infection was classified as new. The results of this study confirm the paramount importance of providing curative treatment for all malaria infections. Although new and recrudescent infections caused febrile illnesses at a similar rate, recurrence due to recrudescent infection did have a worsened haemological outcome than recurrence due to new infections. Local decision-makers should take into account the results of genotyping to distinguish new from recrudescent infections when determining treatment policy on a population level. It is appropriate to weigh recrudescent malaria more heavily than new infection in assessing treatment efficacy.


Stimulation of calcium influx by platelet activating factor in Dictyostelium.
Platelet activating factor (PAF) induces Ca2+ influx in Dictyostelium discoideum. In this investigation we used this activity to analyze the mechanism of PAF action. We found that PAF activity was confined to the period of spike-shaped oscillations and suggest that the role of PAF is to augment cAMP relay. PAF seems to act only a few times during this time period of two hours, since Ca2+ entry adapted to a subsequent stimulus for about 30 minutes. PAF showed a reduced response in the G protein beta- strain LW14 and was unable to induce Ca2+ influx in the G alpha 2- strains HC85 and JM1. The latter expresses the cAMP receptors cAR1 constitutively, and exhibits cAMP-induced Ca2+ influx, albeit at a reduced level. In order to decide whether the inability of PAF to elicit a Ca2+ response in JM1 cells was due to the lack of differentiation and/or the lack of G alpha 2, we inhibited the IP3-dependent pathway with compound U73122 and found that Ca2+ entry was blocked, whereas a closely related inactive compound, U73343, did not alter the response. In agreement with this, NBD-Cl, an inhibitor of Ca2+ uptake into the IP3-sensitive store in Dictyostelium, also abolished PAF activity. The latter was not inhibited by the plasma membrane antagonists BN-52021 or WEB 2170. Therefore PAF seems to operate intracellularly via the IP3-signalling pathway at or upstream of the IP3-sensitive store.


Are fission-fusion dynamics consistent among populations? A large-scale study with Cape buffalo.
Fission-fusion dynamics allow animals to manage costs and benefits of group living by adjusting group size. The degree of intraspecific variation in fission-fusion dynamics across the geographical range is poorly known. During 2008-2016, 38 adult female Cape buffalo were equipped with GPS collars in three populations located in different protected areas (Gonarezhou National Park and Hwange National Park, Zimbabwe; Kruger National Park, South Africa) to investigate the patterns and environmental drivers of fission-fusion dynamics among populations. We estimated home range overlap and fission and fusion events between Cape buffalo dyads. We investigated the temporal dynamics of both events at daily and seasonal scales and examined the influence of habitat and distance to water on event location. Fission-fusion dynamics were generally consistent across populations: Fission and fusion periods lasted on average between less than one day and three days. However, we found seasonal differences in the underlying patterns of fission and fusion, which point out the likely influence of resource availability and distribution in time on group dynamics: During the wet season, Cape buffalo split and associated more frequently and were in the same or in a different subgroup for shorter periods. Cape buffalo subgroups were more likely to merge than to split in open areas located near water, but overall vegetation and distance to water were very poor predictors of where fission and fusion events occurred. This study is one of the first to quantify fission-fusion dynamics in a single species across several populations with a common methodology, thus robustly questioning the behavioral flexibility of fission-fusion dynamics among environments.


Quantifying the extent of lateral gene transfer required to Avert a 'genome of Eden'.
The complex pattern of presence and absence of many genes across different species provides tantalising clues as to how genes evolved through the processes of gene genesis, gene loss, and lateral gene transfer (LGT). The extent of LGT, particularly in prokaryotes, and its implications for creating a 'network of life' rather than a 'tree of life' is controversial. In this paper, we formally model the problem of quantifying LGT, and provide exact mathematical bounds, and new computational results. In particular, we investigate the computational complexity of quantifying the extent of LGT under the simple models of gene genesis, loss, and transfer on which a recent heuristic analysis of biological data relied. Our approach takes advantage of a relationship between LGT optimization and graph-theoretical concepts such as tree width and network flow.


Phase synchronization in brain networks derived from correlation between probabilities of recurrences in functional MRI data.
It is increasingly being recognized that resting state brain connectivity derived from functional magnetic resonance imaging (fMRI) data is an important marker of brain function both in healthy and clinical populations. Though linear correlation has been extensively used to characterize brain connectivity, it is limited to detecting first order dependencies. In this study, we propose a framework where in phase synchronization (PS) between brain regions is characterized using a new metric "correlation between probabilities of recurrence" (CPR) and subsequent graph-theoretic analysis of the ensuing networks. We applied this method to resting state fMRI data obtained from human subjects with and without administration of propofol anesthetic. Our results showed decreased PS during anesthesia and a biologically more plausible community structure using CPR rather than linear correlation. We conclude that CPR provides an attractive nonparametric method for modeling interactions in brain networks as compared to standard correlation for obtaining physiologically meaningful insights about brain function.


Aristolochic acid and the risk of cancers in patients with type 2 diabetes: Nationwide population-based cohort study.
Both aristolochic acid (AA) exposure and diabetic can increase risk of certain cancers,whetherAAexposureincreases cancer risk in diabetic patientsisunknown. The purpose of this study was to investigate the association between the use of Chinese herbal products containing AA and the risk of cancer in diabetic patients. A cohort study was conducted using the National Health Insurance Research Database in Taiwan. Patients older than 18 years who were diagnosed with diabetes between 1997 and 2010 were enrolled in our cohort. The use of Chinese herbal products containing AA was recorded from the beginning of 1997 until the ban of herbs containing AA in November 2003. Patients were individually tracked to identify cancer incidence between 1997 and 2013. Only patients who visited traditional Chinese medicine clinics between 1997 and 1 year before the end of follow-up were included in the cohort to ensure comparability. Cox proportional hazards regression was used to calculate the hazard ratio for the association between the use of Chinese herbal products containing AA and the occurrence of cancer. Among the 430 377 male and 431 956 female patients with diabetes enrolled in our cohort, 37 554 and 31 535 cancer diagnoses were recorded during the study period, respectively. The use of AA-containing herbal products was associated with a significantly higher risk of liver, colorectum, kidney, bladder, prostate, pelvis, and ureter cancer in a dose-dependent manner. An increased risk of extrahepatic bile duct cancer in women was also associated with AA exposure at doses of more than 500 mg. Association between AA exposure and the risk of some cancers were found in this study. AA exposure might increase risk of kidney,bladder,pelvis, ureter,liver,colorectum,andprostatecancer in all patientsandextrahepatic bile duct cancerin women.


Screening Positive for Cognitive Impairment: Impact on Healthcare Utilization and Provider Action in Primary and Specialty Care Practices.
Alzheimer's disease, the most common cause of dementia, goes unrecognized in half of patients presenting to healthcare providers and is associated with increased acute care utilization. Routine cognitive screening of older adults in healthcare settings could improve rates of dementia diagnosis and patterns of healthcare utilization. To evaluate the impact of screening positive for cognitive impairment on provider action in primary and specialty care practices and patient healthcare utilization. Individuals asymptomatic for cognitive impairment completed cognitive screening with the Mini-Cog (MC). Outcomes included MC screen-positive rates, provider follow-up actions, and healthcare utilization for all participants over a period of 36 months (18 months prior to and following MC screening). Data were extracted from the electronic medical record (EMR). Healthcare provider interventions and healthcare utilization for screen-positive and -negative groups, before and after screening, were compared. Primary and specialty care patients (n = 787) aged ≥ 65 without history of cognitive impairment seen in HealthPartners, an integrated healthcare system in Minnesota and Western Wisconsin. In primary care and neurology practices combined, over the entire 36-month study window, individuals screening positive showed 32% higher rates of ED visits (p < 0.05) pre and post-screening compared to those screening negative. Screen positive also showed 39% higher rates of hospitalizations pre-screening (p < 0.05) and 58% higher rates post-screening (p < 0.01). While screen-detected cognitive impairment was associated with some relevant provider follow-up action in 32% of individuals, subsequent healthcare utilization did not change between the 18-month pre- and post-screening periods. Despite being associated with higher rates of healthcare utilization, screening positive on the MC led to a change in provider action in a minority of cases and did not reduce post-screening healthcare utilization. Screening for cognitive impairment alone is not sufficient to alter patterns of provider practice or patient healthcare utilization.