Prehospital extracorporeal cardiopulmonary resuscitation for cardiac arrest patients in rural areas: a case report of two patients.
The prognosis of out-of-hospital cardiac arrest remains poor, especially for cardiopulmonary arrest patients in rural areas with longer transport duration to hospitals. In June 2016, we began providing prehospital extracorporeal life support using a mobile operating room for emergency surgery. We report two patients who survived after receiving prehospital extracorporeal cardiopulmonary resuscitation and were discharged. A patient with cardiopulmonary arrest from accidental hypothermia due to drowning survived with good neurological outcomes after on-site extracorporeal cardiopulmonary resuscitation immediately after rescue. The other patient who survived experienced cardiopulmonary arrest at his workplace, which was approximately 90 min from the center. Prehospital extracorporeal cardiopulmonary resuscitation shortened the cardiopulmonary arrest time by an estimated 30 min, and the patient survived until the hospital. Prehospital extracorporeal cardiopulmonary resuscitation has the potential to save lives in rural areas by reducing low-flow time.


Multiple-Organ Deceased Donation Is Associated With Superior Outcomes for Grafts and Transplant Recipients Compared With Kidney-Only Donation.
Since the development of Kidney Donor Profile Index, outcome differences based on number of donated organs per donor have not been evaluated. We retrospectively analyzed data from the United Network for Organ Sharing national database, which identified 176 311 adult renal transplant recipients from 2000 to 2019 with a deceased donor kidney from a kidney-only donor, from a donor of kidney and liver but no other organs, or from a multiorgan donor. Graft failure and transplant recipient survival were primary outcomes. A multivariate Cox proportional hazards model controlled for Kidney Donor Profile Index differences. Overall, multiorgan donors had a lower Kidney Donor Profile Index versus other donor types (odds ratio, 0.042; P < .001). Kidneys from donors with a higher Kidney Donor Profile Index were 95% less likely to be procured with other organs (P < .001). The recipient and graft survival rates for kidney transplants from kidney-only donors and from donors of kidney and liver but no other organs were 76% and 70%, respectively, whereas recipient and graft survival rates for kidney transplants from multiorgan donors were approximately 82% and 77%, respectively, at 5 years. After adjustment for the Kidney Donor Profile Index, the recipients of multiorgan donor grafts demonstrated superior outcomes for graft survival and mortality compared with kidney-only donors or kidney and liver only donors. The multiorgan donor status may be an additional consideration in future renal allocation calculators.


Human body shape index based on an experimentally derived model of human growth.
To test the assumption of geometrically similar growth by developing experimentally derived models of human body growth during the age interval of 5 to 18 years; to use these derived growth models to establish a new human body shape index (HBSI) based on natural age-related changes in human body shape (HBS); and to compare various metrics of relative body weight (body mass index [BMI], ponderal index [PI], and HBSI) in a sample of 5- to 18-year-old children. Nondisabled Polish children (n = 847) participated in this descriptive study. To model growth, the best fit between body height (H) and body mass (M) was calculated for each sex using the allometric equation M = m(i) H(chi). HBSI was calculated separately for girls and boys, using sex-specific values for chi and a general HBSI from combined data. The customary BMI and PI were calculated and compared with HBSI values. The models of growth were M = 13.11H(2.84) (R2 = 0.90) for girls and M = 13.64H(2.68) (R2 = 0.91) for boys. HBSI values contained less inherent variability and were less influenced by growth (age and height) compared with BMI and PI. Age-related growth during childhood is sex-specific and not geometrically similar. Therefore, indices of HBS formulated from experimentally derived models of human growth are superior to customary geometric similarity-based indices for characterizing HBS in children during the formative growth years.


Low-dose intravenous calcitriol treatment of secondary hyperparathyroidism in hemodialysis patients. Italian Group for the Study of Intravenous Calcitriol.
Intravenous calcitriol is known to directly suppress PTH secretion and release. We evaluated the effect of four months of treatment with low-dose intravenous calcitriol on PTH levels in 83 hemodialysis patients. The criteria for including patients in the study were a serum PTH levels at least four times the normal limit, a serum total calcium less than 10 mg/dl and good control of the serum phosphorus level. All patients underwent standard bicarbonate or acetate dialysis; dialysate calcium level was maintained at the usual 3.5 mEq/liter concentration. Initial calcitriol dose was 0.87 +/- 0.02 (SEM) micrograms (0.015 micrograms/kg body wt) thrice weekly at the end of dialysis, and it was reduced in case of hypercalcemia or elevated calcium-phosphate product. Seven out of 83 patients dropped out during treatment. Among the 76 patients who completed the study, 58 (76%) showed a highly significant decrease of intact PTH levels (average reduction 48%) and of alkaline phosphatase levels after four months of therapy. Total serum calcium increased slightly but significantly in the responder group but remained unchanged in the non-responders. No significant changes in ionized calcium levels could be detected, even in responders. Treatment was well tolerated by patients, but 60% of them had transient episodes of hyperphosphatemia. Mean serum phosphate was 4.95 mg/dl at the beginning of the study. It increased significantly after four months of treatment in patients who showed a decrease of PTH levels, although it remained within acceptable limits, below 5.5 mg/dl. Twenty-eight of 76 patients (37%) reduced the dose of calcitriol because their calcium-phosphate products exceeded 60.(ABSTRACT TRUNCATED AT 250 WORDS)


Characteristics and Unidimensionality of Non-suicidal Self-injury in a Community Sample of Spanish Adolescents.
Few studies have explored the prevalence and unidimensional structure of Non-Suicidal Self-Injury (NSSI) in Spanish adolescents. In this study, we estimated the prevalence, types, and functions of NSSI in 1,733 Spanish adolescents, and we tested the unidimensional factorial structure of non-suicidal self-injury. 24.6% of the adolescents referred to having self-injured at least once during their lifetime, and 12.7% had self-injured using more severe methods of NSSI. The most frequent types of NSSI were interfering with wounds (14.6%), scratching (12.5%), and hitting (11.7%). We found no differences between genders in NSSI frequency. The majority of the participants who self-injured referred to intrapersonal functions. The confirmatory factor analyses of the ISAS-I structure showed a single factor with 10 items, thus supporting the unidimensionality of the construct of NSSI. NSSIs reflect difficulties in regulating emotions or managing interpersonal relationships in young Spanish people, and these behaviours seem to constitute a unique and latent dimension. Thus, there is a need for intervention programmes focused on managing problems of emotional regulation and maladaptive self-injury behaviours.


Cryptosporidium infection in major histocompatibility complex congeneic strains of mice: variation in susceptibility and the role of T-cell cytokine responses.
Studies with murine infection models have shown that immunity to the protozoan parasite Cryptosporidium involves T-cells and interferon-gamma (IFN-gamma) activity. The present study was performed to compare the course of infection of Cryptosporidium muris in major histocompatibility complex (MHC) congeneic strains of mice and examine the relationship between susceptibility to infection and production of T-cell cytokines. In experiments with BALB mice, the BALB/c strain (H-2d) produced significantly fewer oocysts and recovered from infection sooner than the BALB/B (H-2b) or BALB/K (H-2k) strains. BALB/B X BALB/c F1 hybrid mice were found to express the more susceptible phenotype of the BALB/B parent strain, indicating that the gene(s) in the H-2 locus conferring increased susceptibility to C. muris infection was dominant. At different times during infection of the resistant BALB/c strain and the susceptible BALB/B strain, splenocytes were cultured with soluble parasite antigen and measurements were made of production of a number of T-cell cytokines. Similar patterns of increasing levels of IFN-gamma and interleukin 2 (IL-2) were observed in both the resistant and susceptible strains during the patent stage of infection, indicating that production of these type 1 T-helper-cell (TH1) cytokines (i.e. involved in cell-mediated responses) correlated with the development of immunity. This also suggested that the increased susceptibility of BALB/B mice was not associated with a defective TH1 cytokine response. In the study of TH2 cytokines (involved in induction of an antibody response), low levels of IL-10 were detected during infection of BALB/c and BALB/B mice. In contrast, although IL-4 was released by splenocytes of both strains, significantly larger amounts were obtained from cells of the susceptible BALB/B mice in the early stages of infection. Thus, the H-2-dependent variation in susceptibility to infection between these BALB strains correlated with a difference in the pattern of IL-4 secretion.


K-Cell activity in lamina proprial lymphocytes from the human colon.
Using an enzymatic method for their isolation, it has been shown that human colonic lamina proprial lymphocytes, isolated from patients with various colonic diseases and depleted of polymorphonuclear leukocytes and macrophages, demonstrated K-cell activity in two antibody-dependent cell-mediated cytotoxicity assays in vitro. No differences were found between the activities of lamina proprial lymphocytes isolated from colonic specimens involved by Crohn's disease, chronic ulcerative colitis, or colonorectal carcinoma. K-cell activity was demonstrable using lymphoid cells isolated from the colons of patients receiving steroid therapy at the time of the therapeutic resections. These findings indicate the need for further investigation of possible roles for K-cells in local immune responses in the human bowel mucosa in inflammatory and neoplastic diseases.


Detection of cellular traction forces via the force-triggered Cas12a-mediated catalytic cleavage of a fluorogenic reporter strand.
Molecular forces generated by cell receptors are infrequent and transient, and hence difficult to detect. Here we report an assay that leverages the CRISPR-associated protein 12a (Cas12a) to amplify the detection of cellular traction forces generated by as few as 50 adherent cells. The assay involves the immobilization of a DNA duplex modified with a ligand specific for a cell receptor. Traction forces of tens of piconewtons trigger the dehybridization of the duplex, exposing a cryptic Cas12-activating strand that sets off the indiscriminate Cas12-mediated cleavage of a fluorogenic reporter strand. We used the assay to perform hundreds of force measurements using human platelets from a single blood draw to extract individualized dose-response curves and half-maximal inhibitory concentrations for a panel of antiplatelet drugs. For seven patients who had undergone cardiopulmonary bypass, platelet dysfunction strongly correlated with the need for platelet transfusion to limit bleeding. The Cas12a-mediated detection of cellular traction forces may be used to assess cell state, and to screen for genes, cell-adhesion ligands, drugs or metabolites that modulate cell mechanics.


Structuring Research Rotations to Facilitate Surgery Residents' Academic Productivity.
We sought to enhance opportunities for general surgery residents to conduct research during residency without having to take dedicated time out of clinical training. To this end, we created structured research rotations to facilitate and support resident research. Research blocks of four week's duration were introduced for categorical interns and post-graduate year (PGY) 4 residents. Interns had no clinical responsibilities during their research blocks while PGY 4 residents shadowed their mentor in the clinical setting. Research projects were developed and prepared in advance to maximize productivity during the research rotation. General surgery residency program at an urban, academic, safety-net, tertiary care hospital PARTICIPANTS: Categorical general surgery interns and PGY 4 general surgery residents RESULTS: The research rotations were first offered in the 2019 to 2020 academic year (AY). 10 interns and 11 PGY 4 residents have since completed the rotations; of the PGY 4 residents, 6 had not previously taken any time off for research activities. Research projects varied between residents and focused on basic science, clinical outcomes, quality improvement, and education. Through establishment of dedicated research rotations, we were able to increase resident engagement in a variety of research activities. We provide a simple model for training programs seeking increased research engagement and productivity for their residents without extending training time.


Dopaminergic control of foregut contractions in Locusta migratoria.
Tyrosine hydroxylase-like immunoreactivity is present in cell bodies and processes in the brain and optic lobes of Locusta migratoria, with processes projecting along the frontal connectives to form a neuropile within the frontal ganglion. Immunoreactive cell bodies and processes are also evident in the hypocerebral and ventricular ganglia with processes extending over the foregut. Tyrosine hydroxylase is the rate-limiting enzyme in dopamine biosynthesis, and high-performance liquid chromatography coupled to electrochemical detection was used to confirm the presence of dopamine in the innervation to the foregut. Spontaneous foregut contractions are under the control of the ventricular ganglia and are absent when these ganglia are removed. Dopamine leads to an inhibition of both the amplitude and frequency of phasic contractions of the foregut that are produced when the ventricular ganglia are left attached. Dopamine has direct effects on the foregut muscle in the absence of the ventricular ganglia, inhibiting a proctolin-induced contraction in a dose-dependent manner.


Mortality of Surgically Treated Neurotrauma in Elderly Patients and the Development of a Prediction Score: Geriatric Neurotrauma Mortality Score.
As the population worldwide is aging, the need for surgery in elderly patients with neurotrauma is increasing. The aim of this study was to compare the outcome of elderly patients undergoing surgery for neurotrauma with younger patients and to identify the risk factors for mortality. We retrospectively analyzed consecutive patients undergoing craniotomy or craniectomy for neurotrauma at our institution from 2012 to 2019. Patients were divided into two groups (≥70 years or <70 years) and compared. The primary outcome was the 30-day mortality rate. Potential risk factors for 30-day mortality were assessed in a uni- and multivariate regression model for both age groups, forming the basis of a 30-day mortality prediction score. We included 163 consecutive patients (average age 57.98 ± 19.87 years); 54 patients were ≥70 years. Patients ≥70 years showed a significantly better median preoperative Glasgow Coma Scale (GCS) score compared with young patients (P < 0.001), and fewer pupil asymmetry (P = 0.001), despite having a higher Marshall score (P = 0.07) at admission. Multivariate regression analysis identified low pre- and postoperative GCS scores and the lack of prompt postoperative prophylactic low-molecular-weight heparin treatment as risk factors for 30-day mortality. Our score showed moderate accuracy in predicting 30-day mortality with an area under the curve of 0.76. Elderly patients after neurotrauma present with a better GCS at admission despite having more severe radiographic injuries. Mortality and favorable outcome rates are comparable between the age groups.


Electrochemical analysis in charge-transfer science: The devil in the details.
It is easy to carry out electrochemical analysis. It is demanding, however, to do it right, as inherent challenges, emerging from details in the data collection and the result interpretation, frequently present themselves. In pertinence to electron-donor-acceptor interactions, herein, we focus on voltammetrically obtained electrochemical potentials and their immense utility for extracting important characteristics of molecular analytes. Recommendations how to address key pending challenges, based on recent developments in electroanalysis and charge-transfer science, accompany the discussions on undesired impacts from irreversibility of oxidation and reduction, supporting electrolytes, choices of reference, liquid junctions, and 'nonideality' of molecular shapes. As the wide implications of charge transfer are indisputable, using the tools at our disposal for improving the reliability of electroanalysis is crucial for advancing modern science and engineering.


Morphometrical analysis of glomerular changes induced by cyclosporine in the rat.
Functional and morphologic techniques were used to study the renal changes induced by a long-term exposure of normal rats to cyclosporine A (CsA), as well as their potential reversibility. CsA treatment for 3 months resulted in a significant (P less than 0.01) reduction of glomerular filtration rate (GFR) as compared with vehicle-treated animals. Histological examination of the kidneys showed mild glomerular damage characterized by ischemic lesions, increased mesangial matrix, and intracapillary hypercellularity in the CsA-treated group, but not in the vehicle-treated group. Proximal tubular abnormalities and limited areas of interstitial fibrosis were also present in the CsA group. A complete reconstruction of glomerular corpuscle was used to evaluate the consequence of CsA-induced renal ischemia on capillary tuft volume. The results showed that in rats administered CsA for 3 months glomerular volume distribution was shifted toward small glomeruli. Prolongation of CsA administration for 5 months did not result in a further decrease in GFR, and was associated with the appearance of a subset of glomeruli that became larger than normal. We have also investigated whether, once established, CsA-induced renal injury is reversible. In rats that were administered CsA for 3 months and then treatment discontinued for 2 months, GFR returned to pretreatment values and partial reversibility of morphologic changes was observed. Morphometric analysis showed that 2 months after withdrawal of CsA, glomerular volume distribution was almost comparable to that observed in vehicle-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)


Hypoxia-induced β-catenin downregulation involves p53-dependent activation of Siah-1.
Solid tumors contain extensive hypoxic areas and it is of considerable importance to decipher the potential role of hypoxia in signaling pathway regulation. In the present study, we examined the impact of hypoxia on β-catenin status and the mechanisms involved. Hypoxia significantly decreased β-catenin protein, but had no effect on glycogen synthase kinase (GSK)-3β or adenomatous polyposis coli (APC) levels. However, hypoxia-induced β-catenin downregulation seemed to require APC but not GSK-3β. Further investigation revealed that hypoxia significantly upregulated Siah-1, the human homolog of Drosophila seven in absentia. In addition, hypoxia augmented the interaction between β-catenin and SIP and Skp1. Silencing of Siah-1, as well as the use of a dominant negative Siah-1 mutant, attenuated these responses to hypoxia and rescued β-catenin transactivation. The Siah-1-mediated degradation of β-catenin during hypoxia may involve p53, but not hypoxia-inducible factor-1, activation. Together, the results suggest that hypoxia downregulates β-catenin by increasing Siah-1 expression in a p53-dependent manner.


Genetic interactions between the Polycomb locus and the Antennapedia and Bithorax complexes of Drosophila.
We have studied the embryonic and adult phenotypes of genetic combinations between Polycomb (Pc), Regulator of bithorax (Rg-bx) and the genes of the Bithorax complex (BX-C) and the Antennapedia complex (ANT-C). The products of Pc and Rg-bx genes act antagonistically, their mutant combinations leading to the ectopic expression of genes of the BX-C and ANT-C. The genetic analysis of the Pc locus suggests it is a complex gene. Pc+ products behave as members of a "regulatory set" that negatively control the expression of BX-C and ANT-C genes. Genetic combinations between different doses of Pc, Rg-bx and the genes of the BX-C and ANT-C have phenotypes which may be interpreted as resulting from ectopic derepression of posterior selector genes repressing selector genes of anterior segments. The transformation phenotypes of certain genetic combinations differ in embryos and adults. A model of regulation of the BX-C and the ANT-C genes during the imaginal cell proliferation is presented, in which the specification state is maintained by self-activation of a given selector gene and down modulation of other selector genes in the same cell.


'Levodopa Phobia': a review of a not uncommon and consequential phenomenon.
'Levodopa Phobia' is under-recognised in Parkinson's disease but can cause profound detrimental clinical complications if left to continue. Several types can be encountered in clinical practice and can be driven by a misplaced fear of levodopa-induced dyskinesias, other gastrointestinal side effects and also the theoretical notion that levodopa may be toxic to dopaminergic neurons in the brain. The condition can be underpinned by a sense of strong influence from the physicians or carers who are unwilling to prescribe or consider levodopa, and also high levels of anxiety or even impulsive compulsive traits in patients who have been influenced by available literature or social media-based information. If unrecognised, the clinical issue may lead to motor deterioration and related muscle contractures leading to social isolation as well as a range of non-motor symptoms. In some, there may be emergence of intrusive impulse control disorders because of reliance on only dopamine agonists related to the fear of taking levodopa. Four cases illustrate the different patterns of 'Levodopa Phobia' in this study. Management of levodopa phobia is complex and includes recognition and skilled neuropsychological interventions to break the misperceptions about the complications of levodopa therapy.


Inhibition of the tumor-associated urokinase-type plasminogen activation system: effects of high-level synthesis of soluble urokinase receptor in ovarian and breast cancer cells in vitro and in vivo.
Tumor cell invasion and metastasis depend on the coordinated and temporal expression of proteolytic enzymes to degrade the surrounding extracellular matrix and of adhesion molecules to remodel cell-cell and/or cell-matrix attachments. The tumor cell-associated urokinase-type plasminogen activator system, consisting of the serine protease uPA, its substrate plasminogen, its membrane-bound receptor uPAR, as well as its inhibitors PAI-1 and PAI-2, plays an important role in these pericellular processes. Especially, association of the proteolytic activity of uPA with the cell surface via interaction with uPAR significantly increases the invasive capacity of tumor cells. Consequently, various approaches have been pursued to interfere with the expression or activity of uPA and/or uPAR, including antisense strategies and the development of active-site inhibitors of uPA or inhibitors of uPA/uPAR interaction. In this review, we focus on the results obtained in vitro and in vivo with tumor cells producing high levels of a recombinant soluble form of uPAR, which efficiently inhibits uPA binding to cell surface-associated uPAR and, by this, acts as a scavenger for uPA.


Delays in seeking, reaching and access to quality cancer care in sub-Saharan Africa: a systematic review.
Late presentation and delays in diagnosis and treatment consistently translate into poor outcomes in sub-Saharan Africa (SSA). The aim of this study was to collate and appraise the factors influencing diagnostic and treatment delays of adult solid tumours in SSA. Systematic review with assessment of bias using Risk of Bias in Non-randomised Studies of Exposures (ROBINS-E) tool. PubMed and Embase, for publications from January 1995 to March 2021. Inclusion criteria: quantitative or mixed-method research, publications in English, on solid cancers in SSA countries. paediatric populations, haematologic malignancies, and assessments of public perceptions and awareness of cancer (since the focus was on patients with a cancer diagnosis and treatment pathways). Two reviewers extracted and validated the studies. Data included year of publication; country; demographic characteristics; country-level setting; disease subsite; study design; type of delay, reasons for delay and primary outcomes. 57 out of 193 full-text reviews were included. 40% were from Nigeria or Ethiopia. 70% focused on breast or cervical cancer. 43 studies had a high risk of bias at preliminary stages of quality assessment. 14 studies met the criteria for full assessment and all totaled to either high or very high risk of bias across seven domains. Reasons for delays included high costs of diagnostic and treatment services; lack of coordination between primary, secondary and tertiary healthcare sectors; inadequate staffing; and continued reliance on traditional healers and complimentary medicines. Robust research to inform policy on the barriers to quality cancer care in SSA is absent. The focus of most research is on breast and cervical cancers. Research outputs are from few countries. It is imperative that we investigate the complex interaction of these factors to build resilient and effective cancer control programmes.


Validation of the Welch Allyn SureBP (inflation) and StepBP (deflation) algorithms by AAMI standard testing and BHS data analysis.
We evaluated two new Welch Allyn automated blood pressure (BP) algorithms. The first, SureBP, estimates BP during cuff inflation; the second, StepBP, does so during deflation. We followed the American National Standards Institute/Association for the Advancement of Medical Instrumentation SP10:2006 standard for testing and data analysis. The data were also analyzed using the British Hypertension Society analysis strategy. We tested children, adolescents, and adults. The requirements of the American National Standards Institute/Association for the Advancement of Medical Instrumentation SP10:2006 standard were fulfilled with respect to BP levels, arm sizes, and ages. Association for the Advancement of Medical Instrumentation SP10 Method 1 data analysis was used. The mean±standard deviation for the device readings compared with auscultation by paired, trained, blinded observers in the SureBP mode were -2.14±7.44 mmHg for systolic BP (SBP) and -0.55±5.98 mmHg for diastolic BP (DBP). In the StepBP mode, the differences were -3.61±6.30 mmHg for SBP and -2.03±5.30 mmHg for DBP. Both algorithms achieved an A grade for both SBP and DBP by British Hypertension Society analysis. The SureBP inflation-based algorithm will be available in many new-generation Welch Allyn monitors. Its use will reduce the time it takes to estimate BP in critical patient care circumstances. The device will not need to inflate to excessive suprasystolic BPs to obtain the SBP values. Deflation is rapid once SBP has been determined, thus reducing the total time of cuff inflation and reducing patient discomfort. If the SureBP fails to obtain a BP value, the StepBP algorithm is activated to estimate BP by traditional deflation methodology.


Methodologic considerations in the design and analysis of nested case-control studies: association between cytokines and postoperative delirium.
The nested case-control study (NCC) design within a prospective cohort study is used when outcome data are available for all subjects, but the exposure of interest has not been collected, and is difficult or prohibitively expensive to obtain for all subjects. A NCC analysis with good matching procedures yields estimates that are as efficient and unbiased as estimates from the full cohort study. We present methodological considerations in a matched NCC design and analysis, which include the choice of match algorithms, analysis methods to evaluate the association of exposures of interest with outcomes, and consideration of overmatching. Matched, NCC design within a longitudinal observational prospective cohort study in the setting of two academic hospitals. Study participants are patients aged over 70 years who underwent scheduled major non-cardiac surgery. The primary outcome was postoperative delirium from in-hospital interviews and medical record review. The main exposure was IL-6 concentration (pg/ml) from blood sampled at three time points before delirium occurred. We used nonparametric signed ranked test to test for the median of the paired differences. We used conditional logistic regression to model the risk of IL-6 on delirium incidence. Simulation was used to generate a sample of cohort data on which unconditional multivariable logistic regression was used, and the results were compared to those of the conditional logistic regression. Partial R-square was used to assess the level of overmatching. We found that the optimal match algorithm yielded more matched pairs than the greedy algorithm. The choice of analytic strategy-whether to consider measured cytokine levels as the predictor or outcome-- yielded inferences that have different clinical interpretations but similar levels of statistical significance. Estimation results from NCC design using conditional logistic regression, and from simulated cohort design using unconditional logistic regression, were similar. We found minimal evidence for overmatching. Using a matched NCC approach introduces methodological challenges into the study design and data analysis. Nonetheless, with careful selection of the match algorithm, match factors, and analysis methods, this design is cost effective and, for our study, yields estimates that are similar to those from a prospective cohort study design.


Self-other discrepancies in electrophysiological response to outcome evaluation in the Balloon Analogue Risk Task.
The topic of self-other differences in decision-making has gained considerable attention in recent years. Despite a broad range of behavior studies that have shown self-other discrepancy in decision-making, few neuroimaging studies with event-related potentials (ERPs) have directly compared decisions made for oneself with those made for others. It remains controversial whether self-other differences of outcome evaluations in gambling tasks can also be shown in brain potentials. In this study, we used event-related potentials with a Balloon Analogue Risk Task (BART) paradigm, a sequential, dynamic decision-making task to examine the effects of self-other differences on evaluation outcome in brain activity. Feedback Related Negativity (FRN) and P300 components were analyzed with respect to feedback valence (win vs. loss) and beneficiary (self vs. stranger). The ERP results showed that when making decisions for oneself, the negative outcome feedback evoked a larger P300 compared to making decisions for a stranger. However, there was no significant effect of self-other differences when the outcome feedback was positive. In contrast, regardless of whether the feedback was positive or negative, the FRN amplitude was insensitive to the self-other manipulation. Furthermore, we found that both components were modulated by the valence of the feedback. More pronounced FRN and P300 were induced when the feedback was negative, relative to when the feedback was positive. Our findings indicate that brain responses to outcome evaluation on the BART may be divided into an early semi-automatic processing stage and a later cognitive appraisal stage and that the self-other differences in sequential, dynamic decision-making tasks under uncertainty mainly affect the allocation of attention resources in the late cognitive processing stage.


Autoimmune hemolytic anemia: magnetic resonance findings.
Idiopathic autoimmune hemolytic anemia (AIHA) is a rare hematological disease typically characterized by extracellular hemolysis. An unusual case of AIHA with interesting magnetic resonance imaging (MRI) appearances is presented. Possible explanations for the MRI findings are discussed.


Preparative separation of four individual flavonoids in Scutellaria barbata D. Don based on high selectivity polymeric adsorbents with different polarities.
The individual flavonoid component, scutellarin, scutellarein, luteolin and apigenin, in Scutellaria barbata plant was isolated based on the macro porous adsorbent with high adsorption selectivity. These adsorbents were synthesized based on the copolymerization of methyl acrylate and divinylbenzene (MA-co-DVB). So the polarity and the adsorption affinity of these adsorbents can be adjusted through changing MA content in the adsorbents. And then the ability of the adsorbent with different MA contents for isolation of these four individual flavonoid was also investigated. Adsorbents M2 and M4, with MA content of 25% and 45%, respectively, demonstrated the best separation ability. Complete separation of the four flavone compounds was achieved in a continuous process based on combination of adsorbents with different polarities (M2 and M4). Gradient elution using adsorbent M4 separated the four flavonoids into three fractions, which were determined to contain scutellarin, scutellarein and a mixture of luteolin and apigenin. The latter was separated completely by adsorbent M2 subsequently. All four compounds were obtained at high resolution and high recovery yield (96.7%, 94.1%, 95.8% and 93.8%, respectively), suggesting the efficiency of sequentially combined columns with different segregation patterns.


Orthodontic Force-Induced BMAL1 in PDLCs Is a Vital Osteoclastic Activator.
Orthodontic tooth movement (OTM) depends on periodontal ligament cells (PDLCs) sensing biomechanical stimuli and subsequently releasing signals to initiate alveolar bone remodeling. However, the mechanisms by which PDLCs sense biomechanical stimuli and affect osteoclastic activities are still unclear. This study demonstrates that the core circadian protein aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) in PDLCs is highly involved in sensing and delivering biomechanical signals. Orthodontic force upregulates BMAL1 expression in periodontal tissues and cultured PDLCs in manners dependent on ERK (extracellular signal-regulated kinase) and AP1 (activator protein 1). Increased BMAL1 expression can enhance secretion of CCL2 (C-C motif chemokine 2) and RANKL (receptor activator of nuclear factor-κB ligand) in PDLCs, which subsequently promotes the recruitment of monocytes that differentiate into osteoclasts. The mechanistic delineation clarifies that AP1 induced by orthodontic force can directly interact with the BMAL1 promoter and activate gene transcription in PDLCs. Localized administration of the ERK phosphorylation inhibitor U0126 or the BMAL1 inhibitor GSK4112 suppressed ERK/AP1/BMAL1 signaling. These treatments dramatically reduced osteoclastic activity in the compression side of a rat orthodontic model, and the OTM rate was almost nonexistent. In summary, our results suggest that force-induced expression of BMAL1 in PDLCs is closely involved in controlling osteoclastic activities during OTM and plays a vital role in alveolar bone remodeling. It could be a useful therapeutic target for accelerating the OTM rate and controlling pathologic bone-remodeling activities.


Cytogenetic analysis of 1508 spontaneous abortions originating from south Slovakia.
Knowledge with regard to the spontaneous abortion cytogenetics has been derived exclusively from populations of the highly developed countries; its full applicability to east-european populations living in the peculiar conditions of the former 'socialist countries' may be questioned. The consecutive series of 1912 spontaneous abortion products with identifiable embryonal tissue was collected in six maternal clinics in south Slovakia. 1508 specimens were set in culture. Among 926 (61.4%) successfully karyotyped abortions, 46.0% were chromosomally abnormal specimens. The proportion of the groups of abnormalities is similar to that in other large series, with the exception of a higher proportion of mosaics (14.3% of the abnormalities). The abnormality rate in the whole sample also lies within the range of values published. However, significant inter-regional variability has been established: the chromosome abnormality rate in the urban subsample is 47.8%, whereas the value was only 35.3% for rural southern districts. The anomaly rates are lower for all maternal ages and gestation phases in the country subsample. The possibility of the environmental diversity effect was discussed. No other major peculiarity of cytogenetic abortion characteristics can be determined in the population studied.


Making the most of a wall calendar. Kingston Regional Health creates three for the price of one.
In a few short weeks, Kingston Regional Health, Kingston, N.Y., produced three versions of its 2002 wall calendar, one representing the health system itself, another its Women's Health Services subsidiary and the third, its Lifeline personal response and support service.


Later Surgical Start Time Is Associated With Longer Length of Stay and Higher Cost in Cervical Spine Surgery.
Retrospective study of a surgical cohort from a single, large academic institution. The aim of this study was to investigate associations between surgical start time, length of stay, cost, perioperative outcomes, and readmission. One retrospective study with a smaller cohort investigated associations between surgical start time and outcomes in spine surgery and found that early start times were correlated with shorter length of stay. No examinations of perioperative outcomes or cost have been performed. All patients undergoing anterior cervical discectomy and fusion (ACDF) and posterior cervical decompression and fusion (PCDF) were queried from a single institution from January 1, 2008 to November 30, 2016. Patients undergoing surgery that started between 12:00 AM and 6:00 AM were excluded due to their likely emergent nature. Cases starting before and after 2:00 PM were compared on the basis of length of stay and cost as the primary outcomes using multivariable logistic regression. The patients undergoing ACDF and PCDF were both similar on the basis of comorbidity burden, preoperative diagnosis, and number of segments fused. The patients undergoing ACDF starting after 2 PM had longer LOS values (adjusted difference of 0.65 days; 95% confidence interval [CI]: 0.28-1.03; P = 0.0006) and higher costs of hospitalization (adjusted difference of $1177; 95% CI: $549-$1806; P = 0.0002). Patients undergoing PCDF starting after 2 PM also had longer LOS values (adjusted difference of 1.19 days; 95% CI: 0.46-1.91; P = 0.001) and higher costs of hospitalization (adjusted difference of $2305; 95% CI: $826-$3785; P = 0.002). Later surgical start time is associated with longer LOS and higher cost. These findings should be further confirmed in the spine surgical literature to investigate surgical start time as a potential cost-saving measure. 3.


How we treat medulloblastoma in adults.
Medulloblastoma is a rare tumour in postpubertal patients and adults that is potentially curable. Several subgroups have been defined that are associated with clinical features, have different prognoses, and in some cases offer personalized treatment options. In adults, the sonic hedgehog (SHH) subtype is the most common subtype, followed by the wingless (WNT) and group 4 subtypes. Multimodal therapies allow 5-year overall survival rates of up to 70%. However, in adults, therapeutic evidence from prospective randomized trials is largely lacking. Therefore, regardless of individual risk, most patients are currently treated uniformly with craniospinal chemoradiation with a boost to the tumour bed, followed by maintenance chemotherapy, usually with alkylating agents. In Europe, the so-called Packer regimen, together with cisplatin-etoposide regimens, is the most commonly used chemotherapy option. Targeted treatment approaches have not yet been implemented, although tumour biology is well understood and offers personalized approaches, especially for the SHH subgroup. At relapse, rapid resistance occurs frequently, necessitating repositioning of these agents in an earlier treatment phase. Due to the good to intermediate prognosis, patients with medulloblastoma require structured long-term clinical follow-up including MRI of the brain, monitoring of side effects, and psychosocial and fertility counselling. Recently, clinical trials have been initiated with the aim of de-escalating treatment to reduce toxicity and adding targeted therapies to increase efficacy, with the main goal of therapy to cure the tumour while maintaining the physical and psychosocial integrity of affected patients. This article summarizes our opinion on the diagnosis and treatment of medulloblastoma in adults.


Characteristics of the inhibition of rat brain monoamine oxidase in vitro by MD780515.
The inhibiton of type A and B MAO in rat forebrain crude membrane preparation by MD780515, (3-(4-[(3-cyanophenyl)methoxy]phenyl)-5-(methoxymethyl)-2-oxazolidinone-Centre de Recherche Delalande, France) has been investigated in vitro with 5-hydroxytryptamine and beta-phenylethylamine as substrates. The inhibition of the high-affinity binding of [3H]harmaline, a specific marker of type A MAO, was also studied. In the experimental conditions used, MD780515 appeared to be a pure mixed MAO inhibitor (MAOI) of 5-HT deamination, both Km and Vmax being altered [Ki (Dixon) = Ki, (slope) = 2 nM; Ki (intercept) = 12 nM]. Phenylethylamine oxidation could be considered to be noncompetitively inhibited by MD780515 (Ki (slope) = 78 nM; Ki (intercept) = 103 nM). Dixon and intercept replots were hyperbolic, suggesting that, at high concentrations, PEA could be deaminated by both forms of MAO. This hypothesis was confirmed by biphasic inhibition curves of 80 microM-PEA obtained when MD780515, clorgyline, harmaline and deprenyl were used at MAOIs. MD780515 was a potent inhibitor (IC50 = 1-2 nM) of [3H]harmaline binding. Comparatively, clorgyline, 'cold' harmaline and Lilly 51641 inhibited 3H ligand binding, with IC50 of 5, 7 and 40 nM respectively. In conclusion, MD780515 is a reversible, specific and potent type A MAOI.


Protective athletic mouthguards: do they cause harm?
Protective athletic mouthguards (PAMs) have been worn in competitive sports for more than 100 years. Today, participants in contact and noncontact sports wear PAMs. Wearing a PAM produces oral injury. Case series. Sixty-two Division I football players voluntarily participated in the study. Before the beginning of the season, each player underwent a thorough oral examination, and all abnormal oral findings were photographed (hyperkeratosis, erythema, ulceration, and combinations thereof). At midseason, 14 players were given complete oral examinations, with all abnormal oral findings documented. At season end, all remaining players (n = 53) had complete oral examinations and photographs taken of abnormal oral findings. The preseason examination of 62 players found a total of 85 lesions (1.4 lesions per player) on the gingiva (n = 17), buccal mucosa (n = 60), and palate (n = 8). The 14 midseason players had 28 lesions (2.0 lesions per player) on gingiva (n = 8), buccal mucosa (n = 16), and tongue (n = 4). At season end, the 53 remaining players had 198 lesions (3.7 per player) on the gingiva (n = 96), buccal mucosa (n = 79), tongue (n = 18), and palate (n = 5). In addition, the lesion intensity scores progressively increased over the season. Because the palate did not come into direct contact with the PAM, it was used as an internal control. The wearing of a PAM may increase the number and intensity of oral mucosal injuries, which may cause localized soft tissue reactions such as hyperkeratosis, erythema, and ulceration. Because the PAM reduces tooth injury but may cause oral lesions, it should be sanitized daily and changed regularly and replaced whenever it becomes sharp and jagged or when the athlete develops an irritation in the mouth.


Mathematical study of the dynamics of lymphatic filariasis infection via fractional-calculus.
The infection of lymphatic filariasis (LF) is the primary cause of poverty and disability in individuals living with the disease. Many organizations globally are working toward mitigating the disease's impact and enhancing the quality of life of the affected patients. It is paramount to inspect the transmission pattern of this infection to provide effective interventions for its prevention and control. Here, we formulate an epidemic model for the progression process of LF with acute and chronic infection in the fractional framework. The basic concept of the novel Atangana-Baleanu operator is presented for the analysis of suggested system. We determine the basic reproduction number of the system via the approach of next-generation matrix and investigate the equilibria of the system for stability analysis. We have shown the impact of input factors on the outcomes of reproduction parameter with the help of partial rank correlation coefficient approach and visualize the most critical factors. To conceptualize the time series analysis of the suggested dynamics, we propose utilizing a numerical approach. The solution pathways of the system are illustrated to demonstrate how different settings affect the system. We demonstrate the dynamics of the infection numerically to educate the policy makers and health authorities about the mechanisms necessary for management and control.


[Clinical aspects and therapeutic positioning in addictology].
The concept of addiction emerged subsequent to the moral approaches of the end ofthe 19th century as a pathological behaviour. The manuals which classify mental disorders, together with the notion of substance-related disorders, enable them to be approached with a medical vision. The subject of numerous, often heated or divisive debates, addictology requires a clinical approach. The treatment of addiction must involve professionals from the medical, nursing, psychological and social fields. This multi-disciplinarity encourages each player to consider their own nursing identity while taking into account that of each other.


Increased galectin-1 expression in muscle of Astragalus polysaccharide-treated Type 1 diabetic mice.
In order to investigate the immunopharmacological function of Astragalus polysaccharide (APS) in Type 1 diabetes mellitus (T1DM), multiple low-dose streptozotocin-induced diabetic mice and normal mice were administered either APS or saline intraperitoneally once daily. The changes in galectin-1 expression in different organs of the mice were detected by ELISA, Real-time fluorescence quantitative RT-PCR and Western blot. The percentages of apoptotic CD8(+) T cells from spleens of APS-treated diabetic mice were measured by flow cytometry. We found that the expression of galectin-1 was increased in serum of APS-treated diabetic mice compared to the non-treated diabetic mice (*p < 0.05). Increased galectin-1 was mainly expressed in the muscle of APS-treated mice. In vitro, APS up-regulated the expression of galectin-1 in muscle cells in a dose-dependent manner. The percentage of apoptotic CD8(+) T cells in spleens of APS-treated mice was positively correlated with the concentration of APS treatment, and the blocking of galectin-1 in vivo by specific antibody reduced the percentage of apoptotic CD8(+) T cells in APS-treated mice. Our findings indicated that APS could up-regulate the expression of galectin-1 in muscle of T1DM mice, resulting in the apoptosis of CD8(+) T cells. This may be an important mechanism by which APS protects β cells of the pancreatic islets from apoptosis induced by CD8(+) T cells in T1DM in vivo.


Realization of a multinode quantum network of remote solid-state qubits.
The distribution of entangled states across the nodes of a future quantum internet will unlock fundamentally new technologies. Here, we report on the realization of a three-node entanglement-based quantum network. We combine remote quantum nodes based on diamond communication qubits into a scalable phase-stabilized architecture, supplemented with a robust memory qubit and local quantum logic. In addition, we achieve real-time communication and feed-forward gate operations across the network. We demonstrate two quantum network protocols without postselection: the distribution of genuine multipartite entangled states across the three nodes and entanglement swapping through an intermediary node. Our work establishes a key platform for exploring, testing, and developing multinode quantum network protocols and a quantum network control stack.


A cell ELISA technique. The direct detection and semi-quantitation of immunoglobulin positive cells in 7 day lymphocyte cultures using the microtitre culture plates as the solid phase.
A sensitive ELISA is described which allows the detection and quantitation of immunoglobulin positive Peyer's patch and spleen lymphocytes in tissue culture microtitre plates. A methanol fixation step is used to fix the cells to the microtitre plate. The effects of various mitogens and an antigen on the number of immunoglobulin positive cells present after a 7 day culture were studied. Results were expressed either in optical densities or as percentages of the unstimulated control. The method proves a useful addition to existing techniques for studying the effects of mitogens and other agents on in vitro immunoglobulin synthesis by lymphocytes, and reflects immunoglobulin levels in the culture supernatants.


Vascular access in hemodialysis: issues, management, and emerging concepts.
This article (1) identifies the types of hemodialysis access, (2) summarizes the clinical standard of care for dialysis access grafts and fistulae, (3) describes the pathology and pathogenesis of venous stenosis in dialysis access grafts and fistulae, (4) tabulates avail-able therapies for hemodialysis vascular access dysfunction and speculates on the rea-sons for the lack of effective therapies, and (5) discusses the development and application of novel therapeutic interventions for this difficult clinical problem. The possibility that dialysis access grafts and fistulae could be the ideal clinical model for testing novel local therapies to block neointimal hyperplasia is discussed.


A multicenter longitudinal study of the prevalence and mortality rate of systemic lupus erythematosus patients in Oman: Oman Lupus Study.
This study is a longitudinal multicenter study which aims to find the prevalence, the demographic data, survival and mortality rates of patients with systemic lupus erythematosus (SLE) in Oman. All Omani patients, pediatrics and adults diagnosed with SLE, who fulfill either the 1997 American College of Rheumatology or Systemic Lupus International Collaborating Clinics classifications criteria for SLE were included from January 2006 till February 2020. In total 1160 patients were included in this cohort. Data analysis showed that patient's ages ranged from 2-82 years with female predominance and female-to-male ratio of 7:1 (87.7% female,12.3% male). The mean prevalence of SLE among different age groups was 38.8 (range 5-63 per 100 000 inhabitants). The mortality rate was found to be 5%. Male patients had significantly higher mortality rate than females (7.6% vs 5.4%, P value = .04). Sepsis was the commonest cause of mortality (34%). The coexistence of systemic sclerosis correlates significantly with death (P = .002). Survival analysis in our data showed 5, 10, 20, 40-year survival rates of 100%, 100%, 99% and 90% respectively for antinuclear antibody (ANA) positive patients and lower survival rate for ANA negative patients with 5,10, 20, 40-year survival rates of 100, 99%, 99% and 75%, respectively. This study showed that the mean prevalence of SLE in Oman to be 38.8 (range 5-63) per 100 000 inhabitants. The 40-year survival rate among patients with positive ANA was found to be 90%, while patients with negative ANA had worse survival outcomes.


Disruptive mutations in TANC2 define a neurodevelopmental syndrome associated with psychiatric disorders.
Postsynaptic density (PSD) proteins have been implicated in the pathophysiology of neurodevelopmental and psychiatric disorders. Here, we present detailed clinical and genetic data for 20 patients with likely gene-disrupting mutations in TANC2-whose protein product interacts with multiple PSD proteins. Pediatric patients with disruptive mutations present with autism, intellectual disability, and delayed language and motor development. In addition to a variable degree of epilepsy and facial dysmorphism, we observe a pattern of more complex psychiatric dysfunction or behavioral problems in adult probands or carrier parents. Although this observation requires replication to establish statistical significance, it also suggests that mutations in this gene are associated with a variety of neuropsychiatric disorders consistent with its postsynaptic function. We find that TANC2 is expressed broadly in the human developing brain, especially in excitatory neurons and glial cells, but shows a more restricted pattern in Drosophila glial cells where its disruption affects behavioral outcomes.


Hydrodynamic Injection for Developing NASH Model.
The hydrodynamic tail vein injection (HTVi) is a technique that is used to deliver plasmid genes into live mice or rats. The HTVi leads to the in vivo transfection of exogenous DNA primarily in the liver, serving as a reliable approach of establishing animal models for the study of liver diseases. The nonalcoholic steatohepatitis (NASH) is liver inflammation and damage resulting from an accumulation of fat in the liver. With the rising prevalence of obesity worldwide, NASH is becoming an increasingly common health problem. The pathogenesis of NASH is a multi-step process involving complicated pathways. The molecular mechanisms of NASH remain poorly understood. Here, we describe the use of HTVi to establish animal models for the study of NASH.


An assessment of opioids on respiratory depression in children with and without obstructive sleep apnea.
Obstructive sleep apnea is a risk factor for respiratory depression following opioid administration as well as opioid-induced hyperalgesia. Little is known on how obstructive sleep apnea status is associated with central ventilatory depression in pediatric surgical patients given a single dose of fentanyl. This was a single-center, prospective trial in children undergoing surgery requiring intubation and opioid administration. Sixty patients between the ages of 2-8 years presenting for surgery at Texas Children's Hospital were recruited. Twenty non-obstructive sleep apnea controls and 30 patients with moderate to severe obstructive sleep apnea met inclusion criteria. Following induction of general anesthesia and establishment of steady-state ventilation, participants received 1 mcg/kg intravenous fentanyl. Ventilatory variables (tidal volume, respiratory rate, end-tidal CO2 , and minute ventilation) were assessed each minute for 10 min. The primary outcome was the extent of opioid-induced central ventilatory depression over time by obstructive sleep apnea status when compared with baseline values. Secondary aims assessed the impact of demographics and SpO2 nadir on ventilatory depression. We found no significant difference in percent decrease in respiratory rate (38.1% and 37.1%; p = .950), tidal volume (6.4% and 5.4%; p = .992), and minute ventilation (35.0 L/min and 35.0 L/min; p = .890) in control and obstructive sleep apnea patients, respectively. Both groups experienced similar percent increases in end-tidal CO2 (4.0% vs. 2.2%; p = .512) in control and obstructive sleep apnea patients, respectively. In pediatric surgical patients, obstructive sleep apnea status was not associated with significant differences in central respiratory depression following a single dose of fentanyl (1 mcg/kg). These findings can help determine safe opioid doses in future pediatric obstructive sleep apneapatients.


SVCV infection triggers fish IFN response through RLR signaling pathway.
In mammals, virus infection of host cells triggers innate immune response, characterized by induction of interferon (IFN) and downstream IFN-stimulated genes (ISGs). The initiation of IFN antiviral response is dependent on host recognition of virus infection. In fish, similar IFN antiviral response is induced in response to RNA or DNA virus infection; however, the detailed mechanisms underlying recognition of a given virus and activation of downstream signaling remain largely unexplored. Using an infection model with Epithelioma papulosum cyprini (EPC) cells and spring viremia of carp virus (SVCV), a negative sense single-stranded RNA virus, we reported that fish RLR signaling pathway was involved in SVCV-triggered fish IFN response. IFN response was significantly initiated in EPC cells when infected with SVCV, as evidenced by activation of fish IFN promoters, upregulation of IFN and ISGs at mRNA and protein levels. However, function blockade of RIG-I and MDA5, two cytosolic receptors of fish RLR family, significantly attenuated the activation of fish IFN promoters and also the induction of fish IFN and ISGs by SVCV infection. Consistently, SVCV infection-triggered IFN response were blocked in EPC cells when transfected with the dominant negative mutants of pivotal RLR signaling factors, including MAVS, MITA, TBK1, IRF3 and IRF7. These results together shed light on the conservation of RLR-mediated IFN signaling that contributes to fish cells responding to RNA virus infection.


Intravalvular implantation of aortic valve prosthesis.
A simplified technique is described to overcome the problem of aortic valve replacement in a severely dilated aortic root (> 30-mm diameter). Intravalvular implantation of an inverted mitral prosthesis after imbrication of aortic cusps was performed in a patient with severe aortic regurgitation with gross annular dilatation. The technique may be applicable in a select subset of patients.


pipsqueak encodes a novel nuclear protein required downstream of seven-up for the development of photoreceptors R3 and R4.
Photoreceptor induction in the Drosophila eye is mediated by activation of the Ras signal transduction cascade. Although this process is well understood, little is known about how the diversity of photoreceptor subtypes is generated. The pipsqueak (psq) gene is expressed at high levels in the R3/R4 precursors during eye development and this expression depends on seven-up (svp) gene function. Moreover, strong psq alleles are dominant suppressors of a svp-induced cone cell transformation phenotype. Although the gene was previously identified and described as a member of the maternal posterior group of genes, the strong semilethal alleles isolated here demonstrate a specific requirement for psq function downstream of svp for the development of photoreceptors R3/R4. The gene has three independent 5' ends and codes for several nuclear protein isoforms, some containing the POZ domain which has been implicated in protein-protein interactions. Interestingly, all viable alleles with a maternal posterior group phenotype cluster around one specific 5' exon, while all semilethal alleles have lesions which map to a different alternative 5' exon.


Systematic review and meta-analysis of hepatic resection versus transarterial chemoembolization for solitary large hepatocellular carcinoma.
Surgical techniques and pre-operative patient evaluation have improved since the initial development of the Barcelona clinic liver cancer staging system. The optimal treatment for solitary hepatocellular carcinoma ≥5 cm remains unclear. The aim of this study was to review the long-term survival outcomes of hepatic resection versus transarterial chemoembolisation (TACE) for solitary large tumours. EMBASE, MEDLINE, Pubmed and the Cochrane database were searched for studies comparing resection with TACE for solitary HCC ≥5 cm. The primary outcome was overall survival at 1, 3 and 5 years. The meta-analysis combined the results of four cohort studies including 861 patients where 452 underwent hepatic resection and 409 were treated with TACE to an absence of viable tumour. The pooled HR for 3 year OS rate calculated using the random effects model was 0.60 (95% CI 0.46-0.79, p < 0.001; I2 = 54%, P = 0.087). The pooled HR for 5 year OS rate calculated using the random effects model was 0.59 (95% CI 0.43-0.81, p = 0.001; I2 = 80%, P = 0.002). Hepatic resection has been shown to result in greater survivability and time to disease progression than TACE for solitary HCC ≥5 cm. Where a patient is fit for surgery, has adequate liver function and a favourable tumour, resection should be considered.


Curriculum framework to facilitate critical thinking skills of undergraduate nursing students: A cooperative inquiry approach.
Critical thinking (CT) is vital in assisting nurses to function efficiently in the ever-changing health care environment. A CT-based curriculum framework provides the impetus necessary to drive the acquisition of CT skills of students. Yet, there is no known CT-based framework contextualized to developing countries where seniority tradition is a norm. Therefore, the aim of this study was to develop a CT-based curriculum framework to facilitate the development of CT skills of nursing students in developing countries. Cooperative inquiry. Using purposive sampling, 11 participants comprising students, educators and preceptors developed a CT-based curriculum framework. Findings were organized into a framework illustrating interconnected concepts required to foster CT skills of nursing students. These concepts include authentic student-facilitator partnership, a facilitator that makes a difference; a learner that is free to question and encouraged to reflect; a conducive and participatory learning environment; curriculum renewal processes and contextual realities.


Impact of a 24-hour discharge pathway on outcomes of pediatric appendectomy.
Clinical pathways for simple (nonperforated, nongangrenous) appendicitis potentially could decrease hospital length of stay (LOS) through standardization of patient care. Our institution initiated a simple appendicitis pathway for children with the goal of less than 24-hour discharge (same-day discharge, SDD) and evaluated its effectiveness. A prospective cohort of pediatric patients (<18 years of age) who underwent appendectomy for simple appendicitis after implementation of a SDD pathway were compared with a historic cohort of similar patients in this same large children's hospital. Primary outcomes included LOS, surgical-site infections, and readmissions. Mann Whitney U test, Fischer exact test, χ(2) test, and logistic regression were used. Between June 2009 and May 2013, 1,382 appendectomies were performed; 794 (57%) were for simple appendicitis (316 prepathway and 478 pathway). Hospital LOS decreased 37% after pathway implementation from a median (interquartile range) of 35 (20-50) hours to 22 (9-55) hours (P < .001). SDD increased from 13% to 58% (P < .001). Infectious complications were unchanged (1.6% vs 1.8%, P = .82), but readmissions increased (1.2% vs 4.2%, P = .02). A standardized pathway for simple appendicitis that targets SDD can be achieved in children; however, a slight increase in readmissions was noted. High risk for readmission, cost effectiveness, and generalizability need to be further determined.


How and When Leisure Crafting Enhances College Students' Well-Being: A (Quantitative) Weekly Diary Study.
College students' well-being is important for their self-growth and the whole society. However, we still know relatively little about how college students could proactively, strategically improve their well-being in the leisure context. Following the self-determination theory and proactivity literature, this study examines how and when leisure crafting (ie, a proactive act whereby individuals balance their leisure resources and demands by utilizing their personal abilities and needs) can enhance college students' well-being. Conducting a quantitative weekly diary study of 80 Chinese students in an engineering college (320 observations), we drew a moderated mediation model. We found that weekly leisure crafting behaviors (ie, seeking structural leisure resources, seeking social leisure resources, seeking leisure challenges, and reducing hindering leisure demands) were positively related to weekly intrinsic need satisfaction (ie, need for competence, autonomy, and relatedness), then resulting in higher weekly subjective well-being (ie, physical thriving, mental health, and life meaningfulness). Moreover, this indirect effect was stronger for those who had a higher level of leisure boredom. Our study contributes to student development and well-being literature by focusing on the students' leisure context and providing a means to enhance their well-being. We unfold how the leisure crafting strategy boosts college students' well-being via increasing their intrinsic need satisfaction. We also highlight the compensating role of leisure crafting when one is in an unfavorable personal state (eg, leisure boredom).


Rap2B promotes migration and invasion of human suprarenal epithelioma.
The aim of our study was to elucidate the role of Rap2B in the development of human suprarenal epithelioma and to investigate the effect of Rap2B on suprarenal epithelioma cells migration and invasion. We use tissue microarray and immunohistochemistry to evaluate Rap2B staining in 75 suprarenal epithelioma tissues and 75 tumor-adjacent normal renal tissues. And the expression of Rap2B protein in human suprarenal epithelioma cells and tissues was detected by western blot simultaneously. The role of Rap2B in suprarenal epithelioma cells migration and invasion was detected by using wound healing assay, cell migration assay, and matrigel invasion assay. After that, we performed western blot analysis and gelatin zymography to detect MMP-2 protein expression and enzyme activity. Our research showed that Rap2B expression was increased in tumor tissues compared with tumor-adjacent normal renal tissues. But no correlation was found between Rap2B expression and clinicopathological parameters. In addition, we found that Rap2B promoted the cell migration and invasion abilities, and Rap2B increased MMP-2 expression and enzyme activity in suprarenal epithelioma cells. Our data indicated that Rap2B expression is significantly increased in human suprarenal epithelioma and Rap2B can promote the cell migration and invasion abilities, which may provide a new target for the treatment of suprarenal epithelioma.


Human duodenal mucosal bicarbonate secretion. Evidence suggesting active transport under basal and stimulated conditions.
When the proximal duodenum of animals or humans is perfused with isoosmolar NaCl, bicarbonate enters the luminal effluent. In addition, duodenal bicarbonate output is stimulated by luminal acidification and prostaglandins of the E class. The hypothesis that in vivo human duodenal bicarbonate transport persists in the absence of a plasma-to-lumen bicarbonate gradient and therefore is probably an active transport process was tested. In healthy subjects, a 4-cm segment of the proximal duodenum was isolated from gastric and pancreaticobillary secretions. Net duodenal bicarbonate secretion remained similar to basal levels during luminal perfusion with either 24 or 32 mM bicarbonate (each isoosmolar with plasma by the addition of NaCl). In addition, peak increases in acid-induced bicarbonate outputs with luminal perfusion of 154 mM NaCl and 32 mM NaHCO3 (+122 mM NaCl) were similar. Moreover, prostaglandin E2-stimulated bicarbonate secretion with perfusion of 154 mM NaCl and 32 mM NaHCO3 (+122 mM NaCl) was similar. It was concluded that in humans, proximal duodenal mucosal bicarbonate transport remains unaltered in the absence of a plasma-to-lumen bicarbonate gradient at rest and after stimulation with HCl or prostaglandin E2. These observations suggest that human proximal duodenal bicarbonate secretion involves active transport.


Development of a dual-factor measure of adolescent mental health: an analysis of cross-sectional data from the 2014 Canadian Health Behaviour in School-aged Children (HBSC) study.
Studies of adolescent mental health require valid measures that are supported by evidence-based theories. An established theory is the dual-factor model, which argues that mental health status is only fully understood by incorporating information on both subjective well-being and psychopathology. To develop a novel measure of adolescent mental health based on the dual-factor model and test its construct validity. Cross-sectional analysis of national health survey data. Nationally weighted sample of 21 993 grade 6-10 students; average age: 14.0 (SD 1.4) years from the 2014 Canadian Health Behaviour in School-aged Children study. Self-report indicators of subjective well-being (life satisfaction, positive and negative affect), and psychopathology (psychological symptoms and overt risk-taking behaviour) were incorporated into the dual-factor measure. Characteristics of adolescents families, specific mental health indicators and measures of academic and social functioning were used in the assessment of construct validity. Proportions of students categorised to the four mental health groups indicated by the dual-factor measure were 67.6% 'mentally healthy', 17.5% 'symptomatic yet content', 5.5% 'asymptomatic yet discontent' and 9.4% 'mentally unhealthy'. Being mentally healthy was associated with the highest functioning (greater social support and academic functioning) and being mentally unhealthy was associated with the worst. A one-unit increase (ranges=0-10) in peer support (OR 1.19; 95% CI 1.15 to 1.22), family support (OR 1.32; 95% CI 1.28 to 1.36), student support (OR 1.20; 95% CI 1.17 to 1.24) and average school marks (OR 1.18; 95% CI 1.10 to 1.27) increased the odds of being symptomatic yet content versus mentally unhealthy. Mentally healthy youth were the most likely to live with both parents (77% vs ≤65%) and report their family as well-off (62% vs ≤53%). We developed a novel, construct valid dual-factor measure of adolescent mental health. This potentially provides a nuanced and comprehensive approach to the assessment of adolescent mental health that is direly needed.


Assessing an electronic self-report method for improving quality of ethnicity and race data in the Veterans Health Administration.
Evaluate self-reported electronic screening (eScreening) in a VA Transition Care Management Program (TCM) to improve the accuracy and completeness of administrative ethnicity and race data. We compared missing, declined, and complete (neither missing nor declined) rates between (1) TCM-eScreening (ethnicity and race entered into electronic tablet directly by patient using eScreening), (2) TCM-EHR (Veteran-completed paper form plus interview, data entered by staff), and (3) Standard-EHR (multiple processes, data entered by staff). The TCM-eScreening (n = 7113) and TCM-EHR groups (n = 7113) included post-9/11 Veterans. Standard-EHR Veterans included all non-TCM Gulf War and post-9/11 Veterans at VA San Diego (n = 92 921). Ethnicity: TCM-eScreening had lower rates of missingness than TCM-EHR and Standard-EHR (3.0% vs 5.3% and 8.6%, respectively, P < .05), but higher rates of "decline to answer" (7% vs 0.5% and 1.2%, P < .05). TCM-EHR had higher data completeness than TCM-eScreening and Standard-EHR (94.2% vs 90% and 90.2%, respectively, P < .05). Race: No differences between TCM-eScreening and TCM-EHR for missingness (3.5% vs 3.4%, P > .05) or data completeness (89.9% vs 91%, P > .05). Both had better data completeness than Standard-EHR (P < .05), which despite the lowest rate of "decline to answer" (3%) had the highest missingness (10.3%) and lowest overall completeness (86.6%). There was strong agreement between TCM-eScreening and TCM-EHR for ethnicity (Kappa = .92) and for Asian, Black, and White Veteran race (Kappas = .87 to .97), but lower agreement for American Indian/Alaska Native (Kappa = .59) and Native Hawaiian/Other Pacific Islander (Kappa = .50) Veterans. eScreening is a promising method for improving ethnicity and race data accuracy and completeness in VA.


Best Practices for Conducting and Interpreting Studies to Validate Self-Report Dietary Assessment Methods.
Careful consideration of the validity and reliability of methods intended to assess dietary intake is central to the robustness of nutrition research. A dietary assessment method with high validity is capable of providing useful measurement for a given purpose and context. More specifically, a method with high validity is well grounded in theory; its performance is consistent with that theory; and it is precise, dependable, and accurate within specified performance standards. Assessing the extent to which dietary assessment methods possess these characteristics can be difficult due to the complexity of dietary intake, as well as difficulties capturing true intake. We identified challenges and best practices related to the validation of self-report dietary assessment methods. The term validation is used to encompass various dimensions that must be assessed and considered to determine whether a given method is suitable for a specific purpose. Evidence on the varied concepts of validity and reliability should be interpreted in combination to inform judgments about the suitability of a method for a specified purpose. Self-report methods are the focus because they are used in most studies seeking to measure dietary intake. Biomarkers are important reference measures to validate self-report methods and are also discussed. A checklist is proposed to contribute to strengthening the literature on the validation of dietary assessment methods and ultimately, the nutrition literature more broadly.


Cardiac tamponade revisited: a postmortem look at a cautionary case.
Cardiac tamponade is a life-threatening clinical syndrome that requires timely diagnosis. Herein, we present an instructive case of a patient who had cardiac tamponade. The condition went undiagnosed and resulted in the patient's death because almost all of the pathognomonic clinical findings of tamponade were unrecognized or not manifest. To better prepare health care professionals for similar challenges, we discuss the symptoms and clinical signs typical of cardiac tamponade, review the medical literature, and highlight current investigative methods that enable quick, efficient diagnosis and treatment.


Does the perceived neighborhood environment promote mental health during pregnancy? Confirmation of a pathway through social cohesion in two Spanish samples.
Physical neighborhood attributes such as greenness, walkability and environmental pollution may have an influence on people's behavior and health. It has been claimed that part of such effects may come from the promotion of physical activity and the strengthening of social cohesion. In this study, we recruited samples of pregnant women in two Spanish cities (Donostia-San Sebastián, 440 participants and Barcelona, 360 participants) who filled in a questionnaire and wore an accelerometer for 1 week during the first trimester of pregnancy. The influence of perceived residential greenness, walkability and environmental pollution on mental health (GHQ-12) was tested in two structural equation models that included light physical activity, moderate-to-vigorous physical activity and social cohesion as mediators. Two solutions showing excellent and good fits (Donostia-San Sebastián: X2(3) = 2.56, p = .465, CFI = 1, RMSEA < 0.001; Barcelona: X2(6) = 4.86, p = .566, CFI = 1, RMSEA = 0.048) consistently showed that neighborhood attributes promote mental health through social cohesion in the two cities. Stratified analyses revealed that the social cohesion-mental health effect was only statistically significant for low and medium socioeconomic status groups in the Donostia-San Sebastián sample. Pathways through physical activity were not confirmed.


Effect of Artificial Intelligence Tutoring vs Expert Instruction on Learning Simulated Surgical Skills Among Medical Students: A Randomized Clinical Trial.
To better understand the emerging role of artificial intelligence (AI) in surgical training, efficacy of AI tutoring systems, such as the Virtual Operative Assistant (VOA), must be tested and compared with conventional approaches. To determine how VOA and remote expert instruction compare in learners' skill acquisition, affective, and cognitive outcomes during surgical simulation training. This instructor-blinded randomized clinical trial included medical students (undergraduate years 0-2) from 4 institutions in Canada during a single simulation training at McGill Neurosurgical Simulation and Artificial Intelligence Learning Centre, Montreal, Canada. Cross-sectional data were collected from January to April 2021. Analysis was conducted based on intention-to-treat. Data were analyzed from April to June 2021. The interventions included 5 feedback sessions, 5 minutes each, during a single 75-minute training, including 5 practice sessions followed by 1 realistic virtual reality brain tumor resection. The 3 intervention arms included 2 treatment groups, AI audiovisual metric-based feedback (VOA group) and synchronous verbal scripted debriefing and instruction from a remote expert (instructor group), and a control group that received no feedback. The coprimary outcomes were change in procedural performance, quantified as Expertise Score by a validated assessment algorithm (Intelligent Continuous Expertise Monitoring System [ICEMS]; range, -1.00 to 1.00) for each practice resection, and learning and retention, measured from performance in realistic resections by ICEMS and blinded Objective Structured Assessment of Technical Skills (OSATS; range 1-7). Secondary outcomes included strength of emotions before, during, and after the intervention and cognitive load after intervention, measured in self-reports. A total of 70 medical students (41 [59%] women and 29 [41%] men; mean [SD] age, 21.8 [2.3] years) from 4 institutions were randomized, including 23 students in the VOA group, 24 students in the instructor group, and 23 students in the control group. All participants were included in the final analysis. ICEMS assessed 350 practice resections, and ICEMS and OSATS evaluated 70 realistic resections. VOA significantly improved practice Expertise Scores by 0.66 (95% CI, 0.55 to 0.77) points compared with the instructor group and by 0.65 (95% CI, 0.54 to 0.77) points compared with the control group (P < .001). Realistic Expertise Scores were significantly higher for the VOA group compared with instructor (mean difference, 0.53 [95% CI, 0.40 to 0.67] points; P < .001) and control (mean difference. 0.49 [95% CI, 0.34 to 0.61] points; P < .001) groups. Mean global OSATS ratings were not statistically significant among the VOA (4.63 [95% CI, 4.06 to 5.20] points), instructor (4.40 [95% CI, 3.88-4.91] points), and control (3.86 [95% CI, 3.44 to 4.27] points) groups. However, on the OSATS subscores, VOA significantly enhanced the mean OSATS overall subscore compared with the control group (mean difference, 1.04 [95% CI, 0.13 to 1.96] points; P = .02), whereas expert instruction significantly improved OSATS subscores for instrument handling vs control (mean difference, 1.18 [95% CI, 0.22 to 2.14]; P = .01). No significant differences in cognitive load, positive activating, and negative emotions were found. In this randomized clinical trial, VOA feedback demonstrated superior performance outcome and skill transfer, with equivalent OSATS ratings and cognitive and emotional responses compared with remote expert instruction, indicating advantages for its use in simulation training. ClinicalTrials.gov Identifier: NCT04700384.


Evaluation of the effects of sire and dam calving group on age at first calving in Brahman heifers.
This study evaluated the possible effects of sire and dam calving groups on age at first calving in Brahman heifers. A total of 570 heifers born between the years 2004 and 2017 were exposed as yearlings to fertile bulls through time of pregnancy determination. A calving group was determined by calculating the mean (993 d) and standard deviation (187 d) of heifer age at first calving. Heifers considered to calve early (≤899 d; calving group = 1) or late (≥1087 d; calving group = 3) were at least half a standard deviation (94 d) away from the mean. All other heifers were considered to have an intermediate age at first calving (900-1086 d; calving group = 2). Of the 570 heifers, only heifers from a dam (n = 182) with a known age at first calving and from a sire (n = 35) with 5 or more daughters were kept to determine the effect of dam calving group and the effect of sire calving group on age at first calving and calving group in daughters, resulting in a total of 284 heifers available for analysis. Variables included were dam and sire calving groups of the heifer, heifer age at first calving, heifer calving group, heifer season of birth, and heifer year of birth. Data were analyzed using the GLM procedures of SAS and proportions were tested using Chi-square. Sire calving group did affect (P < 0.01) age at first calving and calving group in heifers, but dam calving group did not affect (P > 0.10) daughter age at first calving or calving group. Analysis of dam calving group and sire calving group effects identified a year of birth effect (P < 0.01) on daughter age at first calving and calving group, whereas there was no significant season of birth effect. The proportion of daughters calving early for sire calving groups differed significantly from the expected proportion (P < 0.01), whereas the proportion of daughters calving early for dam calving groups did not differ. An effort to produce a greater proportion of Brahman heifers capable of calving early will not be effective from the dam side but may be effective from the sire side.


Are immunoglobulins with lupus anticoagulant activity specific for phospholipids?
Recent studies have suggested that the lupus anticoagulant (LA) may be specific for prothrombin, prothrombin-phospholipid complexes, or beta 2 glycoprotein 1 (beta 2GP1) rather than phospholipids. We performed a series of experiments to determine whether LA is indeed phospholipid specific. IgG was purified from sera of six patients with the antiphospholipid syndrome (APS) and 10 healthy controls. The six IgG-APS preparations had both LA and anticardiolipin (aCL) activity. Incubation of the six IgG-APS preparations with cardiolipin (CL), phosphatidylserine (PS), phosphatidylcholine (PC), or PS/PC (20:80) liposomes in Tris-buffered saline, resulted in loss of LA activity from the supernatant. We postulated that loss of activity might have resulted from absorption of IgG LA antibodies by phospholipids, a dilutional effect, or the presence of phospholipids in the supernatant causing 'by-pass' of IgG LA inhibitory activity. To distinguish between these possibilities, we re-isolated IgG from the supernatants and re-tested them for LA activity. IgG re-isolated from the PS. CL and PS/PC supernatants had no LA activity, but LA activity remained in the PC supernatant. This suggested that IgG with LA activity was absorbed by negatively charged but not by zwitterionic phospholipids. In like manner, PS, CL and PS/PC, but not PC liposomes, absorbed IgG with aCL activity. Mixtures of the phospholipid liposomes with beta 2GP1 did not modify the absorption of IgG with LA or aCL activity. Finally, we demonstrated that IgG eluted from immunoglobulin-cardiolipin liposome complexes had LA activity. Based on these findings, we conclude that at least one population of antibodies with LA activity is phospholipid specific.


Histopathological alterations after single epidural injection of ropivacaine, methylprednizolone acetate, or contrast material in swine.
The consequences from the injection of different types of drugs in the epidural space remains unknown. Increasing evidence suggests that localized inflammation, fibrosis, and arachnoiditis can complicate sequential epidural blockades, or even epidural contrast injection. We investigate the in vivo effect of epidural injections in the epidural space in an animal model. A group of ten male adult pigs, five punctures to each at distinct vertebral interspaces under general anesthesia, were examined, testing different drugs, used regularly in the epidural space (iopamidol, methylprednisolone acetate, ropivacaine). Each site was marked with a percutaneous hook wire marker. Histological analysis of the epidural space, the meninges, and the underlying spinal cord of the punctured sites along with staining for caspase-3 followed 20 days later. The epidural space did not manifest adhesions or any other pathology, and the outer surface of the dura was not impaired in any specimen. The group that had the contrast media injection showed a higher inflammation response compared to the other groups (P = 0.001). Positive staining for caspase-3 was limited to <5% of neurons with all substances used. No proof of arachnoiditis and/or fibrosis was noted in the epidural space with the use of the above-described drugs. A higher inflammation rate was noted with the use of contrast media.


Bi-faceted delivery of phytochemicals through chitosan nanoparticles impregnated nanofibers for cancer therapeutics.
Drug delivery through nanotechnological approaches has predominantly gained significance owing to the enhanced bioavailability, stability and targeted sequel. Multiple drug delivery is also on its stride to achieve holistic therapeutic regime. In our quest for such a treatment for cancer we selected two phytochemicals namely resveratrol (RS) and ferulic acid (FA) that have gained wide attention in the field of medicine due to their array of properties. Albeit their multifaceted application their therapeutic potential is mired due to its physicochemical instability and low bioavailability. Therefore, in the present study combinatorial effect of these compounds in cancer therapeutics have been scrutinized by fabricating chitosan nanoparticle loaded polycaprolactone nanofibers for delivering RS and FA. The materials were physico-chemical characterized. The nanoparticle incorporation within the nanofibers was corroborated through FITC tagging. The anti-cancer effect of drug loaded nanofibers were studied using A431 cells which displayed 30% and 50% reduction in the cell viability when treated with nanoparticles and nanofibrous scaffold. In congruence, the anti-angiogenic potential of the scaffold was elucidated using Chick chorioallantoic membrane assay and aortic ring assay. Thus, the nanofibrous delivery system opens up new venue in the field of cancer therapeutics with reduced side effects and efficient cancer targeting.


Human urine proteome analysis by three separation approaches.
The urinary proteome is known to be a valuable field of study related to organ functions. There have been several extensive urine proteome studies. However, the overlapping rate among different studies is relatively low. Whether the low overlapping rate was caused by different sample sources, preparation, separation and identification methods is unknown. Moreover, low molecular mass (<10 kDa) proteins have not been studied extensively. In this report, male and female pooled urine samples were collected from healthy volunteers. The urinary proteins were acetone precipitated, separated and identified by three approaches, 1-DE plus 1-D LC/MS/MS, direct 1-D LC/MS/MS and 2-D LC/MS/MS. 1-D tricine gels were used to separate low molecular mass proteins. The tandem mass spectra of positive identifications were quality controlled both by manual validation and using advanced mass spectrum scanner software. A total of 226 urinary proteins were identified; 171 proteins were identified by proteomics approach for the first time, including 4 male-specific proteins. Twelve low molecular mass proteins were identified. Most urinary proteins had a molecular mass between 30 and 60 kDa and a pI between 4 and 10. The apparent molecular masses of many proteins were different from theoretical ones, which indicated their post-translational modification and degradation. The effects of sample preparation, separation and identification methods on the overlapping rate of different experiments are discussed.


Disturbance of approach-avoidance behaviors in non-human primates by stimulation of the limbic territories of basal ganglia and anterior insula.
The basal ganglia (BG) are involved in motivation and goal-directed behavior. Recent studies suggest that limbic territories of BG not only support reward seeking (appetitive approach) but also the encoding of aversive conditioned stimuli (CS) and the production of aversive-related behaviors (avoidance or escape). This study aimed to identify inside two BG nuclei, the striatum and pallidum, the territories involved in aversive behaviors and to compare the effects of stimulating these territories to those resulting from stimulation of the anterior Insula (aIns), a region that is well-known to be involved in aversive encoding and associated behaviors. Two monkeys performed an approach/avoidance task in which they had to choose a behavior (approach or avoidance) in an appetitive (reward) or aversive (air-puff) context. During this task, either one (single-cue) or two (dual-cue) CS provided essential information about which context-adapted behavior should be selected. Microstimulation was applied during the CS presentation. Stimulation generally reduced approaches in the appetitive contexts and increased escape behaviors (premature responses) and/or passive avoidance (noninitiated action) in aversive context. These effects were more pronounced in ventral parts of all examined structures, with significant differences observed between stimulated structures. Thresholds to induce effects were lowest in the pallidum. Striatal stimulation led to the largest diversity of effects, with a subregion even leading to enhanced active avoidance. Finally, aIns stimulations produced stronger effects in the dual-cue context. These results provide causal evidence that limbic territories of BG, like aIns, play crucial roles in the selection of context-motivated behaviors.


A surveillance system for lymphatic filariasis after its elimination in Sri Lanka.
Lymphatic filariasis (LF) has been declared eliminated in Sri Lanka in September 2016. To maintain elimination status, a surveillance system to detect hidden endemic foci or LF resurgence is of highest priority. In this paper, we have reported an investigation of LF transmission in Trincomalee district where a surveillance program was not carried out due to 30 years of civil unrest. Proposed surveillance system included, measurement of anti-filarial IgG4 in urine of schoolchildren in areas where LF transmission could exist and assessment of circulating filarial antigen (CFA) and microfilaria (mf) in all urine antibody positive schoolchildren, their family members and 10-15 neighbours of each urine antibody positive household. Spatial distribution of the anti-filarial antibody titers in urine in a high antibody suspected area was analyzed using GPS logger data. Among 2301 school children from 11 schools studied, 41 (1.8%) urine antibody positives were found. The antibody positive rates of the schools ranged between 0 and 4.0%. Nine of the 630 (1.4%) examined became positive for CFA but were negative for mf. Although there were no mf positives, positive CFA and antibody results indicated the existence of Wuchereria bancrofti in Trincomalee. Highest antibody titres in an area correlated with the prevalences of urine antibodies and CFA. Spatial analysis showed LF transmission foci. Therefore, a combination of the non-invasive methods, urine ELISA and GPS mapping, will be a new effective surveillance system to identify hidden LF transmission foci.


Development and evaluation of a novel radioiodinated vesamicol analog as a sigma receptor imaging agent.
Sigma receptors are highly expressed in human tumors and should be appropriate targets for developing tumor imaging agents. Previously, we synthesized a vesamicol analog, (+)-2-[4-(4-iodophenyl)piperidino]cyclohexanol ((+)-pIV), with a high affinity for sigma receptors and prepared radioiodinated (+)-pIV. As a result, (+)-[125I]pIV showed high tumor uptake in biodistribution experiments. However, the accumulation of radioactivity in normal tissues, such as the liver, was high. We supposed that some parts of the accumulation of (+)-pIV in the liver should be because of its high lipophilicity, and prepared and evaluated a more hydrophilic radiolabeled vesamicol analog, (+)-4-[1-(2-hydroxycyclohexyl)piperidine-4-yl]-2-iodophenol ((+)-IV-OH). (+)-[125I]IV-OH was prepared by the chloramine T method from the precursor. The partition coefficient of (+)-[125I]IV-OH was measured. Biodistribution experiments were performed by intravenous administration of a mixed solution of (+)-[125I]IV-OH and (+)-[131I]pIV into DU-145 tumor-bearing mice. Blocking studies were performed by intravenous injection of (+)-[125I]IV-OH mixed with an excess amount of ligand into DU-145 tumor-bearing mice. The hydrophilicity of (+)-[125I]IV-OH was much higher than that of (+)-[125I]pIV. In biodistribution experiments, (+)-[125I]IV-OH and (+)-[131I]pIV showed high uptake in tumor tissues at 10-min post-injection. Although (+)-[131I]pIV tended to be retained in most tissues, (+)-[125I]IV-OH was cleared from most tissues. In the liver, the radioactivity level of (+)-[125I]IV-OH was significantly lower at all time points compared to those of (+)-[131I]pIV. In the blocking studies, co-injection of an excess amount of sigma ligands resulted in significant decreases of tumor/blood uptake ratios after injection of (+)-[125I]IV-OH. The results indicate that radioiodinated (+)-IV-OH holds a potential as a sigma receptor imaging agent.


Turn-on fluorescence sensor for the detection of heparin based on rhodamine B-modified polyethyleneimine-graphene oxide complex.
Rhodamine B modified Polyethyleneimine (PEI) (called RB-PEI) with strong fluorescence intensity was synthesized, which contained high positively charged amine groups. The fluorescence intensity of RB-PEI can be quenched by graphene oxide (GO). The high efficiency of the quenching was caused by the non-covalent binding of RB-PEI to the GO surface by electrostatic and π-π interactions, forming a RB-PEI/GO complex. However, adding heparin caused intense fluorescence to be recovered, and this was caused by the anionic heparin removing the RB-PEI from the GO surface, forming a fluorescent RB-PEI/heparin complex. Under optimal conditions, the change in the fluorescence intensity when heparin was added was proportional to the heparin concentration over the range 0.09-0.9 U mL(-1). The detection limit for heparin was 0.00132 U mL(-1), which was lower than that has been achieved using other methods. This approach offers a new quantitative method for determining heparin.


Determination of the main hydrolysis products of organophosphorus nerve agents, methylphosphonic acids, in human serum by indirect photometric detection ion chromatography.
For the verification of the use of chemical warfare agents (CWA), sarin, soman and VX, a simple rapid and accurate method which allows us to simultaneously determine their degradation products, isopropyl methylphosphonic acid (IPMPA), pinacolyl methylphosphonic acid (PMPA), ethyl methylphosphonic acid (EMPA) and methylphosphonic acid (MPA), in human serum, was explored by indirect photometric detection ion chromatography (IPD-IC) which employs an anion-exchange column. IC analysis was performed after sample preparation with an Ag+-form cation-exchange resin cartridge, and the four methylphosphonic acids could be separated well. The proposed conditions are as follows: eluent, 0.5 mM phthalic acid-0.1 mM Tris (hydroxymethyl) aminomethane-5% acetonitrile; flow-rate, 1.0 ml/min; temperature, 50 degrees C; UV detector, 266 nm. All four methylphosphonic acids were eluted within 30 min with hardly any disturbance by impurities in the serum. Linear calibration curves were obtained for MPA, EMPA and IPMPA in the concentration range from 50 ng/ml to 1 microg/ml and for PMPA from 100 ng/ml to 1 microg/ml. The relative standard deviation for the methylphosphonic acids ranged from 3.8 to 6.9% at 500 ng/ml and the detection limits were 40 ng/ml for MPA, EMPA and IPMPA and 80 ng/ml for PMPA. The method would be suitable for analysis of human serum samples.


Long insular artery damage might be a key sign for predicting functional prognosis of putaminal hemorrhage.
Although the putamen is the most common area of spontaneous intracerebral hemorrhage, previous reports about the effects of surgery are limited. We sometimes experience a poor prognosis in patients in whom there is no damage to the internal capsule, but with injury in the long insular artery (LIA) region. The purpose of this study was to confirm the relationship between LIA damage and patient prognosis following surgery for putaminal hemorrhage. We retrospectively collected data of 287 surgical cases who presented with putaminal hemorrhage between January 2004 and March 2022. Among them, we chose patients without initial damage to the posterior limb of the internal capsule, and divided these patients into two groups, those without (Group A) and with (Group B) final damage in the LIA region. We compared positivity rates of final manual muscle test (MMT) scores≥3 and related factors. Sixty-three of the 287 patients were included in this study. Of them, 11 cases in Group A were positive for MMT scores≥3 (68.8%) and 9 cases (19.1%) in Group B had MMT scores≥3 seven days after surgery. Group A thus had a significantly higher rate of MMT scores≥3 than group B (p=0.00). In patients without initial damage to the internal capsule, LIA injury might be a key sign for predicting the functional prognosis of putaminal hemorrhage.