On-chip detection of myoglobin based on fluorescence.
A disposable immunosensor cartridge was developed that allows antibodies to be immobilized on the surface for the detection of myoglobin, a marker for the early assessment of acute myocardial infarction (AMI) using fluorescence techniques. The anti-myoglobin antibody was immobilized on a polystyrene substrate based on covalent bonding via silanization. The immunosensor chip layers were fabricated from sheets by CO(2)-laser ablation. The functionalized polystyrene surfaces were characterized by contact angle measurement, X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). After the antigen-antibody reaction as a sandwich enzyme-linked immunosorbent assay (ELISA) with a horseradish peroxidase-conjugated secondary antibody (HRP-anti-myoglobin), addition of fluorogenic substrate produced a fluorescent dye which was quantified on-chip using fluorescent technique. The immunosensor response was linear for myoglobin concentrations between 20 and 230 ng/ml (r=0.991, n=3). The detection limit was found to be 16 ng/ml, which is lower than the clinical cut-off value for myoglobin in healthy patients. This protocol could be extended to the detection of other important cardiac markers simultaneously in microchannels.


Advanced immunotherapies for glioblastoma: tumor neoantigen vaccines in combination with immunomodulators.
Glial-origin brain tumors, including glioblastomas (GBM), have one of the worst prognoses due to their rapid and fatal progression. From an oncological point of view, advances in complete surgical resection fail to eliminate the entire tumor and the remaining cells allow a rapid recurrence, which does not respond to traditional therapeutic treatments. Here, we have reviewed new immunotherapy strategies in association with the knowledge of the immune micro-environment. To understand the best lines for the future, we address the advances in the design of neoantigen vaccines and possible new immune modulators. Recently, the efficacy and availability of vaccine development with different formulations, especially liposome plus mRNA vaccines, has been observed. We believe that the application of new strategies used with mRNA vaccines in combination with personalized medicine (guided by different omic's strategies) could give good results in glioma therapy. In addition, a large part of the possible advances in new immunotherapy strategies focused on GBM may be key improving current therapies of immune checkpoint inhibitors (ICI), given the fact that this type of tumor has been highly refractory to ICI.


Association of allelic combinations of FSHR gene polymorphisms with ovarian response.
During an IVF protocol, exogenous FSH is administered to women for ovulation induction. The ovarian response to gonadotrophin stimulation is variable and unpredictable in these women. The FSHR is the most studied gene in relation to ovarian response. The association of a FSHR gene polymorphism at position 680 (p.Asn680Ser) with ovarian response has been well documented. Recently, a polymorphism at position -29 in the 5'-untranslated region of FSHR (g.-29G>A) has been reported to be associated with poor ovarian response and reduced FSHR expression. The present study evaluated the combined effect of the polymorphisms at positions -29 and 680 of FSHR with type of ovarian response and receptor expression. The two FSHR gene polymorphisms together formed four discrete haplotypes and nine allelic combinations. Various clinical parameters revealed that 75% of the subjects with A/A-Asn/Asn genotype were poor ovarian responders (odds ratio 7.92; P=0.009). The relative FSHR mRNA expression in granulosa cells indicated that subjects with A/A-Asn/Asn genotype express significantly lower level of FSHR as compared to the subjects with G/G-Asn/Ser genotype (P=0.029). These results indicate that A/A-Asn/Asn genotype could be used as a potential marker to predict poor ovarian response. The action of FSH is mediated by its receptor (FSHR) present on the granulosa cells in the ovary. Any alterations in the hormone or its receptor are likely to disrupt its normal function, thus causing infertility. Several alterations (mutations/polymorphisms) of the FSHR gene have been reported in women with primary or secondary amenorrhoea. It has also been reported that FSHR gene polymorphisms are associated with variable ovarian response to FSH stimulation during IVF. Women may show poor or normal or hyperovarian response to FSH stimulation. It is well documented that the level of FSHR expression has a great effect on FSH action and is associated with ovarian response. In the present study, we screened normally menstruating women undergoing IVF due to tubal/male factor or unexplained infertility. We analysed two polymorphisms of FSHR, g-29G>A and p.Asn680Ser, in these women. In the subjects studied, 75% women with A/A-Asn/Asn genotype were observed to be poor ovarian responders to FSH stimulation. FSHR expression at the transcript level was observed to be significantly lower in women with A/A-Asn/Asn genotype as compared to women with G/G-Asn/Ser genotype. We also observed that women with A/A-Ser/Ser genotype were not present in the study population. These findings indicate the significance of A/A-Asn/Asn genotype as a predictive marker for poor ovarian response to FSH stimulation.


Metabolic response to omega-3 fatty acid supplementation in patients with diabetic nephropathy: A randomized, double-blind, placebo-controlled trial.
This study was carried out to evaluate the effects of omega-3 fatty acid administration on markers of insulin resistance, lipid concentrations, biomarkers of inflammation and oxidative stress in patients with diabetic nephropathy (DN). This parallel randomized double-blind placebo-controlled clinical trial was performed among 60 patients with DN. Patients were randomly allocated into two groups to receive either 1000 mg/day omega-3 fatty acid from flaxseed oil (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were taken at the onset of the study and 12 weeks after supplementation to assess glycaemic status, lipid concentrations, biomarkers of inflammation and oxidative stress. After 12 weeks of treatment, patients who consumed omega-3 fatty acid supplements compared with the placebo had significantly decreased serum insulin levels (-39.6 ± 10.8 vs. -7.2 ± 8.4 pmol/L, P = 0.001), homeostasis model of assessment-estimated b cell function (HOMA-B) (-30.2 ± 11.2 vs. -1.5 ± 6.8, P = 0.03) and improved quantitative insulin sensitivity check index (QUICKI) (+0.01 ± 0.004 vs. +0.002 ± 0.004, P = 0.03). Additionally, compared with the placebo, omega-3 fatty acid administration led to a significant reduction in serum triglycerides (-19.8 ± 8.8 vs. +12.6 ± 10.2 mg/dL, P = 0.01) and VLDL-cholesterol concentrations (-4.0 ± 1.8 vs. +2.5 ± 2.0 mg/dL, P = 0.01). Supplementation with omega-3 fatty acid had no significant effects on other lipid subfractions, biomarkers of inflammation and oxidative stress compared with the placebo. In addition, within-group differences revealed significant reductions in serum insulin (P = 0.001), HOMA-IR (P = 0.004), HOMA-B (P = 0.01), serum triglycerides (P = 0.03), VLDL- (P = 0.03), total- (P < 0.001), LDL- (P = 0.002), total-/HDL-cholesterol ratio (P = 0.001), blood urea nitrogen (P = 0.04), and significant increases in QUICKI (P = 0.001) and nitric oxide (P = 0.005) and total antioxidant capacity concentrations (P = 0.02) in the omega-3 fatty acid group. Our findings indicated that omega-3 fatty acid administration for 12 weeks among DN patients had favorable effects on insulin levels, HOMA-B, QUICKI, serum triglycerides and VLDL-cholesterol; however, it did not influence biomarkers of inflammation and oxidative stress.


Low frequency voltage clamp: recording of voltage transients at constant average command voltage.
We implemented a simple feedback system that modifies the conventional current clamp mode of a patch clamp amplifier so that transient potentials, such as action potentials and synaptic potentials, can be measured as in the usual current clamp, while the average membrane potential is kept constant at a value chosen by the user. The circuit thus works like the current clamp for high frequency signals and like a voltage clamp for low frequency signals. We delineate its transfer properties and give application examples.


Oh8dG induces G1 arrest in a human acute leukemia cell line by upregulating P21 and blocking the RAS to ERK signaling pathway.
We reported previously that KG-1, a human acute leukemia cell line, has mutational loss of 8-oxoguanine (8-hydroxyguanine; oh8Gua) glycosylase 1 (OGG1) activity and undergoes apoptotic death after treatment with 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodeoxyguanosine, 8-hydroxydeoxyguanosine; oh8dG). In our present study, we further characterized the effects of oh8dG in KG-1 cells and found that, in addition to apoptosis, oh8dG induced the arrest of KG-1 at the G1 phase. Simultaneously, oh8dG-treated KG-1 showed an increase in the oh8Gua content of DNA, upregulation of p21 (an inhibitor of cdk), and Ras inactivation. Moreover, the upregulation of p21 was followed by the inactivations of cdk4 and cdk2, the hypophosphorylation of Rb, and a marked decline in the expression of c-myc (a gene regulated by E2F that is a transcription factor whose activity is suppressed when it is bound to hypophosphorylated Rb). Ras inactivation was also followed by the inactivation of ERK kinase (MEK) and the inactivation of AP-1, a downstream target of the Ras signaling pathway. The specific MEK inhibitors, PD98059 and U0126, also induced G1 arrest. These findings suggest that p21 upregulation and Ras inactivation contribute to G1 arrest. An increase of oh8Gua content in DNA does not seem to be a principal contributor to G1 arrest, however, because the kinetics of increases of oh8Gua content in DNA and of G1 cell number did not coincide. We report that oh8dG induces the arrest of KG-1 growth at the G1 phase mainly by upregulating p21 and inactivating Ras.


Cryptosporidium and Giardia infections in humans in Tigray, Northern Ethiopia: an unexpectedly low occurrence of anthropozoonotic transmission.
Enteric protozoans Cryptosporidium spp. and Giardia duodenalis are among the leading causes of diarrhoea in children. These parasites have particular impact in low- and middle-income countries. In these countries, people often live in close contact with their animals, highlighting the potential role of zoonotic routes of transmission in disease spread. The occurrence and species/genotypes of Cryptosporidium and Giardia duodenalis infecting humans in Tigray, Ethiopia were investigated, along with the risk associated with infection. Stool samples from 249 asymptomatic people (4-80 years of age) in four rural districts in Tigray and 58 from symptomatic young children (1-33 months) attending health centres in Mekelle, Tigray's main city, were analysed for Cryptosporidium oocysts and Giardia cysts. Participants in the rural areas completed questionnaires regarding potential risk factors, with emphasis on livestock contact and sources of water. The occurrence of Cryptosporidium infection was 6% and 5% in people in the rural districts and young children from Mekelle, respectively; equivalent figures for Giardia infection were 29% and 14%. Molecular characterization of Cryptosporidium isolates revealed C. ubiquitum, subtype XIIa in a sample from rural districts, and C. hominis subtype IdA17 (1 sample) and IbA9G3 (2 samples) in infants from Mekelle with diarrhoea. For Giardia, Assemblage B predominated (22/25; 88%), but we also identified three samples with Assemblage A (AII). Our major finding was that, despite the close contact between people and livestock in our rural study sites, transmission of Cryptosporidium and Giardia between humans and their animals seems to be surprisingly uncommon. Our results are discussed in relation to other relevant studies, and also draws attention to the possibility that introduction of zoonotic species and/or subtypes, such as C. parvum, could have serious consequences for both human and animal health. As our study was conducted in Tigray, further investigation in different settings in Ethiopia could provide relevant information on transmission and zoonotic potential, and the potential for spread of zoonotic transmission. In addition, given the importance of these two parasites in causing diarrhoea in children, this information is vital for developing effective appropriate interventions against transmission that can be applied not only in Tigray or Ethiopia, but throughout Africa and beyond.


Mixed donor chimerism and low level iduronidase expression may be adequate for neurodevelopmental protection in Hurler Syndrome.
Hurler syndrome is a lysosomal storage disease resulting in fatal cardiac or neurologic sequelae unless alpha-iduronidase production is reconstituted with hematopoietic stem cell transplantation. We report on a 4-year, 6-month-old boy with mixed donor chimerism and low enzyme levels but a normal neurodevelopmental trajectory.


A new binuclear Ni(II) complex, an effective A3-coupling catalyst in solvent-free condition.
A newly binuclear nickel(II) complex, [Ni2(en)4(ox)](ClO4)2 (1) (where en = ethylenediamine, and ox = oxalate), has been isolated from a reaction of NiCl2·6H2O, ethylenediamine, ammonium oxalate and sodium perchlorate in water and its crystal structure has been determined by X-ray crystallography and infra-red techniques. Compound 1 was successfully employed to promote the one-pot reaction of aldehydes, amines and acetylenes for the construction of corresponding propargylamines under solvent-free media with fine yields. Further studies reveal this catalytic system can be refreshed and used again in five runs.


Age-related susceptibility of the gerbil, Meriones unguiculatus, to the bovine parasite, Babesia divergens.
Immature gerbils (4 weeks of age or less) proved to be more resistant to Babesia divergens infections than did mature animals (greater than 8 weeks old). Nutritional studies showed that a milk diet contributes little to this innate resistance. Similarly, the apparent predilection of B. divergens for mature erythrocytes, and also in vitro serum incubation studies, suggested that blood factors do not contribute to any major degree. Splenectomy of immature gerbils abolished their nonspecific resistance and studies with splenocyte incubations with the piroplasm imply that splenic integrity is necessary for the maintenance of this, apparently antibody-independent, resistance to infection with B. divergens.


High prevalence of small vessel disease long after cranial irradiation.
Accelerated atherosclerosis of intra- or extracranial large arteries is a major cause of radiation-induced strokes. Recent development of MRI techniques has enabled detection of another important vasculopathy: microinfarcts or microbleeds after cranial irradiation. The purpose of this study was to investigate the incidence and characteristics of small vessel disease after cranial irradiation. MR images and clinical records of 102 outpatients who had undergone cranial irradiation to brain tumors were retrospectively reviewed. Only those who had undergone T1WI, T2WI, FLAIR, and T2∗WI during follow-up were included. Small vessel disease including small subcortical infracts, microbleeds, and volume of white matter lesions were assessed on the latest MR images of each patient. Ischemic or hemorrhagic stroke during the follow-up period was also reviewed. Twelve patients (mean age at the latest MRI, 38.5years; 8men) were assessed. The total radiation dose was 52.3±9.7Gy in these patients, 9 of whom received whole brain irradiation. Small subcortical infarcts (mean 2.3) were detected in 8 patients, microbleeds (mean 19.4) were detected in 11, and white matter lesion volume was 38.3±11.6ml. During the follow-up period of 19.8±9.7years, 5 patients experienced stroke (4 lacunar, 1 hemorrhagic). These strokes occurred as long as a median 21.9 (range, 10.4-30.2) years after cranial irradiation. In conclusion, small vessel disease is not a rare complication after cranial irradiation, even in young patients. Patients after cranial irradiation should be followed up with MR imaging including a hemosiderin-sensitive sequence.


Effect of 1.5% potassium oxalate on sensitivity control, color change, and quality of life after at-home tooth whitening: A randomized, placebo-controlled clinical trial.
This clinical trial evaluated the effect of 1.5% potassium oxalate (PO) in controlling sensitivity and color change after at-home tooth whitening. It also evaluated the influence of PO on health-related quality of life (HRQoL) and the degree of patient satisfaction after bleaching treatment. Fifty volunteers were randomized into two groups (n = 25): At-home bleaching gel with 22% carbamide peroxide for 45 min + placebo gel (GP) or 1.5% PO (GPO) for 10 min. The intensity of tooth sensitivity was assessed daily through the visual analog scale. The color analysis was performed three times: baseline, 21 days, and 1 month after the last application of the whitening gel. The impact of the oral condition on the patient's quality of life (OIDP) was used to measure the impact caused by the whitening treatment in relation to the individuals' ability to carry out their daily activities and its influence on HRQOL. No difference in tooth sensitivity was observed (p > 0.05). In addition, there was no difference in color change between groups (p > 0.05). However, there was an intragroup statistical difference throughout the evaluation period (p <0.05). The OIDP analysis showed a statistical difference between the groups (p > 0.05) and there was no difference between the groups regarding the degree of satisfaction with the bleaching (p > 0.05). The 1.5% PO was effective in preventing sensitivity and did not interfere with tooth whitening. Desensitizing therapy had a positive impact on quality of life and patient satisfaction.


Iron-deficiency anemia in infancy and poorer cognitive inhibitory control at age 10 years.
The aim of this study was to assess the effects of iron-deficiency anemia (IDA) in infancy on executive functioning at age 10 years, specifically inhibitory control on the Go/No-Go task. We predicted that children who had IDA in infancy would show poorer inhibitory control. We assessed cognitive inhibitory control in 132 Chilean children (mean [SD] age 10 y [1 mo]): 69 children had IDA in infancy (45 males, 24 females) and 63 comparison children who did not have IDA (26 males, 37 females). Participants performed the Go/No-Go task with event-related potentials. Group differences in behavioral (accuracy, reaction time) and electrophysiological outcomes (N2 and P300 components) were analyzed using repeated-measures analyses of variance. N2 and P300 are interpreted to reflect attention and resource allocation respectively. Relative to comparison participants, children who had IDA in infancy showed slower reaction time (mean [SE], 528.7 ms [14.2] vs 485.0 ms [15.0], 95% confidence interval [CI] for difference between groups 0.9-86.5); lower accuracy (95.4% [0.5] vs 96.9% [0.6], 95% CI -3.0 to -0.1); longer latency to N2 peak (378.9 ms [4.9] vs 356.9 ms [5.0], 95% CI 7.5-36.6); and smaller P300 amplitude (4.5 μV [0.8] vs 7.6 μV [0.9], 95% CI-5.5 to -0.5). IDA in infancy was associated with slower reaction times and poorer inhibitory control 8 to 9 years after iron therapy. These findings are consistent with the long-lasting effects of early IDA on myelination and/or prefrontal-striatal circuits where dopamine is the major neurotransmitter.


Variation in Fetal Weight Percentile Estimates.
Weight percentiles are generally reported without any indication of error. This variation can lead a fetus being mistakenly classified erroneously as having intrauterine growth restriction (IUGR) or macrosomia. The goal of this study was to compare estimated weight percentiles with the actual observed weight percentile for each gestational age in a large cohort of fetuses being scanned in our institution. After IRB approval the radiology information system data base was retrospectively searched for all obstetrical US reports obtained during the late second and third trimesters from July 1, 2014, until July 1, 2020. Demographic information, fetal weight, and weight percentile information were obtained from these reports. Quantile-quantile plots were created for all gestational ages and all ethnicities. Our study included 6259 ultrasounds in 4060 patients. Mean maternal age of the total group was 31.68 years (ranging 15-53 years). When all subjects were considered, the median values in our QQ plots approximated the line of identity. However, there was considerable variation for a given estimate, implying that estimated fetal weight percentiles are only very rough predictors of the actual percentile. Estimated fetal weight percentiles are only very rough predictors of the actual percentile. We therefore suggest that estimates of the weight percentile should be reported along with an estimate of the expected variation. Recognition of variations in weight percentile should be considered in the greater clinical context, and could potentially prevent misdiagnosis of growth restriction and macrosomia as well as the subsequent overutilization of resources, unnecessary interventions, and maternal stress.


Signaling interplay in Ras superfamily function.
Ras proteins function as signaling hubs that are activated by convergent signaling pathways initiated by extracellular stimuli. Activated Ras in turn regulates a diversity of downstream cytoplasmic signaling cascades. Ras proteins are founding members of a large superfamily of small GTPases that have significant sequence and biochemical similarities. Recent observations have established a complex signaling interplay between Ras and other members of the family. A key biochemical mechanism facilitating this crosstalk involves guanine nucleotide exchange factors (GEFs), which serve as regulators and effectors, as well as signaling integrators, of Ras signaling.


Autoradiographic localization of sex steroid hormones in the lymphatic organs of baboons.
The localization of radiolabeled estradiol and dihydrotestosterone was examined in the lymphatic organs of both male and female baboons. A total of 12 baboons were divided into two groups, each containing three males and three females. Each animal in one group, both males and females, was injected intravenously with 1 microgram/kg body weight of 3H-estradiol while those in the second group were each injected with 1 microgram/kg body weight of 3H-dihydrotestosterone. As controls, one male and one female from each group also received a dose of 100 micrograms/kg body weight of the corresponding unlabeled steroid. One and a half hours after the injections, the animals were sacrificed and the spleen, thymus, and inguinal lymph nodes removed and processed for autoradiography. The localization of 3H-estradiol was similar in both males and females. In the thymus fibroblasts and epithelio-reticular cells, but not thymocytes, localized 3H-estradiol. In lymph node and spleen, non-lymphoid tissue concentrated the labeled estrogen. Additionally, in the paracortical region of the lymph node, an unknown cell type was labeled with estrogen. Only one male baboon demonstrated nuclear localization of 3H-dihydrotestosterone. This was observed in the reticular cells in the spleen and lymph nodes. The same cell type in the organs of the remaining animals was unlabeled.


Relational Peer Victimization Interacts With Depression Severity to Predict the Timing of Alcohol Use Initiation in Adolescent Girls.
Peer victimization is consistently linked to adolescents' alcohol use. However, the relative influence of relational and physical peer victimization on alcohol use, and timing of drinking initiation, is not well understood. In this study, we evaluate the impact of both relational and physical peer victimization on adolescent girls' alcohol use initiation, and the extent to which depression severity moderates these associations. Participants were 2,125 girls in the Pittsburgh Girls Study, a longitudinal community-based study. Participants reported experiences of relational and physical peer victimization, depression severity, and alcohol use each year from ages 10 to 17. Cox proportional hazards (PH) regression analyses predicting the timing of first drink were conducted in 2 stages, testing for main effects of peer victimization in Model 1 and moderation by depression severity in Model 2. Analyses were split at age 14 to adjust for PH violations. Model 1 results supported a main effect for relational (Hazards ratio [HR] = 1.83, CI: 1.46 to 2.28 ≤ age 13; HR = 1.23, CI: 1.05 to 1.45 ≥ age 14) but not physical victimization on timing of alcohol use onset (HR = 1.10, CI: 0.88 to 1.39). Model 2 results show that depression severity moderates the association between relational victimization and alcohol use initiation: the association between relational victimization and early alcohol use onset was stronger for lower depression severity (-1 SD HR = 2.38, CI: 1.68 to 3.39 ≤ age 13; -1 SD HR = 1.48, CI: 1.10 to 1.52 ≥ age 14). Results demonstrate that relational (and not physical) victimization predicts earlier drinking among adolescent girls. Relational peer victimization conferred greater risk for alcohol use initiation when depression severity was lower, whereas girls with high depression severity engaged in early alcohol use regardless of peer victimization. Results suggest that interventions focused on relational peer victimization may have spillover effects for delaying girls' alcohol use initiation, particularly in early adolescence, when this association is most robust.


Successful limb reperfusion by temporary arterial shunt during a 950-mile air transfer: case report.
Plastic vascular shunts successfully reperfused a trauma victim's severely ischemic leg for 16 hours during a 950-mile transfer to a regional trauma center. Although the limb ultimately was lost, this case suggests the potential value of temporary shunts in managing complex extremity vascular injuries in settings remote from the trauma center.


Nonfamilial hematuria associated with glomerular basement membrane alterations characteristic of hereditary nephritis: comparison with hereditary nephritis.
Characteristic ultrastructural alterations of the glomerular basement membrane (GBM) have been reported in hereditary nephritis and in children without a family history of renal disease. The clinical features, renal biopsy findings, and subsequent course were studied retrospectively in 48 children with such GBM changes to compare findings in those with and without a family history of nephritis and to determine the significance of the GBM changes in patients with nonfamilial disease. All 48 patients had hematuria. For 30, there was hematuria in at least one other member of the family (familial hematuria group); for 18, there was no familial incidence. There were no differences between the two groups with regard to clinical and pathologic findings. At the latest follow-up six boys with familial hematuria and three boys with nonfamilial hematuria had reduced renal function, and nine boys with familial hematuria and four boys and one girl with nonfamilial hematuria had neurosensory deafness. Our study results show that children with these GBM changes, with or without a family history of hematuria, tend to have a progressive course, with frequent occurrence of neurosensory deafness, and that the prognosis is more severe in boys. These observations suggest that such GBM changes in patients with nonfamilial hematuria may represent new mutations for hereditary nephritis.


Small-scale spatial distribution of marine meiobenthos: the effects of decaying macrofauna.
To evaluate the effects of decaying animals on small-scale horizontal distribution of meiobenthos in muddy habitats, a laboratory experiment was performed at the Askö Laboratory in the northwestern Baltic Sea. A microcosm (35×55×28 cm) containing a ca. 7-cm thick layer of sieved (0.5 mm) sublittoral mud was established in June 1990. Three months later specimens of the bivalve Macoma balthica were collected and killed in boiling water. The sediment inside the microcosm was implanted with empty shell, empty shell and dead animal or left alone. At the end of the experiment (17 days) visual examination of the microcosm revealed black spots at the sediment surface where dead animals had been implanted. The densities of nematodes, the most abundant group (98%), were not significantly different between areas. However total non-nematode fauna was found in much lower numbers (P<0.01) in the black spot areas. A multivariate analysis (detrended correspondence ordination) of nematode species abundance data separated samples from the black spot areas from the others. Of the 25 nematode species recorded in the microcosm, there was a significant difference between areas for four species. The decaying animals clearly attracted Monhystera disjuncta which was almost 6 times as abundant in the black spot areas compared to control and shell areas. Both the overall dominant species, Leptolaimus elegans and Calomicrolaimus honestus were found in lower numbers in the areas of dead Macoma than in control and shell areas. Sabatieria pulchra was found in lower numbers in the control areas compared to shell and dead animal areas. The overall structure of the nematode assemblage indicated a shift to lower dominance in the dead animal areas and it is speculated that decomposing animal tissue may be of primary importance regarding spatial distribution of meiobenthos.


Biomechanical analysis of sagittal correction parameters for surgical instrumentation with pedicle subtraction osteotomy in adult spinal deformity.
High complication rate has been documented in spinal instrumentation with pedicle subtraction osteotomy. The objective was to analyze the biomechanics of spinal instrumentation with pedicle subtraction osteotomy as functions of three instrumentation parameters. Patient-specific biomechanical computer models of 3 adult patients who were instrumented with pedicle subtraction osteotomy were used to simulate the actual instrumentations and alternative instrumentations derived by varying instrumentation parameters: pedicle subtraction osteotomy wedge angle and rod contouring angle, location of the osteotomy, and number of rods (2 vs. 4). A change of the sagittal correction by +7.5° (-7.5°) resulted in a change in the screw axial forces and rods bending loads around the osteotomy by +38% (-19%) and +28% (-11%), respectively. The bending moments in the rods were 31% lower at the osteotomy site when it was located at one level above, and 20% higher when it was located at a level below. Additional rods allowed the rod bending and screw axial loads to be reduced by 24% and 22%, respectively. The amount of sagittal correction was positively correlated with loads sustained by the screws and rods. Rods were subjected to higher bending loads at the pedicle subtraction osteotomy site when it was done at a lower level. A 4-rod construct is an effective way to reduce the risk of rod breakage by reducing the loads sustained by the rods.


Adopting moderate alcohol consumption in middle age: subsequent cardiovascular events.
Moderate alcohol use is part of a healthy lifestyle, yet current guidelines caution nondrinkers against starting to drink alcohol in middle age. The purpose of this study was to evaluate whether adopting moderate alcohol consumption in middle age would result in subsequent lower cardiovascular risk. This study examined a cohort of adults aged 45-64 years participating in the Atherosclerosis Risk in Communities study over a 10-year period. The primary outcome was fatal or nonfatal cardiovascular events. Of 7697 participants who had no history of cardiovascular disease and were nondrinkers at baseline, within a 6-year follow-up period, 6.0% began moderate alcohol consumption (2 drinks per day or fewer for men, 1 drink per day or fewer for women) and 0.4% began heavier drinking. After 4 years of follow-up, new moderate drinkers had a 38% lower chance of developing cardiovascular disease than did their persistently nondrinking counterparts. This difference persisted after adjustment for demographic and cardiovascular risk factors (odds ratio 0.62, 95% confidence interval, 0.40-0.95). There was no difference in all-cause mortality between the new drinkers and persistent nondrinkers (odds ratio 0.71, 95% confidence interval, 0.31-1.64). People who newly begin consuming alcohol in middle age rarely do so beyond recommended amounts. Those who begin drinking moderately experience a relatively prompt benefit of lower rates of cardiovascular disease morbidity with no change in mortality rates after 4 years.


Long-term functional evaluation of diaphragmatic motility after repair of congenital diaphragmatic hernia.
A few studies have taken into account the diaphragmatic function in patients successfully treated for congenital diaphragmatic hernia (CDH). Monodimensional sonography has been reported to be useful in assessing the diaphragmatic motility. Aim of the present study was to investigate, in a long-term follow-up, the diaphragmatic function after CDH repair. Ten patients, with a mean age of 16 (5-26) years, were enrolled. All had had a left diaphragmatic hernia repaired, but no one received a patch. Ten subjects of matched age were used as controls. The diaphragmatic excursions appear, at M-mode sonography, as a sinusoid; the amplitude of the curve on the vertical axis measured the movement in centimeters. Chest x-ray and spirometry were also performed in CDH patients. A reduced diaphragmatic motility on the left (treated) side was recorded. The amplitude of the contraction was significantly reduced when compared with the contralateral side (1.19 +/- 0.2 vs 2.33 +/- 0.9 cm; P = .017) and was also significantly reduced in comparison with the motion of the left side of controls (1.19 +/- 0.2 vs 1.83 +/- 0.4 cm; P = .01). There was no difference in the amplitude of contraction between the left and right sides of control patients and between the right side of CDH patients and the controls. Spirometry was normal in all patients but one, who had a slight reduction of ventilation on the left side. M-mode sonography appears as a very useful tool in quantitative evaluation of diaphragmatic movements and should be extensively used during follow-up of patients after CDH repair. Motility of the repaired diaphragmatic is reduced, even after a long period, but this does not affect the respiratory function in patients who survived CDH repair.


[Studies on the synthesis of antiulcer agents. V. Synthesis and antiulcer activity of dihydrobenzofuranone derivatives].
In the preceding paper, we reported that 1-[3-[3-oxospiro[benzofuran-2(3H),1'-cyclopropan]-5- yl]acryloyl]piperidine(1a) and 4-[3-[3-oxospiro[benzofuran-2(3H),1'-cyclopropan]-5- yl]acryloyl]morpholine(1b) have potent antiulcer activities. In this paper, propionic acid derivatives (2,3) and oxyacetic acid derivatives (4, 5, 10) were prepared by converting the acryloyl moiety into propionyl and oxyacetyl groups, and tested for antiulcer activities. As a result, [3-oxospiro[benzofuran-2(3H),1'-cyclopropan]5-yloxy]-a cetamide(4j) exhibited significant antiulcer activities.


Evaluation of a community-based integrated care model (CIE) for frail older people in rural Foshan, China: study protocol for a stepped-wedge cluster randomized controlled trial {1}.
While community-based eldercare has proven to be effective in qualitative studies, there is limited evidence on the effectiveness of this geriatric care model in rural communities where caring for older people is traditionally the responsibility of family members, but a formal long-term care was recently introduced in China. CIE is a rural community-embedded intervention using multidisciplinary team, to provide evidenced-based integrated care services for frail older people including social care services and allied primary healthcare and community-based rehabilitation services. CIE is a prospective stepped-wedge cluster randomized trial conducted at 5 community eldercare centers in rural China. The multifaceted CIE intervention, guided by chronic care model and integrated care model, consists of five components: comprehensive geriatric assessment, individualized care planning, community-based rehabilitation, interdisciplinary case management, and care coordination. The intervention is rolled out in a staggered manner in these clusters of centers at an interval of 1 month. The primary outcomes include functional status, quality of life, and social support. Process evaluation will also be conducted. Generalized linear mixed model is employed for binary outcomes. This study is expected to provide important new evidence on clinical effectiveness and implementation process of an integrated care model for frail older people. The CIE model is also unique as the first registered trial implementing a community-based eldercare model using multidisciplinary team to promote individualized social care services integrated with primary healthcare and community-based rehabilitation services for frail older people in rural China, where formal long-term care was recently introduced. TRIAL REGISTRATION {2A}: China Clinical Trials Register ( http://www.chictr.org.cn/historyversionpub.aspx?regno=ChiCTR2200060326 ). May 28th, 2022.


[The pulmonary hemodynamic changes under experimental myocardial ischemia in rabbits following beta-adrenoreceptors blockade].
In acute experiments in anesthetized rabbits, changes of the pulmonary hemodynamics following myocardial ischemia in the region of the descendent left coronary artery were studied as well as in control animals and after the blockade of beta-adrenoreceptors. The myocardial ischemia decreased the left ventricular myocardial contractility, cardiac output and arterial pressure, decreased the pulmonary artery pressure and flow. Following myocardial ischemia, the pulmonary artery pressure decreased less than pulmonary artery blood flow as the result of elevating of the left atrial pressure, meanwhile pulmonary vascular resistance was not changed. Following myocardial ischemia in animals after the blockade of the beta-adrenoreceptors, the pulmonary flow decreased the same as in control animals. However, the pulmonary artery pressure was decreased twofold more significantly than in control animals, and its diminishing was in the same degree as the pulmonary artery flow. Following myocardial ischemia after the blockade of the beta-adrenoreceptors, the pulmonary vascular resistance decreased whereas the left atrial pressure did not change significantly because the myocardial contractility decreased less than in control animals.