Complications of axial lumbar interbody fusion.
Axial lumbar interbody fusion (AxiaLIF) is a novel minimally invasive approach for fusion of L4-5 and L5-S1. This technique uses the presacral space for percutaneous access to the anterior sacrum. The AxiaLIF procedure has the potential to decrease patient recovery time, length of hospital stay, and overall occurrence of surgical complications. It can be used alone or in combination with minimally invasive or traditional open fusion procedures. The purpose of this study was to evaluate complications of the AxiaLIF procedure at the authors' institutions. Patients who underwent AxiaLIF surgery between October 2005 and June 2009 at the authors' institutions were identified. The authors retrospectively reviewed these patients' charts, including operative reports and postoperative medical records, to determine what complications were encountered. A total of 68 patients underwent AxiaLIF surgery, with an average follow-up time of 34 months. Sixteen patients (23.5%) experienced a total of 18 complications (26.5%); this group included 8 men and 8 women (mean age 52.1 years). These complications included pseudarthrosis (8.8%), superficial infection (5.9%), sacral fracture (2.9%), pelvic hematoma (2.9%), failure of wound closure (1.5%), transient nerve root irritation (1.5%), and rectal perforation (2.9%). The complication rate associated with AxiaLIF in the present study was relatively low (26.5%). The most common complications were superficial infection and pseudarthrosis. There were 2 cases of rectal perforation associated with AxiaLIF; one case was found intraoperatively and the other presented 4 days postoperatively. Both patients underwent emergency repair by a general surgeon and had no long-term sequelae as a result of the rectal injuries. It is important for surgeons to be aware of the potential for these complications. Many of these complications can probably be avoided with proper patient selection and operative planning. Preoperative MR imaging, a detailed patient physical examination and history, full bowel preparation, and the use of live fluoroscopy can all help to prevent complications with AxiaLIF surgery.


Automatic segmentation of atrial fibrillation and flutter in single-lead electrocardiograms by self-supervised learning and Transformer architecture.
Automatic detection of atrial fibrillation and flutter (AF/AFL) is a significant concern in preventing stroke and mitigating hemodynamic instability. Herein, we developed a Transformer-based deep learning model for AF/AFL segmentation in single-lead electrocardiograms (ECGs) by self-supervised learning with masked signal modeling (MSM). We retrieved data from 11 open-source databases on PhysioNet; 7 of these databases included labeled ECGs, while the other 4 were without labels. Each database contained ECG recordings with durations of ≥30 s. A total of 24 intradialytic ECGs with paroxysmal AF/AFL during 4 h of hemodialysis sessions at Seoul National University Hospital were used for external validation. The model was pretrained by predicting masked areas of ECG signals and fine-tuned by predicting AF/AFL areas. Cross-database validation was used for evaluation, and the intersection over union (IOU) was used as a main performance metric in external database validation. In the 7 labeled databases, the areas marked as AF/AFL constituted 41.1% of the total ECG signals, ranging from 0.19% to 51.31%. In the evaluation per ECG segment, the model achieved IOU values of 0.9254 and 0.9477 for AF/AFL segmentation and other segmentation tasks, respectively. When applied to intradialytic ECGs with paroxysmal AF/AFL, the IOUs for the segmentation of AF/AFL and non-AF/AFL were 0.9896 and 0.9650, respectively. Model performance by different training procedure indicated that pretraining with MSM and the application of an appropriate masking ratio both contributed to the model performance. It also showed higher IOUs of AF/AFL labels than in previous studies when training and test databases were matched. The present model with self-supervised learning by MSM performs robustly in segmenting AF/AFL.


Characterization of norovirus 3Dpol RNA-dependent RNA polymerase activity and initiation of RNA synthesis.
Norovirus (NV) 3D(pol) is a non-structural protein predicted to play an essential role in the replication of the NV genome. In this study, the characteristics of NV 3D(pol) activity and initiation of RNA synthesis have been examined in vitro. Recombinant NV 3D(pol), as well as a 3D(pol) active-site mutant were expressed in Escherichia coli and purified. NV 3D(pol) was able to synthesize RNA in vitro and displayed flexibility with respect to the use of Mg(2+) or Mn(2+) as a cofactor. NV 3D(pol) yielded two different products when incubated with synthetic RNA in vitro: (i) a double-stranded RNA consisting of two single strands of opposite polarity or (ii) the single-stranded RNA template labelled at its 3' terminus by terminal transferase activity. Initiation of RNA synthesis occurred de novo rather than by back-priming, as evidenced by the fact that the two strands of the double-stranded RNA product could be separated, and by dissociation in time-course analysis of terminal transferase and RNA synthesis activities. In addition, RNA synthesis was not affected by blocking of the 3' terminus of the RNA template by a chain terminator, sustaining de novo initiation of RNA synthesis. NV 3D(pol) displays in vitro properties characteristic of RNA-dependent RNA polymerases, allowing the implementation of this in vitro enzymic assay for the development and validation of antiviral drugs against NV, a so far non-cultivated virus and an important human pathogen.


A Unified Framework for Dopamine Signals across Timescales.
Rapid phasic activity of midbrain dopamine neurons is thought to signal reward prediction errors (RPEs), resembling temporal difference errors used in machine learning. However, recent studies describing slowly increasing dopamine signals have instead proposed that they represent state values and arise independent from somatic spiking activity. Here we developed experimental paradigms using virtual reality that disambiguate RPEs from values. We examined dopamine circuit activity at various stages, including somatic spiking, calcium signals at somata and axons, and striatal dopamine concentrations. Our results demonstrate that ramping dopamine signals are consistent with RPEs rather than value, and this ramping is observed at all stages examined. Ramping dopamine signals can be driven by a dynamic stimulus that indicates a gradual approach to a reward. We provide a unified computational understanding of rapid phasic and slowly ramping dopamine signals: dopamine neurons perform a derivative-like computation over values on a moment-by-moment basis.


PSMA-specific CAR-engineered T cells eradicate disseminated prostate cancer in preclinical models.
Immunology-based interventions have been proposed as a promising curative chance to effectively attack postoperative minimal residual disease and distant metastatic localizations of prostate tumors. We developed a chimeric antigen receptor (CAR) construct targeting the human prostate-specific membrane antigen (hPSMA), based on a novel and high affinity specific mAb. As a transfer method, we employed last-generation lentiviral vectors (LV) carrying a synthetic bidirectional promoter capable of robust and coordinated expression of the CAR molecule, and a bioluminescent reporter gene to allow the tracking of transgenic T cells after in vivo adoptive transfer. Overall, we demonstrated that CAR-expressing LV efficiently transduced short-term activated PBMC, which in turn were readily stimulated to produce cytokines and to exert a relevant cytotoxic activity by engagement with PSMA+ prostate tumor cells. Upon in vivo transfer in tumor-bearing mice, CAR-transduced T cells were capable to completely eradicate a disseminated neoplasia in the majority of treated animals, thus supporting the translation of such approach in the clinical setting.


Identification and molecular characterization of TM7SF2 in the FAUNA gene cluster on human chromosome 11q13.
In this report, the identification and molecular characterization of a novel gene, designated TM7SF2, is reported. This gene was found in the FAU neighboring area (FAUNA) to which other genes have been mapped previously. The FAUNA gene cluster is located at chromosome 11q13 between landmarks H4B and D11S2196E. The TM7SF2 gene contains eight coding exons, and their splice site consensus sequences are consistent with AG/GT rule. Northern blot analysis with a cDNA probe corresponding to TM7SF2 revealed varying expression levels of a 1.7-kb transcript in adult human heart, brain, pancreas, lung, liver, skeletal muscle, kidney, ovary, prostate, and testis, but no detectable expression in placenta, spleen, thymus, small intestine, colon (mucosal lining), or peripheral blood leukocytes. The open reading frame in the cDNA sequence codes for a protein of 590 amino acids that is rich in glycine (23%) and arginine (17%) residues in its amino-terminal half and contains seven transmembrane domains in its carboxy-terminal half. The transmembrane region of the putative TM7SF2 protein shows amino acid sequence similarity to those of the lamin B receptor and the C14/C24 sterol reductase.


Association of Maternal Secretor Status and Human Milk Oligosaccharides With Milk Microbiota: An Observational Pilot Study.
Breast milk contains several bioactive factors including human milk oligosaccharides (HMOs) and microbes that shape the infant gut microbiota. HMO profile is determined by secretor status; however, their influence on milk microbiota is still uncovered. This study is aimed to determine the impact of the FUT2 genotype on the milk microbiota during the first month of lactation and the association with HMO. Milk microbiota from 25 healthy lactating women was determined by quantitative polymerase chain reaction and 16S gene pyrosequencing. Secretor genotype was obtained by polymerase chain reaction-random fragment length polymorphisms and by HMO identification and quantification. The most abundant bacteria were Staphylococcus and Streptococcus, followed by Enterobacteriaceae-related bacteria. The predominant HMO in secretor milk samples were 2'FL and lacto-N-fucopentaose I, whereas non-secretor milk was characterized by lacto-N-fucopentaose II and lacto-N-difucohexaose II. Differences in microbiota composition and quantity were found depending on secretor/non-secretor status. Lactobacillus spp, Enterococcus spp, and Streptococcus spp were lower in non-secretor than in secretor samples. Bifidobacterium genus and species were less prevalent in non-secretor samples. Despite no differences on diversity and richness, non-secretor samples had lower Actinobacteria and higher relative abundance of Enterobacteriaceae, Lactobacillaceae, and Staphylococcaceae. Maternal secretor status is associated with the human milk microbiota composition and is maintained during the first 4 weeks. Specific associations between milk microbiota, HMO, and secretor status were observed, although the potential biological impact on the neonate remains elusive. Future studies are needed to reveal the early nutrition influence on the reduction of risk of disease.


Early measles virus infection is associated with the development of inflammatory bowel disease.
The measles virus has been implicated as a possible etiological agent in the development of inflammatory bowel disease (IBD). Measles infection at an early age is associated with subacute sclerosing panencephalitis, a degenerative neurological condition caused by persistent measles infection of the central nervous system. We sought to determine whether infection with measles virus at an early age was also associated with an increased risk of developing IBD. Patients with measles infection diagnosed before the age of 5 yr were identified through the diagnostic indices of the Mayo Clinic and the Rochester Epidemiology Project. A questionnaire was used to ascertain a subsequent history of IBD, which was confirmed by records from the subjects' physicians. The risks of developing Crohn's disease and ulcerative colitis were calculated relative to expected rates for these conditions in the Olmsted County, Minnesota population. Of 1164 eligible cases, 662 (57%) completed the questionnaire. There were six confirmed cases of Crohn's disease and six of ulcerative colitis. The expected number of cases was 1.9 for Crohn's disease (standardized incidence ratio [SIR] 3.1, 95% confidence interval [CI] 1.1-6.8) and 2.0 for ulcerative colitis (SIR 3.0, CI 1.1-6.5). There was a trend towards a higher risk of developing IBD with an earlier age of infection. Early measles infection is associated with an increased risk of developing Crohn's disease and ulcerative colitis. The risk may be higher with earlier infection.


Increased risk of colon cancer associated with a genetic polymorphism of SMAD7.
Genome-wide association studies (GWAS) have identified SMAD7 on 8q21 as being associated with colorectal cancer. We evaluated single nucleotide polymorphisms (SNP) in the SMAD7 gene, including rs4939827, rs12953717, and rs4464148, previously identified from GWAS in a large population-based case-control study of colon cancer. We observed that rs12953717 was associated with a statistically significant increased risk of colon cancer [odds ratio, 1.38; 95% confidence intervals (CI), 1.13-1.68; P linear trend < 0.01] for the TT genotype compared with the CC genotype, whereas the CC genotype of the rs4939827 SNP was inversely associated with colon cancer (0.77; 95% CI, 0.64-0.93) relative to the TT genotype. There were no significant differences in association for either of these polymorphisms when stratified by age, tumor site, sex, or family history. The odds ratios between SMAD7 and colon cancer among individuals reporting recent aspirin/nonsteroidal anti-inflammatory drug use was 0.60 (95% CI, 0.43-0.85) for the CC genotype of the rs4939827 polymorphism and 1.69 (95% CI, 1.20-2.38) for the TT genotype of the rs1295371 polymorphism. This result compares to odds ratios of 0.86 (95% CI, 0.68-1.09) for rs4939827 and 1.22 (95% CI, 0.96-1.56) among individuals who did not use aspirin/nonsteroidal anti-inflammatory drugs. An assessment of SMAD7 genotypes with tumor markers did not reveal any significant differences by KRAS2, TP53, CpG island methylator phenotype, or microsatellite instability status. No significant associations were observed for the rs4464148 SNP or other SNPs evaluated in the SMAD7. These results corroborate the findings of GWAS in colon cancer pointing to SMAD7 and reinforce interest in SNPs in this gene.


Evaluation of left ventricular dyssynchrony by onset of active myocardial force generation: a novel method that differentiates between electrical and mechanical etiologies.
Better clinical tools for measuring left ventricular electrical dyssynchrony are needed. The present study investigates if onset of active myocardial force generation (AFG) may serve as a measure of electrical dyssynchrony. In anesthetized dogs, we evaluated left ventricular mechanical dyssynchrony by 2 different approaches. First, we measured timing of peak myocardial shortening velocity and strain. Second, we measured the first sign of tension development by onset AFG as defined by the myocardial pressure-segment length loop upward shift from its passive-elastic state. Electrical dyssynchrony was measured by intramyocardial electromyograms (IM-EMG). Dyssynchrony was quantified as peak intersegment time difference and as standard deviation of timing for 6 to 8 myocardial segments. During baseline, reduced preload and myocardial ischemia shortening velocity and strain indicated segmental mechanical heterogeneity, whereas onset AFG and onset R in IM-EMG indicated synchronous activation of all segments. After induction of left bundle-branch block, all methods indicated dyssynchrony. Peak intersegment time difference for shortening velocity and strain showed weak correlations (r=0.17 and 0.16) and weak agreements (mean differences, -48+/-27 ms and -28+/-27 ms, respectively) with IM-EMG. Onset AFG by pressure-segment length loops, however, correlated well with IM-EMG (r=0.93), and agreement was good (mean difference, -0.6+/-6.8 ms). Results were similar for standard deviation of timing. Onset AFG from pressure-strain analysis by echocardiography showed accuracy similar to sonomicrometry. Onset AFG was an accurate marker of myocardial electrical activation and was superior to shortening velocity and strain. Identification of electrical dyssynchrony by onset AFG may be feasible clinically using left ventricular pressure-strain analysis.


Serial order reconstruction in Down syndrome: evidence for a selective deficit in verbal short-term memory.
Individuals with Down syndrome consistently perform less well than appropriately matched comparison groups on tests of verbal short-term memory, despite performing relatively well on non-verbal short-term memory tasks. However, it is not clear whether these findings constitute evidence for a selective deficit in verbal short-term memory, or whether they instead reflect the influence of non-central factors such as speech difficulties or poor number knowledge. Twenty-six individuals with Down syndrome and 32 typically developing children were tested on a digit reconstruction task in which participants were presented with auditory digit sequences and responded by pressing the corresponding digits on a touch-screen in the correct serial order. Background measures were performance on a closely matched visuo-spatial reconstruction task, reaction time on a simple digit identification task, receptive vocabulary age and non-verbal ability (Raven's matrices). Participants were also tested on a conventional digit recall task. All four background measures accounted for significant individual variation in digit reconstruction performance, but there remained a significant effect of group that reflected relatively poor performance of individuals with Down syndrome. Hierarchical regression showed that group membership accounted for unique variation in both digit reconstruction and recall performance, even after all group differences on background measures had been accounted for. The results provide strong evidence that Down syndrome is associated with a selective deficit in verbal short-term memory, and a deficit in verbal serial order memory in particular. Implications for the language difficulties associated with Down syndrome are discussed.


Spontaneous and induced chromosome aberrations in Balkan endemic nephropathy.
The aim of the present study was to investigate the spontaneous aberrations and chromosome breakages induced by X-rays and folic acid deficiency. In patients with Balkan endemic nephropathy (BEN) a higher frequency of spontaneous aberrations and chromosome lesions in medium TC 199 and radiation induced breakages were found compared with the healthy individuals. In BEN patients the 3q25 band was most frequently involved in the aberrations. These results support the idea that 3q25 may play a specific role and be a marker for BEN. Three of the additional five bands with increased frequencies of lesions in BEN patients contain oncogenes: 1q36-c src, 3p25-raf-1, and 6q23-myb. The frequent association of BEN and cancer can be explained by the chromosomal hypothesis of oncogenesis.


[Sensitivity of the haemoccult test in colorectal tumours (author's transl)].
157 patients with histologically investigated colorectal tumours from 5 hospitals of the University of Munich were tested with the Haemoccult test. In 30 (35.7%) of 84 patients with malignancy of the colon and in 31 (58.5%) of 53 patients with adenomas or polyps the correctly performed test was negative. The test result showed no dependency on age or sex of the patient, nor on size, stage or localisation of the tumour. A problem-orientated history lowered the rate of false negative tests to 2.4%. The high rate of false negative results was not attributable to organisational or technical errors.


Improving Safe Use of Medications During Pregnancy: The Roles of Patients, Physicians, and Pharmacists.
Our study sought to explore the actual and potential roles of patients, physicians, and pharmacists, as well as their shared challenges and opportunities, in improving the safety of medication use during pregnancy. We conducted virtual focus groups with 48 women and in-depth interviews with nine physicians and five pharmacists. Qualitative analysis revealed that all three groups of participants reported "playing it safe," the need for an engaged patient making informed decisions, challenges surrounding communication about pregnancy status, and a lack of patient-centric resources. Patients, physicians, and pharmacists are highly motivated to protect developing babies from potential harms of medication use during pregnancy while maintaining the patient's health. Strategic messaging could maximize the effectiveness of these interactions by helping physicians discuss the benefits and risks of medication use during pregnancy, pharmacists screen for pregnancy and counsel on medication safety, and patients using medications to share pregnancy intentions with their providers pre-pregnancy.


Neonates Hospitalized with Community-Acquired SARS-CoV-2 in a Colorado Neonatal Intensive Care Unit.
The novel coronavirus 2019 (SARS-CoV-2) has been well described in adults. Further, the impact on older children and during the perinatal time is becoming better studied. As community spread increases, it is important to recognize that neonates are vulnerable to community spread as well. The impact that community-acquired SARS-CoV-2 has in the neonatal time period is unclear, as this population has unique immunity considerations. To report on a case series of SARS-CoV-2 in neonates through community acquisition in the USA. This is an early retrospective study of patients admitted to the Neonatal Intensive Care Unit (NICU) identified as having SAR-CoV-2 through positive real-time polymerase chain reaction assay of nasopharyngeal swabs. Three patients who required admission to the NICU between the ages of 17 and 33 days old were identified. All 3 had ill contacts in the home or had been to the pediatrician and presented with mild to moderate symptoms including fever, rhinorrhea, and hypoxia, requiring supplemental oxygen during their hospital stay. One patient was admitted with neutropenia, and the other 2 patients became neutropenic during hospitalization. None of the patients had meningitis or multiorgan failure. Infants with community-acquired SARS-CoV-2 may require hospitalization due to rule-out sepsis guidelines if found to have fever and/or hypoxia. Caregivers of neonates should exercise recommended guidelines before contact with neonates to limit community spread of SARS-CoV-2 to this potentially vulnerable population, including isolation, particularly as asymptomatic cases become prevalent.


Controlling stereoselectivity in the aminocatalytic enantioselective Mannich reaction of aldehydes with in situ generated N-carbamoyl imines.
A simple and convenient method for the direct, aminocatalytic, and highly enantioselective Mannich reactions of aldehydes with in situ generated N-carbamoyl imines has been developed. Both alpha-imino esters and aromatic imines serve as suitable electrophilic components. Moreover, the judicious selection of commercially available secondary amine catalysts allows selective access to the desired stereoisomer of the N-tert-butoxycarbonyl (Boc) or N-carbobenzyloxy (Cbz) Mannich adducts, with high control over the syn or anti relative configuration and almost perfect enantioselectivity. Besides the possibility to fully control the stereochemistry of the Mannich reaction, the main advantage of this method lies in the operational simplicity; the highly reactive N-carbamate-protected imines are generated in situ from stable and easily handled alpha-amido sulfones.


Expression of HSP27, HSP72 and MRP proteins in in vitro co-culture of colon tumour cell spheroids with normal cells after incubation with rhTGF- beta1 and/or CPT-11.
We studied the expression of inducible heat shock protein (HSP27, HSP72) and multidrug-resistance protein (MRP) in co-cultures of human colon carcinoma cell spheroids obtained from different grades of tumour with normal human colon epithelium, myofibroblast and endothelial cell monolayers. We also measured the influence of recombinant human transforming growth factor beta1 (rhTGF-beta1) and camptothecin (CPT-11), added as single agents or in combination, on the levels of the HSPs, MRP, interleukin (IL)-6 and nitric oxide (NO). An immunoblotting analysis with densitometry showed that rhTGF-beta1 and/or CPT-11 increased HSP27, HSP72 and MRP expression in tumour cells and myofibroblasts, as well as in co-cultures compared with appropriate controls. By contrast, in colonic epithelium, inhibition of HSPs and MRP was comparable with that of the control. In endothelial cells, HSP72 was undetectable. Direct interaction of colon tumour spheroids with normal myofibroblasts caused a significant, tumour-grade dependent increase in IL-6 production. Production of IL-6 was significantly lowered by rhTGF-beta1 and/or CPT-11. Tumour cell spheroids cultivated alone produced larger amounts of NO than normal cells. In co-culture, the level of the radical decreased compared with the sum of NO produced by the monocultures of the two types of cells. rhTGF-beta1 and/or CPT-11 decreased NO production both in tumour and normal cell monocultures and their co-cultures. In conclusion, direct interactions between tumour and normal cells influence the expression of HSP27, HSP72 and MRP, and alter IL-6 and NO production. rhTGF-beta1 and/or CPT-11 may potentate resistance to chemotherapy by increasing HSP and MRP expression but, on the other hand, they may limit tumour cell spread by decreasing the level of some soluble mediators of inflammation (IL-6 and NO).


Severe scurvy: an underestimated disease.
Scurvy is one of the oldest diseases in human history. Nowadays, although scurvy tends to become a forgotten disease in developed country, rare cases still occur, especially in people undergoing extreme diet, old people or children with poor diet and patients with malabsorption. We describe three cases of scurvy. The first case is a patient diagnosed with Crohn's disease, the second one is in a context of anorexia nervosa and drug addiction, and the third case is in a context of social isolation. Early recognition of scurvy can be difficult because symptoms may appear nonspecific and can mimic more common conditions. In any patient with spontaneous hematoma and purpura, in the context of nutritional disorder, scurvy should be systematically considered. As this disease can lead to severe complications, such as bone pain, heart failure or gastrointestinal symptoms, nothing should delay vitamin C supplementation, which is a simple and rapidly effective treatment.


Attention-deficit-hyperactivity disorder increases risk of bone fracture: a population-based cohort study.
Attention-deficit-hyperactivity disorder (ADHD) is a disorder that is associated with accidental injuries. The aim of this study was to evaluate the relationship between ADHD and bone fracture in children. The study cohort comprised 3640 children (2874 males, 766 females; mean age 8y 5mo, SD 3y) with ADHD (International Classification of Diseases, Ninth Revision) who were matched to children without ADHD at a ratio of 1:4 (n=14 560; 11 496 males, 3064 females; mean age 8y 5mo, SD 3y). A Cox proportional hazard regression analysis was conducted to estimate how ADHD affected the risk of bone fracture. The incidence of fracture among the ADHD cohort was 197.67 per 10,000 person-years, and was 1.3-fold greater than in the comparison cohort (147.54 per 10,000 person-years). The risk in children with ADHD was higher than that in children without ADHD (p value for log-rank test < 0.001). After adjusting for potential confounding factors, the ADHD cohort was 1.32 times more likely to have bone fracture accidents than the comparison cohort (hazard ratio, 1.32; 95% confidence interval 1.17-1.49). Children with ADHD have a higher risk of experiencing bone fracture accidents than do children without ADHD.


[Recovery processes in the cerebral cortex, myocardium and thymus of rats with experimental atherosclerosis exposed to low-frequency electromagnetic fields on the head].
Studies of animals with experimental sclerosis has shown that a course of 10 procedures of alternative magnetic field (AMF) (50 Hz, 30 mT, 3 min daily) promotes partial recovery of the lipid spectrum and corrects vasomotor-metabolic disturbances in the cerebral cortex, myocardium and thymus caused by atherosclerosis. Combination of AMF with constant magnetic field in the same regime and location does not produce a hypolipidemic effect in atherosclerotic animals and this, in combination with increased vascular permeability may aggravate the condition. Activated microcirculation, antioxidant and antiproteinase effects in activation of biosynthetic processes in the cerebral cortex reflect inhibition in the CNS in this combined effect and create conditions for a hypotensive effect.


Adoption of reminder and recall messages for immunizations by pediatricians and public health clinics.
Strong scientific evidence and national recommendations support the use of reminder and recall messages to improve immunization coverage rates, yet reports have suggested that only a minority of pediatric practices use such messages. Our aims were to 1) determine the proportions of pediatric practices and public clinics that currently use practice-based reminder or recall messages and routinely undergo immunization assessment efforts, 2) evaluate barriers and supports to implementing these practices, and 3) identify predictors of either current use or plans for future adoption of these practices. This study combined qualitative and quantitative methods in sequential phases. In the qualitative phase, we conducted semistructured, open-ended interviews with a convenience sample of 18 clinician-administrators representing adopters and nonadopters of these messages in both private practices and public health clinics. In the subsequent quantitative phase, we mailed a structured, closed-ended survey to national samples of randomly selected pediatricians (n = 600) and public clinics (n = 600). Response rates were 75% for pediatricians and 77% for public clinics. Among pediatricians, 38% were conducting regular assessments of immunization coverage but only 16% were currently using routine reminder or recall messages. Among public clinics, 85% were conducting regular assessments and 51% were using reminder or recall messages. Among pediatricians' practices, the most commonly reported barriers to the adoption of reminder or recall messages were lack of time and funding and the inability to identify children at specified ages. For pediatricians' practices, the strongest predictors of current use of reminder or recall messages were having a champion who led efforts to improve immunization delivery (odds ratio: 1.85; 95% confidence interval: 1.08-3.18) and current use of regular immunization assessments (odds ratio: 2.30; 95% confidence interval: 1.33-3.84). Likewise, for public health clinics, having a champion to lead immunization improvement efforts and believing that their current system needed improvement was associated with current use of reminder or recall messages. Reminder and recall messages remain underused by both pediatricians and public health clinics. Promising strategies to promote adoption of these approaches in both the private and the public sectors include identifying and training champions to promote immunization delivery improvement efforts and helping practices develop methods to identify children at specific ages.


Cordycepin Inhibits Cancer Cell Proliferation and Angiogenesis through a DEK Interaction via ERK Signaling in Cholangiocarcinoma.
Cholangiocarcinoma (CCA) is a malignant tumor that arises from the epithelial cells of the bile duct and is notorious for its poor prognosis. The clinical outcome remains disappointing, and thus more effective therapeutic options are urgently required. Cordycepin, a traditional Chinese medicine, provides multiple pharmacological strategies in antitumors, but its mechanisms have not been fully elucidated. In this study, we reported that cordycepin inhibited the viability and proliferation capacity of CCA cells in a time- and dose-dependent manner determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and colony formation assay. Flow cytometry and Hoechst dye showed that cordycepin induced cancer cell apoptosis via extracellular signal-regulated kinase (ERK) 1/2 deactivation. Moreover, cordycepin significantly reduced the angiogenetic capabilities of CCA in vitro as examined by tube formation assay. We also discovered that cordycepin inhibited DEK expression by using Western blot assay. DEK serves as an oncogenic protein that is overexpressed in various gastrointestinal tumors. DEK silencing inhibited CCA cell viability and angiogenesis but not apoptosis induction determined by Western blot and flow cytometry. Furthermore, cordycepin significantly inhibited tumor growth and angiogenic capacities in a xenograft model by downregulating the expression of DEK, phosphorylated ERK1/2 CD31 and von Willebrand factor (vWF). Taken together, we demonstrated that cordycepin inhibited CCA cell proliferation and angiogenesis with a DEK interaction via downregulation in ERK signaling. These data indicate that cordycepin may serve as a novel agent for CCA clinical treatment and prognosis improvement. SIGNIFICANCE STATEMENT: Cordycepin provides multiple strategies in antitumors, but its mechanisms are not fully elucidated, especially on cholangiocarcinoma (CCA). We reported that cordycepin inhibited the viability of CCA cells, induced apoptosis via extracellular signal-regulated kinase 1/2 deactivation and DEK inhibition, and reduced the angiogenetic capabilities of CCA both in vivo and in vitro.


The role of paracentesis in the management of infants with necrotizing enterocolitis.
Necrotizing enterocolitis (NEC) is the single most common surgical emergency of the newborn. Yet the indications for surgery in NEC are still not clearly established. Pneumoperitoneum is an absolute indication for surgery. A paracentesis indicative of intestinal gangrene, prior to intestinal perforation, has also been proposed as an indication for surgery. A prospective study was conducted to answer two questions: 1) How accurate and safe is paracentesis in detecting bowel necrosis in neonates with NEC? and 2) Do infants with NEC who are operated on for a positive paracentesis have a decreased morbidity and mortality over those operated on for pneumoperitoneum? Between July 1980 through June 1984, 39 infants with definite NEC and without pneumoperitoneum underwent a paracentesis because of suspected bowel necrosis. There were no false "positive" taps. There were 34 "positive" taps in 36 infants who were proven to have bowel necrosis, for an accuracy of 94 per cent. There were two false "negative" taps (40%) and three true "negative" taps (60%). There were no complications related to the procedure. During this same time period, 68 infants with NEC were operated upon. The indication for surgery was pneumoperitoneum in 29, a "positive" paracentesis in 34, and other reasons in 5. A comparison was made between those operated upon for pneumoperitoneum and those operated upon for a "positive" paracentesis. There was no significant difference in survival between the two groups (76% versus 71%). The early and late complications and the causes of death in each group were similar. A positive paracentesis is a valid objective indication for operation in infants with NEC.(ABSTRACT TRUNCATED AT 250 WORDS)


Isolated gallbladder perforation following blunt abdominal trauma: a missed diagnosis.
This is a case of a 21-year-old man who presented with history of abdominal pain following blunt abdominal trauma. Although the initial ultrasound scan showed mild free peritoneal fluid, the patient was managed conservatively as a probable case of splenic injury and was discharged in satisfactory condition after 6 days of admission. He presented again 7 days later with recurring epigastric pain and had exploratory laparotomy on the presumptive diagnosis of peritonitis, probably due to peptic ulcer perforation. Intraoperatively, he was then discovered to have an isolated gallbladder perforation. This is a rare condition in which the diagnosis is often delayed or missed as was the case in our patient. To the best of our knowledge, this is the first reported case of isolated gallbladder perforation in Nigeria, and it behooves the clinician to be aware of the likelihood of this condition in patients with blunt abdominal injury.


Quantitative analysis of segmental wall motion during maximal upright dynamic exercise: variability in normal adults.
Twenty-five healthy adults underwent subcostal-view, four-chamber two-dimensional echocardiographic examination while upright at rest and at the peak of maximal bicycle exercise. The purpose of the study was to determine whether the variability in regional left ventricular endocardial motion, previously demonstrated to be present at rest, persisted at peak exercise. The rest and exercise end-diastolic and end-systolic endocardial contours were visually identified, digitized, and divided into 32 radial segments after realignment by the computer. At rest there was similar percent segmental area reduction for the septum (segments 1 to 12) (54 +/- 4%, mean +/- 1 SD), apex (segments 13 to 20) (67 +/- 3%), and lateral wall (segments 21 to 32) (67 +/- 8%). At peak exercise the percent area reduction increased significantly: septum 84 +/- 5%, apex 88 +/- 2%, lateral wall 83 +/- 6% (p less than .001 compared with rest for all areas). However, there was considerable variability in percent area reduction between different radial segments in the same individual. At rest the difference between minimal and maximal percent area reduction within the same individual was 49 +/- 17 percentage units (range 21 to 83) and that at peak exercise was 32 +/- 17 percentage units (range 0 to 66). It is concluded that, because the range of standard deviation of normal endocardial motion and the degree of variability between radial segments in the same healthy individual are significant, qualitatively determined "hypokinesis," as commonly assessed clinically, may be a normal event. However, segmental akinesis or dyskinesis, which occurred rarely at rest and never at peak exercise, must be considered abnormal events.


The Neutrophil Nucleus: An Important Influence on Neutrophil Migration and Function.
Neutrophil nuclear morphology has historically been used in haematology for neutrophil identification and characterisation, but its exact role in neutrophil function has remained enigmatic. During maturation, segmentation of the neutrophil nucleus into its mature, multi-lobulated shape is accompanied by distinct changes in nuclear envelope composition, resulting in a unique nucleus that is believed to be imbued with extraordinary nuclear flexibility. As a rate-limiting factor for cell migration, nuclear morphology and biomechanics are particularly important in the context of neutrophil migration during immune responses. Being an extremely plastic and fast migrating cell type, it is to be expected that neutrophils have an especially deformable nucleus. However, many questions still surround the dynamic capacities of the neutrophil nucleus, and which nuclear and cytoskeletal elements determine these dynamics. The biomechanics of the neutrophil nucleus should also be considered for their influences on the production of neutrophil extracellular traps (NETs), given this process sees the release of chromatin "nets" from nucleoplasm to extracellular space. Although past studies have investigated neutrophil nuclear composition and shape, in a new era of more sophisticated biomechanical and genetic techniques, 3D migration studies, and higher resolution microscopy we now have the ability to further investigate and understand neutrophil nuclear plasticity at an unprecedented level. This review addresses what is currently understood about neutrophil nuclear structure and its role in migration and the release of NETs, whilst highlighting open questions surrounding neutrophil nuclear dynamics.


Hierarchical organization of the human auditory cortex revealed by functional magnetic resonance imaging.
The concept of hierarchical processing--that the sensory world is broken down into basic features later integrated into more complex stimulus preferences--originated from investigations of the visual cortex. Recent studies of the auditory cortex in nonhuman primates revealed a comparable architecture, in which core areas, receiving direct input from the thalamus, in turn, provide input to a surrounding belt. Here functional magnetic resonance imaging (fMRI) shows that the human auditory cortex displays a similar hierarchical organization: pure tones (PTs) activate primarily the core, whereas belt areas prefer complex sounds, such as narrow-band noise bursts.


Benefits of mindfulness training for patients with progressive cognitive decline and their caregivers.
New strategies are needed to help people cope with the repercussions of neurodegenerative disorders such as Alzheimer's disease. Patients and caregivers face different challenges, but here we investigated an intervention tailored for this combined population. The program focused on training skills such as attending to the present moment nonjudgmentally, which may help reduce maladaptive emotional responses. Patients participated together with caregivers in weekly group sessions over 8 weeks. An assessment battery was individually administered before and after the program. Pre-post analyses revealed several benefits, including increased quality-of-life ratings, fewer depressive symptoms, and better subjective sleep quality. In addition, participants indicated that they were grateful for the opportunity to learn to apply mindfulness skills and that they would recommend the program to others. In conclusion, mindfulness training can be beneficial for patients and their caregivers, it can be delivered at low cost to combined groups, and it is worthy of further investigation.


Binding of Cob(II)alamin to the adenosylcobalamin-dependent ribonucleotide reductase from Lactobacillus leichmannii. Identification of dimethylbenzimidazole as the axial ligand.
The ribonucleoside triphosphate reductase (RTPR) from Lactobacillus leichmannii catalyzes the reduction of nucleoside 5'-triphosphates to 2'-deoxynucleoside 5'-triphosphates and uses coenzyme B12, adenosylcobalamin (AdoCbl), as a cofactor. Use of a mechanism-based inhibitor, 2'-deoxy-2'-methylenecytidine 5'-triphosphate, and isotopically labeled RTPR and AdoCbl in conjunction with EPR spectroscopy has allowed identification of the lower axial ligand of cob(II)alamin when bound to RTPR. In common with the AdoCbl-dependent enzymes catalyzing irreversible heteroatom migrations and in contrast to the enzymes catalyzing reversible carbon skeleton rearrangements, the dimethylbenzimidazole moiety of the cofactor is not displaced by a protein histidine upon binding to RTPR.


Women Are More Infected and Seek Care Faster but Are Less Severely Ill: Gender Gaps in COVID-19 Morbidity and Mortality during Two Years of a Pandemic in Israel.
In the context of COVID-19 outcomes, global data have deduced a gender bias towards severe disease among males. The aim is to compare morbidity and mortality during two years of the COVID-19 pandemic in female and male patients with COVID-19, as well as to assess length of stay, time of health-seeking behavior after positive diagnosis, and vaccination differences. A retrospective-archive study was conducted in Israel from 1 March 2020 to 1 March 2022 (two consecutive years). Data were obtained from the Israeli Ministry of Health's (MOH) open COVID-19 database. The findings indicate female infections are 1.12 times more likely, across almost all age groups, apart from the youngest (0-19) age groups. Despite this, the relative risk of severe illness, intubation and mortality is higher among men. In addition, our findings indicate that the mean number of days taken by unvaccinated men from positive diagnosis to hospital admission was greater than among unvaccinated women among the deceased population. The findings of this study reveal lessons learned from the COVID-19 global pandemic. Specifically, the study shows how human biological sex may have played a role in COVID-19 transmission, illness, and death in Israel. The conclusions of this study indicate that targeted approaches, which take into consideration sex and gender and the intersecting factors are necessary to engage in the fight against COVID-19 and ensure the most effective and equitable pandemic response.


Proteomic identification of insulin-like growth factor-binding protein-6 induced by sublethal H2O2 stress from human diploid fibroblasts.
Fibroblasts are the most ubiquitous cell types within our body. They produce various factors to maintain the texture and structure of a particular organ or tissue. To identify protein factors secreted by fibroblasts and alteration of these protein factors upon oxidative stress, HCA3 human skin diploid fibroblasts were exposed to a sublethal dose of H2O2, which induces a prematurely senescent phenotype. Conditioned media from prematurely senescent cells versus control cells were analyzed for proteins using an LC-MS/MS-based proteomic technique. Collagen alpha1(VI), collagen alpha2(I), fibronectin, lumican, and matrix metalloproteinase 2 were among the proteins consistently detected from control and H2O2-treated cells. Insulin-like growth factor-binding protein-6 (IGFBP-6) consistently showed up in the conditioned medium of H2O2-treated cells but not from untreated cells. Increased IGFBP-6 production due to H2O2 treatment was confirmed by RT-PCR and Western blot analyses. While H2O2 induced a dose-dependent elevation of IGFBP-6 mRNA, Western blot analyses detected elevated levels of IGFBP-6 protein in the conditioned medium of H2O2-treated cells. In comparison, fibronectin or matrix metalloproteinase 2 did not show changes at the mRNA level in cell lysates or at the protein level in the conditioned medium by H2O2 treatment. Using several types of toxins at sublethal doses, including cis-platin, hydroxyurea, colchicine, L-mimosine, rhodamine, dithiothreitol, or N-ethylmaleimide, we found that these agents induced increases of IGFBP-6 at mRNA and protein levels. An increased level of IGFBP-6 protein was detected in the plasma of aging mice and of young mice treated with doxorubicin. These data suggest that IGFBP-6 may serve as a sensitive biomarker of cell degeneration or injury in vitro and in vivo.


Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation.
Protein acetylation, especially histone acetylation, is the subject of both research and clinical investigation. At least four small-molecule histone deacetylase inhibitors are currently in clinical trials for the treatment of cancer. These and other inhibitors also affect microtubule acetylation. A multidimensional, chemical genetic screen of 7,392 small molecules was used to discover "tubacin," which inhibits alpha-tubulin deacetylation in mammalian cells. Tubacin does not affect the level of histone acetylation, gene-expression patterns, or cell-cycle progression. We provide evidence that class II histone deacetylase 6 (HDAC6) is the intracellular target of tubacin. Only one of the two catalytic domains of HDAC6 possesses tubulin deacetylase activity, and only this domain is bound by tubacin. Tubacin treatment did not affect the stability of microtubules but did decrease cell motility. HDAC6 overexpression disrupted the localization of p58, a protein that mediates binding of Golgi elements to microtubules. Our results highlight the role of alpha-tubulin acetylation in mediating the localization of microtubule-associated proteins. They also suggest that small molecules that selectively inhibit HDAC6-mediated alpha-tubulin deacetylation, a first example of which is tubacin, might have therapeutic applications as antimetastatic and antiangiogenic agents.


Airway wall remodeling in asthma: from the epithelial layer to the adventitia.
Asthma is an episodic respiratory syndrome caused by several pathogenic processes. This recurrent syndrome is associated with an accelerated decline in lung function and increase in airway obstruction over time. The reduced lung function is a consequence of tissue restructuring of all the components of the airway wall: 1) epithelium metaplasia; 2) altered quantity, composition, and distribution of extracellular matrix components; 3) microvascular remodeling; and 4) increase of airway smooth muscle mass. How these structural changes affect lung functions is not entirely clear. Deeper understandings of the altered structure and related functional impairment are important for gaining insights into the mechanisms underlying asthma. This review describes the tissue remodeling observed in different compartments of the asthmatic airway wall, from the airway lumen to adventitia. The underlying mechanisms driving the remodeling processes are also briefly reviewed.


Intelligent wound dressing for simultaneous in situ detection and elimination of pathogenic bacteria.
Wound infections hinder the healing process and potentially result in life-threatening complications, which urgently require rapid and timely detection and treatment pathogens during the early stages of infection. Here, an intelligent wound dressing was developed to enable in situ detection and elimination of pathogenic bacteria through a combination of point-of-care testing and antibacterial photodynamic therapy technology. The dressing is an injectable hydrogel composed of carboxymethyl chitosan and oxidized sodium alginate, with addition of 4-methylumphulone beta-D-glucoside (MUG) and up-converted nanoparticles coated with titanium dioxide (UCNPs@TiO2). The presence of bacteria can be visually detected by monitoring the blue fluorescence of 4-methylumbellione, generated through the reaction between MUG and the pathogen-associated enzyme. The UCNPs@TiO2 photosensitizers were synthesized and demonstrated high antibacterial activity through the generation of reactive oxygen species when exposed to near-infrared irradiation. Meanwhile, a smartphone-based portable detection system equipped with a self-developed Android app was constructed for in situ detection of pathogens in mere seconds, detecting as few as 103 colony-forming unit. Additionally, the dressing was tested in a rat infected wound model and showed good antibacterial activity and pro-healing ability. These results suggest that the proposed intelligent wound dressing has potential for use in the diagnosis and management of wound infections. STATEMENT OF SIGNIFICANCE: An intelligent wound dressing has been prepared for simultaneous in situ detection and elimination of pathogenic bacteria. The presence of bacteria can be visually detected by tracking the blue fluorescence of the dressing. Moreover, a smartphone-based detection system was constructed to detect and diagnose pathogenic bacteria before reaching the infection limit. Meanwhile, the dressing was able to effectively eliminate key pathogenic bacteria on demand through antibacterial photodynamic therapy under NIR irradiation. The proposed intelligent wound dressing enables timely detection and treatment of infectious pathogens at an early stage, which is beneficial for wound management.


Identification of a novel type IV pilus gene cluster required for gastrointestinal colonization of Citrobacter rodentium.
Citrobacter rodentium is used as an in vivo model system for clinically significant enteric pathogens such as enterohaemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC). These pathogens all colonize the lumen side of the host gastrointestinal tract via attaching and effacing (A/E) lesion formation. In order to identify genes required for the colonization of A/E-forming pathogens, a library of signature-tagged transposon mutants of C. rodentium was constructed and screened in mice. Of the 576 mutants tested, 14 were attenuated in their ability to colonize the descending colon. Of these, eight mapped to the locus of enterocyte effacement (LEE), which is required for the formation of A/E lesions, underlying the importance of this mechanism for pathogenesis. Another mutant, P5H2, was found to have a transposon insertion in an open reading frame that has strong similarity to type IV pilus nucleotide-binding proteins. The region flanking the transposon insertion was sequenced, identifying a cluster of 12 genes that encode the first described pilus of C. rodentium (named colonization factor Citrobacter, CFC). The proteins encoded by cfc genes have identity to proteins of the type IV COF pilus of enterotoxigenic E. coli (ETEC), the toxin co-regulated pilus of Vibrio cholerae and the bundle-forming pilus of EPEC. A non-polar mutation in cfcI, complementation of this strain with wild-type cfcI and complementation of strain P5H2 with wild-type cfcH confirmed that these genes are required for colonization of the gastrointestinal tract by C. rodentium. Thus, CFC provides a convenient model to study type IV pilus-mediated pathogen-host interactions under physiological conditions in the natural colonic environment.


Laparoscopic partial nephrectomy: fifty cases.
Laparoscopic partial nephrectomy (LPN) is a technically challenging procedure. The goal of this study is to describe the outcomes of 50 consecutive patients undergoing LPN performed by one surgeon. Records were reviewed for clinical, pathologic, and follow-up information for patients undergoing LPN. Clinical parameters were assessed in both the first 25 and last 25 cases to see if there was a measurable learning curve. Fifty-two patients underwent attempted LPN; 50 were successful and 2 were converted to open partial nephrectomy. Mean operating room time was 155 minutes, mean estimated blood loss was 172 mL, and mean pathologic size was 2.6 cm. Final pathology revealed malignancy in 60% of cases and oncocytoma in 22% of cases. Margins were clear for all of the primary lesions. Overall complications were 16%, with cardiopulmonary complications being the most common. There were no significant differences in the outcomes of the first 25 and the last 25 patients, with the exception of length of stay (3.1 days v 2.5 days). After laparoendoscopic fellowship training in LPN, acceptable outcomes are achievable, and the learning curve is minimal. Long-term studies are needed on the efficacy of LPN, and further studies need to be performed to optimize the learning process for this technique.


Myofibrosarcoma of the adrenal gland.
Adrenal masses have varying presentations. Most commonly, adrenal masses are discovered incidentally on CT or MRI during an evaluation for an unrelated complaint. Although the majority of these are nonfunctional cortical adenomas, hormonally active tumors and adrenocortical carcinoma must also be considered in the differential diagnosis. Rarely, retroperitoneal tumors may mimic an adrenal mass. We report a case of a 49-year-old man with anemia and weight loss who was found to have a large retroperitoneal mass arising from the adrenal gland. Surgical treatment involved en bloc resection of the right kidney, adrenal gland, segments 7 and 8 of the liver, and a portion of the right hemidiaphragm. Final pathology revealed a low-grade myofibrosarcoma. We believe that this is the first case report of a myofibrosarcoma of the adrenal gland. Myofibrosarcomas are rare malignant tumors composed of myofibroblasts that arise from the deep soft tissues. These tumors have a predilection for the head and neck, trunk, or extremities. Myofibrosarcomas can be differentiated from other sarcomas by immunohistochemical staining and pathologic features. We will briefly discuss the workup of an adrenal mass and focus on the diagnosis of myofibrosarcoma.


Rapid identification of full-length genome and tracing variations of monkeypox virus in clinical specimens based on mNGS and amplicon sequencing.
The monkeypox virus (MPXV) has triggered a current outbreak globally. Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control. It is a significant challenge but necessary to optimize the strategy and application of rapid full-length genome identification and to track variations of MPXV in clinical specimens with low viral loads, as it is one of the DNA viruses with the largest genome and the most AT-biased, and has a significant number of tandem repeats. Here we evaluated the performance of metagenomic and amplicon sequencing techniques, and three sequencing platforms in MPXV genome sequencing based on multiple clinical specimens of five mpox cases in Chinese mainland. We rapidly identified the full-length genome of MPXV with the assembly of accurate tandem repeats in multiple clinical specimens. Amplicon sequencing enables cost-effective and rapid sequencing of clinical specimens to obtain high-quality MPXV genomes. Third-generation sequencing facilitates the assembly of the terminal tandem repeat regions in the monkeypox virus genome and corrects a common misassembly in published sequences. Besides, several intra-host single nucleotide variations were identified in the first imported mpox case. This study offers an evaluation of various strategies aimed at identifying the complete genome of MPXV in clinical specimens. The findings of this study will significantly enhance the surveillance of MPXV.


An in vivo method for measuring the adsorption of plasma proteins to titanium in humans.
A novel method of collecting in vivo plasma proteins of humans from osteotomies prepared during insertion of an oral implant is described. A rod containing a collecting portion with a predetermined surface is introduced into the osteomy, removed, and transferred for enzyme-linked immunosorbent assay analysis. Two experiments were used to examine the feasibility of the method. In the first, titanium (Ti) rods with different roughness were exposed for 10 min to the blood. Blasted and acid-etched surfaces adsorbed four times more and acid-etched surfaces adosorbed two times more plasma proteins as compared to machined surfaces. In the second experiment, blasted and acid-etched rods were wetted for 10 s prior to the insertion. The adsorption for fibronectin, albumin, fibrinogen, and IgG was enhanced significantly compared with nonwetted rods. These results are discussed in the light of previous methods used in studies on adsorption. Thus, use of the collecting instrument enables aspects of human plasma-implant interface to be studied in a more realistic manner.


Mode of action of RNase BN/RNase Z on tRNA precursors: RNase BN does not remove the CCA sequence from tRNA.
RNase BN, the Escherichia coli homolog of RNase Z, was previously shown to act as both a distributive exoribonuclease and an endoribonuclease on model RNA substrates and to be inhibited by the presence of a 3'-terminal CCA sequence. Here, we examined the mode of action of RNase BN on bacteriophage and bacterial tRNA precursors, particularly in light of a recent report suggesting that RNase BN removes CCA sequences (Takaku, H., and Nashimoto, M. (2008) Genes Cells 13, 1087-1097). We show that purified RNase BN can process both CCA-less and CCA-containing tRNA precursors. On CCA-less precursors, RNase BN cleaved endonucleolytically after the discriminator nucleotide to allow subsequent CCA addition. On CCA-containing precursors, RNase BN acted as either an exoribonuclease or endoribonuclease depending on the nature of the added divalent cation. Addition of Co(2+) resulted in higher activity and predominantly exoribonucleolytic activity, whereas in the presence of Mg(2+), RNase BN was primarily an endoribonuclease. In no case was any evidence obtained for removal of the CCA sequence. Certain tRNA precursors were extremely poor substrates under any conditions tested. These findings provide important information on the ability of RNase BN to process tRNA precursors and help explain the known physiological properties of this enzyme. In addition, they call into question the removal of CCA sequences by RNase BN.


A classification system and algorithm for reconstruction of maxillectomy and midfacial defects.
Maxillectomy defects become more complex when critical structures such as the orbit, globe, and cranial base are resected, and reconstruction with distant tissues becomes essential. This study reviews all maxillectomy defects reconstructed immediately using pedicled and free flaps to establish (1) a classification system and (2) an algorithm for reconstruction of these complex problems. Over a 5-year period, 60 flaps were used to reconstruct defects classified as the following: type I, limited maxillectomy (n = 7); type II, subtotal maxillectomy (n = 10); type IIIa, total maxillectomy with preservation of the orbital contents (n = 13); type IIIb, total maxillectomy with orbital exenteration (n = 18); and type IV, orbitomaxillectomy (n = 10). Free flaps (45 rectus abdominis and 10 radial forearm) were used in 55 patients (91.7 percent), and the temporalis muscle was transposed in five elderly patients who were not free-flap candidates. Vascularized (radial forearm osteocutaneous) bone flaps were used in four of the 60 patients (6.7 percent) and nonvascularized bone grafts in 17 (28.3 percent). Simultaneous reconstruction of the oral commissure using an Estandler procedure was performed in 10 patients with maxillectomy and through-and-through soft-tissue defects. Free-flap survival was 100 percent, with reexploration in five of 55 patients (9.1 percent) and partial-flap necrosis in one patient. Seven of the 60 patients (11.7 percent) had systemic complications, and four died within 30 days of hospitalization. Fifty patients had more than 6 months of follow-up with a mean time of 27.7 (+/- 15.6) months. Postoperative radiotherapy was administered in 32 of these patients (64.0 percent). Chewing and speech functions were assessed in 36 patients with type II, IIIa, and IIIb defects. A prosthetic denture was fixed in 15 of 36 patients (41.7 percent). Return to an unrestricted diet was seen in 16 patients (44.4 percent), a soft diet in 17 (47.2 percent), and a liquid diet in three (8.3 percent). Speech was assessed as normal in 14 of 36 patients (38.9 percent), near normal in 15 (41.7 percent), intelligible in six (16.7 percent), and unintelligible in one patient (2.8 percent). Globe and periorbital soft-tissue position was assessed in 14 patients with type I and IIIa defects. There were no cases of enophthalmos, and one patient had a mild vertical dystopia. Ectropion was observed in 10 of 14 patients (71.4 percent). Oral competence was considered good in all 10 patients with excision/reconstruction of the oral commissure; however, two patients (20 percent) developed microstomia after receiving radiotherapy. Aesthetic results were evaluated at least 6 months after reconstruction in 50 patients. They were good to excellent in 29 patients (58 percent) for whom cheek skin and lip were not resected, and poor to fair (42 percent) when the external skin or orbital contents were excised. Secondary procedures were required in 16 of 50 patients (32.0 percent). Free-tissue transfer provides the most effective and reliable form of immediate reconstruction for complex maxillectomy defects. The rectus abdominis and radial forearm flaps in combination with immediate bone grafting or as osteocutaneous flaps reliably provide the best aesthetic and functional results. An algorithm based on the type of maxillary resection can be followed to determine the best approach to reconstruction.


Effects of physical activity during pregnancy and gestational weight gain on newborn weight and length at birth in Warmińsko-Mazurskie province.
Epidemiological research has identified a relationship between maternal physical activity, early nutrition and infant birth weight with likelihood of developing future diseases. The aim of the study was to determine a relationship between gestational weight gain and physical activity during pregnancy to the nutritional status of newborns. The presented study was conducted in the period from February 2010 until November 2012 in the gynecological and obstetric clinics in Warmińsko-Mazurskie voivodeship with various levels of reference. The research subjects included 510 women in the puerperal period aged 18-36. The scope of the research included an assessment of the selected anthropometric parameters of both pregnant women (body mass, height, BMI, gestational weight gain) and newborns (infant birth weight, infant length, Ponderal Index), as well as an analysis of the connections between the gestational weight gain, physical activity during pregnancy and anthropometric parameters of newborns. In the study group there was a significant percentage of women characterised by an inactive lifestyle and excessive gestational weight gain. There were significantly higher neonatal birth anthropometric parameters in women with abnormal excessive gestational weight gain than in women with normal and inappropriate - low gestational weight gain. The highest percentage of women with appropriate weight gain was observed in the group of women who are physically active, although this requires confirmation in larger population. Our studies have not shown statistically significant differences between the gestational weight gain and nutritional status of newborns in relation to the level of physical activity of pregnant women.


Cervical cancer, human papillomavirus and vaccines: assessment of the information retrieved from general knowledge websites in Chile.
Cervical cancer is the most common gynaecologic malignancy worldwide and is the sixth cause of cancer death in Chile. Human papillomavirus (HPV) is responsible for most cervical cancers. Individuals seeking basic information about HPV frequently turn to health information websites. We hypothesized that some of their data may be inaccurate. Comparative analysis of information. We analyze the content of highly accessed websites such as the Spanish version of Wikipedia and Yahoo Answers through the application of a questionnaire, as well as a website managed by the Chilean Ministry of Health (Minsal). The accuracy of each answer was confirmed by comparison with information retrieved from articles published by indexed journals. The information provided by the Spanish version of Wikipedia was accurate; nevertheless a few omissions were detected. The quality of the information provided by the Spanish version of Yahoo Answers was inaccurate and confusing. The Minsal website lacked important information on several topics about HPV even though it is managed and endorsed by the government. We suggest periodical content reviews to increase the completeness, transparency and correctness of the website.


Vitamin K-responsive coagulopathy in Henoch-Schölein purpura.
Henoch-Schönlein purpura is classically described as a systemic vasculitis without known platelet or clotting abnormality. A 15-year-old boy with Henoch-Schönlein purpura experienced a major hemorrhagic diathesis that was responsive to parenterally administered vitamin K. We believe that the gastrointestinal vasculitis prevented the absorption of available vitamin K necessary for the synthesis of clotting factors. Early treatment with parenteral vitamin K in similar cases should be considered.


Plaque reduction, a sensitive test for eastern encephalitis antibody.
Serologic surveys of vertebrates to determine rates of eastern encephalitis infection were made to discover the most likely disseminators of virus in nature. Of the techniques available, neutralization is the most specific, and antibody is known to persist for many years. This communication reports a fivefold increase in sensitivity of neutralizing-antibody detection by the application of a plaquereducing technique.


Risk Factors for Vitamin D Deficiency in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.
To identify risk factors for hypovitaminosis D in inflammatory bowel disease and conduct a comprehensive systematic review with meta-analysis to quantify the impact on vitamin D deficiency. We conducted a literature search of studies through PubMed, Embase, Cochrane Library, and Web of Science. In addition, relevant articles were searched manually. Studies were included if the odds ratios (OR) and 95% CI of each risk factor were reported or could be calculated. We will use the fixed-effects or random-effects model to estimate the pooled effect. Out of 1018 articles, 25 eligible studies were identified, including 5826 participants. The risk factors associated with hypovitaminosis D were non-Caucasian (OR: 3.79, 95% CI: 2.68-5.34), Crohn's disease (OR: 1.38, 95% CI: 1.21-1.56), disease activity (OR: 1.85, 95% CI: 1.61-2.13), inflammatory bowel disease-related surgery (OR: 1.61, 95% CI: 1.38-1.89), exposure to steroid (OR: 1.61, 95% CI: 1.28-2.03), and biologics (OR: 1.78, 95% CI: 1.48-2.14). In 30 ng/mL and adjusted OR subgroup, male (OR: 1.84, 95% CI: 1.47-2.31) and winter season (OR: 2.49, 95% CI: 1.69-3.67) also were risk factors, respectively. 5-aminosalicylic acid (OR: 1.10, 95% CI: 0.74-1.63) and smoking (OR: 1.19, 95% CI: 0.98-1.45) were unrelated to vitamin D deficiency. For vitamin D deficiency in inflammatory bowel disease, non-Caucasian, Crohn's disease, disease activity, surgery, exposure to steroid and biologics, males are risk factors, while 5-aminosalicylic acid and smoking are not. The relationship between body mass index, winter season, exposure to immunomodulators, and vitamin D deficiency remains unclear.


Dengue Virus Serotype 4 Is Responsible for the Outbreak of Dengue in East Java City of Jember, Indonesia.
Outbreaks of dengue virus (DENV) in Indonesia have been mainly caused by the DENV serotype-1; -2; or -3. The DENV-4 was the least-reported serotype in Indonesia during the last five decades. We recently conducted a molecular epidemiology study of dengue in the Jember regency, East Java province, Indonesia. Dengue is endemic in the region and outbreaks occur annually. We investigated the clinical characteristics and etiology of dengue-like febrile illness in this regency to understand the disease dynamics. A total of 191 patients with clinical symptoms similar to dengue were recruited during an 11-month study in 2019-2020. Children accounted for the majority of cases and dengue burden was estimated in 41.4% of the cases based on NS1 antigen, viral RNA, and IgG/IgM antibody detection with the majority (73.4%) being primary infections. Secondary infection was significantly associated with a higher risk of severe dengue manifestation. All four DENV serotypes were detected in Jember. Strikingly, we observed the predominance of DENV-4, followed by DENV-3, DENV-1, and DENV-2. Genotype determination using Envelope gene sequence revealed the classification into Genotype I, Cosmopolitan Genotype, Genotype I, and Genotype II for DENV-1, -2, -3, and -4, respectively. The predominance of DENV-4 in Jember may be associated with a new wave of DENV infections and spread in a non-immune population lacking a herd-immunity to this particular serotype.


Effects of hypercapnic hypoxia on inactivation and elimination of Vibrio campbellii in the Eastern oyster, Crassostrea virginica.
The Eastern oyster, Crassostrea virginica, inhabits shallow coastal waters that frequently experience periods of low dissolved oxygen (hypoxia) and elevated CO(2) (hypercapnia) levels. Bacteria are extremely abundant in these environments and accumulate in large numbers in filter-feeding oysters, which can act as passive carriers of human pathogens. Although hypercapnic hypoxia (HH) can affect certain specific immune mechanisms, its direct effect on the inactivation, degradation and elimination of bacteria in oysters is unknown. This research was conducted to determine whether exposure to HH reduces the ability of C. virginica to inactivate and eliminate Vibrio campbellii following its injection into the adductor muscle. Oysters were held in fully air-saturated (normoxic; partial O(2) pressure [P(O2)] = 20.7 kPa, CO(2) < 0.06 kPa, pH 7.8 to 8.0) or HH (P(O2) = 4 kPa, CO(2) = 1.8 kPa, pH 6.5 to 6.8) seawater at 25 degrees C for 4 h before being injected in the adductor muscle with 10(5) live Vibrio campbellii bacteria and remained under these conditions for the remainder of the experiment (up to 24 h postinjection). Real-time PCR was used to quantify the number of intact V. campbellii bacteria, while selective plating was used to quantify the number of injected bacteria remaining culturable in whole-oyster tissues, seawater, and feces/pseudofeces at 0, 1, 4, and 24 h postinjection. We found that oysters maintained under normoxic conditions were very efficient at inactivating and degrading large numbers of injected bacteria within their tissues. Moreover, a small percentage ( approximately 10%) of injected bacteria were passed into the surrounding seawater, while less than 1% were recovered in the feces/pseudofeces. In contrast, HH increased the percentage of culturable bacteria recovered from the tissues of oysters, suggesting an overall decrease in bacteriostasis. We suggest that poor water quality may increase the risk that oysters will harbor and transmit bacterial pathogens hazardous to human and ecosystem health.


Chaperone Activity and Dimerization Properties of Hsp90α and Hsp90β in Glucocorticoid Receptor Activation by the Multiprotein Hsp90/Hsp70-Dependent Chaperone Machinery.
Several hundred proteins cycle into heterocomplexes with a dimer of the chaperone heat shock protein 90 (Hsp90), regulating their activity and turnover. There are two isoforms of Hsp90, Hsp90α and Hsp90β, and their relative chaperone activities and composition in these client protein•Hsp90 heterocomplexes has not been determined. Here, we examined the activity of human Hsp90α and Hsp90β in a purified five-protein chaperone machinery that assembles glucocorticoid receptor (GR)•Hsp90 heterocomplexes to generate high-affinity steroid-binding activity. We found that human Hsp90α and Hsp90β have equivalent chaperone activities, and when mixed together in this assay, they formed only GR•Hsp90αα and GR•Hsp90ββ homodimers and no GR•Hsp90αβ heterodimers. In contrast, GR•Hsp90 heterocomplexes formed in human embryonic kidney (HEK) cells also contain GR•Hsp90αβ heterodimers. The formation of GR•Hsp90αβ heterodimers in HEK cells probably reflects the longer time permitted for exchange to form Hsp90αβ heterodimers in the cell versus in the cell-free assembly conditions. This purified GR-activating chaperone machinery can be used to determine how modifications of Hsp90 affect its chaperone activity. To that effect, we have tested whether the unique phosphorylation of Hsp90α at threonines 5 and 7 that occurs during DNA damage repair affects its chaperone activity. We showed that the phosphomimetic mutant Hsp90α T5/7D has the same intrinsic chaperone activity as wild-type human Hsp90α in activation of GR steroid-binding activity by the five-protein machinery, supporting the conclusion that T5/7 phosphorylation does not affect Hsp90α chaperone activity.


Evolutionary and temporal dynamics of emerging influenza D virus in Europe (2009-22).
Influenza D virus (IDV) is an emerging influenza virus that was isolated for the first time in 2011 in the USA from swine with respiratory illness. Since then, IDV has been detected worldwide in different animal species, and it was also reported in humans. Molecular epidemiological studies revealed the circulation of two major clades, named D/OK and D/660. Additional divergent clades have been described but have been limited to specific geographic areas (i.e. Japan and California). In Europe, IDV was detected for the first time in France in 2012 and subsequently also in Italy, Luxembourg, Ireland, the UK, Switzerland, and Denmark. To understand the time of introduction and the evolutionary dynamics of IDV on the continent, molecular screening of bovine and swine clinical samples was carried out in different European countries, and phylogenetic analyses were performed on all available and newly generated sequences. Until recently, D/OK was the only clade detected in this area. Starting from 2019, an increase in D/660 clade detections was observed, accompanied by an increase in the overall viral genetic diversity and genetic reassortments. The time to the most recent common ancestor (tMRCA) of all existing IDV sequences was estimated as 1995-16 years before its discovery, indicating that the virus could have started its global spread in this time frame. Despite the D/OK and D/660 clades having a similar mean tMRCA (2007), the mean tMRCA for European D/OK sequences was estimated as January 2013 compared to July 2014 for European D/660 sequences. This indicated that the two clades were likely introduced on the European continent at different time points, as confirmed by virological screening findings. The mean nucleotide substitution rate of the hemagglutinin-esterase-fusion (HEF) glycoprotein segment was estimated as 1.403 × 10-3 substitutions/site/year, which is significantly higher than the one of the HEF of human influenza C virus (P < 0.0001). IDV genetic drift, the introduction of new clades on the continent, and multiple reassortment patterns shape the increasing viral diversity observed in the last years. Its elevated substitution rate, diffusion in various animal species, and the growing evidence pointing towards zoonotic potential justify continuous surveillance of this emerging influenza virus.


Anti-cardiolipin and anti-beta2-glycoprotein I (beta2GP-I) antibody assays as screening for anti-phospholipid syndrome.
Antiphospholipid antibodies are a family of autoantibodies that exhibit a broad range of target specificities and affinities, all recognizing various combinations of phospholipids, phospholipid binding proteins or both. To evaluate the frequency of anticardiolipin (aCL) or anti-beta-2 glycoprotein I (anti-beta2GPI) antibodies in a cohort of patients with primary (PAPS) and secondary (SAPS) antiphospholipid syndrome and other rheumatic and infectious conditions. Sera were drawn from 226 patients with PAPS (n= 66), SAPS (n= 60), rheumatoid arthritis (RA) (n= 30), scleroderma (SSc) (n= 30) or syphilis (n= 30). IgG, IgM, IgA aCL and anti-beta2GPI antibodies were determined for all patients. We employed Varelisa diagnostic kits (Pharmacia Diagnostics GmbH & Co.KG, Germany). In APS patients: aCL and anti-betaGP1 antibodies were detected in 81.8% and 70% in PAPS and SAPS patients, respectively. In PAPS, aCL were detected in 71.2%, and anti-beta2GP1 in 50% of patients. In SAPS, aCL were detected in 63.3%, and anti-beta2GP1 in 53.3% of patients. In syphilis, aCL and anti-beta2GP1 antibodies were detected in 46.7% of patients in low levels: aCL in 36.7% and anti-beta2GP1 in 20% of patients. aCL antibodies were detected in 10%, 13.3%, and 0% of RA patients, SSc patients, and healthy persons, respectively. Anti-beta2GP1 antibodies were not detected in RA patients, SSc patients, and healthy persons. aCL and anti-beta2GP1 antibodies are more frequently found in sera of APS patients, and can be found in low levels in syphilis. Anti-beta2GP1 assay found to be more specific than aCL in antiphospholipid antibodies determination.


Significance of CSF area measurements in cervical spondylitic myelopathy.
Mild clinical myelopathy can occur without cord compression, and asymptomatic cord compression seen on MRI is common. The aim of this study was to ascertain the MRI features which best correlate with early clinical myelopathy. The study was conducted on three groups: group A, 20 patients with clinical myelopathy and MRI evidence of cervical spondylosis; group B, 20 patients without myelopathy, but with other clinical and MRI evidence of cervical spondylosis; and group C, 10 normal volunteers with no MRI evidence of spondylosis. The cross-sectional area (CSA) of the spinal cord (SP-CSA), spinal canal (SC-CSA) and CSF space (CSF-CSA) were measured on T1-weighted axial images at the level of the most severe spinal canal stenosis. The severity of myelopathy was assessed using a simple scoring system giving a score from 0 (normal) to 11 (severe). Subjective demonstration of cord compression on sagittal images was an insensitive indicator of clinical myelopathy. All three measures of cross-sectional area were significantly smaller in Group A than in B (p<0.01). The reduction in SP-CSA was the only independent prognosticator for severity of myelopathy (p<0.005) accounting for 63% of the variation in myelopathy score. All three variables showed a significant correlation with the presence of myelopathy (p<0.01); however, logistic regression analysis showed a decrease in CSF-CSA to be the only independent significant prognosticator of the presence of clinical myelopathy (p<0.02). Reduction of the CSF space to less than 0.7 cm2 was associated with a 90% chance of clinical myelopathy (specificity 83%).


[Gene chips-aided analysis on the profiles of hippocampal whole-genome expression in depression rats following electroacupuncture treatment].
To observe the effect of electroacupuncture (EA) on the profiles of hippocampal whole-genome expression in depression rats so as to study its underlying mechanism in relieving depression. Thirty male SD rats were randomized into normal, model and EA groups (n = 10/group). Depression model was established by chronic unpredictable stress stimulation (forced ice-water swimming, electric shock, tail-clamping, etc.) and lonely raising for 21 days. EA (2 Hz, 1 mA) was applied to "Baihui"(GV 20) and "Yintang" (EX-HN 3) for 15 min, once daily for 7 days. The rats' ethological activities (horizontal and vertical movements) were detected with Open-field test in Morris labyrinth, and 1% sucrose solution consumption was detected. After termination of the treatment, the rats were killed and their hippocampal tissues were taken out for analyzing the whole-genome expression with Roche-NimbleGen chips (Rattus norvegicus 12 x 135 Karray). Compared with normal group, the distance of horizontal movement, rearing times, and sucrose consumption at day 21 and day 28 of model group decreased considerably (P < 0.01). In comparison with model group, the sucrose consumption at day 28 in EA group increased significantly (P < 0.05). Results of gene expression microarray displayed that compared with normal group, of the down-regulated and up-regulated genes due to modeling, 101 and 125 turned to normal in their expression, respectively following EA treatment. The down-regulated genes involve energy and substance metabolism, protein biosynthesis, etc., and the up-regulated genes involve blood clotting, immunity, inflammation, apoptosis, etc. EA of GV 20 and EX-HN 3 can normalize chronic stress stimulation induced down- and up-regulated expression of many genes in depression rats, which may contribute to its clinical effect in relieving depression.


Health status after cancer: does it matter which hospital you belong to?
Survival rates are widely used to compare the quality of cancer care. However, the extent to which cancer survivors regain full physical or cognitive functioning is not captured by this statistic. To address this concern we introduce post-diagnosis employment as a supplemental measure of the quality of cancer care. This study is based on individual level data from the Norwegian Cancer Registry (n = 46,720) linked with data on labor market outcomes and socioeconomic status from Statistics Norway. We study variation across Norwegian hospital catchment areas (n = 55) with respect to survival and employment five years after cancer diagnosis. To handle the selection problem, we exploit the fact that cancer patients in Norway (until 2001) have been allocated to local hospitals based on their place of residence. We document substantial differences across catchment areas with respect to patients' post-diagnosis employment rates. Conventional quality indicators based on survival rates indicate smaller differences. The two sets of indicators are only moderately correlated. This analysis shows that indicators based on survival and post-diagnosis employment may capture different parts of the health status distribution, and that using only one of them to capture quality of care may be insufficient.


A separation of innate and learned vocal behaviors defines the symptomatology of spasmodic dysphonia.
Spasmodic dysphonia (SD) is a neurological disorder characterized by involuntary spasms in the laryngeal muscles. It is thought to selectively affect speaking; other vocal behaviors remain intact. However, the patients' own perspective on their symptoms is largely missing, leading to partial understanding of the full spectrum of voice alterations in SD. A cohort of 178 SD patients rated their symptoms on the visual analog scale based on the level of effort required for speaking, singing, shouting, whispering, crying, laughing, and yawning. Statistical differences between the effort for speaking and the effort for other vocal behaviors were assessed using nonparametric Wilcoxon rank-sum tests within the overall SD cohort as well as within different subgroups of SD. Speech production was found to be the most impaired behavior, ranking as the most effortful type of voice production in all SD patients. In addition, singing required nearly similar effort as speaking, ranking as the second most altered vocal behavior. Shouting showed a range of variability in its alterations, being especially difficult to produce for patients with adductor form, co-occurring voice tremor, late onset of disorder, and familial history of dystonia. Other vocal behaviors, such as crying, laughing, whispering, and yawning, were within the normal ranges across all SD patients. Our findings widen the symptomatology of SD, which has predominantly been focused on selective speech impairments. We suggest that a separation of SD symptoms is rooted in selective aberrations of the neural circuitry controlling learned but not innate vocal behaviors. 4 Laryngoscope, 129:1627-1633, 2019.


Intracellular monosaccharide and amino acid concentrations and activities and the mechanisms of insulin action.
Current amino acid and monosaccharide transport models are based on an assumption which equates the intracellular chemical activity of a solute with its concentration. This assumption was tested for alpha-aminoisobutyric acid and 3-O-methylglucose in a giant cell, the amphibian oocyte, by using recently developed cryomicrodissection and internal reference phase techniques. We found the following. (i) alpha-Aminoisobutyric acid and 3-O-methylglucose activities were much greater in cytoplasm than was suggested by concentration data; i.e., activity coefficients were higher than in ordinary water solutions. This is attributable to the inaccessibility of considerable water as solvent (solute exclusion). (ii) Solute concentrations varied regionally as follows: nucleus > > animal cytoplasm > vegetal cytoplasm. Insulin increased the nucleus/cytoplasm concentration asymmetry, apparently by increasing cytoplasmic solute exclusion. (iii) Nuclear activity coefficients more closely resembled those of ordinary saline solutions so that nucleus/ extracellular concentration ratios reflected transmembrane activity gradients better than did cytoplasm (or whole cell)/extracellular ratios. (iv) Mediated passive alpha-aminoisobutyric acid and 3-O-methylglucose transport were constituent oocyte membrane properties. Membrane active transport was initiated with time (in the presence of substrate) and by insulin. (v) Increased temperature mimicked insulin in enhancing transmembrane alpha-aminoisobutyric acid activity gradients and increasing the nucleus/cytoplasm concentration asymmetry. These results indicated that concentration data are a misleading measure of cellular amino acid and monosaccharide activity; some consequences of this observation were explored. A model is proposed in which cell water has reduced solvent capacity or is compartmentalized (considered less likely) and is susceptible to physiological modulation. The model accounts for many observations in small cells, suggesting generality of the exclusion phenomenon and a previously unrecognized metabolic control mechanism.


Lethal trap trees: a potential option for emerald ash borer (Agrilus planipennis Fairmaire) management.
Economic and ecological impacts of ash (Fraxinus spp.) mortality resulting from emerald ash borer (EAB) (Agrilus planipennis Fairmaire) invasion are severe in forested, residential and urban areas. Management options include girdling ash trees to attract ovipositing adult beetles and then destroying infested trees before larvae develop or protecting ash with a highly effective, systemic emamectin benzoate insecticide. Injecting this insecticide and then girdling injected trees a few weeks later could effectively create lethal trap trees, similar to a bait-and-kill tactic, if girdling does not interfere with insecticide translocation. We compared EAB larval densities on girdled trees, trees injected with the emamectin benzoate insecticide, trees injected with the insecticide and then girdled 18-21 days later and untreated controls at multiple sites. Pretreatment larval densities did not differ among treatments. Current-year larval densities were higher on girdled and control trees than on any trees treated with insecticide at all sites. Foliar residue analysis and adult EAB bioassays showed that girdling trees after insecticide injections did not reduce insecticide translocation. Girdling ash trees to attract adult EAB did not reduce efficacy of emamectin benzoate trunk injections applied ≥ 18 days earlier and could potentially be used in integrated management programs to slow EAB population growth.


Reduction of nocturnal diuresis and natriuresis during treatment of obstructive sleep apnea (OSA) with nasal continuous positive air pressure (nCPAP) correlates to cGMP excretion.
In ten patients with severe obstructive sleep apnea (OSA) profound changes in renal function could be demonstrated at night during nCPAP therapy. Natriuresis and diuresis decreased by about 50% while creatinine excretion rate and urinary osmolality did not change. We found parallel changes in the excretion of ANP's second messenger cyclic guanosine monophosphate (cGMP) in a dose-response-related manner to natriuresis respectively diuresis. These data are in agreement with recently demonstrated decrease of nocturnal plasma levels of atrial natriuretic peptide (ANP) during nCPAP therapy in apneic patients. This may be an indicator for an increased cardiac volume load during obstructive apnea. The decrease of diuresis, natriuresis and cGMP excretion demonstrate the beneficial effects of nCPAP treatment on the cardiovascular system. Therefore measurements of cGMP excretion may be a useful parameter to assess the cardiovascular function of apneic patients before and during treatment.


Differential binding of fluorescein-labeled lectins to mouse thymocytes: subsets revealed by flow microfluorometry.
Fluorescein-labeled lectins bound to mouse thymocytes were analyzed by flow microfluorometry. This technique has identified several lectins that bind differentially to thymocyte subsets. The most complex fluorescence distributions were obtained using lectins with nominal specificities for galactose or N-acetylglucosamine. Inhibition of binding by sugars confirmed that the fluoresceinated lectins were bound to cells at their carbohydrate binding site. Simultaneous analyses of lectin fluorescence and forward light scatter intensity showed that cell subpopulations of different sizes can exhibit marked differences in the level of binding such that the amount of lectin bound per cell is often independent of cell size. A minor population of dull or unstained cells, delineated by several of these lectins, correlates with the subpopulation of medium-sized thymocytes resistant to in vivo cortisone treatment.


Comparison of the effect of vanadium and deferoxamine on acetaminophen toxicity in rats.
Acetaminophen (APAP) can change to toxic metabolites at high dose; if these metabolites are in high amounts, the body will be unable to neutralize them, and several tissues including liver will be damaged. In the present study, the effect of vanadium was compared with deferoxamine on hepatotoxicity and also kidney function during APAP administration in rats. The study was done in 5 groups (5 rats in each group): group I to V, respectively, received normal saline, APAP, APAP + deferoxamine, APAP + vanadium, and vanadium. At the end of the study, blood was collected and serum was separated for laboratory tests. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine, sodium, and potassium were determined. The liver of the rats were separated for tissue processing and light microscopic examination. APAP significantly increased; ALT level and deferoxamine and vanadium prevented its elevation. Also, deferoxamine and vanadium prevented increase of AST by APAP. The change of factors, which are related to the kidney function, i.e., BUN, creatinine, sodium, and potassium were not considerable. Thus, it was observed that vanadium had better effect than deferoxamine in the prevention of hepatotoxicity induced by APAP.


The Effects of Compression Garments on Stability and Lower Limb Kinematics During a Forward Lunge.
Compression garments have been used to minimise injury risk, through improvements in stability and joint positioning; yet, it is unclear whether there is an optimal length or tightness of these garments that may maximise observed benefits. This study measured the effect of three different garment types, at two different tightness levels, on lower extremity stability and alignment during a forward lunge movement. Sixteen healthy adults (7 female, 9 male; 24.3 ± 2.9 years) were recruited as participants. Stability of the lead foot, as well as lower body joint kinematics, were recorded using an Oqus 12-camera system, surrounding participants as they executed three forward lunges onto a Matscan pressure mat under seven compression conditions (Control, Light/Heavy Calf, Light/Heavy Socks, Light/Heavy Leggings). Mean minimum time-to-boundary (mmTtB) (derived from centre of pressure measures) and frontal plane kinematics (lateral pelvic tilt, knee valgus, ankle inversion/eversion) were used to assess the effect of garment tightness and length on lunge stability and joint alignment, respectively. A significant effect of tightness on mmTtB was observed (F(1,105) = 8.192; p = .005, η2 = .072), with Heavy garments eliciting longer mmTtB compared to their corresponding Light (-.18 ± .06 s; p = .015) or Control (-.28 ± .09 s; p = .007) conditions. No significant effects of garment tightness or length on lower body kinematics were evident. The results of this study suggest stability during a forward lunge is improved through the use of tight-fitted compression garments.


Characterization of regulatory pathways in Xylella fastidiosa: genes and phenotypes controlled by algU.
Many virulence genes in plant bacterial pathogens are coordinately regulated by "global" regulatory genes. Conducting DNA microarray analysis of bacterial mutants of such genes, compared with the wild type, can help to refine the list of genes that may contribute to virulence in bacterial pathogens. The regulatory gene algU, with roles in stress response and regulation of the biosynthesis of the exopolysaccharide alginate in Pseudomonas aeruginosa and many other bacteria, has been extensively studied. The role of algU in Xylella fastidiosa, the cause of Pierce's disease of grapevines, was analyzed by mutation and whole-genome microarray analysis to define its involvement in aggregation, biofilm formation, and virulence. In this study, an algU::nptII mutant had reduced cell-cell aggregation, attachment, and biofilm formation and lower virulence in grapevines. Microarray analysis showed that 42 genes had significantly lower expression in the algU::nptII mutant than in the wild type. Among these are several genes that could contribute to cell aggregation and biofilm formation, as well as other physiological processes such as virulence, competition, and survival.


History of Psychoactive Medication a Risk Factor for Neurocognitive Decline After Cardiac Surgery.
Neurocognitive decline (NCD) is a common complication after cardiac surgery with implications for outcomes and quality of life. Identifying risk factors can help surgeons implement preventative measures, optimize modifiable risk factors, and counsel patients about risk and prognosis. Prospective cohort study at a single academic center. 104 patients planned to undergo cardiac surgery were enrolled. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to measure neurocognitive function preoperatively, on postoperative day four, and postoperative day 30. NCD is defined as a change in RBANS scaled score of < -8 from baseline to postoperative day 4. Patient charts were reviewed for medication history: beta-blockers, angiotensin-converting enzyme and angiotensin receptor blockers, calcium channel blockers, statins, oral hypoglycemic agents, and psychoactive medications. Charts were also reviewed to calculate postoperative opioid usage. NCD was detected in 42.9% of patients. Incidence of NCD was significantly higher in patients taking a psychoactive medication (56.8%) than patients not (31.9%), P < 0.03. There was no relationship between historical use of beta-blocker, calcium-channel blocker, statin, or oral hypoglycemic medications and incidence of NCD. Simple linear regression showed no relationship between change in RBANS total scaled score and opioid usage. There was no difference in incidence of NCD at 1 mo. Patients with a history of taking psychoactive medications prior to cardiac surgery have an increased risk of acute postoperative NCD.