Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine.
The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace and scale. However, many challenges remain, including: the emergence of vaccine-resistant mutant viruses, vaccine stability during storage and transport, waning vaccine-induced immunity, and concerns about infrequent adverse events associated with existing vaccines. We report on a protein subunit vaccine comprising the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein, dimerised with an immunoglobulin IgG1 Fc domain. These were tested in conjunction with three different adjuvants: a TLR2 agonist R4-Pam2Cys, an NKT cell agonist glycolipid α-Galactosylceramide, or MF59® squalene oil-in-water adjuvant, using mice, rats and hamsters. We also developed an RBD-human IgG1 Fc vaccine with an RBD sequence of the immuno-evasive beta variant (N501Y, E484K, K417N). These vaccines were also tested as a heterologous third dose booster in mice, following priming with whole spike vaccine. Each formulation of the RBD-Fc vaccines drove strong neutralising antibody (nAb) responses and provided durable and highly protective immunity against lower and upper airway infection in mouse models of COVID-19. The 'beta variant' RBD vaccine, combined with MF59® adjuvant, induced strong protection in mice against the beta strain as well as the ancestral strain. Furthermore, when used as a heterologous third dose booster, the RBD-Fc vaccines combined with MF59® increased titres of nAb against other variants including alpha, delta, delta+, gamma, lambda, mu, and omicron BA.1, BA.2 and BA.5. These results demonstrated that an RBD-Fc protein subunit/MF59® adjuvanted vaccine can induce high levels of broadly reactive nAbs, including when used as a booster following prior immunisation of mice with whole ancestral-strain spike vaccines. This vaccine platform offers a potential approach to augment some of the currently approved vaccines in the face of emerging variants of concern, and it has now entered a phase I clinical trial. This work was supported by grants from the Medical Research Future Fund (MRFF) (2005846), The Jack Ma Foundation, National Health and Medical Research Council of Australia (NHMRC; 1113293) and Singapore National Medical Research Council (MOH-COVID19RF-003). Individual researchers were supported by an NHMRC Senior Principal Research Fellowship (1117766), NHMRC Investigator Awards (2008913 and 1173871), Australian Research Council Discovery Early Career Research Award (ARC DECRA; DE210100705) and philanthropic awards from IFM investors and the A2 Milk Company.


Application prospect of peptide-modified nano targeting drug delivery system combined with PD-1/PD-L1 based immune checkpoint blockade in glioblastoma.
Glioblastoma (GBM) is a type of primary malignant brain tumor with low median survival time, high recurrence rate and poor prognosis. The blood-brain barrier (BBB) and the diffuse infiltration of invasive GBM cells lead to a lower efficacy of traditional treatment. Recently, nanocarriers have become a promising method of brain drug delivery due to their ability to effectively cross the BBB. Especially, the peptide-modified nanocarriers can enhance the permeability, targeting and efficacy of chemotherapeutic agents against GBM. Moreover, the clinical application of immune checkpoint blockade (ICB) therapy in cancer treatment has attracted increasing attention, and the programmed death-1 receptor (PD-1) and PD-ligand-1 (PD-L1) monoclonal antibodies are considered to be a possible therapy for GBM. Consequently, we review the advances both in peptide-modified nano targeted drug delivery system and PD-1/PD-L1 based ICB in GBM treatment, and propose a new strategy combining the two methods, which may provide a novel approach for GBM treatment.


Heterologous production of five Hepatitis C virus-derived antigens in three Saccharomyces cerevisiae host strains.
In this study, the production of recombinant Hepatitis C virus (HCV) derived proteins from transformed Saccharomyces cerevisiae yeast cells is reported. Three different yeast strains (GRF18U, BY4743-4A and CENPK 113-5D) have been transformed for the intracellular expression of five antigens of different dimensions (from 32.8 to 85.2 kDa), all derived from the non-structural (NS) region of different HCV viruses' genotypes and posed under the control of a glycolytic promoter. The putative trans-membrane domains contained in four antigens seem responsible of their accumulation as protein aggregates. Good productions of the smaller and of the bigger antigens (50 and 30 mgl(-1), respectively) have been observed in simple flask batch cultures. Productions are strongly dependent from the genetic background of the yeast host and from the cellular localization of the antigen, while they appear independent from the growth rate of the transformed hosts. For every recombinant antigen tested, the highest production levels were achieved with the CENPK 113-5D-host strain, while the GRF18U strain shows symptoms of a heavily stressed phenotype.


NSAIDs Overcome PIK3CA Mutation-Mediated Resistance to EGFR Inhibition in Head and Neck Cancer Preclinical Models.
Epidermal growth factor receptor (EGFR) inhibitors are approved by the Food and Drug Administration (FDA) but remain under active clinical investigation for the treatment of both newly diagnosed and recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Despite EGFR expression in the majority of HNSCC tumors, the levels of total or phosphorylated EGFR have not consistently been correlated with a response to EGFR targeting agents. The lack of predictive biomarkers represents a major obstacle to successful use of these drugs. Activation of phosphatidylinositol 3-kinase (PI3K) signaling by mutation of the PIK3CA oncogene represents a plausible mechanism for EGFR inhibitor drug resistance. We compared the impact of EGFR inhibitors, alone or in combination with non-steroidal anti-inflammatory drugs (NSAIDs), in preclinical HNSCC models harboring mutant versus wild-type PIK3CA. Our results demonstrate additive or synergistic effects of NSAIDs and EGFR inhibitors in vitro and in vivo in PIK3CA-mutated HNSCC models. These findings suggest that the addition of NSAIDs to EGFR inhibitors for the treatment of HNSCC may represent a promising therapeutic strategy in PIK3CA-mutated cancers.


Early and late outcomes following aortic root enlargement: A multicenter propensity score-matched cohort analysis.
The safety and efficacy of aortic root enlargement (ARE) at the time of aortic valve replacement (AVR) remains unknown. The objective of this multicenter study was to compare AVR with ARE to AVR for early and late mortality and secondary safety outcomes. Clinical and administrative databases in Ontario, Canada, were linked to obtain patients undergoing AVR with or without ARE from 2008 to 2017. Baseline characteristics were compared and 1:1 propensity score matching was performed to account for differences in baseline characteristics. Early outcomes were compared in the matched groups. Late mortality was compared using Kaplan-Meier survival curves and a Cox-proportional hazard model. Sixteen thousand six hundred fifty-six patients undergoing AVR in 11 Ontario institutions were reviewed. Patients who underwent ARE were younger, nonurgent, more likely to be men and had lower rates of hypertension, ischemic heart disease, and congestive heart failure. Propensity score matching yielded similar groups for comparison, with 809 pairs for AVR versus AVR with ARE. There was no difference in 30-day mortality between AVR with ARE versus AVR (2.0% vs 2.1%; P = 1.00). Rates of chest reopening for bleeding, permanent pacemaker implantation, and blood transfusions were similar. Late mortality over 8 years was similar between AVR with ARE and AVR (P = .45). In a sensitivity analysis, results were similar in 525 pairs comparing AVR with coronary artery bypass grafting and ARE to AVR with coronary artery bypass grafting, except that chest reopening for bleeding was higher with AVR with coronary artery bypass grafting and ARE (7.2% vs 3.2%; P = .006). The addition of ARE to isolated AVR can be safely performed to increase implanted prosthesis size without compromising early mortality. Additional studies with longer follow-up are necessary.


Prolonged prostaglandin E1 stimulation of cyclic AMP production in transformed and normal WI-38 fibroblasts.
Long-term (48-hr) incubations of either the fibroblast strain WI-38 or its SV40-transformed counterpart, WI-38-VA13-2RA, in growth medium containing 1 micron prostaglandin E1 (PGE1) resulted in a sustained production and release of cyclic AMP from the cells into the medium. Despite the steady production, intracellular levels of the nucleotide decreased, reaching steady-state values within 4 hr of the initial exposure to PGE1. These values were maintained for the remainder of the 48-hr experimental period. The steady-state levels of intracellular cyclic AMP were higher than those observed in unstimulated cells, and cyclic AMP-dependent protein phosphokinase was in a highly activated state as compared to controls. Under these conditions little change in the growth or morphology of either the normal or transformed cells was observed. In contrast, inhibition of growth, apparent cell death, and unusual morphological changes were observed in both normal and transformed cells when high concentrations of either PGE1 (10 micron) or the phosphodiesterase inhibitor 1-methyl, 3-isobutylxanthine (0.5 mM to 2 mM) were used, which was indicative of toxic effects of the drugs. It was concluded that cyclic AMP-mediated activation of protein phosphokinase does not completely inhibit growth in WI-38 cells or restore normal growth and morphology to the SV40-transformed cells.


COVID-19 vaccine coverage disparities in rural and farm children.
The risks of severe outcomes associated with SARS-CoV-2 (COVID-19) are elevated in unvaccinated individuals. It remains crucial to understand patterns of COVID-19 vaccination, particularly in younger and remote populations where coverage often lags. This study examined disparities in COVID-19 vaccine coverage in farm children and adolescents. A cross-sectional analysis was conducted in patients of the Marshfield Clinic Health System (MCHS) in Wisconsin. The sample included children/adolescents age 5-17 years who were eligible for COVID-19 vaccine initiation for ≥ 90 days (as of September 30, 2022), stratified by those who lived vs did not live on a farm. Outcomes included COVID-19 vaccine initiation, series completion, and booster receipt. Multivariable regression was used to examine associations between COVID-19 vaccination and farm, as well as rural and non-rural, residence. There were 47,104 individuals (5% farm residents) in the sample. Overall, 33% of participants initiated and 31% completed the COVID-19 vaccine series. After adjustment, farm residence was associated with significantly lower odds of COVID-19 vaccine initiation (aOR [95% CI] = 0.68 [0.61, 0.75], p < 0.001), series completion (aOR = 0.67 [0.60, 0.75], p < 0.001), and booster receipt (aOR = 0.73 [0.61, 0.88], p = 0.001). Secondary analyses found COVID-19 vaccine coverage was lowest in young children who lived on dairy farms. COVID-19 vaccine coverage is low in north-central Wisconsin children and adolescents. Those who live on farms have significantly lower likelihood of COVID-19 vaccine initiation, series completion, and booster receipt compared to non-farm counterparts. Farm families are an underserved group and require more effective public health interventions designed to prevent COVID-19.


Modeled Health Economic Impact of a Hypothetical Certolizumab Pegol Risk-Sharing Scheme for Patients with Moderate-to-Severe Rheumatoid Arthritis in Finland.
To model the American College of Rheumatology (ACR) outcomes, cost-effectiveness, and budget impact of certolizumab pegol (CZP) (with and without a hypothetical risk-sharing scheme at treatment initiation for biologic-naïve patients) versus the current mix of reimbursed biologics for treatment of moderate-to-severe rheumatoid arthritis (RA) in Finland. A probabilistic model with 12-week cycles and a societal approach was developed for the years 2015-2019, accounting for differences in ACR responses (meta-analysis), mortality, and persistence. The risk-sharing scheme included a treatment switch and refund of the costs associated with CZP acquisition if patients failed to achieve ACR20 response at week 12. For the current treatment mix, ACR20 at week 24 determined treatment continuation. Quality-adjusted life years were derived on the basis of the Health Utilities Index. In the Finnish target population, CZP treatment with a risk-sharing scheme led to a estimated annual net expenditure decrease ranging from 1.7% in 2015 to 5.6% in 2019 compared with the current treatment mix. Per patient over the 5 years, CZP risk sharing was estimated to decrease the time without ACR response by 5%-units, decrease work absenteeism by 24 days, and increase the time with ACR20, ACR50, and ACR70 responses by 5%-, 6%-, and 1%-units, respectively, with a gain of 0.03 quality-adjusted life years. The modeled risk-sharing scheme showed reduced costs of €7866 per patient, with a more than 95% probability of cost-effectiveness when compared with the current treatment mix. The present analysis estimated that CZP, with or without the risk-sharing scheme, is a cost-effective alternative treatment for RA patients in Finland. The surplus provided by the CZP risk-sharing scheme could fund treatment for 6% more Finnish RA patients. UCB Pharma.


Ecological factors shaping the ectoparasite community assembly of the Azara's Grass Mouse, Akodon azarae (Rodentia: Cricetidae).
Parasites are integral members of the global biodiversity. They are useful indicators of environmental stress, food web structure and diversity. Ectoparasites have the potential to transmit vector-borne diseases of public health and veterinary importance and to play an important role in the regulation and evolution of host populations. The interlinkages between hosts, parasites and the environment are complex and challenging to study, leading to controversial results. Most previous studies have been focused on one or two parasite groups, while hosts are often co-infected by different taxa. The present study aims to assess the influence of environmental and host traits on the entire ectoparasite community composition of the rodent Akodon azarae. A total of 278 rodents were examined and mites (Mesostigmata), lice (Phthiraptera), ticks (Ixodida) and fleas (Siphonaptera) were determined. A multi-correspondence analysis was performed in order to analyze interactions within the ectoparasite community and the influence of environmental and host variables on this assembly. We found that environmental variables have a stronger influence on the composition of the ectoparasite community of A. azarae than the host variables analyzed. Minimum temperature was the most influential variable among the studied. In addition, we found evidence of agonistic and antagonistic interactions between ticks and mites, lice and fleas. The present study supports the hypothesis that minimum temperature plays a major role in the dynamics that shape the ectoparasite community of A. azarae, probably through both direct and indirect processes. This finding becomes particularly relevant in a climate change scenario.


The site of action of six different ribosome-inactivating proteins from plants on eukaryotic ribosomes: the RNA N-glycosidase activity of the proteins.
The site of action of six different ribosome-inactivating proteins from plants on eukaryotic ribosomes was studied. Treatment of ribosomes with any one of these proteins caused the 28S rRNA extracted from the inactivated ribosomes to become sensitive to treatment with aniline. A fragment containing about 450 nucleotides was released from the 28S rRNA. Further analysis of the nucleotide sequences of the 450-nucleotide fragments revealed that the aniline-sensitive phosphodiester bond was between A-4324 and G-4325 of the 28S rRNA. These results indicate that all six ribosome-inactivating proteins damage eukaryotic ribosomes by cleaving the N-glycosidic bond at A-4324 of the 28S rRNA of the ribosomes, as does ricin A-chain.


Extrinsic vs. intrinsic food shortage and the strength of feeding links: effects of density and food availability on feeding rate of Hyphydrus ovatus.
We use field and laboratory experiments to determine whether Hyphydrus ovatus, a predatory aquatic beetle, is food limited, and whether any food shortage results from depletion of prey by these predators (intrinsic food shortage) or is independent of predation by these beetles (extrinsic food shortage). In the laboratory, differences in feeding rate influence body fat content, thus making fat content a useful index of recent feeding history. H. ovatus collected during the breeding season have fat contents significantly greater than those of H. ovatus starved for 25 days, but not significantly different from those of H. ovatus fed ad libitum for 25 days, indicating that natural feeding rates are near the maximum possible. H. ovatus confined at a density 60 times greater than natural show reduced fat content and feeding rate relative to natural, indicating that at very high densities H. ovatus is capable of depleting its prey. Addition of supplemental natural prey (primarily Cladocera) to experimental enclosures resulted in an order of magnitude increase in prey availability, and a significant increase in fat content and feeding rate of confined H. ovatus. Adults of this species do not appear to be food limited during the breeding season, and extraordinarily high densities of adults seem to be necessary to produce intrinsic food shortage. These results suggest that feeding links between H. ovatus an its principal prey do not have major effects on population dynamics under typical field conditions, and call into question the assumption that closely coupled predator-prey interactions are the sole explanation for observed food-web patterns.


Extrauterine environment influences spontaneous low-frequency oscillations in the preterm brain.
Low-frequency oscillations in cerebral blood flow that are suggestive of resting-state brain activity have recently been reported, but no study on the development of resting-state brain activity in preterm infants has been performed. The objective of this study was to measure the cerebral blood flow oscillations, which are assumed to represent brain function in the resting state, in preterm and term infants of the same postconceptional age. The subjects were 9 preterm infants who had reached full term (gestational age (GA): 23-34 weeks, postconceptional age: 37-46 weeks) and 10 term infants (GA: 37-40 weeks, postconceptional age: 37-41 weeks). Their changes in concentration of oxyhemoglobin ([oxyHb]) and deoxyhemoglobin ([deoxyHb]) were measured in the parieto-temporal region during quiet sleep using multi-channel near-infrared spectroscopy, and the power spectral densities (PSD) of the oscillations in the concentrations of these molecules were analyzed and compared. The preterm infants displayed a higher proportion of 0.06-0.10 Hz low frequency oscillations of [oxyHb] and [deoxyHb] than the term infants, and the gestational age and the proportion of low frequency oscillations were inversely correlated. These findings suggest that resting-state cerebral blood flow oscillations differ between preterm and term infants, and that the development of circulatory regulation and nerve activity in preterm infants are influenced by the extrauterine environment.


Dual Ectopic Thyroid Gland in an Elderly Male: Double Trouble?
Double ectopic thyroid tissue is a rare phenomenon. We report a case of a 75-year-old man who was referred with two painless swellings in the anterior midline of neck with a tracheostomy tube in situ with the suspicion of malignancy. Such patients should be investigated completely prior to definitive treatment.


Relationship of hormonally induced developmental changes in preovulatory follicles of the rabbit.
Observations made during these investigations agree with the findings of various authors concerning atresia and follicular growth. In addition the results demonstrate that it is possible to induce the resumption of meiosis in rabbit oocytes without ovulation. This will be a useful tool for further investigations of changes in the chromosomal events during preovulatory ageing.


The kinetics of ultrafiltration during peritoneal dialysis: the role of lymphatics.
Net ultrafiltration was measured directly during hypertonic peritoneal dialysis exchanges in rats. Simultaneously, lymphatic absorption was measured by monitoring the disappearance of albumin in the instilled dialysis solution from the peritoneal cavity. The albumin method for measuring lymphatic absorption was also tested in rats absorbing Lactated Ringer's solution from the peritoneal cavity where absorption rate could also be measured directly. The findings suggest the following: 1.) lymphatic absorption rate is similar with both hypertonic dialysis solutions and Lactated Ringer's solution; 2.) lymphatic absorption is substantial and net ultrafiltration is well below true transcapillary ultrafiltration; and 3.) in our model, lymphatic absorption occurs at a relatively constant rate over six hours of dwell time.


Routine sterile glove and instrument change at the time of abdominal wound closure to prevent surgical site infection (ChEETAh): a pragmatic, cluster-randomised trial in seven low-income and middle-income countries.
Surgical site infection (SSI) remains the most common complication of surgery around the world. WHO does not make recommendations for changing gloves and instruments before wound closure owing to a lack of evidence. This study aimed to test whether a routine change of gloves and instruments before wound closure reduced abdominal SSI. ChEETAh was a multicentre, cluster randomised trial in seven low-income and middle-income countries (Benin, Ghana, India, Mexico, Nigeria, Rwanda, South Africa). Any hospitals (clusters) doing abdominal surgery in participating countries were eligible. Clusters were randomly assigned to current practice (42) versus intervention (39; routine change of gloves and instruments before wound closure for the whole scrub team). Consecutive adults and children undergoing emergency or elective abdominal surgery (excluding caesarean section) for a clean-contaminated, contaminated, or dirty operation within each cluster were identified and included. It was not possible to mask the site investigators, nor the outcome assessors, but patients were masked to the treatment allocation. The primary outcome was SSI within 30 days after surgery (participant-level), assessed by US Centers for Disease Control and Prevention criteria and on the basis of the intention-to-treat principle. The trial has 90% power to detect a minimum reduction in the primary outcome from 16% to 12%, requiring 12 800 participants from at least 64 clusters. The trial was registered with ClinicalTrials.gov, NCT03700749. Between June 24, 2020 and March 31, 2022, 81 clusters were randomly assigned, which included a total of 13 301 consecutive patients (7157 to current practice and 6144 to intervention group). Overall, 11 825 (88·9%) of 13 301 patients were adults, 6125 (46·0%) of 13 301 underwent elective surgery, and 8086 (60·8%) of 13 301 underwent surgery that was clean-contaminated or 5215 (39·2%) of 13 301 underwent surgery that was contaminated-dirty. Glove and instrument change took place in 58 (0·8%) of 7157 patients in the current practice group and 6044 (98·3%) of 6144 patients in the intervention group. The SSI rate was 1280 (18·9%) of 6768 in the current practice group versus 931 (16·0%) of 5789 in the intervention group (adjusted risk ratio: 0·87, 95% CI 0·79-0·95; p=0·0032). There was no evidence to suggest heterogeneity of effect across any of the prespecified subgroup analyses. We did not anticipate or collect any specific data on serious adverse events. This trial showed a robust benefit to routinely changing gloves and instruments before abdominal wound closure. We suggest that it should be widely implemented into surgical practice around the world. National Institute for Health Research (NIHR) Clinician Scientist Award, NIHR Global Health Research Unit Grant, Mölnlycke Healthcare.


Effects of fluorescent carbon dots from the baked lamb on energy and lipid metabolism.
Food-borne carbon dots (CDs) may cause health risks due to their unique properties. However, previous efforts were mainly focused on the characterization of their physicochemical properties, their effects on cellular metabolism are not entirely revealed. Herein, the features and potential toxicity of CDs from lamb baked for 15, 30, and 45 min were evaluated, their cytotoxicity increased with the extension of baking time. Furthermore, the metabolic responses of PC12 cells after exposure to CDs from lamb baked for 45 min were investigated. The CDs perturbed purine metabolism, causing reactive oxygen species accumulation. Meanwhile, the CDs down-regulated glycolysis and TCA cycle, led to a significant decrease in ATP. Additionally, the CDs induced triglyceride accumulation, mainly through enhanced fatty acid biosynthesis. The adverse effects of CDs from baked lamb involved the perturbation of energy production, purine metabolism, and triglyceride biosynthesis, which provided additional information about the risks of CDs from food items.


Effect of plant tannin and glycerol on thermoplastic starch: Mechanical, structural, antimicrobial and biodegradable properties.
Thermoplastic starch is a good candidate for preparing biobased plastics. However, certain deficiencies in the ingredient, such as its poor mechanical strength and lack of antibacterial activity, need to be strengthened. In this work, a new method of producing TPS via extrusion and injection at a large scale was explored using tannin and glycerol simultaneously. The effect of the tannin content on the performance of TPS was investigated. The results showed that the synergistic effect of a small amount of tannin (2.5-7.5 wt%) and glycerol increased the tensile strength and maintained a stable elongation at break, and tannin aggregation occurred in TPS at higher tannin contents, which corresponded to increased tensile and flexural strengths. 15T-TPS has optimal mechanical performance with maximal relative crystallinity. The introduced tannin in TPS effectively enhanced the thermal stability but slightly reduced the biodegradability in soil and endowed TPS with antibacterial activity. Therefore, TPS containing tannins has the potential to be used in biomedical, food packaging and agricultural areas.


Urinary tract infection in patients with lower urinary tract dysfunction.
Lower urinary tract dysfunction (LUTD) is becoming more common in aging societies worldwide. In patients with LUTD, the risk of urinary tract infection (UTI) rises due to several distinct mechanisms, including easy bacterial access to the urinary tract, impaired bacterial washout, and an impaired innate defense system. The pathophysiology of LUTD varies depending on whether it is neurogenic or non-neurogenic, as well as by gender; therefore, the etiology and characteristics of UTI differ according to the type of LUTD. Patients with neurogenic LUTD, especially those with spinal cord injury, have a high risk of febrile UTI, and strict bladder management is required to prevent UTI. Clean intermittent catheterization with or without appropriate pharmacological therapy is also strongly recommended for patients with neurogenic LUTD at risk of febrile UTI, unable to void, or with high post-void residual volume. In contrast, both male and female patients with non-neurogenic LUTD have a lower risk of symptomatic UTI. There is insufficient evidence for non-neurogenic LUTD regarding the association between symptomatic UTI but not asymptomatic bacteriuria and LUTD severity, including the presence of post-void residual volume, or whether therapeutic intervention for LUTS reduces the incidence of UTI, particularly in male patients. In this narrative review, we aimed to highlight the pathogenesis, epidemiology, and management of UTI in patients with LUTD.


Trends in the prevalence of chronic liver disease in the Korean adult population, 1998-2017.
Data on the trends in the prevalence of chronic liver disease (CLD) in Korea are scarce. This study aimed to evaluate whether the CLD prevalence changed between 1998-2001 and 2016-2017. Data were extracted from the Korea National Health and Nutrition Examination Survey (1998-2001 to 2016-2017; n=25,893). Non-alcoholic fatty liver disease (NAFLD) was defined as a hepatic steatosis index >36 in the absence of any other evidence of CLD. The definition of alcoholrelated liver disease (ALD) was excessive alcohol consumption (≥210 g/week for men and ≥140 g/week for women) and an ALD/NAFLD index >0. The prevalence of NAFLD increased from 18.6% (95% confidence interval [CI], 17.8-19.5%) in 1998-2001 to 21.5% (95% CI, 20.6-22.6%) in 2016-2017. During the same time period, increases were observed in the prevalence of obesity (27.0 vs. 35.1%), central obesity (29.4 vs. 36.0%), diabetes (7.5 vs. 10.6%), and excessive drinking (7.3 vs. 10.5%). ALD prevalence also increased from 3.8% (95% CI, 3.4-4.2%) to 7.0% (95% CI, 6.4-7.6%). In contrast, chronic hepatitis B decreased from 5.1% (95% CI, 4.6-5.5%) to 3.4% (95% CI, 3.0-3.8%). The prevalence of chronic hepatitis C was approximately 0.3% in 2016-2017. The prevalence of NAFLD and ALD increase among Korean adults. Our results suggest potential targets for interventions to reduce the future burden of CLD.


Pelvic exenteration for recurrent gynecologic malignancy: survival and morbidity analysis of the 45-year experience at UCLA.
To retrospectively assess the outcome of patients undergoing pelvic exenteration for recurrent or persistence gynecologic malignancy and the clinical features associated with outcome and survival. A review was conducted of patients who underwent pelvic exenteration over a 45-year period (1956-2001) at the UCLA Medical Center. Numerous clinical variables were analyzed, including time to relapse, type of exenteration and reconstructive operation, early (<60 days) and late (>60 days) morbidity, and survival. Variables were analyzed by chi-square and life-table analysis. Seventy-five patients (ages 26-74 years) had persistent cervical and vaginal (67) and uterine (8) cancer. Forty-six patients underwent total exenteration, 23 anterior, and 6 posterior. Sixty-nine (92%) patients underwent urinary diversion or neocystoplasty, 54 (72%) patients had a simultaneous neovagina created, and 43 of 52 (83%) patients who had a low colon resection had a primary reanastomosis. Twenty-nine patients died from recurrent malignancy, 28 were alive without disease, 11 were alive with disease, and 7 died from other causes at last follow-up. Survival for patients with cervical and vaginal cancer was 73% at 1 year, 57% at 3 years, and 54% at 5 years. Survival for patients with uterine cancer was 86% at 1 year, 62% at 3 and 5 years. The most frequent early morbidity was urinary tract infection, wound infection, and intestinal fistula; the most frequent late morbidity was urinary tract infection and intestinal obstruction. Pelvic exenteration in patients with recurrent cervical and vaginal malignancy is associated with a durable > 50% 5-year survival. Simultaneously performed pelvic reconstructive operations with a continent urinary diversion, the creation of a neovagina, and the reanastomosis of the colon with the formation of a J-pouch is now our standard; and these operations tend to improve the outcome of patients. Based on our initial experience, recurrent uterine corpus cancer in young women (< 55 years) should be included as an indication for the surgery.


Peri-operative cardiac protection for non-cardiac surgery.
Cardiovascular complications are an important cause of morbidity and mortality after non-cardiac surgery. Pre-operative identification of high-risk individuals and appropriate peri-operative management can reduce cardiovascular risk. It is important to continue chronic beta-blocker and statin therapy. Statins are relatively safe and peri-operative initiation may be beneficial in high-risk patients and those scheduled for vascular surgery. The pre-operative introduction of beta-blockers reduces myocardial injury but increases rates of stroke and mortality, possibly due to hypotension. They should only be considered in high-risk patients and the dose should be titrated to heart rate. Alpha-2 agonists may also contribute to hypotension. Aspirin continuation can increase the risk of major bleeding and offset the benefit of reduced myocardial risk. Contrary to the initial ENIGMA study, nitrous oxide does not seem to increase the risk of myocardial injury. Volatile anaesthetic agents and opioids have been shown to be cardioprotective in animal laboratory studies but these effects have, so far, not been conclusively reproduced clinically.


Isolated plexiform neurofibroma over left palm: a case report and review of literature.
Plexiform neurofibroma is common over the branches of trigeminal and cervical nerves over the face. Plexiform neurofibroma over palm is rare and affects the individuals with fine motor functions of hand. Here, we report a case of isolated plexiform neurofibroma over the palm with review of literature.


Diagnosis, Prognosis, and Therapy of Transthyretin Amyloidosis.
Transthyretin amyloidosis is a fatal disorder that is characterized primarily by progressive neuropathy and cardiomyopathy. It occurs in both a mutant form (with autosomal dominant inheritance) and a wild-type form (with predominant cardiac involvement). This article guides clinicians as to when the disease should be suspected, describes the appropriate diagnostic evaluation for those with known or suspected amyloidosis, and reviews the interventions currently available for affected patients.


Increased O6-alkylguanine alkyltransferase activity in Chinese hamster V79 cells following selection with chloroethylating agents.
Chinese hamster V79 lung fibroblasts express low levels (specific activity 2-4 fmol/mg protein) of O6-alkylguanine (O6-AG) alkyltransferase (ATase). In cells surviving selection with low doses (10 micrograms/ml) of the chloroethylating agent, mitozolomide (Mz), ATase activity was increased 5- to 8-fold. Repeated selection of such cells produced a maximal specific activity of 36-40 fmol/mg protein, whilst selection at 20 or 40 micrograms/ml result in specific activities of approximately 50 and 70 fmol/mg respectively. Only slight decreases in ATase activity were seen by 51 days after an initial selection with 10 micrograms/ml Mz. A similar effect was observed using chlorozotocin. Selected cells had a higher D37 for Mz (2.5-6.0 micrograms/ml) in comparison with control cell (D37, 0.8 micrograms/ml) but the D37s for nitrogen mustard and vincristine were closely similar in selected and control cells. Possible explanations for the increase in ATase activity are discussed.


Janus kinase 2 variants associated with the transformation of myeloproliferative neoplasms into acute myeloid leukemia.
Canonical Janus kinase 2 (JAK2) V617F and exon 12 mutations in myeloid neoplasms are well described. There are limited reports of other JAK2 variants of potential clinical relevance. This study was designed to survey JAK2 variants in patients with myeloproliferative neoplasms (MPNs) and acute myeloid leukemia (AML) and to determine their contributions to disease pathogenesis. Next-generation sequencing of the coding region of JAK2 and 27 other genes was performed on bone marrow DNA samples. The study population was classified into 3 cohorts: chronic MPNs only (the MPN cohort); MPNs transformed into AML (the MPN>>AML cohort); and AML only, with MPN>>AML patients excluded (the AML cohort). Testing was performed for 2154 patients, and non-V617F/non-exon 12 JAK2 sequence variants were identified in 114 (5.3%). They included 35 unique JAK2 variants across all functional domains. Sixteen of the 114 JAK2 variants occurred without somatic mutations in the remaining 27 genes. JAK2 variants were detected at a higher frequency in the MPN>>AML cohort (15.3%) in comparison with the MPN (4.6%; P < .001) and AML cohorts (5.2%; P < .001). Detected variants occurred at higher than expected frequencies in patients with MPNs and AML in comparison with the population, and N1108S had a significantly increased prevalence in patients with AML. A JAK2 variant in addition to JAK2 V617F (n = 13) in myelofibrosis was associated with an increased cumulative risk of transformation into AML (P = .003). Specific JAK2 variants detected in MPNs may be predictors for transformation into AML.


Prevalence, knowledge and factors associated with e-cigarette use among parents of secondary school children.
Identify prevalence rates and attitudes towards e-cigarette use among parents to inform prevention strategies designed to reduce uptake in young people. A mixed methods sequential study guided by the Theory of Planned Behaviour. This research involved two phases. Phase one was an elicitation study using focus groups, interviews and open-ended questionnaires (N = 17) to elicit parental behavioural, normative, and control beliefs around e-cigarette use. Findings from phase 1 were used to inform a questionnaire administered to a sample of 612 parents in phase 2. The aim of phase 2 was to identify and explain factors that influence parental attitudes and motivations towards e-cigarette use. Parents were recruited through post-primary schools and were sent a link to an online survey. Approximately 19% of parents had tried an e-cigarette, with 9% reporting current use. Sociodemographic variables, TPB constructs and knowledge of e-cigarettes, accounted for 43% and 60% of ever use and intention to use an e-cigarette, respectively. Intention, gender, age and free school meal entitlement were associated with ever use. Intention to use an e-cigarette was related to lower educational level, current smoking of traditional cigarettes, more positive attitudes, greater social pressure, having greater control over use and knowledge. Prevention strategies designed to reduce uptake in young people should raise awareness of the health risks of e-cigarette use, legislation and regulations and highlight the role parents play in encouraging young people to abstain from using an e-cigarette.


Investigation and management of the long-term ventilated premature infant.
Bronchopulmonary dysplasia (BPD) is a common complication of prematurity, and despite significant advances in neonatal care over recent decades its incidence has not diminished. Although most affected infants have mild disease requiring a short period of oxygen supplementation or respiratory support, severely affected infants can become dependent on positive pressure support for a prolonged duration. In such cases, investigations should be carried out to ascertain whether there are secondary disease processes exacerbating the child's respiratory status. In case of established severe BPD, respiratory support with non-invasive or invasive positive pressure ventilation is required. In this paper we discuss the indications for, and practicalities of, the various modalities available. Potential cardiorespiratory sequelae of BPD include recurrent respiratory infections, childhood wheezing illnesses, abnormalities of lung structure and function, and pulmonary hypertension.


Hepatocytes respond differently to major dietary trans fatty acid isomers, elaidic acid and trans-vaccenic acid.
It has been discussed if the adverse health effect associated with the ingestion of trans fatty acids correlates with the food source, as the composition of the isomers varies in different foods. We have investigated the hepatocellular responses to the predominant trans fatty acid isomers in industrially produced partially hydrogenated vegetable oils (elaidic acid) and products of ruminant origin (trans-vaccenic acid). The responses of HepG2-SF cells exposed to 100 μM fatty acids during 7 days were examined. Elaidic acid decreased the cellular proliferation rate while trans-vaccenic acid had no effect. Analysis of cellular triacylglycerol fractions showed, that both trans fatty acids were metabolized by HepG2-SF cells, although elaidic acid, to a higher degree than trans-vaccenic, accumulated in the triacylglycerol fraction. Proteome analysis revealed that the overlap of differentially regulated proteins only contained four proteins, suggesting that the two trans fatty acid isomers affect the cells in different ways. The data are available via ProteomeXchange with identifier PXD000760. Our investigations revealed that the hepatocellular response to the two most abundant dietary positional C18:1 trans fatty acid isomers differ substantially. In addition, the results suggest that trans-vaccenic acid does not affect cholesterol metabolism adversely compared to elaidic acid.


Insights from the Complete Genome Sequence of Bacillus circulans GN03, a Plant Growth-Promoting Bacterium Isolated from Pak Choi Cabbage (Brassica chinensis L.) Root Surface.
A plant growth-promoting rhizobacterium, Bacillus circulans GN03, was isolated from the root surface of pak choi cabbage. Here, we report the whole-genome sequence of the GN03 strain, which includes a circular chromosome (5,217,129 bp; GC content, 35.64%) and a plasmid (181,705 bp; GC content, 31.62%).


The metabolic status of internal intensive care patients as indicated by 3-methylhistidine excretion and nitrogen balance.
The metabolic status of 15 intensive care patients receiving a standardized total parenteral nutrition regimen was followed up to 15 days immediately after admission by measuring 3-methylhistidine, total nitrogen, and creatinine excretion. The average 3-methylhistidine excretion was within the normal range during the first 3 days, rising on day 4 and reached a maximum of 70% above normal values on day 5. It declined to within normal range thereafter in most of the patients. Mean values for creatinine excretion remained relatively constant within the normal range throughout the study. During all days 3-methylhistidine was negatively correlated with N-balance. It is concluded that these patients had increasing catabolism with a maximum on day 5 and that the catabolic condition was associated with an increased muscle protein breakdown.


Specific radial positions of centromeres of human chromosomes X, 1, and 19 remain unchanged in chromatin-depleted nuclei of primary human fibroblasts: evidence for the organizing role of the nuclear matrix.
Radial positions of centromeres of human chromosomes X, 1, and 19 were determined in the nuclei of primary fibroblasts before and after removal of 60%-80% of chromatin. It has been demonstrated that the specific radial positions of these centromeres (more central for the chromosome 19 centromere and more peripheral for the centromeres of chromosomes 1 and X) remain unchanged in chromatin-depleted nuclei. Additional digestion of nuclear RNA did not influence this specific distribution. These results strongly suggest that the characteristic organization of interphase chromosomes is supported by the proteinous nuclear matrix and is not maintained by simple repulsing of negatively charged chromosomes.


Diagnosis of catheter-related infections.
Catheter-related infections (CRI) are a major cause of febrile episodes in hospitalized patients. Additionally, approximately 40% of primary infections in intensive care patients are directly related to central venous catheters. Despite the clinical significance of CRI diagnostic procedures are still under debate. Clinical diagnosis which includes systemic signs of infection and suppuration at the catheter entry site is altogether a rare event. Therefore, most cases are still diagnosed by laboratory methods. Although the semiquantitative roll-plate technique is widely used and frequently regarded as gold standard, the disadvantages of a post-hoc diagnosis are obvious. In-situ techniques which leave the suspected catheter in place include differential blood cultures, skin and hub cultures and a new method of microscopic screening of blood drawn through the inflicted catheter. However, until now the true value of all these methods still lack unanimous acceptance. Further research is necessary to close the gap between clinical expectations and laboratory results.


Percutaneous fixation of displaced intraarticular fractures of the calcaneus. A retrospective case series study and a review of the literature.
To evaluate the outcome of displaced intraarticular calcaneal fractures (DIACFs) of a case series of patients who were treated with a percutaneous fixation technique. Eight patients were operated for DIACFs and they were evaluated for the outcome and complications in a mean follow up of 9 months (range: 6 - 12 months). At the last follow up the AOFAS score, the Boehlers' angle and the presence of any complication were noted. The time from injury to surgery was also reported. The correlation of the AOFAS score and the development of post traumatic subtalar arthritis to the type of fracture, to the post operative Boehler's angle and to the time from injury to surgery were investigated. The overall mean AOFAS (Americal Orthopaedic Foot and Ankle Society) score was 84,625 (Range: 73 - 96). The mean AOFAS score of type II and type III fractures was 87,667 and 75,500 respectively. The mean AOFAS score for fractures with a postoperative Boehler's angle of less than 10° and more or equal to 10° was 76,750 and 92,500 respectively. This difference was found to be statistically significant. The mean AOFAS score for fractures who were treated less or equal to six days and more than six days post injury was 91,250 and 78 respectively. Two out of four patients with a post operative Boehler's angle less than 10° developed post traumatic subtalar arthritis. No patient out of four for whom a Boehler's angle of more than 10° has been achieved, developed subtalar arthritis. No infection occurred in any of the patients. Percutaneous fixation is a safe and effective way of treating DIACFs. The outcome is directly related to the quality of reduction, which is significantly dependent to the timing of surgery. The earlier the fracture is operated the better the reduction by closed means is.


Seasonal allocation of dry mass and nitrogen in a fynbos endemic Restionaceae species Thamnochortus punctatus Pill.
The annual growth pattern of male plants of the endemic, dioecious fynbos species, Thamnochortus punctatus, revealed sequential growth of the various below-and above-ground organs. Root and rhizome development were favoured in the wet winter months while culm elongation occurred in the warmer but drier spring to summer period. The reproductive phase of development followed in the hot dry summer and autumn. The asynchronous pattern of growth is suggested to enable the plant to maximize utilization of scarce resources within the confines of the environmental controls determined by the mediterranean-climate. Maximum root and rhizome activity in the rainy season enabled the plant to absorb and store nitrogen in mature culms for later above ground organ development. As the absorption of nitrogen from senscing material is essential for this pattern of organ development to assist in alleviating nutrient scarcity the high degree of nitrogen reabsorption, 35 to 70% for branches and culms respectively, shows the potential importance of asynchronous organ growth in overcoming nitrogen limitation of plant growth. Comparisons of dry mass and nitrogen allocation patterns indicate that developmental strategies employed by evergreen, perennial plants in climatically and edaphically constrained environments cannot be deduced from biomass allocation patterns alone as they do not appear to reflect strategies evolved to overcome nutrient limitation.


Effects of a flaxseed mixture and plant oils rich in alpha-linolenic acid on the adenoma formation in multiple intestinal neoplasia (Min) mice.
Flaxseed is a dietary source of possible chemopreventive compounds such as lignans and alpha-linolenic acid (ALA). To study the effects of a flaxseed mixture on adenoma formation in multiple intestinal neoplasia mice, the mice were fed a diet containing 2.7 % flaxseed, 4.5 % fibre and 3.7 % ALA. To elucidate the effect of oils of the mixture we also composed a diet without flaxseed but with the same oil composition. The median number of adenomas in the small intestine was fifty-four for the control group, and thirty-seven (P=0.023) and forty-two (P=0.095) for flaxseed and oil groups, respectively. Compared with controls (1.2 mm), the adenoma size was smaller in the flaxseed (0.9 mm; P=0.002) and oil (1.0 mm; P=0.012) groups. Both diets changed the proportions of n-3 and n-6 fatty acids in the colonic mucosa. Membrane beta-catenin and protein kinase C (PKC)-zeta levels were reduced in the adenoma v. mucosa (P<0.05), and an inverse association was found between the membrane PKC-zeta in the mucosa and the adenoma number (r -0.460, P=0.008, n 32). Only the flaxseed diet increased lignan levels in the caecum (P=0.002) and in plasma (P=0.002) but they were not associated with tumour formation. The results suggest that the preventive effect of flaxseed on colon carcinogenesis may be due to the oil part of flaxseed, and the loss of beta-catenin and PKC-zeta from the membranes of the mucosal tissue may play a permissive role in intestinal tumour development.


Burkholderia cepacia immobilized on eucalyptus leaves used to simultaneously remove malachite green (MG) and Cr(VI).
A multifunctional biomaterial capable of simultaneously removing malachite green (MG) and Cr(VI) was prepared by immobilizing Burkholderia cepacia (B. cepacia) on eucalyptus leaves (EL). The maximum uptake of MG (60 mg/L) and Cr(VI) (20 mg/L) were 94.8% and 71.9% respectively, which was more efficient than when using EL or free cells alone. SEM-EDS demonstrated that B. cepacia was attached to EL and that Cr(VI) was biosorbed into the immobilized cells. FTIR showed that the degradation by functional groups of immobilized cells was in keeping with the products, detected by GC-MS, which suggested that MG could be degraded to 4-dimethylamino benzophenone and 4-dimethylamino phenol. The removal of both MG and Cr(VI) by EL immobilized cells fit the pseudo-second order adsorption kinetic model well (with both R2>0.983). The equilibrium adsorption capacity of MG was 9.59, 18.67 and 28.64 mg/g for initial MG concentrations of from 30, 60, 90 mg/L, respectively when the concentration of Cr(VI) was held constant at 20 mg/L. The adsorption capacity of Cr(VI) increased from 3.49, 7.68 to 9.79 mg/g as the initial Cr(VI) concentrations increased (10, 20, 30 mg/L) while the MG concentration was kept constant at 60 mg/L. The results showed that eucalyptus leaves as a low cost and eco-friendly material have some potential to be an effective immobilization for environmental applications.


A study of the binding energies of efavirenz to wild-type and K103N/Y181C HIV-1 reverse transcriptase based on the ONIOM method.
A three-layered ONIOM model was used to study the interactions between efavirenz and the binding sites of HIV-1 reverse transcriptase (RT): wild-type and double mutant K103N/Y181C enzyme forms. Binding energies were determined and compared to describe the loss of activity of efavirenz with the mutant HIV-1 RT binding pocket. The calculated binding energy for the efavirenz-K103N/Y181C HIV-1 RT complex is less than that with the wild-type complex by approximately 8 kcal mol(-1). The interaction energies, calculated at the MP2/6-31G(d,p) level between efavirenz and individual residues surrounding the binding pocket of the K103N/Y181C enzyme, demonstrate that the attractive interactions between efavirenz and residue positions 101 and 103 were less than those for wild-type RT by 5.52 and 3.62 kcal mol(-1), respectively. Understanding these interactions could be useful in the design of inhibitors specific for the HIV-1 RT allosteric site and that have greater potency against the mutant enzyme.


Comparison of adherence between twice- and thrice-daily regimens of oral amoxicillin/clavulanic acid.
Few studies have analysed adherence with antibiotic treatment in patients with respiratory tract infections. The aim of this study was to compare the compliance of patients taking a pharmacokinetically enhanced formulation of amoxicillin/clavulanic acid twice daily with that of patients taking the standard formulation thrice daily. Patients with suspected bacterial lower respiratory tract infections, pharyngitis and dental infections were included. Adherence was assessed by electronic monitoring, which recorded every opening of the patient's bottle of pills. The outcome variables were compliance with taking the medication, taking the correct dose and with timing of the dose. A total of 240 patients were enrolled (167 in the thrice-daily group and 73 in the twice-daily group). The percentage of doses taken was greater with the twice-daily regimen (84.5 ± 22.8%) than with the thrice-daily regimen (72.7 ± 20.1%; P < 0.001). Forty patients in the twice-daily group opened the container every 12 ± 6 h during at least 80% of the course (54.8%), while only 19.6% of the patients assigned to the thrice-daily formulation did so every 8 ± 4 h (P < 0.001). The percentage of patients who opened the container a satisfactory number of times per day was significantly higher among those taking the twice-daily regimen on days three, four, five, six and seven. Moreover, the thrice-daily group more frequently forgot to take the afternoon dose. The rate of compliance with amoxicillin/clavulanic acid therapy was very low. However, compliance with the new formulation that is taken twice-daily was significantly better.


Isolation and characterization of microcrystalline cellulose from oil palm biomass residue.
In this work, we successfully isolated microcrystalline cellulose (MCC) from oil palm empty fruit bunch (OPEFB) fiber-total chlorine free (TCF) pulp using acid hydrolysis method. TCF pulp bleaching carried out using an oxygen-ozone-hydrogen peroxide bleaching sequence. Fourier transform infrared (FT-IR) spectroscopy indicates that acid hydrolysis does not affect the chemical structure of the cellulosic fragments. The morphology of the hydrolyzed MCC was investigated using scanning electron microscopy (SEM), showing a compact structure and a rough surface. Furthermore, atomic force microscopy (AFM) image of the surface indicates the presence of spherical features. X-ray diffraction (XRD) shows that the MCC produced is a cellulose-I polymorph, with 87% crystallinity. The MCC obtained from OPEFB-pulp is shown to have a good thermal stability. The potential for a range of applications such as green nano biocomposites reinforced with this form of MCC and pharmaceutical tableting material is discussed.


Risk-Stratified Pancreatectomy Clinical Pathway Implementation and Delayed Gastric Emptying.
Delayed gastric emptying (DGE) is a frequent complication after pancreaticoduodenectomy (PD) that impairs recovery and quality of life. The purpose of this study was to assess the impact risk-stratified pancreatectomy clinical pathways (RSPCPs) had on delayed gastric emptying (DGE) and identify factors associated with DGE in a contemporary period. A single-institution, prospective database was queried for consecutive PDs during July 2011-November 2019. Using international definitions, DGE rates were compared between periods before and after RSPCPs were implemented in 2016, classifying patients according to their postoperative pancreatic fistula (POPF) risk. Risk factors were analyzed to identify modifiable targets. Among 724 elective PDs, 552 (76%) were for adenocarcinoma and 172 (24%) for other diagnoses. Of the 197 (27%) patients with DGE, 119 (16%) had type A, 41 (6%) type B, and 38 (5%) type C. In the overall cohort, DGE rates were higher with pylorus-preserving vs. classic hand-sewn reconstruction (odds ratio [OR] - 1.84; p < 0.001), postoperative abscess (OR - 2.54; p = 0.003), and non-white patients (p = 0.007), but lower after implementation of RSPCPs (OR - 0.34, p < 0.001). In the 374 patients treated with RSPCPs, only 17% (n = 65/374) developed DGE. Patients with protocol-compliant NGT removal ≤ 48 h were less likely to experience DGE (OR - 1.46, p = 0.042). Our data suggest that implementation of preoperatively assigned RSPCPs as a care bundle was the most important factor in decreasing DGE. These gains were accentuated in patients who underwent early nasogastric tube removal and had a classic hand-sewn gastro-jejunostomy reconstruction. Application of these modifiable factors is generalizable with low implementation barriers.


[Bone scanning in the diagnosis of infection bone disease (author's transl)].
Authors report their experience in bone scanning in patients with a diagnosis of osteomyelitis. Classical X-Ray and bacteriologic studies are of poor diagnostic value in cases early diagnosed and treated. Bone scanning is certainly a valuable alternative, but since gammagraphic pictures are not specific, they must be interpreted together with the clinical and analytical date.


Forage communication, nest moving recruitment, and prey specialization in the oriental ponerine Leptogenys chinensis.
In North Central Sri Lanka the ant Leptogenys chinensis specialises in feeding on fungus-growing Macrotermitinae (Odontotermes, Hypotermes), which are the commonest termites in this area. They are captured at their feeding sites. The ants recognize the termites by the scent that they emit. Workers and sexuals are the preferred prey. Termites of other taxa (Nasutitermitinae, Rhinotermitidae) are sometimes accepted and sometimes rejected. Refusal and acceptance are not correlated with the systematic position of the termites. Usually the nests of L. chinensis comprise 200-300 workers. Externally the female ergatoids do not differ from the workers. The ants live in naturally available cavities and move nests frequently. We investigated the communication of this species in relation to foraging and nest-moving. While foraging, single workers lay a light and nest-moving. While foraging, single workers lay a light exploration trail with venom. Successful scouts return to the nest and perform recruiting runs. Experiments with various blocked pheromone glands and decoys showed that the secretions of the poison gland and the Janet gland have to be applied to the ground. By this means groups of workers are recruited and led to a feeding place by a scout. When the scout was removed such groups would still, although slightly disturbed, find their way to the prey. Workers running alone are also observed. The secretion of the Janet gland has a recruiting effect, whereas the venom consists of two compounds: a compound of low volatility responsible for orientation, and a highly volatile compound which we interpret as being a way of estimating the age of the trail. In most cases, the recruited workers return singly to the nest. Retrieval of prey in groups is primarily observed with captured termite sexuals. Males use the trails to find and enter alien nests.In addition to the three chemical signals, stridulation with the gastral stridulatory organ is used as a mechanical signal in the frequent event of nest-moving. This induces general stridulation in the nest and initiates nest-moving, which is accomplished within a few minutes.


Somatosensory evoked potential monitoring of temporary middle cerebral artery occlusion during aneurysm operation.
Somatosensory evoked potentials (SEPs) in response to median nerve stimulation were used as a guide to cortical function during temporary occlusion of the distal M1 segment of the middle cerebral artery (MCA) in the surgical treatment of five large aneurysms of the MCA bifurcation. MCA occlusion times ranged from 8 to 19 minutes under moderate hypothermia at 28.8 degrees to 30.3 degrees C. SEPs were preserved for variable times during MCA occlusion, ranging from no increase in latency after 13 minutes of occlusion to severe deterioration after 6 minutes. In no case was MCA occlusion maintained for longer than 3 minutes in the presence of a severely disturbed SEP. Recovery of the SEP to its preoperative relationship with that of the nonoperated hemisphere was seen in all cases before the end of operation. All patients were awake after rewarming at the end of operation without any neurological deficit. Monitoring the SEP pertaining to the territory of a cerebral artery during its temporary occlusion can help avoid ischemic damage and will allow the surgeon to take advantage of the several benefits of this technique in aneurysm surgery.


Non-sporeforming anaerobic bacteria in clean surgical wounds--air and skin contamination.
The contamination of clean surgical wounds with anaerobic and aerobic bacteria was studied in 52 hip operations. In addition to wound samples, samples from air and the patients' skin were taken. The median of the total number of bacteria isolated from the wounds was 26 colony-forming units (cfu). The median percentage of anaerobic bacteria in the wound counts was 30. Propionibacterium spp. were found in 71 per cent of the wounds and anaerobic or microaerophilic cocci, most often Peptococcus spp., were found in 23 per cent. In six of 43 patients the same bacterial flora was seen in the skin samples and wounds. The geometric mean of the total number of bacteria in the air was 70.3 cfu/m3. Of these the median percentage of anaerobic bacteria was 30.3. When operating clothing of a disposable fabric (Barrier 450, Johnson & Johnson) was used, the counts of airborne bacteria were a little less than half those found when conventional cotton clothing was worn. Probably because of the overall low air counts in the operating theatre and the great variability in the individual bacterial counts from the operation wounds, a significant decrease in wound contamination was not observed. A positive correlation was found between the duration of operation and wound contamination.


Determining informativity of marker typing for genetic counseling in a pedigree.
For the situation of a Mendelian disease linked to a genetic marker, a new method is described that allows evaluating for genetic counseling the information potentially available from the linked marker before the marker data are actually obtained, that is, prior to drawing blood for marker typing. For a consultand in a family pedigree, the method determines the risk distribution (small families) or an approximation to it (larger families) and calculates the probability that the risk will deviate beyond certain limits from its a priori value, which exists without marker data, for example, that the risk will be smaller than 0.10 or larger than 0.90. The method was applied here to a pedigree of 15 individuals for which analytical calculations would be difficult to carry out.


Urocortin 1 and Urocortin 2 induce macrophage apoptosis via CRFR2.
Macrophages undergo apoptosis as a mechanism of regulating their activation and the inflammatory reaction. Macrophages express the Corticotropin-Releasing Factor Receptor-2 (CRFR2) the endogenous agonists of which, the urocortins, are also present at the site of inflammation. We have found that urocortins induced macrophage apoptosis in a dose- and time-dependent manner via CRFR2. In contrast to lipopolysaccharide (LPS)-induced apoptosis, the pro-apoptosis pathway activated by urocortins involved the pro-apoptotic Bax and Bad proteins and not nitric oxide, JNK and p38MAPK characteristic of LPS. In conclusion, our data suggest that endogenous CRFR2 ligands exert an anti-inflammatory effect via induction of macrophage apoptosis.


The role of multimodal ultrasonic flow imaging in Thyroid Imaging Reporting and Data System (TI-RADS) 4 nodules.
Color Doppler imaging (CDFI), contrast-enhanced ultrasound (CEUS), and superb micro-vascular imaging (SMI) are used to observe blood flow characteristics in Thyroid Imaging Reporting and Data System (TI-RADS) 4 nodules. The ability of these techniques to distinguish benign from malignant nodules was investigated. A total of 75 TI-RADS 4 nodules were examined using CDFI, SMI, and CEUS. The blood flow characteristics shown by the three methods were added to the current TI-RADS classification to establish a new TI-RADS classification. The value of the three methods and the diagnostic accuracy of the new and old TI-RADS classification were compared. SMI better captured type II flow in benign nodules and type III flow in malignant nodules relative to CDFI. Malignant nodules detected with CEUS manifested mainly with hypo-enhancement, whereas benign nodules showed iso- and hyper-enhancement. The areas under the receiver operating characteristic (ROC) curves (AUC) obtained through the aforementioned flow distribution models were 0.690 (CDFI), 0.840 (SMI), 0.910 (CEUS), and 0.903 (CEUS and SMI combined mode), respectively. The diagnostic value of CEUS was the highest. Joint inspection using SMI with CEUS showed certain advantages in sensitivity, although the overall accuracy was equal to that of CEUS alone. Except for CDFI, the AUC of the new TI-RADS classification was significantly higher than that of the old one. Perforating vessels and low enhancement were independent predictors of thyroid carcinoma. Both SMI and CEUS visualized lower-velocity blood flow within TI-RADS 4 nodules. The new TI-RADS classification described here could improve diagnostic accuracy.


The expression level of threonine synthase and cystathionine-gamma-synthase is influenced by the level of both threonine and methionine in Arabidopsis plants.
The biosynthesis pathways of the essential amino acids methionine and threonine diverge from O-phosphohomoserine, an intermediate metabolite in the aspartate family of amino acids. Thus, the enzymes cystathionine-gamma-synthase (CGS) in the methionine pathway and threonine synthase (TS), the last enzyme in the threonine pathway, compete for this common substrate. To study this branching point, we overexpressed TS in sense and antisense orientation in Arabidopsis plants with the aim to study its effect on the level of threonine but more importantly on the methionine content. Positive correlation was found not only between TS expression level and threonine content, but also between TS/threonine and CGS expression level. Plants expressing the sense orientation of TS showed a higher level of threonine, increased expression level of CGS, and a significantly higher level of S-methylmethionine, the transport form of methionine. By contrast, plants expressing the antisense form of TS showed lower levels of threonine and of CGS expression level. In these antisense plants, the methionine level increased up to 47-fold compared to wild-type plants. To study further the effect of threonine on CGS expression level, wild-type plants were irrigated with threonine and control plants were irrigated with methionine or water. While threonine increased the expression level of CGS but reduced that of TS, methionine reduced the expression level of CGS but increased that of TS. This data demonstrate that both methionine and threonine affect the two enzymes at the branching point, thus controlling not only their own level, but also the level of each other. This mechanism probably aids in keeping the levels of these two essential amino acids sufficiently high to support plant growth.


Studies on productivity and characterization of polygalacturonase from Aspergillus giganteus submerged culture using citrus pectin and orange waste.
Polygalacturonases are part of the group of enzymes involved in pectin degradation. The aim of this work was to investigate some of the factors affecting polygalacturonase production by an Aspergillus giganteus strain and to characterize this pectinolytic activity. Several carbon sources, both pure substances and natural substrates, were tested in standing cultures, and the best results were obtained with orange bagasse and purified citrus pectin. On citrus pectin as sole carbon source, the highest extracellular activity (9.5 U/ml and 40.6 U/mg protein) was obtained in 4.5-day-old cultures shaken at 120 rpm, pH 3.5 and 30 degrees C, while on orange bagasse, the highest extracellular activity (48.5 U/ml and 78.3 U/mg protein) was obtained in 3.5-day-old cultures shaken at 120 rpm, pH 6.0 and 30 degrees C. Optimal polygalacturonase activity was observed in assays conducted at pH 5.5-6.5 and 55-60 degrees C. The activity showed good thermal stability, with half-lives of 90 and 30 min when incubated at 55 and 60 degrees C, respectively. High stability was observed from pH 4.5 to 8.5; more than 90% of the activity remained after 24 h in this pH range.


Distribution of adrenomedullin-like immunoreactivity in the brain of the adult sea lamprey.
Adrenomedullin (AM) is a neuropeptide widely distributed in vertebrates. In jawed vertebrates it has been localized in distinct regions of the central nervous system by means of antisera against human AM because the molecule seems to be well conserved across species. In this study, we have analyzed the localization of AM-like immunoreactive (AM-ir) cell bodies and fibers throughout the brain of the adult sea lamprey Petromyzon marinus, by using immunohistochemistry. Several AM-ir cell populations were found in the basal plate of the secondary prosencephalon, being more numerous in the hypothalamus, as well as two in the diencephalon and one in the mesencephalon; in addition two cell populations were found in the rhombencephalic alar plate, one in the isthmic region and other in the nucleus of the solitary tract. Immunolabeled fibers were widespread throughout the lamprey brain, but were more abundant in the basal plate. Of particular interest was the conspicuous innervation of the striatum by AM-ir fibers. In addition, our results indicate that AM-ir cells and fibers are present in the lamprey hypothalamo-neurohypophyseal system, suggesting that AM plays some important role in the control of pituitary gland function.


Menopausal state in breast cancer: how reliable is the data?
Despite the high importance of the menopausal state for the management of breast cancer, above all, when planning antihormonal adjuvant therapy, the menopausal state cannot be defined at the time of diagnosis ina significant proportion of women. The scope of uncertainties regarding the recording of the menopausal state in a cohort of patients with breast cancer is evaluated. Menopause is a cornerstone both in breast cancer (BC) pathophysiology and in clinical management. The scope of uncertainties regarding the recording of the menopausal state in a cohort of patients with BC is evaluated in this study. The data of a Swiss prospective relational BC database that covered a 20-year period (1990-2009; n=1457) was analyzed. For the definition of menopause, the guidelines of the National Comprehensive Cancer Network were used. The menopausal state was unclear in 150 patients (10.2%). Of these, 122 (81.3%) had undergone a hysterectomy before menopause; in 28 women (18.7%), an endocrine therapy obscured the patient's actual endocrine status. When taking only the subgroup of women in which menopause usually occurs (45-55 years) into consideration, the menopausal state was unclear in 91 cases of 337 women (27.0%). From the entire cohort, the date of last menstruation remained obscure in 450 patients (30.9%). Despite the high importance of the menopausal state for the management of BC, above all, when planning antihormonal adjuvant therapy, the menopausal state was unable to be defined at the time of BC diagnosis in a significant proportion of women. The dilemma that menopause cannot be assessed in some BC cases is increasingly being recognized. Close cooperation between oncologists and endocrinologists is desirable to establish an optimal, individually tailored therapy for women with an unclear menopausal state due to hormonal therapies, hysterectomy, or chemotherapy.


Cross-border strategies for access to healthcare in violent conflict - A scoping review.
The geographical reconfiguration of healthcare systems in times of violent conflict is increasingly being recognised in academic literature. This includes conflict-induced, cross-border travel for medical treatment. Yet the conceptual approach to this healthcare-seeking behaviour, by a population here referred to as cross-border population, remains poorly understood. This scoping review identifies academic literature on cross-border populations to map the current approach to cross-border populations and to propose a research agenda. The study used a scoping review following the Joanna Briggs Institute Scoping Review methodology. We included articles on conflicts between 1980 and 2019. A total of 53 articles met the inclusion criteria. From these articles, we distinguished four types of studies on cross-border healthcare: Direct analysis, implicit analysis, clinical research, and identification. The 45 articles belonging to the first three categories were then searched for themes specifically relevant to healthcare for cross-border populations and linked with sub-themes such as border crossing time and the types of healthcare available. These themes were structured into three main areas: access to care; quality of care; and governance of care. Our analysis then describes the available knowledge, documented practices, and challenges of cross-border healthcare specifically in conflict settings. A better understanding of cross-border healthcare systems is required to inform local practices and develop related regional and international policies. While the reviewed literature provides some highlights on various practices of cross-border healthcare, there are many gaps in available knowledge of this topic. To address these gaps, our study proposes a research framework outlining key themes and research questions to be investigated by signposting where major research and operational gaps remain. This facilitates well-directed future work on cross-border therapeutic geographies in the context of armed conflict and furthers understanding of a hitherto largely ignored area of the international healthcare system.


Determining factors associated with the prevalence of knowledge, attitude, and practice in seeking skilled maternal healthcare services among women in a remote area of Gesha district.
Skilled health care is essential for the mother's and newborn's health and well-being during pregnancy, labor, and the postpartum period. This study aimed to analyze women's knowledge, attitudes, and practices while requesting competent assistance for maternity healthcare in Gesha District, Southwest Region of Ethiopia. A community-based cross-sectional study design was conducted from September 20, 2021 to October 19, 2021. A total of 424 mothers participated in this study and a systematic sampling technique was used to select the respondents. The data were collected using a pretested and structured questionnaire. Statistical software SPSS-20 and R-4.1.2 were used to enter and analyze the data respectively. The factors associated with the prevalence of Knowledge, Attitude, and Practice in seeking Skilled Maternal Healthcare Services were identified using descriptive analysis and a binary logistic regression model. This study result revealed that the overall proportions of good knowledge, positive attitude, and good practice in seeking skilled maternal health care services were 39.15%, 37.5%, and 34.67% respectively. Estimated odds of having knowledge, attitude, and practice were as follows: for having age between 20-24 years at first pregnancy 1.859, 1.86, and 1.799; having a plan for pregnancy 2.74,2.315 and 2.579; mothers attended elementary education 2.337, 2.565 and 3.312; having maternal age 20-24 years 4.336,4.989 and 5.870; maternal age 25-29 years 2.917, 3.794 and 4.017; maternal age 35-49 years 2.837, 2.991 and 3.412; having husbands who had attended elementary education level 2.736, 2.542 and 2.134; secondary and above education 3.464, 3.360 and 2.508; rich mothers 2.261, 1.995 and 2.452; having antenatal care 4 times and above 2.606, 2.570, 2.682; having transportation access 1.921, 1.956 and 2.404; having media access 1.979, 2.171 and 2.715 respectively. The odds of having attitude and practice respectively were as follows: married 1.762, and 2.208; having medium wealth index 1.933 and 2.424. The odds of having previous pregnancy complications was 2.147 which significantly affect the practice of seeking skilled maternal care assistance. This study discovered that the study participants' knowledge, attitude, and practice of skilled maternal health care are low. Associated factors included age at first pregnancy, planned pregnancy, maternal education level, husband's education level, maternal age, antenatal care service visits, transport access, and access to media were found to significantly affect the knowledge, attitude, and practice of the respondents in seeking skilled maternal care assistance in common. The household wealth index was also associated with attitude. Pregnancy complications, current marital status, and household wealth index also significantly affect the practice of seeking skilled maternal care assistance. As a result of the findings, initiatives to increase women's knowledge, attitudes, and use of expert maternal health services in the research area are needed for women residing in rural areas.


Intermediate Levels of Antibiotics May Increase Diversity of Colony Size Phenotype in Bacteria.
Antibiotics select for resistant bacteria whose existence and emergence is more likely in populations with high phenotypic and genetic diversity. Identifying the mechanisms that generate this diversity can thus have clinical consequences for drug-resistant pathogens. We show here that intermediate levels of antibiotics are associated with higher levels of phenotypic diversity in size of colony forming units (cfus), within a single bacterial population. We examine experimentally thousands of populations of bacteria subjected to different disturbance levels that are created by varying antibiotic concentrations. Based on colony sizes, we find that intermediate levels of antibiotics always result in the highest phenotypic variation of this trait. This result is supported across bacterial densities and in the presence of three different antibiotics with two different mechanisms of action. Our results suggest intermediate levels of a stressor (as opposed to very low or very high levels) could affect the phenotypic diversity of a population, at least with regards to the single trait measured here. While this study is limited to a single phenotypic trait within a single species, the results suggest examining phenotypic and genetic variation created by disturbances and stressors could be a promising way to understand and limit variation in pathogens.


193-nm excimer laser sclerostomy using a modified open mask delivery system in rhesus monkeys with experimental glaucoma.
Excimer laser sclerostomy is a new glaucoma filtration procedure in which the argon fluoride excimer laser at 193 nm is delivered ab externo through a modified open mask system incorporating an en-face air jet to dry the target area and preserve hemostasis during ablation and a conjunctival plication mechanism, which allows the conjunctival and scleral wounds created by through-and-through ablation to separate once the mask is removed. No preparatory dissection of the conjunctiva is required. Five 200-microns and five 500-microns sclerostomies were formed by ablation at a pulse repetition rate of 20 Hz and a fluence per pulse of 400 mJ/cm2 in fellow eyes of five rhesus monkeys with experimental glaucoma. Overall, seven of the ten eyes attained a functional result, with intraocular pressures remaining below 21 mmHg for 6 +/- 1 days and rising to the pre-operative level after 10 +/- 3 days without adjunctive antifibroblast medication. The duration of filtration for 200-microns and 500-microns sclerostomies was similar, and parallels that previously observed for posterior lip sclerectomy in the same animal model. The three eyes with no functional result all had incorrectly positioned sclerostomies. Choroidal detachment and significant shallowing of the anterior chamber did not occur. Excimer laser sclerostomy appears to be a viable technique for filtration, provided that mask placement is accurate.


Retraction: Creation of ultrasound and temperature-triggered bubble liposomes from economical precursors to enhance the therapeutic efficacy of curcumin in cancer cells.
[This retracts the article DOI: 10.1039/C6RA14584A.].


Treatment strategy optimization for patients with non-small-cell lung cancer harboring EGFR mutation: a Delphi consensus.
To stablish a consensus on the treatment strategy for advanced non-small-cell lung cancer (aNSCLC) with epidermal growth factor receptor mutation (EGFRm) in Spain. After a systematic literature review, the scientific committee developed 33 statements in 4 fields: molecular diagnosis (10 items); histologic profile and patient clinical characteristics (7 items); first-line (1L) treatment in EGFRm aNSCLC (8 items); and subsequent-line treatment (8 items). A panel of 31 experts completed 2 Delphi online questionnaires rating their degree of agreement/disagreement for each statement through a 1-9 range scale (1-3 = disagree, 7-9 = agree). Consensus was reached if 2/3 of the participants are in the median range. In the first Delphi round consensus was achieved for 24/33 of the statements. One of the assertions was deleted, proceeding to a second round with the eight remaining questions with no consensus or in the range of indeterminacy. Determination of the EGFR status from tissue and analysis of the different biomarkers are two important variables that influenced treatment decision in patients with aNSCLC. 1L treatment should be the best therapeutic option, independently of the subsequent lines of treatment. For patients with the most common activating mutations osimertinib was considered the most efficient and safe 1L option. In case of disease progression, a new biopsy was needed. A consensus document is proposed to optimize the treatment strategy for untreated patients with a NSCLC with EGFR sensitizing mutations.


Association of maternal Body Mass Index and parity on induced labor stages.
Obesity is a widespread pandemic and obstetric care must adapt to meet the needs of obese pregnant women. Little is known about the impact of Body Mass Index (BMI) on the induction of labor (IOL). Therefore, our objective was to evaluate if the duration of the first and second stages of IOL is affected by maternal BMI in nulliparous and multiparous women. We included singleton pregnancies at term with cephalic presentation whose labor was induced from June 2018 to December 2019. Women were divided into two groups according to pre-pregnancy BMI in normal weight and obese women. A total of 668 women with IOL were included in the study, among them, 349 had a normal weight and 321 were obese. The first stage of labor was longer in obese multiparous than normal-weight women (normal weight 81.98±71.7 vs. obese 134.3±158.1 min, P=0.000), while the second stage resulted significantly shorter (normal weight 22.2±27.8 vs. obese 14.3±14.2 min, P=0.000). The total time elapsed from IOL beginning and delivery was significantly higher in obese nulliparous (normal weight 10.4±19.7 vs. obese 22.0±26.2 h, P=0.000). Operative vaginal deliveries, emergency cesarean section, and failed IOL resulted to be similar between the groups. Obese multiparous women have longer first stages of labor while shorter second stages. The total time for induced obese nulliparous to reach delivery is higher than the normal weight. It might be reasonable to reconsider the partographs according to maternal BMI in case of induced labor for future obstetric practice.


Free and protein-bound homocysteine and cysteine in cystathionine beta-synthase deficiency: interrelations during short- and long-term changes in plasma concentrations.
Homocysteine interacts in a complex way in the plasma with cysteine and plasma proteins. To explore the interrelations between free and protein-bound homocysteine and cysteine during short- and long-term changes in plasma levels, free and bound homocysteine and cysteine were measured in 13 patients with homocystinuria due to cystathionine beta-synthase deficiency. Levels were measured during oral methionine loads (4 g/m2 body surface area) and after oral betaine (3 g twice daily). In six pyridoxine-responsive patients, free and bound levels of homocysteine and cysteine, measured 4 to 24 hours after oral methionine, changed in a parallel manner. Similar close tracking occurred in fasting plasma samples collected from two pyridoxine-nonresponsive patients before and during betaine therapy. Oral betaine given to seven pyridoxine-nonresponsive patients decreased free and bound homocysteine and increased free and bound cysteine toward normal levels during monitoring periods of up to 300 days. In these studies as the level of homocysteine decreased, the proportion of protein-bound homocysteine and cysteine increased. The present study establishes that changes in bound and free levels of either homocysteine or cysteine track closely in the short-term (four hours or less) and generally also in the long-term (up to 300 days).


State-of-the-science on postacute rehabilitation: measurement and methodologies for assessing quality and establishing policy for postacute care.
We present an overview of commonly used postacute outcome measures and review new methodologies for postacute assessment. We question the impact that current measurement has had on improvement of quality of postacute care (PAC) and its utility in informing health policy. We suggest that Donabedian's model of health care quality should be endorsed for measurement. Specifically, measurement of outcomes and process should be used jointly in assessment of PAC.


Glutamate receptor 4 as a fluid biomarker for the diagnosis of psychiatric disorders.
Psychiatric disorders are widely underreported diseases, especially in their early stages. So far, there is no fluid biomarker to confirm the diagnosis of these disorders. Proteomics data suggest the synaptic protein glutamate receptor 4 (GluR4), part of the AMPA receptor, as a potential diagnostic biomarker of major depressive disorder (MDD). A novel sandwich ELISA was established and analytically validated to detect GluR4 in cerebrospinal fluid (CSF) samples. A total of 85 subjects diagnosed with MDD (n = 36), bipolar disorder (BD, n = 12), schizophrenia (SCZ, n = 12) and neurological controls (CON, n = 25) were analysed. The data exhibited a significant correlation (r = 0.74; CI:0.62 to 0.82; p < 0.0001) with the antibody-free multiple reaction monitoring (MRM) mass spectrometry (MS) data. CSF GluR4 levels were lower in MDD (p < 0.002) and BD (p = 0.012) than in CON. Moreover, subjects with SCZ described a trend towards lower levels than CON (p = 0.13). The novel GluR4 ELISA may favour the clinical application of this protein as a potential diagnostic biomarker of psychiatric disorders and may facilitate the understanding of the pathophysiological mechanisms behind these disorders.


Social avoidance and social adjustment in Chinese preschool migrant children: the moderating role of teacher-child relationships.
This study aimed to explore the moderating role of teacher-child relationships in the relations between social avoidance and social adjustment (i.e., prosocial behavior, peer exclusion, and anxious-fearful behavior) in Chinese migrant preschoolers. Participants were 148 migrant children aged 4-6 years (82 boys, Mage = 62.32, SD = 6.67) attending kindergartens in Shanghai, People's Republic of China. Mothers reported children's social avoidance, and teachers rated teacher-child relationships and children's social adjustment. Results indicated that social avoidance was positively related to peer exclusion and negatively related to prosocial behavior. Teacher-child relationships moderated those associations. Specifically, teacher-child closeness buffered the relationship between social avoidance and peer exclusion, whereas teacher-child conflict exacerbated the relations between social avoidance and peer exclusion and anxious-fearful behavior. The current finding informs us of the importance of improving teacher-child closeness and reducing teacher-child conflict to buffer the negative adjustment among socially avoidant young children who migrated from rural-to-urban China. The findings also highlight the importance of considering the meaning and implication of social avoidance for migrant preschoolers in Chinese culture.


Apicoaortic conduit and cerebral perfusion in mixed aortic valve disease: a computational analysis.
The revival of the apicoaortic conduit has attracted new interest in this alternative treatment for severe aortic stenosis unsuitable for conventional valve replacement. However, doubts still exist about the perfusion of the epiaortic vessels after apicoaortic conduit implantation, especially when severe aortic stenosis is associated with aortic valve insufficiency. The aim of the study was to evaluate the perfusion of the epiaortic vessels (innominate artery, left carotid artery and left subclavian artery) in cases of mixed aortic valve disease before and after apicoaortic conduit implantation. Starting from the data of a real patient with severe aortic stenosis and mild aortic insufficiency who underwent apicoaortic conduit implantation, we created a computational model where severe aortic valve stenosis was associated with different grades of aortic insufficiency (mild, medium and moderate). A total of six combinations were analysed. In all simulations, the more severe the concomitant aortic insufficiency, the more the flow through the epiaortic vessels was diminished. After apicoaortic conduit implantation, there was an absolute augmentation of the median output in each epiaortic vessel compared with the same combination of mixed aortic valve disease before implantation. Interestingly, retrograde flow from the conduit in the descending aorta was minimal and did not contribute to the improved output of the epiaortic vessels. The computational analysis suggested a protective effect, rather than steal phenomenon, of the apicoaortic conduit towards the cerebral perfusion, even in cases of mixed aortic valve disease.


Successful closure of a tracheocutaneous fistula after tracheostomy using two skin flaps: a case report.
A tracheocutaneous fistula may develop when a tracheostomy orifice epithelializes during a prolonged course of healing or undernutrition. Various techniques for closing such fistulae have been reported. However, a standard procedure has not yet been established. We, herein, present a case involving a 35-year-old woman who developed a tracheocutaneous fistula after tracheostomy. We closed the fistula using two skin flaps to cover the tracheal lumen and skin defect, respectively. The advantage of this technique is that it allows the tracheal lumen to be covered by inversed skin epithelium and ensures that the suture line of the skin does not match up with that of the subcutaneous tissue.


Dissecting Spatial and Temporal Sensing in Dictyostelium Chemotaxis Using a Wave Gradient Generator.
External cues that dictate the direction of cell migration are likely dynamic during many biological processes such as embryonic development and wound healing. Until recently, how cells integrate spatial and temporal information to determine the direction of migration has remained elusive. In Dictyostelium discoideum, the chemoattractant cAMP that directs cell aggregation propagates as periodic waves. In light of the fact that any temporally evolving complex signals, in principle, can be expressed as a sum of sinusoidal functions with various frequencies, the Dictyostelium system serves as a minimal example, where the dynamic signal is in the simplest form of near sinusoidal wave with one dominant frequency. Here, we describe a method to emulate the traveling waves in a fluidics device. The text provides step-by-step instructions on the device setup and describes ways to analyze the acquired data. These include quantification of membrane translocation of fluorescently labeled proteins in individual Dictyostelium cells and estimation of exogenous cAMP profiles. The described approach has already helped decipher spatial and temporal aspects of chemotactic sensing in Dictyostelium. More specifically, it allowed one to discriminate the temporal and the spatial sensing aspects of directional sensing. With some modifications, one should be able to implement similar analysis in other cell types.


To a young basic scientist, about to embark on a program of translational research.
From recent commentaries about the role of basic behavior scientists in translational research, I distill some advice to young investigators who seek to apply their basic science training to translational studies. Among the challenges are (a) devising use-inspired research programs that complement, and are not redundant with, existing efforts in basic and applied behavior analysis; and (b) making tactical decisions, such as the selection of methods and collaborators, based on the research topic rather than, necessarily, the existing traditions in behavioral research. Finally, it must be recognized that although use-inspired basic research has the potential to attract support to basic laboratories and contribute to "saving the world," neither of these outcomes is guaranteed. I discuss the relative risks for basic scientists who proceed with use-inspired basic research rather than ignore such translational questions.


Fine needle aspiration cytology of benign adrenal cortical nodules. A comparison of cytologic findings with those of primary and metastatic adrenal malignancies.
To determine the specific cytomorphologic criteria for diagnosing benign adrenal cortical nodule (BACN) by fine needle aspiration (FNA). The smears from 162 adrenal FNA biopsies were reviewed. A diagnosis of BACN was rendered in 50 cases (31%). The cytologic features of BACN were compared to those of primary and metastatic malignant tumors of the adrenal gland, and the size of BACN as measured by computed tomography was recorded. Bubbly, vacuolated, lipid background; large, cohesive tissue fragments with a syncytial nesting arrangement admixed with sinusoidal endothelial cells; and abundant oval, round, bare nuclei are the three cytomorphologic features most often seen in BACN. The combination of these three features was observed in 40 cases (89%) of BACN and was seen in 4 cases of metastatic carcinoma (6%) in which there was also coexisting adrenal cortical hyperplasia. None of the other primary or metastatic malignancies showed this combination of cytomorphologic features. The mean size of BACN was 2.5 cm, with a standard deviation of 1 cm and a range of 1-5 cm. The sizes of the four metastatic carcinomas with coexisting adrenal cortical hyperplasia were 6.5, 6, 5 and 1.5 cm, respectively (mean, 4.8). Our data suggest that combined cytologic features of bare nuclei; bubbly, vacuolated background; and large, cohesive tissue fragments with sinusoidal endothelial cells in a small adrenal nodule (< 3.5 cm) are highly specific to FNA diagnosis of BACN.


A principal component analysis of coagulation after trauma.
Clotting factor abnormalities underlying acute traumatic coagulopathy are poorly understood, with application of traditional regression techniques confounded by colinearity. We hypothesized that principal components analysis (PCA), a pattern-finding and data reduction technique, would identify clinically predictive patterns in the complex clotting factor milieu after trauma. Plasma was prospectively collected from 163 critically injured trauma patients. Prothrombin; factors V, VII, VIII, IX, X; D-dimer; activated and native protein C; and antithrombin III levels were assayed and subjected to nonlinear PCA to identify principal components (PCs). Of 163 patients, 19.0% were coagulopathic on admission. PCA identified 3 significant PCs, accounting for 67.5% of overall variance. PC1 identified global clotting factor depletion; PC2 the activation of protein C and fibrinolysis; and PC3 factor VII elevation and VIII depletion. PC1 score correlated with penetrating injury and injury severity, predicting coagulopathy (odds ratio [OR], 4.67; p < 0.001) and mortality (OR, 1.47; p = 0.032). PC2 score correlated with injury severity, acidosis, and shock, and significantly predicted ventilator-associated pneumonia (OR, 1.59; p = 0.008), acute lung injury (OR, 2.24; p < 0.001), multiorgan failure (OR, 1.83; p = 0.002), and mortality (OR, 1.62; p = 0.006) but was not associated with international normalized ratio (INR)-based or partial thromboplastin time (PTT)-based coagulopathy (p > 0.200). PC3 did not significantly predict outcomes. PCA identifies distinct patterns of coagulopathy: depletion coagulopathy predicts mortality and INR/PTT elevation, while fibrinolytic coagulopathy predicts infection, end-organ failure, and mortality, without detectable differences in INR or PTT. While depletion coagulopathy is intuitive, fibrinolytic coagulopathy may be a distinct but often overlapping entity with differential effects on outcomes.


Faà di Bruno's formula and the distributions of random partitions in population genetics and physics.
We show that the formula of Faà di Bruno for the derivative of a composite function gives, in special cases, the sampling distributions in population genetics that are due to Ewens and to Pitman. The composite function is the same in each case. Other sampling distributions also arise in this way, such as those arising from Dirichlet, multivariate hypergeometric, and multinomial models, special cases of which correspond to Bose-Einstein, Fermi-Dirac, and Maxwell-Boltzmann distributions in physics. Connections are made to compound sampling models.


Myostatin: biology and clinical relevance.
Myostatin is a negative regulator of muscle mass. Important advances in our understanding of the complex biology of this factor have revealed the therapeutic potential of antagonizing the myostatin pathway. Here we present the rationale for evaluating anti-myostatin therapies in human muscle-wasting disorders.