Use of real-world data and clinical registries to identify new uses of existing vascular endografts: combined use of GORE EXCLUDER Iliac Branch Endoprosthesis and GORE VIABAHN VBX Balloon Expandable Endoprosthesis.
To assess the feasibility of collecting, examining and reporting observational, real-world evidence regarding the novel use of the GORE EXCLUDER Iliac Branch Endoprosthesis (IBE) in conjunction with the GORE VIABAHN VBX Balloon Expandable Endoprosthesis (IBE+VBX stent graft). Multicentre retrospective cohort study. Four real-world data sources were used: a national quality improvement registry, a statewide clinical research network, a regional quaternary health system and two tertiary academic medical centres. In total, 30 patients with 37 IBE+VBX stent graft were identified. Of those, the mean age was 72±10.2 years and 90% were male. The cohort was 77% white, 10% black, 3% Hispanic and 10% other. Outcome measures included: proportion of percutaneous vs open surgical access, intensive care admission, intensive care unit (ICU) length-of-stay (LOS), total LOS, postoperative complications, discharge disposition and 30-day mortality. The majority (89%) of cases were performed percutaneously, 5% required surgical exposure following failed percutaneous access and 6% required open surgical exposure outright. Nearly half (43%) required intensive care admission with a median ICU LOS of 1 day (range: 1-2). Median total LOS was 1 day (IQR: 1-2). There were zero postoperative myocardial infarctions, zero reported leg embolisations and no reported reinterventions. Access site complications were described in 1 of 28 patients, manifesting as a haematoma or pseudoaneurysm. Ultimately, 97% were discharged to home and one patient was discharged to a nursing home or rehabilitation facility. There were no 30-day perioperative deaths. This project demonstrates the feasibility of identifying and integrating real-world evidence, as it pertains to an unapproved combination of endovascular devices (IBE+VBX stent graft), for short-term outcomes analysis. This new paradigm of evidence has potential to be used for device monitoring, submission to regulatory agencies, or consideration in indication expansions and approvals with further efforts to systematise data collection and transmission mechanisms.


Use of Chitosan and Other Natural Compounds Alone or in Different Strategies with Copper Hydroxide for Control of Grapevine Downy Mildew.
Grapevine downy mildew (GDM) is one of the most serious diseases of grapevines. Limitations to the use of copper-based products in organic agriculture according to the European Union (EU) regulation EU/2002/473 and the later EU Commission implementing regulation 2018/1981 have promoted a search for alternatives. This 5-year field trial evaluated the effectiveness of several strategies against GDM using different chitosan-based formulations and application rates in comparison with other natural compounds applied individually or with copper hydroxide. Trials were performed in commercial vineyards with different environmental conditions and grapevine cultivars. For the natural compounds applied as individual treatments, a 0.5%/0.8% chitosan formulation provided the best protection against GDM; the other compounds and formulations were less effective. When copper hydroxide use was halved by combining it with the natural compounds according to three different strategies, the GDM incidence, severity, and McKinney index were reduced, particularly for copper hydroxide applied in combination with the 0.5%/0.8% chitosan formulation. The 0.5%/0.8% chitosan formulation alone and with copper hydroxide provided good protection against GDM during both high-pressure and low-pressure disease seasons. Therefore, chitosan represents a good alternative to copper formulations for the control of GDM and both organic and integrated disease management.


Tracheostomy with thyroidectomy: indications, management and outcome: a prospective study.
This study aims to determine the indications, course and outcome of pre-operative and post-thyroidectomy tracheostomy. This is a prospective descriptive study conducted in Khartoum Teaching Hospital in the period between March 2000 and March 2005. Fifty-nine patients had tracheostomy out of 964 thyroidectomy patients, giving an incidence of 6%. The decision of doing tracheostomy was taken intra-operatively in 41 patients (69%), all presenting with strider. In 25 of those 41 patients there was intra-operative tracheal deformity with narrowing (>50% of tracheal circumference on radiology) and gland adherence to the tracheal wall; the remaining 16 patients had tracheomalacia. Of those 41 patients, 25 presented with severe strider and needed urgent surgery (5 with recurrent anaplastic carcinoma, 5 with intrathoracic goitres that necessitated median sternotomy and 15 with huge goitres (of whom 7 were recurrent goitres). In the remaining 18 patients (31%) emergency post-operative tracheostomy was done following endotracheal extubation up to 48 h post-operatively. There were 2 deaths (3.4%); one patient died due to tracheostomy care and the other from myocardial infarction. Tracheostomy is a safe procedure and gives a good alternative to delayed endotracheal extubation in post-thyroidectomy patients expected to have respiratory failure in places where post-operative anaesthetic care is lacking.


[Current epidemiological and clinical aspects of tuberculosis: A study in the Hospital of Pisa].
To describe epidemiological and clinical features of tuberculosis (tbc) cases identified recently in the Pisa area (Tuscany, Italy). We performed a retrospective study of all cases of tbc notified to the Public Health Service in Pisa during January 1996-December 1998. The diagnosis of tbc was made following the criteria of the Public Health Ministry. Eighty-eight patients affected by tbc were identified. Diagnosis was microbiologically proven (positive culture for M. tuberculosis) in 42 patients. Sixty-nine patients had pulmonary tbc, 14 extrapulmonary and 5 mixed tbc. Mean age was 56.4 years (range 16-87 years). Nineteen patients were extra European Community citizens. The incidence of tbc (N./100,000) was 8.4 in 1996, 10 in 1997 and 3.2 in 1998. In 5.7% of the cases tbc was associated with advanced HIV infection. The chest X-ray showed pleural effusion in 12 patients and cavitation in 26 patients. Fever was not present in 36.4% of the patients at the moment of diagnosis. 12% of the isolated strains of M. tuberculosis were in vitro multidrug-resistant. The data presented showed an important rate of tbc in Pisa, similar to the incidence of tbc reported by other studies carried out on a national scale. We have yet to understand if the decreased rate observed in 1998 represents a new trend. The isolation rate of multidrug-resistant strains of M. tuberculosis in Pisa seems higher than the rates reported in other geographical areas. Therefore monitoring of M. tuberculosis susceptibility to antimicrobial agents is necessary.


Correlated Protein Function Prediction via Maximization of Data-Knowledge Consistency.
Conventional computational approaches for protein function prediction usually predict one function at a time, fundamentally. As a result, the protein functions are treated as separate target classes. However, biological processes are highly correlated in reality, which makes multiple functions assigned to a protein not independent. Therefore, it would be beneficial to make use of function category correlations when predicting protein functions. In this article, we propose a novel Maximization of Data-Knowledge Consistency (MDKC) approach to exploit function category correlations for protein function prediction. Our approach banks on the assumption that two proteins are likely to have large overlap in their annotated functions if they are highly similar according to certain experimental data. We first establish a new pairwise protein similarity using protein annotations from knowledge perspective. Then by maximizing the consistency between the established knowledge similarity upon annotations and the data similarity upon biological experiments, putative functions are assigned to unannotated proteins. Most importantly, function category correlations are gracefully incorporated into our learning objective through the knowledge similarity. Comprehensive experimental evaluations on the Saccharomyces cerevisiae species have demonstrated promising results that validate the performance of our methods.


New species and additional records of Tetrabothrus Bernhauer from China (Coleoptera, Staphylinidae, Aleocharinae).
Material of the lomechusine genus Tetrabothrus Bernhauer, 1915 from China was studied. A new species is described and illustrated under the name T. xizangensis Z.-Q. Yan and L.-Z. Li, sp. nov. (Xizang). Tetrabothrus japonicus is reported in China for the first time, and the new locality for T. puezti and T. inflexus are given. All Chinese species are mapped, and an identification key is provided.


Neuroprotection of microglia conditioned media from apoptotic death induced by staurosporine and glutamate in cultures of rat cerebellar granule cells.
Microglia, the immune cells of the mammalian CNS, have often been indicated as dangerous effector cells for their activation in response to traumatic CNS injuries or immunological stimuli and for their involvement in many chronic neurodegenerative diseases. Recently, several in vitro and in vivo studies have emphasized that microglial activity is essential in promoting neuronal survival. We have tested the efficacy of media directly conditioned by microglia or conditioned by microglia after having been exposed to apoptotic neurons, towards neuroprotection of rat cerebellar granule cells (CGCs) challenged with staurosporine or glutamate. Apoptotic death of CGC caused by staurosporine, as well as by a mild excitotoxic stimulus delivered through sub-chronic glutamate treatment, was significantly counteracted by microglia conditioned media. On the other hand, an acute excitotoxic insult delivered through a short pulse of glutamate exposure in the absence of magnesium and resulting in a mix of apoptotic and necrotic death was only marginally counteracted by microglia conditioned media. The present results extend the available information regarding the neuroprotective role of microglia and support the usefulness of employing the culture approach for perspective identification of neuroprotective factors released by these cells. Furthermore, the use of media previously exposed to apoptotic neurons to elicit the neuroprotective response of microglia, indicate the feasibility to re-create also in the isolated culture conditions, at least some of the elements at the basis of neuron/microglia cross-talk.


Prospective validation in epithelial tumors of a gene expression predictor of liver metastasis derived from uveal melanoma.
Predicting the risk of liver metastasis can have important prognostic and therapeutic implications, given the availability of liver-directed therapy. Uveal melanoma has a striking predisposition for liver metastasis despite the absence of anatomical proximity. Understanding its biology may uncover factors promoting liver metastasis in other malignancies. We quantified gene expression by RNAseq in 76 uveal melanomas and combined with public data in a meta-analysis of 196 patients. The meta-analysis of uveal melanoma gene expression identified 63 genes which remained prognostic after adjustment for chromosome 3 status. Two genes, PTP4A3 and JPH1, were selected by L1-penalized regression and combined in a prognostic score. The score predicted liver-specific relapse in a public pan-cancer dataset and in two public colorectal cancer datasets. The score varied between colorectal consensus molecular subtypes (CMS), as did the risk of liver relapse, which was lowest in CMS1. Additional prospective validation was done by real-time PCR in 463 breast cancer patients. The score was significantly correlated with liver relapse in hormone receptor positive tumors. In conclusion, the expression of PTP4A3 and JPH1 correlates with risk of liver metastasis in colorectal cancer and breast cancer. The underlying biological mechanism is an interesting area for further research.


Determinants of cutaneous leishmaniasis among students in Delanta district, Northeast Ethiopia: A case-control study.
Cutaneous leishmaniasis (CL) is the most common form of leishmaniasis that causes skin lesions on exposed parts of the body. It is endemic in over 170 districts and highly prevalent in the northern and southern parts of Ethiopia. Thus, the aim of this study was to assess the determinants of CL among students of Wegeltena secondary school in Delanta district, Northeast Ethiopia. This unmatched case-control study was conducted from January 4 to 20, 2021 at Wegeltena secondary school. Cases were students who had an active lesion of CL and controls were students who had never been infected with CL (no active lesions). A simple random sampling technique was utilized to select participants in the control group. Data were collected by using a pretested, interviewer-administered structured questionnaire. Bivariable and multivariable logistic regression analyses were performed and variables were declared determinants of CL at a p value of <0.05. A total of 225 students (58 cases and 167 controls) participated in the study. The mean age of cases and controls was 18.6 (SD ± 0.99 years) and 18.5 years (SD ± 1.17 years), respectively. In this study, 74.1% of cases and 51.5% of controls have been living in rural areas. Furthermore, being male (adjusted odds ratio [AOR] = 4.11; 95% confidence interval [CI]: 1.94-8.69), rural residents (AOR = 2.95; 95% CI: 1.33-6.52), living in areas where caves (AOR = 3.63; 95% CI: 1.24-10.59), nearby forest (AOR = 4.04; 95% CI: 1.42-11.51), and hyrax available (AOR = 2.43; 95% CI: 1.16-5.08) were significantly associated with CL. In our study, sociodemographic and environmental factors were found to be determinants of CL. Therefore, reducing outdoor activities, wearing protective clothes, use of insecticide-treated nets, and destruction of sand fly breeding sites shall be implemented targeting the rural population that resides in areas where forests, caves, and hyraxes are prominent.


Cardiac variation of inferior vena cava: new concept in the evaluation of intravascular blood volume.
Evaluation of the intravascular blood volume is an important assessment in emergency and critical care medicine. Measurement of the inferior vena cava (IVC) respiratory variation by ultrasound echography is useful, but it entails subjective problems. We have hypothesized that IVC cardiac variation is also correlated with intravascular blood volume and analyzed it automatically using computer software of two kinds, later comparing the results. Snakes, software to track boundaries by curve line continuity, and template matching software were incorporated into a computer with an ultrasound machine to track the short-axis view of IVC automatically and analyze it with approximation by ellipse. Eight healthy volunteers with temporary mild hypovolemia underwent echography before and after passive leg raising and while wearing medical anti-shock trousers. IVC cardiac variation was visually decreased by both leg raising and medical anti-shock trousers. The collapse index (maximum - minimum/maximum) of area during three cardiac beats was decreased showing a good relationship to fluid load simulations; 0.24 ± 0.03 at baseline versus 0.11 ± 0.01 with leg raising and 0.12 ± 0.01 with medical anti-shock trousers. In conclusion, IVC cardiac variation has the potential to provide an evaluation of water volume. It presents some advantages in mechanical analysis over respiratory variation. At the very least, we need to exercise some caution with cardiac variation when evaluating respiratory variation.


Fetal haemoglobin production and the sickle gene in the oases of Eastern Saudi Arabia.
Fetal haemoglobin (HbF) levels have been measured in 137 normal (AA) subjects, 109 with the sickle-cell trait (AS) and 237 with sickle-cell anaemia (SS) from the oasis population of Eastern Saudi Arabia. In addition the proportion of F-cells has been estimated in 71 AA, 51 AS and 34 SS subjects. The mean HbF% (and the range of F-cells %) were: AA 0.77 (0.3--18), AS 1.38 (2.3--43) and SS 25.56 (33--98). The distribution of Hb F was always heterocellular. The influence of pregnancy accounts for most of the excess female subjects with sickle-cell trait showing raised Hb F and F-cells. Whilst the normal Arabs and those with sickle-cell trait did not differ from comparable groups of American blacks, both the % Hb F and % F-cells in Saudi Arabian patients with sickle-cell anaemia were much higher than in Blacks. The high Hb F levels in individuals with sickle-cell anaemia are not due to coexistent glucose-6-phosphate dehydrogenase deficiency or alpha-thalassaemia trait, and the Hb F level showed an inverse correlation with the degree of haemolysis. These findings indicate that the unusually elevated levels of Hb F are not due to an associated high frequency of a gene for hetero-cellular hereditary persistence of fetal haemoglobin in the oasis population, but rather from a genetically determined absolute increase in Hb F production related in some way to the SS genotype.


CFTR mutations and host susceptibility to Pseudomonas aeruginosa lung infection.
The susceptibility of cystic fibrosis patients to bacterial pathogens is associated with deficient airway antimicrobial peptide activity, and airway-surface-liquid dehydration with decreased transport velocity and hypersecretion of mucus. Susceptibility to Pseudomonas aeruginosa infection has been linked to the role of the cystic fibrosis transmembrane conductance regulator protein as a receptor for P. aeruginosa. Binding of P. aeruginosa coordinates lung clearance as part of innate immunity. The function of CFTR in innate immunity to P. aeruginosa infection is multifactorial, with one key component being a specific ligand-receptor interaction between the protein and the microbe.


Effect of varying concentration of ethanol on systemic hemodynamics and regional circulation.
The effect of ethanol (0.5 g/kg, IV) at different concentrations (30%, 60%, and 90%) was studied in male cats using radioactive microspheres on systemic hemodynamics and regional circulation. Ethanol produced a significant fall in systolic, diastolic and mean blood pressure. A significant reduction in heart rate, left ventricular work, cardiac output and total peripheral resistance was also observed. No change occurred in stroke volume. A significant decrease in blood flow to left ventricle, right ventricle and interventricular septum was observed, but the vascular resistance of these regions was unaltered. Brain blood flow was not affected by various concentrations of ethanol. The vascular resistance significantly decreased in spinal cord, medulla, pons, midbrain, hypothalamus, thalamus, caudate nucleus, cerebellum and cortex. The average brain blood flow (ml/min/100 g) was 35.63 in control, 37.17 in 30%, 35.56 in 60% and 35.05 in 90% ethanol-treated cats. Spleen, liver, pancreas, gastrointestinal tract, skin, muscle and bone did not show any significant change in the blood flow, while vascular resistance following ethanol treatment. The blood passing through the arteriovenous shunts was significantly decreased by ethanol. It is concluded that ethanol produces marked cardiovascular changes which are not affected by varying the concentration of ethanol.


Biological and clinical significance of cancer stem cell plasticity.
In the past decade, the traditional view of cancers as a homogeneous collection of malignant cells is being replaced by a model of ever increasing complexity suggesting that cancers are complex tissues composed of multiple cell types. This complex model of tumorigenesis has been well supported by a growing body of evidence indicating that most cancers including those derived from blood and solid tissues display a hierarchical organization of tumor cells with phenotypic and functional heterogeneity and at the apex of this hierarchy are cells capable of self-renewal. These "tumor imitating cells" or "cancer stem cells" drive tumorigenesis and contribute to metastasis, treatment resistance and tumor relapse. Although tumor stem cells themselves may display both genetic and phenotypic heterogeneity, recent studies have demonstrated that cancer stem cells maintain plasticity to transition between mesenchymal-like (EMT) and epithelial-like (MET) states, which may be regulated by the tumor microenvironment. These stem cell state transitions may play a fundamental role in tumor progression and treatment resistance. In this review, we discuss the emerging knowledge regarding the plasticity of cancer stem cells with an emphasis on the signaling pathways and noncoding RNAs including microRNAs (miRNA) and long non-coding RNAs (lncRNAs) in regulation of this plasticity during tumor growth and metastasis. Lastly, we point out the importance of targeting both the EMT and MET states of CSCs in order to eliminate these lethal seeds of cancers.


Assessing Right Ventricular Function in the Perioperative Setting, Part II: What About Catheters?
An-depth assessment of right ventricular function is important in a many perioperative settings. After exploring 2-dimensional echo-based evaluation, other proposed monitoring modalities are discussed. Pressure-based methods of right ventricular appraisal is discussed. Flow-based assessment is reviewed. An overview of the state of current right ventricular 3-dimensional echocardiography and its potential to construct clinical pressure-volume loops in conjunction with pressure measurements is provided. An overview of right ventricular assessment modalities that do not rely on 2-dimensional echocardiography is discussed. Tailored selection of monitoring modalities can be of great benefit for the perioperative physician. Integrating modalities offers optimal estimations of right ventricular function.


Urinary excretion of the water channel aquaporin 2 correlated with the pharmacological effect of tolvaptan in cirrhotic patients with ascites.
The water channel aquaporin 2 (AQP2) at the apical membrane of renal collecting duct cells mediates water reabsorption. The expression of AQP2 at the apical membrane is tightly regulated by vasopressin and was quantitated by measurement of the urinary form by a recently developed ELISA. Tolvaptan, an antagonist of vasopressin type 2 receptor, inhibits water reabsorption in cirrhosis. The aim of this study was to determine the correlation between the pharmacological effect of tolvaptan and the dynamics of urinary AQP2 levels. Tolvaptan was administered to 41 cirrhotic patients with ascites unresponsive to standard diuretic therapy. Urinary excretion of AQP2 and urinary osmolarity were measured at the baseline and at 4, 8, and 24 h after administration of tolvaptan. At the baseline, urinary AQP2/creatinine ratios were significantly higher in cirrhotic patients with ascites than in healthy controls (P < 0.0001). After administration of tolvaptan, urinary AQP2/creatinine ratios decreased by 45.0 % at 4 h and 77.0 % at 8 h. Similarly, urinary osmolarity decreased by 42.0 % at 4 h and 41.5 % at 8 h. Urinary AQP2 levels and urinary osmolarity significantly correlated at the baseline and at all time points after tolvaptan administration. The degree of the decrease in urinary AQP2 levels and degree of the decrease in urinary osmolarity correlated significantly at 4 h (r = 0.452, P = 0.009) and 8 h (r = 0.384, P = 0.030) after tolvaptan administration. These results indicate that the vasopressin-AQP2 system plays a major role in fluid retention in cirrhosis and that the pharmacological effect of tolvaptan to inhibit water reabsorption can be monitored by measurement of the dynamics of urinary AQP2 levels.


Relationship between maternal exposure to heavy metal titanium and offspring congenital heart defects in Lanzhou, China: A nested case-control study.
Previous studies have found that exposure to heavy metals increased the incidence of congenital heart defects (CHDs). However, there is a paucity of information about the connection between exposure to titanium and CHDs. This study sought to examine the relationship between prenatal titanium exposure and the risk of CHDs in offspring. We looked back on a birth cohort study that was carried out in our hospital between 2010 and 2012. The associations between titanium exposure and the risk of CHDs were analyzed by using logistic regression analysis to investigate titanium concentrations in maternal whole blood and fetal umbilical cord blood. A total of 97 case groups and 194 control groups were included for a nested case-control study. The [P50 (P25, P75)] of titanium were 371.91 (188.85, 659.15) μg/L and 370.43 (264.86, 459.76) μg/L in serum titanium levels in pregnant women and in umbilical cord serum titanium content in the CHDs group, respectively. There was a moderate positive correlation between the concentration of titanium in pregnant women's blood and that in umbilical cord blood. A higher concentrations of maternal blood titanium level was associated with a greater risk of CHDs (OR 2.706, 95% CI 1.547-4.734), the multiple CHDs (OR 2.382, 95% CI 1.219-4.655), atrial septal defects (OR 2.367, 95% CI 1.215-4.609), and patent ductus arteriosus (OR 2.412, 95% CI 1.336-4.357). Dramatically higher concentrations of umbilical cord blood levels had an increased risk of CHDs and different heart defects. Titanium can cross the placental barrier and the occurrence of CHDs may be related to titanium exposure.


Hypomethylation of ras oncogenes in primary human cancers.
We have examined the methylation status of two cellular oncogenes, c-Ha-ras and c-Ki-ras, in primary human carcinomas and the adjacent analogous normal tissues from which the tumors derived. The c-Ha-ras gene was hypomethylated in six of eight carcinomas, including five colonic adenocarcinomas and one small cell lung carcinoma, when compared to adjacent normal tissues. The c-Ki-ras gene was hypomethylated to a lesser extent in two colonic adenocarcinomas. This is the first demonstration of alterations in methylation of cellular oncogenes in human cancer.


Cocaine exposure during the early postnatal period diminishes medial frontal cortex Gs coupling to dopamine D1-like receptors in adult rat.
The effect of cocaine exposure during early postnatal ages on coupling of dopamine (DA) D(1)- and D(2)-like receptors to their respective Gs/olf and Gi was examined in striatum and medial frontal cortex (MFC). Sprague-Dawley rats were subcutaneously injected with either 50 mg/kg cocaine or vehicle during postnatal day (PnD) 11-20 and dopaminergic D(1)- and D(2)-like receptor signaling was evaluated at PnD 60. Results showed that cocaine exposure did not affect the magnitude of both DA D(1)- and D(2)-like receptor coupling to their respective Gs/olf and Gi in striatum. However, in the medial frontal cortex, the basal and the DA D(1)-like receptor and Gs association were reduced in cocaine-exposed brains. However, there was no change in basal or DA D(2)-like receptor-Gi linkage in medial frontal cortex. Since frontal cortex plays a critical role in regulating cognition and working memory, disruption of DA-modulated circuits or alteration of dopaminergic activity resulting from postnatal cocaine exposure may result in abnormal responses to environmental challenges leading to long-term behavioral changes.


Magnetic cellulose nanocrystals hybrids reinforced phase change fiber composites with highly thermal energy storage efficiencies.
The intrinsic intermittence of solar energy raises the necessity for thermal energy storage (TES) systems to balance the contradiction between energy supply and demand energy. This work experimentally provides solid-liquid phase change materials (PCMs) with sufficient storage capacity and discharging rate to offer heating for agriculture products by enhancing heat transfer in phase change fiber composites (PCF). To achieve this, we prepared dipole responsive magnetic/solar-driven PCF composites reinforced with magnetic cellulose nanocrystals hybrids (MCNC). The obtained PCF/MCNC-5% showed excellent magnetic property with a saturation magnetization (MS) value of 1.3 emu/g and effective latent heat phase change enthalpies of 69.2 ± 3.5 J/g - 83.1 ± 4.2 J/g. More importantly, PCF/MCNC-5% showed robust high magnetic to thermal energy storage efficiency of 32.5 % and solar light accelerated energy storage efficiency of 58.5 %. These advantages make the PCF composites promising and more desirable for drying and preservation of the fruits and other agriculture products.


Cardiovascular effects of airborne particulate matter: A review of rodent model studies.
In recent year, animal models have been growingly used to increase our knowledge about the toxicity of PM and underlying mechanisms leading to cardiovascular diseases. In this article, we review the current state of knowledge and findings of studies investigating the cardiovascular effects of PM in rats and mice. The six main areas covered in this review include: I) nature of particulate matter and toxicity mechanisms, II) systemic inflammation, III) heart rate and heart rate variability, IV) histopathological effects, V) atherosclerosis, VI) thrombosis, and VI) myocardial infarction. This review showed that animal model studies have been successful to bring new insights into the mechanisms underlying PM-induced cardiovascular diseases. However, there are some areas that the exact mechanisms are still unclear. In conclusion, investigating the cardiovascular effects of PM in vivo or interpreting the results should attempt to justify the role of different PM compositions, which may vastly affect the overall cytotoxicity of particles.


Can a facial action coding system (CatFACS) be used to determine the welfare state of cats with cerebellar hypoplasia?
The impaired motor skills of cats living with cerebellar hypoplasia (CH) suggests they would be unable to practice normal behaviour, one of the five welfare needs. This study aimed to explore the use of facial action coding system (CatFACS) as a welfare assessment tool for cats with CH. Facial expressions (action units [AUs]) were defined as neutral/positive or negative by recording healthy cats (n = 89) during presumed aversive or relaxed scenarios. CH cats (n = 33) were then filmed and their facial expressions compared to those of the presumed positively- and negatively-valenced healthy cats. Sixteen negative AUs were defined. CH cats performed more of these than healthy cats (p = 0.023) in the relaxed scenario. There was no difference in AU expression between three levels of CH severity (mild, moderate or severe) (p = 0.461). Cats perform distinct AUs when experiencing negatively-valenced arousal, the presence or absence of these AUs could be used to infer the welfare of healthy and CH cats. As there was no difference in AU expression between the three levels of CH severity, the behavioural restrictions CH imposes on cats does not necessarily indicate lower welfare and the reasons why CH cats perform more negatively associated AUs warrant further research.


Effect of patellar strap and sports tape on pain in patellar tendinopathy: A randomized controlled trial.
Numerous athletes with patellar tendinopathy (PT) use a patellar strap or sports tape during sports. This study's aim was to investigate the short-term effect of these orthoses on patellar tendon pain. Participants performed the single-leg decline squat, vertical jump test, and triple-hop test under four different conditions (patellar strap, sports tape, placebo, and control). Subsequently, participants practiced sports as usual for 2 weeks; during 1 week, they were assigned to one of the four conditions. Pain was measured with the visual analog scale (VAS). In total, 97 athletes with PT [61% male, age 27.0 (SD8.1), VISA-P 58.5 (SD12.7)] were analyzed. On the single-leg decline squat, the VAS pain score reduced significantly in the patellar strap (14 mm, P = 0.04) and the sports tape condition (13 mm, P = 0.04), compared with control, but not placebo. A significant decrease in VAS pain during sports was found in the sports tape (7 mm, P = 0.04) and placebo group (6 mm, P = 0.04). The VAS pain score two hours after sports decreased significantly in the patellar strap, sports tape and placebo group (8-mm, P < 0.001, 10 mm, P = 0.001 and 7 mm, P = 0.03, respectively). This study's findings indicate that an orthosis (including placebo tape) during sports can reduce pain in PT patients in the short term.


Caregiver burden and correlates among caregivers of children and adolescents with psychiatric morbidity: a descriptive cross sectional study.
To determine levels and correlates of caregiver burden among caregivers of children and adolescents with psychiatric morbidity. Over a period of four months, a total of 252 caregivers of children and adolescents with psychiatric morbidity were recruited. Data on socio-demographic factors, psychiatric morbidity among caregivers, and level of caregiver burden was collected using a researcher-designed socio-demographic questionnaire, Mini International Neuropsychiatric Interview, and Zarit burden interview, respectively. Data was analysed using statistical package for social sciences (SPSS) version 21. Females (n = 211, 83.7%) and mothers (n = 182, 72.2%) accounted for the majority of the study participants. The majority of caregivers reported moderate to severe caregiver burden; (n = 100, 39.7%). Being single or separated (B = -6.91, p = 0.001, β = -0.18) and presence of psychiatric morbidity (B = 7.44, p = 0.009, β = 0.22) in the caregiver significantly contributed to the high levels of caregiver burden. Caregivers of children and adolescents with psychiatric morbidity suffer high levels of caregiver burden. A multidisciplinary approach to management of children with psychiatric morbidity to address challenges faced by the caregivers may alleviate the burden; thereby improving clinical outcomes of children and adolescents with psychiatric morbidity.


When parents disclose BRCA1/2 test results: their communication and perceptions of offspring response.
BRCA1/2 testing is not recommended for children, as risk reduction measures and screening are not generally recommended before 25 years old (YO). Little is known about the prevalence and predictors of parent communication to offspring and how offspring respond to this communication. Semi-structured interviews were conducted with parents who had BRCA1/2 testing and at least 1 child <25 YO. Logistic regressions were utilized to evaluate associations with communication. Framework analysis was utilized to analyze open-ended responses. A total of 253 parents completed interviews (61% response rate), reporting on 505 offspring. Twenty-nine percent of parents were BRCA1/2 mutation carriers. Three hundred thirty-four (66%) offspring learned of their parent's test result. Older offspring age (P ≤ .01), offspring gender (female, P = .05), parents' negative test result (P = .03), and parents' education (high school only, P = .02) were associated with communication to offspring. The most frequently reported initial offspring responses were neutral (41%) or relief (28%). Thirteen percent of offspring were reported to experience concern or distress (11%) in response to parental communication of their test results. Distress was more frequently perceived among offspring learning of their parent's BRCA1/2 positive or variant of uncertain significance result. Many parents communicate their BRCA1/2 test results to young offspring. Parents' perceptions of offspring responses appear to vary by offspring age and parent test result. A better understanding of how young offspring respond to information about hereditary risk for adult cancer could provide opportunities to optimize adaptive psychosocial responses to risk information and performance of health behaviors, in adolescence and throughout an at-risk life span.


Total Center Percutaneous Coronary Intervention Volume and 30-Day Mortality: A Contemporary National Cohort Study of 427 467 Elective, Urgent, and Emergency Cases.
The relationship between procedural volume and prognosis after percutaneous coronary intervention (PCI) remains uncertain, with some studies finding in favor of an inverse association and some against. This UK study provides a contemporary reassessment in one of the few countries in the world with a nationally representative PCI registry. A nationwide cohort study was performed using the national British Cardiovascular Intervention Society registry. All adult patients undergoing PCI in 93 English and Welsh NHS hospitals between 2007 and 2013 were analyzed using hierarchical modeling with adjustment for patient risk. Of 427 467 procedures (22.0% primary PCI) in 93 hospitals, 30-day mortality was 1.9% (4.8% primary PCI). 87.1% of centers undertook between 200 and 2000 procedures annually. Case mix varied with center volume. In centers with 200 to 399 PCI cases per year, a smaller proportion were PCI for ST-segment-elevation myocardial infarction (8.4%) than in centers with 1500 to 1999 PCI cases per year (24.2%), but proportionally more were for ST-segment-elevation myocardial infarction with cardiogenic shock (8.4% versus 4.3%). For the overall PCI cohort, after risk adjustment, there was no significant evidence of worse, or better, outcomes in lower volume centers from our own study, or in combination with results from other studies. For primary PCI, there was also no evidence for increased or decreased mortality in lower volume centers. After adjustment for differences in case mix and clinical presentation, this study supports the conclusion of no trend for increased mortality in lower volume centers for PCI in the UK healthcare system. https://www.clinicaltrials.gov. Unique identifier: NCT02184949.


Activity of natural killer cells in normal pregnancy and edema-proteinuria-hypertension gestosis.
Natural killer cytotoxicity of peripheral blood lymphocytes in normal pregnancy and edema-proteinuria-hypertension (EPH) gestosis was investigated and compared to natural killer cytotoxicity in lymphocytes of normal nonpregnant control donors. These lymphocytes were also compared for their ability to respond to interferon treatment in vitro. Natural killer activity was found to be only slightly decreased in normal pregnant women but was found to be increased in patients with EPH gestosis. Interferon treatment of peripheral lymphocytes caused strong enhancement of natural killer activity in lymphocytes of normal pregnant women but resulted in only weak activities in lymphocytes from patients with EPH gestosis. We consequently concluded that pre-natural killer lymphocyte subpopulations from patients with EPH gestosis have already been activated by a presently still unknown stimulator.


Characterization of extramedullary tumors in a case of Ph-positive chronic myelogenous leukemia: possible involvement of immature T lymphocytes.
A 42-year-old male with chronic myelogenous leukemia (CML) developed acute transformation associated with subcutaneous tumors. Histopathologic examinations of the tumors were done on two occasions; the first study revealed reticulum cell sarcoma-like features, and the second suggested a blastoma. Chromosomal analysis showed that the cells of the tumors originated from the CML clone. The cells had a negative reaction for myeloperoxidase by electron microscopy. Furthermore, biochemical and surface marker studies revealed that the tumor cells contained a significant terminal transferase activity. However, they did not express E- or EAC-rosette receptors, Ia-like antigens, or common ALL antigens.


Analysis of risk factors for cervical lymph node metastasis of papillary thyroid microcarcinoma: a study of 268 patients.
To investigate the risk factors of cervical lymph node (LN) metastasis in papillary thyroid microcarcinoma (PTMC) patients. We retrospectively analyzed the clinicopathologic data of all patients who received standard lobectomy for PTMC at our institution between October 2017 and January 2019. Central LNs were dissected in all patients. Lateral LNs were dissected if metastasis to the lateral LNs was suggested based on pre-op fine-needle aspiration biopsy. The relationship between variables available prior to surgery and cervical LN metastasis was examined using multivariate regression. Post-op pathologic examination revealed cervical LN metastasis in 79 (29.5%) patients. Seventy subjects had metastasis only to central LNs, and 4 (1.5%) patients had metastasis only to lateral LNs. Five patients had metastasis to both central and lateral LNs. In comparison to patients without cervical LN metastasis, those with LN metastasis were significantly younger (40.63 ± 13.07 vs. 44.52 ± 12.23 years; P = 0.021) and had significantly larger tumor diameter on pathology (6.7 ± 2.2 vs. 5.9 ± 2.4 mm; P = 0.010). Multivariate regression analysis identified the following independent risks for cervical LN metastasis: male sex (OR 2.362, 95%CI 1.261~4.425; P = 0.007), age (OR 0.977, 95%CI 0.956~0.999; P = 0.042) and ultrasound tumor diameter at > 5 mm (OR 3.172, 95%CI 1.389~7.240; P = 0.006). Cervical LN metastasis occurs in a non-insignificant proportion of PTMC patients. Independent risks included male sex, younger age and larger tumor diameter on ultrasound.


Efficient 1,4-addition of alpha-substituted fluoro(phenylsulfonyl)methane derivatives to alpha,beta-unsaturated compounds.
The 1,4-addition of a monofluoromethyl nucleophile to a variety of alpha,beta-unsaturated compounds has been achieved under mild conditions using either phosphines or potassium carbonate at room temperature. alpha-Substituted fluoro(phenylsulfonyl)methane easily undergoes Michael addition to alpha,beta-unsaturated ketones, esters, nitriles, sulfones, as well as propynoates at room temperature to yield the corresponding adducts in moderate to excellent yields.


Dynamic changes in monoterpene accumulation and biosynthesis during grape ripening in three Vitis vinifera L. cultivars.
Monoterpenes are important aroma components in grapes and wines. We analyzed the free and bound monoterpene profiles and the transcript levels of terpenoid biosynthesis genes in Vitis Vinifera cvs. Muscat Hamburg, Riesling, and Sauvignon Blanc grapes at five ripening stages. Principal component analyses revealed that the three cultivars had different free monoterpene profiles at harvest and the early stage of ripening. In all cultivars, the total bound monoterpene contents were higher than the free monoterpene contents during grape ripening. The changes in monoterpene profiles in different grape varieties were correlated with the transcript levels of some VviTPS and VviGT genes. In Riesling, the VviGT14 and VviUGT88A1L1 transcript levels were related to geraniol glucoside accumulation. In Muscat Hamburg, the VviPNLGl1, VviPNLGl2, and VviPNLGl4 transcript levels were related to linalool accumulation. Understanding the dynamic changes in monoterpene accumulation and biosynthesis will allow winemakers to devise strategies to improve grape and wine aromas.


Orbital Cellulitis: Defining Multidisciplinary Approach as the Need of the Hour.
The aim of the study is to determine epidemiological profile of cases admitted with suspicion of pre or post septal cellulitis and to define and evaluate the various factors associated with the aetiology, presentation, diagnosis and management of orbital and preseptal cellulitis via a one year study of ten cases presenting to a tertiary care hospital in western Rajasthan, India. All patients presenting to our department or being transferred from other departments to us with the diagnosis of pre/post septal cellulitis from the March of 2017 to February 2018 were considered for this case series. Data compilation of these patients was done which included age, sex, chief complain, duration of illness, associated co-morbidities, time of presentation, management plan undertaken and associated radiological findings. All these aspects were then evaluated. Our study included 10 cases. Of these 8 were less than 14 years and 2 were over 50 years. Both the adults were female and were positive for Diabetes Mellitus type two. 80% of these patients presented between the duration of November to February with maximum (40%) in the month of December. In 7 of these 10 patients, the cellulitis was associated with underlying sinusitis. Six patients were admitted directly from ENT OPD while other 4 were being managed in other ward before being transferred to us. All patients were managed conservatively except 1 who required surgical intervention. Pre/post septal cellulitis is a dangerous condition in which prompt intervention needs to be undertaken as it can be difficult to predict what course it will follow. Radiological evaluation should be done in all cases as most cases are associated with an underlying sinus infection. Also, it is more common in paediatric age group and the patient may initially be referred to an ophthalmologist or a paediatrician in which case it becomes very important that a good working interdepartmental collaboration be present so that correct management plan can be followed.


Posterior migration of Ahmed glaucoma valve tube in a patient with Reiger anomaly: a case report.
To describe, a yet non-documented complication of GDI surgery (glaucoma drainage incision surgery)--anterior to posterior segment migration of Ahmed Glaucoma Valve (AGV) tube. We report a young 9 year old boy, diagnosed with refractory glaucoma with Reiger anomaly. History included of poor vision in both eyes, left more than right with glare since childhood. He underwent GDI surgery with AGV implantation following which he developed posterior migration of AGV tube. The detailed ocular history, ophthalmic findings, clinical course, surgical management and development of the posterior tube migration is discussed. Posterior Migration of AGV tube has yet not been described. Also there is a role of expectant management of the complication in this case as evidenced by the benign course of events.


Electrophoretic characterization of muscarinic receptors under denaturating and nondenaturating conditions: computer-assisted Ferguson plot analysis.
The physical properties of the covalently labeled [( 3H]propylbenzilycholine mustard) muscarinic acetylcholine receptor from rat brain were studied by sodium dodecyl sulfate-polyacrylamide electrophoresis and computer-assisted Ferguson plot analysis. No proteolytic degradation or dimerization of the ligand binding subunit was found. No clues for different molecular weight forms or anomalous migration of the muscarinic receptor were detected. The weighted regression analysis of Ferguson plots gave an apparent molecular mass of 64-65 kDa. A new method for the electrophoretic separation of native (quinuclidinyl[3H]benzilate labeled) muscarinic receptor-detergent complexes was used for the comparison of wheat germ agglutinin binding, and not lectin binding receptors which were obtained by selective solubilization from porcine striatum. For this purpose, the computer-assisted Ferguson plot analysis is particularly suitable, since it renders possible the statistical assessment of both size and charge differences. Both receptor-detergent complexes were found to differ; statistically significant in their net charge but not in their size. The data support the view that muscarinic receptors from different sources may differ considerably in their glycosylation and that the receptor from porcine striatum can reversibly associate with a low-molecular-mass component which contains sialic acid.


Reclaiming a theoretical orientation to reflection in medical education research: a critical narrative review.
Reflection and reflective practice have become popular topics of scholarly dialogue in medical education. This popularity has given rise to checklists, portfolios and other tools to inspire and document reflection. We argue that some of the common ways in which reflection has been applied are influenced by broader discourses of assessment and evidence, and divorced from original theories of reflection and reflective practice. This paper was developed using a critical narrative approach. First we present two theoretical lenses provided by theories of reflection. Next we present a summary of relevant literature, indexed in PubMed from 2004 to 2014, relating to the application of reflection or reflective practice to undergraduate and postgraduate medical education. We categorise these articles broadly by trends and problematise the trends relative to the two theoretical lenses of reflection. Two relevant theoretical orientations of reflection for medical education are: (i) reflection as epistemology of practice, and (ii) reflection as critical social inquiry. Three prevalent trends in the application of reflection to medical education are: (i) utilitarian applications of reflection; (ii) a focus on the self as the object of reflection, and (iii) reflection and assessment. These trends align with dominant epistemological positions in medicine, but not with those that underpin reflection. We argue for continued theorising of and theoretically informed applications of reflection, drawing upon epistemologies of practice and critical reflection as critical social inquiry. These directions offer medical education research broad and deep potential in theories of reflection, particularly in relation to knowledge creation within uncertain and complex situations, and challenging of dominant discourses and structures. Future work could explore how dominant epistemological positions and discourses in medicine influence theories from other disciplines when these theories are deployed in medical education.


Autoradiographic studies with 3H 1,25 (OH)2 vitamin D2 and 3H 25 (OH) vitamin D3 in rat parathyroid glands.
After injection of radiolabeled 1,35 (OH)s vitamin D3, nuclear concentration of radioactivity is observed in parenchymal cells o hte parathyroid gland in pregnant, adult male, and 10-day male neonatal rats. In competition studies with unlabeled 1,25 (OH)2 vitamin D3, but not with 25 (OH) vitamin D3, in contrast to 3H 1,25 (OH)2 vitamin D3, do not show nuclear concentration in cells of te parathyroid. The results of te autoradiographic studies suggest the presence of receptors for a direct effect of 1,35 (OH)2 vitamin D3 on the parathyroid gland for modulation of parathyroid hormone secretion.


Mechanical Performance Assessment of Physician Modified Aortic Stent Graft.
This study aimed to compare various fenestration configurations of physician modified aortic stent grafts in order to identify which design parameters have a significant influence on the mechanical behaviour of the fenestration. the fenestration configurations were considered according to different manufacturing parameters: cutting technique, fenestration reinforcement, suture material, reinforcement loop design, and number of suture points. The performance of the graft/bridging stent assembly was assessed at various levels: (1) branch pull out force; (2) fenestration enlargement and rupture strength; (3) balloon angioplasty resistance; and (4) behaviour under cyclic fatigue. Sixty manual fenestrations were created. The tests performed on the fenestrations had several main findings. First, reinforcement increased the radial force on the branch, which increased the pull out force; this may limit migration of the bridging stent in vivo. The phenomenon was amplified with a snare reinforced fenestration, which seemed to be the most efficient. Moreover, increasing the number of suture passes also appeared to increase the branch extraction force securing the assembly. The enlargement tests showed that non-reinforced fenestrations had the weakest radial strength. This was confirmed with the balloon angioplasty test, which showed that these latter specimens undergo the most significant textile degradation. After fatigue tests, all fenestrations were larger, showing that elastic recoil was incomplete in all samples. The largest recoil was observed in the non-reinforced ophthalmological cautery (OC) fenestrations (40%). Regarding the behaviour of the samples up to rupture, all samples behaved in a similar way; however, the double loop fenestration strength level was the highest. This study demonstrated that the snare double loop reinforcement has an advantage regarding durability of the graft branch assembly. Moreover, non-reinforced fenestrations show signs of weakness and lack of stability, which questions the in situ or laser fenestration procedures.


Diagnosis of mucopolysaccharidoses: how to avoid false positives and false negatives.
This paper advocates a complete procedure, which includes both quantitative and qualitative analysis of urinary GAGs in the diagnosis of MPS in a clinically suspected population. Urine samples from 219 clinically suspected mucopolysaccharidoses (MPS) patients and 91 controls were analysed using a combination of methods. Quantitation of isolated urinary glycosaminoglycans (GAGs) were carried out using acid alcian blue complex formation method and qualitative urinary GAG analysis by multisolvent sequential thin layer chromatography Of the 219 patients analysed, 131 were confirmed to be suffering from MPS. Quantitation of urinary GAGs alone would have missed 60 low GAG excreting MPS patients and misdiagnosed 26 high GAG excreting nonMPS as MPS patients. Further qualitative analysis and enzyme estimation were needed to identify these 60 low GAG excreting MPS patients and 26 high GAG excreting non MPS patients. These results emphasize that quantitation of urinary GAGs alone cannot diagnose MPS patients, it should be coupled with qualitative analysis and enzyme estimations for differential/definitive diagnosis.


Diffusion Tensor Imaging Analysis Along the Perivascular Space Index in Primary Parkinson's Disease Patients With and Without Freezing of Gait.
Parkinson's disease (PD) is a common neurodegeneration disease associated with the abnormal deposition and spread of misfolded proteins (α-synuclein and Tau protein), which progressively damages the glymphatic system. This research intended to investigate the activity of the glymphatic system in PD individuals with freezing of gait (PD-FOG) and PD patients without it (PD-nFOG), as well as their relationship to the clinical neural scale. Diffusion tensor imaging (DTI) was performed in 28 PD-FOG individuals, 31 PD-nFOG individuals, and 34 healthy controls (HC). The DTI analysis along the perivascular space (DTI-ALPS) index was computed after post-processing of DTI images, representing brain glymphatic functions. The DTI-ALPS index was assessed for the association with the clinical variables. Compared to the HC group, the DTI-ALPS index of both PD-FOG and PD-nFOG patients was significantly decreased; however, no notable difference was found between the PD-FOG and PD-nFOG group. In addition, the DTI-ALPS index of PD-nFOG patients were positively correlated with disease duration, Unified Parkinson's Disease Rating-III Right (UPDRS-III R), UPDRS-III TOTAL, UPDRS-IV. Taken together, these findings highlighted the weakening of function of the glymphatic system in PD individuals, which is associated with motor symptoms and treatment complications. We speculate that treatment aimed at enhancing the flow and clearance of the glymphatic system may alleviate clinical symptoms of PD.


Energy cost of contraction in rat urinary bladder smooth muscle during anoxia.
1. The aim of the present study was to investigate the effects of hypoxia on energy metabolism and contraction of rat urinary bladder smooth muscle, thereby gaining insight into the capacity of this smooth muscle to maintain contractile function when rendered hypoxic. 2. Isometric force, oxygen consumption, lactate production, heat production and unloaded shortening velocity were measured in isolated muscle strips under both aerobic and anaerobic conditions. Muscle strips were bathed in physiological saline solution with the anaerobic condition being created by replacing the oxygen bubbling the solution with nitrogen. 3. During contraction under anaerobic conditions, the rate of lactate production was increased 2.5-fold above that observed under aerobic conditions. This, however, only provided for a rate of ATP production of approximately 30% of that measured under aerobic conditions. Despite this, force maintenance was only slightly depressed, indicating that the metabolic cost of contraction was reduced in hypoxia. In support of this, the rate of heat production during contractions in anoxia was only approximately half of that under aerobic conditions, whereas, again, force was only slightly lower. Unloaded shortening velocity was significantly lower in anoxia, suggesting a slower cross-bridge turnover rate. 4. The results indicate that the economy of force maintenance is increased in bladder smooth muscle under hypoxic conditions and that this is due, at least in part, to a reduced rate of cross-bridge cycling. This may help to preserve bladder contractile function during periods of ischaemia that may be associated with bladder filling and emptying.


Mandibular movements and jaw muscles' activity while voluntarily chewing at different rates.
As a way of learning about the motor control of chewing, we studied how well a subject could voluntarily chew in time with a metronome and defined the changes in the spatial and temporal aspects of the chewing pattern with changes in chewing rate. Timing and extent of mandibular movements were assessed in nine adults from Kinesiograph recordings; timing and level of activity in digastric and both masseter muscles were determined from surface EMGs. Each subject chewed gum in time with a metronome set randomly at 46, 100, 160 beats per minute or at a frequency close to his automatic chewing rate. Cycle-by-cycle analysis showed that subjects varied in their ability to keep pace with the metronome. When chewing at high frequencies, six subjects reduced gape, three did not. Contralateral deflection in opening, when present, was significantly reduced when chewing at high frequencies and this decrease was independent of vertical gape. Durations of opening, closing, and occlusal phases decreased in proportion to the decrease in total cycle duration. Burst duration of diagastric activity decreased about 29% compared with a 77% decrease in cycle duration over all chewing rates. At low frequencies onset of digastric activity occurred after onset of opening. At high frequencies digastric onset preceded opening. Burst durations of both masseter muscles decreased in concert with the decrease in cycle duration. Termination of activity in both masseters was synchronous and always occurred 100 +/- 20 ms prior to the next opening. Therefore, we conclude that (i) individuals vary in ability and strategy for controlling chewing rate voluntarily and (ii) with increases in chewing rates the shortening of burst duration for the digastrics is significantly less than for the masseters.


Cationic rhodium(I)/segphos-catalyzed cycloisomerization of 1,6- and 1,7-diynes in the presence of 1,2-cyclohexanedione.
We have developed the first catalytic cycloisomerization of 1,6- and 1,7-diynes leading to trienes and vinylpyrroles by using a cationic rhodium(I)/Segphos complex (2.5-10 mol %) and 1,2-cyclohexanedione (100 mol %). 1,2-Cyclohexanedione may effectively occupy vacant coordination sites and thus promote the present cycloisomerization.


'Those who cannot remember the past are condemned to repeat it': Drug-susceptibility testing for bedaquiline and delamanid.
Despite being fundamental to all treatment decisions, the breakpoints that define susceptibility and resistance to conventional anti-tuberculosis (TB) drugs were traditionally defined based on expert opinion as opposed to modern microbiological principles. As a result, the breakpoints for several key drugs (i.e. amikacin, levofloxacin, and moxifloxacin) were too high, resulting in the systematic misclassification of a proportion of resistant strains as susceptible. Moreover, a recent systematic review of clinical outcome data prompted the World Health Organization (WHO) to make significant changes to its treatment guidelines. For example, capreomycin and kanamycin are no longer recommended for TB treatment because their use correlates with worse clinical outcomes. This history notwithstanding, robust breakpoints still do not exist for bedaquiline and delamanid six years after their approval. This was compounded by the fact that access to both agents for drug-susceptibility testing had initially been restricted. It is incumbent upon the European Medicines Agency, the United States Food and Drug Administration, and WHO to ensure that drug developers generate the necessary data to set breakpoints as a prerequisite for the approval of new agents.


Surgical Anatomy of the Labyrinthine and Subarcuate Arteries and Clinical Implications.
To study the surgical anatomy of the labyrinthine artery (LA) and the subarcuate artery (SA), their anatomic relationships, and clinical implications, as injury of the LA can result in hearing loss. Ten formalin-fixed, latex-colored specimens were studied (20 sides). After retrosigmoid craniotomy and neurovascular dissection under microscopic magnification, 4-mm 0° and 30° endoscopic lenses were used to improve visualization. Results were statistically analyzed. The LA was a constant artery that followed the vestibulocochlear nerve into the internal auditory canal. The SA was an inconstant artery that ended in the dura mater around the subarcuate fossa in 35% of cases. The LA originated from the anterior inferior cerebellar artery in 89.3% of specimens and from the basilar artery in 10.7% of specimens. The SA branched off from the anterior inferior cerebellar artery when present. The origin of the LA was inferomedial to the vestibulocochlear nerve in most cases (71.4%), whereas the SA was usually lateral (70%). The distal portion of the LA was inferomedial to the vestibulocochlear nerve in 71.4% of cases. The distal portion of the SA was superolateral to the nerve in all cases (P < 0.00001). Knowledge of the different trajectory and anatomic relationship of the LA and the SA with the vestibulocochlear nerve is of paramount importance to differentiate them during surgery. The LA is usually inferomedial to the vestibulocochlear nerve at its distal and proximal aspects, whereas the SA usually originates lateral and ends superolateral to the nerve.


Suicidal behaviors, social support and reasons for living among nursing students.
The transition to higher education involves many changes for students. The aim of the study was to characterize nursing students' suicidal behaviors, use of medication, social support and reasons for living. A quantitative cross-sectional and correlational descriptive study was conducted at a Portuguese nursing college. The Social Support Satisfaction Scale (Pais-Ribeiro, 1999) and the Reasons for Living Inventory (Matias and Santos, 2014) were used. Most nursing students are women, with a mean age of 20years, and most of them have siblings. The majority of them lives outside the city of Coimbra. Approximately 5% of students showed suicidal behaviors, being more frequent among women. Around 20% of the students take medication, with a higher prevalence among women. Fourth-year students had the lowest reasons for living and satisfaction with social support scores. Five percent of the students had a history of suicidal behaviors. Nine percent of the students take psychotropic medications. The students who take medication are 2.3578 times more likely to have suicidal behaviors. Fourth-year students had the lowest mental health scores. Third-year students were the most satisfied with social support, whereas fourthyear students were the least satisfied. First-year students had the highest reasons for living scores, whereas fourth-year students had the lowest scores.


The effect of treating obstructive sleep apnea with positive airway pressure on depression and other subjective symptoms: A systematic review and meta-analysis.
Patients with obstructive sleep apnea (OSA) frequently present with symptoms of depression and anxiety. The objective of this study is to determine if treatment with positive airway pressure (PAP) improves symptoms of depression and anxiety. A systematic review was conducted to identify clinical trials of PAP that contained a validated measure of depression severity. Meta-analysis was conducted for depression, anxiety, excessive daytime sleepiness (EDS), quality of life (QoL) and respiratory variables. The systematic review included 33 reports. Pre-post-test analysis of PAP showed a moderate effect size (Hedge's g, 95% CI) for depression 0.524 [0.401-0.647], but a low effect size compared to oral placebo (0.355 [0.187-0.524]) and no effect when compared to dental appliances (0.107 [-0.72-0.287]) and sham PAP (-0.049 [-0.292-0.194]). Anxiety, EDS, and QoL showed similar improvement in pre-post-test analysis, but a lack of superiority to dental appliances and sham PAP. PAP was superior to all comparators for respiratory variables. PAP has a moderate clinical effect on symptoms of depression and anxiety in OSA, but it is not superior to dental appliances or sham PAP. The improvement in subjective symptoms, such as depression and anxiety, may be mediated by patient expectations and contact with healthcare providers.


[Effect of the saccharide chain length of bacterial lipopolysacchrides on the stimulation of immune system].
Three lipopolysaccharides (LPS) of different chain length were used as adjuvant. The one of shortest chain length is the most effective in enhancing antibody titer in rats against sheep red blood cells, suggesting that lipid A and KDO were responsible for the stimulatory effect of LPS.


Cloning and functional analysis of the orotidine-5'-phosphate decarboxylase gene (PbrURA3) of the pathogenic fungus Paracoccidioides brasiliensis.
A genomic clone encoding the Paracoccidioides brasiliensis orotidine monophosphate decarboxylase gene (PbrURA3) was isolated by screening a subgenomic plasmid DNA library of this fungus, using a PCR amplification product of the gene as a probe. Sequence analysis revealed that the gene contains an open reading frame of 855 bp with a single intron (162 bp), and encodes a putative 285 amino acids polypeptide of estimated molecular weight 31.1 kDa and isoelectric point 6.5. The deduced amino acid sequence predicted a 73.4% identity with orotidine monophosphate decarboxylase of Aspergillus nidulans. Functionality of the gene was demonstrated by transformation into a Saccharomyces cerevisiae ura3 null mutant.


Photic release of radioactivity from rabbit retina preloaded with [3H]GABA.
The in vitro release of radioactivity by light from rabbit retina was studied after intravitreal injection of [3H]GABA (gamma-aminobutyric acid). The site of uptake of [3H]GABA into the retina after intravitreal injection was checked by autoradiography and was localized at 2 h after the injection mainly in glia but at 4 h in amacrine cells and some ganglion cells. If the retina loaded with [3H]GABA was stimulated by light flashes the efflux of radioactivity increased significantly. Chromatographic analysis of the superfusate demonstrated that [3H]GABA was released by light stimulation. However, the efflux was not elicited by constant light, and was abolished in a medium containing 20 mM Mg++ and 0.2 mM++. When the metabolism of GABA was inhibited by amino-oxyacetic acid, light flashes no longer increased the efflux of radioactivity significantly. No light-evoked release of radioactivity could be demonstrated from glia. Pentobarbitone inhibited the spontaneous efflux and prior anaesthetization with pentobarbitone abolished the light-evoked release. These results support the view that GABA is a retinal neurotransmitter in the rabbit.


Metastatic Ewing's sarcoma to the skull: CNS involvement excluded by MRI.
A case of metastatic Ewing's sarcoma to the skull is presented, demonstrating the superiority of magnetic resonance imaging over other imaging modalities to exclude CNS involvement. Precise delineation of different tumor components in extradural location contained in an intact dural rim together with compressed cortex showing no signs of tumorous involvement constituted a MRI appearance allowing us to exclude tumor outgrowth into the brain.


Comparative therapy evaluation of intravitreal bevacizumab and triamcinolone acetonide on persistent diffuse diabetic macular edema.
To compare the effect of an intravitreal injection of bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, with that of triamcinolone acetonide, a corticosteroid for reduction of diabetic macular edema (DME). Prospective, comparative interventional case series. Twenty-eight eyes of 14 patients with bilateral DME participated in this study. In each patient, one eye received an intravitreal injection of 4 mg triamcinolone acetonide and the other eye received 1.25 mg bevacizumab. The clinical course of best-corrected visual acuity (VA) with a logarithm of the minimum angle of resolution chart and averaged foveal thickness using optical coherence tomography was monitored for up to 24 weeks after the injection. Before the injection, foveal thickness and VA were 522.3 +/- 91.3 microm and 0.64 +/- 0.28 microm in the triamcinolone-injected eye, and 527.6 +/- 78.8 microm and 0.61 +/- 0.18 microm in the bevacizumab-injected eye, respectively; there was no significant difference between the eyes. One week after the injection, both eyes showed significant regression of macular edema. The triamcinolone-injected eye (342.6 +/- 85.5 microm and 0.33 +/- 0.21 microm) showed significantly better results than the bevacizumab-injected eye (397.6 +/- 103.0 microm and 0.37 +/- 0.17 microm). However, both eyes showed the recurrence of macular edema with time, even at 24 weeks. Triamcinolone (410.4 +/- 82.4 microm and 0.47 +/- 0.25 microm) kept better results than bevacizumab (501.6 +/- 92.5 microm and 0.61 +/- 0.17 microm). With the generally used concentration, intravitreal injection of triamcinolone acetonide showed better results in reducing DME and in the improvement of VA than that of bevacizumab, suggesting that the pathogenesis of DME is not only attributable to VEGF-dependency, but is also attributable to other mechanisms suppressed by corticosteroid.


Effects of staff grade, overcrowding and presentations on emergency department performance: A regression model.
To examine the effect of staffing levels by experience of medical officers and overcrowding on ED key performance indicators (KPIs). Presentations to Nepean ED from 6 May to 3 November 2019 were examined. Staff were designated either Fellows of the Australasian College for Emergency Medicine (FACEMs), non-FACEM senior decision-makers (SDMs), non-senior decision-makers greater than 2 years postgraduate (non-SDMs) and junior medical officers up to 2 years postgraduate (JMOs). The number of admitted patients boarded in the ED waiting for a ward bed at 8 am was used as a marker for overcrowding. Multivariable regression analysis was performed using staffing levels, number of admissions at 8 am and total presentations as the independent variables and various ED KPIs as the dependent variables. FACEM and SDM had a significant effect on most ED KPIs, with the effect of FACEM consistently larger than the effect of SDM. There was minimal effect on performance by non-SDM and JMO staffing. There was significant effect of overcrowding as measured by the number of admitted patients in ED at 8 am on most ED KPIs. Almost no variables had an effect on Emergency Treatment Performance (4-h target) for admitted patients, suggesting poor performance was caused by factors outside of the ED. Increasing numbers of FACEM and non-FACEM SDM, but not junior staff, and a reduction in overcrowding as measured by the number of admitted patients boarded in the ED at 8 am, were associated with improvements in the ED performance.


Quality management in laboratory medicine.
In the context of total quality management the paper is focused on analytical quality with special emphasis on the preanalytical steps from the patient to the sample. At the present time those are the most important limiting factors of the quality of laboratory results.


Fractures of the acetabulum in elderly patients: an update.
The incidence of acetabular fractures in elderly patients is increasing. Poor bone quality and concomitant diseases are the main features of these patients. Fracture patterns are marked by a high degree of variability in terms of patient and fracture characteristics. Preoperative planning with plain radiographs and computed tomography, including 3-dimensional reconstructions, is recommended. Treatment remains challenging because of precarious general health, severe osteopenia, comminution, and associated femoral head damage. Treatment options available include closed management, open reduction with internal fixation, percutaneous fixation in situ, and acute or staged total hip arthroplasty (THA) whether alone or combined with osteosynthesis. In the case of significant destruction of the articular cartilage, primary THA may provide the best solution. Whichever surgical method is chosen, the objective is rapid mobilisation of the patient on a walker or crutches. Late local complications that may occur after nonoperative or operative treatment include posttraumatic arthritis, nonunion, malunion, wound infection, dislocation, intrusive hardware, nerve palsy, and heterotopic bone formation. In this article an overview of the current trends in the management of acetabulum fractures in the elderly is presented.


A mismatch process in brief delayed matching-to-sample task: an fMRI study.
Our previous ERP studies have consistently demonstrated that a negativity N270 elicited by incongruent information in visual S1-S2 matching task represents a type of conflict process, which is distinct from that represented by the classic conflict task or other negative components in delayed matching-to-sample stimulus presentation patterns, since the inter-stimulus interval between S1 and S2 was presented as shorter as 500 ms. The N270 component of ERP was shown to reflect conflict processing during the simple working memory operations. In the present study, a functional MRI (fMRI) was used to investigate the visuospatial characteristics of brain activation associated with the task eliciting N270. The fMRI data showed an increased activation in the right anterior cingulate cortex (ACC, BA 24) and right dorsolateral prefrontal cortex (DLPFC, BA 46), and activation biased to the left occipitotemporal cortex (BA 37) in the incongruent condition. It is suggested that the greater activations of the right ACC coupling with right DLPFC to incongruent task reflect functional efficiency of the right cingulo-prefrontal network during the brief visual delayed period discrimination performance and mismatched information processing.


Clinical trial on the characteristics of zheng classification of pulmonary diseases based on infrared thermal imaging technology.
Zheng classification study based on infrared thermal imaging technology has not been reported before. To detect the relative temperature of viscera and bowels of different syndromes patients with pulmonary disease and to summarize the characteristics of different Zheng classifications, the infrared thermal imaging technology was used in the clinical trial. The results showed that the infrared thermal images characteristics of different Zheng classifications of pulmonary disease were distinctly different. The influence on viscera and bowels was deeper in phlegm-heat obstructing lung syndrome group than in cold-phlegm obstructing lung syndrome group. It is helpful to diagnose Zheng classification and to improve the diagnosis rate by analyzing the infrared thermal images of patients. The application of infrared thermal imaging technology provided objective measures for medical diagnosis and treatment in the field of Zheng studies and provided a new methodology for Zheng classification.


Development of support vector machine-based model and comparative analysis with artificial neural network for modeling the plant tissue culture procedures: effect of plant growth regulators on somatic embryogenesis of chrysanthemum, as a case study.
Optimizing the somatic embryogenesis protocol can be considered as the first and foremost step in successful gene transformation studies. However, it is usually difficult to achieve an optimized embryogenesis protocol due to the cost and time-consuming as well as the complexity of this process. Therefore, it is necessary to use a novel computational approach, such as machine learning algorithms for this aim. In the present study, two machine learning algorithms, including Multilayer Perceptron (MLP) as an artificial neural network (ANN) and support vector regression (SVR), were employed to model somatic embryogenesis of chrysanthemum, as a case study, and compare their prediction accuracy. The results showed that SVR (R2 > 0.92) had better performance accuracy than MLP (R2 > 0.82). Moreover, the Non-dominated Sorting Genetic Algorithm-II (NSGA-II) was also applied for the optimization of the somatic embryogenesis and the results showed that the highest embryogenesis rate (99.09%) and the maximum number of somatic embryos per explant (56.24) can be obtained from a medium containing 9.10 μM 2,4-dichlorophenoxyacetic acid (2,4-D), 4.70 μM kinetin (KIN), and 18.73 μM sodium nitroprusside (SNP). According to our results, SVR-NSGA-II was able to optimize the chrysanthemum's somatic embryogenesis accurately. SVR-NSGA-II can be employed as a reliable and applicable computational methodology in future plant tissue culture studies.


Medical students' risk of infection with bloodborne viruses at home and abroad: questionnaire survey.
To determine risks of exposure to and prevention of bloodborne virus infections among medical students during their elective period. Questionnaire study of students returning from their electives in 1997-8. Urban teaching hospital. 220 final year medical students. 148 students (67%) returned questionnaires; all had been vaccinated against hepatitis B. 65 respondents (44%) had visited areas of relatively high endemicity for HIV, although 27 (42%) of these, all of whom had visited areas other than sub-Saharan Africa, were unaware of this. All but one had discussed their elective with advisers. Four students experienced percutaneous or mucosal exposure to potentially infectious body fluids, three in areas with a high prevalence of HIV infection. 44 respondents (30%) had experienced at least one such exposure during their clinical training; 75% of these exposures were unreported. 34% (13/38) students who visited areas known to have a high prevalence of HIV infection took with them a starter pack of zidovudine for post-exposure prophylaxis; 53% (20) took latex gloves and 63% (24) a medi-kit. None of the 27 students who were unaware that the areas they visited had a relatively high prevalence of HIV infection took zidovudine; only 15% (4) took gloves and 30% (8) a medi-kit. Medical schools should produce, regularly update, and implement guidelines regarding protection from bloodborne viruses during clinical studies, including electives. Education and training in infection control should start at the earliest opportunity.


Human telomerase inhibitors from microbial source.
Telomerase enzyme inhibitors have gained attention of scientific field due to the specificity of action of telomerase based therapies. Some telomerase have good combinatorial action with certain DNA damaging drugs. Natural compounds isolated from microbes provide a new scope of screening and large scale production of telomerase inhibitors. This review emphasizes the biochemistry and mode of action of different types of telomerase inhibitors isolated from microbial sources. Also elaborates on classification of telomerase inhibitors based on their mode of action in cancer cells.


Role of air pollution in chronic kidney disease: an update on evidence, mechanisms and mitigation strategies.
Air pollution results from a variable and complex mixture of harmful gases and suspended particles and is the most worrisome of all environmental hazards. It is implicated in several non -communicable diseases and is recognized to be a public health problem. Though the initial exposure to air pollution is through the respiratory system, kidneys are thought to be exposed to higher concentrations owing to their filtration function. Chronic kidney disease is the insidious end result of several disease processes which cumulatively form a large healthcare burden, particularly in low- and middle-income countries. There is a growing body of evidence that air pollution may be a contributing factor that leads to CKD by not only its direct effects, but can also compound the effect of other factors/diseases causing kidney injury. PM2.5 exposure particularly has been implicated, although there is some evidence regarding other air pollutants as well. These pollutants are thought to act on kidneys through several interlinked systemic pathways and mechanisms which individually and collectively damage the nephrons. Long-term exposures seem to gradually diminish renal function and lead to end-stage renal disease. A thorough understanding of the mechanism of kidney injury is the key for formulating and implementing effective strategies for reducing this burden. Maintaining the air quality, promoting education, improving health quality and promotion of targeted nephroprotective measures through effective policy and research support are required in addressing this global public health problem.


Hospital cost and clinical effectiveness of robotic-assisted versus video-assisted thoracoscopic and open lobectomy: A propensity score-weighted comparison.
To compare cost and perioperative outcomes of robotic, video-assisted thoracoscopic surgery (VATS), and open surgical approaches to pulmonary lobectomy. Patients who underwent pulmonary lobectomy between 2012 and 2017 at a single tertiary referral center were reviewed. Propensity score adjustment by inverse probability of treatment weighting (IPTW) was used to balance baseline patient characteristics. The primary outcomes of the study were direct hospital cost and perioperative outcomes, including operative time, complications rates, and length of stay. Indirect cost and charges were secondary financial outcomes. A total of 697 patients underwent pulmonary lobectomy by robotic (n = 296), VATS (n = 161), and open thoracotomy (n = 240). In the IPTW-adjusted analysis, open thoracotomy had the shortest mean operating room time (robotic 278 minutes vs VATS 298 minutes vs open 265 minutes, P = .05), and lowest operating room costs (robotic $9,912 vs VATS $9491 vs open $8698, P = .001). Length of stay was significantly shorter after robotic and VATS lobectomy (robotic 3.8 days vs VATS 3.8 days vs open 5.4 days, P < .001), with significantly fewer events of atelectasis and pneumonia as compared with the open group. In sum, no significant differences were seen in IPTW-adjusted direct cost (robotic $17,223 vs VATS $17,260 vs open $18,075, P = .48), indirect cost, or charges for the total hospital stay. Robotic and VATS lobectomy were associated with similar cost and improved clinical effectiveness as compared with the open thoracotomy approach. Increased procedural cost of minimally invasive lobectomy can be recovered by postoperative costs reductions, associated with improved postoperative outcomes and shorter hospital stay.


Surgical treatment for chronic pulmonary coccidioidomycosis: a retrospective study from a single institution.
Coccidioidomycosis, caused by the Coccidioides species, is a well-known disease in the Southwestern United States and North Mexico, with scattered reports in Latin America countries. While this disease is still rare in Japan and other Asian countries, its incidence has been increasing over the last two decades. Coccidioides species are highly infectious and require caution when encountered. This study presents a case series of chronic pulmonary coccidioidomycosis surgically treated at a single institution. We conducted a retrospective chart review of six patients who underwent lung resection for pulmonary coccidioidomycosis at Chiba University Hospital between January 2007 and December 2021. All six patients had travelled to the Southwestern United States. Preoperative serology was negative for the anti-Coccidioides antibody in four patients and positive in two. Chest computed tomography revealed a single, well-defined round nodule in all patients. Preoperative biopsy taken from three patients failed to obtain a definitive diagnosis. Histopathological examination of the resected pulmonary nodules revealed granulomas that contained numerous spherules with many endospores, thereby confirming the diagnosis of pulmonary coccidioidomycosis. Pulmonary coccidioidomycosis should be suspected based on travel history and radiological findings. Meticulous care should be taken during specimen processing to prevent cross infection.


Prospective study of 5-day challenge with penicillins in children.
To examine if a 5-day challenge with penicillin improves the diagnostic sensitivity compared with a single full dose in children with mild skin reactions. Subjects referred with suspected allergy to penicillin were consecutively included. Irrespectively of the morphology of the index reaction and the result of specific IgE, all subjects underwent a two-step titrated drug provocation test (DPT) with the culprit drug followed by a 5-day challenge at home. Children and adolescents aged 0-18 years referred to allergic workup for penicillin hypersensitivity at two paediatric Danish centres. Only subjects with non-severe skin reactions were included. A total of 305 subjects were included and 22 (7%) of the DPTs were positive. Three subjects reacted within 1 hour of the first full dose and nine reacted 1-8 hours after the first full dose. Additional 10 positive reactions were observed during the prolonged provocation. Seven subjects reacted after the second full dose and three reacted after 3-6 days. Only mild skin rashes were observed. Eighteen subjects had a specific IgE to a penicillin >0.1 kU/L. Only one of these had a positive DPT. In children, a DPT with penicillins should include at least two full doses. In children with mild hypersensitivity reactions it may be safe to perform DPTs despite a low specific IgE. NCT04331522.


Characterization of insulin binding in the UMR-106 rat osteoblastic osteosarcoma cell.
The correlation of insulin receptor occupancy with classic insulin effects, such as stimulation of glucose uptake, have not been examined in osteoblastlike cells. Accordingly, we characterized insulin binding and examined its relationship to stimulation of glucose analog transport in the UMR-106 rat osteoblastic osteosarcoma cell line. Insulin binding in UMR-106 cells was found to be pH sensitive, temperature dependent, saturable, and specific. Proinsulin was 100-fold less effective than insulin in displacing specific [125I]insulin binding in these cells, whereas IGF-I at concentrations between 0.1 and 10 nM produced no displacement of [125I]insulin but did produce significant displacement of insulin binding at 100 and 1000 nM. Insulin receptor downregulation was observed after exposure to 100 nM insulin for 6 h at 37 degrees C and was temperature dependent. Insulin binding was reversible after 24 h at 4 degrees C. Insulin binding correlated directly with stimulation of 2-deoxyglucose uptake at insulin concentrations between 0.1 and 100 nM, with a half-maximal concentration (ED50) of 0.9 nM for both [125I]insulin binding displacement and stimulation of 2-deoxyglucose uptake. Hence, there was no evidence for spare insulin receptors with regard to stimulation of glucose analog transport. Scatchard analysis of insulin binding kinetics yielded a curvilinear plot, suggesting negative cooperativity. Analysis of insulin binding kinetics using a two-site model yielded a KD of 0.9 nM for the apparent high-affinity binding site and an estimated 80,000 high-affinity binding sites per cell. These findings demonstrate that osteoblastlike cells exhibit a relationship between insulin binding and glucose transport stimulation that is similar to that in liver cells and other insulin-sensitive tissues.(ABSTRACT TRUNCATED AT 250 WORDS)


The lip gene contributes to the virulence of Aeromonas veronii strain TH0426.
Aeromonas veronii (A. veronii) is a pathogen that can infect aquatic organisms and mammals and has caused irrecoverable economic losses to the aquaculture industry. The results of an epidemiological investigation showed that the number of cases of A. veronii have increased gradually in recent years, and its drug resistance and virulence has shown an upward trend. In this study, we constructed an A. veronii mutant strain Δlip, by homologous recombination and studied its function. The results showed that there was no significant difference in the biofilm formation ability between the Δlip and the wild-type strain, but the toxicity of the Δlip to EPC cells and its ability to adhere to EPC cells were significantly reduced. The LD50 value of the Δlip to zebrafish was 7.40-fold higher than that of the wild-type strain. In addition, after 24 h and 72 h, the bacterial loads of the Δlip in the organs of crucian carp were significantly lower than those in the wild-type strain. In conclusion, the mutant strain Δlip led to a decrease in the adhesion and virulence of the wild-type strain, which lays a foundation to further understand lip gene function and the pathogenic mechanism of A. veronii.


Raman spectroscopy of different types of Mexican copal resins.
Dispersive Raman spectra of six copal resins, that were purchased in local markets in Mexico, are presented. The spectra were interpreted and compared with each other. For all these spectra, the relative intensity of the Raman band at approximately 1645 cm(-1), attributed to the exomethylene nu(C=C) stretching vibration, was rather low, especially as fresh samples are involved. In one resin, viz. Incienso, CaCO3 was detected. Probably this inorganic pigment was added as a whitener. In the spectrum of Lágrima a starch fraction was present. Raman spectra of a sample from an Aztec figurine were recorded. It was shown that its composition was inhomogeneous at the micrometer level. Here, too, CaCO3 was observed. It was not possible to identify the resin applied in the antique figurine due to material degradation by age and environmental exposure.


Racism and pediatric health outcomes.
Racism- a system operating at the intrapersonal, interpersonal, institutional, and structural levels- is a serious threat to the health and wellbeing of children and adolescents. This narrative review highlights racism as a social determinant of health, and describes how racism breeds disparate pediatric health outcomes in infant health, asthma, Type 1 diabetes, mental health, and pediatric surgical conditions. Key examples include the association of residential racial segregation and the alarming infant mortality rate among Black infants as well as the role of redlining and discriminatory housing practices on asthma morbidity among Black children and adolescents. Furthermore, inequitable care practices such as (1) racial and ethnic disparities in insulin pump usage in patients with Type 1 diabetes, (2) lower rates pharmacotherapy initiation in racialized children with mental health disorders, and (3) decreased pain medication management and confirmatory imaging in Black children with acute appendicitis, highlight the role of interpersonal racism in propagating poor health outcomes. An urgent call to action is needed to address pediatric health inequities and ensure all children can live healthy lives. Key strategies must tackle racism at the individual, institutional, and structural levels and include building a diverse workforce, prioritizing research to describe the impact of racism on pediatric health outcomes, initiating improvement efforts to close equity gaps, building community partnerships, co-designing solutions alongside patients and families, and advocating for policy change to address the social conditions that impact children and adolescents of color.


Relationship between Mycobacterium avium, Mycobacterium paratuberculosis and "wood pigeon mycobacteria". Determinations by DNA-DNA hybridization.
The DNA-DNA homology percentages obtained in this study indicate that M. avium and M. paratuberculosis belong to one species. Consequently, M. paratuberculosis ought to be considered a variant of M. avium, and the following designations are proposed: Mycobacterium avium, subsp. avium. Mycobacterium avium, subsp. paratuberculosis. Identification and classification of "wood pigeon mycobacteria" occurring in wild animals have been problematic due to their dysgonic and mycobactin-dependent growth. DNA-DNA homology percentages indicate that these bacteria are closely related to reference strains both of M. avium and of M. paratuberculosis. "Wood pigeon mycobacteria" should therefore be classified as atypical strains of M. avium, and the following designation is proposed: Mycobacterium avium subsp. columbae.


E-WASTE threatens health: The scientific solution adopts the one health strategy.
The aggressively extractive advanced technology industry thrives on intensive use of non-renewable resources and hyper-consumeristic culture. The environmental impact of its exponential growth means extreme mining, hazardous labour practices including child labour, and exposure burden to inorganic and organic hazardous chemicals for the environment and current and future human generations. Globally, processes such as in-country reduce, reuse and recycle have so far received less attention than outer-circle strategies like the uncontrolled dumping of e-waste in countries that are unprotected by regulatory frameworks. Here, in the absence of infrastructures for sound hazardous e-waste management, the crude recycling, open burning and dumping into landfills of e-waste severely expose people, animal and the environment. Along with economic, political, social, and cultural solutions to the e-waste global problem, the scientific approach based on risk analysis encompassing risk assessment, risk management and risk communication can foster a technical support to resist transgenerational e-waste exposure and health inequalities. This paper presents the latest public health strategies based on the use of integrated human and animal biomonitoring and appropriate biomarkers to assess and manage the risk of e-waste embracing the One Health approach. Advantages and challenges of integrated biomonitoring are described, along with ad-hoc biomarkers of exposure, effect and susceptibility with special focus on metals and metalloids. Indeed, the safe and sustainable management of novel technologies will benefit of the integration and coordination of human and animal biomonitoring.


Cellular internalization and gene silencing of siRNA polyplexes by cytocleavable cationic polyrotaxanes with tailored rigid backbones.
To achieve successful delivery of siRNA therapeutics, cytocleavable cationic polyrotaxanes (PRXs) composed of N,N-dimethylaminoethyl (DMAE) group-modified α-cyclodextrins (CDs) that were threaded onto a poly(ethylene glycol) (PEG) axis and capped with a bulky stopper using cytocleavable disulfide linkages (DMAE-PRX) were utilized as an siRNA carrier. DMAE-PRXs with various numbers of threading CDs and modified DMAE groups were synthesized, and the physicochemical properties, cellular internalization, and gene silencing activity of DMAE-PRX/siRNA were investigated to elucidate the relationship between its supramolecular structure and its function. When the numbers of modified DMAE groups were increased, the DMAE-PRXs formed closely associated polyplexes with siRNA and increased their polyanion exchange resistance. Additionally, the DMAE-PRXs with 52 threading CDs (52CD-PRXs) showed greater binding capabilities with siRNA and greater resistance to polyanion competition than 31CD-PRXs, indicating that the highly CD-threaded PRX structure in the 52CD-PRXs is superior in forming stable polyplexes with siRNA. Indeed, 52CD-PRX/siRNA showed greater intracellular uptake of siRNA than 31CD-PRX/siRNA with comparable numbers of DMAE groups. 52CD-PRX/siRNA successfully induced gene silencing of a targeted luciferase expressed in human cervical carcinoma without marked cytotoxicity and non-specific gene silencing. Although the gene silencing activities of DMAE-PRX/siRNA were comparable to those of linear poly(ethylenimine) (L-PEI), L-PEI showed cytotoxicity and non-specific gene silencing. Additionally, DMAE-PRXs with cytocleavable capabilities were found to enhance gene silencing, in comparison with non-cleavable DMAE-PRX. Thus, the cytocleavable cationic PRXs are suggested to be attractive supermolecules for the delivery of therapeutic siRNAs.


Dental implant surgery and risk of bleeding in patients on antithrombotic medications: A review of the literature.
This literature review was performed to assess the risk of bleeding in dental implantation procedures in patients taking antiplatelet drugs (APs), oral anticoagulants (OACs) and direct oral anticoagulants (DOACs). MEDLINE and SCOPUS databases were searched for English language publications through October 2019, using the keywords "dental implants," "dental implantation," "anticoagulants," "platelet aggregation inhibitors," and "hemorrhage." Reference lists of relevant articles were also hand searched. Collected data regarding dental implantation procedures, type of medications (APs, OACs and DOAC), and postoperative bleeding episodes were analyzed. Nine studies were included in the review. Postoperative bleeding occurred in 10 (2.2%) of 456 of cases involving dental implant placements; in all of those cases, bleeding was controlled with the use of local hemostatic agents. The bleeding incidence in patients on antiplatelet medications was 0.4% (range 1 of 253 to 1 of 261). Among those taking oral anticoagulants, the bleeding incidence was 5.7% (range 6 of 105 to 6 of 113), and among those on direct oral anticoagulants, the bleeding incidence was 3.3% (3 of 90). The numbers of more extensive surgical procedures (i.e., sinus lift and bone augmentation procedures) were small, and additional information regarding the surgery, the specific antithrombotic used, or bleeding was often not provided, so further analysis was not possible. Evidence supports continuing OACs, DOACs, or APs during dental implant surgery.