Bronchoscopic Re-biopsy for Mutational Analysis of Non-small Cell Lung Cancer.
Currently, several acquired resistance mechanisms and rare driver oncogenes are identified in non-small cell lung cancer (NSCLC) relapses. Re-biopsy increases valuable information to guide treatment strategies, but the utility and feasibility of bronchoscopic re-biopsy has not been investigated. We studied 70 patients who underwent bronchoscopic for re-biopsy of NSCLC that was resistant to at least one regimen of chemotherapy or molecular-targeted therapy between January 2013 and December 2014. We assessed clinical data, technical success rate, and mutational analysis. Procedures performed were transbronchial biopsy (n = 52) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) (n = 18). Overall detection rate of re-biopsy for malignant cells was 87 % (83 % for TBB and 100 % for EBUS-TBNA). Mutational analysis was possible in almost all technically successful cases; likewise, acquired-resistant mutations (55 % of EGFR mutants) and small cell lung cancer transformation were identified from the bronchoscopy specimens. Other driver mutations were seen in four cases, including ALK fusion gene (n = 2) and ROS1 fusion gene (n = 2). There were no associated severe complications. This study shows that bronchoscopic re-biopsy for NSCLC is feasible and provides adequate samples that enable identification of resistance mutations and rare driver oncogenes.


Intellectual prognosis of status epilepticus in adult epilepsy patients: analysis with Wechsler Adult Intelligence Scale-revised.
Status epilepticus (SE) appears to cause cognitive dysfunction as well as other serious neurologic sequelae. To confirm whether SE produces a subsequent intellectual decline, we evaluated intellectual function prospectively in adult epilepsy patients with and without SE. Of 1,685 patients with epilepsy who underwent comprehensive neuropsychological testing in two national hospitals in Japan, 15 patients experienced an episode of SE afterward and underwent the second neuropsychological examination after the SE episode. Forty clinically matched patients with epilepsy, but without an episode of SE since their initial neuropsychological examination, were also reevaluated. We compared IQs and subscores from the Wechsler Adult Intelligence Scale-Revised between the two groups by repeated measures analysis of variance. In the patients who experienced an SE episode, SE-related variables (i.e., age at the SE episode and type and duration of SE) and epilepsy-related variables such as epilepsy type, lateralization of EEG abnormalities, the presence of mesial temporal sclerosis, and previous history of SE, were evaluated in relation to intellectual outcome. Patients with SE, in comparison to those without SE, failed to show any significant post-SE intellectual decline. Furthermore, neither the SE-related variables nor the clinical characteristics were correlated with intellectual outcome. Our findings suggest that SE does not lead to a significant intellectual decline in adult patients receiving treatment for epilepsy.


123I-5-IA-85380 SPECT measurement of nicotinic acetylcholine receptors in human brain by the constant infusion paradigm: feasibility and reproducibility.
(123)I-5-IA-85380 ((123)I-5-IA; [(123)I]-5-iodo-3-[2(S)-azetidinylmethoxy]pyridine) is a promising SPECT radiotracer for imaging beta(2)-containing nicotinic acetylcholine receptors (beta(2)-nAChRs) in brain. Beta(2)-nAChRs are the initial site of action of nicotine and are implicated in various neuropsychiatric disorders. The feasibility and reproducibility of the bolus-plus-constant-infusion paradigm for equilibrium modeling of (123)I-5-IA using SPECT in healthy nonsmokers was studied. Ten healthy nonsmokers (mean age +/- SD, 43.7 +/- 9.9 y) underwent two (123)I-5-IA SPECT scans within 4 wk. (123)I-5-IA was administered as a bolus (125.8 +/- 14.6 MBq) plus constant infusion (18.1 +/- 1.5 MBq/h). SPECT acquisitions (30 min) and venous blood sampling were performed every 60 min throughout the infusion (10-14 h). The test-retest variability and reliability of plasma activity (kBq/mL), the regional brain activity reflected by units of kBq/mL and %ID/mL (injected dose/mL brain tissue), and the equilibrium outcome measures V(T)' (ratio of total uptake to total plasma parent concentration) and V(T) (ratio of total uptake to free plasma parent concentration) were evaluated in 4 brain areas, including thalamus, striatum, cortex, and cerebellum. Linear regression analysis revealed that time-activity curves for both plasma and brain (123)I-5-IA activity stabilized by 5 h, with an average change of [2.5%/h between 6 and 8 h of infusion, permitting equilibrium modeling. The plasma free fraction (f(1)), total parent, and clearance demonstrated good test-retest variability (mean, 10.9%-12.5%), whereas the variability of free parent was greater (mean, 24.3%). Regional brain activity (kBq/mL) demonstrated good test-retest variability (11.1%-16.4%) that improved when corrected for infusion rate (mean, 8.2%-9.9%) or for injected dose (mean, 9.5%-13.3%). V(T)' demonstrated better test-retest variability (mean, 7.0%-8.9%) than V(T) (mean, 12.9%-14.6%). Reliability assessed by the intraclass correlation coefficient (ICC) was superior for kBq/mL (ICC = 0.83-0.90) and %ID/mL (ICC = 0.93-0.96) compared with V(T)' (ICC = 0.30-0.64) and V(T) (ICC = 0.28-0.60). The lower reliability of V(T) was attributed to the poor reliability of the free fraction (ICC = 0.35) and free parent (ICC = 0.68). These results support the feasibility and reproducibility of equilibrium imaging with (123)I-5-IA for measurement of beta(2)-nAChRs in human brain.


The parasites of Anolis lizards in the northern Lesser Antilles : I. Patterns of distribution and abundance.
The helminth communities from ten species of lizard on seven islands in the Caribbean were sampled by collecting one hundred specimens of each species. Nine genera of parasites were identified; these included six nematodes, two digeneans and an acanthocephalan. No relationship was discernible between parasite density or abundance and island area or altitude, although dry islands tend to have fewer species of parasites. Anolis lizards of the bimaculatus and wattsi series share similar parasites with four out of nine species common to both series. The parasite community of lizards on these islands is depauperate with respect to similar surveys on the larger islands of the Greater Antilles.On three of the islands lizards were sub-sampled by collecting from moist woodland and more xeric habitats. These data suggest that differences between habitats are as significant as differences between islands in determining parasite burdens. Worm burdens of the commonest parasite species, T. cubensis, increased monotonically with host body size and no evidence was found to suggest that these parasites affect either host survival or fecundity. The sex-ratio of this species correlated with mean abundance of the parasite, with females the dominant sex on islands or in habitats where the parasite was common. This pattern may reflect haplodiploid sexual determination in this species.


First investigations of mountainous cold condensation effects with the CliMoChem model.
We present first results of a modeling study to explore the occurrence and extent of cold condensation effects in mountains with the CliMoChem model for a group of substances with different volatility and persistence. The mountainous region is set up in a generic way by modifying the precipitation rate and annual temperature course in a northern temperate zone. The results illustrate substance-specific tendencies to exhibit a cold condensation. While strong effects are observed for alpha-hexachlorocyclohexane and PCB-28, the less volatile compounds mirex and PCB-180 are less susceptible to mountainous cold condensation. An analysis of the temporal trends in concentrations indicates that mountain ranges first act as cold condensers, but may eventually become secondary emitters. Limitations of the modeling approach used are discussed and an outlook on further steps of model development and application is given.


Hydrocephalus-dementia-complex in Paget's disease.
The clinical triad of gait disturbances, memory impairment and urinary incontinence is associated with a communicating hydrocephalus in the 'normal pressure hydrocephalus'-syndrome. The authors present a case of H.D.C. (hydrocephalus-dementia-complex) in Paget's disease with an identical syndrome, but with obstructive hydrocephalus, causing a triventricular dilatation. Today, each case of mental deterioration in Paget's disease, should be immediately observed and neurosurgical intervention kept in view. An X-ray of the skull, a CT-scan of the brain and a cisternography are performed as routine procedure. If there are indications of involvement of the basis of the skull, hydrocephalus and/or disturbed pattern of the tracer-migration around the convexities, associated with a certain degree of dementia, impaired gait or urinary incontinence, a ventriculo-subcutaneous drain should be inserted. If clinical improvement follows, a ventriculatrial shunt is indicated. The post-operative clinical outcome seems to be dependent on some clinical and technical factors. The most eventful outcome is observed in cases where the clinial triad, described in patients with a classical 'normal pressure hydrocephalus'-syndrome, is associated with an obstructive hydrocephalus, due to a stenosis of the Sylvian aqueduct.


The CYP3A4*18 allele, the most frequent coding variant in asian populations, does not significantly affect the midazolam disposition in heterozygous individuals.
The objective of this study was to identify CYP3A4 variants in Koreans and to characterize their functional consequences in vitro and in vivo. Four single nucleotide polymorphisms were identified in 50 Koreans by direct DNA sequencing. In an additional genotyping using 248 subjects, CYP3A4(*)18 was confirmed as the most frequent coding variant in Koreans at 1.7%, and its frequency was similar to that of Asians, suggesting that CYP3A4(*)18 would be the highest coding variant in Asians. The recombinant CYP3A4.18 protein prepared in baculovirus expression system showed 67.4% lower Vmax and 1.8-fold higher K(m) for midazolam 1'-hydroxylation compared with the wild type. The mean values of Cmax and area under the concentration curve (AUC) in the CYP3A4(*)1/(*)18 and CYP3A5(*)1/(*)3 subjects (n = 8) were 63% and 32% higher than in CYP3A4(*)1/(*)1 and CYP3A5(*)1/(*)3 carriers (n = 8), respectively. Although the in vitro assay exhibited a significant reduction of the enzyme activity for midazolam, the in vivo differences associated with the CYP3A4(*)1/(*)18 tend to be low (P < 0.07 in Cmax and P < 0.09 in AUC). In summary, the heterozygous CYP3A4(*)1/(*)18 does not appear to cause a significant change of midazolam disposition in vivo; however, the clinical relevance of CYP3A4(*)18/(*)18 remains to be evaluated.


Safety profile and SARS-CoV-2 breakthrough infections among HCWs receiving anti-SARS-CoV-2 and influenza vaccines simultaneously: an Italian observational study.
In October/December 2021, World Health Organization and other international agencies recommended the offer of the third dose of anti-SARS-CoV-2 vaccine. In this period, the routine offer of seasonal influenza vaccination was also guaranteed and simultaneous administration of the two vaccines was encouraged. This study aims to evaluate the safety profile and to estimate the incidence of SARS-CoV-2 breakthrough infections in subjects receiving the anti-SARS-CoV-2 and influenza vaccines simultaneously. The study population was represented by healthcare workers (HCWs) of Bari Policlinico General Hospital who received the influenza (Flucelvax Tetra®) and/or anti-SARS-CoV-2 vaccination (BNT162b2 mRNA COVID-19 vaccine, Comirnaty®) either in coadministration or separately in October 2021. Reports of adverse events following immunization (AEFIs) were investigated to study the safety of both vaccines in coadministration and in separate-instance administration. Post-vaccination SARS-CoV-2 breakthrough infection was also studied. 942 HCWs accepted to join our study. 610/942 received both vaccines simultaneously. 25.26 % subjects (238/942) were only vaccinated against SARS-CoV-2, while the remaining 94 HCWs received the influenza vaccination first and subsequently received the anti-SARS-CoV2 booster dose. 717 HCWs reported AEFIs (Reporting Rate 76.1 per 100 subjects). Simultaneous administration of the two vaccines was not related with an increase of the rate of AEFIs compared to the single administration of SARS-CoV-2 vaccine, but the AEFIs' rate was lower among subjects who received only influenza vaccine. Post-vaccination SARS-CoV-2 infections were notified for 41.5 % of enrolled subjects (391/942). Incidence of breakthrough infection and symptomatic disease was not significantly different between the simultaneous administration group and other subjects. Our data suggests that simultaneous administration of a quadrivalent influenza vaccine and an mRNA anti-SARS-CoV-2 vaccine neither affected the safety of said products nor was associated with a higher risk of SARS-CoV-2 breakthrough infection.


Incidence of and Risk Factors for Glenohumeral Osteoarthritis After Anterior Shoulder Instability: A US Population-Based Study With Average 15-Year Follow-up.
The rate of osteoarthritis (OA) in patients with a history of previous anterior shoulder instability (ASI) varies within the literature, with the majority of studies investigating rates after surgical stabilization. ASI appears to lead to increased rates of OA, although risk factors for developing OA in cohorts treated nonoperatively and operatively are not well-defined. To determine the incidence of clinically symptomatic OA and identify potential risk factors for the development of OA in patients younger than 40 years with a known history of ASI. Case-control study; Level of evidence, 3. An established, geographically based database was used to identify patients in the United States who were younger than 40 years and were diagnosed with ASI between 1994 and 2014. Patient information, including demographic, imaging, and surgical details, was collected. Comparative analysis was performed between groups with and without OA at final follow-up as well as between patients who underwent surgical and nonsurgical management. The study population consisted of 154 patients with a mean follow-up of 15.2 years (range, 5.1-29.8 years). The mean age at initial instability event was 20.9 years (95% CI, 19.9-22.0 years). Overall, 22.7% of patients developed clinically symptomatic glenohumeral OA. Multivariate analysis revealed that current or former smokers (odds ratio [OR], 4.3; 95% CI, 1.1-16.5; P = .030), hyperlaxity (OR, 10.1; 95% CI, 1.4-72.4; P = .020), laborer occupation (OR, 6.1; 95% CI, 1.02-36.1; P = .043), body mass index (BMI) (OR, 1.2; 95% CI, 1.03-1.3; P = .012), and age at initial instability (OR, 1.1; 95% CI, 1.02-1.2; P = .013) as potential independent risk factors when accounting for other demographic and clinical variables. In a US geographic population of patients younger than 40 years with ASI, approximately one-fourth of patients developed symptomatic OA at a mean follow-up of 15 years from their first instability event. When accounting for differences in patient demographic and clinical data, we noted a potentially increased risk for the development of OA in patients who are current or former smokers, have hyperlaxity, are laborers, have higher BMI, and have increased age at initial instability event. Smoking status, occupation, and BMI are modifiable factors that could potentially decrease risk for the development of symptomatic OA in these patients.


[Mastocytosis in children].
Mastocytosis in children is a rare disease characterized by an abnormal accumulation of tissue mast cells. Mastocytosis in children presents with typical skin alterations that are classified as maculopapular cutaneous mastocytosis, diffuse cutaneous mastocytosis, or mastocytoma. Some patients also develop mast cell mediator symptoms, such as pruritus, flush, and anaphylaxis. In many children, the disease is characterized by a benign and usually self-limiting course; systemic mastocytosis with extracutaneous involvement and a chronic or progressive course is found only rarely. Therapeutically, H1 antihistamines are primarily used on an as-needed basis or as continuous treatment, depending on the severity. Children, parents and caregivers should be thoroughly educated about the clinical picture and possible trigger factors of mast cell mediator release. For children with extensive skin alterations and severe symptoms, the prescription of an epinephrine auto-injector is recommended for emergency treatment.


Human papillomavirus as a marker of the natural history and response to therapy of head and neck squamous cell carcinoma.
There has been a gradual change in the demographics of head and neck carcinoma. Although relatively uncommon, the incidence of oropharyngeal carcinoma has been increasing despite declining tobacco consumption and contrary to a diminishing incidence of cancers at other head and neck sites. It is now clear that the incidence of human papillomavirus (HPV)-associated oropharyngeal cancers is rising, likely as a consequence of changing life styles and sexual behaviors. Many studies have contributed to understanding the characteristics of HPV-related oropharyngeal carcinoma, which usually presents as nonkeratinizing squamous cell carcinoma of low to intermediate T-category and affects middle-aged white men, having higher socioeconomic status and no or brief history of tobacco consumption. The diagnosis of this distinct neoplastic entity can be firmly established by a combination of p16 immunohistochemical and in situ hybridization assays. Compared with the traditional smoking-associated head and neck squamous cell carcinoma, HPV-related oropharyngeal carcinoma has a favorable natural history and responds better to treatment. Consequently, patients with this cancer have better long-term survival than those with HPV-unrelated head and neck squamous cell carcinoma (eg, 5-year overall survival rate of >80% versus ∼40% for patients with stage III-IV tumors), and hence they are more likely to experience chronic therapy-induced morbidity. Therefore, changes in evaluation, staging, and treatment are needed for this patient group. However, attempts to change the treatment for HPV-associated oropharyngeal carcinoma should take place in a closely monitored clinical trial setting. In this article, we summarize the epidemiology, diagnosis, and clinical behavior of HPV-associated oropharyngeal carcinoma, with emphasis on prognostic and biomarker discovery aspects, and discuss briefly the current thoughts on changing the treatment paradigms aimed at reducing morbidity while preserving the high tumor control probability through well-coordinated prospective trials.


[Tobacco reduction in a prison of France].
Little is known about free nicotine transdermal patch efficacy on tobacco reduction in prisoners. The objective is to study this efficacy in prison as well as motivations to reduce and influence of socioeconomic conditions and other addictions in prisoners' aspiration to stop smoking. A prospective study was proposed to prisoners candidate to tobacco cessation. Assessment was made by questionnaires and visits to physicians working at the prison. Nicotinic patches were systematically proposed to patients with a starting 15 mg/16 h dose (or 10 mg/16 h if the dependence was low), followed by a 10 and 5 mg/16 h dose reduction. Prisoners motivated to smoking cessation (N=73) generally had multiaddictive behaviours and precarious socioeconomic profile. Thirty percent of prisoners self-reported a reduction of 50% of their cigarettes consumption until they left prison. Median duration of this successful treatment was 45 days. Median duration of treatment response for patients who relapsed in prison (15 %) was 75 days. No predictive factor of success was found. Tobacco reduction is possible in prison even if living conditions are not favourable.


HIV symptoms.
People with HIV/AIDS are a vulnerable group whose symptoms can seriously affect their quality of life. HIV/AIDS symptoms can result from the disease itself, from secondary complications of the disease, or from side-effects of highly active antiretroviral therapy (HAART) and other medications related to comorbidities. HIV symptoms are the single most important indicators for patients and practitioners. Symptoms prompt patients to seek medical attention and provide health care providers with essential clues about changes in health status and quality of life. Despite increased recognition of the importance of addressing symptoms among people with HIV/AIDS, few studies have examined the management of HIV symptoms. This chapter introduces HIV symptoms, reports on the methods of review, provides an overview of contextual issues including the literature on symptoms, issues related to symptom measures, theoretical foundations on symptom management, HIV-specific measures, non-HIV-specific measures, translation of findings into practice, and implications for future research and policy.


Rapid determination of polycyclic aromatic hydrocarbons in sewage sludges using microwave-assisted solvent extraction. Comparison with other extraction methods.
The presence of toxic organic micropollutants in municipal sewage sludges is a major problem on account of risks associated with the agricultural use of the sludges and therefore maximum tolerance limits are imposed. The aim of our study was to develop a reliable and fast analytical procedure for the determination of polycyclic aromatic hydrocarbons in sewage sludges, using focused microwave-assisted extraction. Optimization of the extraction conditions was performed on real matrices. The results of a 2(3) factorial design showed that extraction time was the only influential factor. The selected conditions (30 W, 10 min, 30 ml solvent) were used for real sludges and a certified marine sediment, leading to recoveries of between 56 and 75%. Results of an interlaboratory test confirmed these values. Finally, the technique was compared to traditional techniques (Soxhlet, sonication), and the more recent pressurized liquid extraction technique. Focused microwave-assisted extraction remains an attractive alternative technique due to its rapidity, the low solvent volume required and its moderate investment cost.


Sodium alginate as a mould release agent.
The use of sodium alginate as a mould release agent during the casting of epoxy or polyester resins in plaster moulds is discussed. The optimal concentration of a retarder is determined, taking into consideration the setting behaviour and the adhesive bond strength. The above characteristics are critical for the application and efficiency of the coating.


The influence of cocaine and desipramine on the cardiac responses to exogenous and endogenous norepinephrine.
In open-chest, anesthetized dogs, cocaine and desipramine potentiated the pressor, chronotropic, inotropic and coronary sinus blood flow responses to norepinephrine (NE) infusions. The chronotropic and inotropic responses were also prolonged, the former more markedly than the later and the extraction of exogenous NE from the coronary blood stream was diminished. Cocaine and desipramine also potentiated the pressor and coronary sinus blood flow responses, but not the chronotropic or inotropic responses, to stimulation of the left ansa subclavia. The inotropic response was slightly prolonged, however, and the chronotropic response was markedly prolonged. The overflow of NE into the coronary sinus blood was not increased by either neuronal uptake blocking agent. It is proposed that cocaine and desipramine, at the doses employed, diminish the release of NE from the cardiac nerve endings at the same time that they inhibit reuptake of the neurotransmitter. Their mechanisms of action and their side effects on the circulatory system do not appear to differ significantly.


Inducible NO synthase is constitutively expressed in porcine myocardium and its level decreases along with tachycardia-induced heart failure.
The adverse effects of oxidative stress and the presence of proinflammatory factors in the heart have been widely demonstrated mainly on rodent models. However, larger clinical trials focusing on inflammation or oxidative stress in heart failure (HF) have not been carried out. This may be due to differences in the anatomy and physiology of the cardiovascular system between small rodents and large mammals. Thus, we investigated myocardial inflammatory factors, such as inducible NO synthase (iNOS) and oxidative stress indices in female pigs with chronic tachycardia-induced cardiomyopathy. Homogenous female siblings of Large White breed swine (n=15) underwent continuous right ventricular (RV) pacing at 170bpm, whereas five sham-operated subjects served as controls. In the course of RV pacing, animals developed a clinical picture of HF and were euthanized at subsequent stages of the disease: mild, moderate and severe HF. Left ventricle (LV) sections were examined with electron microscopy. The relative expression of iNOS in LV was determined by quantitative PCR. The protein level of iNOS was determined by Western blotting and immunohistochemistry. The level of the S-nitrosylated (S-NO) protein in LV was determined after S-NO moieties were substituted by biotin, followed by a colorimetrical detection with streptavidin. Malondialdehyde (MDA), a marker of lipid peroxidation, was evaluated in the LV and serum using thiobarbituric acid. The aconitase activity (based on measurement of the concomitant formation of NADPH from NADP(+)), a marker of oxidative stress, was analyzed in mitochondrial and cytosolic LV fractions. The concentration of interleukin-1β (IL-1β) was measured in LV homogenates using enzyme-linked immunosorbent assay. RV pacing resulted in an impairment of LV systolic function, LV dilatation and neurohormonal activation. The electron microscopy revealed abnormalities within the cardiomyocytes of failing hearts, i.e. swollen mitochondria and myofibril derangement. iNOS was expressed in the control LV myocardium. The development of HF was accompanied by a decrease in iNOS mRNA (P<.05), which was also reflected at a protein level, and a decrease in the protein S-nitrosylation (P<.05). Both iNOS mRNA and S-NO relative moiety levels were inversely related to the dilatation of the LV (P<.05). There was no difference in the concentration of MDA in the LV and serum. Similarly, no differences in the concentration of IL-1β LV were found between diseased and healthy animals. Aconitase activity was decreased only in the LV mitochondrial fraction of pigs with severe HF. iNOS was shown to be constitutively expressed within porcine LV. Its level decreases during the progression of systolic nonischemic HF in the pig model. Thus, it can be assumed that an up-regulation of proinflammatory factors is not involved in porcine tachycardia-induced cardiomyopathy and that the impact of oxidative stress may be restricted to the mitochondria in this HF model.


Acylated cyanidin 3-sophoroside-5-glucoside in purple-violet flowers of Moricandia arvensis (Brassicaceae).
A new acylated anthocyanin was isolated as a major pigment, along with a known anthocyanin (Moricandia arvensis anthocyanin 1: MAA-1), from a strain of Moricandia arvensis (Code No. MOR-ARV-3) with purple-violet flowers, and identified as cyanidin 3-O-[2-O-(2-O-(4-O-(6-O-(4-O-(β-glucopyranosyl)-trans-caffeoyl)-β-glucopyranosyl)-trans-sinapoyl)-β-glucopyranoside]-5-O-[6-O-(malonyl)-β-glucopyranoside].


Opioid replacement therapy with methadone or buprenorphine effects on male mice reproduction.
Opioid use disorders are commonly treated by long-acting agonist opioids including methadone and buprenorphine which could affect various aspects of male reproduction especially spermatogenesis. We aimed to determine whether detoxification with methadone or buprenorphine was associated with reproductive disorders in male mice. We orally induced morphine dependence in NMRI male mice, and then performed detoxification programs using either methadone or buprenorphine. Testis architecture and sperm parameters including sperm nuclear DNA integrity, mitochondrial activity, oxidative stress in seminal plasma, and routine sperm parameters were assessed to find the involved mechanisms. The number of Leydig cells and the thickness of germinal epithelium reduced following morphine use and increased differently after detoxification with methadone or buprenorphine. Morphine dependence and detoxification with methadone and buprenorphine had different effects on sperm parameters. Morphine altered chromatin integrity, mitochondrial activity, and oxidative stress in sperm. Detoxification with methadone improved mitochondrial activity but worsened chromatin integrity, whereas detoxification with buprenorphine improved neither chromatin integrity nor mitochondrial activity. Seminal plasma oxidative stress was higher in the treated groups compared to control groups but was comparable among treatment groups. Our study revealed that long-term morphine use followed by detoxification with methadone or buprenorphine impairs testis structure and sperm parameters. Detoxification from morphine use with methadone and buprenorphine led to different preclinical outcomes in semen quality parameters, including chromatin integrity. Therefore, clinical detoxification protocols should be performed more cautiously, considering the desire of the individuals to reproduce.


Palladium-catalyzed coupling of amides and cyclopropanols for the synthesis of γ-diketones.
A palladium catalytic method has been developed for the coupling of amides and cyclopropanols to γ-diketones, through simultaneous C-N and C-C activation. Heteroatom ligand exchange and heteroatom-to-carbon ligation mode switching enable the achievement of molecular cross-coupling in an amide N-atom structural context-dependent manner, avoiding any stoichiometric organometallic reagent or base.


Transplantation of human adipose-derived stem cells in a rabbit model of traumatic degeneration of lumbar discs.
The purpose of the present study is to assess the possibility of disc regeneration by treatment with adipose-derived stem cells (ADSCs) in a rabbit model of degenerative disc disease, and to evaluate the efficacy of a percutaneous technique for constructing a model of degenerative disc disease in rabbits. The study sample consisted of 20 mature male New Zealand white rabbits. Intervertebral discs were injured in each rabbit by a percutaneous technique at L2-3, L3-4, and L4-5 under C-arm guidance with a 19-gauge spinal needle. Magnetic resonance images (MRI) were checked at 6, 9, 12, and 15 weeks after injury to evaluate disc degeneration. Nineteen weeks after injury, ADSCs were injected into the L4-5 disc space, with saline injected into the L3-4 disc as a control, using a 21-gauge spinal needle. Histologic confirmations of degenerated discs were performed at 10 and 18 weeks after injury with safranin O and trichrome stains. MRI revealed intervertebral disc degeneration from 9 weeks after injury, and full degeneration at 15 weeks after injury, when compared with uninjured control discs. We confirmed the proliferation of ADSCs at the L4-5 level in 10-week rabbits after cell injection. Histologically, the ADSC-injected discs exhibited elevated extracellular matrix secretion and little ossification of damaged cartilage in the nucleus pulposus compared with degenerative control discs. These results suggest that the injection of ADSCs into injured lumbar discs could be an effective treatment for degenerative disc disease by promoting the cartilage regeneration.


Understanding Perspectives of African American Medicaid-Insured Women on the Process of Perinatal Care: An Opportunity for Systems Improvement.
Objectives To address disparities in adverse birth outcomes, communities are challenged to improve the quality of health services and foster systems integration. The purpose of this study was to explore the perspectives of Medicaid-insured women about their experiences of perinatal care (PNC) across a continuum of clinical and community-based services. Methods Three focus groups (N = 21) were conducted and thematic analysis methods were used to identify basic and global themes about experiences of care. Women were recruited through a local Federal Healthy Start (HS) program in Michigan that targets services to African American women. Results Four basic themes were identified: (1) Pursuit of PNC; (2) Experiences of traditional PNC; (3) Enhanced prenatal and postnatal care; and (4) Women's health: A missed opportunity. Two global themes were also identified: (1) Communication with providers, and (2) Perceived socio-economic and racial bias. Many women experienced difficulties engaging in early care, getting more help, and understanding and communicating with their providers, with some reporting socio-economic and racial bias in care. Delays in PNC limited early access to HS and enhanced prenatal care (EPC) programs with little evidence of supportive transitions to primary care. Notably, women's narratives revealed few connections among clinical and community-based services. Conclusions The process of participating in PNC and community-based programs is challenging for women, especially for those with multiple health problems and living in difficult life circumstances. PNC, HS and other EPC programs could partner to streamline processes, improve the content and process of care, and enhance engagement in services.


Determination of imidazole derivatives by micellar electrokinetic chromatography combined with solid-phase microextraction using activated carbon-polymer monolith as adsorbent.
In this study, an effective method for the separation of imidazole derivatives 2-methylimidazole (2-MEI), 4- methylimidazole (4-MEI) and 2-acetyl-4-tetrahydroxybutylimidazole (THI) in caramel colors using cation-selective exhaustive injection and sweeping micellar electrokinetic chromatography (CSEI-sweeping-MEKC) was developed. The limits of detection (LOD) and quantitation (LOQ) for the CSEI-sweeping-MEKC method were in the range of 4.3-80μgL(-1) and 14-270μgL(-1), respectively. Meanwhile, a rapid fabrication activated carbon-polymer (AC-polymer) monolithic column as adsorbent for solid-phase microextraction (SPME) of imidazole colors was developed. Under the optimized SPME condition, the extraction recoveries for intra-day, inter-day and column-to-column were in the range of 84.5-95.1% (<6.3% RSDs), 85.6-96.1% (<4.9% RSDs), and 81.3-96.1% (<7.1% RSDs), respectively. The LODs and LOQs of AC-polymer monolithic column combined with CSEI-sweeping-MEKC method were in the range of 33.4-60.4μgL(-1) and 111.7-201.2μgL(-1), respectively. The use of AC-polymer as SPME adsorbent demonstrated the reduction of matrix effect in food samples such as soft drink and alcoholic beverage thereby benefiting successful determination of trace-level caramel colors residues using CSEI-sweeping-MEKC method. The developed AC-polymer monolithic column can be reused for more than 30 times without any significant loss in the extraction recovery for imidazole derivatives.


Systemic Treatment of Soft Tissue Sarcomas in the Geriatric Population.
As the population ages, there will be an increase in the incidence and prevalence of soft tissue sarcoma (STS) within the geriatric population. As this disease disproportionately affects older adults, the percentage of adults >65 years old is expected to increase in the coming years. Geriatric patients are often more vulnerable to disease-related symptoms and have more difficulty tolerating treatment-related side effects. While there are no formal existing guidelines to direct the care of this geriatric patient population, it is of utmost importance to consider each patients' fitness and co-morbidities when selecting treatment plans. This review focuses on the current state of research of older adults with advanced or metastatic soft tissue sarcoma, highlighting the lack of representation of this patient population in clinical trials. Given that chronological age does not necessarily equate to physiologic age, integration of comprehensive geriatric and quality of life assessments is needed in the care of geriatric patients to help guide therapeutic decisions.


Globin chain separation by SDS polyacrylamide gel electrophoresis. Simple screening method for elongated hemoglobin chains.
A simple method for the separation of hemoglobin chains from hemolysate or globin, by sodium dodecyl sulfate polyacrylamide gel electrophoresis, is described. The alpha, beta, and gamma chains can be clearly separated from each other. The alpha chain has the highest mobility, the beta chain has a slower mobility than the gamma chain, while the delta chain has about the same mobility as the beta chain. Hemoglobins with elongated chains can easily be detected by this method. Tak-beta, elongated by 11 residues, moves much more slowly than betaA but is much faster than alpha Constant Spring which is elongated by 31 residues. Screening of several individuals with slow-moving hemoglobins using this method led to the finding of a case with Hb Tak-beta thalassemia and other carriers of Hb Tak.


Single and choice reaction time during prolonged exercise in trained subjects: influence of carbohydrate availability.
The aim of the present study was to examine the effects of prolonged exercise at the ventilatory threshold and carbohydrate ingestion on single (SRT) and choice (CRT) reaction time. Eight well-trained triathletes completed three testing sessions within a 3-week period. Maximal oxygen uptake was determined in the first test, whereas the second and the third sessions were composed of a 100-min run (treadmill 15 min, overground 70 min, treadmill 15 min) performed at the velocity associated with the ventilatory threshold. During these submaximal tests, the subjects ingested (in random order) 8 ml x kg(-1) body weight of either a placebo (Pl) or 5.5% carbohydrate (CHO) solution prior to the first submaximal run and 2 ml x kg(-1) body weight every 15 min after that. The cognitive tasks were performed before and after exercise for CRT, and before, during each submaximal run and after exercise for SRT. Furthermore, at the end of each submaximal test subjects were asked to report their rating of perceived exertion (RPE). Results showed a significant positive effect of CHO ingestion on RPE and CRT performance at the end of exercise, while no effect of exercise duration was found in the Pl condition. After a 100-min run, during the CHO condition, CRT mean (SD) group values decreased from 688.5 (51) ms to 654 (63) ms, while during the Pl condition, RPE mean group values increased from 11 (2) to 16 (1.02) and CRT mean values remained stable [688 (104) ms vs 676 (73.4) ms, P > 0.05]. No similar effect was observed for SRT. These results suggest that CHO-electrolyte ingestion during a 100-min run results in an improvement in the complex cognitive performance measured at the end of that run.


Reproductive performance of two generations of female semidomesticated mink fed diets containing organic mercury contaminated freshwater fish.
Semidomesticated female mink (Mustela vison) were fed daily diets containing 0.1 ppm, 0.5 ppm, and 1.0 ppm of total mercury. Piscivorous and nonpiscivorous fish naturally contaminated with organic mercury were used to prepare the diets. Twenty-month-old females (G1 generation) that were exposed to the experimental diets for approximately 400 days in 1994 and 1995 and their 10-month-old female offspring (G2 generation) that were exposed to mercury for approximately 300 days in 1995, were all mated to 10-month-old males. Males were fed the diet containing 0.1 ppm mercury 60 days prior to the mating season. Diets containing 0.1 ppm and 0.5 ppm were not lethal to G1 and G2 females for an exposure period of up to 704 days. At the age of 11 months, mortalities occurred in 1994 for G1 females (30/50) and in 1995 for G2 females (6/7) fed the 1.0 ppm mercury diet after 90 days and 330 days of exposure, respectively. The length of the gestation periods and the number of kits born per female were not different among dietary groups for the two generations of females. The proportion of females giving birth was low for all groups, except for the G1 females fed the 0.1 ppm diet. There was an inverse relationship between whelping proportion and exposure group, but was not statistically significant. There was evidence that kits were exposed to mercury both in utero and/or during lactation as indicated by the presence of mercury in their livers. Mercury exposure did not influence the survival and growth of neonatal kits.


Autolysis loop restricts the specificity of activated protein C: analysis by FRET and functional assays.
We previously demonstrated that the substitution of the autolysis loop (residues 143-154 in chymotrypsin numbering) of APC with the corresponding loop of trypsin (APC-Tryp 143-154) has no influence on the proteolytic activity of the protease toward fVa, however, this substitution increases the reactivity of APC with plasma inhibitors so that the mutant exhibits no anticoagulant activity in plasma. To further investigate the role of the autolysis loop in APC and determine whether this loop is a target for modulation by protein S, we evaluated the activity of APC-Tryp 143-154 toward fVa and several plasma inhibitors both in the absence and presence of protein S. Furthermore, we evaluated the active-site topography of APC-Tryp 143-154 by determining the average distance of the closest approach (L) between a fluorescein dye tethered to a tripeptide inhibitor, attached to the active-site of APC-Tryp 143-154, and octadecylrhodamine dyes incorporated into PCPS vesicles both in the absence and presence of protein S. The activity of APC-Tryp 143-154 toward fVa was identical to that of wild-type APC both in the presence and absence of protein S. However, the reactivity of APC-Tryp 143-154 with plasma inhibitors was preferentially improved independent of protein S. The FRET analysis revealed a dramatic change in the active-site topography of APC both in the absence and presence of protein S. Anisotropy measurements revealed that the fluorescein dye has a remarkable degree of rotational freedom in the active-site of APC-Tryp 143-154. These results suggest that the autolysis loop of APC may not be a target for modulation by protein S. This loop, however, plays a critical role in restricting both the specificity and spatial environment of the active-site groove of APC.


Preconcentration and frontal electroelution of amino acids for in-line solid-phase extraction-capillary electrophoresis.
A new frontal electroelution approach that can be used for the preconcentration of amino acids in in-line solid-phase extraction-capillary electrophoresis (SPE-CE) has been developed. A single capillary was employed featuring a short monolithic SPE column created inside the capillary via photo-initiated, free-radical polymerisation of 3-sulfopropyl methacrylate and butyl methacrylate monomers. A weak electrolyte of dilute H2SO4, pH 2.9, was found to promote adsorption of the amino acids onto the SPE column. Elution of the amino acids was achieved using a dual solvation/ion-exchange transient boundary mobilised via EOF by using a strong electrolyte containing 62.5mM ethylenediamine, pH 2.9 with H2SO4 and 40% (v/v) acetonitrile. Using these two electrolytes, tryptophan was adsorbed onto the SPE column in weak electrolyte and eluted via a frontal electroelution mechanism in the strong electrolyte. Injections up to 20 min, corresponding to over 14 column volumes (or 1400% of the capillary volume) of sample provided quantitative extraction of tryptophan from the weak electrolyte and were eluted without any loss in efficiency. This represents a practical increase of approximately 300-fold when compared to a typical hydrodynamic injection occupying 5% of the capillary volume.


Short-term modulation of the ipsilateral primary sensory cortex by nociceptive interference revealed by SEPs.
We studied the modulation of the topographic arrangement of the human ipsilateral primary somatosensory cortex following interference of nociceptive stimuli by means of dipole source analysis. Multichannel somatosensory evoked potentials were obtained by electrical stimulation of digits 1 and 5 of the left hand before, during and after the application of pain to digits 2-4 of the right hand. The primary cortical response of the SEP (N20) was obtained for dipole localization of the representation of the primary sensory cortex receiving input from digits 1 to 5. The 3D-distance between these sides was calculated for further analysis. To account for possible attentional effects recordings were performed while simultaneously to this intervention subjects were asked to turn their attention to the right or left hand in a pseudorandom order. The application of pain induced an expansion of the 3D-distance between digits 1 and 5. Focusing attention to the stimulated limb or the site of the intervention did not yield to an additional effect. Our results provide further evidence for the presence of a quickly adapting interaction between primary somatosensory areas of both hemispheres following an interference of nociceptive stimulation in SEPs. This modifying process is probably mediated by interhemispheric and intercortical connections leading to hyperexcitability of the primary sensory cortex contralateral to that receiving nociceptive input. Spatial attention does not seem to have an impact on this kind of short-term intercortical plasticity.


Heavy metal and mineral concentrations and their relationship to histopathological findings in the bowhead whale (Balaena mysticetus).
The bowhead whale (Balaena mysticetus) is a species endangered over much of its range that is of great cultural significance and subsistence value to the Inuit of Northern Alaska. This species occupies subarctic and arctic regions presently undergoing significant ecological change and hydrocarbon development. Thus, understanding the health status of the Bering-Chukchi-Beaufort Sea (BCBS) stock of bowhead whales is of importance. In this study, we evaluated the concentrations of six essential and non-essential elements (Zn, tHg, Ag, Se, Cu and Cd) in liver and kidney of bowhead whales (n=64). These tissues were collected from the Inuit subsistence hunt in Barrow, Wainwright and Kaktovik, Alaska between 1983 and 2001. Reference ranges of these elements (including previously reported data from 1983-1997) were developed for this species as part of a health assessment effort, and interpreted using improved aging techniques (aspartic acid racemization and baleen isotopic (13)C methods) to evaluate trends over time with increased statistical power. Interactions between element concentrations and age, sex and harvest season were assessed. Age was found to be of highest significance. Sex and harvest season did not effect the concentrations of these elements, with the exception of renal Se levels, which were significantly higher in fall seasons. In addition, histological evaluation of tissues from whales collected between 1998-2001 was performed. Associations between concentrations of Cd in kidney and liver and scored histopathological changes were evaluated. Liver Cd concentration was strongly associated with the degree of lung fibromuscular hyperplasia (P=0.001) and moderately associated with the degree of renal fibrosis (P=0.03). Renal Cd concentration influenced the degree of lung fibromuscular hyperplasia and renal fibrosis (P=0.01). A significant age effect was found for both pulmonary fibromuscular hyperplasia and renal fibrosis, indicating age may be a causative factor. Improvements in aging techniques and the addition of histological indices help clarify the relationships between elements and the influence of life history parameters on concentrations of these elements and potential impacts on health. These data provide essential baseline input useful for monitoring the effects of arctic ecosystem change as it relates to global climate change and industrial development, as well as help inform epidemiological studies examining the public health implications of heavy metals in subsistence foods.


Prostate cancer.
Essential facts Prostate cancer starts in the prostate gland, at the base of the bladder in men. It surrounds the first part of the urethra, which carries urine from the bladder. The prostate gland helps in the production of semen, which is also carried in the urethra. It is the most common cancer in men - one in eight will develop it during their lifetime.


Reliability, sensitivity, and predictive value of fMRI during multiple object tracking as a marker of cognitive training gain in combination with tDCS in stroke survivors.
Computerized cognitive training (CCT) combined with transcranial direct current stimulation (tDCS) has showed some promise in alleviating cognitive impairments in patients with brain disorders, but the robustness and possible mechanisms are unclear. In this prospective double-blind randomized clinical trial, we investigated the feasibility and effectiveness of combining CCT and tDCS, and tested the predictive value of and training-related changes in fMRI-based brain activation during attentive performance (multiple object tracking) obtained at inclusion, before initiating training, and after the three-weeks intervention in chronic stroke patients (>6 months since hospital admission). Patients were randomized to one of two groups, receiving CCT and either (a) tDCS targeting left dorsolateral prefrontal cortex (1 mA), or (b) sham tDCS, with 40s active stimulation (1 mA) before fade out of the current. Of note, 77 patients were enrolled in the study, 54 completed the cognitive training, and 48 completed all training and MRI sessions. We found significant improvement in performance across all trained tasks, but no additional gain of tDCS. fMRI-based brain activation showed high reliability, and higher cognitive performance was associated with increased tracking-related activation in the dorsal attention network and default mode network as well as anterior cingulate after compared to before the intervention. We found no significant associations between cognitive gain and brain activation measured before training or in the difference in activation after intervention. Combined, these results show significant training effects on trained cognitive tasks in stroke survivors, with no clear evidence of additional gain of concurrent tDCS.


Tomato marchitez virus, a new plant picorna-like virus from tomato related to tomato torrado virus.
A new virus was isolated from a tomato plant from the state of Sinaloa in Mexico. This plant showed symptoms locally known as 'marchitez disease': severe leaf necrosis, beginning at the base of the leaflets, and necrotic rings on the fruits. A virus was isolated from the infected plant consisting of isometric particles with a diameter of approximately 28 nm. The viral genome consists of two (+)ssRNA molecules of 7221 (RNA1) and 4898 nts (RNA2). The viral capsid contains three coat proteins of 35, 26 and 24 kDa, respectively. The abovementioned characteristics: symptoms, morphology, number and size of coat proteins, and number of RNAs are similar to those of the previously described tomato torrado virus (ToTV). Sequence analysis of the entire viral genome shows that this new virus is related to, but distinct from, ToTV and that these members of two obviously new virus species belong to the recently proposed plant virus genus Torradovirus. For this new virus, the name tomato marchitez virus (ToMarV) is proposed.


Potential next-generation medications for self-administered platforms.
The Coronavirus Disease (COVID-19) pandemic has reshaped clinical chronic disease management. Patients reduced the number of physical clinic visits for regular follow-up care because of the pandemic. However, in developing countries, the scattered healthcare system hindered accessibility to clinical consultation, and poorly controlled chronic diseases resulted in numerous complications. Furthermore, the longer patients suffered from the chronic disease being treated, the more physical and psychological stress they experienced. "Diabetes Burnout," as an example, is a term to describe the phenomenon of psychological reluctance in long-term glycemic control. A comprehensive, patient-centered, and automatic drug administration and delivery model may reduce patient stress and increase compliance. Potential next-generation medication platforms, consisting of internal regulation and external interaction, may conduct autonomous dose adjustment and continuous selfmonitoring with the assistance of artificial intelligence, telemedicine, and wireless technologies. Internal regulation forms a closed-loop system in which drug administration is optimized in an implanted drug-releasing device according to a patient's physiopathological response. The other feature, external interaction, creates an ecosystem among patients, healthcare providers, and pharmaceutical researchers to monitor and adjust post-market therapeutic efficacy and safety. These platforms may provide a solution for self-medication and self-care for a wide variety of patients but may be life-changing for patients who live in developing countries where the healthcare system is scattered, as they could effectively remove healthcare barriers. As the technology matures, these self-administrated platforms may become more available and increasingly affordable, offering considerable impact to health and wellness efforts worldwide.


Detection of a novel human class II HLA antigen.
Genetic, molecular and cellular analyses of the HLA-D region of the major histocompatability complex (MHC) in man have led to the definition of three different products. Two of these, DR and MB (the latter also known as DC (ref. 1) and LB-E (ref. 2)) are defined with serological reagents; the third, known as SB (ref. 3) and PL-3 (ref. 4) is defined with primed lymphocyte typing (PLT) cells. The classical features attributed to HLA-D region encoded (class II) molecules are that they are cell-surface dimers consisting of a structurally conserved alpha-chain noncovalently associated with a polymorphic beta-chain and that they are found primarily on B lymphocytes, some monocyte populations, endothelial and certain other cells. Using these criteria a monoclonal antibody, B7/21, was described as reactive with HLA-DR (ref. 7). We have now re-evaluated B7/21 antibody reactivity using mutant lymphoblastoid cell lines. It appears that this antibody does not react with the molecularly defined D region products described to date but instead, recognizes a class II antigen with distinctive molecular characteristics. We provisionally refer to this antigen as FA.


Pollinator-dependent crops: an increasingly risky business.
Three-quarters of leading global food crops rely on animal pollination. With both managed and wild pollinators declining, is there reason for concern? Researchers are beginning to pin down the possible long-term risks.


Gender differences in cardiovascular risk factors among adolescents in Aseer Region, southwestern Saudi Arabia.
The objective of this study was to explore gender differences in the prevalence of silent and clinical apparent cardiovascular risk factors among adolescents in Aseer Region, southwestern Saudi Arabia. A cross-sectional study on a stratified sample of 1869 adolescents was carried out. They were interviewed and examined for weight and height, systolic and diastolic blood pressure using standardized techniques. The study revealed high prevalence of some potential behavioral and biological cardiovascular diseases (CVD) risk factors among adolescent males and females in the study area. Behavioral risk factors included inadequate low consumption of fruits and vegetables, physical inactivity, and smoking. Physical inactivity was significantly more prevalent among females than males (42.9% and 25.7%, respectively). Smoking was significantly more among females than males (11.8% and 1.3%, respectively). Biological risk factors found were family history of CVD, obesity and high blood pressure. Obesity was significantly prevalent among females (29.4%) compared to males (20.6%). Males had significantly more high blood pressure than females. In logistic regression analysis, being male (aOR = 2.992, 95% CI = 1.933-4.742) and obesity (aOR = 2.995, 95% CI = 2.342-3.991) were found to be significant risk factors in developing high blood pressure among adolescents in the region. Presence of cardiovascular risk factors among adolescents is a public health problem in the region. There is a need for a national program in the country to prevent and control cardiovascular risk factors among adolescents.


Interaction of inorganic nanoparticles with the skin barrier: current status and critical review.
Integration of nanotechnology with biology leads to various advantages in applied pharmaceutical and medical sciences. In that regard, the behavior of nanoparticles (NPs) in relation to the skin, an important biological barrier, has been the target of several recent studies. Yet the potential ability of NPs to penetrate into the underlying viable tissue lies at the center of debate. This review briefly highlights the current applications of inorganic NPs, then discusses the current status of their skin penetration in view of the vast variation among the experimental setups in use. Determinants of particle penetration, adopted approaches for enhanced penetration, the underlying mechanism, as well as qualitative and quantitative analysis of NPs present in the skin are also within the scope of this review article. We emphasize analyzing the data generated from experiments on human skin, the "gold standard" for assessment of in vitro skin penetration. Based on this, we include some recommendations for future research. Transdermal application of inorganic nanoparticle-based medications is of growing interest in nanomedicine research. This critical review discusses the knowns and the unknowns of this field, providing insightful recommendations for future research.


Isolation and preliminary characterization of bacteriocins produced by Vibrio vulnificus.
The aim of this work was to isolate bacteriocins from the environment that would be effective in neutralizing Vibrio vulnificus in seafood. Water samples from Wilmington (NC, USA) were plated to determine total viable counts and to isolate presumptive Vibrio spp. Isolates containing plasmids were checked for antimicrobial activity which was not due to lytic bacteriophage or small, non-specific molecules. Three bacteriocin producers were detected and their inhibitory spectra determined: IW1 inhibited few strains of V. vulnificus; BC1 inhibited several strains of V. vulnificus, V. cholerae and V. parahaemolyticus and BC2 inhibited all tested Vibrio spp., Plesiomonas shigelloides and Escherichia coli. Loss of inhibitory activity coincided with loss of the bacteriocinogenic plasmid. The bacteriocins were found to be between 1.3 and 9.0 kDa. IW1 was heat labile, while BC1 was moderately stable except at extreme temperatures. BC2 was very stable and maintained its activity when frozen, autoclaved or exposed to extreme pH values. Bacteriocins have been isolated from environmental isolates of V. vulnificus and V. cholerae. BC2, with its broad spectrum and stability, may be useful in neutralizing V. vulnificus. The results have significance in relation to reducing the occurrence of food poisoning caused by V. vulnificus.


[Popliteal pseudoaneurysm as a complication in total knee replacement. Presentation of a case and an updated literature review].
Vascular complications are rare after total knee arthroplasty, and popliteal pseudoaneurysms are even more so. There are few cases reported in the literature. We present a case of an 80 year-old woman with osteoarthritis of the left knee, secondary to Genu varum, who was treated with total knee arthroplasty. On the discharge day after surgery, the patient suffered a popliteal pseudoaneurysm that was successfully treated with an intravascular stent introduced by an inguinal approach.


Structural basis of the myosin X PH1(N)-PH2-PH1(C) tandem as a specific and acute cellular PI(3,4,5)P(3) sensor.
Myosin X (MyoX) is an unconventional myosin that is known to induce the formation and elongation of filopodia in many cell types. MyoX-induced filopodial induction requires the three PH domains in its tail region, although with unknown underlying molecular mechanisms. MyoX's first PH domain is split into halves by its second PH domain. We show here that the PH1(N)-PH2-PH1(C) tandem allows MyoX to bind to phosphatidylinositol (3,4,5)-triphosphate [PI(3,4,5)P(3)] with high specificity and cooperativity. We further show that PH2 is responsible for the specificity of the PI(3,4,5)P(3) interaction, whereas PH1 functions to enhance the lipid membrane-binding avidity of the tandem. The structure of the MyoX PH1(N)-PH2-PH1(C) tandem reveals that the split PH1, PH2, and the highly conserved interdomain linker sequences together form a rigid supramodule with two lipid-binding pockets positioned side by side for binding to phosphoinositide membrane bilayers with cooperativity. Finally, we demonstrate that disruption of PH2-mediated binding to PI(3,4,5)P(3) abolishes MyoX's function in inducing filopodial formation and elongation.


Effect of sera from acute lymphoblastic leukemia children on proliferation and differentiation of HL-60 promyelocytic leukemia cell line.
Influence of sera of children with ALL on character (dispersed or compact) and composition (granulocyte or macrophage) of colonies, formed from the human promyelocytic leukemia cell line HL-60, was estimated. An increased activities stimulating formation of dispersed G and M colonies was found in the sera of patients before therapy. Dynamics of colonies formation and their composition in the course of treatment point to some changes in the serum the levels of these activities with a tendency to full normalization in remission.


Incidence of anti-heparin/platelet factor 4 antibodies and heparin-induced thrombocytopenia in medical patients.
Heparin-induced thrombocytopenia (HIT) is a life threatening complication of heparin therapy, causing thrombosis. The aim of our study was to find out the frequencies of HIT antibody seroconversion and clinical HIT in Turkish medical patients on different forms of heparins. Our study included 61 patients who were on unfractionated heparin (UFH) (n: 37) and low molecular weight heparin (LMWH) (n: 24) therapies. The frequency of HIT antibody formation was determined by means of antigenic (ELISA), and functional assays (serotonin release assay-SRA). The seroconversion rates in UFH and LMWH groups were found to be 18.9% and 4.1% (ELISA), and 8.1% and 4.1% (SRA), respectively. One patient (2.1%) on UFH therapy developed deep vein thrombosis. No thromboembolic event was observed in patients taking LMWH. Seroconversion rates by means of antigenic and functional assays and clinical HIT were more common in patients on UFH than patients on LMWH therapy.


Research culture in Australian and New Zealand radiation oncology: Fact or fantasy?
Fostering a research culture is a key goal of the Royal Australian and New Zealand College of Radiologists, yet there has never been an organization-wide enquiry into the extent to which this is being realized. The purpose of this work was to address that deficit for the Radiation Oncology (RO) Faculty to serve as a baseline for future comparison. The hypothesis was that such a culture is closer to fact than fantasy. With College approval, three de-identified Excel spreadsheets detailing 25 research-related sub-categories of the Faculty's Continuing Professional Development (CPD) database were interrogated for the 2019-21 triennium, accepting that research activity in 2020-21 would be COVID-19 suppressed. The numbers obligated to self-report CPD were 482, 496 and 511, respectively. Primary endpoints were the percentages of ROs claiming at least one research-related activity overall, and in each of the sub-categories individually, by year. Secondary endpoints were the "breadth" (number of sub-categories claimed/individual) and "depth" (percentages solely claiming in one of four lower-level sub-categories), by year. ROs claimed in 23/25 sub-categories. The percentages of ROs claiming at least one research-related activity were 71%, 44%, and 62% in 2019-21, respectively. The median number of sub-categories claimed by these ROs was 2 (range 1-10) in each year. The commonest activity was journal article co-author (25%, 16% and 27%, respectively). For 2019, the most representative year, other common activities were inhouse/local meeting presentation (17%), invited lecture at state level or above (15%), manuscript peer review and research project principal investigator (14% each). The percentages of ROs solely claiming in one lower-level activity ranged between 4.4% and 5.9% per year. A culture of research is arguably more fact than fantasy in ANZ. It is likely that Faculty curriculum requirements, research funding and other promotional initiatives have contributed substantively to this.


Cleaning up alpha-1 antitrypsin deficiency related liver disease.
Alpha-1 antitrypsin deficiency (AATD) is one of the most common genetic disorders arising due to mutations in alpha-1 antitrypsin (AAT) gene affecting primarily the lung and the liver. This review summarizes the pathophysiology and clinical manifestation of different AATD genotypes and discusses the recent therapeutic developments. The focus is on the severe, rare homozygous Pi∗ZZ and the common heterozygous Pi∗MZ genotype. Pi∗ZZ individuals harbor an up to 20 times higher risk of liver fibrosis and cirrhosis than noncarriers and liver transplantation is currently the only available therapeutic option. AATD constitutes a proteotoxic disorder arising from hepatic AAT accumulation and the currently most promising data come from a phase 2, open-label trial of fazirsiran, a hepatocyte-targeted siRNA. Pi∗MZ subjects display an increased risk of advanced liver disease and at the latter stage, a faster deterioration than individuals without AAT mutation. Although the fazirsiran data offer a glimpse of hope to AATD patients, a consensus on appropriate study endpoint, a careful patient selection as well as monitoring of long-term safety will be essential for an approval.


Implementation of the pre-operative rehabilitation recovery protocol and its effect on the quality of recovery after colorectal surgeries.
Patients' recovery after surgery is the major concern for all perioperative clinicians. This study aims to minimize the side effects of peri-operative surgical stress and accelerate patients' recovery of gastrointestinal (GI) function and quality of life after colorectal surgeries, an enhanced recovery protocol based on pre-operative rehabilitation was implemented and its effect was explored. A prospective randomized controlled clinical trial was conducted, patients were recruited from January 2018 to September 2019 in this study. Patients scheduled for elective colorectal surgeries were randomly allocated to receive either standardized enhanced recovery after surgery (S-ERAS) group or enhanced recovery after surgery based on pre-operative rehabilitation (group PR-ERAS). In the group PR-ERAS, on top of recommended peri-operative strategies for enhanced recovery, formatted rehabilitation exercises pre-operatively were carried out. The primary outcome was the quality of GI recovery measured with I-FEED scoring. Secondary outcomes were quality of life scores and strength of handgrip; the incidence of adverse events till 30 days post-operatively was also analyzed. A total of 240 patients were scrutinized and 213 eligible patients were enrolled, who were randomly allocated to the group S-ERAS (n = 104) and group PR-ERAS (n = 109). The percentage of normal recovery graded by I-FEED scoring was higher in group PR-ERAS (79.0% vs. 64.3%, P < 0.050). The subscores of life ability and physical well-being at post-operative 72 h were significantly improved in the group PR-ERAS using quality of recovery score (QOR-40) questionnaire (P < 0.050). The strength of hand grip post-operatively was also improved in the group PR-ERAS (P < 0.050). The incidence of bowel-related and other adverse events was similar in both groups till 30 days post-operatively (P > 0.050). Peri-operative rehabilitation exercise might be another benevolent factor for early recovery of GI function and life of quality after colorectal surgery. Newer, more surgery-specific rehabilitation recovery protocol merits further exploration for these patients. ChiCTR.org.cn, ChiCTR-ONRC-14005096.


2,5-Bis[(E)-2-phenyl-ethen-yl]-3,6-bis-(pyridin-2-yl)pyrazine.
The mol-ecule of the title compound, C30H22N4, exhibits inversion symmetry adopting the shape of a St Andrew's Cross. It shows dihedral angles between adjacent aryl units of around 50° whereas torsion angles of ca 10° are found along the aryl-ene vinyl-ene path.


Population genetic structure of Theileria parva field isolates from indigenous cattle populations of Uganda.
Theileria parva causes East Coast Fever (ECF) a protozoan infection which manifests as a non-symptomatic syndrome among endemically stable indigenous cattle populations. Knowledge of the current genetic diversity and population structure of T. parva is critical for predicting pathogen evolutionary trends to inform development of effective control strategies. In this study the population genetic structure of 78 field isolates of T. parva from indigenous cattle (Ankole, n=41 and East African shorthorn Zebu (EASZ), n=37) sampled from the different agro ecological zones (AEZs) of Uganda was investigated. A total of eight mini- and micro-satellite markers encompassing the four chromosomes of T. parva were used to genotype the study field isolates. The genetic diversity of the surveyed T. parva populations was observed to range from 0.643±0.55 to 0.663±0.41 among the Central and Western AEZs respectively. The overall Wright's F index showed significant genetic variation between the surveyed T. parva populations based on the different AEZs and indigenous cattle breeds (FST=0.133, p<0.01) and (FST=0.101, p<0.01) respectively. Significant pairwise population genetic differentiations (p<0.05) were observed with FST values ranging from 0.048 to 0.173 between the eastern and northern, eastern and western populations respectively. The principal component analysis (PCA) showed a high level of genetic and geographic sub-structuring among populations. Linkage disequilibrium was observed when populations from all the study AEZs were treated as a single population and when analysed separately. On the overall, the significant genetic diversity and geographic sub-structuring exhibited among the study T. parva isolates has critical implications for ECF control.


Impact of Adjuvant Treatment in pN3 Penile Cancer.
Due to the lack of high-quality evidence and consensus on adjuvant treatment for locoregionally advanced penile cancer, we reviewed the outcomes of pN3 patients to determine the suitable adjuvant treatment options. All consecutive pN3 penile cancer patients treated at our institution between January 2010 and December 2018 were reviewed to assess the impact of demographical, pathological and treatment factors on disease-free survival (DFS) and overall survival. The DFS and overall survival were estimated using the Kaplan-Meier method and association was tested using the Cox regression model (two-sided test with P < 0.05 considered significant). Of 128 patients, 31 (24%) had pelvic nodal involvement. Twenty-six patients (20.3%) received no adjuvant treatment, 40 (31.3%) received single modality adjuvant treatment and 62 (48.4%) received multimodality adjuvant treatment (a combination of chemotherapy and radiotherapy). At a median follow-up of 22 months, the DFS and overall survival were 55.4 and 62%, respectively. The best DFS and overall survival was noted with chemotherapy followed by concurrent chemoradiation (C-CTRT; 93% each). On multivariate analysis, both DFS and overall survival were worse with pelvic node involvement (2.2 [1.3-4], P = 0.027 and 2.2 [1.3-4], P = 0.027, respectively) and better with any adjuvant treatment (single modality: 3 [1.5-5.5], P < 0.001; multimodality: 3.1 [1.6-6], P < 0.001). C-CTRT was associated with improved DFS over chemotherapy alone (0.17 [0.4-0.78], P = 0.02) but not over radiotherapy alone (0.35 [0.07-1.6], P = 0.19). In patients with no pelvic nodes involved, chemotherapy and radiotherapy as single modalities were associated with similar DFS and overall survival. In patients with pelvic nodes, multimodality treatment was associated with better DFS than single modality treatment (0.3 [0.1-1], P = 0.05). pN3 penile cancer is a diverse prognostic group with poorer outcomes associated with pelvic nodes. Single modality adjuvant treatment may be adequate in inguinal nodes with extranodal extension, but multimodality treatment should be given in patients with pelvic nodal involvement.


Molecular evolution in yeast of biotechnological interest.
The importance of yeast in the food and beverage industries was only realized about 1860, when the role of these organisms in food manufacture became evident. Since they grow on a wide range of substrates and can tolerate extreme physicochemical conditions, yeasts, especially the genera Saccharomyces and Kluyveromyces, have been applied to many industrial processes, Industrial strains of these genera are highly specialized organisms that have evolved to utilize a range of environments and ecological niches to their full potential. This adaptation is called "domestication". This review describes the phylogenetic relationships among Saccharomyces and Kluyveromyces species and the different mechanisms involved in the adaptive evolution of industrial yeast strains.


Monitoring antimicrobial resistance trends in Salmonella spp. from poultry in Eastern Spain.
Salmonella spp. is one of the most important zoonotic pathogens with economic impact in public health worldwide. The relevance of Salmonella increases with the appearance of resistant strains. The aim of this study was to determine the level of antimicrobial resistance in 332 Salmonella isolates selected from 3 different poultry productive orientations in Eastern Spain during 3 yr (2015-2017). Antimicrobial susceptibly was evaluated by broth microdilution method using 14 antibiotics. Epidemiological cut-off values (ECOFF) were used to evaluate the microbiological resistance to antibiotics. The rates of Salmonella resistance at least to one antibiotic were 96, 98, and 56% in broilers, turkeys, and layers, respectively. Regarding multidrug resistance, all productive orientations seems to present a decreasing trend along the study, being the mean rates 80% in turkeys followed by broilers (40%) and layers (6%). Throughout the study, the highest percentage of resistance was found to sulfamethoxazole in all productive orientations. Strains from broilers showed the highest resistance rates to sulfamethoxazole (73%), gentamicin (57%), ciprofloxacin (50%), nalidixic acid (29%), and tetracycline (24%). Relative to turkeys the highest resistance rates were to sulfamethoxazole (76%), ciprofloxacin (69%), tetracycline (75%), nalidixic acid (63%), and ampicillin (63%). Layers presented the most elevated resistance rates to sulfamethoxazole (39%) and tetracycline (13%). Regarding serovars the most MDR common serovars to the 3 productive orientations were S. Kentucky and S. Hadar. In the other hand, high MDR rates were found in other serovars like S. Infantis and S. Typhimurium in broilers and turkeys. Results shown in the present study suggest that the reduction in the use of antibiotics begins to be reflected in the reduction of the number of MDRs, especially in layers, with no MDR Salmonella strains in the last period. However, the level of resistances found in this study suggests the necessity of continuing working on the limitation of the use of antimicrobials in poultry to achieve (as in layers) the control of MDRs.


Metastasis of differentiated thyroid cancer in the subchondral bone of the femoral head: a case report.
Differentiated thyroid cancer (DTC) is relatively rare and can metastasize to both the lungs and bones. The great majority of bone metastases occur in red marrow regions where blood flow is high. Only one patient has been described with direct DTC metastasis to the subchondral bone of the femoral head. The patient was a 68-year-old Japanese female who had presented with left hip joint pain at age 63 years. At age 51 years, she had been diagnosed with DTC and underwent partial excision. X-rays showed partial femoral head collapse, suggesting osteoarthritis or idiopathic necrosis of the left femoral head. Three years later, a (131) I whole-body scan showed accumulation in the left femoral head, resulting in a diagnosis of DTC metastasis to the left femoral head. Bipolar hip arthroplasty was performed. Examination of the excised femoral head resulted in a final diagnosis of metastasis of follicular thyroid cancer, which was limited histopathologically to the subchondral bone of the femoral head. Tumor metastasis to the subchondral bone of the femoral head is exceedingly rare. Overall survival of patients with bone metastasis is improved by complete resection. Differential diagnosis of patients with a previous history of DTC who present with femoral head collapse should include bone metastasis of DTC.


Bactericidal activities and action mechanism of the novel antimicrobial peptide Hylin a1 and its analog peptides against Acinetobacter baumannii infection.
We developed an antimicrobial peptide (AMP) as a candidate substance for replacing antibiotics. Previously, a novel 18-amino acid antimicrobial peptide Hylin a1 was isolated from an electro-stimulated arboreal South American frog Hypsiboas albopunctatus, and was found to demonstrate antimicrobial activity and cytotoxicity. In a recent study, the analog peptides were designed based on the parent peptide Hylin a1 to decrease toxicity and to maintain antimicrobial efficacy. The analog peptides were substituted with alanine and lysine, resulting in the formation of amphipathic α-helical structures in membrane-mimicking environments and in the induction of hydrophobic moments and net charges. Moreover, the analog peptides showed lower hemolytic effects and mammalian cell selectivity than Hylin a1. In particularly Hylin a1-11K and Hylin a1-15K exhibited broad-spectrum antimicrobial activity and anti-biofilm activity against carbapenem-resistant Acinetobacter baumannii. Permeability assays indicated that analog peptides eliminated bacteria by binding to lipopolysaccharide and by disrupting the bacterial membrane. Hylin a1-11K and Hylin a1-15K reduced inflammation by suppressing pro-inflammatory cytokines expression by A. baumannii infection and effectively ameliorated carbapenem-resistant A. baumannii infection in mice. Therefore, our results suggest that the analog peptide substituted with several residues based on Hylin a1 have antibacterial and anti-inflammatory activity, and may be effective in the treatment of carbapenem-resistant A. baumannii infection.


Get the facts about Health Care Staffing Services certification.
HCSS evaluates a staffing firm's ability to provide competent staffing services.


Isolation and characterization of Saccharomyces cerevisiae mutants supersensitive to G1 arrest by the mating hormone a-factor.
Nine independent mutants which are supersensitive (ssl-) to G1 arrest by the mating hormone a-factor were isolated by screening mutagenized Saccharomyces cerevisiae MAT alpha cells on solid medium for increased growth inhibition with a-factor. These mutants carried lesions in two complementation groups, ssl1 and ssl2. Mutations at the ssl1 locus were mating type specific: MAT alpha ssl1- cells were supersensitive to a-factor but MATa ssl1- were not supersensitive to alpha-factor. In contrast, mutations at the ssl2 locus conferred supersensitivity to the mating hormone of the opposite mating type on both MAT alpha and MATa cells. The alpha-cell specific capacity to inactivate externally added a-factor was shown to be lacking in MAT alpha ssl1- mutants whereas MAT alpha ssl2- cells were able to inactivate a-factor. Complementation analysis showed that ssl2 and sst2, a mutation originally isolated as conferring supersensitivity to alpha-factor to MATa cells, are lesions in the same gene. The ssl1 gene was mapped 30.5 centiMorgans distal to ilv5 on chromosome XII.


Anion-Tunable Properties and Electrochemical Performance of Functionalized Ferrocene Compounds.
We report a series of ionically modified ferrocene compounds for hybrid lithium-organic non-aqueous redox flow batteries, based on the ferrocene/ferrocenium redox couple as the active catholyte material. Tetraalkylammonium ionic moieties were incorporated into the ferrocene structure, in order to enhance the solubility of the otherwise relatively insoluble ferrocene. The effect of various counter anions of the tetraalkylammonium ionized species appended to the ferrocene, such as bis(trifluoromethanesulfonyl)imide, hexafluorophosphate, perchlorate, tetrafluoroborate, and dicyanamide on the solubility of the ferrocene was investigated. The solution chemistry of the ferrocene species was studied, in order to understand the mechanism of solubility enhancement. Finally, the electrochemical performance of these ionized ferrocene species was evaluated and shown to have excellent cell efficiency and superior cycling stability.


Study on the presence of abnormal proteins in the serum of oral contraceptive users.
Beaumont reported that current and former oral contraceptive users and subjects with thromboembolic disease characteristically demonstrate elevated amounts of precipitated proteins, designated as "globulines anormalement precipitables (GAP)," following treatment of their sera with 25% saturated ammonium sulfate. In the present study, the reproducibility of Beaumont's methods and results was investigated in groups of women consisting of never users, current users, former users, and thrombosis subjects. The current users had the lowest serum GAP levels and no bimodal distribution. Values were higher for the never users and former users and highest in the thrombosis group. Race affected serum GAP values; mean values for blacks were significantly higher than for Caucasians. This study does not support Beaumont's earlier findings.


Open-channel microfluidics via resonant wireless power transfer.
Open-channel microfluidics enables precise positioning and confinement of liquid volume to interface with tightly integrated optics, sensors, and circuit elements. Active actuation via electric fields can offer a reduced footprint compared to passive microfluidic ensembles and removes the burden of intricate mechanical assembly of enclosed systems. Typical systems actuate via manipulating surface wettability (i.e., electrowetting), which can render low-voltage but forfeits open-microchannel confinement. The dielectric polarization force is an alternative which can generate open liquid microchannels (sub-100 µm) but requires large operating voltages (50-200 VRMS) and low conductivity solutions. Here we show actuation of microchannels as narrow as 1 µm using voltages as low as 0.5 VRMS for both deionized water and physiological buffer. This was achieved using resonant, nanoscale focusing of radio frequency power and an electrode geometry designed to abate surface tension. We demonstrate practical fluidic applications including open mixing, lateral-flow protein labeling, filtration, and viral transport for infrared biosensing-known to suffer strong absorption losses from enclosed channel material and water. This tube-free system is coupled with resonant wireless power transfer to remove all obstructing hardware - ideal for high-numerical-aperture microscopy. Wireless, smartphone-driven fluidics is presented to fully showcase the practical application of this technology.


The prevalence and characteristics of coronary atherosclerosis in asymptomatic subjects classified as low risk based on traditional risk stratification algorithm: assessment with coronary CT angiography.
To evaluate the prevalence and characteristics of coronary atherosclerosis in asymptomatic subjects classified as low risk by National Cholesterol Education Program (NCEP) guideline using coronary CT angiography (CCTA). An observational study. A single tertiary referral centre. 2133 (49.2%) subjects, who were classified as low risk by the NCEP guideline, of 4339 consecutive middle-aged asymptomatic subjects who underwent CCTA with 64-slice scanners as part of a general health evaluation. The incidence of atherosclerosis plaques, significant stenosis. In the subjects at low risk, 11.4% (243 of 2133) of subjects had atherosclerosis plaques, 1.3% (28 of 2133) of subjects had significant stenosis, and 0.8% (18 of 2133) of subjects had significant stenosis caused by non-calcified plaque (NCP). Especially, 75.0% (21 of 28) of subjects with significant stenosis and 94.4% (17 of 18) of subjects with significant stenosis caused by NCP were young adults. Mid-term follow-up (29.3 ± 14.9 months) revealed four subjects with cardiac events: three subjects with unstable angina requiring hospital stay and one subject with percutaneous coronary intervention. Although an asymptomatic population classified as low risk by the NCEP guideline has been regarded as a minimal risk group, the prevalence of atherosclerosis plaques and significant stenosis were not negligible. However, considering very low event rate for those patients, CCTA should not be performed in low-risk asymptomatic subjects, although CCTA might have the potential for identification of high-risk groups in the selected subjects regarded as a minimal-risk group by NCEP guideline.


Aqueous extract from leaves of Ludwigia hyssopifolia (G. Don) Exell as potential bioherbicide.
Ludwigia hyssopifolia (G. Don) Exell, one of the problem weeds in some rice-producing countries, was studied to determine its allelopathic potential based on the effects of aqueous extracts of its tissues (leaves, roots and stem) on seedling growth of selected weeds and rice. The major phenolic compound of its leaves was also isolated and characterized. L. hyssopifolia aqueous leaf extract showed significant inhibition of shoot growth and biomass accumulation of weeds (Amaranthus spinosus L., Dactyloctenium aegyptium L., Cyperus iria L.) while maintaining less adverse effects on rice (crop) compared to other aqueous extracts of roots and stem. Phytochemical screening showed that phenols, tannins, flavonoids, terpenoids, saponins and coumarins are found in its leaf aqueous extract. The Folin-Ciocalteu method revealed that its leaves contain 26.66 ± 0.30 mg GAE g-1 leaf. The extract was then acid-hydrolyzed to liberate the phenolics (25 mg phenolics g-1 leaf). The major compound was isolated via preparative thin-layer chromatography using formic acid-ethyl acetate-n-hexane (0.05:4:6) solvent system. It had maximum UV absorption at 272 nm while its Fourier transform infrared spectrum revealed phenol, carboxylic acid and ether functionalities. This also had similar chromatographic mobility when run together with syringic acid in two-dimensional paper chromatography and thin-layer chromatography. L. hyssopifolia has potential allelopathic activity and its leaf aqueous extract showed the highest phytotoxic activity (P ≤ 0.05) indicating its potential as a bioherbicide. The most probable identity of the major phenolic compound is syringic acid. © 2019 Society of Chemical Industry.


Collegial ethics: what, why and how.
Collegial ethics (CE) proposes that we support our colleagues whenever possible. It is more of a focus on the feelings of others rather than on our own. In spite of the importance of collegial interactions, CE is not usually taught. Courses in CE need to be developed, and collegial skills need to be identified, taught and practiced. Such skills would include: use of the golden rule, supportive communication, conflict resolution, and even the development of greater courage in our actions.


Mucolysis by ascorbic acid and hydrogen peroxide on compact mucin secreted in pseudomyxoma peritonei.
This study examines the potential efficacy of hydrogen peroxide and ascorbic acid in the dissolution of mucinous ascites from pseudomyxoma peritonei. The mucolytic action of both ascorbic acid (0%-0.2%) and hydrogen peroxide (0%-3%) are investigated as single agent on mucin samples derived from patient. This was followed by examining the joint action of ascorbic acid (0.2%) and hydrogen peroxide (0%-3.0%) on mucin. To lower the concentration of hydrogen peroxide in the mixture, the action of equal concentration of ascorbic acid/hydrogen peroxide ranging from 0%-0.3% are then examined. Finally, the pH (4.5-7.0) effect on mucolytic properties of equal concentration (0.2%) of ascorbic acid/hydrogen peroxide was studied. At the concentrations examined (0%-0.2%), ascorbic acid showed highest mucolytic activity at 0.2%. Similarly, hydrogen peroxide as a single agent (0%-3.0%) showed highest mucolytic activity at 3.0%. The mucolytic action of hydrogen peroxide (0%-3.0%) containing 0.2% ascorbic acid demonstrated synergistic effects. At equal concentration of the two agents, ranging from 0%-0.5%, maximal mucolytic action was observed at 0.2%. The mucolytic property of the final mixture (0.2% ascorbic acid/0.2% hydrogen peroxide) was pH-dependent and showed maximal degradation at pH 4.5 and declined as it reached towards neutral pH. The current study introduces the potential applicability of a formulation that holds promise as a mucolytic agent in patients with mucinous ascites from pseudomyxoma peritonei.


Development of a simplified and cost-effective sample preparation method for genotyping of human papillomavirus by next-generation sequencing.
High-risk human papillomavirus (HPV) infection is the most common cause of cervical cancer, but low-risk HPV strains can sometimes also be involved. Although HPV genotyping techniques used in clinical diagnosis cannot detect low-risk HPV, next-generation sequencing (NGS) can detect both types. However, DNA library preparation is complicated and expensive. The aim of this study was to develop a simplified, cost-effective sample preparation procedure for HPV genotyping based on next-generation sequencing (NGS). After DNA extraction, a first round of PCR was performed using modified MY09/11 primers specific for the L1 region of the HPV genome, followed by a second round of PCR to add the indexes and adaptors. Then, the DNA libraries were purified and quantified, and high-throughput sequencing was performed using an Illumina MiSeq platform. The sequencing reads were compared with reference sequences for HPV genotyping. The limit of detection for HPV amplification was 100 copies/µl. Analysis of the correlation of pathological cytology with the HPV genotype in individual clinical samples showed that HPV66 was the most common genotype found in the normal stage, whereas HPV16 was the main genotype found in low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and cervical cancer. This NGS method can detect and identify several HPV genotypes with 92% accuracy and 100% reproducibility, and it shows potential as a simplified and cost-effective technique for large-scale HPV genotyping in clinical samples.


Mania associated olfactory dysfunction: A comparison between bipolar subjects in mania and remission.
The aim of this study was to assess the olfactory functions of patients with bipolar disorder in manic phase and to compare them to those of bipolar subjects in remission and healthy controls. We recruited 96 participants divided in 3 groups: bipolar mania (MB), euthymic bipolar in remission (EB) and healthy controls (HC). All participants underwent an assessment of their olfactory functions using the Sniffin' sticks threshold and identification tests. Odors' pleasantness, intensity, familiarity and emotion were assessed. All participants were screened for the presence of psychiatric disorder through the MINI questionnaire. Clinical evaluation explored dimensions of mania, depression, anxiety respectively through YMRS, MADRS and STAI scales. Anhedonia was explored through the Chapman physical and social anhedonia questionnaire. Patients in mania had deficits in identifying positive smells compared to bipolar subjects in remission and to healthy controls (MB < EB < HC; p < 0.001). Hedonic (MB < EB = HC; p < 0.001) and emotional (MB < EB = HC; p < 0.001) ratings of positive smells were lower in patients in manic phase compared to remitted subjects or controls. Mania was associated to higher emotion rating of negative smells compared to remitted subjects and controls (MB > EB = HC; p < 0.001). There was no difference between the 3 groups in the ratings of intensity and familiarity of smells, as well as in the olfactory threshold testing. The 3 groups showed no difference in the identification of negative smells. Patients in manic episodes showed deficits in identifying positive odors. They evaluated these smells as less pleasant and less emotional compared to remitted bipolar subjects and healthy controls. These olfactory dysfunctions may constitute potential indicators of manic state. The persistence of olfactory dysfunction in remission phase (deficit in the olfactory identification of positive odors compared to healthy controls) may constitute a potential trait indicator of bipolarity.


Dealing With Death in Custody: Psychosocial Consequences for Correctional Staff.
This study investigated experiences of trauma and psychosocial mediators in correctional staff who had dealt with a death in custody within the previous year. A total of 211 participants completed the Trauma Symptom Index as well as measures of self-efficacy, optimism, problem-solving style, social support, and growth. The data showed that around 32% of participants were exhibiting symptoms at a clinical level. Prior experience with suicide and level of involvement in the incident were direct predictors of symptom level. Support, optimism, self-efficacy, and confidence in problem-solving seemed to be potential protective factors and were also predictive of trauma-related growth. Although the study was cross sectional, the data suggest that it may be possible to predict factors that are protective and therefore offer some hope in terms of developing preventive strategies.


Effects of graded levels of starch on the non-specific immune responses, antioxidant capacities and intestinal health in Chinese mitten crab, Eriocheir inensis.
A 9-week feeding trial was conducted to investigate the effects of graded levels of dietary starch (12%, 17%, 22%, 27% and 32%) on growth, non-specific immune responses, antioxidant capacities, immunity genes expression levels and pathogen resistance in Chinese mitten crab, Eriocheir inensis (initial body weight: 10.5 ± 0.5 g). Results showed that the highest weight gain rate of crabs was obtained in group containing 22% dietary starch. The highest activity of acid phosphatase, phenoloxidase and lysozyme in blood was found in crabs fed with 22-27% dietary starch. Additionally, 17%-27% dietary starch significantly increased the activities of superoxide dismutase and glutathione peroxidase, reduced malondinaldehyde content and then increased the total antioxidant capacities in hepatopancreas of crabs. The highest activity of alanine aminotransferase and aspartate aminotransferase was found in crabs fed with 32% dietary starch, indicating that excess starch had a negative effect on the liver function of crabs. With the dietary starch level increased, the transcription factors gene expression of the pro-inflammatory factors were significantly up-regulated, and the highest ILF2, IL-16, Relish and ADAM10 was found in crabs fed with dietary 32% starch, which may potentially promote the inflammatory response in intestines. Moreover, with the dietary starch increased, the activity of phenoloxidase and lysozyme, as well as the gene expression of crustin, were all increased in crabs after challenge against Citrobacter freundii, which demonstrated that additional dietary starch could provide immune-protection and help crabs improve their resistance against pathogens. In conclusion, these results suggest that adequate dietary starch can increase growth, enhance innate immune responses and promote disease resistance, reduce oxidative stress and inflammatory response in E. inensis. Taken together, 22-27% dietary starch (25.9-30.8% dietary carbohydrate) was suggested as a digestible energy source in crabs feed.


Outcomes of the retrograde approach through epicardial versus non-epicardial collaterals in chronic total occlusion percutaneous coronary intervention.
The retrograde approach through epicardial collaterals (EC) for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is a challenging procedure. Our study aim was to evaluate the outcomes of patients undergoing CTO PCI using a retrograde approach through epicardial versus non-epicardial collaterals (NEC). We collected data from our single-center registry of consecutive patients undergoing retrograde CTO PCI, performed by an experienced operator through EC and NEC (septals and bypass grafts). Clinical, angiographic and procedural data were recorded. The primary endpoint (major adverse cardiac events, MACE) was a composite of cardiac death, target-vessel myocardial infarction (MI) and target-vessel revascularization (TVR) on follow-up. During the study period, 318 CTO PCIs were performed. Of these, 81 procedures (25%) were performed retrogradely in 75 patients (38 using NEC [31 septals, 7 bypass grafts], 37 through EC [34 contralateral, 3 ipsilateral]). Clinical characteristics were balanced between EC and NEC. J-CTO score was 2.1±1.1 and 2.2±1.2, respectively (p=0.92). Collateral tortuosity was more marked in EC. Technical and procedural success was lower in EC (35% vs. 76%, p<0.001; 30% vs. 76%, p<0.001; respectively). There were two perforations (5%) with need for intervention in EC, and none in NEC (p=0.15). After a median follow-up of 443 (331-744) days, MACE were observed in 12.9% (n=4) of EC vs. 5.4% (n=2) in NEC patients (p=0.28). In our experience, retrograde CTO PCI through EC was associated with lower success rate, and a numerically higher rate of perforation, as compared with NEC. Clinical outcomes on follow-up were similar.