Parasternal mediastinoscopy. Assessment of operability in left upper lobe lung cancer: a prospective analysis.
Between 1976 and 1984, 242 patients with presumably operable lung cancer were treated surgically. In the Canisius Wilhelmina Hospital, Nijmegen, The Netherlands, in the period 1976 to 1980, 109 of 131 (83.2%) patients underwent cervical mediastinoscopy to assess operability. They were studied retrospectively. During this examination, lymph node metastasis was demonstrated in three of 19 (15.8%) patients with left upper lobe lung cancer. At thoracotomy after a normal cervical mediastinoscopic study or no mediastinoscopic study, periaortic lymph node metastases were found in eight of 34 (23.5%) patients with left upper lobe lung cancer. In the period 1981 to 1984, the value of left parasternal mediastinoscopy was studied prospectively in patients with left lung cancer in the Canisius Wilhelmina Hospital, Nijmegen; in the Lung Centre of the Radboud University Hospital, Nijmegen; and in the Lung Center of the Dekkerswald Medical Centre, Groesbeek. Cervical or cervical and parasternal mediastinoscopy were performed in 69 of 111 (62.2%) patients. At parasternal mediastinoscopy performed after a normal cervical mediastinoscopic study, periaortic lymph node metastases were found in seven of 31 (22.6%) patients with left upper lobe lung cancer. All periaortic lymph node metastases showed intranodal and extranodal growth. The resectability rate in left upper lobe lung cancer was 79.4% in the retrospective group and 96.5% in the prospective group. There were no serious complications after parasternal mediastinoscopy. These data point to the reliability of parasternal mediastinoscopy in the assessment of left upper lobe lung cancer. The study provides essential information for the staging and treatment of non-small cell lung cancer of the left upper lobe.


Nucleotide binding site/leucine-rich repeats, Pto-like and receptor-like kinases related to disease resistance in grapevine.
Nucleotide Binding Site/Leucine-Rich Repeat (NBS-LRR) and Serine/Threonine Kinase (STK) genes are two of the known classes of resistance (R-) genes in plants, and occur in large multigene families. Systematic identification of genes for NBS-LRRs and STKs provides a means of access to genomic regions that may be involved in disease resistance. Here we present a picture of these two families of R-gene analogs (RGAs) in grape with the aim of developing a set of resistance-related sequence-tagged-site (STS) markers. One hundred and three NBS-LRR sequences were isolated. They included members of the CC (coiled-coil) and TIR (Toll-interleukin receptor) sub-classes. A comparative analysis with other angiosperm NBSs is provided. Fifty-three genes for receptor-like kinases (RLKs) with serine/threonine specificity were identified. RLK sequences formed a putative monophyletic group within the kinase superfamily. They were similar to both cytoplasmic RLKs, such as Pto, and RLKs with LRR, S-locus, lectin-like and thaumatin-like extracellular binding-domains. The latter resembled the products of the R-related genes Xa21, FLS2, Rlk10, SFR2, and PR5K. Forty-five reference RGAs were converted into STSs by using appropriately designed specific primers. RGA-STSs were present in diverse grape genotypes, and >85% of the primers were capable of amplifying the STSs across the taxa Vitis and Muscadinia. DNA sequence polymorphism among these RGAs was assessed by SSCP (single-strand conformation polymorphism) analysis in over 20 Vitis spp. Finally, 45 universal primers for grape RGAs are proposed that should permit tagging of R-related regions in any grape genome.


Inflammation-induced protein carbonylation contributes to poor prognosis for cholangiocarcinoma.
Carbonylation is an irreversible and irreparable protein modification induced by oxidative stress. Cholangiocarcinoma (CCA) is associated with chronic inflammation caused by liver fluke infection. To investigate the relationship between protein carbonylation and CCA progression, carbonylated proteins were detected by 2D OxyBlot and identified by MALDI-TOF/TOF analyses in pooled CCA tissues in comparison to adjacent nontumor tissues and normal liver tissues. We identified 14 highly carbonylated proteins in CCA tissues. Immunoprecipitation and Western blot analyses of individual samples confirmed significantly greater carbonylation of serotransferrin, heat shock protein 70-kDa protein 1 (HSP70.1), and α1-antitrypsin (A1AT) in tumor tissues compared to normal tissues. The oxidative modification of these proteins was significantly associated with poor prognoses as determined by the Kaplan-Meier method. LC-MALDI-TOF/TOF mass spectrometry identified R50, K327, and P357 as carbonylated sites in serotransferrin, HSP70.1, and A1AT, respectively. Moreover, iron accumulation was significantly higher in CCA tissues with, compared to those without, carbonylated serotransferrin. We conclude that carbonylated serotransferrin-associated iron accumulation may induce oxidative stress via the Fenton reaction, and the carbonylation of HSP70.1 with antioxidative property and A1AT with protease inhibitory capacity may cause them to become dysfunctional, leading to CCA progression.


Does quality of life outweigh the cardiovascular risks of stimulant medication in a child with ADHD and hypertrophic cardiomyopathy?
A 10-year-old girl with attention-deficit hyperactivity disorder (ADHD) is diagnosed with hypertrophic cardiomyopathy. The stimulant medications used to control her ADHD pose possibly fatal risks to her cardiovascular health, so stimulant medication is stopped. Due to very poor quality of life off of medication, alternative therapies are used without improvement. The patient's caretakers decide that the benefits of stimulant medication outweigh the risks to the patient. The healthcare team clears the patient to be put back on stimulant medication with a signed waiver of liability by her caretakers.


Comparison of ESBL contamination in organic and conventional retail chicken meat.
Contamination of retail chicken meat by Extended Spectrum Beta-Lactamase (ESBL) producing bacteria likely contributes to the increasing incidence of infections with these bacteria in humans. This study aimed to compare the prevalence and load of ESBL positive isolates between organic and conventional retail chicken meat samples, and to compare the distribution of ESBL genes, strain genotypes and co-resistance. In 2010, 98 raw chicken breasts (n=60 conventional; n=38 organic) were collected from 12 local stores in the Netherlands. Prevalence of ESBL producing micro-organisms was 100% on conventional and 84% on organic samples (p<0.001). Median loads of ESBL producing micro-organisms were 80 (range <20-1360) in conventional, and <20 (range 0-260) CFU/25 g in organic samples (p=0.001). The distribution of ESBL genes in conventional samples and organic samples was 42% versus 56%, respectively (N.S.), for CTX-M-1, 20% versus 42% (N.S.) for TEM-52, and 23% versus 3% (p<0.001) for SHV-12. CTX-M-2 (7%), SHV-2 (5%) and TEM-20 (3%) were exclusively found in conventional samples. Co-resistance rates of ESBL positive isolates were not different between conventional and organic samples (co-trimoxazole 56%, ciprofloxacin 14%, and tobramycin 2%), except for tetracycline, 73% and 46%, respectively, p<0.001). Six of 14 conventional meat samples harbored 4 MLST types also reported in humans and 5 of 10 organic samples harbored 3 MLST types also reported in humans (2 ST10, 2 ST23, ST354). In conclusion, the majority of organic chicken meat samples were also contaminated with ESBL producing E. coli, and the ESBL genes and strain types were largely the same as in conventional meat samples.


Investigation of virus-like particles in Leishmania hertigi.
The promastigote forms of an isolate of Leishmania hertigi contain large numbers of virus-like particles (VLPs) in paracrystalline arrays. The VLPs are not present in the amastigote form and it was not possible to purify them from large amounts of the promastigotes.


Mucopolysaccharidosis IIIA (Sanfilippo syndrome) in a New Zealand Huntaway dog with ataxia.
To investigate the nature of a progressive ataxia in a New Zealand Huntaway dog. The affected dog was examined clinically before being humanely killed and necropsied. Selected tissues were submitted to light and electron microscopy and to biochemical analyses. The histological lesions were interpreted as indicative of one of the forms of mucopolysaccharidosis type-III (MPS-III), a lysosomal storage disease. Biochemically there was a deficiency of heparan sulphamidase. All the heparan sulphate chains had non-reducing-end glucosamine-N-sulphate residues. The disease is MPS-IIIA (Sanfilippo syndrome). An autosomal recessive mode of inheritance can be provisionally assumed from the nature of this disease in other species.


Ketamine for Monitored Anesthesia Care During Transcatheter Aortic Valve Replacement.
To study the feasibility and outcomes of ketamine as an anesthetic adjunct during monitored anesthesia care (MAC) in transcatheter aortic valve replacement (TAVR). This was a retrospective study. Data from 155 consecutive TAVR patients at a tertiary care high-volume TAVR medical center were reviewed and analyzed. Among the 155 TAVR cases under MAC, intravenous ketamine was administered as an adjunct in 126 patients. The most common ketamine dose was 20 mg. There was no significant difference for postoperative stroke, intraoperative conversion to general anesthesia, postoperative delirium, need for permanent pacemaker implantation, perivalvular leak and length of stay between the ketamine and non-ketamine groups. The ketamine group demonstrated a statistically significant lower 30-day mortality (P = .0381) and intraoperative cardiac arrest (P = .0025) rate when compared to the nonketamine group. Our results demonstrated that employing ketamine as an adjunct during MAC for TAVR is a feasible option.


Long-term effects of a tailored mindfulness-based program for Chinese intensive care unit nurses: A randomized parallel-group trial.
This study investigated the direct and long-term improvements that mindfulness-based interventions exert on intensive care unit nurses. We assessed an abbreviated four-week, twice-weekly mindfulness-based intervention program's effect on work-related mental health variables and examined whether the intervention impact was maintained at two- and six-month follow-up assessments. We also examined the training program's effects on work and life. Previous research has shown that mindfulness interventions exert positive effects immediately after treatment. However, few studies have examined whether treatment effects are maintained over time or under different circumstances. Moreover, treatment effects among Chinese intensive care unit nurses have rarely been examined. We conducted a randomized, non-blinded, parallel-group trial. Participants included 90 intensive care unit nurses, divided into two cohorts, who participated in the program in October 2016 and April 2017. They completed validated measures of mindfulness, burnout syndromes, anxiety and depressive symptoms and well-being at baseline (T1), immediately after intervention (T2), two months after (T3) and six months after (T4) the intervention. We observed a significant group effect (1) immediately post-intervention and two months after intervention for mindfulness; (2) at two months after intervention for anxiety, depression and subjective well-being and (3) at post-intervention, two months after and six months after for emotional exhaustion. These findings suggest that the tailored four-week mindfulness-based intervention program improved intensive care unit nurses' mental health, although further research is needed to verify its feasibility in a clinical working environment.


Environmental sustainability through aggregate demand and knowledge economy interaction-a case of very high-HDI countries.
The magnitude of the economic activities is immense in very high-Human Development Index (HDI) countries, leading to environmental degradation, a crucial problem. This study is aimed at testing aggregate demand's role in the environmental Kuznets curve (EKC) perspective and explores the role of four pillars of the knowledge economy, viz., technology, innovations, education, and institutions, as proposed by World Bank, in maintaining sustainable development of environmental quality in these countries. The analysis covers the period ranging from 1995 to 2022. The departure of normality of the variables provides a solid base for panel quantile regression (PQR). Unlike ordinary least squares (OLS) regression, which estimates the conditional mean of the dependent variable, PQR estimates the conditional quantiles. The estimated results using PQR confirm both U and inverted U-shaped aggregate demand-based EKC. In fact, these knowledge pillars in the model determine the shape of EKC. Results also reveal that two knowledge pillars, i.e., technology and innovations, are responsible for significantly reducing carbon emissions. In comparison, education and institutions are responsible for expanding carbon emissions. As a moderator, all knowledge pillars except institutions are shifting the EKC downward. The key lessons from these findings are that technology and innovation can reduce carbon emissions, while education and institutions may have a mixed impact. The relationship between knowledge pillars and emissions may be moderated by other factors, underscoring the need for further research. Moreover, urbanization, energy intensity, financial development, and trade openness significantly contribute to environmental deterioration.


Transposition flaps in cutaneous surgery.
Transposition flaps are powerful reconstructive tools that are frequently called on in cutaneous reconstruction. Transposition flaps tap into adjacent areas that may have relative laxity while redirecting the vectors of tension during closure. As with the closure of any surgical defect, the goal is to achieve the best possible functional and esthetic result. Manual manipulation is used to "feel" for areas of relative laxity and test the effects of various tension vectors on adjacent structures. Every effort should be made to avoid distortion of the free margins of structures such as the nose and eyelids. Consideration must be taken to best camouflage incision lines within existing lines or creases, at the junction of cosmetic units, or at least parallel to lines of relaxed skin tension. A complete knowledge of the possible variations and modifications of transposition flaps can help fine-tune the execution of the flap to provide the patient with the best possible result. Good surgical technique and proper wound eversion through meticulous suture placement also help tremendously in consistently attaining esthetically pleasing results. At the surgical bedside, an artistic eye should meet the science of cutaneous biomechanics.


The changing face of septic arthritis complicating rheumatoid arthritis in the era of biotherapies. Retrospective single-center study over 35years.
To see whether the frequency and features of septic arthritis (SA) complicating rheumatoid arthritis (RA) have changed over the last 35years. This retrospective single-center study included all patients hospitalized at the rheumatology department for SA bacteriologically documented by synovial fluid and/or blood culture samples. The periods 1979-2002 (before biotherapies) and 2003-2013 (the era of biotherapies) were compared. Between 1979 and 2013, 64/514 (12.5%) SA presented with a RA - 21/157 (13.4%) in the 2003-2013 period and 43/357 (12.0%) in the 1979-2002 period. Over the past decade, median age of RA SA patients increased (61 vs. 68 years; P<0.02) and predominant gender became males (52% vs. 40%). The features of the RA remained unchanged: history (18 vs. 16years), rheumatoid factor (95% vs. 87%), and corticosteroids (91% vs. 81%). Over the last decade 24% (vs. 0; P<0.003) of the patients received a biologic DMARD: etanercept (n=2), adalimumab (n=1), rituximab (n=1), tocilizumab (n=1). Proportion of polyarticular infection had decreased strongly (9.5% vs. 37%; P<0.02). Proportion of Staphyloccus aureus infections remained stable, but there was a higher incidence of MRSA infections (31 vs. 6%; P<0.05). Blood cultures less often tested positive (29% vs. 47%; NS). Case fatality rate had fallen slightly in RA SA (5% vs. 9%; NS), but not in non-RA SA cases (7% vs. 6%; NS). This study brings reassuring findings - in the era of biotherapies, the rate of septic arthritis amongst patients with RA has not increased, and the most severe septic polyarticular forms are on the decline.


The pharmacological properties of some crustacean neuronal acetylcholine, gamma-aminobutyric acid, and L-glutamate responses.
1. A study was performed of the L-glutamate, gamma-aminobutyric acid (GABA), and acetylcholine (ACh) responses of cells in the stomatogastric ganglion of the crab, Cancer pagurus. 2. Ionophoretic or pressure application of L-glutamate revealed three classes of responses: a K+-dependent inhibition which reversed at 15-20 mV more negative than the resting potential; a Cl- dependent inhibitory response which was at equilibrium at the resting potential; and a depolarizing response. 3. Ionophoretic or pressure applications of GABA likewise produced three kinds of responses: an increase in K+ conductance, an increase in Cl- conductance, and a depolarizing response. 4. Picrotoxin (10(-6)-10(-5) M) was effective in blocking both the glutamate inhibitory responses. 10(-4) M-picrotoxin, which was necessary to produce a 50% block of the GABA-K+-dependent response, had no effect on the GABA-Cl- response. 5. beta-Guanidinopropionic acid (beta-GP) was found to be an agonist for the GABA-K+ response, but was ineffective in mimicking or blocking the GABA-Cl- response. 6. ACh applications produced large depolarizing responses with a pharmacological profile similar to that of the nicotinic ganglionic response in vertebrates. 7. The muscarinic agonist, acetyl-beta-methyl choline (MeCh), produced depolarizations which decreased in amplitude as the membrane was hyperpolarized from -40 to -100 mV. Pilocarpine and oxotremorine produced changes in the endogenous activity of ganglionic neurones. 8. Implications of these results for the identification of synaptic transmitters in the somatogastric ganglion are discussed.


Sociodemographic profiles and determinants of relapse risks among people with substance use disorders in the Philippines: A survey in community and residential care settings.
Methamphetamine use is a major social and health issue in the Philippines. Former president Rodrigo Duterte prioritized combating illicit drugs, and the government launched an anti-drug campaign. People with substance use disorders (SUD) receive treatment and care in the community or residential treatment at Treatment and Rehabilitation Centers (TRCs) established by the Department of Health. However, since the content and quality of service are not sufficient, there is an urgent need for improvement. To this end, it is necessary to understand demographic characteristics, the severity of drug use, and treatment needs of this population. We conducted a questionnaire survey of people with SUD in the community (n=308) and all TRC patients (n=1770) to obtain their demographic profiles. We also used the Drug Abuse Screening Test-20 (DAST-20) and the Stimulant Relapse Risk Scale (SRRS). Based on DAST-20 scores, the severity of dependence was not well-matched to the care provided; 12.4% of the community sample was in the severe or substantial categories and 14.2% of the TRC sample was in the low category. The TRC sample had a significantly higher relapse risk than the community sample, which was associated with a lower educational attainment level and comorbid alcohol dependence. It is important to use standardized psychometric tools to match treatment with the severity of drug dependence. In addition, a wide variety of medical and social services need to be provided based on consideration of treatment needs to improve the well-being of this population.


The use of physical agents in rehabilitation of athletic injuries.
The competitive athlete's motivation to return to activity following injury presents a challenge to the sports medicine specialist to utilize the most effective rehabilitation procedures available. Safe return to competition necessitates maximal restoration of those components of physical fitness affected by injury (such as muscular strength, power, endurance). Various forms of superficial heat and cold application, deep heat modalities, and electrical currents have been used to supplement therapeutic exercise in this process. In recent years, the therapeutic benefits of cold for the control of exercise-induced edema and as a prelude to performance of prescribed exercise have been widely recognized. Although short wave and microwave diathermy appear to have lost much of their appeal as deep tissue heating modalities, the thermal and mechanical effects of ultrasound continue to make it a widely used modality in sports medicine. Adaptation of alternating electrical currents for use in transcutaneous nerve stimulation has given the sports medicine clinician a useful modality for pain management. The more recently developed "Russian" electrical stimulator provides a promising modality for muscle re-education and restoration of muscular strength.


Hepatic fatty acid and glucose handling in metabolic disease: Potential impact on cardiovascular disease risk.
The prevalence of metabolic diseases, including type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing. Although invariably associated with obesity, the importance of fat deposition in non-adipose tissue organs has yet to be fully explored. Pathological ectopic fat deposition within the liver (known as (MASLD)) has been suggested to underlie the development of T2DM and is now emerging as an independent risk factor for cardiovascular disease (CVD). The process of hepatic de novo lipogenesis (DNL), that is the synthesis of fatty acids from non-lipid precursors (e.g. glucose), has received much attention as it sits at the intersect of hepatic glucose and fatty acid handling. An upregulation of the DNL pathway has been suggested to be central in the development of metabolic diseases (including MASLD, insulin resistance, and T2DM). Here we review the evidence to determine if hepatic DNL may play a role in the development of MASLD and T2DM and therefore underlie an increased risk of CVD.


Lactobacillus reuteri normalizes altered fear memory in male Cntnap4 knockout mice.
Autism spectrum disorder (ASD) is a common neurodevelopmental disease, characterized by deficits in social communication, restricted and repetitive behaviours, and impaired fear memory processing. Severe gastrointestinal dysfunction and altered gut microbiome have been reported in ASD patients and animal models. Contactin associated protein-like 4 (CNTNAP4) has been suggested to be a novel risk gene, though its role in ASD remains unelucidated. Cntnap4-/- mice were generated to explore its role in ASD-related behavioural abnormalities. Electrophysiological recording was employed to examine GABAergic transmission in the basolateral amygdala (BLA) and prefrontal cortex. RNA-sequencing was performed to assess underlying mechanisms. 16S rDNA analysis was performed to explore changes in faecal microbial composition. Male Cntnap4-/- mice were fed with Lactobacillus reuteri (L. reuteri) or faecal microbiota to evaluate the effects of microbiota supplementation on the impaired fear conditioning mediated by Cntnap4 deficiency. Male Cntnap4-/- mice manifested deficiency in social behaviours and tone-cue fear conditioning. Notably, reduced GABAergic transmission and GABA receptor expression were found in the BLA but not the prefrontal cortex. In addition, gut Lactobacillus were less abundant in male Cntnap4-/- mice, and L. reuteri treatment or faecal microbiota transplantation rescued abnormal tone-cued fear memory and improved local GABAergic transmission in the BLA of male Cntnap4-/- mice. Cntnap4 shapes GABAergic transmission of amygdala and fear conditioning, and microbial intervention represents a promising therapy in ASD intervention. National Natural Science Foundation of China, Science and Technology Planning Project of Guangzhou, Guangzhou Medical University, and China Postdoctoral Science Foundation.


Stigma of Opioid Use Disorder and Its Indirect Effects on Student Pharmacists' Perceptions and Attitudes.
Pharmacists play a vital role in serving patients during the ongoing nationwide opioid epidemic, and so it is also critical to educate the next generation of pharmacists on opioids and opioid use disorder (OUD). The primary objective of this study was to quantitatively characterize student perceptions of opioid use and the stigma associated with OUD. Secondary aims were to determine whether differences in perceptions exist based upon the student's year in the Doctor of Pharmacy program or employment in a community pharmacy. First-, second-, third-, and fourth-year student pharmacists voluntarily completed an electronic survey regarding perceptions of opioid use and stigma associated with OUD. Of the 9 survey items, students were most uncomfortable referring patients to community resources for addiction support and/or treatment (25.3% comfortable or very comfortable). Students working in a community pharmacy were significantly more comfortable talking to patients attempting to refill opioids early and providing opioid counseling as compared to their peers not working in community pharmacy. Fourth-year students reported a higher level of comfort talking to a patient attempting to refill an opioid prescription early, counseling a patient on an opioid prescription, and providing information about alternatives to opioids. Third-year students responded most favorably to the items regarding how well the curriculum has prepared them to interact with patients taking opioids and those with OUD. These findings reveal that students are comfortable counseling on opioids and discussing alternative options. Differences in perceptions were observed based upon the student's year in the program and whether or not they were employed in a community pharmacy setting.


A Comparison of Surgery Wait Times and Postoperative Length of Hospital Stay Among Patients with Brain Tumors by Country-Level Income and Healthcare System: A Systematic Review and Meta-analysis.
The current study highlights the differences in surgery wait times and postoperative length of hospital stay (LOS) for brain tumor patients between high income countries (HICs) and low- and middle-income countries (LMICs), and across countries with different payer health systems. A systematic review and meta-analysis were performed in accordance with the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines. Outcomes of interest were surgery wait time and postoperative LOS. Fifty-three articles were included totaling 456,432 patients. Five studies discussed surgery wait times and 27 discussed LOS. Three HIC studies reported mean surgery wait time of 4 days (SD not reported), 33 ± 13 days, and 34 ± 39 days, and 2 LMIC studies reported median surgery wait time of 4.6 (1-15) and 50 (13-703) days. Mean LOS was 5.1 days (95% CI: 4.2-6.1 days) from 24 HIC studies and 10.0 days (95% CI: 4.6-15.6 days) from 8 LMIC studies respectively. Mean LOS was 5.0 days (95% CI: 3.9-6.0 days) from countries with mixed payer system, and 7.7 days (95% CI: 4.8-10.5 days) from countries with single payer systems. There are limited data on surgery wait-times yet slightly more data on postoperative LOS. Despite a wide range of wait times, mean LOS in brain tumor patients tended to be longer in LMICs than HICs and longer for countries with single payer health systems than mixed payer health systems. Further studies are needed to evaluate surgery wait times and LOS for brain tumor patients more accurately.


Amino acid sequence of a kappa I primary (AL) amyloid protein (AND).
The complete amino acid sequence of amyloid protein AND is presented. Amyloid fibrils were isolated from the spleen of patient AND, and the subunit protein was isolated from the fibrils after reduction and carboxymethylation. Sequence analysis of intact protein AND identified it as a kappa I immunoglobulin light chain. The complete sequence was determined from its tryptic peptides. The protein contained the entire variable region and the constant region to position 145 of the light chain. Several unique amino acid substitutions were found in protein AND compared to other kappa I proteins. The glycine, serine, arginine, threonine, alanine and arginine at positions 31, 45, 55, 76, 85 and 107, respectively, are reported for the first time in a kappa I protein. A number of uncommon amino acid substitutions were found in the framework regions in protein AND around the contact region of the dimer which may result in the molecule becoming more susceptible to fibril formation.


Age-related hearing loss and dementia-related neuropathology: An analysis of the United Kingdom brains for dementia research cohort.
Age-related hearing loss frequently precedes or coexists with mild cognitive impairment and dementia. The role specific neuropathologies play in this association, as either a cause or a consequence, is unclear. We therefore aimed to investigate whether specific dementia related neuropathologies were associated with hearing impairment in later life. We analysed data on ante-mortem hearing impairment with post-mortem neuropathological data for 442 participants from the Brains for Dementia Research Cohort. Binary logistic regression models were used to estimate the association of hearing impairment with the presence of each dementia-related neuropathology overall, and with specific staged changes. All analyses adjusted for age and sex, and several sensitivity analyses were conducted to test the robustness of findings. Presence and density of neuritic plaques were associated with higher odds of hearing impairment ante-mortem (OR = 3.65, 95% CI 1.78-7.46 for frequent density of plaques). Presence of any LB disease was likewise associated with hearing impairment (OR = 2.10, 95% CI 1.27-3.48), but this did not increase with higher cortical pathology (OR = 1.53, 95% CI 0.75-3.11). Nonspecific amyloid deposition, neurofibrillary tangle staging, overall AD neuropathology level, and cerebrovascular disease were not clearly associated with increased risks of hearing impairment. Our results provide some support for an association between dementia-related neuropathology and hearing loss and suggest that hearing loss may be associated with a high neuritic plaque burden and more common in Lewy body disease.


Corneal endothelial cell changes after cataract surgery in patients on systemic sympathetic α-1a antagonist medication (tamsulosin).
The purpose of this study was to assess the incidence of intraoperative floppy iris syndrome (IFIS) and the morphology of the corneal endothelium after cataract extraction in Caucasian male patients exposed to the α-1a adrenergic receptor antagonist tamsulosin. In a clinical prospective study, 23 male patients (23 eyes) treated with tamsulosin due to benign prostatic hyperplasia and 25 male patients (25 eyes) with no tamsulosin treatment had cataract surgery. The divide-and-conquer technique was used with the Infinity OZil(®) machine. A combination of Healon and Healon5 was used in all patients, but the use of additional Vision Blue, iris retractors or intracameral phenylephrine in the tamsulosin group was at the discretion of the surgeon. The endothelial cell density, variation in endothelial cell size (CV), percentage of hexagonal cells and central corneal thickness (CCT) were recorded at baseline and at 3 months postoperatively. In the tamsulosin-treated group, 19 of 23 eyes (83%) developed IFIS, compared with no IFIS in the control group. Compared with the control group, the tamsulosin group showed significantly less dilatation at the start of the operation, significant miosis during surgery and significantly greater corneal endothelial cell loss 3 months postoperatively (12% versus 3%; p< 0.001). Intraoperative floppy iris syndrome during cataract surgery is significantly associated with tamsulosin-treated male patients. Patients on tamsulosin showed less preoperative dilatation, significant miosis during surgery, and had significantly greater postoperative endothelial cell loss compared with nontreated patients despite recommended precautions.


Disrupted white matter structure underlies cognitive deficit in hypertensive patients.
Hypertension is considered a risk factor of cognitive impairments and could result in white matter changes. Current studies on hypertension-related white matter (WM) changes focus only on regional changes, and the information about global changes in WM structure network is limited. We assessed the cognitive function in 39 hypertensive patients and 37 healthy controls with a battery of neuropsychological tests. The WM structural networks were constructed by utilizing diffusion tensor tractography and calculated topological properties of the networks using a graph theoretical method. The direct and indirect correlations among cognitive impairments, brain WM network disruptions and hypertension were analyzed with structural equation modelling (SEM). Hypertensive patients showed deficits in executive function, memory and attention compared with controls. An aberrant connectivity of WM networks was found in the hypertensive patients (P Eglob = 0.005, P Lp = 0.005), especially in the frontal and parietal regions. Importantly, SEM analysis showed that the decline of executive function resulted from aberrant WM networks in hypertensive patients (p = 0.3788, CFI = 0.99). These results suggest that the cognitive decline in hypertensive patients was due to frontal and parietal WM disconnections. Our findings highlight the importance of brain protection in hypertension patients. • Hypertension has a negative effect on the performance of the cognitive domains • Reduced efficiencies of white matter networks were shown in hypertension • Disrupted white matter networks are responsible for poor cognitive function in hypertension.


Modeling Management Strategies for Clinical Stage I Seminoma: Direct and Indirect Costs for the First 5 Years.
Clinical stage I seminoma can be managed with surveillance, chemotherapy or radiotherapy with similar survival rates. However, costs and side effects vary among these treatment modalities. We created a model to estimate the direct and indirect costs during the first 5 years of treatment for the 3 treatment strategies. Markov model based analyses were conducted to compare the costs of the 3 management strategies during the first 5 years. In this model clinicians and patients were assumed to be 100% compliant with the 2012 NCCN Guidelines® for testicular cancer. Model parameters were collected from the Washington State CHARS (Comprehensive Hospital Abstract Reporting System), published literature and Medicare reimbursement amounts. A 5% annual health inflation rate was assumed. The model predicts an initial cost premium for carboplatin (1 cycle-$9,199.49; 2 cycles-$10,613.85) and radiotherapy ($9,532.80) compared with surveillance ($9,065.31). Radiotherapy (145.8 hours) and surveillance (123.0 hours) require more patient time than carboplatin (1 cycle-93.2 hours, 2 cycles-106.3 hours). When the direct and indirect costs are considered, the least expensive management strategy is surveillance. Surveillance is the most cost-effective management strategy for clinical stage I seminoma during the first 5 years of treatment. Although not evaluated in this analysis, costs of late side effects associated with radiotherapy and chemotherapy should be considered. Due to potentially minimal late side effects and superior cost-effectiveness, surveillance represents a safe, cost-effective and time effective option for the management of stage I seminoma.


The effects of motor skill and physical activity interventions on preschoolers' cognitive and academic skills: A systematic review.
The present systematic review aimed to investigate the methodological quality and the effects of fundamental motor skills and physical activity interventions on cognitive and academic skills in typically developing 3 to 7-year-old children. The review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A literature search was carried out in April 2020 using seven electronic databases. The methodological quality of the studies was assessed with the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool. Cohen's d effect size calculations and post hoc power analyses were conducted for the included studies. A total of 35 studies, representing 2472 children met the inclusion criteria. Two of the studies demonstrated a strong methodological quality, while 24 were considered as methodologically weak. The majority (71%) of the included studies demonstrated the beneficial effects of the intervention on cognitive and academic skills. The most evidence was found for executive functions, language, and numeracy, and the effects were largest in enhancing memory. The effects were larger on cognitive and academic skills in the combined interventions compared to only fundamental motor skill and physical activity interventions, while fundamental motor skill interventions had larger effects than physical activity interventions. These findings indicate that it may be possible to support typically developing preschoolers' cognitive and academic learning with fundamental motor skill and physical activity interventions. However, most of the studies in this field have a weak methodological quality and thus, the presented evidence was considered weak in nature.


Aqueous-phase aerobic oxidation of alcohols by soluble Pt nanoclusters in the absence of base.
A soluble Pt nanocluster catalyst (Pt-GLY) is efficient in the absence of base for aqueous-phase aerobic oxidation of, in particular, non-activated alcohols with high recyclability.


The phenomenon and cause of the dose-dependent oral absorption of chlorothiazide in rats: extrapolation to human data based on the body surface area concept.
The reported incomplete and dose-dependent absorption of chlorothiazide in humans was demonstrated in six rats after five oral solutions at doses of 0.93, 2.55, 9.23, 25.6, and 70.2 mg/kg. Mean 48-hr urinary recoveries of intact drug were 57.3, 50.4, 36.7, 22.8, and 15.3%, respectively. A similar degree of dose dependency in absorption was found in rat, dog, and human when the doses were related to unit body surface area (BSA) but not on unit body weight, indicating similar interspecies absorptive capacity in terms of unit BSA. This finding may be partly rationalized by marked similarities in the reported solution transit time (2-3 hr) in the small intestine as well as in the calculated gross surface area of the small intestine per unit BSA (0.163 for rat and 0.132 for human). Contrary to the previous postulation of a specific absorption site, the drug was absorbed from different regions of the GI tract with apparent 1-hr absorption rates, studied by the in situ closed-loop method, in the following rank order: jejunum (34.6%) greater than duodenum (32.7%) greater than large intestine (20.1%) greater than ileum (18.0%) greater than stomach (12.4%). Different from the commonly assumed first-order absorption process, the intestinal loop absorption was concentration-dependent, suggesting a saturable mechanism. For example, the absorption rate at 0.008 mg/mL was higher than that at 0.2 mg/mL in ileal loops (61%, p less than 0.01) and jejunal loops (22%, p less than 0.1). In addition, the absorption rates at pH 6 and 7.4 were statistically identical, indicating a lack of ionization effect that is important in the passive absorption process. The solubility-limited absorption could probably be ruled out at doses below 2.55 mg/kg for rat and 125 mg for human in view of higher aqueous solubilities at 37 degrees C (e.g., 1.3 mg/mL at pH 7) found in the present study. Contrary to the previous hypothesis of low membrane permeability as a limiting factor for absorption, the "intrinsic" partition coefficient in 1-octanol/aqueous buffer was moderate, 0.6. Furthermore, the absorption in ileal and jejunal loops was enhanced by an apparent increase in mesenteric blood flow by caffeine. The existence of prolonged oral absorption in rats and humans is discussed.


Spore germination.
Despite being relatively insensitive to environmental insult, the spore is responsive to low concentrations of chemical germinants, which induce germination. The process of bacterial spore germination involves membrane permeability changes, ion fluxes and the activation of enzymes that degrade the outer layers of the spore. A number of components in the spore that are required for the germination response have been identified, including a spore-specific family of receptor proteins (the GerA family), an ion transporter and cortex lytic enzymes. The germinant traverses the outer layers of the spore and interacts with its receptor in the inner membrane to initiate the cascade of germination events, but the molecular details of this signal transduction process remain to be identified.


The role of mast cells in asthma.
While the role of mast cells in allergic reactions is unequivocal, their precise functions in asthma remain controversial. Mast cells uniquely populate all vascularized organs and tissues, including the upper and lower respiratory tree, even in healthy individuals. Histologic evidence suggests that asthma is accompanied by a mast cell hyperplasia in the inflamed mucosal epithelium and the adjacent smooth muscle. The mechanisms responsible for constitutive mast cell development have been partly elucidated. Moreover, both in vitro studies and in vivo disease models indicate that mast cells have a remarkably flexible program of gene expression, and this program can be drastically altered by the T-cell-derived Th2 cytokines relevant to asthma. Moreover, the role of mast cells in innate immunity is now firmly established, and the capacity for numerous microbial pathogens to initiate their activation in vitro and in vivo suggest mechanisms by which microbes could initiate disease exacerbations.


Transcervical sperm transport in the rat: the roles of pre-ejaculatory behavior and copulatory plug fit.
In the rat, the transport of sperm from the vagina, where they are deposited at ejaculation, into the uterus is not automatic. Various behavioral and physiological factors influence this transport process: the number of pre-ejaculatory intromissions, the duration of immobility at ejaculation, and the fit of the copulatory plug. The interplay of these three factors in producing adequate sperm transport, and their relations with each other, were examined in 52 female rats that received various numbers of pre-ejaculatory intromissions (from 0 to more than 15). The number of intromissions was strongly related to all other measures. Ejaculatory immobility was associated with better fitting copulatory plugs when females received few intromissions. Sperm transport was most strongly predicted by plug fit. Intromissions were a major predictor of good fitting copulatory plugs and transcervical sperm transport; immobility did not mediate intromission's influence and did not have a major independent role.


The Use of a Mobile Van for School Vision Screening: Results of 63 841 Evaluations.
To present data from an established mobile screening program for children in the amblyogenic age group using gold-standard examination techniques by eye care professionals. Retrospective 12-year, cross-sectional study. setting: Single center. All children enrolled in pre-kindergarten, kindergarten, and first grades in public schools in Cleveland, Ohio were eligible for evaluations. intervention procedure: An ophthalmic technician and/or optometrist examined children in a customized van that visits all elementary schools. The initial screening included testing of monocular near and distance visual acuity, stereoacuity, ocular alignment, motility, pupils, and external abnormalities. Children meeting the 2003 American Academy of Pediatrics vision screening referral criteria underwent cycloplegic retinoscopy and ophthalmoscopy by the on-site optometrist and received glasses. In addition, these children were referred to pediatric ophthalmology for ongoing care. Determination of the proportion of children with refractive errors, amblyopia, and/or strabismus. Between 2002 and 2014, 63 841 evaluations were performed, representing approximately 55% of eligible children. Overall, 6386 (10.0%) of children met 1 or more referral criteria: 5355 (8.39%) received glasses, 873 (1.37%) had amblyopia, and 1125 (1.76%) had strabismus. Over the 12-year period, there was no statistically significant change in the prevalence of strabismus (1.73%-2.24%, P = .91) or amblyopia (0.9%-2.08%, P = .13) among first grade students. Amblyopia, strabismus, and refractive errors are common in young children. During the study period, the rates of amblyopia and strabismus remained stable, indicating the need for continued vision screening and treatment services. A van-based model, traveling directly to schools, appears to be effective in reaching young children in underserved communities.


Characterization of [3H]inositol 1,4,5-trisphosphate binding sites in human temporal cortical and cerebellar membranes.
The characteristics of [3H]Ins(1,4,5)P3 binding to human temporal cortical and cerebellar membranes have been determined and compared with the binding to calf cerebellar membranes. Association and dissociation of ligand was very rapid, k1 and k-1 values of the order of 7 x 10(7) M-1 min-1 and 0.2 min-1, respectively. KD values were 2.7 and 3.5 nM for temporal cortex and cerebellum, respectively. The corresponding Bmax values were 165 and 482 fmol/mg protein. Binding was influenced in a biphasic manner by calcium. The temporal cortical binding was inhibited by Ins(1,4,5)P3 and analogues with the following IC50 values (nM): Ins(1,4,5)P3 9.5 and 6.2 (two different salts from different sources), Ins(2,4,5)P3 42, Ins(1,3,4,5)P4 670, Ins(1,2,5,6)P4 2620, Ins(3,4,5,6)P4 4300, Ins(1,3,4,5,6)P5 5490, InsP(6)5280, Ins(4,5)P2 2600, Ins(1)P 3300, with the IC50 values for Ins(1,5,6)P3, Ins(1,4)P2 and Ins(4)P being > 25 microM. The IC50 value for heparin was 2.1 micrograms/ml. A similar pattern was seen in the cerebellum. In both tissues, the Hill slopes were near unity for all compounds except Ins(3,4,5,6)P4, where the slope was 0.4. The calf cerebellum had a similar ligand specificity (although the potency was generally lower) when values were expressed relative to that of Ins(1,4,5)P3, with the possible exception of Ins(1,3,4,5)P4, which had a greater relative potency. These data would suggest that in the human temporal cortex and cerebellum, [3H]Ins(1,4,5)P3 binding sites are expressed in different densities, but have similar properties. There may, however, be species differences in the [3H]Ins(1,4,5)P3 recognition site.


Bacterial levels and diversity in kitchen sponges and dishwashing brushes used by consumers.
The purpose of the work was to investigate bacterial levels and diversity as well as survival of Salmonella in used dish washing sponges and brushes and identify consumer practices that can potentially explain bacterial status of these items. Used washing up utensils were collected from consumers. The bacterial numbers (TVC) were very variable with an extremely high median level (10.3 log cfu/item) in Portuguese sponges and lower levels in Norwegian items (7.3 and 7.0 cfu/item for sponges and brushes). No self-reported practices or household composition could explain differences found in TVC levels among the collected sponges. Lower mean TVC levels were found in unworn brushes and brushes regularly cleaned with soap, but the differences were modest (1.5 log or less). A common set of bacteria was found in brushes and sponges, dominated by Acinetobacter, Chryseobacterium, Enhydrobacter, Enterobacteriaceae and Pseudomonas. There was no difference in TVC or bacterial diversity between conventional and antimicrobial sponges containing silver after 4 weeks of use. For used brushes inoculated with Salmonella and allowed to dry overnight, a significant reduction in Salmonella numbers was observed. No reduction was observed for brushes stored in humid conditions (in a plastic bag) or for sponges regardless of storing conditions. Overall, lower bacterial levels were observed in used brushes than in sponges, and Salmonella died more rapidly in brushes. A common set of non-pathogenic bacteria dominated in brushes and sponges. The study demonstrates that the use of brushes may be more hygienic than the use of sponges.


Polymerized-type I collagen downregulates inflammation and improves clinical outcomes in patients with symptomatic knee osteoarthritis following arthroscopic lavage: a randomized, double-blind, and placebo-controlled clinical trial.
Polymerized-type I collagen (polymerized collagen) is a downmodulator of inflammation and cartilage regenerator biodrug. To evaluate the effect of intraarticular injections of polymerized collagen after arthroscopic lavage on inflammation and clinical improvement in patients with knee osteoarthritis (OA). Patients (n = 19) were treated with 6 intraarticular injections of 2 mL of polymerized collagen (n = 10) or 2 mL of placebo (n = 9) during 3 months. Followup was 3 months. The primary endpoints included Lequesne index, pain on a visual analogue scale (VAS), WOMAC, analgesic usage, the number of Tregs and proinflammatory/anti-inflammatory cytokine-expressing peripheral cells. Secondary outcomes were Likert score and drug evaluation. Clinical and immunological improvement was determined if the decrease in pain exceeds 20 mm on a VAS, 20% of clinical outcomes, and inflammatory parameters from baseline. Urinary levels of C-terminal crosslinking telopeptide of collagen type II (CTXII) and erythrocyte sedimentation rate (ESR) were determined. Polymerized collagen was safe and well tolerated. Patients had a statistically significant improvement (P < 0.05) from baseline versus polymerized collagen and versus placebo at 6 months on Lequesne index, VAS, ESR, Tregs IL-1β, and IL-10 peripheral-expressing cells. Urinary levels of CTXII were decreased 44% in polymerized collagen versus placebo. No differences were found on incidence of adverse events between groups. Polymerized collagen is safe and effective on downregulation of inflammation in patients with knee OA.


Food aflatoxin exposure assessment in Sichuan Province, China.
Aflatoxins (AFs) are frequent contaminants in crops worldwide and can cause adverse health effects in exposed humans. Since foods AFs (AFB1, AFB2, AFG1, AFG2) contamination in Sichuan Province are unexplored, we conducted a study to assess AFs exposure in the population. In total, 318 samples, including grains, red chilli, red chilli powder, and vegetable protein beverages, were collected from 13 cities of Sichuan Province, China, in 2022. AFs were detected in all types of foods except for wheat flour, the highest incidence was found in red chilli powder (75.0%). The concentrations of AFtot (the total aflatoxins) ranged between ND (not detected) and 54.20 μg kg-1. It was observed that the AFs profile was dominated by AFB1. The AFB1 content ranged from ND to 52.60 μg kg-1 across food types. According to EU maximum limits (ML) of AFs, 2.8% of samples exceeded the AFtot limits. For AFB1, 0.4% and 4.3% of samples exceeded the China and EU limits, respectively. In this study, packaging types and sampling sites were selected as parameters influence food aflatoxin contamination. Nevertheless, there was no significant difference between different samples. According to exposure assessment and risk characterization, AFtot daily exposure was shown to be 0.263 and 283.936 ng kg-1 bw for the lower and upper exposure. The MOE value derived from consumption grains and red chilli pepper products were generally bellow 10 000, and liver cancer cases based on these two foods consumption could range from < 0.001 to 0.16 cases per year/10 000 persons.


Chemotherapy as a therapeutic option for congenital neuroblastoma complicated by paraplegia.
Spinal compression can be a complication of neuroblastoma (NBL). Delayed or insufficient treatment of this condition may lead to permanent neurological sequelae. Therefore, appropriate treatment should be introduced promptly. Therapeutic options include neurosurgery, chemotherapy, and radiation therapy. We report on a newborn male with congenital NBL who presented with complete paraplegia of the legs at birth. Tumor size diminished quickly and neurological symptoms partly recovered after the patient received chemotherapy consisting of vincristine, doxorubicine, and cyclophosphamide. Rapid initiation of chemotherapy was safe and effective in a neonate with NBL complicated by spinal cord compression.


The effect of preconditioning on the Cu, Zn superoxide dismutase expression and enzyme activity in rat brain at the early period after severe hypobaric hypoxia.
Severe hypoxia results in functional and structural injury of the brain. A preconditioning with repetitive episodes of mild hypoxia considerably ameliorates neuronal resistance to subsequent severe hypoxia. Activation of endogenous antioxidants including Cu, Zn-depending superoxide dismutase (Cu, Zn-SOD) (EC.188.8.131.52) is one of the main cell defense mechanisms against oxidative stress induced by hypoxia. Alterations of expression and enzyme activity of Cu, Zn-SOD 3 and 24h after severe hypobaric hypoxia in forebrain structures of preconditioned and non-preconditioned rats were investigated. We found that hypoxia without preconditioning suppressed the Cu, Zn-SOD enzyme activity at 3h time-point but preconditioning essentially modified the reaction to severe hypoxia by increasing the expression and activity of Cu, Zn-SOD during early stages of reoxygenation crucial for apoptosis initiation.


A novel interlayer-expanded tin disulfide/reduced graphene oxide nanocomposite as anode material for high-performance sodium-ion batteries.
As a kind of negative electrode material for sodium-ion batteries (SIBs), tin-based active compounds have attracted numerous research efforts in recent years due to relatively high theoretical capacity. However, sluggish reaction kinetics for large-radius sodium ions hinders the practical application of layered tin-based anodes such as tin disulfide (SnS2) in SIBs. In this study, polyethylene glycol (PEG) is introduced as an intercalant and reduced graphene oxide (rGO) is utilized as the substrate to prepare a novel PEG-SnS2/rGO composite with expanded layer spacing (0.921 nm) through a facile hydrothermal process. SnS2 flakes in a size range of 50-100 nm are uniformly grown on the graphene sheet, the CS covalent bonding demonstrates a tight connection between the active SnS2 particles and the graphene skeleton, which is conductive to convenient charge transfer during the electrochemical process. Owing to the significantly improved sodium ions transport kinetics and fast electronic conductive network, the PEG-SnS2/rGO composite presents a high capacitance contribution of 90.69% at a scan rate of 0.6 mV s-1. It delivers a high reversible capacity of 960.6 mAh g-1 at 0.1 A g-1, good cycling performance with 770 mAh g-1 remained after 100 charge/discharge cycles, and excellent rate capability with an ultrahigh capacity of 720 mAh g-1 at 5 A g-1. This work provides new insights into the design of a kinetically favorable anode material for SIBs.


Open calcaneal fractures: assessment and management.
Open calcaneal fractures are obscure fractures. Typically, these injuries result in a high-energy, polytraumatized patient population. Initial management consists of irrigation and debridement. Secondary forms of management continue to evolve. High-energy fracture subtypes and severe soft tissue injuries portend an unsatisfactory outcome, despite appropriate management. Standards for the type and timing of treatment have not been established.


[Associated placenta praevia and placenta accreta. Clinical case].
Personal experience of a case of placenta praevia and accreta is reported. In agreement with other authorities, it is thought that since the condition is not immediately apparent, it should always be suspected when hemorrhaging occurs in the 7th-9th month of pregnancy. It is also confirmed that rapid diagnosis and radical treatment will generally prevent serious problems.


Filia Is an ESC-Specific Regulator of DNA Damage Response and Safeguards Genomic Stability.
Pluripotent stem cells (PSCs) hold great promise in cell-based therapy, but the genomic instability seen in culture hampers their full application. A greater understanding of the factors that regulate genomic stability in PSCs could help address this issue. Here we describe the identification of Filia as a specific regulator of genomic stability in mouse embryonic stem cells (ESCs). Filia expression is induced by genotoxic stress. Filia promotes centrosome integrity and regulates the DNA damage response (DDR) through multiple pathways, including DDR signaling, cell-cycle checkpoints and damage repair, ESC differentiation, and apoptosis. Filia depletion causes ESC genomic instability, induces resistance to apoptosis, and promotes malignant transformation. As part of its role in DDR, Filia interacts with PARP1 and stimulates its enzymatic activity. Filia also constitutively resides on centrosomes and translocates to DNA damage sites and mitochondria, consistent with its multifaceted roles in regulating centrosome integrity, damage repair, and apoptosis.


A review on the added value of whole-body MRI in metastatic lobular breast cancer.
Invasive lobular breast carcinomas (ILC) account for approximately 15% of breast cancer diagnoses. They can be difficult to diagnose both clinically and radiologically, due to their infiltrative growth pattern. The pattern of metastasis of ILC is unusual, with spread to the serosal surfaces (pleura and peritoneum), retroperitoneum and gastrointestinal (GI)/genitourinary (GU) tracts and a higher rate of leptomeningeal spread than IDC. Routine staging and response assessment with computed tomography (CT) can be undertaken quickly and measurements can be reproduced easily, but this is challenging with metastatic ILC as bone-only/bone-predominant patterns are frequently seen and assessment of the disease status is limited in these scenarios. Functional imaging such as whole-body MRI (WBMRI) allows the assessment of bone and soft tissue disease by providing functional information related to differences in cellular density between malignant and benign tissues. A number of recent studies have shown that WBMRI can detect additional sites of disease in metastatic breast cancer (MBC), resulting in a change in systemic anti-cancer therapy. Although WBMRI and fluorodeoxyglucose-positron-emission tomography-computed tomography (FDG-PET/CT) have a comparable performance in the assessment of MBC, WBMRI can be particularly valuable as a proportion of ILC are non-FDG-avid, resulting in the underestimation of the disease extent. In this review, we explore the added value of WBMRI in the evaluation of metastatic ILC and compare it with other imaging modalities such as CT and FDG-PET/CT. We also discuss the spectrum of WBMRI findings of the different metastatic sites of ILC with CT and FDG-PET/CT correlation. KEY POINTS: • ILC has an unusual pattern of spread compared to IDC, with metastases to the peritoneum, retroperitoneum and GI and GU tracts, but the bones and liver are the commonest sites. • WBMRI allows functional assessment of metastatic disease, particularly in bone-only and bone-predominant metastatic cancers such as ILC where evaluation with CT can be challenging and limited. • WBMRI can detect more sites of disease compared with CT, can reveal disease progression earlier and provides the opportunity to change ineffective systemic treatment sooner.


Controversies in ulcerative colitis: a survey comparing decision making of experts versus community gastroenterologists.
Despite the development of consensus guidelines in ulcerative colitis (UC), there remain several areas of uncertainty in the everyday management of this incompletely understood disease. We performed a national vignette survey to measure variations in decision-making in areas of controversy. We constructed a survey with 3 vignettes to measure decision-making in 4 areas of controversy in UC: (1) dysplasia management, (2) mesalamine dosing, (3) diagnostic testing for underlying Crohn's disease, and (4) treatment of steroid-refractory inpatient UC. We compared responses between a group of community gastroenterologists and UC experts. We received 192 responses (36% response). Compared with community gastroenterologists, UC experts were more likely to endorse colectomy for both unifocal and multifocal low-grade dysplasia, use narrow band imaging and chromoendoscopy for surveillance colonoscopy, use high-dose mesalamine for inducing remission, use long-term mesalamine for cancer chemoprevention, order computed tomography enterography to evaluate for Crohn's disease, and to have a lower threshold to call for surgery consultation in steroid-refractory UC. There was little agreement regarding the optimal frequency of surveillance colonoscopy, even among experts. Most respondents favored using infliximab over cyclosporine in steroid-refractory UC. Community gastroenterologists and UC experts vary dramatically in their approach to many areas of uncertainty in UC. The only area of consensus between groups is the use of infliximab over cyclosporine in steroid-refractory UC, itself a controversial decision. These data suggest that current practice patterns are highly disparate and focus attention on specific areas of disconnect that should be further investigated.


Pan-cancer gene expression analysis: Identification of deregulated autophagy genes and drugs to target them.
Identifying suitable deregulated targets in autophagy pathway is essential for developing autophagy modulating cancer therapies. With this aim, we systematically analyzed the expression levels of genes that contribute to the execution of autophagy in 21 cancers. Deregulated genes for 21 cancers were analyzed using the level 3 mRNA data from TCGAbiolinks. A total of 574 autophagy genes were mapped to the deregulated genes across 21 cancers. PPI network, cluster analysis, gene enrichment, gene ontology, KEGG pathway, patient survival, protein expression and cMap analysis were performed. Among the autophagy genes, 260 were upregulated, and 43 were downregulated across pan-cancer. The upregulated autophagy genes - CDKN2A and BIRC5 - were the most frequent signatures in cancers and could be universal cancer biomarkers. Significant involvement of autophagy process was found in 8 cancers (CHOL, HNSC, GBM, KICH, KIRC, KIRP, LIHC and SARC). Fifteen autophagy hub genes (ATP6V0C, BIRC5, HDAC1, IL4, ITGB1, ITGB4, MAPK3, mTOR, cMYC, PTK2, SRC, TCIRG1, TP63, TP73 and ULK1) were found to be linked with patients survival and also expressed in cancer patients tissue samples, making them as potential drug targets for these cancers. The deregulated autophagy genes were further used to identify drugs Losartan, BMS-345541, Embelin, Abexinostat, Panobinostat, Vorinostat, PD-184352, PP-1, XMD-1150, Triplotide, Doxorubicin and Ouabain, which could target one or more autophagy hub genes. Overall, our findings shed light on the most frequent cancer-associated autophagy genes, potential autophagy targets and molecules for cancer treatment. These findings can accelerate autophagy modulation in cancer therapy.


Alterations in blood pressure, antioxidant status and caspase 8 expression in cobalt chloride-induced cardio-renal dysfunction are reversed by Ocimum gratissimum and gallic acid in Wistar rats.
The protective abilities of the chloroform extract of Ocimum gratissimum (COG) and gallic acid against cobalt chloride (CoCl2) - induced cardiac and renal toxicity were evaluated. Rats were exposed to CoCl2 (350ppm) for 7 days, either alone, or in combination with COG (100 and 200mg/kg) or gallic acid (120mg/kg). CoCl2 given alone, caused significant increases (p<0.05) in oxidative stress parameters (hydrogen peroxide, H2O2 and malondialdehyde, MDA) and increased expression of the apoptotic initiator caspase 8 in the heart and kidneys. There was significant reduction (p<0.05) in reduced glutathione (GSH) in cardiac and renal tissues; reduction in superoxide dismutase (SOD) activity in the kidneys and adaptive increases in Glutathione S-transferase (GST) and catalase (CAT). CoCl2 also produced significant reduction (p<0.05) in systolic (SBP), diastolic (DBP) and mean arterial (MAP) blood pressures. Oral COG and gallic acid treatment significantly reduced (p<0.05) the levels of H2O2 and MDA; with reduced expression of caspase 8 and restoration of GSH levels, GPx, SOD and CAT activities, howbeit, to varying degrees in the heart and kidneys. COG (200mg/kg) was most effective in restoring the blood pressures in the rats to near control levels. CoCl2-induced histopathological lesions including myocardial infarction and inflammation and renal tubular necrosis and inflammation were effectively ameliorated by the treatments administered. This study provides evidence for the protective roles of O. gratissimum and gallic acid by modulation of CoCl2-induced alterations in blood pressure, antioxidant status and pro-apoptotic caspase 8 in Wistar rats.


In situ organic Fenton-like catalysis triggered by anodic polymeric intermediates for electrochemical water purification.
Organic Fenton-like catalysis has been recently developed for water purification, but redox-active compounds have to be ex situ added as oxidant activators, causing secondary pollution problem. Electrochemical oxidation is widely used for pollutant degradation, but suffers from severe electrode fouling caused by high-resistance polymeric intermediates. Herein, we develop an in situ organic Fenton-like catalysis by using the redox-active polymeric intermediates, e.g., benzoquinone, hydroquinone, and quinhydrone, generated in electrochemical pollutant oxidation as H2O2 activators. By taking phenol as a target pollutant, we demonstrate that the in situ organic Fenton-like catalysis not only improves pollutant degradation, but also refreshes working electrode with a better catalytic stability. Both 1O2 nonradical and ·OH radical are generated in the anodic phenol conversion in the in situ organic Fenton-like catalysis. Our findings might provide a new opportunity to develop a simple, efficient, and cost-effective strategy for electrochemical water purification.


An eigenvalue approach for the automatic scaling of unknowns in model-based reconstructions: Application to real-time phase-contrast flow MRI.
The purpose of this work is to develop an automatic method for the scaling of unknowns in model-based nonlinear inverse reconstructions and to evaluate its application to real-time phase-contrast (RT-PC) flow magnetic resonance imaging (MRI). Model-based MRI reconstructions of parametric maps which describe a physical or physiological function require the solution of a nonlinear inverse problem, because the list of unknowns in the extended MRI signal equation comprises multiple functional parameters and all coil sensitivity profiles. Iterative solutions therefore rely on an appropriate scaling of unknowns to numerically balance partial derivatives and regularization terms. The scaling of unknowns emerges as a self-adjoint and positive-definite matrix which is expressible by its maximal eigenvalue and solved by power iterations. The proposed method is applied to RT-PC flow MRI based on highly undersampled acquisitions. Experimental validations include numerical phantoms providing ground truth and a wide range of human studies in the ascending aorta, carotid arteries, deep veins during muscular exercise and cerebrospinal fluid during deep respiration. For RT-PC flow MRI, model-based reconstructions with automatic scaling not only offer velocity maps with high spatiotemporal acuity and much reduced phase noise, but also ensure fast convergence as well as accurate and precise velocities for all conditions tested, i.e. for different velocity ranges, vessel sizes and the simultaneous presence of signals with velocity aliasing. In summary, the proposed automatic scaling of unknowns in model-based MRI reconstructions yields quantitatively reliable velocities for RT-PC flow MRI in various experimental scenarios.


Pylorus-preserving gastrectomy with radical lymph node dissection based on anatomical variations of the infrapyloric artery.
We devised a method for performing pylorus-preserving gastrectomy (PPG) with radical lymph node dissection without compromising pyloric blood flow, based on vascular anatomical evaluation of 210 celiac angiograms. The origin of the infrapyloric artery was variable, but consistently supplied blood flow to the pylorus and the posterior wall of the antrum. When the infrapyloric artery originated from the gastroduodenal artery or from one of its pancreatic branches (type A, 88%), the right gastroepiploic artery was divided at its origin, allowing the excision of all adjacent lymph nodes. When the infrapyloric artery originated from the right gastroepiploic artery (type B, 12%), the right gastroepiploic artery was divided distal to the infrapyloric artery origin and the short right gastroepiploic artery remnant was skeletonized of lymph nodes. We have used this technique to perform PPG on 25 patients with early gastric cancer in the middle third of the stomach with minimal morbidity and no mortality.


Impact of unsolicited reporting notifications on providers' prescribing behavior: An experimental study on Maryland PDMP data.
Unsolicited Reporting Notifications(URNs) have been a component of Maryland's Prescription Drug Monitoring Program (PDMP) since 2016. We evaluated the effect of URNs on providers' prescription behaviors. This is a quasi-experimental study of providers who were issued at least one URN from January 2018 to April 2021. Providers for whom URNs were not successfully delivered were designated as a comparison group. The outcome variables were average daily opioid and benzodiazepine prescriptions, average morphine milligram equivalents per patient, and proportion of overlapping opioid and benzodiazepine, either with or without muscle relaxant prescriptions. Changes were compared before versus after the issuance of a URN among the intervention and comparison groups using "Generalized Estimation Equation" and "Generalized Linear" Models. We also conducted stratified analyses by types of URN, including notifications for multiple provider episodes (MPE), overdose fatality (ODF), and dangerous drug combinations (DDC). The average daily number of opioids prescriptions (3.3% decrease in the intervention group vs 22.7% increase in the comparison group, P<0.001), co-prescription of opioids and benzodiazepines either with muscle relaxants (68.0% decrease vs. 36.1% decrease, P<0.001), or without muscle relaxants (6.0% decrease vs. 16.3% increase, P<0.001), significantly reduced after the first URN regardless of the type of URN. Stratified analysis by types of URNs showed that ODF and DDC URNs had a significant effect on most of the outcomes of interest. The findings suggest that unsolicited reporting, especially particular types of URNs including ODF and DDC, is associated with subsequent changes in unsafe prescribing behaviors.


Angiodysplasia of the lower gastrointestinal tract: an entity readily diagnosed by colonoscopy and primarily managed nonoperatively.
The characteristics of patients who develop clinically significant angiodysplasia of the lower gastrointestinal (GI) tract are unknown, and methods of treatment are evolving. This study was undertaken to identify patient characteristics, methods of diagnosis, and current management of patients who require operation and outcome. Patients with the diagnosis of angiodysplasia of the lower GI tract at St. Louis University affiliated hospitals over the past five years were reviewed. Thirty-two consecutive patients were identified. The mean age was 69.8 (range, 29-86) years; 62.5 percent were males. Patient characteristics included: age greater than 65 years, 22 of 32 patients (69 percent); documented coagulopathy, 9 of 32 patients (28 percent); and cardiac valvular disease, 8 of 32 patients (25 percent). Diagnosis was established by colonoscopy in 27 of 32 patients (84 percent), enteroscopy in 3 of 32 patients (9 percent), and angiography in 2 of 32 patients (6 percent). Seventy-eight percent of the angiodysplasias were located in the right colon. Patients were treated by endoscopic coagulation in 16 of 32 patients (50 percent), surgical resection in 9 of 32 (12.5 percent), or observation in 3 of 32 patients (9 percent). Four of 32 patients (12.5 percent) developed recurrent bleeding. Four of 32 patients (12.5 percent) died of various causes. Follow-up was possible in 25 of 28 surviving patients, and the follow-up period ranged from 3 to 42 months, during which rebleeding occurred in 5 patients who had been previously treated by endoscopic coagulation and in 1 patient who had been treated by transfusion alone. Two patients died of unrelated causes and one from a recurrent lower GI bleed. Angiodysplasia is primarily a disease of elderly patients. These patients are frequently anticoagulated and often have co-existing cardiac valvular disease. Endoscopy usually establishes the diagnosis, and endoscopic coagulation is an effective and safe method of treatment. Most patients can be managed without operation.


Anticoagulation in patients with valvular heart disease, atrial fibrillation, or both.
Despite the availability of anticoagulant drugs for many years, there are still controversies regarding their use in many cardiovascular conditions. In this article, the pharmacology of warfarin and heparin are reviewed, and the clinical applications of these therapies in patients with valvular heart disease, atrial fibrillation, or both, discussed.


Aldehyde Dehydragenase 1 and Nodal as Significant Prognostic Markers in Colorectal Cancer.
This study aimed to analyze prognostic significance of aldehyde dehydragenase 1 (ALDH1) and Nodal expression in patients with colorectal cancer. ALDH1 and Nodal expressions were observed based on the immunohistochemistry staining from 108 colorectal cancer patients. Scores were given to the staining intensity and percentage of positive cells, and sum of two scores for each case was used to define the groups of ALDH1 and Nodal. We also investigated the protein and mRNA levels of ALDH1 and Nodal by Western blot and qRT-PCR assays. The results were analyzed with the clinicopathologic parameters of these patients. The results indicated that expressions of ALDH1 and Nodal were significantly correlated with the differentiation degree, metastasis, number of tumor positive lymph nodes and AJCC stage. ALDH1 was inclined to express more in the worse differentiated degrees, lymph node metastasis, and worse AJCC stage of colorectal cancer patients. And the expression of Nodal was inversely compared with ALDH1.While the expression of ALDH1 was inversely correlated with the Nodal (r = -0.709, P < 0.01).


Urinary low-molecular-weight protein excretion in pediatric idiopathic nephrotic syndrome.
Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are the most common causes of idiopathic nephrotic syndrome (INS). We have evaluated the reliability of urinary neutrophil-gelatinase-associated lipocalin (uNGAL), urinary alpha1-microglobulin (uα1M) and urinary N-acetyl-beta-D-glucosaminidase (uβNAG) as markers for differentiating MCD from FSGS. We have also evaluated whether these proteins are associated to INS relapses or to glomerular filtration rate (GFR). The patient cohort comprised 35 children with MCD and nine with FSGS; 19 healthy age-matched children were included in the study as controls. Of the 35 patients, 28 were in remission (21 MCD, 7 FSGS) and 16 were in relapse (14 MCD, 2 FSGS). The prognostic accuracies of these proteins were assessed by receiver operating characteristic (ROC) curve analyses. The level of uNGAL, indexed or not to urinary creatinine (uCreat), was significantly different between children with INS and healthy children (p = 0.02), between healthy children and those with FSGS (p = 0.007) and between children with MCD and those with FSGS (p = 0.01). It was not significantly correlated to proteinuria or GFR levels. The ROC curve analysis showed that a cut-off value of 17 ng/mg for the uNGAL/uCreat ratio could be used to distinguish MCD from FSGS with a sensitivity of 0.77 and specificity of 0.78. uβNAG was not significantly different in patients with MCD and those with FSGS (p = 0.86). Only uα1M, indexed or not to uCreat, was significantly (p < 0.001) higher for patients in relapse compared to those in remission. Our results indicate that in our patient cohort uNGAL was a reliable biomarker for differentiating MCD from FSGS independently of proteinuria or GFR levels.


Measurement of physician specimen-handling errors and its contribution to laboratory information system quality.
To reduce the frequency of errors associated with hematology specimens and requisitions arriving in the hematology laboratories of a large urban teaching hospital, an intervention was conducted to alter the behavior of the medical students, interns, residents, and board-qualified physicians who ordered the tests, completed the requisitions, and drew the specimens. This paper presents the method used for measuring specimen quality, certain results derived from the method, and corresponding considerations for changes in the design of the system by which specimens are collected and delivered to the laboratory. These changes should improve the quality of the entire laboratory information system.


The permeability of mammalian nonkeratinized oral epithelia to horseradish peroxidase applied in vivo and in vitro.
Horseradish peroxidase, an intercellular tracer, was injected sub-epithelially beneath keratinized gingiva and a variety of nonkeratinized oral epithelia. Fresh tissue biopsies from the same regions were also incubated with this tracer for 1 h. In separate experiments, horseradish peroxidase was applied topically to biopsies of oral mucosa maintained in tissue culture for periods up to 12 h. All specimens were treated so as to visualize the site of peroxidase penetration and the tissues were examined with the light and electron microscopes. In all the epithelia, a surface barrier was evident from which the tracer had been excluded. This was often narrow in the thin, nonkeratinized epithelia and could only be identified unambiguously with the electron microscope. Membrane-coating granules of the so-called nonkeratinized type were invariably associated with superficial plasma membrane of epithelial cells at the level where the barrier was first seen. The results suggest that a permeability barrier exists to horseradish peroxidase in all nonkeratinized oral epithelia with a similar location to that seen in the keratinized oral tissues. However, results obtained with a water-soluble tracer such as horseradish peroxidase may not apply to many drugs, the ready absorption of which may reflect their high lipid solubility.


[MORPHOLOGICAL PECULIARITIES OF MUSCULO-APONEUROTIC TISSUES OF ANTERIOR ABDOMINAL WALL IN PATIENTS, SUFFERING MORBID OBESITY].
Results of morphological investigation of musculo-aponeurotic structures of anterior abdominal wall were presented in the morbid obesity patients. The role of obesity as a primary cause for morphofunctional insufficience of musculo-aponeurotic structures was established.


Acute aerobic exercise and information processing: energizing motor processes during a choice reaction time task.
The immediate and short-term after effects of a bout of aerobic exercise on young adults' information processing were investigated. Seventeen participants performed an auditory two-choice reaction time (RT) task before, during, and after 40 min of ergometer cycling. In a separate session, the same sequence of testing was completed while seated on an ergometer without pedalling. Results indicate that exercise (1) improves the speed of reactions by energizing motor outputs; (2) interacts with the arousing effect of a loud auditory signal suggesting a direct link between arousal and activation; (3) gradually reduces RT and peaks between 15 and 20 min; (4) effects on RT disappear very quickly after exercise cessation; and (5) effects on motor processes cannot be explained by increases in body temperature caused by exercise. Taken together, these results support a selective influence of acute aerobic exercise on motor adjustment stage.


Effects of a short outpatient rehabilitation treatment on disability of multiple sclerosis patients--a randomised controlled trial.
It is well known that neurorehabilitation can reduce disability or improve handicap of people with multiple sclerosis (MS). The aim of this study was to evaluate the effectiveness of a short period (6 weeks) of a tailored, individualised outpatient rehabilitation program in people with progressive MS. A randomised-controlled trial was undertaken in patients with primary and secondary progressive MS referred to the Centro Sclerosi Multipla of Catania. One hundred and eleven patients were assessed at baseline and at 12 weeks with validated measures of disability (Functional Independence Measure (FIM)) and impairment (Expanded Disability Status Scale (EDSS) and Functional Systems Scale). Of the 111, 58 were randomly assigned to the treatment group and 53 to the control group. All patients had been previously trained in a home exercise program. Both groups were well matched for age, sex, disease duration and severity, disability and quality of life (Short Form-36). At the end of 6 weeks patients allocated to the rehabilitation treatment group showed significant improvement in their level of disability compared with the control group,while the level of impairment did not change. Thirty-two patients of the treatment group and four of the control group improved on the FIM by two or more steps at 12 weeks (p<0.0001). An improvement by 1 EDSS step occurred in only two patients of the treatment group and in one patient of the control group. Benefits were maintained for a further six weeks. This study demonstrates that a short outpatient rehabilitation treatment improves disability of MS patients, without changing their impairment and confirms the effectiveness of rehabilitation in people with MS.


First functional analysis of a novel splicing mutation in the B3GALTL gene by an ex vivo approach in Tunisian patients with typical Peters plus syndrome.
Peters plus syndrome is a rare recessive autosomal disorder comprising ocular anterior segment dysgenesis, short stature, hand abnormalities and distinctive facial features. It was related only to mutations in the B3GALTL gene in the 13q12.3 region. In this study, we undertook the first functional analysis of a novel c.597-2 A>G splicing mutation within the B3GALTL gene using an ex-vivo approach. The results showed a complete skipping of exon 8 in the B3GALTL cDNA, which altered the open reading frame of the mutant transcript and generated a PTC within exon 9. This finding potentially elicits the nonsense mRNA to degradation by NMD (nonsense-mediated mRNA decay). The theoretical consequences of splice site mutations, predicted with the bioinformatics tool Human Splice Finder, were investigated and evaluated in relation to ex-vivo results. The findings confirmed the key role played by the B3GALTL gene in typical Peters-plus syndromes and the utility of mRNA analysis to understand the primary impacts of this mutation and the phenotype of the disease.


The Effect of an Aerobic Exercise Programme on Blood Glucose Level, Cardiovascular Parameters, Peripheral Oxygen Saturation, and Body Mass Index among Southern Nigerians with Type 2 Diabetes Mellitus, Undergoing Concurrent Sulfonylurea and Metformin Treatment.
Diabetes mellitus increases the risk of cardiovascular diseases and all-cause mortality. The present study investigated the effect of an eight-week aerobics programme on fasting blood sugar (FBS), cardiovascular parameters, peripheral oxygen saturation (SpO2), and body mass index (BMI) among subjects with type-2 diabetes mellitus (T2DM). A pretest-posttest experimental design was employed. Fifty subjects, diagnosed with T2DM, attending the Diabetes Clinic of the University of Nigeria Teaching Hospital, Enugu, were conveniently recruited, gender and age-matched, and randomised into exercise and control groups. The intervention included an eight-week aerobic exercise at 60%-79% HRmax for 45 min-60 min, 3-days per week. The FBS, SpO2, BMI, resting heart rate (RHR), and systolic (SBP) and diastolic blood pressure (DBP) of the subjects were measured before and after the intervention. The paired and independent t-test(s) were used for the analyses within and between the groups, respectively (P ≤ 0.05). The exercise group had a significantly lower SBP (15.0 mmHg, P = 0.001), DBP (7.9 mmHg, P = 0.001), RHR (4.8 bpm, P = 0.001), FBS (34.9 mg/dl, P = 0.001), and BMI (2.3, P = 0.001), while the SpO2 improved by 3.9% with P = 0.001, relative to the control group. Aerobics is an efficacious adjunct therapy in controlling the FBS level, blood pressure, BMI, and improving SpO2 among T2DM subjects.


Acquired heart valve pathology. An update for the millennium.
A survey of 200 surgically excised valves in 1996, from a single academic center, revealed that degenerative disease is by far the most common type of underlying pathology, both for the mitral valve and the aortic valve. This observation relates also to the fact that the vast majority of patients was 60 years or older. Post-inflammatory (rheumatic) disease was relatively rare; younger individuals with post-inflammatory valve pathology usually originated from parts in the world known to be endemic for rheumatic fever. The results further emphasize the shift in health costs related to an aging population.


Carboxypeptidase A-catalyzed dipeptide synthesis in organic media.
The carboxypeptidase A-catalyzed syntheses of dipeptides from L-amino acids (Phe, Tyr, Trp, Leu and Ile) were studied in various water-miscible (acetone, acetonitrile, ethanol, methanol and 1,4-dioxane) organic solvents. The highest yield (43%) was achieved in acetonitrile with L-Phe as substrate, after a 24-h incubation. The optimal conditions of Phe-Phe synthesis in acetonitrile were determined. For maximal conversion 1.2 mM L-Phe, 1.4 mg ml-1 enzyme and about 10% water are needed in buffered aqueous acetonitrile (pH 5.5) at 30 degrees C.


Diurnal changes in apoplast bypass flow of water and ions in salt-stressed wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.).
The aim of the present study was to quantify the contribution of apoplastic bypass flow to the uptake of water and salt across the root cylinder of wheat and barley during day and night. Plants were grown on hydroponics until they were 14-17 days old and then analysed over a single day (16 h) or night (8 h) period while being exposed to different concentrations of NaCl (50, 100, 150 and 200 mM NaCl). Exposure to salt started just before the experiment (short-term stress) or had started 6d before (longer-term stress). Bypass flow was quantified using the apoplastic tracer dye 8-hydroxy-1,3,6-pyrenesulphonic acid (PTS). The percent contribution of bypass flow to root water uptake increased in response to salt stress and during the night and amounted to up to 4.4%. Bypass flow across the root cylinder of Na+ and Cl- made up 2%-12% of the net delivery of these ions to the shoot; this percentage changed little (wheat) or decreased (barley) during the night. Changes in the contribution of bypass flow to the net uptake of water, Na+ and Cl- in response to salt stress and day/night are the combined result of changes in xylem tension, the contribution of alternative cell-to-cell flow path and the requirement to generate xylem osmotic pressure.


Rupture of cornual ectopic pregnancy after dilatation and curretage.
A case of a cornual ectopic pregnancy missed at attempted pregnancy termination and with subsequent rupture is presented. The positive pregnancy test at the time of presentation to the emergency department was mistakenly thought to be due to continued detectable blood levels of human chorionic gonadotrophin from the aborted pregnancy. This caused a delay in surgical intervention and subsequent rupture of the ectopic pregnancy with hypovolemic shock.


Influence of phytic acid and its metal complexes on the activity of pectin degrading polygalacturonase.
Polygalacturonase is one of the important requirements of different microorganism to cause pathogenicity and spoilage of fruits and vegetables that involved in degradation of pectin during plant tissue infections. In current study, 20 mM phytic acid inhibited 70% activity of polygalacturonase. The effect of different concentration of metal ions such as Cu(+2), Al(+3) and V(+4) were studied separately and it was found that the 20 mM of these metal ions inhibited 37.2%, 79%, and 53% activity of polygalacturonase, respectively. Finally, the complexes of phytic acid and these metals ions were prepared and 1:1 ratio of phytic acid and metal ions complexes showed maximum inhibitory activity of enzyme as compared to complexes having 1:2 and 1:3 ratio except phytate-copper complexes which showed no inhibitory effect on the activity of polygalacturonase.


Retracted: A Take-Over Performance Evaluation Model for Automated Vehicles from Automated to Manual Driving.
[This retracts the article DOI: 10.1155/2022/3160449.].


Percutaneous closure versus surgical repair for ruptured sinus of valsalva aneurysm: A systematic review and meta-analysis.
Ruptured sinus of Valsalva aneurysm (RSVA) often has an abrupt onset, and can chest pain, acute heart failure, and even sudden death. The effectiveness of different treatment modalities remains controversial. Thus, we completed a meta-analysis to evaluate the efficiency and safety of traditional surgery vs. percutaneous closure (PC) for RSVA. We carried out a meta-analysis using PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang Data, and the China Science and Technology Journal Database. The primary outcome was comparing in-hospital mortality between the two procedures, and the secondary outcome was documenting postoperative residual shunts, postoperative aortic regurgitation, and length of hospital stay in the two groups. Differences were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) to assess the relationships between predefined surgical variables and clinical outcomes. This meta-analysis was conducted using Review Manager software (version 5.3). The final qualifying studies included 330 patients from 10 trials (123 in the percutaneous closure group, and 207 in the surgical repair group). When PC was compared to surgical repair, there were no statistically significant differences in in-hospital mortality (overall OR: 0.47, 95%CI 0.05-4.31, P = 0.50). However, percutaneous closure did significantly decrease the average length of hospital stay (OR: -2.13, 95% CI -3.05 to -1.20, P < 0.00001) when compared to surgical repair, but there were no significant between-group differences in the rates of postoperative residual shunts (overall OR: 1.54, 95%CI 0.55-4.34, P = 0.41) or postoperative aortic regurgitation (overall OR: 1.54, 95%CI 0.51-4.68, P = 0.45). PC may become a valuable alternative to surgical repair for RSVA.


Preparation of boronic acid-modified polymer dots under mild conditions and their applications in pH and glucose detection.
For the first time, boronic acid-modified polymer dots (B-PDs) were fabricated by a "synthesis-modification integration" route using polyethylenimine (PEI) and phenylboronic acid as precursors. Under optimized preparation conditions, the B-PDs exhibited an average size of 2.2 nm, good water solubility, and high fluorescence quantum yield of 8.69%. The B-PDs showed reversible fluorescence response in acid solutions (blue emissions) and alkaline solutions (green emissions). The fluorescence emissions of B-PDs demonstrated an obvious red shift with varying the pH value from 1 - 13. Moreover, glucose could assemble on the surface of B-PDs due to the reversible reaction between boronic acid and cis-diols, which resulted in a blue shift of emission wavelength and an obvious increase of FL intensity at λex = 380 nm based on the aggregation-induced enhancement effect. The glucose sensing method was thus developed in the range 0.0001 - 1.0 mol L-1. Applications to real human blood and glucose injection samples demonstrated satisfactory results. The B-PDs based on the analytical method display good selectivity, wide detection range, and simplicity in preparation and detection, implying promising applications as a practical platform for biosensing.


Identification and characterization of cyclo(His-Pro)-like immunoreactivity in amniotic fluid.
Amniotic fluid (AF) from 25 term pregnancies was analyzed for cyclo(His-Pro)-like immunoreactivity (CHP-LI). CHP-LI was detected in all AF samples and was indistinguishable from synthetic CHP by immunoidentity, by gel chromatography on Sephadex G-25, and by high pressure liquid chromatography. The mean concentration of CHP-LI in AF was 13,622 +/- 1288 pg/ml (+/- SE) and concentrations were not altered by maternal labor. Plasma concentrations of CHP-LI were similar in 4 pregnant and 4 control subjects [2260 +/- 432 pg/ml vs. 2162 +/- 419 pg/ml (+/- SE), respectively]. We conclude that 1) CHP-LI is readily detected in AF from term pregnancies and is indistinguishable from synthetic CHP, and 2) concentrations of CHP-LI in human AF are significantly higher than concentrations of maternal plasma CHP-LI, suggesting CHP AF originates by mechanisms other than diffusion from maternal plasma.


Interaction between high interleukin-2 and high cortisol levels is associated with psychopathology in patients with chronic schizophrenia.
Both cortisol and interleukins appear at abnormal levels in schizophrenia. Our previous study has shown that cortisol and interleukins are associated with psychopathology and response to antipsychotic medications in a relatively small sample size of patients with schizophrenia. The current study was designed to investigate how cortisol, interleukins (ILs) and their interactions would correlate with clinical presentation in a relatively large sample size of patients with schizophrenia. We compared serum cortisol, IL-2, IL-6, and IL-8 levels in 162 medicated schizophrenia patients (including 27 patients in remission) and 62 healthy controls. Serum levels of cortisol and interleukins were measured by radioimmunoassay and quantitative ELISA, respectively. Clinical symptoms were assessed according to the Positive and Negative Syndrome Scale (PANSS). Patients with schizophrenia had significantly higher levels of cortisol and IL-2 compared to controls. Patients in remission had higher levels of IL-6 than non-remitting patients. PANSS positive symptoms, general psychopathology, cortisol and IL-2 were the most central nodes in the cortisol-IL-symptom network. The interaction between cortisol and IL-2 was associated with PANSS positive symptoms, general psychopathology and depressive factor. For patients with cortisol level above the median, IL-2 was negatively associated with PANSS positive symptoms and general psychopathology. Our results indicated that the interaction between cytokines and cortisol may be associated with the pathophysiology of some symptoms in chronic schizophrenia. In particular, the interaction between cortisol and IL-2 is associated with the clinical phenotypes of schizophrenia.


Enhancement in the visible light induced photocatalytic and antibacterial properties of titanium dioxide codoped with cobalt and sulfur.
In this study, the sol-gel technique was used to develop Cobalt Sulfur codoped Titanium Dioxide (Co-S codoped TiO2) photocatalysts. For structural analysis of the prepared resultant TiO2 samples, XRD, FTIR, UV-Vis DRS, SEM, HR-TEM and EDX measurements were used to describe the produced photocatalysts. The characterization findings indicate that the synthesized nanoparticles possessed great crystallinity, high purity, and superior optical characteristics. For the methylene blue (MB) degradation process, Co-S codoped TiO2 nanoparticles were tested for their photocatalytic degradation performance. The Co-S codoped TiO2 nanoparticles had improved catalytic activity when compared with pure, Co-doped, S-doped TiO2 and decomposed 93% of MB in 120 min. When compared to pure and doped TiO2, the catalysts of Co-S codoped TiO2 showed a synergistic effect and improved the performance of the catalysts. Furthermore, the antibacterial applications of synthesized Co-S codoped TiO2 nanoparticles was studied against E. coli (Gram negative) and S. aureus (Gram positive) bacteria and exhibited strong antibacterial activity against the selected strains.


The role of hydroperoxides as calcium release agents in rat brain mitochondria.
Hydroperoxides have previously been shown to induce Ca2+ release from intact rat liver mitochondria via a specific release pathway. Here it is reported that, in rat brain mitochondria, a hydroperoxide-induced Ca2+ release is also operative but is of minor importance. Hydroperoxide stimulates Ca2+ release in the presence of ruthenium red about twofold at a Ca2+ load of 40 nmol/mg mitochondrial protein. After addition of hydroperoxide, Ca2+ release from brain mitochondria can still be evoked by Na+. In the presence of succinate and rotenone, hydroperoxide induces only a very limited oxidation of pyridine nucleotides, most probably due to the low level of glutathione peroxidase (EC 188.8.131.52) and glutathione reductase (EC 126.96.36.199) found in brain mitochondria. Similar to liver mitochondria, a NADase (EC 184.108.40.206) activity is found in brain mitochondria. Its localization and sensitivity toward ADP and ATP, however, is different from that of the liver mitochondrial enzyme.