Comparison of Outcomes for Elderly Gastric Cancer Patients at Least 80 Years of Age Following Gastrectomy in the United States and China.
The aim of this study was to compare gastric cancer (GC) patients aged 80 years or older undergoing gastrectomy at two high-volume cancer centers in the US and China. Patients aged ≥ 80 years who underwent R0 resection at Memorial Sloan Kettering Cancer Center (MSKCC) in New York, USA (n = 159), and Fujian Medical University Union Hospital (FMUUH) in Fujian, China (n = 118) from January 2000 to December 2013 were included. Demographic, surgical, and pathologic variables were compared, and factors associated with survival were determined via multivariate analysis. The number of patients increased annually in the FMUUH cohort but not in the MSKCC cohort. Patients at MSKCC were slightly older (mean age 83.7 vs. 82.7 years), more commonly female (38 vs. 19%), and had higher average body mass index (BMI; 26 vs. 23). Treatment at FMUUH more frequently employed total gastrectomy (59 vs. 20%) and laparoscopic surgery (65 vs. 7%), and less frequently included adjuvant therapy (11 vs. 18%). In addition, FMUUH patients had larger tumors of more advanced T, N, and TNM stage. Morbidity (35 vs. 25%, p = 0.08) and 30-day mortality (2.5 vs. 3.3%, p = 0.67) were similar between the cohorts. For each TNM stage, there was no significant difference between MSKCC and FMUUH patients in 5-year overall survival and disease-specific survival (DSS). TNM stage was the only independent predictor of DSS for both cohorts. Patients ≥ 80 years of age selected for gastrectomy for GC at MSKCC and FMUUH had acceptable morbidity and mortality, and DSS was primarily dependent on TNM stage.


Visuospatial Neglect - a Theory-Informed Overview of Current and Emerging Strategies and a Systematic Review on the Therapeutic Use of Non-invasive Brain Stimulation.
Visuospatial neglect constitutes a supramodal cognitive deficit characterized by reduction or loss of spatial awareness for the contralesional space. It occurs in over 40% of right- and 20% of left-brain-lesioned stroke patients with lesions located mostly in parietal, frontal and subcortical brain areas. Visuospatial neglect is a multifaceted syndrome - symptoms can be divided into sensory, motor and representational neglect - and therefore requires an individually adapted diagnostic and therapeutic approach. Several models try to explain the origins of visuospatial neglect, of which the "interhemispheric rivalry model" is strongly supported by animal and human research. This model proposes that allocation of spatial attention is balanced by transcallosal inhibition and both hemispheres compete to direct attention to the contralateral hemi-space. Accordingly, a brain lesion causes an interhemispheric imbalance, which may be re-installed by activation of lesioned, or deactivation of unlesioned (over-activated) brain areas through noninvasive brain stimulation. Research in larger patient samples is needed to confirm whether noninvasive brain stimulation can improve long-term outcomes and whether these also affect activities of daily living and discharge destination.


[Clinical features of pulmonary embolism in elderly: a comparative study of 64 patients].
To date only a few studies regarding pulmonary embolism (PE) in elderly have been published. The aim of this study was to determine the clinical features of PE in elderly patients (≥ 75 years). All patients hospitalized for PE in our internal medicine department from January 2005 to December 2010 were included in the study. The aim was to compare the features of PE in elderly patients (≥ 75 years) to those of patients younger than 75 years. The following data were recorded: past medical history, risk factors for venous thrombo-embolism (VTE), clinical features, and PE etiologies. The population was composed of 64 patients (women 56%) with a median age of 82 years (IQR: 13.5). There was no statistical difference for risk factors of VTE. Syncope was more frequent in elderly patients (33% versus 7%, P=0.04) whereas thoracic pain predominated in younger patients (36,5% versus 7%, P=0.005). Chronic obstructive pulmonary disease was more frequent in the past medical history of elderly patients. The diagnostic of PE was less suspected in elderly patients (47% versus 72%, P=0.035). The etiologies were similar between the two groups. Our study highlights the frequency of syncope as the presenting feature of PE in elderly, whereas thoracic pain is uncommon. We confirmed the difficulty to diagnose PE in elderly population.


Application of Continuous Sewing Machine-Like Suture Technique in Meniscus Injury.
Meniscus injury is a common type of knee joint injury and often requires arthroscopic repair. At present, meniscus repair methods mainly include inside-out technology, outside-in technology, and all-inside technology. Among them, all-inside technology has attracted more attention from clinicians because of its better results. To improve the shortcomings of all-inside technology, we describe a "continuous sewing machine-like" suture technique. Our technique can make the meniscus suture continuous, increase its flexibility, and also enhance the stability of the suture knot through multiple puncture suture. Our technology can be applied to more-complex meniscus injuries and can greatly reduce the cost of surgery.


Structure versus function in high myopia using optical coherence tomography and automated perimetry.
To examine the structure-function relationship between retinal thickness using spectral-domain optical coherence tomography and standard automated perimetry in high myopia. The study population comprised 58 highly myopic individuals with no posterior abnormalities (mean spherical equivalent refraction ≤ -6.00 D and axial length ≥ 26.0 mm). All eyes underwent optical coherence tomography with the Spectralis spectral domain optical coherence tomograph and visual field evaluation with the Humphrey Field Analyzer II-i. Average macular layer thicknesses in each quadrant were calculated in a 6 × 6 mm area centred on the fovea. The visual field was assessed from 17 central locations (10°), approximately the equivalent of the area tested by optical coherence tomography in the macular scan. Linear correlations were made between different macular layer thicknesses and peripapillary retinal nerve layer thickness with their matched visual field sensitivities. Participant ages were 28.2 ± 6.4 years, mean spherical equivalent refractions were -8.20 ± 1.40 D and axial lengths were 26.7 ± 0.7 mm. There were significant positive correlations between layer thickness and corresponding visual field sensitivities as follows: ganglion cell layer in all quadrants, temporal quadrant of the nerve fibre layer with nasal quadrant of the visual field, inferior quadrant of the outer nuclear layer with superior visual field, and temporal-superior peripapillary nerve fibre layer with nasal-inferior visual field. The correlation between retinal layer thicknesses and visual field sensitivity could be explained by myopia-related losses due to lateral retinal stretching, with further research required to investigate this.


Tensin is potentially involved in extracellular matrix production in mesangial cells.
Tensin, a focal adhesion protein, is expressed in renal tubular epithelial cells (TECs). Tensin-null mice develop multiple large cysts in the renal proximal tubules. However, the role of tensin in human glomeruli remains unclear. In this study, we assessed tensin localization in human kidney and interaction between tensin and other adhesion components. In human mesangial cells (MCs) and TECs, we confirmed mRNA and protein expressions of tensin by RT-PCR and immunoprecipitation. In normal kidney, immunohistochemistry revealed that tensin was localized in MCs and parietal epithelial cells as well as TECs. In biopsy specimens, the expression of tensin was significantly increased in areas of mesangial expansion in patients with IgA nephropathy and diabetic nephropathy. These results suggest that the expression of tensin is associated with extracellular matrix (ECM) production. In vitro, immunocytochemistry revealed that MCs express tensin mainly at the ends of actin stress fibers and apparently in the focal adhesion areas. Integrin alpha5, but not alpha1 and alpha3, colocalized with tensin. Vinculin and focal adhesion kinase (FAK) were coprecipitated by tensin, suggesting that tensin can mediate signal transduction between cell and ECM through these molecules. Tensin may play important roles in mesangial ECM production through an adhesion complex with integrin alpha5, FAK, and vinculin.


Energy drinks and population health: consumption pattern and adverse effects among Saudi population.
Caffeine containing energy drinks (EDs) are heavily consumed, particularly among young adults. The number of reports of caffeine intoxication from caffeinated EDs and problems related to caffeine dependence and withdrawal is increasing. The objective was to assess the knowledge and perceived beneficial effects of EDs consumers, to assess consumption patterns and determine the adverse effects experienced by different EDs consumer groups residing in Saudi Arabia. An observational cross-sectional study with data from a randomly selected Saudi population was conducted during the period of January 15th, 2015, to April 15th, 2015, using a pre-tested 43-item questionnaire. The data were obtained and collected using interview questionnaires. Sociodemographic characteristics and data on EDs consumption patterns, the level of awareness among study subjects, and the purported benefits and reported adverse effects of EDs were collected. Frequency, percentage, and arithmetic means were calculated using Chi-square and ANOVA tests, and data with p < 0.05 were considered significant. Of the 816 individuals invited to participate in the study, 783 participants responded and completed interviews, response rate was 96%. Consumers attributed the popularity of EDs to massive advertising media (46.7%) and their stimulating and invigorating effects (37.5%). EDs are consumed by subjects for their effects on fatigue reduction (64.6%), increased alertness and focus (75.8%), and assistance during long driving trips (75.7%). Study subjects reported suffering from adverse effects, including mainly diuresis (53.7%), palpitations (50.7%), insomnia (50.7%). Importantly, an inverse association was identified between knowledge of EDs and consumption rate, and a proportional association was identified between experienced adverse effects and consumption frequency. Lower knowledge scores were identified in daily consumers than in 1-3 times monthly consumers; higher adverse events were experienced by daily consumers than by 1-3 times monthly consumers. The majority of consumers (84.6%) recommended that authorities should regulate EDs consumption. Excessive EDs consumption is associated with an increased risk of experiencing several adverse events, which is commensurate with published studies. Increasing knowledge about EDs and their possible risks could decrease their consumption by the general public.


Differential expression of CCR5 and CRTH2 on infiltrated cells in colonic mucosa of patients with ulcerative colitis.
The pathogenesis of ulcerative colitis (UC) is unclear, but abnormal infiltration of T lymphocytes in the colonic mucosa has been implicated in the mucosal tissue damage. The abnormal cytokine production because of a T helper (h)1/Th2 imbalance may play an important role in continuing inflammation in the colonic mucosa. In the present study, the expression of chemokine receptor 5 (CCR5) as a Th1 marker and a chemoattractant receptor-homologs molecule expressed on Th2 cells (CRTH2) were investigated in order to analyze impaired Th1/Th2 responses in the colonic mucosa of UC patients. Tissue samples were obtained by colonic biopsies from patients with UC or colonic polyps, with informed consent. Immunohistochemical analysis was performed on periodate, lysine-paraformaldehyde-fixed serial cryostat sections using the labeled streptavidin biotin method. Monoclonal antibodies against CD4, CCR5 or CRTH2 were used as primary antibodies. The number of cells expressing CD4, CCR5 or CRTH2 per unit area was calculated by using an image analyzer. In the patients with UC, the numbers of CD4- and CCR5-positive cells were significantly increased in inflamed mucosa, and appeared to be correlated with the disease activity. The infiltration of CRTH2-positive cells was predominantly observed in the mildly inflamed or the margin of inflamed mucosa of UC patients. There is a possibility that Th1 responses significantly occur in colonic mucosa with severe inflammation, while Th2 responses mainly occur with mild inflammation in UC patients. The Th1/Th2 imbalance in colonic mucosa may be related to the disease progression of UC.


Relationship between sensibility and ability to read braille in diabetics.
Twenty-five vision-impaired diabetics received an evaluation of sensibility. Each subject had received 2 years of instruction in braille reading at the Konan Rehabilitation Center prior to the sensibility testing. Sensibility evaluation consisted of cutaneous pressure threshold measurements with the Semmes-Weinstein monofilament and evaluation of moving and static two-point discrimination with Disk-Criminator. The ability to read braille was graded by the braille-teaching instructors as good, fair, and unable. The results of the evaluation of sensibility demonstrated that the value of the cutaneous pressure threshold did not correlate with the ability to read braille. Moving and static two-point discrimination were found to correlate highly (P less than .001) with the ability to read braille at a level of fair or good. No patient in this study with a moving two-point discrimination value of 4 or more or a static two-point discrimination value of 5 or more was able to read braille even at the fair level of ability.


[The absence of coupling between the formation of membrane potential and electron transfer via the alternative pathway of cyanide-resistant mitochondria].
The estimation of membrane potential of cyanide-resistant mitochondria of Candida lipolytica yeast was carried out using positively charged dye phenosafranine. The electron transfer via alternative pathway of cynide resistant mitochondria was shown not to be coupled with the formation of potential on membrane mitochondria.


Involvement of the beta3 adrenoceptor in nebivolol-induced vasorelaxation in the rat aorta.
Nebivolol is a highly selective beta(1) adrenoceptor blocker with additional vasodilating properties. Although it has been shown that the nebivolol-induced vasorelaxation is nitric oxide (NO) and cGMP dependent, the receptor that mediates these actions remains controversial, and serotonergic as well as beta-adrenergic pathways may be involved. Therefore, functional experiments investigating the receptor involved in nebivolol-induced vasorelaxation were performed in the rat aorta. Isolated aortic rings were exposed to cumulative concentrations of nebivolol. Nebivolol concentrations of 3 micromol/L and higher caused vasorelaxation, which was inhibited by the presence of the NO synthase inhibitor l-NNA (100 micromol/L), or by mechanical removal of the endothelium. Exposure of the vessel rings to the selective 5-HT(1A) antagonist NAN-190 (1 micromol/L) or the 5-HT(1/2) antagonist methysergide (1 micromol/L) did not influence nebivolol-induced vasorelaxation. Similarly, the incubation with the beta(2)-adrenoceptor antagonist butoxamine (50 micromol/L) did not prevent vasorelaxation. The selective beta(3)-adrenoceptor antagonist S-(-)-cyanopindolol (1 micromol/L), however, significantly counteracted the nebivolol-induced vasorelaxation. Furthermore, exposure of the aortic rings to cumulative concentrations of the beta(3) selective adrenoceptor agonist BRL37344 caused, like nebivolol, NO-dependent vasorelaxation that was antagonized by S-(-)-cyanopindolol. The results suggest that nebivolol-induced NO-dependent vasorelaxation is, at least in part, caused by a beta(3)-adrenoceptor agonistic effect.


Reduced protein synthesis in diabetic retina and secondary reduction of slow axonal transport.
Protein synthesis in the retina in diabetic rabbits decreased as the severity of the diabetes increased, but protein degradation and replacement were not affected. The reduction in the amount of orthograde slow axonal transport in diabetic rabbits closely paralleled the reduction in the amount of fast axonal transport and protein synthesis in the retina. The reduction in slow flow is most probably a simple reflection of reduced protein synthesis in the retinal ganglion cells. The relationships among reduction in axon diameter, volume of perikaryon, slow axonal transport and diabetic neuropathy are discussed.


Bilateral percutaneous nephrostomy as adjunctive treatment in a newborn infant with posterior urethral valves.
A case report illustrates that percutaneous nephrostomy is a simple alternative to surgical ureterostomy when temporary supravesical diversion is necessary in a newborn with posterior urethral valves.


Electrical properties and glucose permeability of bilayer lipid membranes on incorporation of erythrocyte membrane extracts.
1. Extracts of the human erythrocyte membrane have been prepared by solubilization with Triton X-100 and analysed by electrophoresis and gel filtration techniques. 2. The extracts have been incorporated asymmetrically into lecithincholesterol-n-decane planar bilayers. 3. The electrical characteristics and glucose permeabilities of the bilayers have been measured. 4. The extracts increased the electrical conductance of the bilayers and also markedly enhanced the D-glucose permeability but not the L-glucose permeability. 5. The enhanced D-glucose permeability was inhibited by monosaccharide transport inhibitors. 6. The results support the claim that a monosachharide facititated diffusion system has been set-up in vitro which has many of the characteristics of the transport system in the human erythrocyte membrane. 7. The data indicates that the trans membrane polypeptides of band 3 of the electrophoretogram of the erythrocyte membrane proteins (notation of Fairbanks, G., Steck, T.L. and Wallach, D.F.H. (1971) Biochemistry 10, 2606-2616) are implicated in D-glucose transport, although the possibility that relatively minor component of the membrane could be responsible for glucose transport cannot be eliminated.


A simple method for testing and controlling inhibition in soil and sediment samples for qPCR.
The presence of polymerase-chain-reaction (PCR) inhibitors in many environmental samples can make reliable and repeatable quantitative-polymerase-chain-reaction (qPCR) analysis difficult without sample dilution. To estimate an optimal sample dilution for qPCR and reduce effects of inhibition, a simple test based on multiple dilution series of samples is presented that avoids the use of internal controls and standards reducing complexity and cost.


Enhancement of radiation-induced normal tissue damage by a fibrosarcoma.
Normal tissue damage in the legs of mice was enhanced by the presence of a fibrosarcoma (FSa I) in the leg at the time of treatment with single doses of 30 to 70 Gy. Damage was assessed by measuring leg contracture 23 to 365 days after irradiation of 8 mm diameter tumors. Animals with and without tumors were treated with 1.0 mg misonidazole/g body weight 30 min before irradiation to ensure that the tumors did not recur and interfere with the assessment of contracture. The data suggest that in some cases, late damage may be enhanced by destructive effects of the tumor on the tumor bed.


Preparation of betulinic acid derivatives by chemical and biotransformation methods and determination of cytotoxicity against selected cancer cell lines.
Several novel 2,4-dinitrophenylhydrazone betulinic acid derivatives have been prepared by chemical and biotransformation methods using fungi and carrot cells. Some compounds showed significant cytotoxicity and selectivity against some tumor cell lines. The most active, 3-[(2,4-dinitrophenyl)hydrazono]lup-(20R)-29-oxolupan-28-oic acid, showed IC50 values between 1.76 and 2.51 μM against five human cancer cell lines. The most selective, 3-hydroxy-20-[(2,4-dinitrophenyl)hydrazono]-29-norlupan-28-oic acid, was five to seven times more selective for cancer cells when compared to fibroblasts. Cell cycle analysis and apoptosis induction were studied for the most active derivatives.


Association Between Uropathogenic Escherichia coli Virulence Genes and Severity of Infection and Resistance to Antibiotics.
Urinary tract infection (UTI) is the most frequent bacterial infection. Some uropathogenic Escherichia coli (UPEC) genes have been associated with disease severity and antibiotic resistance. The aim was to determine the association of nine UPEC virulence genes with UTI severity and antibiotic resistance of strains collected from adults with community-acquired UTI. A case-control study (1:3) (38 urosepsis/pyelonephritis and 114 cystitis/urethritis) was conducted. The fimH, sfa/foc, cvaC, hlyA, iroN, fyuA, ireA, iutA, and aer (the last five are siderophore genes) virulence genes were determined by PCR. The information of antibiotic susceptibility pattern of the strains was collected from medical records. This pattern was determined using an automated system for antimicrobial susceptibility testing. Multidrug-resistant (MDR) was defined as resistance to three or more antibiotic families. fimH was the most frequently detected virulence gene (94.7%), and sfa/foc was the least frequently detected (9.2%); 55.3% (83/150) of the strains were MDR. The evaluated genes were not associated with UTI severity. Associations were found between the presence of hlyA and carbapenem resistance (Odds ratio [OR] = 7.58, 95% confidence interval [CI], 1.50-35.42), iutA and fluoroquinolone resistance (OR = 2.35, 95% CI, 1.15-4.84, and aer (OR = 2.8, 95% CI, 1.20-6.48) and iutA (OR = 2.95, 95% CI, 1.33-6.69) with penicillin resistance. In addition, iutA was the only gene associated with MDR (OR = 2.09, 95% CI,1.03-4.26). There was no association among virulence genes and UTI severity. Three of the five iron uptake genes were associated with resistance to at least one antibiotic family. Regarding the other four non-siderophore genes, only hlyA was associated with antibiotic resistance to carbapenems. It is essential to continue studying bacterial genetic characteristics that cause the generation of pathogenic and multidrug-resistant phenotypes of UPEC strains.


Effect of some novel synthetic analogues of CCK-4 on insulin and glucagon secretion.
The biologic activities of three synthetic analogues of CCK-4 (Trp-Met-Asp-Phe-NH2) in which (i) the C-terminal residue Phe was N-methylated (peptide I); (ii) the C-terminal Phe residue was N-methylated and Ser is substituted for Met in position 2 (peptide II); (iii) Pro was substituted for Trp in position 1 and the C-terminal amino nitrogen was methylated (peptide III), have been described. Peptides I and II have been found to inhibit the release of both insulin and glucagon, while peptide III was found to be a potent releasing agent for insulin and an inhibitor for glucagon.


Catheter-associated candiduria: Risk factors, medical interventions, and antifungal susceptibility.
Catheter-associated candiduria is a common clinical finding in hospitalized patients, especially in the intensive care unit. The objective of this study was to obtain demographic and clinical data regarding the prevalence of Candida spp in catheterized in-patients and the medical interventions provided to these patients in a northern Israeli hospital between 2011 and 2013. Isolation and identification of microorganisms were performed on 1,408 urine culture samples 48 hours after catheter insertion. Antifungal Etest susceptibility tests were carried out on every Candida-positive urine sample. Demographic and clinical data were gathered to determine risk factors and medical interventions. Candiduria was detected in 146 catheterized in-patients out of the 1,408 patients included in this study. C albicans was detected in most cases (69.1%). Fever was observed in 52 (35.61%) patients, and leukocyturia was observed in 48 cases (32.87%). Diabetes mellitus was associated with C albicans candiduria. There were 93 patients (63.69%) who did not receive any medical intervention for their candiduria. Candida is the second leading pathogen causing catheter-associated urinary tract infection or asymptomatic colonization, whereas previous studies showed Candida as the third leading pathogen. Clinical signs and symptoms, such as fever and laboratory tests, cannot distinguish between asymptomatic colonization and infection. Because the management of catheter-associated candiduria is still controversial, additional studies should be carried out.


Noise-driven growth rate gain in clonal cellular populations.
Cellular populations in both nature and the laboratory are composed of phenotypically heterogeneous individuals that compete with each other resulting in complex population dynamics. Predicting population growth characteristics based on knowledge of heterogeneous single-cell dynamics remains challenging. By observing groups of cells for hundreds of generations at single-cell resolution, we reveal that growth noise causes clonal populations of Escherichia coli to double faster than the mean doubling time of their constituent single cells across a broad set of balanced-growth conditions. We show that the population-level growth rate gain as well as age structures of populations and of cell lineages in competition are predictable. Furthermore, we theoretically reveal that the growth rate gain can be linked with the relative entropy of lineage generation time distributions. Unexpectedly, we find an empirical linear relation between the means and the variances of generation times across conditions, which provides a general constraint on maximal growth rates. Together, these results demonstrate a fundamental benefit of noise for population growth, and identify a growth law that sets a "speed limit" for proliferation.


Tranilast modulates fibrosis, epithelial-mesenchymal transition and peritubular capillary injury in unilateral ureteral obstruction rats.
Tranilast is an anti-allergic compound suppressing transforming growth factor-beta 1 (TGF-β1) induced fibrosis. This study evaluated the efficacy of tranilast to attenuate renal fibrosis induced by unilateral ureteral obstruction (UUO) in rats in relation to epithelial-mesenchymal transition (EMT) and peritubular capillary injury. Rats were divided into four groups: UUO with vehicle or tranilast and sham operation with vehicle or tranilast. Tranilast (400 mg/kg/day) was administrated to rats for 7 and 14 days after UUO. Fibrosis and tubular injuries were attenuated in UUO kidneys with tranilast (Tr-UUO kidneys) compared with UUO kidneys with vehicle (V-UUO kidneys). Decreased E-cadherin and increased vimentin expression in the tubular epithelium and Snail expression in V-UUO kidneys were also attenuated in Tr-UUO kidneys in which heparan sulfate proteoglycan in the tubular basement membrane was preserved and matrix metalloproteinase-2 expression was attenuated. Increased TGF-β1 and phospho-Smad2 expression and increased numbers of myofibroblasts and macrophages in V-UUO kidneys were attenuated by tranilast. Decreased VE-cadherin expression and cytoplasmic swelling of the endothelium of peritubular capillaries that occurred in V-UUO kidneys was prevented by tranilast. Tranilast modulates fibrogenesis by reducing EMT, preventing disintegration of the tubular basement membrane, and reducing peritubular capillary injury in UUO kidneys.


"My Plate is Full": Reasons for Declining a Genetic Evaluation of Hearing Loss.
The aim of this study was to obtain patient and parent perspectives on genetic evaluation of hearing loss, in order to identify motivators, expectations, and barriers. Three focus groups were conducted following a semi-structured discussion guide, led by an independent moderator. Participants were hearing parents of children with permanent hearing loss or deaf adults. Qualitative content analysis was used to develop a codebook and identify major themes and subthemes. Participant views were compared to national guidelines. The 28 participants comprised 23 parents representing 21 unique families and 5 deaf adults. 13/21 families and 0/5 adults reported comorbidities, 4/21 families and 3/5 adults had a positive family history, and 12/21 families versus 0/5 adults had utilized genetics services. A common theme among adults and parents was a curiosity as to the cause of hearing loss. Parents were motivated to detect comorbidities and optimize care for hearing loss. Some parents felt overwhelmed by the hearing loss and unprepared to pursue early genetic evaluation as recommended in guidelines. Several reported positive experiences following genetics consultation, while others reported unease and unmet expectations. Notably, both parents and adults expressed ambivalence regarding the desire for genetic knowledge. Financial concerns and difficulties obtaining a referral were cited as extrinsic barriers. For parents of children with hearing loss, both the presence of comorbidities and a positive family history were drivers of genetics consultation and/or genetic testing. We identified educational opportunities for both patients and providers that would improve informed decision-making and increase access to genetic services. Consideration of the patient/family perspective and their decision-making processes, along with flexibility in the approach to genetics evaluation and its timing, will optimize both the development and implementation of guidelines.


Contribution of loading conditions and material properties to stress shielding near the tibial component of total knee replacements.
This communication reports important preliminary results of a parametric analysis into the stress shielding effects of loading conditions and material properties of a total knee replacement (TKR) prosthesis. A previously developed finite element (FE) model of the proximal tibia that incorporated orthotropic and heterogeneous bone properties was used. Tibiofemoral joint compression and soft tissue (ligament and muscle) forces were also included to better represent the loading condition in the tibia. Stress shielding effects were studied for a prosthesis similar to a commercially available model. Results from the model show that the hypothesis of relatively higher Young's modulus of implant compared to bone as the primary cause of stress shielding is not sufficiently descriptive. Loading conditions as a result of altered bone or implant condylar surface geometry, load placement on the condylar surface, and load pattern created by the TKR are at least as important or, in some cases, more important factors in observed stress shielding immediately post-operation. This finding can be used to focus new implant design on altered loading conditions as well as material selection.


Nitrogen assimilation in plants: current status and future prospects.
Nitrogen (N) is the driving force for crop yields; however, excessive N application in agriculture not only increases production cost, but also causes severe environmental problems. Therefore, comprehensively understanding the molecular mechanisms of N use efficiency (NUE) and breeding crops with higher NUE is essential to tackle these problems. NUE of crops is determined by N uptake, transport, assimilation, and remobilization. In the process of N assimilation, nitrate reductase (NR), nitrite reductase (NiR), glutamine synthetase (GS), and glutamine-2-oxoglutarate aminotransferase (GOGAT, also known as glutamate synthase) are the major enzymes. NR and NiR mediate the initiation of inorganic N utilization, and GS/GOGAT cycle converts inorganic N to organic N, playing a vital role in N assimilation and the final NUE of crops. Besides, asparagine synthetase (ASN), glutamate dehydrogenase (GDH), and carbamoyl phosphate synthetase (CPSase) are also involved. In this review, we summarize the function and regulation of these enzymes reported in three major crops-rice, maize, and wheat, also in the model plant Arabidopsis, and we highlight their application in improving NUE of crops via manipulating N assimilation. Anticipated challenges and prospects toward fully understanding the function of N assimilation and further exploring the potential for NUE improvement are discussed.


Effectiveness of exercise interventions for children with cerebral palsy: A systematic review and meta-analysis of randomized controlled trials.
The results of previous research into exercise interventions for children with cerebral palsy are inconsistent. The aim of this study is to assess the effectiveness of such exercise interventions. Systematic review and meta-analysis. Systematic searches of the PubMed, Embase and Cochrane Library databases for randomized controlled trials involving exercise interventions for children with cerebral palsy, from inception to January 2020, were performed. Pooled weighted mean differences (WMDs) with 95% confidence intervals (95% CI) for gross motor function, gait speed, and muscle strength were calculated using random-effects models. A final total of 27 trials, including 834 children with cerebral palsy, were selected for quantitative analysis. Exercise interventions had no significant effect on the level of gross motor function (WMD 1.19; 95% CI -1.07 to 3.46; p = 0.302). However, exercise interventions were associated with higher levels of gait speed (WMD 0.05; 95% CI 0.00-0.10; p = 0.032) and muscle strength (WMD 0.92; 95% CI 0.19-1.64; p = 0.013). These results suggest that exercise interventions may have beneficial effects on gait speed and muscle strength, but no significant effect on gross motor function in children with cerebral palsy.


Clinical and dermoscopic changes in common melanocytic nevi in school children: the Framingham school nevus study.
Nevi are potential precursors of malignant melanoma and are important risk factors for the development of the disease. Childhood may be a critical time for the formation and evolution of nevi. To document the development of new nevi and to document the clinical and dermoscopic changes in index nevi in school children during a 1-year follow-up. Digital photographs and dermoscopic images of the back of subjects were compared at baseline and 1-year follow-up to assess changes in nevi counts and in clinical and dermoscopic features of index nevi. Overall participation rate was 81% (42/52). 56.4% of study participants were found to have an increased number of nevi at 1-year follow-up. All nevi were small and clinically insignificant. Fifty percent of study participants were found to have dermoscopic changes in their index nevi at 1-year follow-up. Eighty-five percent of these changes were classified as subtle and 15.0% as obvious. A significant portion of students developed new nevi over the course of 1 year. Most index nevi remained stable in pattern and structure. Benign dermoscopic changes occurred in 50.0% of index nevi. However, none of the dermoscopically changed nevi revealed any major changes and the overall nevus pattern remained unchanged. The relevance of these changes is uncertain and further follow-up may elucidate their significance.


Analysis of macromolecular ethylene oxide adducts.
Ethylene oxide is a carcinogenic compound which is also an ethylene metabolite. Ethylene oxide forms macromolecular adducts with proteins and nucleic acids. Targets in proteins are the amino acids cysteine, histidine and valine (if N-terminal, as in hemoglobin). The major DNA adduct is 7-(2-hydroxyethyl)-guanine. Methods for detection of this adduct include radiolabelling and GC-MS. The sensitivity of current GC/MS methods can be improved by selective enrichment of adducts from DNA samples. Studies in this direction are presently being performed.


Grading in superficial bladder cancer. (2). Cytogenetic classification.
Cytogenic analysis was performed in 92 newly diagnosed transitional cell bladder carcinomas and the results were correlated with the clinical course in superficial tumours. Low grade tumours appeared to have hypodiploid or peridiploid chromosomal numbers. Intermediate grade tumours were characterised by chromosomal counts up to the hyperdiploid range but could have a peridiploid modal number. In high grade tumours the modal number was hyperdiploid. The range in chromosomal counts appeared to be more reliable than the modal number as a predictor of the course of superficial tumours. The significant difference in chromosome numbers between low, intermediate and high grade tumours indicates that grading reflects major cytogenetic changes in the tumour cells.


Physiological and geometrical conditions for cell division in Escherichia coli.
During recovery of division in filaments of a temperature-sensitive DNA replication mutant, DNA-less cells were formed with a broad variation in cell lengths. It is argued that segregated nucleoids are necessary to indicate the site of division and that, in their absence, the cell has no additional mechanism to locate the division site. A second condition for division is based on geometrical arguments: the cell must be able to reestablish its original surface to volume ratio or its diameter, either of which may decrease during elongation. Electron microscopy and auto-radiography of radio-labelled sacculi prepared from E. coli MC4100 lysA, cultured in glucose minimal medium, showed that these cells elongate at a constant diameter and double their rate of surface synthesis during the constriction period.


The space between us: a neurophilosophical framework for the investigation of human interpersonal space.
Despite a plethora of knowledge, both behavioural and neural, of the mechanisms defining space around a singular body little is known about the neural mechanisms that encode space between bodies. Yet, the space between people creates and defines the social dynamics of our interactions with others. This review brings together evidence from social psychology, which considers individuals and their interactions as whole beings, with neuroscientific evidence of the factors involved in spatial coding to propose a framework by which we can investigate and interpret the neural substrates of 'social space'. A key feature of this framework is that space around the body is defined from a functional 'action-centred' perspective; the same underlying processes mediate interactions with both inanimate and animate objects, with links to emotive and motivational systems encoding the saliency of those interactions. The investigation of the neural mechanisms underlying interpersonal space is timely given the increasing density of our populations and can provide a richer interpretation of findings from neuroimaging studies of prosocial behaviour which may further insights into populations with social dysfunction.


Radiotherapists and cancer education.
This paper argues three main points. First, that education has a vital part to play in the train of events that might lead to the cure of more patients with cancer in certain sites. Secondly, evidence is presented to show that the type of education that is needed must be of a special, and carefully devised kind. And, thirdly, it is argued that of all medical specialists involved in cancer treatment radiotherapists are uniquely placed to stimulate and to support cancer education programmes.


Oltipraz, the activator of nuclear factor erythroid 2-related factor 2 (Nrf2), protects against the formation of BAPN-induced aneurysms and dissection of the thoracic aorta in mice by inhibiting activation of the ROS-mediated NLRP3 inflammasome.
Thoracic aortic aneurysm and dissection (TAAD) is caused by the apoptosis and phenotypic transformation of vascular smooth muscle cells (VSMCs). The dysfunction of VSMCs affects their secretion of chemokines such as monocyte chemoattractant protein-1 (MCP-1) to recruit the infiltration of macrophages which release proinflammatory cytokines and matrix metalloproteinases (MMPs) to accelerate the process of TAAD formation. We analyzed the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) in aortic tissues of TAAD patients and the β-aminopropionitrile fumarate (BAPN)-induced mouse model, and the levels of Nrf2 were elevated in both aortic lesions. Treatment with the Nrf2 activator oltipraz protects against the formation of BAPN-induced aneurysm and dissection, as demonstrated by a higher survival rate, postponing the time of aortic rupture, and inhibiting aortic luminal dilation. In addition, the thoracic aortas of BAPN-treated mice inhibited the apoptosis and phenotypic transformation of VSMCs. When treated with oltipraz, they had reduced macrophage infiltration proinflammatory cytokines and MMPs. Furthermore, oltipraz treatment promoted the translocation of Nrf2 and downregulated the NLRP3 pathway. Nrf2 plays a crucial role in protecting against TAAD development, and persistent activation of Nrf2 is a promising therapeutic strategy against the progression of TAAD.


[Foreign body retained within ulnar nerve in the distal humerus].
This report describes the procedures applied to remove a metal foreign body retained inside the ulnar nerve in the distal humerus of a 49-year-old patient. Exemplified by an unfavorable primary treatment this article presents the first description of removal of an foreign body retained within a nerve whereby emphasis is placed on the problems associated with the preoperative and intraoperative localization of the foreign particle.


Reduction of methylmercury concentration in neonatal rat brains after administration of dimercaptosuccinic acid to dams while pregnant.
Sprague-Dawley rats were gavaged on day 7 of gestation with 1.62, 3.23 or 10 mg methylmercury/kg. Beginning one day later, the dams were administered 0, 20 or 40 mg 2,3-dimercaptosuccinic acid/kg/day until they delivered their pups. Concentrations of methylmercury in the brains of pups whose dams were treated with 20 mg DMSA/kg/day were reduced 50% compared with control pups. 40 mg DMSA/kg/day decreased brain concentrations 70% compared to non-chelated controls. The data indicate that DMSA might be effective in protecting the developing organism against morphological and/or behavioral teratological consequences of methylmercury poisoning in utero.


Prospective Assessment of Genital Pain in Patients With Urethral Stricture: Incidence, Associations, and Impact of Urethroplasty.
To assess the incidence of genital pain in patients with urethral stricture and examine the impact of urethroplasty. Genital pain is a common and challenging urological condition and potentially associated with urethral stricture. From 2011-2019, patients were offered enrollment in a prospective single-center study assessing patient-reported genital pain pre- and 6-months posturethroplasty. Genital pain was assessed with the question, "Do you experience genital (scrotum or penis) pain?" answered on a five-point scale ["Never" (1), "Occasionally" (2), "Sometimes" (3), "Most of the Time" (4) or "All of the Time" (5)]. Responses of 3, 4, or 5 were considered clinically significant. Wilcoxon signed-rank test was used to compare pre- and postoperative states and logistic regression was used to evaluate the association between genital pain and clinical variables. Of the 387 patients completing enrollment, 36.4% (141/387) reported genital pain preoperatively. Patients with panurethral stricture reported higher rates (57.1%) of pain (Odds Ratio 2.93, 95%CI 1.32-6.50; P = .008). Posturethroplasty, pain scores improved with an incidence of 14.2% (P < .0001). In patients reporting preoperative pain, 88.7% (125/141) experienced improvement, 8.5% were unchanged and 2.8% reported worsening pain. On logistic regression, patients with penile strictures (O.R. 0.24, 95%CI 0.06-0.91; P = .04), hypospadias (O.R. 0.14, 95%CI 0.02-0.88; P = .04), and staged reconstruction (O.R. 0.22, 95%CI 0.05-0.90; P = .04) were less likely to report improvement. Genital pain is common in patients with urethral stricture and improves in the majority of patients undergoing urethroplasty but less so in patients with penile strictures, hypospadias and staged reconstruction.


The unfolding mechanism and the disulfide structures of denatured lysozyme.
The mechanism of denaturation and unfolding of lysozyme has been characterized here using the method of disulfide scrambling. Under denaturing conditions (urea, guanidinium hydrochloride (GdmCl), guanidinium thiocyanate (GdmSCN), or elevated temperature) and in the presence of thiol initiator, lysozyme denatures by shuffling its four native disulfide bonds and converts to a mixture of fully oxidized scrambled isomers. To denature 50% of the native lysozyme requires 1.1 M of GdmSCN, 2.8 M of GdmCl and 7.4 M of urea, respectively. High temperature (75 degrees C) denatures the native lysozyme quantitatively within 20 min. Analysis by reversed-phase high-performance liquid chromatography reveals that urea and GdmCl denatured lysozyme comprise a single predominant disulfide isomer, designated as X-lysozyme-a, regardless of the concentration of the denaturant. X-Lysozyme-a was shown to adopt the beads-form structure with its four disulfide bonds formed by four consecutive pairs of cysteines (Cys6-Cys30, Cys64-Cys76, Cys80-Cys94, Cys115-Cys127). The conspicuous absence of partially structured unfolding intermediates of lysozyme contrasts to that found in the case of alpha-lactalbumin and accounts for the widely observed two-stage mechanism of lysozyme unfolding.


Estimating acoustic peak pressure generated by ultrasound transducers from harmonic distortion level measurement.
Pressure amplitude measurement is important for general research on ultrasound. Because it requires high accuracy, it is usually done using a hydrophone calibrated by an accredited laboratory. In this paper, a method is proposed for estimating the pressure amplitude in the ultrasound field using an uncalibrated single-element transducer and Khokhlov-Zabolotskaya-Kuznetsov simulations of the ultrasound field. The accuracy of the method is shown to be better than 20% for slightly focused and nonfocused transducers. Extending the method to a pulse-echo setup enables pressure measurement of a transducer without the need for an extra transducer or hydrophone.


The effect of trainee involvement on perioperative outcomes of abdominal aortic aneurysm repair.
Although the effect of trainee involvement has been evaluated across different specialties, their effects on perioperative outcomes after abdominal aortic aneurysm (AAA) repair have not been examined. Our goal was to examine the association between resident and fellow intraoperative participation with perioperative outcomes of endovascular AAA repair (EVAR), open infrarenal AAA repair (OIAR), and open juxtarenal AAA repair (OJAR). The American College of Surgeons National Surgical Quality Improvement Program data set (2005-2012) was queried to identify all patients who underwent EVAR, OIAR, or OJAR. Multivariate analysis was performed to assess the association of trainee involvement with perioperative morbidity and mortality. We identified 16,977 patients: 12,003 with EVAR, 3655 with OIAR, and 1319 with OJAR. Propensity matching and multivariate analyses revealed that there was no significant difference in perioperative death, cardiac arrest/myocardial infarction, pulmonary, renal, venous thromboembolic, or wound complications, or return to the operating room. However, trainee involvement in AAA repair led to a significant increase in operative time for EVAR (163 ± 77 vs 140 ± 67 minutes; P < .001), OIAR (217 ± 91 vs 185 ± 76 minutes; P < .001), and OJAR (267 ± 115 vs 214 ± 106 minutes; P < .001) and an extended length of stay for EVAR (3.1 ± 5.3 vs 2.8 ± 4.5 days; P < .001) and OIAR (10.6 ± 11.8 vs 9.1 ± 8.9 days; P < .001). Trainee participation in aneurysm repair was not associated with major adverse perioperative outcomes. However, it was associated with an increased operative time and length of stay and therefore may lead to increased resource utilization and cost.


Increased mononuclear cell activation and apoptosis early after human liver transplantation is associated with a reduced frequency of acute rejection.
Experimental models of orthotopic liver transplantation (OLT) have shown that the very early events post-OLT are critical in distinguishing immunogenic and tolerogenic reactions. In rodents, increased leukocyte apoptosis and cytokine expression have been demonstrated in tolerogenic strain combinations. Information from human OLT recipients is less abundant. The aim of this study was to determine the amount of early leukocyte activation and apoptosis following human OLT, and to correlate this with subsequent rejection status. Peripheral blood mononuclear cells (PBMC) were isolated from 76 patients undergoing OLT - on the day prior, 5 hrs after reperfusion (day 0), and 18-24 hrs post-OLT (day 1). The mean level of apoptotic PBMCs on post OLT day 1 was higher than healthy recipients (0.9% +/- 0.2 vs. 0.2% +/- 0.1, p=0.013). Apoptosis was greater in nonrejecting (NR) (1.1% +/- 0.3) compared with acutely-rejecting (R) (0.3% +/- 0.1, p=0.021) patients. On day 1, PBMC from NR patients had increased expression of IFN-gamma (p=0.006), IL-10 (p=0.016), and CD40 ligand (p=0.02) compared with R. Donor cell chimerism on day 1 did not differ between the groups indicating that this was unlikely to account for increased PBMC apoptosis in the NR group. Interestingly, the level of chimerism on day 0 was significantly higher in NR (3.8% +/- 0.6) compared with R (1.2% +/- 0.4, p=0.004) patients and there was a close correlation between chimerism on day 0 and cytokine expression on day 1. These results imply that similar mechanisms are occurring in the human liver to promote graft acceptance as in the experimental models of liver transplantation and suggest that strategies that promote liver transplant acceptance in rodents might be applicable to humans.


Naloxone Diminishes the Virulence and Modifies the Cellular Immune Responses of BALB/c Mice Infected with Leishmania major.
Leishmania major-infected BALB/c mice display strong susceptibility to the infection due to the induction of Th2 response. The aim of this study was to assess the effects of naloxone on virulence of L. major in BALB/c mice and the ensued cellular immune response. The effects of injection of a single dose of naloxone in the footpad of L. major-infected BALB/c mice were investigated by evaluating the lesion sizes, the parasite burden, cell proliferation, secreted cytokines (IFN-γ, IL-4, IL-10 and IL-12) and their genes expressions due to naloxone treatment while the untreated mice were used as a control. Significantly lower lesion sizes and less parasite burden were measured in the treated mice. Significantly decreased productions of IFN-γ, IL-12, IL-4, and IL-10 were also observed in the treated mice at week 4 post-infection while the production IL-10 remained significantly hindered till 8 weeks post-infection. Our data indicated that although the treatment of L. major-infected BALB/c mice with a single dose of naloxone was unable to improve the cellular immune response, it led to lower virulence, confirmed by significantly reduced lesions and parasite load.


Identification of novel PKD1 and PKD2 mutations in a Chinese population with autosomal dominant polycystic kidney disease.
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most frequently inherited renal diseases caused by mutations in PKD1 and PKD2. We performed mutational analyses of PKD genes in 49 unrelated patients using direct PCR-sequencing and multiplex ligation-dependent probe amplification (MLPA) for PKD1 and PKD2. RT-PCR analysis was also performed in a family with a novel PKD2 splicing mutation. Disease-causing mutations were identified in 44 (89.8%) of the patients: 42 (95.5%) of the patients showed mutations in PKD1, and 2 (4.5%) showed mutations in PKD2. Ten nonsense, 17 frameshift, 4 splicing and one in-frame mutation were found in 32 of the patients. Large rearrangements were found in 3 patients, and missense mutations were found in 9 patients. Approximately 61.4% (27/44) of the mutations are first reported with a known mutation rate of 38.6%. RNA analysis of a novel PKD2 mutation (c.595_595 + 14delGGTAAGAGCGCGCGA) suggested monoallelic expression of the wild-type allele. Furthermore, patients with PKD1-truncating mutations reached end-stage renal disease (ESRD) earlier than patients with non-truncating mutations (47 ± 3.522 years vs. 59 ± 11.687 years, P = 0.016). The mutation screening of PKD genes in Chinese ADPKD patients will enrich our mutation database and significantly contribute to improve genetic counselling for ADPKD patients.


Neuroprotective effects of imidazenil against chemical warfare nerve agent soman toxicity in guinea pigs.
The chemical warfare nerve agent, soman irreversibly inhibits acetylcholinesterase (AChE) leading to hypercholinergy and seizures which trigger glutamate toxicity and status epilepticus ultimately resulting in neuropathology and neurobehavioral deficits. The standard emergency treatment comprising of anticholinergic, AChE reactivator and anticonvulsant does not completely protect against soman toxicity. We have evaluated imidazenil, a new anticonvulsant imidazo benzodiazepine with high affinity and intrinsic efficacy at α5-, α2-, and α3- but low intrinsic efficacy at α1-containing GABA(A) receptors and is devoid of cardiorespiratory depression, sedative/hypnoitc and amnestic actions and does not elicit tolerance and dependence liabilities unlike diazepam, for protection against soman toxicity. Guinea pigs implanted with bipotential radiotelemetry probes for recording EEG and ECG were administered with 26 μg/kg pyridostigmine bromide 30 min prior to 2× LD(50) soman exposure and 1 min later treated with a combination of 2mg/kg atropine sulfate and 25mg/kg 2-pralidoxime and various doses of imidazenil. Intramuscular administration of imidazenil, dose-dependently protected against 2× LD(50) of soman toxicity up to 1mg/kg. Further increase in the dose of imidazenil to 2.5mg/kg was less effective than 1mg/kg probably due to non-specific actions at sites other than GABA(A) receptors. Compared to vehicle group, 1mg/kg imidazenil treatment showed optimal increase in survival rate, reduction in behavioral manifestations and high power of EEG spectrum as well as neuronal necrosis. These data suggest that imidazenil is an effective anticonvulsant for medical countermeasure against soman-induced toxicity.


Molecular design of dye-TiO2 assemblies for green light-induced photocatalytic selective aerobic oxidation of amines.
Dye-semiconductor assemblies are very versatile visible light photocatalysts in terms of tunability by tweaking either dye molecules or semiconductor materials. Here, we adopted a strategy of molecular inverse design of alizarin red S (ARS) to identify the blueprint underlying the superior photocatalytic activity of ARS-TiO2 assembly. We discovered that the substituted -OH groups of anthraquinone provide visible light absorption and binding sites. Importantly, the molecular features of 1,2-dihydroxyanthraquinone (1,2-DHA) contributes mostly to the unique photocatalytic activity after binding with TiO2 with broad visible light absorption which can be maintained at high concentration of amines. Moreover, the electron-withdrawing effect of -SO3-Na+ groups increase the acidities of substituted -OH groups, leading to stronger binding and subsequent higher activity. Ultimately, in situ formed 1,2-DHA-TiO2 assembly can be a powerful photocatalyst for green light-induced selective oxidation of amines into imines with aerial O2. This work makes evident the promise of molecular design in tailoring dye-semiconductor assemblies for visible light-induced photocatalytic selective chemical transformations.


Geriatric nutritional risk index after neoadjuvant chemoradiotherapy and survival in older patients with advanced rectal cancer.
To investigate the clinical impact of malnutrition on the survival of older patients with advanced rectal cancer who underwent neoadjuvant chemoradiotherapy. We investigated the clinical significance of the geriatric nutritional risk index (GNRI) in 237 patients aged over 60 years with clinical stage II/III rectal adenocarcinoma who were treated with neoadjuvant long-course chemoradiotherapy or total neoadjuvant therapy followed by radical resection from 2004 to 2017. Pre-treatment and post-treatment GNRI were evaluated, with patients split into low (< 98) and high (≥ 98) GNRI groups. The prognostic impact of pre-treatment and post-treatment GNRI levels on overall survival (OS), post-recurrence survival (PRS), and disease-free survival (DFS) was evaluated using univariate and multivariate analyses. Fifty-seven patients (24.1%) before neoadjuvant treatment and 94 patients (39.7%) after neoadjuvant treatment were categorized with low GNRI. Pre-treatment GNRI levels were not associated with OS (p = 0.80) or DFS (p = 0.70). Patients in the post-treatment low GNRI group had significantly poorer OS than those in the post-treatment high GNRI group (p = 0.0005). The multivariate analysis showed that post-treatment low GNRI levels were independently associated with poorer OS (hazard ratio, 3.06; 95% confidence interval, 1.55-6.05; p = 0.001). Although post-treatment GNRI levels were not associated with DFS (p = 0.24), among the 50 patients with recurrence, post-treatment low GNRI levels were associated with poorer PRS (p = 0.02). Post-treatment GNRI is a promising nutritional score associated with OS and PRS in patients over 60 years with advanced rectal cancer treated with neoadjuvant chemoradiotherapy.


[Complications of daily dental work and expert opinion aspects].
Complications in dentist's daily work are discussed by aspects of prevention and possible consequences. The procedure in fact of incidents is described to guard against the reproach of malpractice.


The ABI4-RbohD/VTC2 regulatory module promotes reactive oxygen species (ROS) accumulation to decrease seed germination under salinity stress.
Salinity stress enhances reactive oxygen species (ROS) accumulation by activating the transcription of NADPH oxidase genes such as RbohD, thus mediating plant developmental processes, including seed germination. However, how salinity triggers the expression of ROS-metabolism-related genes and represses seed germination has not yet been fully addressed. In this study, we show that Abscisic Acid-Insensitive 4 (ABI4), a key component in abscisic acid (ABA) signaling, directly combines with RbohD and Vitamin C Defective 2 (VTC2), the key genes involved in ROS production and scavenging, to modulate ROS metabolism during seed germination under salinity stress. Salinity-induced ABI4 enhances RbohD expression by physically interacting with its promoter, and subsequently promotes ROS accumulation, thus resulting in cell membrane damage and a decrease in seed vigor. Additional genetic evidence indicated that the rbohd mutant largely rescues the salt-hypersensitive phenotype of ABI4 overexpression seeds. Consistently, the abi4/vtc2 double mutant showed the salt-sensitive phenotype, similar to the vtc2 mutant, suggesting that both RbohD and VTC2 are epistatic to ABI4 genetically. Altogether, these results suggest that the salt-induced RbohD transcription and ROS accumulation is dependent on ABI4, and that the ABI4-RbohD/VTC2 regulatory module integrates both ROS metabolism and cell membrane integrity, ultimately repressing seed germination under salinity stress.


Are bone and serum cefazolin concentrations adequate for antimicrobial prophylaxis?
Antimicrobial prophylaxis is considered beneficial for preventing surgical-site infections in clean orthopaedic surgery. However, whether tissue concentrations of cefazolin achieve the minimum inhibitory concentration for the targeted contaminants have yet to be clarified. We asked whether 2 g of cefazolin would enable effective serum and bone concentrations relative to the current minimum inhibitory concentration for cefazolin-resistant coagulase-negative Staphylococci and methicillin-sensitive Staphylococcus aureus. We enrolled 43 patients (THA, n = 16; TKA, n = 27) scheduled for primary THAs and primary TKAs. Subjects were given 2 g of cefazolin intravenously before incision. One blood sample and two bone samples were collected from each subject before tourniquet deflation before any additional dose. All samples were assayed at the same laboratory. Minimum inhibitory concentration values were defined based on nationwide surveys. Mean (± standard deviation) serum concentration was 170.3 ± 51.3 μg/mL (range, 99.3-370.3 μg/mL). Mean bone concentration was 32.3 ± 15.2 μg/g (range, 11.4-70.0 μg/g) in THA, and 16.0 ± 10.4 μg/g (range, 6.3-46.3 μg/g) in TKA. All serum and bone concentrations exceeded the minimum inhibitory concentration for methicillin-sensitive S. aureus, but some serum levels were marginal and no bone levels exceeded the minimum inhibitory concentration for cefazolin-resistant coagulase-negative Staphylococcus. Our data suggest intravenous administration of 2 g of cefazolin achieves the minimum inhibitory concentration for methicillin-sensitive S. aureus in serum and bone, but not the minimum inhibitory concentration for cefazolin-resistant coagulase-negative Staphylococcus in bone, resulting in a potential risk of deep surgical site infections in THAs and TKAs.


Evidence of oligodendrocyte infection and degeneration in canine distemper encephalomyelitis.
Canine distemper encephalomyelitis is an important neurological disease of the dog and is also of comparative medical interest. With some viral strains, demyelinating encephalomyelitis is seen; whether or not oligodendrocyte infection occurs has remained controversial. By examining very early white matter lesions unequivocal oligodendrocyte infection has been identified. Accordingly the direct effect of virus on oligodendrocyte viability must be weighed in considering the pathogenesis of this canine CNS infection.


Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides.
Mechanical injury to connective tissue causes changes in collagen structure and material behaviour, but the role and mechanisms of molecular damage have not been established. In the case of mechanical subfailure damage, no apparent macroscale damage can be detected, yet this damage initiates and potentiates in pathological processes. Here, we utilize collagen hybridizing peptide (CHP), which binds unfolded collagen by triple helix formation, to detect molecular level subfailure damage to collagen in mechanically stretched rat tail tendon fascicle. Our results directly reveal that collagen triple helix unfolding occurs during tensile loading of collagenous tissues and thus is an important damage mechanism. Steered molecular dynamics simulations suggest that a likely mechanism for triple helix unfolding is intermolecular shearing of collagen α-chains. Our results elucidate a probable molecular failure mechanism associated with subfailure injuries, and demonstrate the potential of CHP targeting for diagnosis, treatment and monitoring of tissue disease and injury.


Biliary complications in living donor liver transplantation: imaging findings and the roles of interventional procedures.
To describe the incidence, types, and findings of biliary complications in living donor liver transplantation (LDLT) and to determine the roles of interventional procedures. Twenty-four biliary complications among 161 LDLT patients (24/161, 14.9%) were identified. These complications were divided into two groups according to the initial manifestation time, i.e., "early" (<60 days) or "late". The CT and cholangiographic findings were reviewed regarding the presence of a stricture or leak and the location, and length, shape, and degree of the stricture. Both groups were categorized into three subgroups: leak, stricture, and both. The type of interventional procedures used and their roles were determined. Early complications were identified in 14 of the 24 patients (58%) and late complications in 11 (46%). One patient showed both early and late complications. Biliary stricture was detected in 10 patients, leak in 10, and both in 5. By cholangiography, all strictures were irregular and short (mean length 15 +/- 6 mm) at the anastomotic site and complete obstruction was observed in 2 patients with late stricture. Twenty-three of the 24 patients were treated using percutaneous and/or endoscopic drainage procedures with or without balloon dilatation. Seventeen (74%) showed a good response, but reoperations were inevitable in 6 (26%). All patients except those with complete obstruction showed a favorable outcome after interventional management. Biliary leaks and strictures are predominant complications in LDLT. Most show good responses to interventional treatment. However, complete obstruction needs additional operative management.


Ventricular tachycardia caused by mesothelial cyst.
A 27 year-old- lady was evaluated due to recurrent ventricular tachycardia. After performing echocardiography and cardiac MRI, she was found to have large pericardial cyst. Pathologic examination confirmed it as mesothelial pericardial cyst. Up to our knowledge it is the first presentation of simple pericardial cyst as ventricular a tachycardia.


Occupational asthma related to mouse allergen exposure and rhinoconjunctivitis due to collagenase inhalation in a laboratory technician.
We describe the case of a 27-year-old patient working in a research laboratory, who developed occupational asthma to mouse proteins and presented symptoms of rhinoconjunctivitis caused by manipulation of collagenase. Specific inhalation challenge confirmed the diagnosis of occupational asthma to mouse proteins, whereas specific challenge with collagenase only evoked symptoms of rhinitis and conjunctivitis. SDS-PAGE and Western blot analysis for collagenase showed that the patient's IgE antibodies bound specifically to a protein with a molecular weight of 92 kDa. Hence, this was an unusual case of double sensitization. The sensitization to collagenase presented in this report may represent a new occupational disease in technicians working in medical or research laboratories.


ESIN in femur fractures in children under 3: is it safe?
Pediatric femur fractures are a major trauma in children. Different treatment algorithms have been developed but indications for surgical treatment, especially in very young patients, are still controversial. Literature recommends surgical stabilization with elastic-stable intramedullary nailing (ESIN) starting at the age of 3 and non-operative treatment in younger patients. This study sought to present the outcome of patients younger than 3 years of age treated with ESIN for femur fractures. Inclusion criteria were patients younger than 3 treated with ESIN in femur fractures. Patient demographics, fracture characteristics, mechanism of injury, outcomes and complications were recorded using charts and X-rays. Primary outcome measures were time to mobility, fracture consolidation and surgical-related complications. Between 2010 and 2020, 159 patients were treated with ESIN in femur fractures in our institution. A total of 30 patients met the criteria. The mean age was 2.1 ± 0.7 years (13 months-2.9 years). Most common mechanism was fall from standing height (60%). Other mechanisms were motor vehicle accidents as a pedestrian (10%) or as a passenger (10%) as well as direct blow trauma (20%). Femoral shaft fracture was the most common injury (80%). 5 subtrochanteric and one distal metaphyseal femur fractures were found. Mean length of stay was 2.0 ± 1.3 days. Radiographic controls were performed on day 1, 14 and 6 weeks after surgery if not otherwise specified or if complications occurred. 4.6 ± 1.2 (n 2-7) X-rays were performed on average after surgery. First radiographic consolidation signs were seen after 2.4 ± 0.6 weeks. Only one child showed surgical-related complication with a leg length discrepancy of 1 cm. In 10% of the patients, shortening after surgery of 1.7 ± 1.4 mm (0.3-3.1 mm) occurred. One child initially treated with traction therapy showed skin irritations and was operated with ESIN. No non-union or ESIN-related complications were found. Mean follow-up was 5.1 ± 4.4 months (4-24 months). First independent mobilization was seen at an average of 3.4 ± 1.1 weeks (2-6 weeks) after surgery. Implant removal was performed after 3.2 ± 1.3 months (2-8 months). No refracture after implant removal occurred. Early results with ESIN show a reasonable and safe treatment option for femur fractures in toddlers and young children under the age of 3 with easy postoperative care, fast fracture union and early independent mobilization.


Age-dependent decrease in 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity in hypertensive patients.
The prevalence of arterial hypertension lacking a defined underlying cause increases with age. Age-related arterial hypertension is insufficiently understood, yet known characteristics suggest an aldosterone-independent activation of the mineralocorticoid receptor. Therefore, we hypothesized that 11beta-HSD2 activity is age-dependently impaired, resulting in a compromised intracellular inactivation of cortisol (F) with F-mediated mineralocorticoid hypertension. Steroid hormone metabolites in 24-h urine samples of 165 consecutive hypertensive patients were analyzed for F and cortisone (E), and their TH-metabolites tetrahydro-F (THF), 5alphaTHF, TH-deoxycortisol (THS), and THE by gas chromatography-mass spectroscopy. Apparent 11beta-HSD2 and 11beta-hydroxylase activity and excretion of F metabolites were assessed. In 72 female and 93 male patients aged 18-84 years, age correlated positively with the ratios of (THF + 5alphaTHF)/THE (P = 0.065) and F/E (P < 0.002) suggesting an age-dependent reduction in the apparent 11beta-HSD2 activity, which persisted (F/E; P = 0.020) after excluding impaired renal function. Excretion of F metabolites remained age-independent most likely as a consequence of an age-dependent diminished apparent 11beta-hydroxylase activity (P = 0.038). Reduced 11beta-HSD2 activity emerges as a previously unrecognized risk factor contributing to the rising prevalence of arterial hypertension in elderly. This opens new perspectives for targeted treatment of age-related hypertension.


Effect of thermosonication process on physicochemical properties and microbial load of goat's milk.
In this study, thermosonication was used as a combined treatment of raw goat milk (RGM) using pasteurization (72 °C for 15 s) and ultrasound treatments (20 kHz at the power variance of 150 W, 200 W, 300 W and 400 W for 10 min). Investigation on the impact of the microbial load, protein content, protein aggregation, the particle size of fat and casein micelles, pH, viscosity, turbidity, color, and soluble calcium and phosphorus contents were carried out, whiles RGM and PGM served as the control. Our results revealed that at 400 W, that thermosonication resulted in a significant reduction (α = 0.05) in the microbial load of the samples to less than 2.3 log cfu/mL in comparison to those of RGM and pasteurized goat milk (PGM) at 5.94 log cfu/mL and 4.76 log cfu/mL respectively. In RGM, the fat size (3.5 µm) decreased to 0.4 µm at 300 W; while those of casein micelles also decreased from 406 to 256.4 nm at 400 W. However, no significant effect was observed in the color and soluble calcium and phosphorus contents of all samples. The effect on the microbial load and fat homogenization would promote thermosonication process in the dairy industry.


Multi-residue analysis of 206 pesticides in grass forage by the one-step quick, easy, cheap, effective, rugged, and safe method combined with ultrahigh-performance liquid chromatography quadrupole orbitrap mass spectrometry.
A novel method for detecting pesticide multi-residue in grass forage (alfalfa and oat) was established based on the one-step automatic extraction and purification technology of quick, easy, cheap, effective, rugged, and safe combined with ultrahigh-performance liquid chromatography quadrupole Orbitrap high-resolution mass spectrometry. The crushed sample was extracted with acetonitrile with 1% acetate, followed by a cleanup step with a primary-secondary amine, octadecylsilane, and graphitized carbon black. The extraction and purification were carried out using the one-step automatic pretreatment equipment. The target pesticides were acquired in positive ion electrospray ionization mode and full scan/data dependent secondary scan mode. The calibration curve shows good linearity over the corresponding concentration range, with the coefficient of determination greater than 0.99. The screening detection limits were 0.5-50 μg/kg, and the limit of quantification for the 206 pesticides was set at 1-50 μg/kg. At the spiking levels of one, two, and 10 times of limit of quantification, more than 95% of pesticides had recovery between 70-120%, with a relative standard deviation ≤20%. The method was proved to be simple, rapid, high-sensitivity, and could be routinely used for the high throughput screening and quantitative analysis of pesticide residues in alfalfa and oat.


[Indicators of severity in chest trauma].
We undertook a review of patients with chest trauma attended between January 1992 and June 2005 in order to establish severity criteria in these cases. During the study period, 1,772 cases (1,346 [76%] males) were treated, with ages ranging from 7 to 98 years (mean, 46.4 years). The Revised Trauma Score (RTS) was calculated and the following variables were also studied as potential indicators of severity: age, extent of the injury, number of rib fractures, presence of lung contusion, hemothorax, cardiorespiratory repercussions, and need for mechanical ventilation. At the time of admission, 84.4% of patients presented only symptoms related to the injury, with no general repercussions, and 66.7% had an RTS of 12. The number of rib fractures was a reliable indicator of severity, as was the presence of multiple injuries, lung contusion, need for mechanical ventilation, and cardiorespiratory repercussions. Neither age nor presence of hemothorax was found to be an indicator of severity. Pleural drainage was performed in 756 cases and was effective in 670 (88.6%). There are a number of indicators of severity in chest trauma, related more closely to the type and repercussions of the trauma than to the age of the patient. There is a high incidence of fluid or gas accumulation in the pleural space, though this can be easily managed by pleural drainage, which constitutes the main therapeutic procedure in chest trauma.


[Combination methods of local treatment of tumors of the abdominal organs].
On the basis of the analysis of the results of treatment by the methods of cryosurgery, roentgeno-endovascular embolization, local use of immobilized chemo-preparations and systemic administration of a high-molecular platinum compound of 218 patients with IV stage tumours of different location, it is shown that the mean lifetime of the patients increases 12-fold, the number of postoperative complications and lethality decrease.


Follow-up of children's oral health-related quality of life after dental general anaesthesia treatment.
Our aim was to analyze longitudinally the impact of young children's dental general anaesthesia (DGA) treatment on their OHRQoL and to determine their post-operative oral health status at the six-month follow-up together with parental ratings of their children's oral health. We conducted a prospective follow-up study of OHRQoL among Lithuanian child patients treated under general anaesthesia (n = 144). The study consisted of clinical dental examinations performed by two examiners at the time of DGA and at the six-month recall, along with OHRQoL surveys and data collected from the patients' files. The dmft index and Silness-Löe plaque index served as clinical measures. The survey tool for assessing the children's OHRQoL was the previously tested Lithuanian version of the ECOHIS. The Wilcoxon signed-rank test served for the statistical analysis (p < 0.05). The ECOHIS scores clearly decreased post-operatively, indicating a significant (p < 0.001) improvement in the children's OHRQoL after the DGA treatment. The ECOHIS scores were lower immediately after the DGA treatment and remained low at the six-month recall. Parents rated their child's oral health as higher after the DGA treatment (p < 0.001). The majority (75%) of the patients had poor or satisfactory oral hygiene at follow-up. This longitudinal study showed a sustained improvement in the children's OHRQoL six months after their DGA treatment. Post-operative parental ratings of their child's oral health were higher after the DGA treatment, but the children exhibited insufficient oral hygiene and new caries lesions. An appropriate follow-up system for children receiving DGA treatment with special focus on preventive care is needed.


Doxycycline-loaded nanotube-modified adhesives inhibit MMP in a dose-dependent fashion.
This article evaluated the drug loading, release kinetics, and matrix metalloproteinase (MMP) inhibition of doxycycline (DOX) released from DOX-loaded nanotube-modified adhesives. DOX was chosen as the model drug, since it is the only MMP inhibitor approved by the U.S. Food and Drug Administration. Drug loading into the nanotubes was accomplished using DOX solution at distinct concentrations. Increased concentrations of DOX significantly improved the amount of loaded DOX. The modified adhesives were fabricated by incorporating DOX-loaded nanotubes into the adhesive resin of a commercial product. The degree of conversion (DC), Knoop microhardness, DOX release kinetics, antimicrobial, cytocompatibility, and anti-MMP activity of the modified adhesives were investigated. Incorporation of DOX-loaded nanotubes did not compromise DC, Knoop microhardness, or cell compatibility. Higher concentrations of DOX led to an increase in DOX release in a concentration-dependent manner from the modified adhesives. DOX released from the modified adhesives did not inhibit the growth of caries-related bacteria, but more importantly, it did inhibit MMP-1 activity. The loading of DOX into the nanotube-modified adhesives did not compromise the physicochemical properties of the adhesives and the released levels of DOX were able to inhibit MMP activity without cytotoxicity. Doxycycline released from the nanotube-modified adhesives inhibited MMP activity in a concentration-dependent fashion. Therefore, the proposed nanotube-modified adhesive may hold clinical potential as a strategy to preserve resin/dentin bond stability.


Importance of Preoperative Vertical Geometric Analysis in Surgery for Anterior Communicating Artery Aneurysm.
In this study, we analyzed the vertical geometry of the anterior communicating artery (AComA) complex with the aim to improve the surgical site orientation during aneurysm operations. Further, the geometric data that can contribute to the success of the surgical technique applied for AComA aneurysms are reported. Computed tomography angiography data of the cerebral arteries of 100 patients who visited our clinic were analyzed. A three-dimensional examination was performed according to the Frankfurt horizontal plane (FHP) using the RadiAnt DICOM Viewer (Medixant, Poznan, Poland), and vertical measurements of the AComA complex were calculated. The Willis polygon values were found to be consistent with those in the literature. The mean height of the AComA complex was 30.58 ± 4.80 mm according to the FHP. Preoperative evaluation of the vertical geometry of the AComA complex is essential for AComA aneurysm surgery. The height of the AComA complex is a key parameter affecting intraoperative surgical site visibility. Preoperative calculation of the height of the AComA complex relative to FHP can facilitate intraoperative surgical site orientation.


Computed tomography of children with pulmonary Mycobacterium tuberculosis infection.
Surveillance and control of tuberculous infection in pediatric patients, especially in those with a contact history, is important to prevent tuberculous infection in the general population. Totally 26 patients, younger than 14 years of age, who had a diagnosis of pulmonary Mycobacterium tuberculosis (TB), underwent both chest radiographs and computed tomography (CT), which were retrospectively reviewed and compared with those of 20 patients with community-acquired bacterial pneumonia (CABP). TB patients were commonly afebrile and had less cavitating lesions or pleural fluid than CABP patients had. Focal or sub-segmental lung opacities suggested the diagnosis of TB than of CABP. Chest CT could also help to identify enlarged, calcified, necrotic mediastinal lymph nodes, which are less frequently found in CABP and frequently obscured by thymic shadows on chest radiographs of children. Low-dose CT for children or infants suspected to have pulmonary TB infection could help to make the decision of further antibiotic treatment.


Molecular biology of medulloblastoma: will it ever make a difference to clinical management?
Over the last 10 years approximately 750 children with medulloblastoma have been treated on consortia based clinical trials at an estimated cost of over 150 million US dollars. Despite this enormous effort, no meaningful molecular data has been generated that will inform the next generation of clinical studies. It is imperative that the neuro-oncology community give greater priority to studies of medulloblastoma molecular biology: unless we do this our patients will face a bleak future in which there is no accurate disease-risk stratification tool and no effective new treatments. We review some of the reasons we have failed to translate knowledge of medulloblastoma disease biology to the clinic and look forward to the next generation of clinical and molecular studies that are seeking to correct this.


Even his friend said he's bad: Children think personal alliances bias gossip.
Children learn about other people through gossip. Although gossip can be a valuable and efficient way to learn about others, evaluating gossip's credibility requires understanding when people may be biased, and using this information to update the truth-value placed on the gossip. For instance, people may be motivated to improve their and their friends' reputations (or to worsen their enemies' reputations). Therefore, testimony that cuts against these social motivations may be more credible. Here, in four studies with 3- to 13-year-old children (total N = 860), we examined (1) children's expectations about the type of gossip people were likely to spread about friends versus enemies, and (2) children's ability to discount testimony that is in line with a speaker's social biases (e.g., negative testimony about a friend). We found that children expect speakers to say nice things about their friends, and mean things about their enemies. And, children were less likely to endorse potentially biased testimony, though the strength of their ability to avoid endorsing biased testimony varied based on the domain of testimony. Overall, these studies suggest that children expect a speaker's testimony to be systematically biased based on her relationships. Our results underscore the importance of tracking and using relationships when evaluating testimony, because relationships have immense power for helping us effectively make sense of an ambiguous world.


Dose-dependent changes in the rat cochlea following aminoglycoside intoxication. II. Histological study.
The structural damages induced by a range of amikacin doses have been studied with SEM and TEM in the adult rat cochlea. Six groups of rats were given daily subcutaneous amikacin injections of either 200, 400, 600, 700, 800, or 1000 mg/kg per day for five consecutive days. Observations were made one month after the end of treatment, following functional recordings [(1987) Hear. Res. 26, 191-197]. In the group treated with 200 mg/kg per day, neither SEM nor TEM revealed any cochlear abnormalities. In the 400-mg group, the only damages were cytoplasmic abnormalities in the OHCs. Changes in the OHC stereocilia occurred at higher doses and were always associated with severe alterations of the underlying cell body. The first missing hair cells were OHCs in the apical regions of the cochleas of the 600-mg group. In the 700-mg group, the loss of OHCs extended to the middle and basal regions, mainly in the third row. By contrast, in the 800- and 1000-mg groups, the usual pattern of hair-cell degeneration was found. Loss of hair cells was greatest in the basal cochlear regions, where the first row of OHCs was more extensively destroyed. These results indicate that metabolic disorders (only visible with TEM) precede stereociliary alterations. Under SEM, the pattern of hair cell degeneration appeared to depend on the dose of the drug. The study clearly demonstrates that both SEM and TEM are needed to determine the true condition of hair cells after drug intoxication.


An electrochemiluminescence sensor based on the CNTs and CdSe@ZnSe for determination of melamine in milk samples.
In this work, a novel electrochemiluminescence (ECL) sensor based on the CdSe@ZnSe and CNTs was constructed for the detection of melamine. CdSe@ZnSe acted as the co-reaction promoter for the enhancement of Ru(bpy)32+/tri-n-propylamine (TPrA) system and CNTs acted as carriers to immobilize more CdSe@ZnSe. The initial ECL signal significantly amplified due to the synergistic effect of CNTs and CdSe@ZnSe. The ECL signal decreased with the addition of melamine, and the change value of ECL intensity (ΔI) was linearly related to the logarithm of melamine concentration. The constructed ECL sensor was able to detect melamine in the range of 1.0 × 10-11 - 1.0 × 10-7 M, and the detection limit was 3.3 × 10-12 M (S/N = 3). It can be used to detect melamine in milk samples.


Ghrelin ameliorates transformation of hepatic ischemia-reperfusion injury to liver fibrosis by blocking Smad and ERK signalling pathways, and promoting anti-inflammation and anti-oxidation effects.
Ghrelin, a gut hormone with pleiotropic effects, may act as a protective signal in parenchymal cells. Hepatic ischemia-reperfusion injury (HIRI) causes acute-on-chronic liver failure and induces transformation of acute to chronic injury. HIRI model of mice was established by a semi-hepatic blocking method and treated with Ghrelin. This process is involved in inflammation, oxidative stress damage and apoptosis, and is associated with the expansion and activation of fibrotic haematopoietic stem cells (HSCs) which express and secrete high levels of collagen that induces liver fibrosis. Therefore, we investigated the effects of Ghrelin during transformation of HIRI to liver fibrosis, and explored the molecular mechanism of Ghrelin's action based on Smad and ERK pathways. Hepatic injury was detected by plasma ALT levels. The hepatic histology and collagen were elucidated by HE staining and Masson staining, respectively. Liver inflammation levels and inflammatory cell counts were assessed by MPO and HE staining, respectively. The antioxidant capacity of plasma was evaluated based on the levels of SOD, MDA, and XOD. The mRNA or protein expression levels of genes related to apoptosis, fibrosis, Smad, and ERK pathways were assessed by real-time quantitative PCR (RT-qPCR), ELISA, or western blotting. The HIRI model was established to investigate the effects of the liver injury transformed to liver fibrosis. Ghrelin exhibited good hepatic protection by ameliorating liver histological changes and decreasing plasma ALT levels. Ghrelin significantly decreased the expression of MPO than that in model group, suggesting that Ghrelin blocked the inflammatory response in the HIRI liver tissue; this supports the anti-inflammatory effects of Ghrelin. Ghrelin significantly decreased apoptosis (enhanced Bcl-2 expression, and down-regulated Bax and Caspase 3). Ghrelin exhibited anti-oxidative effects as it inhibited plasma MDA levels, and promoted plasma SOD and XOD levels. Moreover, Ghrelin inhibited activation of hepatic stellate cells, blocked traditional fibrotic Smad and ERK signalling pathways, and reduced hepatic fibrosis by stimulating degradation of extracellular matrices (ECMs; such as collagen I, collagen III, HA, and LN). This study demonstrates that Ghrelin delays the transformation of HIRI to liver fibrosis process which is correlated to its anti-apoptotic, anti-inflammatory, and anti-oxidative effects. Moreover, Ghrelin alleviates HIRI-mediated liver fibrosis, inhibits activation of HSCs, and reduces accumulation of ECM via inhibition of Smad and ERK signalling pathways.


Formic acid skin burns resulting in systemic toxicity.
Systemic toxicity developed in a 3-year-old girl burned by formic acid over 35% of her total body surface area. The patient presented with profound metabolic acidosis and a serum formate level of 400 micrograms/mL, the highest reported in the literature for poisoning by any route. The patient was successfully treated with hemodialysis, IV bicarbonate, and supportive measures. Reports of formic acid skin burns and systemic toxicity are limited. We discuss the pathophysiology and treatment of these cases.


A synthetic standard for competitive RT-PCR quantitation of 13 GABA receptor type A subunit mRNAs in rats and mice.
We describe a synthetic 769-bp DNA internal standard, GABARQuant 1, for measuring mRNAs of 13 GABA(A) receptor subunits by reverse transcriptase-polymerase chain reaction (RT-PCR). When it is transcribed into cRNA, added in known amounts to target mRNAs in extracts from rat or mouse tissue. competitively reverse transcribed into cDNA, and amplified by the polymerase chain reaction (PCR), the relative intensities of the amplified, stained target and standard DNA bands enable measurement of small amounts of mRNAs for GABA(A) receptor subunits alpha1-6, beta1-3, gamma1-3 and delta and the three cellular markers beta-actin, light neurofilament protein, and glutamine synthetase. For the subunits, most standard products (263-504 bp) differ in size from target products (398-564 bp) by 10-20%. Primer pairs span at least one intron, to prevent interference by genomic DNA, and at least one rat versus mouse restriction fragment length polymorphism (RFLP), to enable rat products to be distinguished from mouse products.


Nav1.7 and other voltage-gated sodium channels as drug targets for pain relief.
Chronic pain is a massive clinical problem. We discuss the potential of subtype selective sodium channel blockers that may provide analgesia with limited side effects. Sodium channel subtypes have been linked to human pain syndromes through genetic studies. Gain of function mutations in Nav1.7, 1.8 and 1.9 can cause pain, whilst loss of function Nav1.7 mutations lead to loss of pain in otherwise normal people. Intriguingly, both human and mouse Nav1.7 null mutants have increased opioid drive, because naloxone, an opioid antagonist, can reverse the analgesia associated with the loss of Nav1.7 expression. We believe there is a great future for sodium channel antagonists, particularly Nav1.7 antagonists in treating most pain syndromes. This review deals with recent attempts to develop specific sodium channel blockers, the mechanisms that underpin the Nav1.7 null pain-free phenotype and new routes to analgesia using, for example, gene therapy or combination therapy with subtype specific sodium channel blockers and opioids. The use of selective Nav1.7 antagonists together with either enkephalinase inhibitors or low dose opioids has the potential for side effect-free analgesia, as well as an important opioid sparing function that may be clinically very significant.


Distinct time courses of microglial and astrocytic hyperactivation and the glial contribution to pain hypersensitivity in a facial cancer model.
Although recent evidence suggests that central glial hyperactivation is involved in cancer-induced persistent pain, the time course of this hyperactivation and the glial contribution to pain hypersensitivity remain unclear. The present study investigated the time-dependent spatial changes of microglial and astrocytic hyperactivation in the trigeminocervical complex, which consists of the medullary (MDH) and upper cervical (UCDH) dorsal horns, and pain-related behaviors in a rat facial cancer model in which Walker 256B-cells are inoculated into the vibrissal pad. In this model, the tumors grew within the vibrissal pad, from which sensory nerve fibers project into the MDH, but did not expand into the infraorbital region, from which fibers project into the UCDH. Nevertheless, mechanical allodynia and thermal hyperalgesia were observed not only in the vibrissal pad but also in the infraorbital region. Western blotting and immunofluorescence studies indicated that microglia were widely activated in the trigeminocervical complex on day 4 and gradually inactivated by day 11. In contrast, astrocytes were only activated in the MDH on day 4; the hyperactivation later expanded into the UCDH. Daily administration of the glial hyperactivation inhibitor propentofylline beginning on day 4 suppressed the glial hyperactivation on later days. Propentofylline treatment largely prevented allodynia/hyperalgesia in the infraorbital region beginning on day 5, although established allodynia/hyperalgesia in the vibrissal pad was less sensitive to the treatment. These results suggest that central glial hyperactivation, transient microglial hyperactivation and persistent astrocytic hyperactivation, contributes to the development of pain hypersensitivity but not to the maintenance of pain in this model.


1000-km 7-core fiber transmission of 10 x 96-Gb/s PDM-16QAM using Raman amplification with 6.5 W per fiber.
We demonstrate 7-core fiber transmission of 10 x 96-Gb/s PDM-16QAM signals over 1000-km using distributed Raman amplification (DRA). DRA gain of 9-12 dB and equivalent noise figure of less than 1 dB are achieved in all cores. We also prove the feasibility of high power multi-core fiber transmission with per fiber power of 6.5 W.


Shifting ear differences in melody recognition through strategy inducement.
In a previous study, the pattern of ear superiority displayed by nonmusicians in a task where dichotically presented target melodies have to be recognized among four probes was found to be correlated with subjects' descriptions of their operating modes: those who reported focusing on critical local differences in pitch tended to show right ear advantage (REA) and the others LEA. The purpose of the present study was to examine if laterality patterns can be affected by treatments designed to induce particular strategies. Treatments supposed to orient toward analytic processing, advising attention to critical notes, with (Experiment 2) or without (Experiment 1) the additional task of reporting their location, produced the expected shift toward REA. To the contrary, treatments supposed to orient toward holistic processing, advising attention to overall contour or requesting aesthetic judgments (Experiment 1), failed to produce the expected shift toward LEA. The result can be attributed either to a basic difference in susceptibility to strategic control between the different operating modes or, more simply, to ineffectiveness of the present holistically oriented treatments.


Clinical Features and Management of Patients Assessed by Cardiology Teleconsultation in the Brazilian Region with the Highest Number of Isolated Cities.
Cardiovascular diseases are the leading cause of adult mortality. Geographically remote and low-income Brazilian regions lack specialized consultations. The telemedicine management of this population by cardiologists is not fully known. To analyze cardiology teleconsultation in the Brazilian region with the highest number of isolated cities. From February 2020 to October 2021, patients from the North Region of Brazil evaluated by local general practitioners were referred for cardiological evaluation by telemedicine. Referral reasons, demographics, clinical history, physical examinations, tests, medications, and prescriptions pre- and post-telemedicine were analyzed (p<0.05 was considered statistically significant). We analyzed 653 patients. The attendance rate was 85.7% (53.1% female, mean age: 54.2±6.5 years). The main reasons for referral were cardiovascular symptoms (58.1%) and risk factors among asymptomatic patients (13.3%). Only 12.6% had a diagnosed disease. Most patients had regular physical examinations and electrocardiograms. Few had recent complementary tests. The prescription of angiotensin receptor blockers (ARBs), calcium channel blockers and statins was significantly increased, while that of digoxin, noncardiac beta-blockers and acetylsalicylic acid (ASA) was decreased at the first teleconsultation. Most of the tests requested were of low complexity and cost: electrocardiogram (28.2%), chest X-ray (14%), echocardiogram (64.5%) and blood tests (71.8%). For 2.1% of patients, interventions were indicated, and 8% were discharged after the first consultation. On-demand cardiology teleconsultation contributes to heart disease treatment optimization. Most patients were referred with syndromic diagnoses without previous complementary tests. The specialist workup requested was usually available locally and at a low cost but precluded early discharge. Local training could optimize the referral.