Biogenesis of prokaryotic pores.
The prokaryotic pore-forming proteins are synthesized in the cytoplasm, and are assembled in their functional form in the outer membrane. They begin to traverse the cytoplasmic membrane via the SecY/SecA export pathway, which is shared also by periplasmic proteins. The sorting signals that direct these proteins to the outer membrane could be present in the three-dimensional conformations of the proteins, but some results suggest that they may be present in short, contiguous sequences. Outer membrane proteins share a rather hydrophilic amino acid composition, and appear to be rich in beta-sheets (with the exception of lipoproteins). This observation as well as the demonstration of periplasmic export intermediates favor the secretion pathway through the periplasm, as opposed to export through fusion sites between the inner and the outer membrane, but such intermediates have not yet been observed with the wild type proteins under physiological conditions.


A study of fetal anomalies detected by ultrasound in Bangladesh and their relative frequencies.
A total of 5,841 obstetric patients were scanned over a period of 34 months. This study was undertaken to establish the anomalies that can be detected by ultrasound and to find out their relative frequencies in Bangladesh. Of the 41 cases of congenital anomalies, seven cases were of hydrocephalus, seven were of hydronephrosis, five were of mild hydrocele (which could be just a physiological variant), five of anencephalus, five of fetal ascites, three of omphalocele, two of small biparietal diameter (BPD), two of short-limb, and one each of gastroschisis, renal cyst, hepatosplenomegaly, pleural effusion with oedema (hydrops fetalis) and bradycardia with irregular fetal heart beats. The benefits of the procedure are that in some cases like hydronephrosis, early detection can lead to early treatment to save the kidney by removing the congenital obstruction soon after birth, and in hydrocephalus and anencephalus it will help in proper management. The problem was there was a chance of higher detection of hydrocephalus and anencephalus as these were clinically suspected by the obstetrician and referred for a scan.


Islet allografts in the cryptorchid testes of spontaneously diabetic BB/Wor dp rats: response to glucose, glipizide, and arginine.
The aim of this study was to examine insulin and glucagon secretory patterns in successfully transplanted spontaneously diabetic BB/Wor dp rats. Diabetic, BB/Wor dp rats received abdominal, intratesticular islet grafts of MHC-compatible BB/Wor dr donor rats without immunosuppression. After a period of 74 +/- 15 days of normoglycemia, they were given the following challenges: 1) glucose, by mouth, 2) a single oral dose of glipizide, with glucose, and 3) arginine, by iv infusion. The pertinent results included the mean fasting plasma glucose levels of control, Sprague-Dawley (C), of transplanted BB/Wor dp (T), and nontransplanted, insulin treated, diabetic BB/Wor dp (D), and they were, respectively, 97 +/- 4 mg/dl, 110 +/- 3 mg/dl, and 350 +/- 40 mg/dl. Fasting plasma insulin levels in C and T rats were 21.9 +/- 3 microU/ml, and 20.4 +/- 2 microU/ml, respectively. Fasting plasma glucagon levels in C, T, and D, were 37.8 +/- 5.7 pg/ml, 43.4 +/- 4.6 pg/ml, and 47.4 +/- 4.9 pg/ml, respectively. During oral glucose tolerance test, the pattern of insulin secretion in the C and T rats was identical with a peak attained at 15 min. Glucose caused a 70% suppression of plasma glucagon levels in C rats (P less than 0.01); T rats suppressed 14%, but this was not statistically significant; D rats failed to suppress. Glipizide plus glucose caused an improved glucose tolerance in T rats without significantly affecting insulin levels. In the same rats, glipizide resulted in a significant suppression of glucagon compared with levels in the presence of glucose alone. Arginine caused a minimal release of insulin in T rats and a major glucagon secretory response in D rats. Pancreatic glucagon content was significantly (P less than 0.03) lower in C and T, compared with D rats. Furthermore, the transplanted testes of T contained substantial amounts of glucagon. In summary, these data suggest that grafted testes in spontaneously diabetic BB/Wor dp rats contain both beta and alpha-cells and that these cells have the capacity to respond to specific secretagogues independently.


Enhancing Brain Lesions during Acute Optic Neuritis and/or Longitudinally Extensive Transverse Myelitis May Portend a Higher Relapse Rate in Neuromyelitis Optica Spectrum Disorders.
Neuromyelitis optica spectrum disorders are inflammatory demyelinating disorders with optic neuritis and/or longitudinally extensive transverse myelitis episodes. We now know that neuromyelitis optica spectrum disorders are associated with antibodies to aquaporin-4, which are highly concentrated on astrocytic end-feet at the blood-brain barrier. Immune-mediated disruption of the blood-brain barrier may manifest as contrast enhancement on brain MR imaging. We aimed to delineate the extent and frequency of contrast enhancement on brain MR imaging within 1 month of optic neuritis and/or longitudinally extensive transverse myelitis attacks and to correlate contrast enhancement with outcome measures. Brain MRIs of patients with neuromyelitis optica spectrum disorders were evaluated for patterns of contrast enhancement (periependymal, cloudlike, leptomeningeal, and so forth). The Fisher exact test was used to evaluate differences between the proportion of contrast enhancement in patients who were seropositive and seronegative for aquaporin-4 antibodies. The Mann-Whitney test was used to compare the annualized relapse rate and disease duration between patients with and without contrast enhancement and with and without seropositivity. Brain MRIs of 77 patients were evaluated; 59 patients (10 males, 49 females) were scanned within 1 month of optic neuritis and/or longitudinally extensive transverse myelitis attacks and were included in the analysis. Forty-eight patients were seropositive, 9 were seronegative, and 2 were not tested for aquaporin-4 antibodies. Having brain contrast enhancement of any type during an acute attack was significantly associated with higher annualized relapse rates (P = .03) and marginally associated with shorter disease duration (P = .05). Having periependymal contrast enhancement was significantly associated with higher annualized relapse rates (P = .03). Brain MRIs of patients with neuromyelitis optica spectrum disorders with contrast enhancement during an acute relapse of optic neuritis and/or longitudinally extensive transverse myelitis are associated with increased annual relapse rates.


A cost-effective approach to simulation-based team training in obstetrics.
Many larger facilities regularly stage obstetric drills in modern simulation departments equipped with expensive simulators. Despite lacking these resources, we wanted to provide effective simulation training at our rural hospital. A team of clinicians and educators developed a cost-effective and time-efficient simulation drill for nurses, which included both a didactic review and a simulation day. The drill included obstetric providers and incorporated scenarios for shoulder dystocia, neonatal resuscitation and postpartum hemorrhage. This was a successful multidisciplinary learning experience that was high in creativity and teamwork, but low in cost.


"Floater scotoma" demonstrated on spectral-domain optical coherence tomography and caused by vitreous opacification.
Patients with prominent vitreous opacities may demonstrate a characteristic shadowing on the volume-scanning protocols using spectral-domain optical coherence tomography. The authors present five cases of this characteristic shadowing artifact. This finding may be useful in objectively documenting the status of vitreous opacification and verifying the patient's complaint of symptomatic floaters, a so-called "floater scotoma".


Protein Sizing with 15 nm Conical Biological Nanopore YaxAB.
Nanopores are promising single-molecule tools for the electrical identification and sequencing of biomolecules. However, the characterization of proteins, especially in real-time and in complex biological samples, is complicated by the sheer variety of sizes and shapes in the proteome. Here, we introduce a large biological nanopore, YaxAB for folded protein analysis. The 15 nm cis-opening and a 3.5 nm trans-constriction describe a conical shape that allows the characterization of a wide range of proteins. Molecular dynamics showed proteins are captured by the electroosmotic flow, and the overall resistance is largely dominated by the narrow trans constriction region of the nanopore. Conveniently, proteins in the 35-125 kDa range remain trapped within the conical lumen of the nanopore for a time that can be tuned by the external bias. Contrary to cylindrical nanopores, in YaxAB, the current blockade decreases with the size of the trapped protein, as smaller proteins penetrate deeper into the constriction region than larger proteins do. These characteristics are especially useful for characterizing large proteins, as shown for pentameric C-reactive protein (125 kDa), a widely used health indicator, which showed a signal that could be identified in the background of other serum proteins.


Sturge-Weber disease--neurophysiological evaluation of a case with secondary epileptogenesis, successfully treated with lobe-ectomy.
A case of Sturge-Weber's disease with a generalized seizure at 7 months of age is described, followed 7 months later by the development of very frequent and therapy resistent myoclonic astatic fits. The neurophysiological evaluation indicated a primary lesion in the right occipital area followed by signs of secondary epileptogenesis. The patient was cured by a right-sided occipital lobe-ectomy including an area of leptomeningeal angiomatosis.


Human sulphotransferases are involved in the activation of aristolochic acids and are expressed in renal target tissue.
Use of herbal preparations containing Aristolochia species has led to progressive nephropathy and urothelial cancer in humans. Analysis of DNA adducts formed in human target tissues and studies in animal models have pointed out a major role of the secondary plant metabolites, aristolochic acids, in these effects. Only a minority of the users of Aristolochia-containing products developed nephropathy and cancer, suggesting differences in individual susceptibility. Differences in metabolic activation and inactivation frequently affect the susceptibility towards chemicals. Others have shown that the activation of aristolochic acids to DNA-reactive and mutagenic metabolites requires reduction of their aryl nitro group. The biological activity of numerous nitro- and aminoarenes, after appropriate phase I metabolism, is strongly enhanced in the presence of acetyltransferases or sulphotransferases (SULTs). In the present study, we demonstrate that expression of human SULTs in bacterial and mammalian target cells reinforces the mutagenic activity of aristolochic acids. Using Salmonella typhimurium TA1538 as the recipient organism, we identified the expression of all 12 human SULT forms. SULT1A1 led to the strongest increase in the mutagenicity of aristolochic acids. Some activation was also observed with SULT1B1, but not with the remaining forms. The role of SULT1A1 in the activation of aristolochic acids was corroborated using S. typhimurium TA100- and Chinese hamster V79-derived target cells engineered for expression of human SULT1A1 when compared with control cells. Furthermore, pentachlorophenol, an inhibitor of SULT1A1, strongly reduced the mutagenic effect of aristolochic acids in V79-hCYP2E1-hSULT1A1 cells. Moreover, we demonstrate that SULT1A1 and SULT1B1 are expressed in human kidney using immunoblot analysis, but their levels are substantially lower than in liver. Finally, we discuss the possibility that reactive sulphuric acid conjugates produced in other tissues are transferred to kidney and ureter.


Behavioral self-organization underlies the resilience of a coastal ecosystem.
Self-organized spatial patterns occur in many terrestrial, aquatic, and marine ecosystems. Theoretical models and observational studies suggest self-organization, the formation of patterns due to ecological interactions, is critical for enhanced ecosystem resilience. However, experimental tests of this cross-ecosystem theory are lacking. In this study, we experimentally test the hypothesis that self-organized pattern formation improves the persistence of mussel beds (Mytilus edulis) on intertidal flats. In natural beds, mussels generate self-organized patterns at two different spatial scales: regularly spaced clusters of mussels at centimeter scale driven by behavioral aggregation and large-scale, regularly spaced bands at meter scale driven by ecological feedback mechanisms. To test for the relative importance of these two spatial scales of self-organization on mussel bed persistence, we conducted field manipulations in which we factorially constructed small-scale and/or large-scale patterns. Our results revealed that both forms of self-organization enhanced the persistence of the constructed mussel beds in comparison to nonorganized beds. Small-scale, behaviorally driven cluster patterns were found to be crucial for persistence, and thus resistance to wave disturbance, whereas large-scale, self-organized patterns facilitated reformation of small-scale patterns if mussels were dislodged. This study provides experimental evidence that self-organization can be paramount to enhancing ecosystem persistence. We conclude that ecosystems with self-organized spatial patterns are likely to benefit greatly from conservation and restoration actions that use the emergent effects of self-organization to increase ecosystem resistance to disturbance.


Male bisexuality and condom use at last sexual encounter: results from a national survey.
Relatively little is known about condom use among bisexual men as separate and distinct from exclusively homosexual and heterosexual men. Most previous research on bisexual men has relied on non-probabilistic, high risk samples with limited generalizability. We examined the relationship between male behavioral bisexuality and condom use in the 2002 cycle of the National Survey of Family Growth (NSFG). Bisexually-active men positively differed from heterosexually- and homosexually-active men on every indicator of confounding risk. However, bisexually-active men did not report using condoms less often than other men during their last sexual encounters with males and females. Indeed, with female partners, bisexually-active men reported higher rates of condom use than other men. These relationships remained when all sociodemographic and confounding risk factors were held constant. Our results suggest that caution must be used when making assumptions about condom use in the general population of bisexual men from non-probabilistic samples.


Computed tomography in metastatic disease of the brain.
Computed tomography has been found to be a more accurate diagnostic tool in the analysis of brain metastases than radionuclide scanning. Of 1,100 patients studied by CT scan, 57 showed evidence of intracerebral metastasis, and 14 showed evidence of hydrocephalus. Density levels below that of normal brain tissue were found in cases of metastases from the lung (13), breast (7), melanoma (4), kidney (3), lymphoma (3), and nasopharynx (1); levels above normal were found in cases of metastases from melanoma (8), lung (3), colon (3), chorionic carcinoma (2), osteogenic sarcoma (1), and kidney (1).


Estimation of Liver Fat by FibroScan in Patients With Nonalcoholic Fatty Liver Disease.
Background Assessment of nonalcoholic fatty liver disease (NAFLD) includes estimation of liver fat (steatosis). Controlled attenuation parameter (CAP) value obtained by FibroScan® (Echosens, Paris, France) is an alternative to liver biopsy for diagnosing and estimating steatosis (S). This study aimed to estimate the liver fat by CAP in NAFLD patients. Methods An observational cross-sectional study was conducted at the Liver Unit of Bir Hospital, from January 2021 to May 2021 after ethical clearance from the Institutional Review Board of the National Academy of Medical Sciences. A convenient sampling method was used. Data were analyzed with descriptive and inferential statistics involving bivariate and multivariate analysis. Results A total of 127 NAFLD patients were enrolled. The mean (±SD) CAP value was 271.53 (±50.69) dB/m. Total cholesterol, triglyceride, and body mass index (BMI) correlated positively (p<0.05) while systolic blood pressure correlated negatively with CAP value (p=0.031). On multivariate analysis, patients with BMI ≥25 kg/m2 were found 3.7 times more likely to have CAP ≥291 dB/m (S3, severe steatosis) than those with BMI <25 kg/m2 (p=0.048, 95% CI 1.01, 13.50). The mean (±SD) CAP values were 276.19 (±49.93) and 246.60 (±48.50) dB/m among those with BMI ≥25 kg/m2 and <25 kg/m2, respectively (p=0.016, using independent t-test). CAP steatosis grading correlated positively with both the ultrasound grading (p<0.001) and fibrosis grading by liver stiffness measurement (p=0.004). Conclusion In this observational cross-sectional study of NAFLD patients, the mean (±SD) CAP value was 271.53 (±50.69) dB/m, which corresponds to moderate steatosis (S2). Obese NAFLD patients with ≥25 kg/m2 were 3.7 times more likely to have severe steatosis (S3) than nonobese NAFLD patients with BMI <25 kg/m2.


Homeless youths' interpersonal perspectives of health care providers.
In the United States, youth run away from home due to poor interpersonal relationships with parents or guardians; often times, they have been the recipients of parental neglect or abuse. As youth become increasingly entrenched in street-based living and problem substance use, their ability to rehabilitate their lives is incumbent upon trusting and engaging relationships with adult service providers. A total of 54 substance-using homeless youth (18-25 years) participated in focus groups to provide their perspectives on encounters and interpersonal relationships with health care providers. Participants were recruited from shelters in Hollywood, California, and from a drop-in shelter in Santa Monica, California. Four themes related to interpersonal barriers to care from service providers were identified: authoritative communication, one-way communication, disrespect, and empathy. Participants appreciate care providers who convey information in a helpful, meaningful manner and prefer providers who can, themselves, share similar life experiences. Implications point to the need for agencies and services specifically tailored to homeless, drug-using youth. These agencies should employ care providers who are trained to understand the developmental needs and histories of runaway youth. For proper reintegration of this vulnerable population into mainstream society, the narratives of these youth underscore the necessity of targeted services.


Recent research progress in galactose-based fluorescent probes for detection of biomarkers of liver diseases.
The liver is the largest detoxification organ in the human body, with an array of functions that help support metabolism, immunity, digestion, and vitamin storage, among other functions, and maintains the health and stability of the internal environment. Liver injury causes the concentration fluctuation of related biomarkers, small molecules, and enzymes, and in turn, the structure and function of the liver are changed by those alterations. With the principles of early detection, early diagnosis, and early treatment, it is crucial to design and synthesise a tool for detecting related biomarkers during liver damage and lesion, among which fluorescent probes have attracted attention in recent years. In the course of liver diseases, the asialoglycoprotein receptors (ASGPR) are overexpressed on the hepatoma cells, which can specifically recognize the galactose variant. Several galactose-based fluorescent probes have been developed to target hepatocytes via specific receptor-mediated endocytosis and release fluorophores after reacting with specific small molecules and enzyme biomarkers. The change in fluorescence intensity reflects the level of substances, such as reactive oxygen species, reactive nitrogen species, reactive sulfur species, enzymes or metal ions, etc. The application of fluorescent probes in vivo can aid in monitoring the dynamic changes of endogenous and exogenous biomarkers. This Highlight provides an update on the progress, limitations, and prospects of galactose-based fluorescent probes applications in the early diagnosis of liver diseases.


Neutrophil Extracellular Traps as an Adhesion Substrate for Different Tumor Cells Expressing RGD-Binding Integrins.
Neutrophil extracellular traps (NETs), in addition to their function as a host defense mechanism, play a relevant role in thrombus formation and metastatic dissemination of cancer cells. Here we screened different cancer cell lines endogenously expressing a variety of integrins for their ability to bind to NETs. To this end, we used NETs isolated from neutrophil-like cells as a substrate for adhesion assays of HT1080, U-87 MG, H1975, DU 145, PC-3 and A-431 cells. Levels of α5, αIIb, αv, β1, β3 and β5 chains were determined by western blot analysis in all cell lines and levels of whole integrins on the plasma membrane were assessed by fluorescence-activated cell sorting (FACS) analysis. We found that high levels of α5β1, αvβ3 and αvβ5 enhance cell adhesion to NETs, whereas low expression of α5β1 prevents cell attachment to NETs. Excess of cyclic RGD peptide inhibited cell adhesion to NETs by competing with fibronectin within NETs. The maximal reduction of such adhesion was similar to that obtained by DNase 1 treatment causing DNA degradation. Our findings indicate that NETs from neutrophil-like cells may be used as a substrate for large screening of the adhesion properties of cancer cells expressing a variety of RGD-binding integrins.


[Safety evaluation of adjuvant chemotherapy by weekly paclitaxel combined with weekly carboplatin in patients with postoperative non-small cell lung cancer].
Favorable results of various comparative studies have been reported in recent years regarding adjuvant chemotherapy for non-small cell lung cancer (NSCLC), resulting in an increase in the number of facilities that proactively conduct adjuvant chemotherapy in Japan. In the present study, we evaluate the tolerability of a postoperative adjuvant chemotherapy regimen conducted in our facility using paclitaxel (PTX) and carboplatin (CBDCA). Thirteen patients who received weekly PTX and CBDCA as postoperative adjuvant chemotherapy were evaluated retrospectively. PTX was administered by iv drip infusion over 1 hour at 70-80 mg/m(2), followed by CBDCA at AUC= 2 by iv drip infusion over 1 hour. This was repeated on Days 1, 8 and 15, followed by a rest on Day 22. Two to 4 cycles were conducted in each patient. Patients were admitted only the first time, and treatment was thereafter conducted on an outpatient basis. The scheduled number of cycles could be completed in all but one patient who developed interstitial pneumonia 2 days after treatment. Non-hematologic toxicities observed included peripheral neuropathy in 3 patients, nausea in 2, general fatigue in 6, stomatitis in 2, and alopecia in 11. Hematologic toxicities include leukopenia in 10, but leukopenia was not febrile, Grade 3 or more severe in any of these patients. In addition, decreases in hemoglobin and thrombopenia were observed in 10 and 2 patients, respectively, but both adverse events were mild (< Grade 3) and could be controlled on an outpatient basis in all cases. Our findings suggested that adjuvant chemotherapy using weekly PTX/weekly CBDCA for NSCLC is well tolerated and can be safely conducted on an outpatient basis.


Aeromonas hydrophila in livestock: incidence, biochemical characteristics and antibiotic susceptibility.
Faecal samples from 110 horses, 115 pigs, 111 sheep and 123 cows were examined for the presence of Aeromonas hydrophila, which was also sought in the available drinking water. The overall faecal rate was 11.8%, but significantly more bovine than other samples were found to be positive. There was significant association between the isolation of A. hydrophila from all animal faeces and its presence in drinking water, but this was not found when individual animal groups were analysed separately. An enrichment technique increased the total number of isolates by 77.1%. Strains of differing origins could not be differentiated by biotyping, although fermentation of sorbitol was associated with bovine isolates. There was a strong positive correlation between positive reactions for V--P, gluconate oxidase and haemolysis of rabbit erythrocytes, tests which had previously been shown to correlate with production of enterotoxin and cytotoxin. Biotypes giving positive reactions for these tests were most frequently isolated from cows, sheep and untreated water, and less frequently from pigs and horses. Most strains of A. hydrophila were resistant to amoxycillin, carbenicillin and cephradine, and sensitive to gentamicin, chloramphenicol and neomycin.


Oral health status of 207 head and neck cancer patients before, during and after radiotherapy.
The aim of this retrospective study was to describe the oral health status of patients before, during, and after radiotherapy (RT) for the treatment of head and neck cancer (HNC). Before RT, the following data was collected: presence of unrecoverable teeth, residual roots, unerupted teeth, use of dentures, periodontal alterations, caries, candidiasis, and xerostomia. Mucositis, candidiasis, and xerostomia were evaluated during RT. Patients continued to be followed after RT for evaluation of mucositis, candidiasis, xerostomia, radiation caries, and osteoradionecrosis. For statistical analysis, 95% confidence intervals (CI) were determined using sample size, population, and percentages. Before RT, 120 (57.9%) patients presented with alterations in the oral cavity namely, 85 (41.0%) with periodontal disease, 44 (21.2%) with residual roots, 25 (12.0%) with caries, 15 (7.2%) with candidiasis, and 12 (5.8%) had an unerupted tooth present. Xerostomia was a complaint of 19 patients (9.1%). Restorations were indicated for 33 patients (15.9%), whereas extraction was indicated for 104 (50.2%) patients. During RT, mucositis was found in 80 (61.7%) patients, candidiasis in 60 (45.8%), and xerostomia was a complaint of 82 patients (62.6%). After RT, mucositis persisted in 21 patients (19.2%), candidiasis was identified in 23 patients (21.1%), and xerostomia was reported by 58 patients (53.2%). Radiation caries developed in 12 patients (11.0%), whereas six patients (5.5%) developed osteoradionecrosis. The demographic profile herein presented will be useful as baseline data to provide additional epidemiological information and to determine future measures for prevention and treatment of RT-induced complications and sequelae.


Regulatory T-cells and micrometastasis in lymph nodes of stage I NSCLC.
Regulatory T-cells (Tregs) have a pivotal role not only in abrogating autoimmune disease, but also in tumor immune escape. The purpose of the present study was to evaluate the clinical significance of the relative expression of forkhead/winged helix transcription factor (FOXP3) and micrometastasis in the regional lymph nodes (RLNs) of patients with stage I non-small cell lung cancer (NSCLC). The RLNs in 131 patients who underwent complete surgical resection for stage I NSCLC were collected at the time of surgery. The relative expression levels of FOXP3 and cytokeratin 19 (CK19) in RLNs were determined by quantitative RT-PCR. The pathological stage was diagnosed as stage IA in 97 patients (74.0%) and stage IB in 34 patients (26.0%). The relative expression levels of FOXP3 and CK19 in the RLNs were 0.062±0.0083% and 0.025±0.056%, respectively. The relative expression of FOXP3 tended to increase with increasing relative expression of CK19. The five-year overall survival rate of the patients with low expression of FOXP3 was better (90.3%) than that of patients with high expression (79.3%) (p=0.0419). A multivariate analysis using the significant variables (gender, age, histology and FOXP3 expression) showed that the FOXP3 expression in RLNs was a significant independent prognostic factor. The expression of CK19 tended to be positively correlated with the expression of FOXP3. High expression of FOXP3 in RLNs was a significant unfavorable prognostic factor in patients with stage I NSCLC.


Clinical outcomes of CATz versus OPDCAT.
To compare refractive outcomes, wavefront outcomes, and corneal asphericity indices (Q values) for patients treated with wavefront-guided or topography-guided custom ablations using the NIDEK Advanced Vision Excimer Laser System (NAVEX). A total of 196 eyes of 98 patients underwent wavefront-guided or topography-guided LASIK. A contralateral study of 28 eyes of 14 patients who underwent customized aspheric treatment zone (CATz) ablation in one eye and optical path difference customized aspheric treatment (OPDCAT) in the fellow eye comprised one part of the study. The second part of the study was a retrospective review of myopic LASIK using CATz in 84 eyes and LASIK using OPDCAT in 84 eyes. In the CATz-treated eyes, the preoperative mean spherical equivalent refraction was -4.06+/-1.69 diopters (D). In OPDCAT-treated eyes, the preoperative mean spherical equivalent refraction was -3.67+/-2.17 D. In the CATz-treated eyes, 95% of eyes achieved > or = 20/20 best spectacle-corrected visual acuity (BSCVA) with 15% gaining lines of BSCVA. In the OPDCAT-treated eyes, 94.5% of eyes achieved > or = 20/20 vision with 4.5% gaining lines of BSCVA. The difference in lines gained between CATz and OPDCAT in the retrospective component was statistically significant (P<.005). OPDCAT-treated eyes showed a statistically significant worsening in OPD root-mean-square (OPD-RMS), higher order wavefront error, and corneal asphericity (P<.005) compared to preoperative in the retrospective portion of the study. In the contralateral arm of the study, OPD-RMS value was significantly higher (P<.005) in the OPDCAT eyes than the fellow CATz-treated eyes. OPDCAT-treated eyes show a larger change in the Strehl ratio compared to the CATz-treated eyes (P<.005). The refractive outcomes were excellent and showed no clinically significant difference between CATz and OPDCAT treatments. The higher induction of aberrations with the OPDCAT ablations may be due to the fact that these treatments are based on Zernike polynomials to drive the ablation.


Alterations in insulin clearance and hepatic blood flow during the night do not contribute to the 'dawn phenomenon' in type 1 diabetes.
To assess mechanisms leading to the 'dawn phenomenon' in type 1 diabetes mellitus, overnight insulin clearance, hepatic blood flow and insulin sensitivity of glucose metabolism were determined in 9 type 1 diabetic subjects treated with continuous subcutaneous insulin infusions. Glucose clamp studies were performed twice, once after midnight (from 24.00 to 02.00 h), and once in the early morning (from 06.00 to 08.00 h) during insulin infusion at 15 mU/m2/min. Insulin clearance was 482 +/- 57 ml/m2/min during the first, and 528 +/- 56 ml/m2/min during the second clamp (nonsignificant). Hepatic plasma flow assessed by measuring indocyanine green clearance was 984 +/- 115 and 1,040 +/- 163 ml/min, after the first and after the second clamp, respectively (nonsignificant). Glucose uptake during the two clamps was not significantly different. Since hepatic blood flow is known to influence insulin clearance and hepatic glucose metabolism, the data demonstrate that overnight changes in hepatic blood flow and insulin clearance do not contribute to the previously described early morning increase in insulin requirements in type 1 diabetic subjects (dawn phenomenon).


Immunosuppressants produced by Streptomyces: evolution, hygiene hypothesis, tumour rapalog resistance and probiotics.
Resistance to a drug and the suppression of inflammatory disorders with immunosuppressive drugs might have happened upon exposure to natural compounds during evolution. Streptomycetes are soil bacteria, but they produce therapeutic drugs. They have been reported to be the low-abundant members of mucosal microbiomes with a higher prevalence in nonhumans ingesting soil compared with humans. Their lower abundance in the human microbiome might be the representations of our current hygienic lifestyle. We suggest that the Streptomyces bacteria producing antiproliferative/immunosuppressive compounds (e.g., rapamycin and tacrolimus) contribute to the rapalog resistance of certain mucosal tumours (e.g., colon cancer) and the 'hygiene hypothesis'. If so, the shortage of exposure to these compounds in the current lifestyle might be an underlying reason for the increase of inflammatory diseases, such as inflammatory bowel diseases (IBD). An investigation on adding certain Streptomycetes (e.g., S. hygroscopicus and S. tubercidicus) to the list of probiotics against inflammatory diseases would be an interesting research area in the future.


Angiotensin-II down-regulates cardiac natriuretic peptide receptor-A mediated anti-hypertrophic signaling in experimental rat hearts.
Atrial natriuretic peptide (ANP) exerts anti-hypertrophic effects in the heart via natriuretic peptide receptor-A (NPR-A). However, ANP mediated anti-hypertrophic activity is decreased in the cardiomyopathic conditions. In the present investigation the in vivo effects of angiotensin II (Ang II), a hypertrophic agonist have been studied on the ventricular expression level of NPR-A in Wistar rat hearts. NPR-A expression at the protein and mRNA levels were found to be markedly reduced by 5-fold respectively in Ang II infused rats heart as compared with sham rat hearts. Moreover, cGMP production in response to ANP was reduced by 77% in the isolated cardiac membrane preparation from the Ang II infused rat hearts. Losartan treatment reversed NPR-A expression and responsiveness to ANP. This study suggests that Ang II down regulates cardiac NPR-A activity by suppressing Npr1 gene transcription.


A preliminary in vivo study of a method for measuring magneto-acoustic sonic source under electrical stimulation.
Stimulating current distribution in the tissue is unknown due to the complex distribution. A preliminary in vivo measurement of the magneto-acoustic (MA) signal of the human finger is performed in this study. The approach for locating the magneto-acoustic source of the stimulating current is studied. We use a lock-in amplifier to measure the MA signal under continuous wave electrical stimulation. The phase of the MA signal is used to extract the location of the sonic source. The experimental system is designed to measure the MA signal under electrical stimulation. Preliminary experiments results show that the amplitude precision is improved to less than 1 μPa. The sonic source is located with millimetre precision. We propose a new MA source-locating method with high measurement and location precision. This method will be significant to the study of the imaging and monitoring of the current distribution of electrical stimulation with high precision.


The use of lithium in mixed states.
Lithium is a unique drug. In more than 60 years of observation, it showed its multiple important clinical properties in treating mania, stabilizing mood alterations, preventing suicide and protecting from neurodegeneration. It was also the most extensively studied drug in psychiatry. Nevertheless, it is generally underprescribed. Specifically, lithium is virtually not considered in the treatment of patients affected by mixed affective states. Lithium is not suggested for the acute treatment of mixed affective states and is considered to be less effective than other mood stabilizers in the long-term management of these patients. The main reason why lithium has no indication for mixed states is the "lack of evidence." Actually, there are several reasons to consider lithium as an effective treatment in patients with mixed affective states.


Environmental interventions to promote healthy eating: a review of models, programs, and evidence.
Environmental interventions are an important part of efforts to improve health in populations. With respect to strategies to encourage positive nutrition behavior, environmental approaches help create opportunities for action by removing barriers to following a healthy diet. This article reviews the rationale, conceptual models, program examples, and recent empirical evidence regarding the extent and effects of environmental interventions to promote healthy eating. The state of the art is described for five types of interventions: (1) changes in the food supply; (2) point of choice nutrition information; (3) collaboration with private sector food vendors; (4) worksite nutrition policies and incentives; and (5) changes in the structure of health and medical care related to nutrition. Environmental approaches to dietary behavior change can reach large segments of the population through increased availability of nutritious foods, provision of quality nutrition services in workplace and health care settings, and accessible information about healthful food choices. Nutrition intervention can also serve as a model for other types of health promotion initiatives using multidimensional environmental and educational technologies.


Donation of the body for scientific purposes in Italy: ethical and medico-legal considerations.
In recent years in Italy (and in the other European Countries) a new debated topic involves anatomists and the scientific world: donation of the body after death for scientific purposes. The aim of our analysis is to analyze the issue of voluntary body donation in Italy focusing first of all, on key principles of the disciplines of donation. Considering the rise of exhibitions and events in which death is spectacularized, the debate is focus on will, on respect and overall on the purpose for which the body is donated. Anatomical dissection is considered necessary in the direct learning of the human body, of surgical practices and new scientific techniques but the scarcity of programmes and regulations regarding the donation of bodies for study and research make it an uncommon practice. After discussing what are the constitutional principles underlying the issue we want to emphasize the need of a more effective and updated regulation to set limits and methods of a practice still essential for scientific progress.


A twin study of dental dimension. II. Independent genetic determinants.
To demonstrate the presence of independent genetic determinants of multiple correlated tooth dimensions from twin data, a multivariate analysis was performed on the covariance matrices of monozygotic and dizygotic within-pair differences for mesiodistal and buccolingual dimensions of 28 teeth of the secondary dentition. The results provided strong evidences that the correlation among tooth dimensions is primarily genetic in origin, probably attributable to the pleiotropic action of either independent genes or groups of genes. Among the genetic factors that were identified, one appeared to affect the maxillary teeth in general while a second influenced primarily the anterior mandibular teeth. There was a striking tendency for homologous measurements on the right and left sides to be associated with the same genetic factor. In contrast, genetic determination of the maxillary and mandibular dentition seemed to be independent of each other, and a wider range of genetic factors were found to influence the mandibular than the maxillary teeth, suggesting that a differential degree of evolutionary stability may have been achieved in the teeth of the two jaws.


[Differential diagnosis of supraventricular rhythm disorders and the tactics in the treatment with cardiac glycosides].
The article discusses the possibilities of differential diagnosis of supraventricular arrhythmians by means of carotid zone stimulation, atrial VCG and ECG recorded from right-bronchial leads. Atrial VCG can reveal the character of the ectopic P-wave and thus helps in the diagnosis of arrhythmias with conspicuous atrial activity. ECG recorded from bronchial leade makes it possible to obtain a large atrial wave and determine elements of decisive importances in the diagnosis of many rhythm disorders: junctional and combined contractions, various types of ectopic P-waves, the character of antero- and retrograde conduction. The tactics of treatment with cardiac glycosides is determined by precise diagnosis of the arrhythmia and its connection with digitalis toxicosis.


Order information in verbal working memory shifts the subjective midpoint in both the line bisection and the landmark tasks.
A largely substantiated view in the domain of working memory is that the maintenance of serial order is achieved by generating associations of each item with an independent representation of its position, so-called position markers. Recent studies reported that the ordinal position of an item in verbal working memory interacts with spatial processing. This suggests that position markers might be spatial in nature. However, these interactions were so far observed in tasks implying a clear binary categorization of space (i.e., with left and right responses or targets). Such binary categorizations leave room for alternative interpretations, such as congruency between non-spatial categorical codes for ordinal position (e.g., begin and end) and spatial categorical codes for response (e.g., left and right). Here we discard this interpretation by providing evidence that this interaction can also be observed in a task that draws upon a continuous processing of space, the line bisection task. Specifically, bisections are modulated by ordinal position in verbal working memory, with lines bisected more towards the right after retrieving items from the end compared to the beginning of the memorized sequence. This supports the idea that position markers are intrinsically spatial in nature.


Micronucleus investigation in human buccal epithelial cells of gutkha users.
Gutkha is a cheap and convenient betel quid substitute, which is popular among all age groups. Various studies reveal its carcinogenic nature that leads to oral submucosus fibrosis and increases the chances of oral cancer. The micronucleus (MN) assay in exfoliated mucosal cells is a useful method for observing genetic damage in humans. To observe the genotoxic effect of gutkha on human buccal epithelial cells. The MN assay was performed to assess the frequency of MN in human buccal epithelial cells. The study comprises 60 individuals of which 30 individuals were gutkha chewers and another 30 were nonusers (control). The MN frequency was scored to estimate the genotoxic damage. In gutkha users, the frequency of MN was highly significant (17.4 ± 0.944) as compared with nonusers (control) groups (4.53 ± 0.331) (P < 0.001). The MN assay in human buccal epithelial cells is a useful and minimally invasive method for monitoring genetic damage in humans. Asignificantly higher frequency of micronucleated cells are found among gutkha users.


A Case Report of Calcifying Pseudoneoplasm of the Neuraxis: An Incidental Finding After a Car Accident.
Calcifying pseudoneoplasms of the neuraxis are rare, poorly understood lesions that can occur anywhere in the central nervous system without any age or sex predilection. Their pathogenesis is still controversial. Patients can present with various symptoms due to lesion location and only few cases have been discovered incidentally. We present a 25-year-old male referred to our hospital after a car accident. Computed tomography scan and magnetic resonance imaging was done because of the patient's head trauma and a calcified intracranial lesion was found and excised surgically. Pathologic evaluation of the specimen was consistent with the diagnosis of calcifying pseudoneoplasm of the neuraxis.


Potential for immune reconstitution through G-CSF treatment of HIV patients.
New treatment strategies for HIV/AIDS are very successful in reducing viral load. However, reconstitution of the immune system takes about one year and may be insufficient or remain incomplete. During this time the patient remains prone to opportunistic infections as a result of the complex immune dysfunction caused by the virus. Recombinant granulocyte colony-stimulating factor (G-CSF) has diverse immunomodulatory properties which may be beneficial in aiding immune reconstitution.


Photodissociation dynamics of phosphorus trichloride (PCl3) at 235 nm using resonance enhanced multiphoton ionization (REMPI) with time-of-flight (TOF) mass spectrometry.
The photodissociation dynamics of phosphorus trichloride (PCl(3)) has been studied in a supersonic beam by resonance enhanced multiphoton ionization (REMPI), using time-of-flight (TOF) mass spectrometry. The study is focused on the nascent state of the primary chlorine atom, formed on excitation of the (n, sigma*) transition of the molecule around 235 nm. Dissociation of PCl(3) and the REMPI detection of chlorine atoms are performed, using the same laser around 235 nm. The photofragments, namely, Cl((2)P(3/2)) and Cl*((2)P(1/2)), are probed, using the 2+1 REMPI scheme in the 234-236 nm region. We have determined the photofragment speed distribution, the recoil anisotropy parameter beta, and the spin-orbit branching ratio for chlorine atom elimination channels. Polarization-dependent and state-specific TOF profiles are converted into kinetic energy distributions, using a least-squares fitting method, taking into account the fragment anisotropies. The anisotropy parameters for Cl and Cl* are characterized by values of 0.0 +/- 0.05 and 0.20 +/- 0.05, respectively. Two components, namely, the fast and the slow, are observed in the speed distribution (P(v)) of Cl and Cl* atoms, formed from different potential energy surfaces. The average translational energies for the Cl and Cl* channels for the fast component are 29.7 and 30.6 kcal/mol, respectively. Similarly, for the slow component, the average translational energies for the Cl and Cl* channels are 9.5 and 9.1 kcal/mol, respectively. The energy partitioning into the translational modes is interpreted with the help of an impulsive model, for the fast component, and a statistical model, for the slow component. Apart from the chlorine atom elimination channel, molecular chlorine (Cl(2)) elimination is also observed in the photodissociation of PCl(3). The observation of the molecular chlorine in the dissociation process and the bimodal translational energy distribution of the chlorine atom clearly indicate the existence of a crossover mechanism from the initially prepared state to the ground state.


Chimeric Antigen Receptor-T Cell Mediated Bilateral Facial Nerve Palsy: A Case Report.
Chimeric antigen receptor (CAR-T) cell therapy is highly effective against hematological cancers but is associated with immune mediated side effects, including neurotoxicity. The most commonly described presentations of immune cell mediated neurotoxicity syndrome (ICANS) include cortical symptoms and generally localize to the central nervous system. In this report, we present a patient with acute onset of bilateral facial nerve palsy following CAR-T cell therapy, followed by a complete clinical recovery. Aside from a temporary anisocoria, he had no other neurologic symptoms and no encephalopathy or seizures. MRI Brain was non-contributory and cerebrospinal fluid revealed a modest increase in lymphocytes without systemic leukocytosis and viral studies were all negative. He was diagnosed with bilateral facial nerve palsy secondary to CAR-T cell therapy and subsequently treated with a course of steroids. Several weeks after presentation he returned to his neurological baseline. The presentation of CAR-T cell mediated facial nerve palsy is both clinically and scientifically relevant for physicians, patients, and researchers.


An analytical hierarchy process-based study on the factors affecting legislation on plastic bags in the USA.
Annually, a large number of used plastic shopping bags are released into the environment, posing significant threats to public health and wildlife. Owing to these concerns, many local, regional, and national governments around the world have passed legislation to ban or restrict the use of plastic shopping bags. However, in the USA there are only 18 states that have approved plastic bag bans/fees, and even within these states these regulations do not cover all cities or counties. There are many factors that could affect the development and implementation of these regulations. This article employs an analytical hierarchy process to analyse the factors that could impact the enactment of plastic bag regulations. Five impact factors are identified based on statistical data, that is, geographical location, interest of industry achievable, cost of living, level of economic development, and educational level of population. The weights of the five impact factors are determined and it is found that the possibility of banning or restricting plastic bags in general follows a certain pattern among all states.


Personalized nuclear imaging protocol in cases with nodular goiter and parathyroid adenoma.
A 62 years old woman was diagnosed with multinodular toxic goiter and primary hyperparathyroidism/left parathyroid adenoma by hormonal assessment, ultrasound and nuclear thyroid/parathyroid scans. Cervical ultrasound illustrated a multinodular aspect of the thyroid with solid nodules and cystic-component nodules; the larger one represented a multinodular complex with necrosis areas in the left thyroid lobe, ACR TI-RADS score 4 (moderately suspicious). Functional nuclear imaging was performed for accurate differential diagnosis between thyroid vs. parathyroid localization, between cold vs. hot nodules, and eventually, for guiding the choice of a subsequent Fine-Needle Aspiration Biopsy (FNAB). Scans described an early intense 99mTc-sestaMIBI uptake with no 99mTc-pertechnetate uptake in the left thyroid lobe larger nodule. Due to the suspicion of malignancy for this nodule, we performed an additional scan (1 hour before the classical 2 hours parathyroid delayed scan). The intense uptake persists in both delayed scans suggesting no malignant phenotype and which was confirmed after surgery by benign histology. In conclusion, using a 99mTc-sestaMIBI personalized protocol, related to the radiotracer cellular uptake mechanisms: 1 hour scan (supplementary image, corresponding to the maximum uptake pattern of 99mTc-sestaMIBI for cancer cells) and 2 hours scan (for parathyroid washout evaluation) may avoid unnecessary extensive thyroid surgery.


State-of-the-Art Strategies for the Vascularization of Three-Dimensional Engineered Organs.
Engineering three-dimensional (3D) implantable tissue constructs is a promising strategy for replacing damaged or diseased tissues and organs with functional replacements. However, the efficient vascularization of new 3D organs is a major scientific and technical challenge since large tissue constructs or organs require a constant blood supply to survive in vivo. Current approaches to solving this problem generally fall into the following three major categories: (a) cell-based, (b) angiogenic factor-based, and (c) scaffold-based. In this review, we summarize state-of-the-art technologies that are used to develop complex, stable, and functional vasculature for engineered 3D tissue constructs and organs; additionally, we have suggested directions for future research.


Hyperglycemia-induced oxidative stress and heart disease-cardioprotective effects of rooibos flavonoids and phenylpyruvic acid-2-O-β-D-glucoside.
Diabetic patients are at an increased risk of developing heart failure when compared to their non-diabetic counter parts. Accumulative evidence suggests chronic hyperglycemia to be central in the development of myocardial infarction in these patients. At present, there are limited therapies aimed at specifically protecting the diabetic heart at risk from hyperglycemia-induced injury. Oxidative stress, through over production of free radical species, has been hypothesized to alter mitochondrial function and abnormally augment the activity of the NADPH oxidase enzyme system resulting in accelerated myocardial injury within a diabetic state. This has led to a dramatic increase in the exploration of plant-derived materials known to possess antioxidative properties. Several edible plants contain various natural constituents, including polyphenols that may counteract oxidative-induced tissue damage through their modulatory effects of intracellular signaling pathways. Rooibos, an indigenous South African plant, well-known for its use as herbal tea, is increasingly studied for its metabolic benefits. Prospective studies linking diet rich in polyphenols from rooibos to reduced diabetes associated cardiovascular complications have not been extensively assessed. Aspalathin, a flavonoid, and phenylpyruvic acid-2-O-β-D-glucoside, a phenolic precursor, are some of the major compounds found in rooibos that can ameliorate hyperglycemia-induced cardiomyocyte damage in vitro. While the latter has demonstrated potential to protect against cell apoptosis, the proposed mechanism of action of aspalathin is linked to its capacity to enhance the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression, an intracellular antioxidant response element. Thus, here we review literature on the potential cardioprotective properties of flavonoids and a phenylpropenoic acid found in rooibos against diabetes-induced oxidative injury.


Effect of Injection Overmolding Parameters on the Interface Bonding Strength of Hybrid Thermoset-Thermoplastic Composites.
In this study, the thermoset-thermoplastic structure was produced through a co-curing technique together with an injection overmolding technique. Continuous fiber reinforced thermoset composite (TSC) was selected as thermoset material, while polyamide 6 (PA 6) was chosen as thermoplastic material. The influence of injection temperature, preheating temperature and injection speed on the interfacial bonding strength of hybrid thermoset-thermoplastic composites was investigated. The results show that increasing injection temperature and preheating temperature have significant effects on the increase in bonding strength, while injection speed has little effect on it. In addition, the bonding strength of the co-cured interface is enhanced after the injection overmolding process, which is further studied through molecular dynamic (MD) simulation. The molecular dynamic simulation result shows that the high temperature and pressure during the injection process only have a weak effect on enhancing the bonding strength of the co-cured interface, while the chemical reaction at the co-cured interface is the main reason for the enhancement. Furthermore, the more chemical reactions occur at the interface, the stronger the interface will be.


Culture and diversity.
'Culture' is such a broad term; 'the sum total of ways of living built up by a group of human beings, which is transmitted from one generation to another'. Having lived in inner Melbourne and travelled extensively I felt I was fairly familiar with different cultures. I had a good working knowledge of different religious beliefs, had been to numerous cultural festivals, had friends of different sexual orientations, conversed comfortably with people from different occupational and socioeconomic groups, had a vague understanding of different national dress, and had eaten lots of fabulous food from many different countries and traditions.


Deletion of Wntless in myeloid cells exacerbates liver fibrosis and the ductular reaction in chronic liver injury.
Macrophages play critical roles in liver regeneration, fibrosis development and resolution. They are among the first responders to liver injury and are implicated in orchestrating the fibrogenic response via multiple mechanisms. Macrophages are also intimately associated with the activated hepatic progenitor cell (HPC) niche or ductular reaction that develops in parallel with fibrosis. Among the many macrophage-derived mediators implicated in liver disease progression, a key role for macrophage-derived Wnt proteins in driving pro-regenerative HPC activation towards a hepatocellular fate has been suggested. Wnt proteins, in general, however, have been associated with both pro- and anti-fibrogenic activities in the liver and other organs. We investigated the role of macrophage-derived Wnt proteins in fibrogenesis and HPC activation in murine models of chronic liver disease by conditionally deleting Wntless expression, which encodes a chaperone essential for Wnt protein secretion, in LysM-Cre-expressing myeloid cells (LysM-Wls mice). Fibrosis and HPC activation were exacerbated in LysM-Wls mice compared to littermate controls, in the absence of an apparent increase in myofibroblast activation or interstitial collagen mRNA expression, in both the TAA and CDE models of chronic liver disease. Increased Epcam mRNA levels paralleled the increased HPC activation and more mature ductular reactions, in LysM-Wls mice. Increased Epcam expression in LysM-Wls HPC was also observed, consistent with a more cholangiocytic phenotype. No differences in the mRNA expression levels of key pro-inflammatory and pro-fibrotic cytokines or the macrophage-derived HPC mitogen, Tweak, were observed. LysM-Wls mice exhibited increased expression of Timp1, encoding the key Mmp inhibitor Timp1 that blocks interstitial collagen degradation, and, in the TAA model, reduced expression of the anti-fibrotic matrix metalloproteinases, Mmp12 and Mmp13, suggesting a role for macrophage-derived Wnt proteins in restraining fibrogenesis during ongoing liver injury. In summary, these data suggest that macrophage-derived Wnt proteins possess anti-fibrogenic potential in chronic liver disease, which may be able to be manipulated for therapeutic benefit.


[Study of the activity of the nucleolus organizer segments in the chromosomes of normal, leukemic and neoplastic human cells by silver nitrate staining].
The application of a modified Ag-1 method for staining nucleolar organizer regions (NOR) in chromosomes has shown that the total number of AgNO3-stained NOR varies from 6 to 8 in cells of normal individuals as well as in the phytohemagglutinin (PHA) stimulated blood cells of patients suffering from acute leukemia (AL) and chronic myelocytic leukemia (CML). No AgNO3-stained NOR were detected either in non-PHA stimulated blood cells of AL or CML patients, apart from one case of a 48 hours blood culture without PHA from blast crisis CML, where 100 per cent mitotic cells displayed 3-6 AgNO3-stained chromosomes. In a Hela cell line with the modal number equal to 50 and the average number od acrocentrics being 9.3 per cell, the AgNO3-stained NOR numbered constantly 5. In tumor cells from pleural fluid of metastatic ovary tumor patient, with the modal number of cells varying from 50 to 160, the total number of AgNO3-stained NOR increased from 13 to 26 per metaphase. A hypothesis is forward to explain the negative Nor staining property in leukemia, according to which the activities of ribosomal cistrons (rDNA) in the miotic cells of relatively mature granulocytic and erythrocytic cells are either very much reduced or totally arrested.


The effect of action observation combined with high-definition transcranial direct current stimulation on motor performance in healthy adults: A randomized controlled trial.
Action observation (AO) can improve motor performance in humans, probably via the human mirror neuron system. In addition, there is some evidence that transcranial direct current stimulation (tDCS) can improve motor performance. However, it is yet to be determined whether AO combined with tDCS has an enhanced effect on motor performance. We investigated the effect of AO combined with high-definition tDCS (HD-tDCS) targeting the inferior parietal lobe (IPL) and inferior frontal gyrus (IFG), the main aggregates of the human mirror neuron system, on motor performance in healthy adults and compared the immediate vs. 24-h retention test effects (anodal electrodes were placed over these regions of interest). Sixty participants were randomly divided into three groups that received one of the following single-session interventions: (1) observation of a video clip that presented reaching movement sequences toward five lighted units + active HD-tDCS stimulation (AO + active HD-tDCS group); (2) observation of a video clip that presented the same reaching movement sequences + sham HD-tDCS stimulation (AO + sham HD-tDCS group); and (3) observation of a video clip that presented neutral movie while receiving sham stimulation (NM + sham HD-tDCS group). Subjects' reaching performance was tested before and immediately after each intervention and following 24 h. Subjects performed reaching movements toward units that were activated in the same order as the observed sequence during pretest, posttest, and retest. Occasionally, the sequence order was changed by beginning the sequence unexpectedly with a different activated unit. Outcome measures included mean Reaching Time and difference between the Reaching Time of the unexpected and expected reaching movements (Delta). In the posttest and retest, Reaching Time and Delta improved in the AO + sham HD-tDCS group compared to the NM + HD-sham tDCS group. In addition, at posttest, Delta improved in the AO + active HD-tDCS group compared to the NM + sham HD-tDCS group. It appears that combining a montage of active HD-tDCS, which targets the IPL and IFG, with AO interferes with the positive effects of AO alone on the performance of reaching movement sequences.


Intracardiac calcification is a marker of generalized atherosclerosis.
Aortic valve calcification (AVC) and carotid artery calcification (CAC) are considered to be markers of generalized atherosclerosis. However, the role of intracardiac calcification (ICC) (valvular and perivalvular calcification) is unclear. The objective of this retrospective study was to analyze the relationship between ICC and CAC, risk factors, and clinical atherosclerotic disease. Risk factors included age, sex, diabetes mellitus, hypercholesterolemia, and hypertension; clinical atherosclerosis comprised stroke, coronary artery disease, and peripheral artery disease. Between January 1, 2001, and January 1, 2004, all consecutive patients were enrolled into the study who underwent both carotid ultrasonography and transthoracic echocardiography examinations within 2 months. Patients with renal failure, substantial aortic stenosis, and carotid artery occlusion were excluded. There were 320 patients (104 men; mean +/- SEM age, 66.6 +/- 0.76 years). Positive results on carotid ultrasonography are defined as any CAC. Patients were categorized as having mild, moderate, or severe CAC. Positive results on transthoracic echocardiography were defined as any ICC; AVC was defined as mitral anulus calcification (MAC) or both. Intracardiac calcification was found in 181 patients, AVC in 51 patients, MAC in 48 patients, and calcification of both structures in 82 patients. Using multiple logistic regression analysis, ICC (odds ratio, 1.9), age (10-year periods) (odds ratio, 2.0), and the presence of peripheral artery disease (odds ratio, 1.7) were independent predictors of CAC. Carotid ultrasonography results were positive in 227 patients. For CAC, the sensitivities of AVC, MAC, both, and any ICC were 52.4%, 52.0%, 33.5%, and 71.2%, respectively, and the specificities were 84.9%, 87.1%, 92.5%, and 78.5%, respectively. The extension of ICC as 0, 1 location (AVC or MAC) , or 2 locations (AVC and MAC) was associated with the severity of CAC (P < .001, tau = 0.42). There was no difference between patients with AVC vs patients with MAC in the presence of different stages of CAC (P = .62). Intracardiac calcification (MAC or AVC) is an independent predictor of CAC as a marker of atherosclerosis, although the lack of ICC does not rule out atherosclerosis. Intracardiac calcification is related to CAC, with high specificity. The extension of ICC is related to the severity of atherosclerosis. Based on our results, antiatherothrombotic therapy should be considered in patients with ICC even before obtaining a positive carotid ultrasonography result.


Aurora B kinase cooperates with CENP-E to promote timely anaphase onset.
Error-free chromosome segregation requires that all chromosomes biorient on the mitotic spindle. The motor protein Centromere-associated protein E (CENP-E) facilitates chromosome congression by mediating the lateral sliding of sister chromatids along existing K-fibers, while the mitotic kinase Aurora B detaches kinetochore-microtubule interactions that are not bioriented. Whether these activities cooperate to promote efficient chromosome biorientation and timely anaphase onset is not known. We here show that the chromosomes that fail to congress after CENP-E depletion displayed high centromeric Aurora B kinase activity. This activity destabilized spindle pole proximal kinetochore-microtubule interactions resulting in a checkpoint-dependent mitotic delay that allowed CENP-E-independent chromosome congression, thus reducing chromosome segregation errors. This shows that Aurora B keeps the mitotic checkpoint active by destabilizing kinetochore fibers of polar chromosomes to permit chromosome congression in CENP-E-compromised cells and implies that this kinase normally prevents pole proximal syntelic attachments to allow CENP-E-mediated congression of mono-oriented chromosomes.


Carotenoid coloration in greenfinches is individually consistent irrespective of foraging ability.
Carotenoid-based plumage coloration of birds has been hypothesized to honestly reflect individual quality, either because carotenoids are difficult to acquire via food or because of a trade-off in allocation of carotenoids between maintenance and signaling functions. We tested whether differential foraging ability is a necessary precondition for maintaining individual differences in carotenoid-based plumage coloration in male greenfinches (Carduelis chloris). Wild-caught birds were brought into captivity, where half of them were supplemented with carotenoids while the other half was maintained on a carotenoid-poor diet. Color of the yellow parts of tail feathers, grown under natural conditions, was compared with that of the replacement feathers, grown in captivity. Carotenoid supplementation increased feather chroma (saturation). Color of wild-grown feathers significantly correlated with the color of lab-grown feathers. This result demonstrates the existence of a significant component of variation in carotenoid coloration, which reflects physiological qualities or genetic differences among individuals independent of foraging ability. Among both experimental groups, plasma carotenoid concentration during feather growth strongly correlated with chroma of the feathers grown in captivity. This indicates that carotenoid-based plumage coloration can reveal circulating carotenoid levels over a very wide range of concentrations, suggesting the ample signaling potential of such a mechanism.


Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase.
Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency. DBA is characterized by anemia, congenital anomalies, and cancer predisposition. Treatment for DBA is associated with significant morbidity. Here, we report the identification of Nemo-like kinase (NLK) as a potential target for DBA therapy. To identify new DBA targets, we screen for small molecules that increase erythroid expansion in mouse models of DBA. This screen identified a compound that inhibits NLK. Chemical and genetic inhibition of NLK increases erythroid expansion in mouse and human progenitors, including bone marrow cells from DBA patients. In DBA models and patient samples, aberrant NLK activation is initiated at the Megakaryocyte/Erythroid Progenitor (MEP) stage of differentiation and is not observed in non-erythroid hematopoietic lineages or healthy erythroblasts. We propose that NLK mediates aberrant erythropoiesis in DBA and is a potential target for therapy.


A novel adhesion molecule in human breast cancer cells: voltage-gated Na+ channel beta1 subunit.
Voltage-gated Na(+) channels (VGSCs), predominantly the 'neonatal' splice form of Na(v)1.5 (nNa(v)1.5), are upregulated in metastatic breast cancer (BCa) and potentiate metastatic cell behaviours. VGSCs comprise one pore-forming alpha subunit and one or more beta subunits. The latter modulate VGSC expression and gating, and can function as cell adhesion molecules of the immunoglobulin superfamily. The aims of this study were (1) to determine which beta subunits were expressed in weakly metastatic MCF-7 and strongly metastatic MDA-MB-231 human BCa cells, and (2) to investigate the possible role of beta subunits in adhesion and migration. In both cell lines, the beta subunit mRNA expression profile was SCN1B (encoding beta1)>>SCN4B (encoding beta4)>SCN2B (encoding beta2); SCN3B (encoding beta3) was not detected. MCF-7 cells had much higher levels of all beta subunit mRNAs than MDA-MB-231 cells, and beta1 mRNA was the most abundant. Similarly, beta1 protein was strongly expressed in MCF-7 and barely detectable in MDA-MB-231 cells. In MCF-7 cells transfected with siRNA targeting beta1, adhesion was reduced by 35%, while migration was increased by 121%. The increase in migration was reversed by tetrodotoxin (TTX). In addition, levels of nNa(v)1.5 mRNA and protein were increased following beta1 down-regulation. Stable expression of beta1 in MDA-MB-231 cells increased functional VGSC activity, process length and adhesion, and reduced lateral motility and proliferation. We conclude that beta1 is a novel cell adhesion molecule in BCa cells and can control VGSC (nNa(v)1.5) expression and, concomitantly, cellular migration.


First steps in exploring prospective exome sequencing of consanguineous couples.
Consanguinity is one of the most frequent risk factors for congenital disorders. In theory, prospective exome sequencing of consanguineous couples could identify couples who both are carriers of autosomal recessive diseases, and empower such couples to make informed reproductive decisions. To investigate this, we sent blood samples to our laboratory of four pairs of consanguineous parents having one or more children affected by an autosomal recessive disorder, without revealing any diagnostic information. The study was restricted to find identical, previously described, or evidently pathogenic mutations in both parents of each couple, in over 400 genes known to result in severe autosomal recessive disorders. Out of the six autosomal recessive disorders known to the four couples studied, two were correctly identified. Carrier status of one not previously known autosomal recessive disorder was discovered. As expected, given the pipeline used, large deletions, mutations in genes not present in the gene list, mutations outside the exons and consensus splice sites, and mutations that were not evidently pathogenic and previously not reported, were not identified. The restriction to detecting only couples with identical mutations diminishes the risk of revealing unsolicited findings and shortens the time needed for analysis, but also results in missing couples with different mutations in the same gene. In addition to the proposed pipeline, couples should be offered testing for carrier status of frequent disorders that can present themselves by large deletions, non-exonic mutations or compound heterozygous mutations (e.g. thalassemia, spinal muscular atrophy, cystic fibrosis). Even though sensitivity is reduced, offering exome sequencing prospectively will increase reproductive options for consanguineous couples.


Single-particle characterization of Aβ oligomers in solution.
Determining the pathological role of amyloids in amyloid-associated diseases will require a method for characterizing the dynamic distributions in size and shape of amyloid oligomers with high resolution. Here, we explored the potential of resistive-pulse sensing through lipid bilayer-coated nanopores to measure the size of individual amyloid-β oligomers directly in solution and without chemical modification. This method classified individual amyloid-β aggregates as spherical oligomers, protofibrils, or mature fibers and made it possible to account for the large heterogeneity of amyloid-β aggregate sizes. The approach revealed the distribution of protofibrillar lengths (12- to 155 -mer) as well as the average cross-sectional area of protofibrils and fibers.


Flavonoid and methoxyellagic acid sodium sulphates from Frankenia laevis L.
Two new flavonol di-sodium sulphates and an ellagic acid methyl ether mono-sodium sulphate have been found in the aqueous alcohol whole plant extract of Frankenia laevis L. They have been identified as the 3,7-di-sodium sulphate of kaempferol, the 3,7-di-sodium sulphates of quercetin and the 4'-mono-sodium sulphate of ellagic acid-3-methyl ether. Also, five known compounds have been isolated and characterized from the same extract. Establishment of all structures has been achieved mainly, by ESI-MS and NMR.


Evaluation of an emergency department observation ward.
To evaluate the usefulness of an observation or holding area in the operation of an emergency department, the 166 cases held in the observation area of the Harbor General Hospital Emergency Department during September, 1974, were reviewed. Among the 166 patients, who made up 2% of the 10,452 patients seen in the ED that month, drug overdose and alcohol withdrawal were the primary disorders admitted, 42 and 34 respectively. Neurological disorders were next with 29 cases. Fluids administered intravenously, analgesics and sedatives were the most common therapeutic modalities used. Psychiatric was the type of consultation required most often. Seventy-seven of the 166 patients went home; 61 were admitted to the hospital and none died. Fifteen were transferred to nursing homes, 8 to to detoxification centers and 5 to a mental hospital. The advantages and disadvantages of an observation ward are listed and discussed.


Dental restoration selection by students at southern Saudi Arabian universities.
Dental caries is a serious oral health concern and restoration of teeth is the main solution to this issue. Various restorative materials having different properties are used for posterior restoration. The aim of this study was to find that which factors can affect the choice of selection of material for posterior restoration among dental graduate students. For this purpose, a questionnaire was shared electronically among students of three different universities (King Khalid University, Jazan University, and Najran University). After collection, data were subjected to a chi-square test to check the significance. It has been observed that almost 50% of participants choose composite resin for posterior restoration. Results showed that according to most (more than 50%) of the dental students in Southern Saudi Arabia, different patient and tooth condition related factors can affect the choice for selection of restorative material.


Lymphocyte subpopulations of sheep in protective immunity to Taenia hydatigena.
Lymphocyte subpopulations entering the liver and surrounding the rejection sites during a 9-day period after infection of immune sheep with Taenia hydatigena were identified with the aid of monoclonal antibodies against lymphocyte cell surface markers. Viable lymphocytes were isolated from the liver tissue and stained by indirect immunofluorescence for subsequent flow cytometry analysis. Over the first 6 days after challenge infection a marked increase in the ratio of T-helper to T-suppressor/cytotoxic lymphocytes was observed. SBU-T19+ lymphocytes, a CD5+ T-cell subpopulation uniquely identified in the sheep, were present in small numbers in sheep liver both before and after infection. There was a large, continuous increase of sIg+ B-cells over the 9-day observation period after infection. Eosinophils were the predominant granulocytes in the liver of infected sheep. The exact location of the leucocyte subpopulations in respect to the rejection sites in infected liver was determined by in-situ immunoperoxidase staining of frozen liver sections. The evolution of the parasite-induced leucocyte response was characterized by the appearance of a central core of eosinophils surrounded by increasing numbers of CD4+ helper T-cells. CD8+ (suppressor/cytotoxic) and SBU-T19+ T-lymphocytes were present in much smaller numbers and by day 9 after infection were located predominantly around the periphery of the lesions. Distinct foci of tightly packed B-cells developed within the lesions and increased dramatically in size over the 9-day observation period. At this time, lesions appeared as compact aggregations of leucocytes encircled by a second band of eosinophils. Both T- and B-lymphocytes within the lesions stained positive for class II major histocompatibility antigens.


New Forms of Electrospun Nanofibers Applied in Cardiovascular Field.
Cardiovascular disease (CVD) is one of the leading causes of death worldwide. In recent years, regenerative medicine, tissue engineering and the development of new materials have become the focus of attention this field, and electrospinning technology to prepare nanofibrous materials for the treatment of cardiovascular diseases has attracted people's attention. Unlike previous reviews, this research enumerates the experimental methods and applications of electrospinning technology combined with nanofibrous materials in the directions of myocardial infarction repair, artificial heart valves, artificial blood vessels and cardiovascular patches from the perspective of cardiovascular surgery. In the end, this review also summarizes the limitations, unresolved technical challenges, and possible future directions of this technology for cardiovascular disease applications.


Contribution of the gasoline distribution cycle to volatile organic compound emissions in the metropolitan area of Mexico City.
Gasoline distribution in the metropolitan area of Mexico City (MAMC) represents an area of opportunity for the abatement of volatile organic compound (VOC) emissions. The gasoline distribution in this huge urban center encompasses several operations: (1) storage in bulk and distribution plants, (2) transportation to gasoline service stations, (3) unloading at service stations' underground tanks, and (4) gasoline dispensing. In this study, hydrocarbon (HC) emissions resulting from breathing losses in closed reservoirs, leakage, and spillage from the operations just listed were calculated using both field measurements and reported emission factors. The results show that the contribution of volatile HC emissions due to storage, distribution, and sales of gasoline is 6651 t/year, approximately 13 times higher than previously reported values. Tank truck transportation results in 53.9% of the gasoline emissions, and 31.5% of emissions are generated when loading the tank trucks. The high concentration of emissions in the gasoline transportation and loading operations by tank trucks has been ascribed to (1) highly frequent trips from distribution plant to gasoline stations, and vice versa, to cope with excessive gasoline sales per gasoline station; (2) low leakproofness of tank trucks; and (3) poor training of employees. In addition, the contribution to HC evaporative and exhaust emissions from the vehicles of the MAMC was also evaluated.


Associations of the Novel Polymorphisms of Periostin and Platelet-Derived Growth Factor Receptor-Like Genes with Egg Production Traits in Local Chinese Dagu Hens.
The periostin (POSTN) and platelet-derived growth factor receptor-like (PDGFRL) genes are implicated in regulation of hen ovarian development. In the present study, these genes were explored as possible molecular markers associated with egg production, egg weight and body weight in Chinese Dagu hens. Samples were analyzed using the PCR-single strand conformation polymorphism (PCR-SSCP) method, followed by sequencing analysis, and three novel single nucleotide polymorphisms (SNPs) were identified within the candidate genes. Among them, an A/T transversion at base position 2727 in intron 2 of POSTN gene was found to be polymorphic and named SNP A2727T; and two transitions, G/A at position 6761 and A/G at base 6839 in exon 2 of PDGFRL gene were detected and named SNPs G6761A and A6839G, respectively. For the SNP A2727T, a total of 360 Dagu hens were classified as AA and AB genotypes, allele A was found present at a higher frequency. Moreover, the AA genotype was significantly correlated with higher hen-housed egg production (HHEP) at 43, 57, and 66 weeks (wks) of age and with a higher egg weight (EW) at 30 wks (P < 0.05). For the two linked SNPs (G6761A and A6839G) in the PDGFRL fragment, the hens were typed into TT, TC and CC genotypes, with the T allele shown to be dominant. The TT genotype was correlated with higher HHEP at 57 and 66 wks of age; genotype CC associated with the highest body weight and EW at 30 and 43 wks (P < 0.05), while it was correlated with the lowest HHEP at 57 and 66 wks of age (P < 0.05). Furthermore, five haplotypes were reconstructed based on these SNPs, with the AATT haplotype associated with the highest HHEP at 43 to 66 wks of age and higher EW at 30 wks (P < 0.05). Collectively, these SNPs identified in this study might be used as a potential molecular marker favorable to genetic improvement of egg productivity in chicken breeding.


Amikacin levels in the human biliary tract.
The concentrations of amikacin in serum, gallbladder, and common duct bile, and gallbladder tissue in patients undergoing surgery of the biliary tract were investigated. Patients received 500 mg amikacin intravenously or intramuscularly from 1 to 11 hours before surgery. Another group had T-tubes inserted and blood and bile levels were studied serially postoperatively. One half hour after 500 mg amikacin, serum levels were high and bile levels were 30 per cent of the serum levels, with tissue levels less than 19 per cent of the serum levels. At 6 hours, serum levels were 37 per cent of the 1-hour levels; however, bile levels were 34 per cent of the simultaneous serum levels. At 11 hours, both postdose serum and bile amikacin levels were low. However, simultaneous bile levels were higher than serum levels. No patient suffered from any side effects from amikacin.


[Chronic mucocutaneous candidiasis].
Chronic mucocutaneous candidiasis is a chronic infection of mucoses, nails and skin due to Candida sp., that does not respond to standard treatment. We report on three patients with chronic mucocutaneous candidiasis in association with iron deficiency, IgA deficiency in one patient and adult onset in another. We review the clinical manifestations, the classification and the treatment of this disorder. The immunologic defects associated with chronic mucocutaneous candidiasis provide a model to study the mechanisms of defense of the host against fungal infections.


Factors affecting reproducibility of numerical classifications.
Results obtained with reference organisms which had been included in each of three different investigations were compared. Positions of the reference organisms in diagrams based on highest-link numerical groupings varied with the composition of the microbial samples studied, but significant correlations were found between the results of different investigations. Correlations between the overall groupings obtained in different studies were often better than the correlations between actual similarity values computed between specific pairs of organisms. Similarity values based on different sets of features showed significant correlations, regardless of the kinds of features involved or of the number of features (above a minimum of about 40). Correlations between values based on totally different features were nearly as good as those between values based on similar features which had been determined by different investigators.


Novel RNA regulatory mechanisms revealed in the epitranscriptome.
Methyl-6-adenosine (m (6)A) has been hypothesized to exist since the 1970s, (1) but little has been known about the specific RNAs, or sites within them, that are affected by this RNA modification. Here, we report that recent work has shown RNA modifications like m (6)A, collectively called the "epitranscriptome," are a pervasive feature of mammalian cells and likely play a role in development and disease. An enrichment of m (6)A near the last CDS of thousands of genes has implicated m (6)A in transcript processing, translational regulation and potentially a mechanism for regulating miRNA maturation. Also, because the sites of m (6)A show strong evolutionary conservation and have been replicated in nearly identical sites between mouse and human, strong evolutionary pressures are likely being maintained for this mark. (2)(,) (3) Finally, we note that m (6)A is one of over 100 modifications of RNA that have been reported, (4) and with the combination of high-throughput, next-generation sequencing (NGS) techniques, immunoprecipitation with appropriate antibodies and splicing-aware peak-finding, the dynamics of the epitranscriptome can now be mapped and characterized to discern their specific cellular roles.


Pharmacological treatment of personality disorders.
Therapists are only now just beginning to clear a way through the jungle of personality disorder and any recommendations about drug treatment have to be tentative and, to some extent, speculative. Nevertheless, it is reasonable to conclude that drug treatment, mainly in the form of antipsychotic agents, should be considered in borderline and antisocial personality disorders and also possibly in the schizotypal group. There is also growing evidence that two drugs used in the treatment of manic-depressive psychosis, lithium and carbamazepine, may have independent effects in controlling aggression and impulsiveness and be of value of borderline and antisocial personality disorders. In histrionic and dependent personality disorders, drug treatment is in general contraindicated and for the remaining group our ignorance of the possible benefit of the drugs is almost total. However, the negative effect of these personality disorders on response to treatment in the presence of depression, anxiety, and other abnormal mental state disorders suggests that drug treatment probably has little part to play in management of these particular personality disorders. A major deficiency in our knowledge, which can only be remedied by long-term studies that are extremely difficult to mount, is the recommended duration of treatment with drugs in personality disorder. No guidelines exist at present but now that some measure of efficacy has been established duration of treatment needs to be addressed.


Coronary atherosclerosis in subjects with mitral stenosis.
The coronary arteries were examined in 60 specimens from patients with mitral stenosis. In three, localized obstruction was nonatherosclerotic in nature (in one, arterial dysplasia; in two, embolic). In 18 of the remaining 57 cases (31.5%), significantly obstructive atherosclerosis in one or more segments of the coronary arterial system was found. This represented 46% of the males and 27% of the females. The incidence of involvement of three or more arteries by significantly obstructive atherosclerosis was 39%, while in a cited series of subjects with angina pectoris three or more vessels were involved in 79% of the cases. It may be concluded that, on the average, the distribution of lesions in patients with mitral stenosis and significant coronary atherosclerosis is less wide than in subjects with clinical coronary disease.


Distribution of FFRCT in single obstructive coronary stenosis and predictors for major adverse cardiac events: a propensity score matching study.
Fractional flow reserve derived from computed tomography (FFRCT) has been demonstrated to improve identification of lesion-specific ischemia significantly compared with coronary computed tomography angiography (CCTA). It remains unclear whether the distribution of FFRCT values in obstructive stenosis between patients who received percutaneous coronary intervention (PCI) or not in routine clinical practice, as well as its association with clinical outcome. This study aims to reveal the distribution of FFRCT value in patients with single obstructive coronary artery stenosis and explored the independent factors for predicting major adverse cardiac events (MACE). This was a retrospective study of adults with non-ST-segment elevation acute coronary syndrome undergoing FFRCT assessment by using CCTA data from January 1, 2016 to December 31, 2020. Propensity score matching (PSM) method was used to account for patient selection bias. The risk factors for predicting MACE were evaluated by a Cox proportional hazards regression analysis. Overall, 655 patients with single obstructive (≥ 50%) stenosis shown on CCTA were enrolled and divided into PCI group (279 cases) and conservative group (376 cases) according to treatment strategy. The PSM cohort analysis demonstrated that the difference in history of unstable angina, Canadian Cardiovascular Society Class (CCSC) and FFRCT between PCI group (188 cases) and conservative group (315 cases) was statistically significant, with all P values < 0.05, while the median follow-up time between them was not statistically significant (24 months vs. 22.5 months, P = 0.912). The incidence of MACE in PCI group and conservative group were 14.9% (28/188) and 23.5% (74/315) respectively, P = 0.020. Multivariate analysis of Cox proportional hazards regression revealed that history of unstable angina (adjusted odds ratio (adjOR), 3.165; 95% confidence interval (CI), 2.087-4.800; P < 0.001), FFRCT ≤ 0.8 (OR, 1.632;95% CI 1.095-2.431; P = 0.016), and PCI therapy (OR 0.481; 95% CI 0.305-0.758) were the independent factors for MACE. History of unstable angina and FFRCT value of ≤ 0.8 were the independent risk factors for MACE, while PCI therapy was the independent protective factor for MACE.


[Diagnostic techniques in breast cancer detection. Part III. The new cytobiological methods].
This publication contains an overview of the cyto-biological technologies utilized in breast cancer diagnosis. It refers to technologies created de novo and heralded as a breakthrough ones, as well as to those existing for years. An integration of new diagnostic biogenetic methods, with imaging techniques such as mammography, have become essential in order to cope with the requirements of early detection of breast tumours. Apart from the new and innovative diagnostic techniques, this publication also presents an outline of recommendations for genetic diagnostics as well as cooperative and multidisciplinary integrative activities, which are prerequisites for successful diagnosis and treatment and, consequently, longer survival periods upon which patients rely.


Discrepancy between ultrasound and oral cholecystography in the assessment of gallstone dissolution.
The Sunnybrook Medical Centre Gallstone Study is a randomized, controlled, double-blind study of chenodeoxycholic acid for dissolution of radiolucent gallstones. Of the first 22 patients whose stones were apparently totally dissolved on oral cholecystography, seven were found to have residual small stone fragments on ultrasound examination of the gallbladder. Continuing chenotherapy was unsuccessful in dissolving these fragments. The possibility that the residual stones represent insoluble nuclei of the original calculi must be considered. Responses to choleitholytic therapy and subsequent stone recurrences need to be reevaluated using ultrasound.


Innovative Programs with Multi-Service Integration for Children and Youth with High Functional Health Needs.
The integration of care services and providers across the health-social-community continuum has helped improve the lives of many children and youth living with complex health conditions. Using environmental scan data, 16 promising multi-service programs were selected and analyzed qualitatively through a deliberative conversation approach. Descriptive data of analyzed programs are presented, as well as the thematic analysis results. An important program strength is its clear founding principles and engagement of patients and families. However, the scale-up of these initiatives remains a challenge unless such programs can be better financed and supported.


Methicillin-resistant Staphylococcus aureus and Candida albicans on denture surfaces.
Infectious diseases caused by methicillin-resistant Staphylococcus aureus, MRSA, and Candida albicans are often serious in compromised hosts. We enumerated MRSA and C. albicans on denture surfaces and in saliva samples from 29 adults. Staphylococcus species, MRSA, and methicillin-resistant Staphylococcus epidermidis, MRSE, were detected on 17, 3, and 1 of the 29 denture surfaces, respectively. C. albicans were detected on 22 denture surfaces. All saliva samples from patients whose dentures carried Staphylococcus species and C. albicans were also found to contain both microorganisms. Adherence of isolated 3H labeled cells of MRSA and C. albicans to resin beads and saliva-coated resin beads was examined. Cells of both microorganisms adhered in significantly higher numbers to saliva-coated resin beads than to resin beads. The hydrophobicity of the MRSA isolated from denture surfaces varied from strain to strain; that of C. albicans strains was moderately high. The zeta potentials of MRSA isolates and of C. albicans isolates determined in KCI buffer were significantly low. The potential of the resin beads decreased after treatment with saliva. Two out of 5 MRSA strains were found to be inhibited in growth by oral Streptococcus, Actinomyces, and gram-negative bacterial strains, suggesting that some oral bacterial species play a role in inhibiting the colonization of Staphylococcus species. No isolates of C. albicans were inhibited in their growth by any of the oral bacteria tested. Isolates of MRSA and C. albicans coaggregated with Porphyromonas gingivalis and Fusobacterium nucleatum strains. Using denture cleaners every night for 2 weeks did not reduce numbers of Staphylococcus species or C. albicans organisms in saliva.


Retrograde type A aortic dissection: a different evil.
Retrograde type A aortic dissection (RTAAD) can be spontaneous or secondary to the instrumentation of the descending and thoraco-abdominal aorta. It has anatomical differences compared to antegrade type A aortic dissection that impact the management and prognosis. Treatment is not standardized. We report our approach to spontaneous RTAAD in our institution between 2018 and 2022 (n = 15). The mean age was 60.1 years and 93% were male. Aortic valve, coronary arteries and supra-aortic trunks were spared by the dissection in 80% of the cases; distal extension to iliacs was common and lower limb malperfusion was present in 4 cases (27%). The ascending aorta was dilated at presentation in 60% of the cases. Emergency surgery with arch/FET replacement was offered to 11 patients (73%); 3 patients (20%) received a limited proximal aortic repair; 1 patient was treated conservatively. Overall mortality was 47% (100% for limited proximal repair and 22% for those who received arch/FET). We advocate for aggressive treatment of RTAAD excluding the primary entry tear to prevent immediate- and mid-term complications.


Diltiazem treatment prevents diastolic heart failure in mice with familial hypertrophic cardiomyopathy.
The cardiac troponin T I79N mutation, linked to familial hypertrophic cardiomyopathy, carries a high risk of sudden cardiac death even in the absence of significant cardiac hypertrophy. The pathology underlying this mechanism has not yet been identified. To study the underlying mechanism of this phenomenon we characterized the left ventricular (LV) performance of transgenic mice carrying the human troponin T mutation I79N under basal and isoproterenol-induced stress conditions. LV function was analyzed by recording pressure-volume loops using a microconductance catheter. Despite a hypercontractile systolic function under basal conditions TnT-I79N mice showed a diastolic dysfunction indicated by an increase in end-diastolic pressure-volume relationship (EDPVR), a load-independent factor of LV stiffness (0.06+/-0.01 vs. 0.02+/-0.01; P<0.05), when compared to mice expressing human wild-type troponin T (TnT-WT). TnT-I79N mutants developed severe diastolic heart failure and cardiac sudden death under isoproterenol stress. This was prevented after pretreatment with the L-type Ca2+ channel inhibitor diltiazem. Diastolic dysfunction due to increased LV stiffness in TnT-I79N mice leads to severe primary diastolic heart failure and finally to cardiac sudden death, which can be prevented by diltiazem.