Hyperacute relapse of Lewis-Sumner syndrome during influenza A (H1N1) virus infection.
Lewis-Sumner Syndrome (LSS) is considered an asymmetric sensory-motor variant of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), mostly affecting the limbs distally, with electrophysiological evidence of multifocal motor conduction blocks. Cranial nerve involvement is present in a minority. Various well-known infectious agents, directly or via the host's immune responses, may trigger or exacerbate acute and chronic peripheral neuropathies, which may manifest clinically through a multitude of signs and symptoms. We present the case of a 57-year-old male with Lewis-Sumner Syndrome, whose clinical course was quite stable over many years. He developed severe hyperacute relapse of his neuropathic disease in the context of active pneumonia due to influenza A (H1N1) virus infection. During this exacerbation, besides the obvious worsening of the previous asymmetric limb involvement, the patient also manifested left peripheral facial palsy and dysphagia that rapidly evolved over minutes, mimicking a stroke. The patient also showed rapid recovery, with marked improvement of the acute neuropathic dysfunction, immediately after initiation of treatment with oseltamivir. Our hypothesis is that the direct modulation of Na + ion channel activity in the host's peripheral nerve cell by H1N1 viral proteins could cause acute and potentially reversible dysfunction in the conduction of nerve action potentials. Direct viral neuritis could also have been the cause. Immunomodulatory agents, namely IVIg, were not administered due to the swift clinical improvement noticed in the following days. We aim to raise awareness of the possibility of atypical neurological presentations of viral infections, especially relevant in the context of the pandemic the world is now facing.


Knowledge of, attitudes towards, and willingness to care for sex workers: Differences between general and mental health nursing students.
It is not common in most nursing education programmes to teach students how to care for sex workers. Little is known about whether nursing students are prepared to care for sex workers upon graduation. This study aims to explore and compare students in the general and mental health nursing programmes in Hong Kong in terms of their knowledge of, support for the human rights of sex workers; attitudes towards, and willingness to care for sex workers. This study also aims to explore the factors associated with attitudes towards and willingness to care for sex workers among all nursing students, general nursing students, and mental health nursing students. A cross-sectional study. Undergraduate nursing students were invited to participate in an online survey in 2019. A total of 317 students completed the questionnaire. The students had little knowledge of sex workers, and their attitudes were polarized. Their attitudes towards sex workers and their support for the human rights of sex workers were significantly associated with their willingness to care for sex workers. A perceived need for education relating to caring for sex workers was positively associated with attitudes towards sex workers and a willingness to care for them. Final year students had a more positive attitude towards sex workers than first-year students. The study may contribute to the development of a nursing curriculum for the promotion of non-judgmental care for sex workers or disadvantaged client groups.


Protein Analyte Sensing with an Outer Membrane Protein G (OmpG) Nanopore.
Nanopore sensing is a powerful lab-on-a-chip technique that allows for the analysis of biomarkers present in small sample sizes. In general, nanopore clogging and low detection accuracy arise when the sample becomes more and more complex such as in blood or lysate. To address this, we developed an OmpG nanopore that distinguishes among not only different proteins in a mixture but also protein homologs. Here, we describe this OmpG-based nanopore system that specifically analyzes targets biomarkers in complex mixtures.


Stomata facilitate foliar sorption of silver nanoparticles by Arabidopsis thaliana.
Application of nanopesticides may substantially increase surface attachment and internalization of engineered nanoparticles (ENPs) in food crops. This study investigated the role of stomata in the internalization of silver nanoparticles (Ag NPs) using abscisic acid (ABA)-responsive ecotypes (Ler and Col-7) and ABA-insensitive mutants (ost1-2 and scord7) of Arabidopsis thaliana in batch sorption experiments, in combination with microscopic visualization. Compared with those of the ABA-free control, stomatal apertures were significantly smaller for the Ler and Col-7 ecotypes (p ˂ 0.05) but remained unchanged for the ost1-2 and scord7 mutants, after exposure to 10 μM ABA for 1 h. Generally Ag NP sorption to the leaves of the Ler and Col-7 ecotypes treated with 10 μM ABA was lower than that in the ABA-free control, mainly due to ABA-induced stomatal closure. The difference in Ag NP sorption with and without ABA was less pronounced for Col-7 than for Ler, suggesting different sorption behaviors between these two ecotypes. In contrast, there was no significant difference in foliar sorption of Ag NPs by the ost1-2 and scord7 mutants with and without ABA treatment. Ag NPs were widely attached to the Arabidopsis leaf surface, and found at cell membrane, cytoplasm, and plasmodesmata, as revealed by scanning electron microscopy and transmission electron microscopy, respectively. These results highlight the important role of stomata in the internationalization of ENPs in plants and may have broad implications in foliar application of nanopesticides and minimizing contamination of food crops by ENPs.


[Features of heart rate, blood pressure, heart rate variability and cerebral blood flow during sequential head-up tilt test].
To investigate the features of BP, HR, cerebral blood flow (CBF) and heart rate variation (HRV) during sequential head-up tilt table test (HUT) and provide information for methodology of testing tendency to syncope in pilots. Sixteen healthy male were exposed to HUT +45 degrees 20 min, +60 degrees 20 min, and +75 degrees 20 min respectively with 5 min rests in between. CBFV, HR, HRV, BP were measured with transcranial doppler image (TCI), 12-Lead in phase ECG. 1) As the tilt angle became larger, HR and DBP increased gradually (P<0.05), with SBP, PP and CBF Velocity (Vs,Vm,Vd) descended. There were significant differences among the various conditions. CV became smaller before +75 degrees, and then it began to increase. 2) Correlation between physiological indices and techno-indices were analyzed. At the point of 1 min, tilt angle was significantly positively correlated with SBP, DBP, MAP, Vd, and sdRR (P<0.01); At the point of 20 min, tilt angle was significantly positively correlated with HR and sdRR (P<0.01), but negatively correlated with SBP, PP, Vs and mRR (P<0.01), time of exposure was positively correlated with HP (P< 0.01), but negatively correlated with Vm, Vd, and mRR (P<0.01). 3) Correlation among physiological indices were also analyzed. HR were negatively correlated with SBP, Vs, Vm and Vd (P<0.01), SBP were significantly positively correlated with Vd, and mRR (P<0.01). Vs, Vm, Vd were significantly positively correlated with mRR and sdRR (P< 0.01). By investigating HR, BP, HRV and CBFV during of different angles, some advises for evaluating the tendency to syncope in pilots were put forward.


Intermixing of dipalmitoylphosphatidylcholine with phospho- and sphingolipids bearing highly asymmetric hydrocarbon chains.
We have used high-sensitivity differential scanning calorimetry to investigate the mixing of dipalmitoylphosphatidylcholine (DPPC) with N-lignoceroylgalactocerebroside, N-lignoceroylsulfogalactocerebroside and 1-lauroyl-2-lignoceroylphosphatidylcholine. These three lignoceroyl species, whose two hydrocarbon chains are quite discrepant in length, are completely miscible with DPPC in the liquid-crystalline state. Mixtures of all three lignoceroyl lipids with DPPC show phase separation in the gel state, which is observed over a limited range of compositions (from less than 10 mol% to just over 40 mol% sulfatide) in the case of N-lignoceroylsulfatide and over a wide range of compositions in the cases of N-lignoceroylcerebroside (less than 10 mol% to greater than 90 mol% cerebroside) and 1-lauroyl-2-lignoceroyl-PC (roughly 10 mol% to 90 mol% lauroyl/lignoceroyl PC). The extensive solid-solid phase separation observed in mixtures of DPPC and 1-lauroyl-2-lignoceroyl-PC, which show eutectic behavior, is somewhat unexpected given the similar transition temperatures of the two components but appears to reflect the ability of the lignoceroyl species to form an interdigitated gel phase. However, we find no evidence that the N-lignoceroylsphingolipids are markedly more prone to segregate laterally in PC-rich bilayers than are previously studied sphingolipid species with shorter N-acyl chains. We suggest on the basis of these results that the primary biological importance of the very long N-acyl chains found in many sphingolipids may lie in some function other than the promotion of lateral segregation of sphingolipid-enriched domains in biological membranes.


Transcriptional activation of the urokinase receptor gene by endothelin-1.
Using an immortalized human glomerular epithelial cell line (E71 A1), we studied the effect of endothelin-1 (ET-1), a potent vasoconstrictor peptide, on the synthesis of urokinase type plasminogen activator (u-PA) and its receptor (u-PAR). The results show that ET-1 had no effect on u-PA synthesis but induced an increase in u-PAR number (2.8 +/- 0.6 x 10(4) vs 1.2 +/- 0.5 x 10(4) sites per cell, p less than 0.001) without change in receptor affinity (280 +/- 80 pM vs 250 +/- 50 pM, NS), maximal effect being observed at 10(-7) M. Time course shows that a plateau was reached after a 24 hour incubation. ET-1 induced-increase in binding capacity was abolished by cycloheximide. ET-1 also induced an increase in u-PAR mRNA level, which was completely blocked by alpha-amanitin (5 micrograms/ml). Cycloheximide (1 microgram/ml) alone induced an increase in u-PAR mRNA level and this effect was enhanced when cycloheximide was combined with ET-1. Our data show that ET-1 can induce an increase in membrane expression of u-PAR through activation of the transcription of the u-PAR gene and de novo protein synthesis.


Implantable defibrillators for high-risk patients with heart failure who are awaiting cardiac transplantation.
The objective of this study was to assess the operative risk and efficacy of implantable defibrillators for preventing sudden death in patients with heart failure awaiting transplantation. The average waiting time for elective cardiac transplantation is 6 months to 1 year. Sudden cardiac death is the major source of mortality in outpatients in stable condition awaiting cardiac transplantation. The efficacy of implantable defibrillator therapy in this population is not established. We analyzed the operative risk, time to appropriate shock, and sudden death in 15 patients determined to be at high risk of sudden death who were accepted onto the outpatient cardiac transplant waiting list. Nonfatal postoperative complications occurred in two (13%) subjects with epicardial defibrillating lead systems and in none with transvenous lead systems. Defibrillation energies were 16 +/- 2 J versus 24 +/- 2 J with epicardial and transvenous lead systems, respectively. Sudden death free survival until transplantation was 93%. Most of the patients (60%) had an appropriate shock during a mean follow-up of 11 +/- 12 months. The mean time to an appropriate shock was 3 +/- 3 months. Hospital readmission was required in three (20%) subjects to await transplantation on an urgent basis. However, two of these subjects had received appropriate shocks before readmission. In selected patients at high risk for sudden death while on the outpatient cardiac transplant waiting list, the operative risk is low and adequate defibrillation energies can be obtained to allow implantable defibrillator placement. Most subjects will have an appropriate shock as outpatients before transplantation, and sudden death free survival is excellent.(ABSTRACT TRUNCATED AT 250 WORDS)


Leishmania donovani in blood smears of asymptomatic persons.
Leishmania amastigotes have been detected in the peripheral blood smears of Indian kala-azar patients mostly during night. It was, therefore, thought worthwhile to find out whether such amastigotes could be shown in healthy subjects who did not have any symptoms by history or signs on clinical examination. Leishmania-stained blood smears of 450 asymptomatic healthy individuals residing in an endemic village in Bihar (India) were examined by oil-immersion microscopy for the detection of amastigote, six people (1.3%) showed the presence of Leishmania amastigotes. Given the low sensitivity of a single smear examination it is likely that a much greater proportion of asymptomatic persons had parasitemia than the observed 1.3%. This finding is important from the point of view of transmission of disease, as also for modifying the current control measures.


Molecular analysis of genetically determined target organ abnormalities in spontaneous autoimmune thyroiditis.
We have shown in earlier studies, that the development of spontaneous autoimmune thyroiditis (SAT) in chickens of the Obese strain (OS) depends on the presence of both, two dominant genes coding for an altered immune regulation and one recessive gene responsible for the susceptibility of the target organ for the autoimmune attack. The product(s) of the latter is (are) still not known. The present study was aimed at identifying possible candidates of cellular components of the thyroid gland of OS chicken and its SAT susceptible parental Cornell C-strain (CS) by high resolution 2-dimensional (2D) gel electrophoresis. For this purpose organ cultures of the thyroid, bursa, thymus and liver were established and the synthesized polypeptides were labelled by 35S-methionine. OS and CS organs were compared with those of healthy normal White Leghorn (NWL) controls. The autoradiographs of the 2D-gels obtained from individual samples after various labelling periods were subjected to comparative analysis. We have found both quantitative and qualitative differences of polypeptide spots between OS/CS and NWL organ samples, some of them specific for the thyroid gland. Although one has to be aware that in this multidimensional analytical approach numerous, still elusive pattern differences are revealed, the thyroid specific phenomena will be further scrutinized.


Chronic effects of nitrendipine on renal hemodynamics and tubular transport.
The effects of nitrendipine (10 mg, during acute clearance experiments) given both acutely and after 2 weeks of administration were examined in normal and hypertensive subjects. At the initiation of therapy, nitrendipine caused an increase in glomerular filtration rate and effective renal plasma flow in the hypertensive, but not in the normal, group. Percentage excretion rates of sodium (%ENa) and phosphate (%EPi) and free water clearance (CW) increased in both groups at the initiation of therapy. After 2 weeks of nitrendipine therapy repeat acute clearance studies showed that the drug no longer increased glomerular filtration rate or effective renal plasma flow in hypertensive subjects, the increases in %ENa and CW persisted in normal subjects and trended upward in hypertensive subjects, and the increase in %EPi persisted in both normal and hypertensive individuals. We conclude that nitrendipine is not sodium retentive after chronic therapy and the acute increase in %ENa, %EPi, and CW after its initial administration suggests a proximal tubular effect.


A case of cardiac tamponade following esophageal resection.
We report a rare case of cardiac tamponade after esophageal resection for esophageal cancer. A 69-year-old man underwent subtotal esophagectomy and reconstruction of the gastric tube with cervical anastomosis via the poststernal route and three-field lymphadectomy via a median sternotomy. On postoperative day 4, the patient developed dyspnea, chest oppression, and hemodynamic instability due to cardiac tamponade. Emergency percutaneous catheter drainage was performed to manage the cardiac tamponade. Acute pericarditis due to the original surgical procedure was suspected to be the cause of the tamponade. Although rare, cardiac tamponade should be considered as a cause of hemodynamic instability after esophageal resection.


Antimicrobial resistance in Salmonella enterica serovars Enteritidis and Typhimurium isolated from animals in Korea: comparison of phenotypic and genotypic resistance characterization.
Fourteen and 22 each of Salmonella Enteritidis and Salmonella Typhimurium (S. Typhimurium) were isolated from animals from 1983 to 1999 in Korea and tested for their antibiotic resistance patterns, phage types and resistance gene patterns. S. Typhimurium isolates were highly resistant to streptomycin, sulfisoxazole and tetracycline, 95, 95 and 86%, respectively. The incidence of multiple antibiotic resistance (resistant to more than two drugs tested) of S. Typhimurium isolates was extremely high (100%) comparing to S. Enteritidis isolates (21%). Two of the five ACSSuT (ampicillin, chloramphenicol, streptomycin, sulfisoxazole and tetracycline) resistant type S. Typhimurium isolates were phage type definitive type 104 (DT104). For the detection of resistance related genes in S. Enteritidis and S. Typhimurium isolates, particularly ACSSuT type S. Typhimurium, antibiotic resistance genes, cmlA/tetR, bla(PSE-1) and bla(TEM), and genus Salmonella specific gene, sipB/C, were amplified using four pairs of primers in a hot-start multiplex polymerase chain reaction (PCR). Two Korean isolates of S. Typhimurium DT104 showed bla(TEM) amplicons instead of bla(PSE-1) for the ampicillin resistance and they were susceptible to florfenicol. The multiplex PCR used in this study was useful in characterization of multiple drug resistant Salmonella isolates, especially ACSSuT type S. Typhimurium, and identification of beta-lactamase gene distribution among Salmonella isolates.


TGF-Β1 & PNPLA3 Genetic Variants and the Risk of Hepatic Fibrosis and HCC in Egyptian Patients with HCV-Related Liver Cirrhosis.
The clinical outcomes of hepatitis C virus (HCV) infection and its sequelae including liver cirrhosis and hepatocellular carcinoma (HCC) are greatly affected by host genetic factors; however, the possible mechanisms are still largely unclear. This work aimed to assess transforming growth factor-β1 (TGF-β1), and patatin-like phospholipase domain containing-protein 3 (PNPLA3) genetic variants as risk factors for hepatic fibrosis and hepatocellular carcinoma (HCC) in Egyptian patients with HCV-related liver cirrhosis. Seventy HCV-related liver cirrhosis patients (Total cirrhosis) who were divided into two groups; 34 patients with HCC (HCC group), and 36 patients without HCC (LC group) and 20 healthy volunteers (control group) were included. Routine laboratory investigations and imaging studies were determined. TGF-β1 (Arg25Pro; 915G>C) and PNPLA3 (I148M; C>G) variants were evaluated using real-time polymerase chain reaction (real-time PCR). HCC group showed a significantly higher GG genotype distribution of TGF-β1 (Arg25Pro) than the LC group (P= 0.008, OR: 7.083, CI 95%: 1.422 - 35.282). The distributions of GG genotype (P= 0.047) and G allele (P= 0.002, OR: 4.395, CI 95%: 1.622 - 11.911) of PNPLA3 (I148M) were significantly higher in total cirrhosis patients than controls. TGF-β1 (Arg25Pro) GG variant may be associated with HCC risk in HCV-related liver cirrhosis patients, while PNPLA3 (I148M) GG variant may be associated with cirrhosis development but not HCC risk in HCV-related liver cirrhosis patients.


Electrocardiographic abnormalities in patients with organic erectile dysfunction: comparison with an age-matched control group.
Our purpose was to determine the incidence of electrocardiographic (ECG) abnormalities in patients with organic erectile dysfunction (ED) and to compare the results with an age-matched control (potent) group. A total of 218 men with ED of organic etiology formed our study group. A total of 210 age-matched men who had urologic disease other than ED served as control group. An experienced cardiologist who was blind to the primary diagnosis evaluated the ECGs in the entire group. The results were reported as either normal or abnormal according to the presence or absence of an abnormality suggestive for cardiovascular disease. The mean age of the study and control groups was 58 years (range for the study group 28-82 years and for the control group 28-80 years). Abnormal ECG rates among patients with ED and control subjects were comparable. The incidences of ECG abnormalities in the study and control groups were 21.1% and 17.1%, respectively (P = 0,298). No ECG abnormality was detected in males younger than 40 in either group. Middle-aged or older men with ED may carry potential risk for cardiovascular diseases in the absence of cardiovascular symptoms. However, patients with organic ED are not under increased risk for ECG abnormalities.


A self-administered test of taste function using "Taste Strips".
Assessment of gustatory function with impregnated taste strips is an established and validated method. In clinical routine, application of the tests is often limited due to lack of time or costs associated with administering the test. The aim of the study was to develop a procedure suitable for self-administration of the "Taste Strips" test. The investigated participants (n = 65; 22 males, 43 females; mean age 36.7 ± 19.2 years; range, 20 to 83 years) were tested twice in a randomized crossover procedure. On 1 occasion, an examiner administered the established and validated "Taste Strips" test. On another occasion, test subjects administered the taste strips themselves. Results of both test methods were compared. The mean score (± standard deviation [SD]) of the assisted taste test (11.6 ± 2.6) was significantly lower compared to the mean self-administered taste test that yielded 12.3 ± 2.6 points (Wilcoxon test: z = 2.836; p < 0.01). Comparison of mean values showed minimal difference of the tested procedures of 0.7 ± 1.9 points with a significant positive correlation of test results (r65 = 0.734; p < 0.01). Although a small difference between test results was observed, the new test procedure seems to be an adequate screening tool for assessment of taste function with less personnel effort, leading to improved management of patients with chemosensory disorders.


Vitreous hemorrhage in patients with high-risk retinopathy of prematurity.
To investigate outcomes in premature infants with high-risk retinopathy of prematurity and secondary vitreous hemorrhage. Retrospective chart review. Patients were selected from a database of infants undergoing retinopathy of prematurity screening from September 1997 to November 1999. Infants with high-risk retinopathy of prematurity (zone I or posterior zone II threshold disease) with and without vitreous hemorrhage were compared. Final stage of retinopathy of prematurity and short-term structural outcome were assessed. Visual acuity and refraction were measured when possible. Twenty-two eyes of 11 patients (group 1) had high-risk (posterior zone II or zone I threshold) retinopathy of prematurity without vitreous hemorrhage. Group 1 patients had a 91% favorable short-term structural outcome. Eight eyes of five infants developed vitreous hemorrhage with high-risk retinopathy of prematurity (group 2). Group 2 patients had only a 12.5% favorable short-term structural outcome. Seven of eight (87.5%) progressed to stage IVa or IVb retinopathy of prematurity. Six eyes underwent vitreoretinal surgery after a median duration of hemorrhage of 36 +/- 29 days (4-70 days). Three eyes developed stage V detachments and three progressed to phthisical degeneration. Final visual acuity was no light perception in three eyes. Vitreous hemorrhage, in association with advanced retinopathy of prematurity, is a poor prognostic sign.


Geographical differentiation of apple ciders based on volatile fingerprint.
With the globalization of food trade, it's traceability and genuineness becomes increasingly more difficult. Therefore, it is necessary to develop analytical tools to define the authenticity and genuineness of food-derived products. In the current work, headspace solid-phase microextraction followed by gas chromatography-mass spectrometry (HS-SPME/GC-MS) combined with chemometric tools was used to establish the volatile fingerprint of apple ciders produced in different geographical regions of Madeira Island, in order to define their typicity and to identify putative geographical markers. A total of 143 volatile organic compounds (VOCs) belonging to different chemical families have been identified, of which 28 were found in all apple ciders independently of geographical region. Esters, terpenic and furanic compounds presented on average a higher contribution for the total volatile fingerprint in cider produced in northern region of the Island, whereas alcohols, acids, volatile phenols, carbonyl compounds and lactones in cider from southern region. Considering the relative areas of the VOCs, 43 revealed statistically significant differences (p < 0.001) between geographical regions, and 11 between northern and southern regions. A clear differentiation among cider-producing regions was observed on the developed partial least squares-discriminant analysis (PLS-DA) model. Two alcohols (1-hexanol, 1-octanol), 6 esters (methyl acetate, (Z)-3-hexen-1-ol acetate, ethyl hexanoate, ethyl nonanote, ethyl octanoate, isoamyl octanoate) and 1 terpenic compound (limonene), can be considered putative geographic markers due to their discriminatory ability. The results obtained recognize the specific and typical geographical characteristics of the cider, which will allow the forthcoming guarantee for the construction of a sustainable platform for the establishment of the authenticity and typicality of the regional cider.


Interferon-hyporesponsiveness in mice in connection with dose interval and site of administration of Newcastle disease virus. Reflexion in serum complement levels.
Intraperitoneal administration of Newcastle disease virus (NDV) resulted in enhanced serum levels of complement not accompanied by an increase of interferon levels, when measured at 24 hours' intervals. On the other hand, intravenous injection of NDV caused a drop of complement levels of short duration with an accompanying increase of interferon levels. Hyporeactivity to induction of serum interferon could not be achieved by intraperitoneal administration of NDV, but an incomplete hyporeactivity could be achieved by intravenous administration of NDV. It might be assumed that production of interferon in mice occurs in different separated compartments depending on the route of inoculation of the inducer.


Risk Factors Related to New-Onset Diabetes after Renal Transplantation in Patients of a High Complexity University Hospital in Colombia, 20 Years of Experience.
New-onset diabetes after transplantation (NODAT) is associated with immunosuppression. Its complications can negatively influence patients' quality of life, which is why it is important to study the associated risk factors and expand the possible therapies in this particular group of patients. Materials and methods. Case-control study nested in a retrospective cohort. It included patients who received kidney transplantation at the high complexity University Hospital Fundación Valle del Lili in Cali, Colombia, between 1995 and 2014. Two controls were assigned for each case, depending on the type of donor and the date of the surgery. Information was collected from clinical records and the institutional TRENAL registry. We carried out a descriptive analysis of the selected variables and identified the risk factors with conditional logistic regression. 122 cases were identified to which 224 controls were assigned. The median age was 44 years (IQR: 34-55), and 54% were men. Having >50 years of age at the time of transplantation (OR: 3.18, 95% CI: 1.6-6.3, p = 0.001), body mass index >30 kg/m2 (OR: 3.6, 95% CI: 1.3-9.7, p = 0.010) and being afro-descendant (OR: 2.74, 95% CI: 1.1-6.5, p = 0.023) were identified as risk factors for the development of NODAT. Pretransplant fasting plasma glucose >100 mg/dl (OR: 2.9, 95% CI: 1.4-6.4, p = 0.005) and serum triglycerides >200 mg/dl (OR: 2.5, 95% CI: 1.4-4.4, p = 0.002) were also reported as independent risk factors. We ratify some risk factors for the development of this important disease, which include certain modifiable characteristics. Interventions aimed at changes in lifestyle could be established in a timely manner before transplant surgery.


A Postacute Care Function Process Quality Measure for the Collection of Standardized Self-Care and Mobility Data: Development, Implementation, and Quality Measure Scores.
To describe the development of and quality measure scores for the cross-setting postacute care function process quality measure that requires the collection of standardized self-care and mobility data at admission and discharge and at least 1 function goal. Description of the development and implementation of the quality measure and the associated standardized self-care and mobility data elements. Descriptive analyses of quality measure scores for the first calendar year using data from the Minimum Data Set, the Inpatient Rehabilitation Facility Patient Assessment Instrument, the Long-Term Care Hospitals (LTCH) Continuity Assessment Record and Evaluation Data Set, and Outcome and Assessment Information Set. 15,127 skilled nursing facilities (SNFs), 1129 inpatient rehabilitation facilities (IRFs), 414 LTCHs, and 10,352 home health agencies (HHAs) in the United States. In total there were 9,216,943 stays/quality episodes (N = 9,216,943), including 2,084,774 SNF Medicare fee-for-service patient stays, 493,209 IRF Medicare patient stays, 161,714 patient stays, and 6,477,246 Medicare and Medicaid quality episodes. Not applicable. Scores for the cross-setting postacute care function process quality measure. The mean process quality measure scores for SNFs, IRFs, LTCHs, and HHAs were 95.5%, 99.7%, 99.1%, and 95.8, respectively. The 10th percentile scores for SNFs, IRFs, LTCHs, and HHAs were 88.5%, 99.3%, 98.4%, and 89.4, respectively, indicating that at least 90% of postacute care providers submitted the standardized data for a large proportion of their patients. Mean quality measure scores did not vary by provider characteristics. Most SNFs, IRFs, LTCHs, and HHAs submitted the self-care and mobility data, resulting in high quality measure scores during the first year of implementation. The availability of the standardized self-care and mobility data across postacute care settings offers the opportunity to compare the characteristics and functional outcomes of patients treated in postacute care.


Sniff nasal inspiratory pressure and sleep disordered breathing in childhood neuromuscular disorders.
The ease of sniff nasal inspiratory pressure testing may extend application of respiratory muscle assessment to younger and cognitively-impaired children. We sought to quantify sniff nasal inspiratory pressure in childhood neuromuscular disorders, and to correlate this measure with conventional pulmonary function tests and overnight polysomnography. Thirty children (mean 9.7 ± 3.8 years, range 4.3-16.5 years) with diagnosed neuromuscular disorders (Duchenne muscular dystrophy, spinal muscular atrophy, Becker muscular dystrophy, congenital myopathy, facioscapulohumeral muscular dystrophy, myotonic dystrophy, multi-minicore disease) underwent assessment. Thirty-seven percent displayed cognitive impairment. Those with neuromuscular disorders were then compared with 32 volunteer age- and gender-matched controls (mean 10.9 ± 2.9 years, range 6.6-17.2 years) with normal respiratory function. Twenty-three children with neuromuscular disorders also underwent overnight polysomnography. Children with neuromuscular disorders demonstrated significantly impaired sniff nasal inspiratory pressure, maximal inspiratory pressure, FEV(1) and FVC (p<0.05). A positive correlation was identified between daytime sniff nasal inspiratory pressure and maximal inspiratory pressure (r=0.58), FEV(1) (r=0.55) and FVC (r=0.46), though not with polysomnography variables (respiratory disturbance index, nadir SpO(2), peak CO(2)). Moderate prevalence of nocturnal hypoxia was observed, and 32% of children demonstrated sleep disordered breathing. Sniff nasal inspiratory pressure assessment was well tolerated, representing a promising surrogate measure for assessment of respiratory function in childhood neuromuscular disorders.


HPV-16 E6 and E7 protein T cell epitopes prediction analysis based on distributions of HLA-A loci across populations: an in silico approach.
Human papillomavirus type 16 (HPV-16) is the most prevalent virus in human cervical cancers, as it is present in more than half of all cases. Many studies have found continued expression of E6 and E7 proteins in the majority of cervical cancer cases, but not in normal tissues. These results indicated that the E6 and E7 proteins could be ideal candidate therapeutic vaccines against HPV-16 infection and cervical cancer. Using the Immune Epitope Database Analysis Resource, cytotoxic T lymphocyte (CTL) epitopes of the HPV-16 E6 and E7 proteins were predicted according to worldwide frequency distributions of HLA-A alleles (HLA-A*01:01, -A*02:01, -A*02:06, -A*03:01, -A*11:01, -A*24:02, -A*26:01, -A*31:01 and -A*33:03). Our results predicted a total of 81 epitopes of HPV-16 E6 (n=59) and E7 (n=22). Epitope cluster analysis showed that among the 20 clusters of HPV-16 E6, cluster 3 contained the most epitopes (10 epitopes), which was represented by HLA-A*31:01 and -A*33:03. Of the 10 clusters of HPV-16 E7, cluster 3 contained the most epitopes (5 epitopes), which was represented by HLA-A*01:01 and -A*26:01. Our results indicated that the combination of epitopes FAFRDLCIVYR₅₂₋₆₂ of E6 (HLA-A*02:06, HLA-A*31:01, and HLA-A*33:03), PYAVCDKCLKF₆₆₋₇₆ of E6 (HLA-A*11:01 and HLA-A*24:02), HGDTPTLHEY₂₋₁₁ of E7 (HLA-A*01:01 and HLA-A*26:01), and YMLDLQPETT₁₁₋₂₀ of E7 (HLA-A*02:01) could vaccinate >50% of all individuals worldwide. Our results propose CTL epitopes or combinations of them predicted in current study for candidate therapeutic vaccines to effectively control HPV-16 infection and development of cervical cancer.


Effect of hexadecane on protein kinase C of pig epidermis.
The application of hexadecane on animals skin induces hyperkeratinization and hyperplasia of the epidermis, however, the initial mechanisms of the epidermal cell proliferation and keratinization by hexadecane stimulation remains unknown. Protein kinase C is reported to be one of the critical enzymes involved in proliferation and differentiation of various cells and tissues. Therefore we investigated the effects of hexadecane on protein kinase C in pig epidermis. Protein kinase C activity of the pig skin increased 10 min after topical application of hexadecane to the back of the pig, normalized at 30 min, and subsequently kept falling for 24 h. In studying hexadecane dropped on floating sliced pig skin in Krebs buffer, similar results were obtained for the short term. Immediately after the hexadecane treatment, protein kinase C activity was not altered as compared with that of the untreated skin. Thus, the alteration of the protein kinase C activity after the hexadecane treatment is not due to the direct effect of hexadecane on the enzyme, but is due to other as yet unknown mechanisms of epidermal cell kinetics in response to hexadecane stimulation. We discuss the mechanisms of protein kinase C activity alteration upon treatment with hexadecane.


Non-traditional markers of metabolic risk in prepubertal children with different levels of cardiorespiratory fitness.
To assess classical and non-classical metabolic risk biomarkers in prepubertal children with different levels of cardiorespiratory fitness (CRF). CRF was assessed by the 20 m shuttle run test. To estimate physical activity, participants were observed while engaged in an after-school programme. Additionally, a short test based on a validated questionnaire was used to obtain information about physical activity practice and sedentary habits. Anthropometric parameters, blood pressure, and classical and non-traditional metabolic risk biomarkers--plasma lipid profile, glucose and insulin, homeostasis model assessment-insulin resistance index (HOMA-IR), plasma uric acid, transaminases and C-reactive protein (CRP)--were measured. The study was conducted in local elementary schools in Córdoba, Spain. One hundred and forty-one healthy children (eighty-eight boys, fifty-three girls) aged 7-12 years, in Tanner stage I, were recruited. They were divided into two groups after they performed the 20 m shuttle run test: equal or higher cardiovascular fitness (EHCF) group and low cardiovascular fitness (LCF) group. The LCF group displayed significantly higher TAG (P = 0.004) and lower HDL cholesterol levels (P = 0.001), as well as significantly lower values for the non-traditional lipid marker apo-A1 (P = 0.001) compared with the EHCF group. The LCF children displayed higher plasma glucose (P = 0.003) and insulin levels, higher HOMA-IR scores (P < 0.001) and higher plasma uric acid and CRP levels (P < 0.05). After adjustment for BMI, age and sex, no statistically significant differences were found between groups for the biomarkers analysed. The study provides new information to understand the role not only of weight status but also of the level of CRF on the metabolic health profile of prepubertal children.


Number-concentration of nanoparticles in liposomal and polymeric multiparticulate preparations: empirical and calculation methods.
The actual number of particles in formulations of nanoparticles (NP) is of importance for quality assurance, comprehensive physicochemical characterization, and pharmacodynamics. Some calculation methods that have been previously employed are limited because they rely on several assumptions and are not applicable for certain preparations. Currently there are no validated experimental methods for determining the particle number-concentration (Nc) of liposomal and polymeric nanoparticulate preparations (<500 nm). This study examines a new empirical method for counting the number of particles in nanoparticulate formulations including drug-containing liposomes and polymeric NP. In the new method, suspended NP are nebulized to form aerosol droplets which are dried and counted using a scanning mobility particle sizer (SMPS). Experiments were conducted with three different preparations, empty liposomes (200 and 400 nm), drug-loaded liposomes (200 nm), and polymeric NP (150 nm). It was verified that no detrimental morphological or structural changes of the formulations have been induced by the SMPS technique, and that the obtained Nc values represent the original particles. It is concluded that nano-formulations with concentrations of up to 10(7) particles per 1 cm3 air, corresponding to approximately 10(12) particles per 1 ml solution, can be directly counted within the size range of 30-900 nm. The measured values are compared to newly developed theoretical calculations to assess the viability of these calculations.


Current chemotherapeutic options for the treatment of advanced bladder cancer: a review.
Advanced bladder cancer is a disease with a high recurrence rate and metastatic capacity exhibiting a poor outcome. The pathologic stage and nodal involvement are independent prognostic factors for survival after cystectomy, and in locally advanced or metastatic disease, the performance status and the presence of visceral metastases have been correlated with treatment outcome. The regimen methotrexate-vinblastine-adriamycin-cisplatin (MVAC) has been the treatment of choice for decades and later the combination of cisplatin with gemcitabine became also the new standard of care, by demonstrating a more favorable toxicity profile. Also, carboplatin-gemcitabine and taxanes have been useful alternatives for patients unfit for cisplatin-based treatment. Additionally, the evaluation of certain chemotherapeutic agents has produced promising results in the second-line setting. Lastly, the past decade has provided information on the molecular mechanism of bladder cancer offering a personalized approach and optimizing the management of the disease.


Detection of hemodynamic transient ischemic attack during hemodialysis with near-infrared monitoring in a patient with internal carotid artery occlusion.
It is still difficult to directly prove the involvement of hemodynamic ischemia in ischemic attacks in patients with occlusive carotid artery diseases. In this report, we describe the case of a 52-year-old woman with right ICA occlusion who experienced repeated transient weakness of the left extremities during HD for chronic renal failure. Single-photon emission computed tomography showed reductions in CBF and CVR to acetazolamide in the right hemisphere. Real-time NIRS monitoring clearly showed a deterioration in the cerebral oxygenation state in the right hemisphere in response to a BP decrease during HD. Superficial temporal artery-MCA anastomosis improved SPECT as well as NIRS findings and resolved ischemic attacks during HD. This is the first study to show that NIRS can be a useful tool in detecting hemodynamic ischemia in patients with impaired cerebral perfusion reserves noninvasively and in real time.


Kidney transplant outcomes in HIV-positive patients: a systematic review and meta-analysis.
Kidney transplantation is now a viable alternative to dialysis in HIV-positive patients who achieve good immunovirological control with the currently available antiretroviral therapy regimens. This systematic review and meta-analysis investigate the published evidence of outcome and risk of kidney transplantation in HIV-positive patients following the PRISMA guidelines. Searches of PubMed, the Cochrane Library and EMBASE identified 27 cohort studies and 1670 case series evaluating the survival of HIV-positive kidney transplant patients published between July 2003 and May 2018. The regimens for induction, maintenance therapy and highly active antiretroviral therapy, acute rejection, patient and graft survival, CD4 count and infectious complications were recorded. We evaluated the patient survival and graft survival at 1 and 3 years respectively, acute rejection rate and also other infectious complications by using a random-effects analysis. At 1 year, patient survival was 0.97 (95% CI 0.95; 0.98), graft survival was 0.91 (95% CI 0.88; 0.94), acute rejection was 0.33 (95% CI 0.28; 0.38), and infectious complications was 0.41 (95% CI 0.34; 0.50), and at 3 years, patient survival was 0.94 (95% CI 0.90; 0.97) and graft survival was 0.81 (95% CI 0.74; 0.87). With careful selection and evaluation, kidney transplantation can be performed with good outcomes in HIV-positive patients.


A multivariate assessment of the coral ecosystem health of two embayments on the lee of the island of Hawai'i.
Four coral-dominated coastal sites within two embayments (Kealakekua Bay and Honokōhau Bay) on the lee of the island of Hawai'i were studied to assess evidence of anthropogenic impacts in these relatively pristine locales. Nutrient-loading parameters were analyzed in relation to benthic composition data. Statistically, there were significant positive relationships between nitrate+nitrite, silicate, and ammonium with the abundance of macroalgae, coralline algae, and dead coral, and between delta(15)N and dead coral abundance. The north outside site of Kealakekua Bay and the south outside site of Honokōhau Bay appear to be most impacted by nutrient-loading factors in each bay, respectively. Comparisons with past nutrient data indicate that nutrient inputs have increased to the two bays, and that early impacts of these increased loadings are evident. It is predicted that at current nutrient-loading rates, the north sites of Kealakekua Bay and the south sites of Honokōhau Bay will exhibit evidence of further degradation in future years.


Alzheimer's and non-alzheimer's dementia: a critical review of pharmacological and nonpharmacological strategies.
Dementia is an age-related progressive neurodegenerative disorder afflicting about 5% of the world's population, and it is expected to grow dramatically in the future keeping in view our ageing society. Currently available medications appear to be able to produce moderate symptomatic benefits but do not to stop disease progression. In this article, the management of the disorder, including the currently available drugs as well as psychosocial strategies, is discussed. A computerized search on Pubmed from 1980 to 2006 was carried out and all articles evaluated and graded on NICE guidelines. Currently evaluated and accepted medications only bring about a reduction in the deteriorating course. A combination of pharmacotherapy and psychosocial management is the need of the hour.


High rates of evolution preceded shifts to sex-biased gene expression in Leucadendron, the most sexually dimorphic angiosperms.
Differences between males and females are usually more subtle in dioecious plants than animals, but strong sexual dimorphism has evolved convergently in the South African Cape plant genus Leucadendron. Such sexual dimorphism in leaf size is expected largely to be due to differential gene expression between the sexes. We compared patterns of gene expression in leaves among 10 Leucadendron species across the genus. Surprisingly, we found no positive association between sexual dimorphism in morphology and the number or the percentage of sex-biased genes (SBGs). Sex bias in most SBGs evolved recently and was species specific. We compared rates of evolutionary change in expression for genes that were sex biased in one species but unbiased in others and found that SBGs evolved faster in expression than unbiased genes. This greater rate of expression evolution of SBGs, also documented in animals, might suggest the possible role of sexual selection in the evolution of gene expression. However, our comparative analysis clearly indicates that the more rapid rate of expression evolution of SBGs predated the origin of bias, and shifts towards bias were depleted in signatures of adaptation. Our results are thus more consistent with the view that sex bias is simply freer to evolve in genes less subject to constraints in expression level.


Information systems' approaches and designs and facility information: survey of acute care hospitals in the United States.
These survey results are based on a national survey of acute care hospitals. A random sample of 813 hospitals was selected with 115 responding and 33 incorrect address returns resulting in a 15% response rate. The purpose of the study was to measure the extent of information systems integration in the financial, medical, and administrative systems of the hospitals. The rate of adoption of information technology or technology transfer is discussed. Facility demographics are presented. Characteristics of information systems' approaches and designs are reviewed and their implications discussed. This information will provide benchmarks for hospitals to determine their information systems position and to set goals.


Effect of Prolonging the Duration of Stenting on Urethral Stricture in Proximal Hypospadias with Severe Curvature Repair: A Prospective Cohort Study.
The aim of this study was to evaluate whether prolonged stenting reduces the risk of urethral stricture after proximal hypospadias (PH) with severe curvature (SC) repair. We prospectively studied a cohort of patients with PH with SC repair who underwent urethral plate transection and urethroplasty between January 2010 and December 2020. According to the duration of stenting, the patients were divided into 2-, 4-, and 6-week groups. Postoperative complications and time of urethral stricture occurrence were analyzed. In total, 665 patients were included in the analysis. The overall incidence of complications was 26.6% (n = 177), including 42 cases of urethral strictures: 27 (64.3%) cases of urethral stricture occurred between 4 and 6 weeks after urethroplasty, 7 cases occurred between 7 weeks and 6 months after urethroplasty, 7 cases occurred more than 6 months after urethroplasty, and 1 case occurred at 3 weeks after urethroplasty. The incidence of urethral stricture in the 6-week group (1.8%) was significantly lower than that in the 4- (5.8%) and 2-week groups (10.9%) (p < 0.05). Prolonged stenting reduces the risk of urethral stricture in PH with SC repair. Four to six weeks after PH with SC repair may be the key period for the formation of early urethral strictures.


Contribution of the comonomers to the bulk and surface properties of methacrylate copolymers.
Relationships between formulation, bulk properties, and surface properties are investigated on series of copolymers prepared with hydroxyethylmethacrylate (HEMA), methylmethacrylate (MMA), and ethylmethacrylate (EMA) monomers, and on the homopolymers PMMA and PHEMA. The bulk water content, swelling ratio, and static (sessile drop and captive bubble) and dynamic (Wilhelmy plate technique) contact angles and the electrokinetic potential (streaming potential) are measured. The bulk water content and swelling ratio of HEMA copolymers are proportional to the amount of HEMA and are linearly correlated to the contact angle hysteresis. Periodic instabilities in the wetting cycles, similar to Haines jumps, are observed with HEMA copolymers and support a bidirectional relaxation of the hydrophilic groups respectively towards external water and capillary water. The origin of the electrokinetic potential of these nonionizable polymers is attributed to specific adsorption of [Formula: see text] ions. Its dependence on surface hydrophobicity and statistical length of the side-chains is interpreted in terms of the properties of water molecules near the interface.


Hearing loss with aging: presbycusis.
Older adults with presbycusis have varied presentations. Early identification requires sensitivity to communication problems described by patients and their families. Early amplification may lead to better success in hearing aid use and may prevent social isolation.


On the spatial phase distribution of cutaneous low-frequency perfusion oscillations.
Distributed cutaneous tissue blood volume oscillations contain information on autonomic nervous system (ANS) regulation of cardiorespiratory activity as well as dominating thermoregulation. ANS associated with low-frequency oscillations can be quantified in terms of frequencies, amplitudes, and phase shifts. The relative order between these faculties may be disturbed by conditions colloquially termed 'stress'. Photoplethysmography imaging, an optical non-invasive diagnostic technique provides information on cutaneous tissue perfusion in the temporal and spatial domains. Using the cold pressure test (CPT) in thirteen healthy volunteers as a well-studied experimental intervention, we present a method for evaluating phase shifts in low- and intermediate frequency bands in forehead cutaneous perfusion mapping. Phase shift changes were analysed in low- and intermediate frequency ranges from 0.05 Hz to 0.18 Hz. We observed that time waveforms increasingly desynchronised in various areas of the scanned area throughout measurements. An increase of IM band phase desynchronization observed throughout measurements was comparable in experimental and control group, suggesting a time effect possibly due to overshooting the optimal relaxation duration. CPT triggered an increase in the number of points phase-shifted to the reference that was specific to the low frequency range for phase-shift thresholds defined as π/4, 3π/8, and π/2 rad, respectively. Phase shifts in forehead blood oscillations may infer changes of vascular tone due to activity of various neural systems. We present an innovative method for the phase shift analysis of cutaneous tissue perfusion that appears promising to assess ANS change processes related to physical or psychological stress. More comprehensive studies are needed to further investigate the reliability and physiological significance of findings.


Nanostructurization of Fe-Ni Alloy.
Data about an effect of cyclic γ-α-γ martensitic transformations on the structure state of reverted austenite Fe-31.7 wt.% Ni-0.06 wt.% C alloy are presented. The effect of multiple direct γ-α and reverse α-γ martensitic transformations on fragmentation of austenitic grains has been investigated by electron microscopy and X-ray diffraction methods. An ultrafine structure has been formed by nanofragmentation inside the initial austenite grains due to the successive misorientation of their crystal lattice. Austenite was nanofragmented as a result of multiple γ-α-γ martensitic transformations. Slow heating of the nanofragmented alloy at a rate below 2 °C/s results in nanograin refinement of the structure by multiplication of the reverted γ-phase orientations. The conditions of structure refinement up to ultrafine and nanocrystalline levels as a result of both shear and diffusion mechanisms of reverse α-γ transformation are determined.


Some geometric properties of the third metacarpal bone: a comparison between the thoroughbred and standardbred racehorse.
Geometric properties of the third metacarpal bone were compared between the young and adult Standardbred and Thoroughbred racehorse. The change in shape during growth and superimposed training was dramatic in both breeds but the Thoroughbred showed the greatest difference in the minimum moment of inertia as the animal matured. Males had larger moments of inertia throughout the length of the diaphysis than did females. The differences in geometric properties of the third metacarpal bone between the Thoroughbred and Standardbred were related to the incidence of fatigue fractures which are common in the racing Thoroughbred but uncommon in the Standardbred racehorse.


Ready-to-use strip for L-ascorbic acid visual detection based on polyaniline/polyamide 66 nano-fibers/nets membranes.
A ready-to-use L-ascorbic acid (L-AA) colorimetric strip based on polyaniline (PANI)/polyamide 66 (PA 66) nanofiber/net (NFN) membrane with spider-web-like structure was fabricated through a facile bend electrospinning/netting process. Introduction of PANI component into the membrane turns the strip undergoes a brilliant brown-to-green color transition within 30 min upon incubation with L-AA. Moreover, ascribing to the three-dimensional microscopic structural, continuous pore channels, and distinctive nano-nets structure, the color change that is caused by 50 ppb L-AA can be easily perceived by naked eyes. Furthermore, RGB (red-green-blue) digital parameters that obtained from photographs of the strips were automatically read out via an iPhone. Subsequently, the parameters were converted into a color-difference map and processed statistically through principal component analysis, then used to elaborate standard curve. Combining the map and curve, we realized a method for assaying and quantifying L-AA concentration in real food samples, which avoids the time-consuming sample preparation, expensive laboratory techniques, and specialized personnel needed to carry out conventional analytical methods.


Strategies for maintaining optimal wellness in the chronic mentally ill.
Ways the chronic mentally ill avoid loss of control and the importance of both the therapeutic environment and the nurse-patient relationship in helping them do this. To examine the strategies people with chronic mental illness use to prevent loss of control and maintain health, and ways nurses can help with this process. Findings from a previously published study of seven chronically mentally ill clients in a rural day-treatment center. Four properties related to the core variable of "preventing loss of control" are relationships, feelings, good attitude, and functional activity. These properties must be examined within the context of the therapeutic environment as well as the nurse-patient relationship.


Gene doping: a review of performance-enhancing genetics.
Unethical athletes and their mentors have long arrogated scientific and medical advances to enhance athletic performance, thus gaining a dishonest competitive advantage. Building on advances in genetics, a new threat arises from athletes using gene therapy techniques in the same manner that some abused performance-enhancing drugs were used. Gene doping, as this is known, may produce spectacular physiologic alterations to dramatically enhance athletic abilities or physical appearance. Furthermore, gene doping may present pernicious problems for the regulatory agencies and investigatory laboratories that are entrusted to keep sporting events fair and ethical. Performance-enhanced genetics will likewise present unique challenges to physicians in many spheres of their practice.


Induction of ornithine decarboxylase and histidine decarboxylase activities in rat colon mucosa after application of 12-o-tetradecanoylphorbol-13-acetate (TPA), sodium deoxycholate and indole.
Ornithine decarboxylase (ODC) and histidine decarboxylase (HDC) activities of rat colon mucosa were induced after intrarectal instillation of 12-o-tetradecanoylphorbol-13-acetate (TPA) and sodium deoxycholate. After instillation of sodium deoxycholate, ODC and HDC activities increased rapidly and reached a peak at 4 h, then decreased quickly towards control levels. Both enzymes activities also increased significantly 4 h after instillation in animals treated with TPA and sodium deoxycholate plus indole. However, there were no changes in ODC and HDC activities from 0-8 h after indole administration. These data are the first to show the induction of HDC activity in colon mucosa by TPA and sodium deoxycholate and suggest that the induction of activities in these two enzymes might be one mechanism of their action as cancer promoters.


Laparoscopic minilaparotomy hysterectomy.
A laparoscopic minilaparotomy hysterectomy technique is described. An abdominal elevator allowed the use of an open 2 cm port in the lower abdomen to introduce the finger and instruments used for laparotomy. The technique was developed in 3 patients with moderate to severe endometriosis. The second and third operations were quicker than could be expected by laparovaginal surgery. The use of laparotomy instruments and techniques make the technique easier to learn, cheaper than techniques using disposable products and has the potential to be faster and possibly safer than current techniques. It retains the advantage of laparoscopy surgery, reduced postoperative pain, small incisions and early discharge from hospital.


Fatal peritonitis after massive blood transfusion: case report.
A case is presented in which successful repair of a superior vena cava gunshot wound was followed by death due to peritonitis. A mild case of endometritis progressed to generalized peritonitis after the patient's immune defenses were compromised by massive transfusion of banked blood. Clinicopathologic correlation is provided.


Bond failure rates of two self-ligating brackets: a randomised clinical trial.
To evaluate the bond failure rates of two self-ligating appliance systems bonded with a self-etching primer. Forty patients were randomly assigned to either Group SC (SmartClip, 3M Unitek, Monrovia, CA, USA) or Group IR (In-Ovation R, GAC International, Bohemia, NY, USA) appliance groups. Seven hundred and sixty six brackets were bonded with Transbond Plus Self-Etching Primer and Transbond Plus Color Change Adhesive according to the manufacturer's instructions. Over a 12-month period, the survival rates of the brackets were estimated with the Kaplan-Meier analysis. The survival distributions for the appliance systems, dental arch and position in the dental arch were compared with the log-rank test. The bond failure rate for SC was significantly lower than IR (p = 0.022). There were no differences in failure rates between either the maxillary and mandibular arches or between the anterior and posterior brackets. SC provided a more reliable bond than IR over the 12-month observation period, however, both brackets had clinically acceptable bond failure rates.


Reduced supply of monocyte-derived macrophages leads to a transition from nodular to diffuse lesions and tissue cell activation in silica-induced pulmonary fibrosis in mice.
Pulmonary fibrosis (PF) is an intractable disorder with a poor prognosis. Lung macrophages have been reported to regulate both progression and remission of bleomycin-induced diffuse PF. However, it remains unclear how macrophages contribute to silica-induced progressive nodular PF and the associated tissue cell responses in vivo. We found that lack of monocyte-derived macrophages results in the formation of diffuse PF after silica instillation. We found that the proportion and the number of monocyte-derived macrophages were persistently higher in silica-induced progressive PF compared with bleomycin-induced PF. Surprisingly, in Ccr2(-/-) mice, in which monocyte-derived macrophage infiltration is impaired, silica administration induced diffuse PF with loose nodule formation and greater activation of tissue cells. In the diffuse lesions, the distribution of epithelial cells, distribution of myofibroblasts, and architecture of the basement membrane were disrupted. Consistent with the development of diffuse lesions, genes that were differentially expressed in CD45(-) tissue cells from the lung of wild-type and Ccr2(-/-) mice were highly enriched in human diffuse, progressive PF. In gene ontology network analyses, many of these genes were associated with tissue remodeling and included genes not previously associated with PF, such as Mmp14, Thbs2, and Fgfr4. Overall, these results indicate that monocyte-derived macrophages prevent transition from nodular to diffuse silica-induced PF, potentially by regulating tissue cell responses.


Chronic central infusion of cocaine- and amphetamine-regulated transcript (CART 55-102): effects on body weight homeostasis in lean and high-fat-fed obese rats.
Cocaine- and amphetamine-regulated transcript (CART) is expressed within hypothalamic nuclei implicated in the regulation of feeding behaviour. It is up-regulated by leptin, and CART-derived peptides acutely inhibit food intake. The present study was designed to assess the long-term effects of central CART administration on food intake, body weight, plasma levels of glucose, insulin, leptin, free fatty acids and triglycerides, and on fuel utilisation in normal and high-fat-fed obese rats. Normal and high-fat-fed obese rats were cannulated intracerebroventricularly (i.c.v.) and infused for 6 days with CART (55-102) or its vehicle. At day 4, animals were placed in an indirect calorimeter for a 24 h period during which the respiratory quotient and the energy expenditure were determined hourly. In both normal and obese animals, the chronic i.c.v. infusion of CART (55-102) had marked, sustained inhibitory effects on food intake and body weight gain that were accompanied by decreases in plasma insulin and leptin levels. Using indirect calorimetry, it was observed that CART infusion promoted an increase in lipid oxidation in normal and in obese animals, although this increase reached statistical significance only in the obese group. The hypothalamic CART mRNA expression was found to be higher in obese rats (displaying hyperleptinaemia) than in normal animals. The data together show that chronic i.c.v. CART infusion is effective in inhibiting food intake, favouring lipid oxidation and limiting fat storage, both in normal and high-fat-diet-induced obese rats. The CART pathway thus seems to be an important determinant of body weight homeostasis in normal animals as well as in a model of nutritionally induced obesity.


Gap junction channels and hemichannels in the CNS: regulation by signaling molecules.
Coordinated interaction among cells is critical to develop the extremely complex and dynamic tasks performed by the central nervous system (CNS). Cell synchronization is in part mediated by connexins and pannexins; two different protein families that form gap junction channels and hemichannels. Whereas gap junction channels connect the cytoplasm of contacting cells and coordinate electric and metabolic activities, hemichannels communicate intra- and extra-cellular compartments and serve as diffusional pathways for ions and small molecules. Cells in the CNS depend on paracrine/autocrine communication via several extracellular signaling molecules, such as, cytokines, growth factors, transmitters and free radical species to sense changes in microenvironment as well as to adapt to them. These signaling molecules modulate crucial processes of the CNS, including, cellular migration and differentiation, synaptic transmission and plasticity, glial activation, cell viability and microvascular blood flow. Gap junction channels and hemichannels are affected by different signaling transduction pathways triggered by these paracrine/autocrine signaling molecules. Most of the modulatory effects induced by these signaling molecules are specific to the cell type and the connexin and pannexin subtype expressed in different brain areas. In this review, we summarized and discussed most of the relevant and recently published information on the effects of signaling molecules on connexin or pannexin based channels and their possible relevance in CNS physiology and pathology. This article is part of the Special Issue Section entitled 'Current Pharmacology of Gap Junction Channels and Hemichannels'.


Hadrontherapy techniques for breast cancer.
Radiotherapy plays a key role in breast cancer treatment, and recent technical advances have been made to improve the therapeutic window by limiting the risk of radiation-induced toxicity or by increasing tumor control. Hadrontherapy is a form a radiotherapy relying on particle beams; compared with photon beams, particle beams have specific physical, radiobiological and immunological properties, which can be valuable in diverse clinical situations. To date, available hadrontherapy techniques for breast cancer irradiation include proton therapy, carbon ion radiation therapy, fast neutron therapy and boron neutron capture therapy. This review analyzes the current rationale and level of evidence for each hadrontherapy technique for breast cancer.


Evidence that the 59-kDa protein synthesis initiation factor from wheat germ is functionally similar to the 80-kDa initiation factor 4B from mammalian cells.
The results of this investigation show that the 59-kDa protein synthesis initiation factor from wheat germ, designated eukaryotic initiation factor (eIF)-4G by Browning et al. (Browning, K.S., Maia, D.M., Lax, S.R., and Ravel, J.M. (1987) J. Biol. Chem. 262, 539-541), cross-links to the 5'-terminal cap of oxidized mRNA in the presence of eIF-4A, eIF-4F, and ATP, stimulates the RNA-dependent ATPase activities of eIF-4A and a mixture of eIF-4A and eIF-4F, and stimulates the unwinding activities of eIF-4A, eIF-4F, and a mixture of eIF-4A and eIF-4F. These findings strongly suggest that the 59-kDa factor from wheat germ is the functional equivalent of the 80-kDa protein synthesis initiation factor, eIF-4B, from mammalian cells. Recent reports indicate that the wheat germ initiation factor which contains two subunits of 80 and 28 kDa and which was given the designation "eIF-4B" by Lax et al. (Lax, S.R., Lauer, S.J., Browning, K. S., and Ravel, J.M. (1986) Methods Enzymol. 118, 109-128) is an isozyme form of eIF-4F and not the functional equivalent of mammalian eIF-4B. On the basis of functional characteristics we propose that the designation for the wheat germ factor containing the 80- and 28-kDa polypeptides be changed from eIF-4B to eIF-(iso)4F and the designation for the 59-kDa factor be changed from eIF-4G to eIF-4B.


Single cell active force generation under dynamic loading - Part I: AFM experiments.
A novel series of experiments are performed on single cells using a bespoke AFM system where the response of cells to dynamic loading at physiologically relevant frequencies is uncovered. Measured forces for the untreated cells are dramatically different to cytochalasin-D (cyto-D) treated cells, indicating that the contractile actin cytoskeleton plays a critical role in the response of cells to dynamic loading. Following a change in applied strain magnitude, while maintaining a constant applied strain rate, the compression force for contractile cells recovers to 88.9±7.8% of the steady state force. In contrast, cyto-D cell compression forces recover to only 38.0±6.7% of the steady state force. Additionally, untreated cells exhibit strongly negative (pulling) forces during unloading half-cycles when the probe is retracted. In comparison, negligible pulling forces are measured for cyto-D cells during probe retraction. The current study demonstrates that active contractile forces, generated by actin-myosin cross-bridge cycling, dominate the response of single cells to dynamic loading. Such active force generation is shown to be independent of applied strain magnitude. Passive forces generated by the applied deformation are shown to be of secondary importance, exhibiting a high dependence on applied strain magnitude, in contrast to the active forces in untreated cells. A novel series of experiments are performed on single cells using a bespoke AFM system where the response of cells to dynamic loading at physiologically relevant frequencies is uncovered. Contractile cells, which contain the active force generation machinery of the actin cytoskeleton, are shown to be insensitive to applied strain magnitude, exhibiting high resistance to dynamic compression and stretching. Such trends are not observed for cells in which the actin cytoskeleton has been chemically disrupted. These biomechanical insights have not been previously reported. This detailed characterisation of single cell active and passive stress during dynamic loading has important implications for tissue engineering strategies, where applied deformation has been reported to significantly affect cell mechanotransduction and matrix synthesis.


Automated Identification of Immunocompromised Status in Critically Ill Children.
Easy identification of immunocompromised hosts (ICHs) would allow for stratification of culture results based on host type. We utilized antimicrobial stewardship program (ASP) team notes written during handshake stewardship rounds in the pediatric intensive care unit (PICU) as the gold standard for host status; clinical notes from the primary team, medication orders during the encounter, problem list, and billing diagnoses documented prior to the ASP documentation were extracted to develop models that predict host status. We calculated performance for three models based on diagnoses/medications, with and without natural language processing from clinical notes. The susceptibility of pathogens causing bacteremia to commonly used empiric antibiotic regimens was then stratified by host status. We identified 844 antimicrobial episodes from 666 unique patients; 160 (18.9%) were identified as ICHs. We randomly selected 675 initiations (80%) for model training and 169 initiations (20%) for testing. A rule-based model using diagnoses and medications alone yielded a sensitivity of 0.87 (08.6-0.88), specificity of 0.93 (0.92-0.93), and positive predictive value (PPV) of 0.74 (0.73-0.75). Adding clinical notes into XGBoost model led to improved specificity of 0.98 (0.98-0.98) and PPV of 0.9 (0.88-0.91), but with decreased sensitivity 0.77 (0.76-0.79). There were 77 bacteremia episodes during the study period identified and a host-specific visualization was created. An electronic health record-based phenotype based on notes, diagnoses, and medications identifies ICH in the PICU with high specificity.


Association between in-hospital guideline adherence and postdischarge major adverse outcomes of patients with acute coronary syndrome in Vietnam: a prospective cohort study.
We aimed to determine the association between physician adherence to prescribing guideline-recommended medications during hospitalisation and 6-month major adverse outcomes of patients with acute coronary syndrome in Vietnam. Prospective cohort study. The study was carried out in two public hospitals in Vietnam between January and October 2015. Patients were followed for 6 months after discharge. Patients who survived during hospitalisation with a discharge diagnosis of acute coronary syndrome and who were eligible for receiving at least one of the four guideline-recommended medications. Guideline adherence was defined as prescribing all guideline-recommended medications at both hospital admission and discharge for eligible patients. Medications were antiplatelet agents, beta-blockers, ACE inhibitors or angiotensin II receptor blockers and statins. Six-month major adverse outcomes were defined as all-cause mortality or hospital readmission due to cardiovascular causes occurring during 6 months after discharge. Cox regression models were used to estimate the association between guideline adherence and 6-month major adverse outcomes. Overall, 512 patients were included. Of those, there were 242 patients (47.3%) in the guideline adherence group and 270 patients (52.3%) in the non-adherence group. The rate of 6-month major adverse outcomes was 30.5%. A 29% reduction in major adverse outcomes at 6 months after discharge was found for patients of the guideline adherence group compared with the non-adherence group (adjusted HR, 0.71; 95% CI, 0.51 to 0.98; p=0.039). Covariates significantly associated with the major adverse outcomes were percutaneous coronary intervention, prior heart failure and renal insufficiency. In-hospital guideline adherence was associated with a significant decrease in major adverse outcomes up to 6 months after discharge. It supports the need for improving adherence to guidelines in hospital practice in low-income and middle-income countries like Vietnam.


Histochemical identification of side chain substituted O-acylated sialic acids: the PAT-KOH-Bh-PAS and the PAPT-KOH-Bh-PAS procedures.
Two new methods, based on the original periodic acid-Thionin Schiff-saponification-periodic acid-Basic Fuchsin Schiff (PAT-KOH-PAS) technique of Culling et al. (1976), have been devised for the histochemical identification of side-chain O-acylated sialic acids. In the first of these, the periodic acid-Thionin Schiff-saponification-borohydride reduction-periodic acid-Basic Fuchsin Schiff (PAT-KOH-Bh-PAS) procedure, the specificity of the original PAT-KOH-PAS technique was improved by: (a) extending, when necessary, the initial period of periodate oxidation, (b) increasing the period of exposure to Thionin Schiff reagent from 30 min to 4 h, (c) using a Thionin Schiff reagent prepared by a different method, (d) interposing a borohydride reduction step between the saponification and PAS steps and, (e) extending the period of oxidation in the final PAS step from 10 to 30 min. In the second procedure, the periodic acid-phenylhydrazine-Thionin Schiff-borohydride reduction-periodic acid-Basic Fuchsin Schiff (PAPT-KOH-Bh-PAS), based on the periodic acid-phenylhydrazine-Schiff (PAPS) technique of Spicer (1961), blue Thionin Schiff staining was confined to sialic acid residues with oxidizable side chain vicinal diols by interposing a treatment with 0.5% (w/v) aqueous phenylhydrazine hydrochloride for 2 h at room temperature between the initial periodic acid oxidation and the Thionin Schiff steps of the PAT-KOH-Bh-PAS procedure. These procedures are discussed within the general framework of the methods available for the histochemical identification of side-chain O-acylated sialic acids.


Mapping the energetics of water-protein and water-ligand interactions with the "natural" HINT forcefield: predictive tools for characterizing the roles of water in biomolecules.
The energetics and hydrogen bonding pattern of water molecules bound to proteins were mapped by analyzing structural data (resolution better than 2.3A) for sets of uncomplexed and ligand-complexed proteins. Water-protein and water-ligand interactions were evaluated using hydropatic interactions (HINT), a non-Newtonian forcefield based on experimentally determined logP(octanol/water) values. Potential water hydrogen bonding ability was assessed by a new Rank algorithm. The HINT-derived binding energies and Ranks for second shell water molecules were -0.04 kcal mol(-1) and 0.0, respectively, for first shell water molecules -0.38 kcal mol(-1) and 1.6, for active site water molecules -0.45 kcal mol(-1) and 2.3, for cavity water molecules -0.55 kcal mol(-1) and 3.3, and for buried water molecules -0.56 kcal mol(-1) and 4.4. For the last four classes, similar energies indicate that internal and external water molecules interact with protein almost equally, despite different degrees of hydrogen bonding. The binding energies and Ranks for water molecules bridging ligand-protein were -1.13 kcal mol(-1) and 4.5, respectively. This energetic contribution is shared equally between protein and ligand, whereas Rank favors the protein. Lastly, by comparing the uncomplexed and complexed forms of proteins, guidelines were developed for prediction of the roles played by active site water molecules in ligand binding. A water molecule with high Rank and HINT score is unlikely to make further interactions with the ligand and is largely irrelevant to the binding process, while a water molecule with moderate Rank and high HINT score is available for ligand interaction. Water molecule displaced for steric reasons were characterized by lower Rank and HINT score. These guidelines, tested by calculating HINT score and Rank for 50 water molecules bound in the active site of four uncomplexed proteins (for which the structures of the liganded forms were also available), correctly predicted the ultimate roles (in the complex) for 76% of water molecules. Some failures were likely due to ambiguities in the structural data.


Analyzing DNA-Immunoprecipitation Sequencing Data.
Genome-wide profiling of DNA modifications has advanced our understanding of epigenetics in mammalian biology. Whereas several different methods for profiling DNA modifications have been developed over the last decade, DNA-immunoprecipitation coupled with high-throughput sequencing (DIP-seq) has proven a particularly adaptable and cost-effective approach. DIP-seq was especially valuable in initial studies of the more recently discovered DNA modifications, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine. As an enrichment-based profiling method, analysis of DIP-seq data poses several unique, and often unappreciated bioinformatics challenges, which if unmet, can profoundly affect the results and conclusions drawn from the data. Here, we outline key considerations in both the design of DIP-seq assays and analysis of DIP-seq data to ensure the accuracy and reproducibility of DIP-seq based studies.


Non-aureus staphylococci and mammaliicocci isolated from bovine milk in Italian dairy farms: a retrospective investigation.
Non-aureus staphylococci and mammaliicocci (NASM) are associated with bovine mastitis and increased milk somatic cell count (SCC) but their relationships with mammary gland health at the species level are not clearly defined. Regional differences have also been reported in their specific prevalence. The implementation of MALDI-TOF MS in milk microbiology is generating large and dependable datasets with the potential of providing useful epidemiological information. We present the retrospective analysis of 17,213 milk samples sent to our laboratory in 2021-2022, including 13,146 quarter samples from cows with subclinical (SCM) or clinical mastitis (CM) from 104 farms, and 4,067 composite herd survey (HS) samples from 21 farms. NASM were isolated from 21.12% of SCM, 11.49% of CM, and 15.59% of HS milk samples. The three most frequently identified NASM in SCM milk were Staphylococcus chromogenes (33.33%), S. haemolyticus (26.07%), and S. epidermidis (10.65%); together with S. microti and S. hyicus, these species were significantly more prevalent in quarters with SCM (p < 0.05). The three most frequently identified NASM in CM milk were S. chromogenes (31.69%), S. haemolyticus (21.42%), and Mammaliicoccus sciuri (18.38%), although no significant associations were found between these NASM species and CM. The three most frequently identified NASM in HS milk were S. chromogenes (44.49%), S. epidermidis (17.84%), and S. haemolyticus (17.23%), with S. chromogenes being isolated in all the farms sending HS milk (100%). In conclusion, this retrospective study provides the first information on the NASM species isolated from cow milk in Italy, expanding our knowledge on the epidemiology of NASM at the species level and providing further insights into their relationships with mammary gland health in modern dairy farms.


Glyoxal Induces Senescence in Human Keratinocytes through Oxidative Stress and Activation of the Protein Kinase B/FOXO3a/p27KIP1 Pathway.
Senescence is a well-characterized cellular state associated with specific markers such as permanent cell proliferation arrest and the secretion of messenger molecules by cells expressing the senescence-associated secretory phenotype. The senescence-associated secretory phenotype composition depends on many factors such as the cell type or the nature of the stress that induces senescence. Because the skin constitutes a barrier with the external environment, it is particularly subjected to different types of stresses and consequently prone to premature cellular aging. The dicarbonyl compounds glyoxal (GO) and methylglyoxal are precursors of advanced glycation end products, whose presence marks normal and pathological aging. In this study, we show that GO treatment provokes oxidative stress by increasing ROS and advanced glycation end-products levels and induces senescence in human keratinocytes. Furthermore, GO-induced senescence bears a unique molecular progression profile: an early-stage senescence when protein kinase B‒FOXO3a-p27KIP1 pathway mediates cell cycle arrest and a late-stage senescence maintained by the p16INK4/pRb pathway. Moreover, we characterized the resulting secretory phenotype during early-stage senescence by mass spectrometry. Our study provides evidence that GO can affect keratinocyte functions and act as a driver of human skin aging. Hence, senotherapeutics aimed at modulating GO-associated senescence phenotype hold promising potential.


Development of a high-performance liquid chromatographic-electrospray mass spectrometric assay for the specific and sensitive quantification of the novel immunosuppressive macrolide 40-O-(2-hydroxyethyl)rapamycin.
It was our objective to develop a rapid, sensitive and specific assay to quantify the immunosuppressive macrolide 40-O-(2-hydroxyethyl)rapamycin (SDZ-RAD) in blood of transplant patients. SDZ-RAD was extracted from blood by solid-liquid extraction. SDZ-RAD and its internal standard 28,40-diacetyl rapamycin were quantified using HPLC-electrospray MS. The assay was linear from 0.1 to 100 microg/l (r2 = 0.99). The mean recovery was 83% for SDZ-RAD and 80.5% for the internal standard. The mean day-to-day precision was 8.0%. Extracted samples were stable at 20 degrees C for at least 48 h and SDZ-RAD blood samples at -80 degrees C for at least six months.


Our patients' safety through our new vision, mission, and strategic plan.
This being my first president's column, I would be remise if I did not provide a heartfelt thanks to the ASHRM membership, who elected me to serve as your 2013 ASHRM President. Thank you all for allowing me to continue to give back to our fine and noble healthcare risk management profession!


Mesh abdominal wall hernia surgery is safe and effective-the harm New Zealand media has done.
Patients in New Zealand have now developed a fear of mesh abdominal wall hernia repair due to inaccurate media reporting. This article outlines the extensive literature that confirms abdominal wall mesh hernia repair is safe and effective. The worsening confidence in the transvaginal mesh prolapse repair should not adversely affect the good results of mesh abdominal wall hernia repair. New Zealand general surgeons are well trained in providing modern hernia surgery.


Prevalence and clinical significance of common respiratory pathogens in the upper respiratory tract of children with community-acquired pneumonia in Zunyi, China.
To estimate the prevalence of common respiratory pathogens among children with community-acquired pneumonia (CAP) in Zunyi City, Guizhou, China, and to assess whether the presence of common respiratory pathogens in patients is associated with disease severity. This retrospective study assessed the prevalence of common respiratory viruses and bacteria in the upper respiratory tract of among infants and children aged 1 month to 5 years hospitalized with radiologically confirmed CAP between April 2017 and March 2018. Direct immunofluorescence assay and bacterial culture were used to identify viruses and bacteria in the upper airway specimens, respectively. The association between severe CAP and the presence of pathogens was determined using multivariate logistic regression models. Of the 685 patients enrolled, 583 cases had viral and/or bacterial pathogens detected, which included the presence of only viral pathogens, only bacterial pathogens, and mixed viral and bacterial pathogens in 34.3%, 29.7%, and 36.0% of cases, respectively. Respiratory syncytial virus (RSV) was the most common viral pathogen, with a prevalence rate of 39.9% (273/685). Haemophilus influenzae was the most commonly detected bacterial pathogen, with a prevalence rate of 15.3% (105/685). The presence of RSV (adjusted odds ratio [aOR], 1.9; 95% confidence interval [CI], 1.3-2.8) and Staphylococcus aureus (aOR, 13.7; 95% CI, 5.5-33.9) in children with CAP was associated with severe pneumonia. In a cohort of Zunyi infants and children hospitalized with CAP, RSV was the most common pathogen.


An electron-transporting host material compatible with diverse triplet emitters used for highly efficient red- and green-electrophosphorescent devices.
A bifluorene analogue, T2N, containing a pyridyl moiety serves as both a host and an efficient electron-transporting material that is compatible with various heavy metal-containing red (Ir, Ru, Os, and Pt) and green (Ir) phosphors for highly efficient phosphorescent OLEDs possessing simple device architectures.


In vivo radiosensitization efficacy of KU-2285 and etanidazole at clinically relevant low radiation doses.
The in vivo radiosensitization efficacy of KU-2285 at clinically relevant low radiation doses (2-4 Gy) was compared with that of etanidazole using four types of assays with EMT6, SCCVII, and C3H mammary tumors. The in vivo-in vitro cytokinesis-block micronucleus assay and the chromosomal aberration assay were used to assess the sensitizing effect at single doses of 2-4 Gy. After in vivo treatment for tumors, tumor cells were cultured in the presence of cytochalasin B for the former assay or demecolcine for the latter assay, and the micronucleus frequency in binucleate cells and the chromosomal frequency in metaphase cells were evaluated after 42 hr and 3 hr of culture. In addition, an in vivo-in vitro colony assay and a growth delay assay were performed using fractionated irradiation regimens (4 Gy x 5). The sensitizer enhancement ratio for 100-400 mg/kg of KU-2285 was between 1.12 and 1.42. KU-2285 was a more efficient sensitizer than etanidazole in 3 of 9 experiments and as efficient as etanidazole in the remaining six experiments. Both the micronucleus assay and the chromosomal aberration assay appeared to be very useful in evaluating the in vivo sensitizing effect at low radiation doses. KU-2285 had a definite radiosensitizing effect even at low radiation doses, and clinical trials of KU-2285 may be warranted.


[Case of thyroid ectopia in the hyoid region in a young Malagasy girl].
Thyroid ectopia is rare. It results from a failure of migration of the thyroid gland during its embryonic development. It is most often asymptomatic. We here report a case of thyroid ectopia in the hyoid region in a young Malagasy girl, presenting as aesthetic discomfort associated with subclinical hypothyroidism. Diagnosis was confirmed using cervical ultrasound and scintigraphy with technetium-99m. Hormone replacement therapy is the gold standard even in patients with subclinical hypothyroidism because it results in physiologic euthyroidism and good clinical evolution.


Safety of lactational exposure to venlafaxine on the rat mammary gland development and carcinogenesis in F1 female offspring.
The chronic use of selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors (SNRIs) may result in human gynecomastia, mammoplasia, galactorrhea, and elevated breast cancer risk. As antidepressants are frequently used for postpartum depression (PPD) treatment, this study investigated the adverse effects of lactational exposure to venlafaxine (VENL, a selective SNRI) on mammary gland development and carcinogenesis in F1 female offspring. Thus, lactating Wistar rats (F0) received VENL by oral gavage at daily doses of 3.85, 7.7, or 15.4 mg/kg (N = 9, each group) from lactational day (LD 1) until the weaning of the offspring (LD 21). F1 female offspring were euthanized for mammary gland, and ovary histological analyses on the post-natal day (PND) 22 and 30 (1 pup/litter/period, N = 9, each group). At PND 22, other females (2 pups/litter, N = 18, each group) received a single dose of carcinogen N-methyl-N-nitrosourea (MNU, 50 mg/kg) intraperitoneally (i.p.) for tumor susceptibility assay until PND 250. Tumor incidence and latency were recorded and representative tumor samples were collected for histopathology. The results indicate that lactational exposure to VENL did not alter the development of the mammary gland (epithelial ductal tree or the mean number of terminal end buds), or the ovary (weight and primary, secondary, tertiary, and Graafian follicles) in prepubertal F1 female offspring. In addition, VENL exposure did not influence tumor incidence or tumor latency in adult female offspring that received MNU. Thus, the findings of this animal study indicated that lactational VENL exposure, a period similar to human PPD, did not exert an adverse effect on the mammary gland development at the prepubertal phase or on chemically induced mammary tumorigenesis in adult F1 female rats.


COVID-19 Vaccine Hesitancy and Experiences of Discrimination Among Black Adults.
Early in the COVID-19 vaccine rollout, Black adults consistently reported more hesitancy than White adults, but few studies have examined variation in hesitancy among Black adults or its associations with racial discrimination. Data were collected from Black Arkansas residents age 18 and older (n = 350) between July 12th and July 30th, 2021, as part of a larger survey of Arkansans (N = 1500). Participants were recruited through random digit dialing of both landline and cell phones, with oversampling of Black and Hispanic residents. Respondents reported COVID-19 vaccine hesitancy, sociodemographic information, influenza vaccination history, pandemic-related experiences, and experiences of racial discrimination. Almost half (48.9%) of Black adults in Arkansas were not hesitant towards COVID-19 vaccines, while the remainder reported some level of hesitancy. Nearly a quarter were very hesitant (22.4%), while fewer reported being somewhat (14.0%) and a little (14.7%) hesitant. Using an ordered logistic regression with partial proportional odds, we find odds of COVID-19 vaccine hesitancy decreased as age and influenza vaccination increased. Odds of COVID-19 vaccine hesitancy were 1.70 times greater for Black adults who experienced the death of a close friend/family member due to COVID-19 and 2.61 times greater for individuals reporting discrimination with police or in the courts. Within-group analysis revealed nearly half of Black adults did not report any COVID-19 vaccine hesitancy and heterogeneity among those who were hesitant. Findings suggest there may be an important link between racial discrimination in the criminal justice system and COVID-19 vaccine hesitancy among Black adults.


Chromosomal fragility, structural rearrangements and mobile element activity may reflect dynamic epigenetic mechanisms of importance in neurobehavioural genetics.
Advances in human genome analyses have not yet allowed identification of specific genetic mechanisms underlying the expression of human neurobehavioural disorders. There is an increasing awareness that several genes may contribute to behavioural phenotypes and these genes appear to interact in as yet undetermined ways. It has been suggested that the problem needs elucidation from an epigenetic, gene expression perspective. Cytogenetic instability manifesting as chromosomal fragile sites, translocations, duplications, deletions and inversions, when co-occurring with neurobehavioural disorders, may offer a doorway to the investigation of such chromatin level, regulatory region, epigenetic processes. Due to earlier indications of non-specificity of chromosomal aberrations, poor phenotype:genotype correlations and a shift to analysing candidate coding regions on high resolution map level, the only utility of chromosomal breakpoints came to be seen as harbouring possible candidate genes of interest when segregating together with particular neurobehavioural disorders. More recent findings of the expression of highly specific subsets of fragile sites in association with Tourette and Rett syndromes need to be extended to other neurobehavioural disorders to ascertain whether observed patterns can be considered representative of 'chromatin endophenotypes' correlating with discrete sets of neurobehavioural symptoms. Environmental/epigenetic factors could affect the chromatin characteristics of the genome arising through DNA strand breakage, mobile element activity and retroinsertion, establishing new architectural features of regulatory control networks very rapidly in comparison to coding region evolution rates. Microarray-based techniques for the genome-wide mapping of in vivo protein-DNA interactions offer increasingly comprehensive views of genetic and epigenetic regulatory networks. It may be informative to include functionally significant chromatin structural variation analyses when considering candidate genes for neurobehavioural disorders.


Relationship Between Moderate-to-Vigorous Physical Activity and Glycemia Among Young Adults with Type 1 Diabetes and Overweight or Obesity: Results from the Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON) Study.
Aims: Using data from the ACT1ON study, we conducted secondary analyses to assess the relationship between minutes of moderate-to-vigorous physical activity (MVPA) and glycemia in adults with type 1 diabetes (T1D) and overweight or obesity. Materials and Methods: Participants (n = 66) with T1D provided measures of glycemia (hemoglobin A1c [HbA1c], percent of time below range <70 mg/dL, time-in-range [TIR 70-180 mg/dL], and time above range [TAR >180 mg/dL]) and self-reported physical activity (Global Physical Activity Questionnaire [GPAQ] and Previous Day Physical Activity Recalls [PDPAR]) at baseline, 3, 6, and 9 months postintervention. Wearable activity data were available for a subset of participants (n = 27). Associations were estimated using mixed effects regression models adjusted for design, demographic, clinical, and dietary covariates. Results: Among young adults 19-30 years of age with a baseline HbA1c of 7.9% ± 1.4% and body mass index of 30.3 (interquartile range 27.9, 33.8), greater habitual weekly MVPA minutes were associated with higher HbA1c through the GPAQ (P < 0.01) and wearable activity data (P = 0.01). We did not observe a significant association between habitual MVPA and any continuous glucose monitoring metrics. Using PDPAR data, however, we observed that greater daily MVPA minutes were associated with more TAR (P < 0.01) and reduced TIR (P < 0.01) on the day following reported physical activity. Conclusions: Among young adults with T1D and overweight or obesity, increased MVPA was associated with worsened glycemia. As physical activity is vital to cardiovascular health and weight management, additional research is needed to determine how to best support young adults with T1D and overweight or obesity in their efforts to increase physical activity. Clinical Trial Registration number: NCT03651622.


Effectiveness of supported employment for veterans with spinal cord injuries: results from a randomized multisite study.
To examine whether supported employment (SE) is more effective than treatment as usual (TAU) in returning veterans to competitive employment after spinal cord injury (SCI). Prospective, randomized, controlled, multisite trial of SE versus TAU for vocational issues with 12 months of follow-up data. SCI centers in the Veterans Health Administration. Subjects (N=201) were enrolled and completed baseline interviews. In interventional sites, subjects were randomly assigned to the SE condition (n=81) or the TAU condition (treatment as usual-interventional site [TAU-IS], n=76). In observational sites where the SE program was not available, 44 subjects were enrolled in a nonrandomized TAU condition (treatment as usual-observational site [TAU-OS]). The intervention consisted of an SE vocational rehabilitation program called the Spinal Cord Injury Vocational Integration Program, which adhered as closely as possible to principles of SE as developed and described in the individual placement and support model of SE for persons with mental illness. The primary study outcome measurement was competitive employment in the community. Subjects in the SE group were 2.5 times more likely than the TAU-IS group and 11.4 times more likely than the TAU-OS group to obtain competitive employment. To the best of our knowledge, this is the first and only controlled study of a specific vocational rehabilitation program to report improved employment outcomes for persons with SCI. SE, a well-prescribed method of integrated vocational care, was superior to usual practices in improving employment outcomes for veterans with SCI.