Endorphins alter acquisition and consolidation of an inhibitory avoidance response in rats.
Peripheral i.p. administration of 1.0 microgram/kg gamma-endorphin to rats, 30 min prior to training in a 1-trial inhibitory avoidance task, enhanced retention performance measured 72 h later. A much smaller dose of 0.1 microgram/kg beta-endorphin administered immediately following training produced a retention deficit. Both of these endorphin effects were time dependent, since gamma-endorphin given 90 min prior to, and beta-endorphin given 90 min after training produced no effect on retention performance. A wide dose range of either gamma-endorphin (0.1-10 micrograms/kg) administered after training or beta-endorphin (0.1-10 micrograms/kg) administered before training had no effect. These results suggest that the behavioral actions of beta-endorphin and smaller beta-lipotropin sequences such as gamma-endorphin, are distinct. We also found that 0.1-100 micrograms/kg of either alpha-endorphin or Met-enkephalin given before or after training was without effect on retention of the response.


Rebeccamycin analogues bearing amine substituents or other groups on the sugar moiety.
In the course of structure-activity relationship studies on rebeccamycin analogues, a series of compounds bearing an amino function on the sugar moiety were synthesized with the aim of improving the solubility and interaction with the macromolecular target(s). The syntheses of amino derivatives and the corresponding chloro, iodo and azido intermediates are described. Their interaction with DNA and effects on human DNA topoisomerases I and II were investigated. Their antimicrobial activities against two Gram-positive bacteria, Bacillus cereus and Streptomyces chartreusis, a Gram-negative bacterium Escherichia coli and a yeast Candida albicans were also determined. 6'-Amino compound 7 and 6'-N-methylamino 14 very efficiently inhibit the growth of E. coli. The introduction of an amino group at the 6'-position strongly enhances the capacity of the drugs to interact with DNA but almost abolishes their poisoning effect on topoisomerase I. Unlike the vast majority of rebeccamycin analogues previously studied, the newly designed compounds do not stimulate DNA cleavage by topoisomerase I. The enhanced capacity of the 6'-amino glycosyl rebeccamycin derivatives to bind to DNA likely account for the improved biological profiles. DNA and topoisomerase I represent two independent targets which can both be used for the development of antitumor rebeccamycin derivatives.


Studies on mechanisms for enhanced clearance of low-density lipoproteins in patients with primary hypertriglyceridaemia.
Patients with primary hypertriglyceridaemia usually have increased clearance rates for plasma low-density lipoproteins (LDL). To evaluate the mechanisms for this effect, simultaneous turnover rates for autologous and normal homologous LDL were determined in 12 patients with primary hypertriglyceridaemia. On average, the autologous LDL was cleared more rapidly than the normal homologous LDL. Fractional catabolic rates (FCRs) for autologous LDL averaged 0.61 +/- 0.06 (SEM) pools d-1, whereas FCRs for homologous LDL averaged 0.49 +/- 0.04 pools d-1. In eight of the 12 patients the FCRs for 'hypertriglyceridaemic' LDL were found to be significantly higher than for normal LDL; in four others both forms of LDL were cleared at essentially the same rate. In all cases, however, both for the normal and 'hypertriglyceridaemic' LDL, clearance rates were higher than normal. Thus, besides the variability in LDL affinity for removal pathways, hypertriglyceridaemic patients appear to have an increased availability of LDL receptors for removal of circulating LDL.


Maternal colonization with extended-spectrum β-lactamase-producing Enterobacteriaceae in term versus preterm pregnancies.
To examine the prevalence and risk factors of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) colonization among women who delivered preterm and at term. A prospective observational study of maternal ESBL-E rectovaginal colonization in threatened preterm labor and low-risk term pregnancies was conducted between March 2017 and August 2021 at the Galilee Medical Center, Israel. Obstetric and neonatal complications were compared between colonized and non-colonized mothers and neonates. ESBL-E colonization was similar in the preterm (n = 202) and term (n = 172) groups: 14.4% and 16.9%, respectively (P = 0.567). The maternal-neonatal transmission rate was higher in the preterm than the term group but the difference was not statistically significant: 42.1% and 22.2%, respectively (P = 0.42). Prematurity was a risk factor of neonatal ESBL-E colonization (odds ratio 1.33, 95% confidence interval 1.01-1.75, P = 0.041). ESBL-E-colonized preterm infants were delivered at an earlier gestational age and were more likely to have complications. Maternal ESBL-E colonization and transmission were more prevalent in pregnancies complicated by threatened preterm labor or premature rupture of membranes than in term pregnancies. These findings emphasize the need for further research on the cost-effectiveness of screening for maternal ESBL-E colonization in preterm labor, to prevent neonatal infectious complications. gov identifier NCT03251885.


Learning - the only way to improve health-care outcomes.
Attempts to improve health care have generally failed. Systems analysis urges addressing processes, such as learning, rather than isolated parts of a system. We apply learning curve theory to health care and then explicate the process of learning. Specific recommendations involve how we learn (and unlearn), who should learn, and what should be learned.


Axonal mRNA translation: an unexpected link to axon survival and the mitochondrion.
Localized mRNA translation plays roles in dendrites and axons, but the regulatory mechanisms and downstream pathways are not well understood. An article in Cell by Yoon et al. (2012) shows that lamin B2, well known as a nuclear protein, undergoes regulated synthesis in axons, promoting mitochondrial function and axon survival.


[Death in the milieu of homeless persons. A comparative retrospective analysis of an autopsy sample of different regional population structures (Middle Hessia/Hamburg)].
For an evaluation concerning different regional population and community characteristics, 23 fatalities of homeless individuals were selected from the current autopsy series of the Institutes of Legal Medicine of Giessen/Germany and Hamburg/Germany from 1990 to 1996. The outcome of this retrospective analysis enables to overcome the deficiency of knowledge of causes, manners and circumstances of death among homeless individuals.


Parallel mapping and simultaneous sequencing reveals deletions in BCAN and FAM83H associated with discrete inherited disorders in a domestic dog breed.
The domestic dog (Canis familiaris) segregates more naturally-occurring diseases and phenotypic variation than any other species and has become established as an unparalled model with which to study the genetics of inherited traits. We used a genome-wide association study (GWAS) and targeted resequencing of DNA from just five dogs to simultaneously map and identify mutations for two distinct inherited disorders that both affect a single breed, the Cavalier King Charles Spaniel. We investigated episodic falling (EF), a paroxysmal exertion-induced dyskinesia, alongside the phenotypically distinct condition congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID), commonly known as dry eye curly coat syndrome. EF is characterised by episodes of exercise-induced muscular hypertonicity and abnormal posturing, usually occurring after exercise or periods of excitement. CKCSID is a congenital disorder that manifests as a rough coat present at birth, with keratoconjunctivitis sicca apparent on eyelid opening at 10-14 days, followed by hyperkeratinisation of footpads and distortion of nails that develops over the next few months. We undertook a GWAS with 31 EF cases, 23 CKCSID cases, and a common set of 38 controls and identified statistically associated signals for EF and CKCSID on chromosome 7 (P(raw) 1.9×10(-14); P(genome) = 1.0×10(-5)) and chromosome 13 (P(raw) 1.2×10(-17); P(genome) = 1.0×10(-5)), respectively. We resequenced both the EF and CKCSID disease-associated regions in just five dogs and identified a 15,724 bp deletion spanning three exons of BCAN associated with EF and a single base-pair exonic deletion in FAM83H associated with CKCSID. Neither BCAN or FAM83H have been associated with equivalent disease phenotypes in any other species, thus demonstrating the ability to use the domestic dog to study the genetic basis of more than one disease simultaneously in a single breed and to identify multiple novel candidate genes in parallel.


Cervical alignment and clinical outcome of anterior cervical discectomy and fusion vs. anterior cervical corpectomy and fusion in local kyphotic cervical spondylotic myelopathy.
Cervical local kyphosis (CLK) is a common degenerative disorder with a potentially debilitating and intractable condition. Currently, there is still debate on the optimal treatment of local kyphotic cervical spondylotic myelopathy (LKCSM) via different anterior approaches. The objective of this study was to evaluate the surgical efficacy of anterior cervical discectomy and fusion (ACDF) vs. anterior cervical corpectomy and fusion (ACCF) for the treatment of LKCSM. In addition, the cervical sagittal alignment parameters and axial symptoms (AS) severity after CLK correction were analyzed. From January 2016 and December 2020, 104 patients who suffered LKCSM were retrospectively reviewed. These patients underwent ACDF (n = 53) and ACCF (n = 51). Pre- and postoperatively, cervical sagittal alignment parameters were measured on the lateral X-rays, including local kyphotic angles (LKA), C2-7 Cobb angle, T1 slope, and C2-7 sagittal vertical axis (C2-7 SVA). The neurological recovery rate was calculated according to the Japanese Orthopedic Association (JOA) score. The AS severity was evaluated using Neck Disability Index (NDI). Significant differences (P < 0.05) were demonstrated between ACDF and ACCF groups regarding LKA, LKA correction, C2-7 Cobb angle, T1 slope, C2-7 SVA, NDI, NDI recovery and NDI ranking system. However, no significant differences (P > 0.05) existed in JOA score, recovery rate, and neurological recovery rate grade. In both groups, significant differences (P < 0.05) were demonstrated between pre- and postoperative LKA, T1 slope, C2-7 Cobb angle, C2-7 SVA, JOA score, and NDI. LKA correction showed the positive correlations with the recovery rate (r = 0.48, P < 0.001), and with the NDI recovery in ACDF group (r = 0.49, P < 0.001) and in ACCF group (r = 0.55, P < 0.001). LKCSM with ≤3 segments of spinal cord compression can be improved with either ACDF or ACCF, resulting in satisfactory neurological outcomes. CLK correction can significantly improve the neurological function and AS, and increase the T1 slope and C2-7 SVA. However, ACDF was more favorable than ACCF in the CLK correction.


Hospice Aide Visits among Nursing Home Residents During the Early Months of the COVID-19 Pandemic.
Hospice aides are vital in delivering care to patients and family members at the end of life. The COVID-19 pandemic resulted in disruptions in hospice care delivery, especially in long-term care settings. We aim to provide a description of hospice aide visits among nursing home residents enrolled in hospice during the first 9 months of 2020, as compared with the same months in 2019. Observational cohort study. 153,109 and 152,077 long-stay nursing home residents enrolled in hospice in 2019 and 2020, respectively. On a monthly basis, we reported estimated probabilities of not having visits from hospice aides and adjusted visit minutes among those who had hospice aide visits for the 2019 and 2020 cohort, respectively. The regression models accounted for resident sociodemographic and clinical characteristics and nursing home fixed effects. The analyses were conducted at the national and state level, separately. More than half of residents did not have any visits from hospice aides in 2020 from April and onward. Among residents who had hospice aide visits, the 2020 cohort had reduced visits in March and onward, with the greatest difference being 155 minutes less in April (95% CI: -163.4, -146.5). State-level analyses suggested that multiple factors besides community spread or state policies might contribute to the reduced presence of hospice aides. Our findings highlight the toll of the pandemic on hospice care delivery in nursing homes and the need for hospice care to be better incorporated into emergency preparedness planning.


An epidemic of dengue-1 in a remote village in rural Laos.
In the Lao PDR (Laos), urban dengue is an increasingly recognised public health problem. We describe a dengue-1 virus outbreak in a rural northwestern Lao forest village during the cool season of 2008. The isolated strain was genotypically "endemic" and not "sylvatic," belonging to the genotype 1, Asia 3 clade. Phylogenetic analyses of 37 other dengue-1 sequences from diverse areas of Laos between 2007 and 2010 showed that the geographic distribution of some strains remained focal overtime while others were dispersed throughout the country. Evidence that dengue viruses have broad circulation in the region, crossing country borders, was also obtained. Whether the outbreak arose from dengue importation from an urban centre into a dengue-naïve community or crossed into the village from a forest cycle is unknown. More epidemiological and entomological investigations are required to understand dengue epidemiology and the importance of rural and forest dengue dynamics in Laos.


A Novel Quantitative Electrocardiography Strategy Reveals the Electroinhibitory Effect of Tamoxifen on the Mouse Heart.
Tamoxifen, a selective estrogen receptor modulator, was initially used to treat cancer in women and more recently to induce conditional gene editing in rodent hearts. However, little is known about the baseline biological effects of tamoxifen on the myocardium. In order to clarify the short-term effects of tamoxifen on cardiac electrophysiology of myocardium, we applied a single-chest-lead quantitative method and analyzed the short-term electrocardiographic phenotypes induced by tamoxifen in the heart of adult female mice. We found that tamoxifen prolonged the PP interval and caused a decreased heartbeat, and further induced atrioventricular block by gradually prolonging the PR interval. Further correlation analysis suggested that tamoxifen had a synergistic and dose-independent inhibition on the time course of the PP interval and PR interval. This prolongation of the critical time course may represent a tamoxifen-specific ECG excitatory-inhibitory mechanism, leading to a reduction in the number of supraventricular action potentials and thus bradycardia. Segmental reconstructions showed that tamoxifen induced a decrease in the conduction velocity of action potentials throughout the atria and parts of the ventricles, resulting in a flattening of the P wave and R wave. In addition, we detected the previously reported prolongation of the QT interval, which may be due to a prolonged duration of the ventricular repolarizing T wave rather than the depolarizing QRS complex. Our study highlights that tamoxifen can produce patterning alternations in the cardiac conduction system, including the formation of inhibitory electrical signals with reduced conduction velocity, implying its involvement in the regulation of myocardial ion transport and the mediation of arrhythmias. A Novel Quantitative Electrocardiography Strategy Reveals the Electroinhibitory Effect of Tamoxifen on the Mouse Heart(Figure 9). A working model of tamoxifen producing acute electrical disturbances in the myocardium. SN, sinus node; AVN, atrioventricular node; RA, right atrium; LA, left atrium; RV, right ventricle; LV, left ventricle.


Perinatal factors impacting echocardiographic left ventricular measurement in small for gestational age infants: a prospective cohort study.
Infants born small for gestational age (SGA) have an increased risk of developing various cardiovascular complications. While many influencing factors can be adjusted or adapt over time, congenital factors also have a significant role. This study, therefore, seeks to explore the effect of perinatal factors on the left ventricular (LV) parameters in SGA infants, as assessed immediately after birth. This single-center prospective cohort study, conducted between 2014 and 2018, involved healthy SGA newborns born > 35 weeks' gestation, delivered at New York-Presbyterian Brooklyn Methodist Hospital, and a gestational age (GA)-matched control group of appropriate for gestational age (AGA) infants. Data analysis was performed using multivariate linear regression in STATA. The study enrolled 528 neonates, 114 SGA and 414 AGA. SGA infants exhibited a mean GA of 38.05 weeks (vs. 38.54), higher male representation (69.3% vs. 51.5%), lower birth weight (BW) (2318g vs 3381g), lower Apgar scores at birth, and a higher rate of neonatal intensive care unit admission compared to AGA infants (41.2% vs.18.9%; p<0.001). Furthermore, SGA infants were more likely to be born to nulliparous women (63.16% vs. 38.16%; p<0.001), with lower body mass index (BMI) (29.8 vs. 31.7; p=0.004), a lower prevalence of gestational maternal diabetes (GDM) (14.9 % vs. 35.5%; p<0.001), and a higher prevalence of preeclampsia (18.4 % vs. 6.52%; p<0.001). BW was identified as the most significant predictor affecting most LV parameters in this study (p<0.001), except shortening fraction, asymmetric interventricular septal hypertrophy and Inter-ventricular septal thickness/LV posterior wall ratio (IVS/LVPW). Lower GA (coefficient = -0.09, p=0.002), insulin use in GDM (coefficient = 0.39, p=0.014), and low APGAR scores at 1 minute (coefficient = -0.07, p<0.001) were significant predictors of IVS during diastole (R-squared [R2]=0.24). High maternal BMI is marginally associated with LVPW during systole (R2=0.27, coefficient = 0.01, p=0.050), while male sex was a significant predictor of LV internal dimension during diastole (R2=0.29, p=0.033). This study highlights the significant influence of perinatal factors on LV parameters in SGA infants, with BW being the most influential factor. Although LV morphology alone may not predict future cardiovascular risk in the SGA population, further research is needed to develop effective strategies for long-term cardiovascular health management in this population.


Contact allergy in patients with rosacea: a clinic-based, prospective epidemiological study.
Rosacea is a relatively common inflammatory skin disease of unknown prevalence. The proportion of contact allergy complicating rosacea and its therapy, respectively, is largely unknown. To estimate the prevalence of specific contact allergy in rosacea patients and to compare this with the prevalence observed in the general population and in general patch test patients. In this prospective monocentre study, 78 patients with rosacea were investigated for contact sensitizations via patch testing the standard series, constituents of topical formulations, preservatives, fragrances, topically applied drugs and, if available, patient's own products. Positive reactions occurred to nickel (II) sulphate (12 of 78, 15.4%), fragrance mix I (4 of 77, 5.2%), balsam of Peru (8 of 77, 10.4%; significantly elevated prevalence compared to that observed in the population-based KORA study), potassium dichromate (4 of 78, 5.1%) and Lyral (3 of 78, 3.8%). Regarding topical antibiotics, only 1 of 78 (1.3%) patients was positive to neomycin sulphate, and none to metronidazole; however, 6 of 75 (8%) patients were positive to gentamicin sulphate, and 4 of 76 (5.3%) patients were positive to framycetin sulphate. No allergic but irritant patch test reactions, instead, were provoked by various patients' own products as well as by the irritant sodium lauryl sulphate (SLS) even in low concentrations. Despite the limited power of the study, a strikingly high prevalence of contact allergy to gentamicin sulphate was observed, which is probably due to antibiotic treatment of rosacea-associated eye symptoms. The reactions to the irritant SLS probably mirror the extreme skin sensitivity in rosacea.


Anomalies in the ionic properties of serum albumin.
The documented difference in the isoionic points of native and unfolded serum albumins is revisited with computational methods. Good agreement between calculated and measured DeltapIs is found, with the molecular origin appearing to reside in a diverse set of carboxyl group titrations. Although histidine ionization plays only a minor role in bringing about the DeltapI, the identification of three histidine residues with low computed pK(a)s (around pH 5) suggests an explanation for the mismatch between experimentally derived group pK(a)s and the pI of the native protein. Computed electrostatic properties (including pI) of native serum albumins are compared with a set of 178 nonenzyme proteins. We find that the degree of interdigitation of positive and negative charges is extreme for serum albumin, and discuss the relationship to protein solubility and pH-dependent structural transitions.


Predictability in orbital reconstruction. A human cadaver study, part III: Implant-oriented navigation for optimized reconstruction.
Navigation-assisted orbital reconstruction remains a challenge, because the surgeon focuses on a two-dimensional multiplanar view in relation to the preoperative planning. This study explored the addition of navigation markers in the implant design for three-dimensional (3D) orientation of the actual implant position relative to the preoperative planning for more fail-safe and consistent results. Pre-injury computed tomography (CT) was performed for 10 orbits in human cadavers, and complex orbital fractures (Class III/IV) were created. The orbits were reconstructed using preformed orbital mesh through a transconjunctival approach under image-guided navigation and navigation by referencing orientating markers in the implant design. Ideal implant positions were planned using preoperative CT scans. Implant placement accuracy was evaluated by comparing the planned and realized implant positions. Significantly better translation (3.53 mm vs. 1.44 mm, p = 0.001) and rotation (pitch: -1.7° vs. -2.2°, P = 0.52; yaw: 10.9° vs. 5.9°, P = 0.02; roll: -2.2° vs. -0.5°, P = 0.16) of the placed implant relative to the planned position were obtained by implant-oriented navigation. Navigation-assisted surgery can be improved by using navigational markers on the orbital implant for orientation, resulting in fail-safe reconstruction of complex orbital defects and consistent implant positioning.


The alteration of neuronal activities of the cuneiform nucleus in non-hypovolemic and hypovolemic hypotensive conditions.
The cuneiform nucleus is located in the center of the circuit that mediates autonomic responses to stress. Hemorrhagic hypotension leads to chemoreceptor anoxia, which consequently results in the reduction of baroreceptor discharge and stimulation of the chemoreceptor. Using the single-unit recording technique, the neuronal activities of the cuneiform nucleus were investigated in hypotensive states induced by hemorrhage and administration of an anti-hypertensive drug (hydralazine). Thirty male rats were divided into the control, hemorrhage, and hydralazine groups. The femoral artery was cannulated for the recording of cardiovascular responses, including systolic blood pressure, mean arterial pressure, and heart rate. Hydralazine was administered via tail vein. The single-unit recording was performed from the cuneiform nucleus. The maximal systolic blood pressure and the mean arterial pressure significantly decreased and heart rate significantly increased after the application of hydralazine as well as the following hemorrhage compared to the control group. Hypotension significantly increased the firing rate of the cuneiform nucleus in both the hemorrhage and hydralazine groups compared to the control group. The present data indicate that the cuneiform nucleus activities following hypotension may play a crucial role in blood vessels and vasomotor tone.


The blood heat exchanger in intra-arterial selective cooling infusion for acute ischemic stroke: A computational fluid-thermodynamics performance, experimental assessment and evaluation on the brain temperature.
Intra-arterial selective cooling infusion with the autologous blood (IA-SCAI) is a promising therapeutic hypothermia induction method for conferring neuroprotection to acute ischemic stroke (AIS) patients. The blood heat exchanger (BHE) plays a crucial role in IA-SCAI's cooling capacity. However, there are no BHEs currently available that are specifically designed for the IA-SCAI, which requires a low blood flow to be compatible with cerebral hemodynamics. In an effort to develop a BHE for AIS patients, a prototype of a commercial BHE, Medtronic MYOtherm XP®, was mathematically modeled; specifically, computational fluid dynamics (CFD) was used to analyze its hemo- and thermo-dynamic characteristics under low blood flow including temperature distribution, velocity field and shear stress. Our numerical model predicted the hemolysis index to be 0.0041%-0.0581% inside the BHE with blood flows rates of 10 ml min-1-50 ml min-1. The in vitro heat transfer experiment showed that the BHE efficiently cooled the simulated blood from the initial 37 °C-5.8 °C within 150 s by using cold water (200 ml·min-1, 0 °C). The cooled simulated blood was able to cool the simulated blood in the middle cerebral artery of an artificial circulating system from 37 °C to 16.8 °C-33.7 °C depending on the blood perfusion rate (10-50 ml/min). A biological heat transfer mathematical model showed that brain tissue could be cooled by 2 °C within the initial 1min of infusion. This study verified the feasibility of using a commercial BHE for IA-SCAI and provided insights into its cooling capacity for therapeutic hypothermia.


Healing of gingival recession following orthodontic treatment: a 30-year case report.
This case report describes the healing of gingival recessions on mandibular incisors resulting from orthodontic treatment of a deep bite malocclusion at a 30-year follow-up observation. The marked improvement in the severe recessions was a consequence of the elimination of the direct trauma, orthodontic intrusion of the affected teeth, and subsequent creeping attachment over time. No periodontal treatment was performed before or after orthodontic treatment.


Development of the Nanobody display technology to target lentiviral vectors to antigen-presenting cells.
Lentiviral vectors (LVs) provide unique opportunities for the development of immunotherapeutic strategies, as they transduce a variety of cells in situ, including antigen-presenting cells (APCs). Engineering LVs to specifically transduce APCs is required to promote their translation towards the clinic. We report on the Nanobody (Nb) display technology to target LVs to dendritic cells (DCs) and macrophages. This innovative approach exploits the budding mechanism of LVs to incorporate an APC-specific Nb and a binding-defective, fusion-competent form of VSV.G in the viral envelope. In addition to production of high titer LVs, we demonstrated selective, Nb-dependent transduction of mouse DCs and macrophages both in vitro and in situ. Moreover, this strategy was translated to a human model in which selective transduction of in vitro generated or lymph node (LN)-derived DCs and macrophages, was demonstrated. In conclusion, the Nb display technology is an attractive approach to generate LVs targeted to specific cell types.


Harm reduction readiness for illicit IV drug use among safety-net primary care practices in the San Fernando Valley.
Harm reduction is an accumulation of strategies aimed at preventing adverse health outcomes associated with illicit substance use. Several harm reduction programs and services exist within Los Angeles County (LAC), however their success relies in part on the application of harm reduction principles by local primary care providers serving patients with substance use disorders. This study aims to assess the readiness of patient-centered medical homes in the San Fernando Valley to provide effective harm reduction to patients who use injection drugs and identify barriers to doing so. An online survey was distributed to primary care providers and social workers via email at federally qualified health centers and LAC Department of Health Services clinics in the San Fernando Valley between May and June 2019. It consisted of 22 multiple-choice, Likert scale, and short answer questions. The survey assessed knowledge of injection drug use (IDU), familiarity and utilization of harm-reduction and resources, and self-evaluation of attitudes and skills. There were a total of 41 survey respondents across all clinics. Of respondents, 98% correctly identified heroin as a drug typically injected, and 93% identified Hepatitis C as an infectious risk of IDU. 63% of respondents use harm reduction strategies every few months or less. 34% prescribe buprenorphine routinely, and 76% prescribe pre-exposure prophylaxis to those at risk for Human Immunodeficiency Virus (HIV). 76% are comfortable discussing IDU with their patients, but 59% indicate that they lack the necessary skills, and 42% agree that they lack the time to address it. Knowledge of IDU was adequate among those surveyed, although overall utilization of harm reduction was infrequent. There is a perceived deficit in skills and time to effectively provide harm reduction to primary care patients in the San Fernando Valley.


Integrated care of childhood disease in Brazil: mothers' response to the recommendations of health workers.
To describe the process of follow-up in primary care facilities where the Integrated Management of Childhood Illness (IMCI) strategy was implemented. IMCI was developed by WHO and UNICEF as an integrated approach to manage sick children under 5 y of age and aims to reduce mortality and morbidity. From August 2001 to February 2002, 229 sick children who had a health condition included in the IMCI case management guidelines were seen in six family healthcare facilities in Brazil. We analysed the care provided to 153 children who were recommended for a 2- or 5-d follow-up visit. Children who did not return were visited and assessed at home. Only 87 children (56.9%) timely returned for follow-up: 70 had improved, eight presented the same health conditions, five were worse and four had a new problem. The main reasons given for not returning for follow-up were: the child had improved (35.1%) and other family priorities (47.4%). Home visits showed that, although most children had improved (n=49), some had a new health problem and one child was sick enough to be referred. Prescription of antibiotics was associated with increased probability of returning for a follow-up visit (RR =1.64 [1.22-2.20], p=0.001). Adherence to follow-up was just over 50%, mostly because the condition had already resolved, but some children were still sick and needed intervention. Training on counselling on the recognition of danger signs and when to return for a follow-up visit must be reinforced.


Aortic origin of right pulmonary artery: early detection by cross-sectional and color-Doppler-echocardiography in two infants submitted to successful surgical repair.
The aortic origin of the right pulmonary artery was recognized in two infants by cross-sectional echocardiography. The sub-costal short axis view was sufficient to make the diagnosis. The Doppler and color-Doppler techniques were useful in adding the hemodynamic information to the anatomical diagnosis. Early surgical correction was performed in the infants with success without needing to resort to cardiac catheterization.


Private sector surgical training: feasibility through the lens of appendicectomy.
Training in medicine and surgery has been a public hospital responsibility in Australia. Increasing specialist training needs has led to pressure on speciality societies to find additional training posts, with one utilized solution being the establishment of private hospital training. This growing use has been despite no previously published evaluations of private hospital training in Australia. This article seeks to evaluate the feasibility of surgical training in private hospitals in appendicectomy. Data were prospectively collected on registrar involvement in appendicectomy cases at a single private tertiary institution over 1 year. These data were divided into groups according to registrar involvement and analysed, looking at training caseload, operating theatre time and complications. A total of 122 cases were analysed over the study period. Registrars were more likely to have increased primary operator responsibility if they were an accredited versus unaccredited registrar (P = 0.04) and if the case was open versus laparoscopic (P < 0.001). There was an increase of 15% in total procedure time when the registrar was involved (P = 0.04). There was no significant difference in complications whether the registrar was involved or not. Training in the private sector in Australia appears feasible, with a small loss of efficiency and no increase in complications. This article hopes to further encourage implementation and evaluation of private sector training programs to expand current training positions. Further studies, in different specialty and procedural domains, are needed to assess and evaluate the ongoing feasibility of private sector training.


Ura- host strains for genetic manipulation and heterologous expression of Torulaspora delbrueckii.
Recently, the industrial and academic interest in the yeast Torulaspora delbrueckii has increased notably due to its high resistance to several stresses. This characteristic has made of this organism a very attractive model to study the molecular basis of the stress response in yeast. However, very little is known about the physiology and genetics of this yeast, and the tools for its manipulation have not been developed. Here, we have generated Ura(-) strains of the baker's yeast T. delbrueckii IGC5323 by either 5-FOA-aided selection or transformation with a PCR-based disruption cassette, natMX4, which confers nourseothricin resistance. Furthermore, the mutant and disruptant strains were used as recipient of a plasmid containing the xlnB cDNA from Aspergillus nidulans. Our results indicate that Torulaspora transformants produce active recombinant protein at a similar level to that found for Saccharomyces.


A free radical scavenger role for daunomycin: inhibition of nonenzymatic oxidation of NADH.
The effect of daunomycin(Dm) on the nonenzymatic oxidation of NADH in the presence of metal ions, H2O2 and various ligands was examined. The results show that daunomycin inhibits the oxidation of NADH by reacting with one or more of the reaction intermediates which include OH., HO2., O2. and NAD.. This reaction is a reductive one involving the anthraquinone moiety of daunomycin as confirmed by control experiments by comparative UV-Vis analysis of the spectral character of daunomycin after reduction by NaBH4. Daunomycin, once reduced, apparently does not transfer its electron to another species such as O2 and is thus thought to play the role of free radical scavenger.


PCDD/Fs in ambient air collected in Zagreb, Croatia.
Levels of PCDD/Fs were measured at four different sites in Zagreb, capital of Croatia. Also one sample was taken during spontaneously initiated open fire on a landfill and one sample where garden waste of unknown content was burnt. Over period 1997-2000, 28 samples were collected and levels ranged between 9 and 306 fgI-TEQm(-3), except in the sample collected during landfill fire. Air PCDD/F levels in Zagreb at four sites were different and the highest levels were observed in industrial area. Seasonal variation of levels is also evident with higher levels in winter than in summer. Our results show that PCDD/F levels in ambient air collected in Zagreb are at lower end of the published data range. In general, homologue profiles were quite similar for all locations, the concentration of PCDD homologues increased while the concentration of PCDF homologues decreased with increasing degree of chlorination. PCDD/F levels in the landfill fire sample was 13,200 fgI-TEQm(-3) which are much higher than levels in garden waste burning sample or in sample collected at industrial site. During landfill fire, the concentration of 2,3,7,8-TCDF becomes even higher than the concentration of OCDF and is equal to the concentration of 1,2,3,4,6,7,8-HpCDF.


Decreased expression of m6A demethylase FTO in ovarian aging.
N6-methyladenosine (m6A) and demethylase fat mass and obesity-associated protein (FTO) were reported to be associated with oocyte development and maturation. But the relationship between FTO and ovarian aging was still unclear. This study was aimed at investigating the FTO expression level and the m6A content during ovarian aging. The expression level of FTO and the content of m6A RNA methylation in human follicular fluid (FF), granulosa cells (GCs) and mouse ovary from different age groups were studied by ELISA, WB, qRT-PCR, IHC and m6A Colorimetric. Human FF ELISA quantified that the level of FTO protein decreased with age (P = 0.025). QRT-PCR results showed that the relative expression of FTO in human GCs was lower in the elderly group than in the young group (P = 0.012). FTO mRNA and protein expression levels were lower in the ovary of 32-week-old mice than in 3- and 8-week-old mice (P < 0.05). Immunohistochemistry showed FTO was relatively decreased in 32-week-old mice (P < 0.05). The m6A content in total RNA from old human GCs and ovary from 32-week-old mice was significantly higher compared with the younger ones. In human FF, GCs and mouse ovary, the expression of FTO decreased while the content of m6A increased with aging. However, the inner mechanism still needs further investigation.


Increased mTORC1 signaling UPRegulates stress.
In this issue of Molecular Cell, Ozcan et al. (2008) show that the loss of the tuberous sclerosis tumor suppressor complex induces endoplasmic reticulum stress, leading to attenuation of insulin receptor signaling activity via the unfolded protein response.


Parameters affecting improvement of excessive daytime sleepiness in obstructive sleep apnea patients.
Obstructive sleep apnea (OSA) is a sleep-related breathing disorder caused by repetitive obstruction of the upper airway; this impairs gaseous exchange, resulting in hypoxia, hypercapnia, and frequent arousals. Excessive daytime sleepiness (EDS) is a common daytime symptom of OSA. EDS manifests as fatigue and impaired attention, leading to poor performance at work and falling asleep while driving, which is a major socioeconomic problem. Therefore, it is important to properly treat EDS and accurately predict the response to treatment. However, few studies have compared OSA patients showing and not showing improvement in EDS. Therefore, this study aimed to objectively analyze and compare EDS improvement and non-improvement groups. We retrospectively reviewed the medical records of 57 OSA patients with EDS. Patients were divided into two groups according to the improvement in EDS after positive airway pressure (PAP) device treatment. We analyzed differences in clinical records including patients' age, sex, history of smoking, hypertension, diabetes, myocardial infarction, and cerebrovascular disease between the two groups. Systolic, diastolic blood pressure, blood test including blood glucose, total cholesterol, high- and low-density lipoprotein cholesterol, and triglyceride levels were also analyzed. Polysomnography (PSG) data, PAP device treatment compliance and scores of questionnaires related to various psychiatric symptoms, subjective sleep quality between the two groups were also analyzed. There was no statistically significant difference in age, gender, or past medical history between the two groups. Systolic and diastolic blood pressure, and blood test results, were also not significantly different. Among the questionnaires related to various psychiatric symptoms, the groups showed statistically significant differences in Social Avoidance and Distress Scale (SADS) and Fear of Negative Evaluation (FNE) scores (P = 0.001 and 0.020, respectively). The group differences in the scores on the other questionnaires were not significantly different. Among the PSG items, significant group differences were observed in the percentage of stage 2 non-REM sleep (N2%, P = 0.023), apnea index (AI, P = 0.005), apnea-hypopnea index (AHI, P = 0.023), and frequency of 3 % oxygen desaturation (ODI3, P = 0.001). No obesity-related parameters showed significant group differences. The percentage of days on which a PAP device was used (out of 90 days; PAP%) and percentage of days on which a PAP device was used for >4 h (Time4%) did not differ significantly. The SADS, FNE, AI, AHI, N2%, and ODI3 parameters differed significantly between the EDS improvement and non-improvement groups. These parameters may help clinicians treat and predict the prognosis of patients suffering with EDS.


A comparison of four prenatal care indices in birth outcome models: comparable results for predicting small-for-gestational-age outcome but different results for preterm birth or infant mortality.
Several different indices of prenatal care have been used in birth outcome models to analyze the relationship between the adequacy of prenatal care and low birthweight, preterm birth, and infant mortality. This investigation compared the performance of the Kessner index, the GINDEX, the adequacy of prenatal care utilization (APNCU) and certain variants of the APNCU in such outcome models. Data from National Center for Health Statistics' (NCHS) Linked Birth and Infant Death Cohort files were used in multivariate logistic regression models to estimate adjusted odds ratios comparing different prenatal care utilization categories for each index. When the indices were used in small-for-gestational-age outcome models, the conclusions suggested by the various indices were similar. In models for preterm birth and infant mortality, by contrast, the various indices gave widely differing results. Unlike the use of other indices, the use of the GINDEX paradoxically suggested that birth outcomes were better in the inadequate, intermediate, and intensive categories than in the adequate category. The conclusions drawn concerning the association between prenatal care utilization and small-for-gestational-age seem relatively robust in the sense of being consistent across indices. In analyzing associations between prenatal care and preterm birth or infant mortality, care must be taken in choosing indices, because results differ substantially across indices.


Efficacy of Diode Laser for the Management of Potentially Malignant Disorders.
Laser dentistry is a one of the upcoming advanced treatment modality for oral mucosal lesions. Diode laser is a soft tissue laser that has found much acceptance in all branches of dentistry. Available compact size and feasibility has render diode laser an enhanced tool for today's clinical practice. The aim of this study is to determine the efficacy and safety of diode laser for the management of white lesions such as oral leukoplakia (OL) and oral lichen planus (OLP). The study was conducted by using diode laser 980 nm on 10 patients with white lesions (5 OL and 5 OLP) aged between 35 to 65 years. Of the 10 patients (5 OL and 5 OLP), 3 patients (30%) complained of moderate pain and 7 patients (70%) complained of mild pain, for first 3 days after laser irradiation, and pain disappeared at end of first week. There was no recurrence of the lesion during the 6-month follow up. Diode lasers provide acceptable clinical improvement of potentially malignant lesions with minimal side effects. It can be considered one of the best alternative treatment modality for oral mucosal lesions.


Lipid shape as a determinant of lipid composition in Clostridium butyricum. The effects of incorporation of various fatty acids on the ratios of the major ether lipids.
The lipid composition of Clostridium butyricum is strongly influenced by the aliphatic chain compositions of the membrane lipids. Growth on cis-monounsaturated fatty acids in the absence of biotin was shown to affect the relative proportions of phosphatidylethanolamine, plasmenylethanolamine, and the glycerol acetal of plasmenylethanolamine most strongly, with smaller effects on the acidic lipids, phosphatidylglycerol and cardiolipin. The ratio of the glycerol acetal of plasmenylethanolamine to total phosphatidylethanolamine in cells grown on a series of fatty acids is shown to decrease in the following order; cis-vaccenic acid greater than or equal to oleic acid = C19-cyclopropane fatty acid greater than linoleic acid greater than petroselinic acid greater than elaidic acid greater than 14-methylhexadecanoic acid (anteiso-C17) greater than 12-methyltridecanoic acid (iso-C14). All fatty acids were extensively incorporated into the lipid acyl, alkenyl, and alkyl chains. There was considerable chain-elongation of the iso-C14 to iso-C16. The results are consistent with the hypothesis that the membrane lipid composition is strongly influenced by lipid shape and that the observed changes in lipid composition serve to stabilize the bilayer arrangement of the cell membrane.


Efficacy of Arthroscopic Surgery in the Management of Adhesive Capsulitis: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.
To determine which interventions optimize clinical outcomes in adhesive capsulitis by performing a network meta-analysis of randomized controlled trials. A systematic review was conducted of all clinical trials on adhesive capsulitis published since 2008. Patient cohorts were grouped into treatment categories; data collected included range of motion (ROM) and patient-reported outcome measures (PROMs). Interventions were compared across groups by means of arm-based Bayesian network meta-analysis in a random-effects model. Sixty-six studies comprising 4042 shoulders (57.6% female patients, age 54.8 ± 3.2 years [mean ± standard deviation]) were included. The most commonly studied interventions were physical therapy (PT) or shoulder injections. Network meta-analysis demonstrated that arthroscopic surgical capsular release was the most effective treatment in increasing ROM. This effect was apparent in forward flexion (effect difference [ED] versus placebo, 44°, 95% confidence interval [CI] 31° to 58°), abduction (ED 58°, 45° to 71°), internal rotation (ED 34°, 24° to 44°), and external rotation (ED 59°, 37° to 80°). Interventions most effective for pain relief included PT supplemented with either medical therapy (ED -4.50, -9.80 to 2.80) or ultrasound therapy (ED -5.10, -5.10 to -1.40). Interventions most effective for improvement of functional status included PT, manipulation under anesthesia (MUA), intra-articular or subacromial steroid injection, surgical capsular release, and supplementation of PT with alternative therapy. No one treatment emerged superior in regard to ROM, pain symptoms, and functional status. Surgery (after failure of conservative treatment) ranked highest across all ROM domains. Treatments that ranked highest for treatment of pain included PT supplemented with either medical therapy or ultrasound. Finally, treatments that ranked highest for improvements in functional status included MUA, PT with medical therapy, surgical intervention, PT with ultrasound, PT with injection, and injection alone. II, systematic review and network meta-analysis of level I and II studies.


Effects of clonidine infusion and withdrawal on blood pressure and behaviour in the rat. A preliminary study.
Clonidine (10 micrograms/kg/hr) was administered continuously to normotensive rats for 5 days using osmotic minipumps. This treatment attenuated the episodic fluctuations in blood pressure normally observed during rapid eye movement (REM) sleep. However, 18-24 hr after withdrawal of clonidine, pronounced fluctuations in blood pressure superimposed upon tonic increases in pressure as well as muscular twitching and irregular respiration were seen during sleep. These responses were abolished by an injection of clonidine or phentolamine. The results demonstrate that after withdrawal of clonidine administration, an increased lability of blood pressure occurs during sleep and probably results from an increased frequency and duration of REM sleep.


The red blood cell as a mediator of endothelial dysfunction in patients with familial hypercholesterolemia and dyslipidemia.
Patients with familial hypercholesterolemia (FH) display high levels of low-density lipoprotein cholesterol (LDL-c), endothelial dysfunction, and increased risk of premature atherosclerosis. We have previously shown that red blood cells (RBCs) from patients with type 2 diabetes induce endothelial dysfunction through increased arginase 1 and reactive oxygen species (ROS). To test the hypothesis that RBCs from patients with FH (FH-RBCs) and elevated LDL-c induce endothelial dysfunction. FH-RBCs and LDL-c >5.0 mM induced endothelial dysfunction following 18-h incubation with isolated aortic rings from healthy rats compared to FH-RBCs and LDL-c <2.5 mM or RBCs from healthy subjects (H-RBCs). Inhibition of vascular but not RBC arginase attenuated the degree of endothelial dysfunction induced by FH-RBCs and LDL-c >5.0 mM. Furthermore, arginase 1 but not arginase 2 was elevated in the vasculature of aortic segments after incubation with FH-RBCs and LDL-c >5.0 mM. A superoxide scavenger, present throughout the 18-h incubation, attenuated the degree of endothelial dysfunction induced by FH-RBCs and LDL-c >5.0 mM. ROS production was elevated in these RBCs in comparison with H-RBCs. Scavenging of vascular ROS through various antioxidants also attenuated the degree of endothelial dysfunction induced by FH-RBCs and LDL-c >5.0 mM. This was corroborated by an increase in the lipid peroxidation product 4-hydroxynonenal. Lipidomic analysis of RBC lysates did not reveal any significant changes across the groups. FH-RBCs induce endothelial dysfunction dependent on LDL-c levels via arginase 1 and ROS-dependent mechanisms.


KeggExp: a web server for visual integration of KEGG pathways and expression profile data.
Effective visualization is important for knowledge discovery when analysing expression profile data. However, existing tools for visually integrating expression profile data with KEGG pathway maps lack extensive interactive visualization operations. KeggExp simultaneously presents the pathway map of one pathway, dendrogram and heatmap of the genes in the pathway and scatter map of one gene; and also provides interactive operations for highlighting specific genes on the pathway map, including differentially-expressed genes, co-expressed genes selected from the heatmap and user-input genes. With KeggExp, researchers, including those without programming skills, can take advantage of its interactive operations to determine key genes or pathways when analysing expression profile data. Freely available at http://www.fgvis.com/expressvis/KeggExp/. Language: JavaScript, python; Libraries: D3.js, Rxjs, Angular, Django, Django rest frame work, Scipy. Supplementary data are available at Bioinformatics online.


X-ray Crystal Structure Analysis of VHH-Protein Antigen Complexes.
VHHs are antigen-binding domains cloned from heavy-chain antibodies found in camelids. These proteins have generated considerable interest in a variety of applications as research reagents, crystallization chaperones, and therapeutics. The evolutionary adaptations of VHHs have resulted in biophysical properties and antigen-binding modalities which are distinct from those of conventional antibodies. A detailed molecular analysis of VHH interactions with their cognate protein antigens is valuable for understanding structure-function relationships and for protein engineering. The majority of VHHs bind to folded proteins and thus recognize discontinuous three-dimensional epitopes. While multiple approaches exist for dissecting the interaction between a protein antigen and a VHH, X-ray crystallography remains the highest resolution method available. Here, we provide an updated procedure for determining and analyzing the X-ray structure of a VHH in complex with a protein antigen. We describe the recombinant expression and purification of VHHs and protein antigens, purification and analysis of protein complexes, crystallization, and optimization, X-ray structure determination by molecular replacement, and analysis of the complex.


Addition of Shewanella oneidensis MR-1 to the Dehalococcoides-containing culture enhances the trichloroethene dechlorination.
Dehalococcoides is able to completely dehalogenate tetrachloroethene (PCE) and trichloroethene (TCE) to ethene (ETH). However, the dechlorination efficiency of Dehalococcoides is low and result in the accumulation of toxic intermediates. In this study, Shewanella oneidensis MR-1 (S. oneidensis MR-1) was added to the Dehalococcoides-containing culture and the complete TCE to ETH dechlorination was shortened from 24 days to 16 days. Dehalococcoides-targeted 16S rRNA gene and two model reductive dehalogenase (RDase) genes (tceA and vcrA), responsible for dechlorinating TCE to vinyl chloride (VC) and VC to ETH respectively, were characterized. Results showed that S. oneidensis MR-1 has no effect on the cell growth while the RDase genes expression was up-regulated and the RDase activity of Dehalococcoides was elevated. The mRNA abundance of vcrA increased approximately tenfold along with the increased concentration of vitamin B12 (cyanocobalamin). Interestingly, the addition of S. oneidensis MR-1 increased the concentration of vitamin B12 by affecting the microbial community structure. Therefore, the addition of S. oneidensis MR-1 might have a positive effect on regulating the activity of RDase of functional microorganisms and uptake of vitamin B12, and further provided a practical vision of chloroethene dechlorination by the Dehalococcoides-containing culture.


Effect of potentially toxic elements on soil multifunctionality at a lead smelting site.
Contaminated soil at smelting sites affects land utilization and environmental regulation, resulting in soil degradation. However, the extent to which potentially toxic elements (PTEs) contribute to site soil degradation and the relationship between soil multifunctionality and microbial diversity in the process remains poorly understood. In this study, we investigated changes in soil multifunctionality and the correlation between soil multifunctionality and microbial diversity under the influence of PTEs. The change in microbial community diversity was closely related to changes in soil multifunctionality caused by PTEs. Microbial diversity, not richness, drives the delivery of ecosystem services in smelting site PTEs-stressed environments. Structural equation modeling identified that soil contamination, microbial taxonomic profile and microbial functional profile could explain 70% of the variance in soil multifunctionality. Furthermore, our findings demonstrate that PTEs limit soil multifunctionality by affecting soil microbial communities and functionality, whilst the positive effect of microorganisms on soil multifunctionality was mainly driven by the fungal diversity and biomass. Finally, specific fungal genera closely related to soil multifunctionality were identified, with saprophytic fungi being particularly important for maintaining multiple soil functions. The results of the study provide potential guidance for the remediation, pollution control practices and mitigation of degraded soils at smelting sites.


Improvement of the method of Karnovsky and Roots for the histochemical demonstration of acetylcholinesterase.
The aqueous reaction medium of Karnovsky and Roots for the demonstration of acetylcholinesterase (AChE) activity was modified to obtain a gel-incubation medium that prevents diffusion of the reaction product and the soluble part of AChE into the incubation medium and along the plane of the section. The incubation medium contained 27% polyvinyl alcohol and suitable concentrations of the components of the medium of Karnovsky and Roots. The application of this incubation medium to sections of rat hippocampus resulted in intense staining, with the reaction products being mainly localized in fibrous structures.


Practical considerations when developing guidelines for managing critical bleeding.
In the critical care environment, clinicians strive to provide the best treatment possible for patients in desperate need. Such motivation, however, can be a key driver of escalating costs, especially when the use of nonreimbursable therapies goes unchecked or when futile attempts are made to improve outcomes in patients who may not benefit from aggressive management. Proactive intervention in the form of protocols is necessary to guide the use of blood products, coagulation factors, and antifibrinolytic agents. Evidence from clinical trials as well as recommendations from opinion leaders and professional societies should be critically evaluated and used to develop institution-specific protocols. If adopted with multidisciplinary cooperation, such protocols can curb the temptation to rely on anecdotal bedside observations to guide care and treat the patient with critical bleeding. Forming an ad hoc group of an institution's pharmacy and therapeutics committee can be an important step toward this end. The processes that a multidisciplinary group might follow are described, thus providing an idealized example of how pharmacists, working collaboratively with other clinicians and administrators, can be positioned at the center of an institution-wide solution to promote carefully considered, safe, effective, and cost-conscious care.


Appendiceal perforation, necrotizing groin infection and spermatic cord necrosis in a case of Amyand's hernia.
Inguinal hernias containing the appendix are described as Amyand's hernias. The surgical approach to these types of hernias is dependent on the type present and associated intra-operative findings. We present a case of complicated type IV Amyand's hernia, which was managed though combined abdominal and inguinal approach. Though the patient had a prolonged post-operative course due to pulmonary embolism, he progressed to full recovery. The different grades of Amyand's hernia are repaired in varying ways, including laparoscopic and open approaches with or without mesh. The type of repair must be tailored to the patient and disease process. Primary repair of a perforated Amyand's hernia provides adequate strength with decreased risk of infection due to synthetic material.


[Serum thiopental values, spontaneous frontal muscle electromyography activity and compressed EEG amplitudes and frequency values in thiopental infusion anesthesia].
Serum thiopentone (S-Thiop) was estimated every 10 minutes using a new high performance liquid chromatographic method during fentanyl-bolus-complemented (0.01 mg) thiopentone infusion anaesthesia (bolus of 5 mg/kg, infusion dosis 23.7 mg/min) for laryngo-microscopic procedures. Before stopping the infusion after 18/17 min (SD 8/5) (male/female) S-Thiop was (mean (SD) range) 16.0/12.4 (4.6/5.7) 5.9-26.8/5.1-26.6 mg/l; after stop of the infusion 12.8/10.5 (4.5/5.3) 7.6-25.5/4.5-23.4 mg/l. Patients reacted to verbal command after 11.5 (10.3) 11-81 min. There were no clinically relevant correlations between S-Thiop and frontal EMG and compressed 1-channel-EEG (ABM, Datex, Helsinki), nor with data recorded during recovery. Reasons may be: the total depolarisation block caused by succinylcholine; the method of compressing the EEG; subjective influences on the recording of recovery data; sampling in intervals of 10 min instead of at certain points of the anaesthesia course. We still recommend this total i.v.-anaesthesia for the short time endolaryngeal procedures need; before using this method for longer periods additional pharmacokinetic studies should be performed.


Mechanisms of action of escapin, a bactericidal agent in the ink secretion of the sea hare Aplysia californica: rapid and long-lasting DNA condensation and involvement of the OxyR-regulated oxidative stress pathway.
The marine snail Aplysia californica produces escapin, an L-amino acid oxidase, in its defensive ink. Escapin uses L-lysine to produce diverse products called escapin intermediate products of L-lysine (EIP-K), including α-amino-ε-caproic acid, Δ¹-piperidine-2-carboxylic acid, and Δ²-piperidine-2-carboxylic acid. EIP-K and H₂O₂ together, but neither alone, is a powerful bactericide. Here, we report bactericidal mechanisms of escapin products on Escherichia coli. We show that EIP-K and H₂O₂ together cause rapid and long-lasting DNA condensation: 2-min treatment causes significant DNA condensation and killing, and 10-min treatment causes maximal effect, lasting at least 70 h. We isolated two mutants resistant to EIP-K plus H₂O₂, both having a single missense mutation in the oxidation regulatory gene, oxyR. A complementation assay showed that the mutated gene, oxyR(A233V), renders resistance to EIP-K plus H₂O₂, and a gene dosage effect leads to reduction of resistance for strains carrying wild-type oxyR. Temperature stress with EIP-K does not produce the bactericidal effect, suggesting the effect is due to a specific response to oxidative stress. The null mutant for any single DNA-binding protein--Dps, H-NS, Hup, Him, or MukB--was not resistant to EIP-K plus H₂O₂, suggesting that no single DNA-binding protein is necessary to mediate this bactericidal effect, but allowing for the possibility that EIP-K plus H₂O₂ could function through a combination of DNA-binding proteins. The bactericidal effect of EIP-K plus H₂O₂ was eliminated by the ferrous ion chelator 1,10-phenanthroline, and it was reduced by the hydroxyl radical scavenger thiourea, suggesting hydroxyl radicals mediate the effects of EIP-K plus H₂O₂.


Indium(III) chloride-sodium borohydride system: a convenient radical reagent for an alternative to tributyltin hydride system.
The indium hydride generated from NaBH4 and InCl3, is a promising candidate of alternative to Bu3SnH. In particular, the catalytic performance of InCl3 in the dehalogenation of alkyl and aryl halides, intramolecular cyclization and intermolecular coupling reaction are noteworthy.


The impact of snow on orthopaedic trauma referrals.
Adverse weather has been shown to increase orthopaedic referrals and place strain on services. This retrospective study undertaken at a teaching hospital concerned referrals between April 2009 and April 2010 comparing days when snow fell to days when it did not. Referrals increased significantly on snow days (to 74.9 per day) in comparison to normal weather days (33.5 per day). During snow days there were significant increases in the number of distal radius and ankle fractures referred but not of fractured necks of femur. Complications during the snow fall period were related to procedures performed outside of the trauma unit with further difficulties related to a lack of operating equipment and implant availability. As a result of our study, we recommend that during periods of heavy snow fall orthopaedic and trauma units should place senior orthopaedic trainees in Accident and Emergency to review patients as a triage service, organise trauma lists related to surgeon specific expertise and avoid sending trauma patients outside the unit for operation.


A double-peak phenomenon in the pharmacokinetics of veralipride after oral administration: a double-site model for drug absorption.
Equal doses of veralipride have been given to 12 healthy volunteers by three different administrations--intravenous infusion, oral solution, and oral capsules--in a randomized cross-over design. After the intake of the solution, but not after infusion or capsules, two maximum plasma concentrations have been observed and interpreted, according to a double-site model for drug absorption.


Influence of various nutrients and their mode of application on plasma cholecystokinin (CCK) bioactivity.
CCK is known to be a major endocrine stimulant of the exocrine pancreas. However, the influence of various compositions of nutrients and their mode of administration on plasma CCK is still not clear. We therefore studied plasma CCK after either oral or intraduodenal administration of various solid and liquid diets. Plasma CCK was measured by bioassay. Nine healthy male volunteers received three different isocaloric diets via intraduodenal perfusion (1 kcal/ml; 300 ml/90 min). Diet A consisted of low-molecular oligopeptides (energy: protein 18%, fat 22%, carbohydrates 60%); diet B was a high molecular diet enriched with fat and fiber (protein 15%, fat 30%, carbohydrates 55%, fiber 1 g/100 ml); and diet C was a high molecular diet, poor in fat and fiber-free (protein 14%, fat 7%, carbohydrates 79%). All diets caused a rapid increase in plasma CCK, followed by a slow decrease. The highest CCK plasma values were achieved with diet B (8.4 +/- 1.6 pM); diets A and C led to similar, rather low plasma CCK values (A: 5.0 +/- 0.7 pM). Another five volunteers received the above-described liquid diets orally. Integrated CCK plasma values were similar for all oral liquid diets studied and not different from those seen after intraduodenal administration of the high-molecular high-fat diet B. Oral administration of a solid diet (ten volunteers) comparable to diet B in calories and nutrient composition caused a rather small and delayed increase in plasma CCK.(ABSTRACT TRUNCATED AT 250 WORDS)


Elastofibroma dorsi: benign chest wall tumor.
Elastofibroma dorsi was diagnosed in seven patients at the Columbia-Presbyterian Medical Center between 1976 and 1986. The ages of the patients ranged from 6 to 79 years (mean 49.3 years). No sex predominance was seen. Five cases of unilateral subscapular tumor and two cases of bilateral masses were identified. Four patients had pain with arm motion, and the remaining patients were free of symptoms. A nonencapsulated soft tissue mass elevating the scapula was identified by computed tomography. Incisional biopsy was performed in all cases, followed by local excision of the tumor. On gross examination, these lesions were firm and rubbery. Histologic evaluation demonstrated a slightly hypercellular fibrous tissue that contained variable numbers of fragmented elastic fibers. All patients with symptomatic tumors had complete relief of their pain after the operation. No recurrences were observed. Clinically, elastofibroma may mimic sarcoma and fibromatosis (extraabdominal desmoid tumors). Whether elastofibroma is a true neoplasm or a reactive fibrous lesion that produces not only collagen, but also abnormal elastic fibers, has been the subject of controversy and remains undetermined.


Erratum: Corrigendum: Plasmonic nanosensors with inverse sensitivity by means of enzyme-guided crystal growth.
Nature Materials 11, 604-607 (2012); published online 27 May 2012; corrected after print 15 December 2017. In the version of this Letter originally published, the x and y values of the data points in Fig. 2c were incorrect. The original and corrected versions are shown below. The authors have also made some changes to the Supplementary Information: Fig.


Comparative effectiveness of self and family forms of the Michigan Alcoholism Screening Test.
Scores on the Michigan Alcoholism Screening Test completed by both patients and members of their families did not differ significantly; the scores indicated agreement with a psychiatric diagnosis of alcoholism in 70% of the cases.


Role of biochemical tests in the diagnosis of large pericardial effusions.
To determine the biochemical characteristics of large pericardial effusions in various disease states, and to assess their utility as diagnostic tools. An academic university hospital in the Western Cape, South Africa. Consecutive, prospective case series. One hundred ten hospital patients > 12 years old, who presented to the echocardiography department with large pericardial effusions, and 12 control subjects who underwent open-heart surgery (coronary artery bypass graft or aortic valve replacement). Fluid was sent for examination of biochemistry, adenosine deaminase, microbiology, hematology, and cytology. The etiology of each pericardial fluid sample was established using predetermined criteria. The biochemistry of pericardial exudates differed significantly from pericardial transudates. Light' s criteria (whereby an exudate is defined as having one or more of the following: pleural fluid/serum protein ratio > 0.5; pleural fluid/serum lactate dehydrogenase [LDH] ratio > 0.6; and/or pleural fluid LDH level > 200 U/L) were applied to pericardial fluids and demonstrated to be the most reliable diagnostic tool for identifying pericardial exudates. The corresponding sensitivity was 98%. Although laboratory tests are a useful guideline when assessing the etiology and pathophysiology of pericardial effusions, the majority of large, clinically significant pericardial effusions result from exudative causes.


The use of Morycz's desire-to-institutionalize scale across three racial/ethnic groups.
The objectives of this study were to assess the dimensionality and reliability of a frequently used scale for predicting the desire to institutionalize among White, African American, and Hispanic caregivers of persons with dementia. Exploratory factor analysis (EFA) and reliability analyses were performed on a slightly modified version of Morycz's (1985) Desire to Institutionalize (DTI) scale separately for each racial group using data from the Resources for Enhancing Alzheimer's Caregiver Health (REACH) II study (Belle et al., 2006). The EFA revealed a one-factor structure that was equivalent across all racial groups. The scale demonstrated moderate reliability with KR-20 alpha of .694 for Whites, .742 for African Americans, and .767 for Hispanics. Findings suggest that Morycz's DTI scale is a consistently reliable measure for assessing the desire to institutionalize across White, African American, and Hispanic dementia caregivers.


Splenectomy in the context of primary cytoreductive operations for advanced epithelial ovarian cancer.
To determine if the need to perform splenectomy due to metastatic disease in the context of complete primary cytoreduction for ovarian cancer diminishes the prognosis for survival. Between 1990 and 2004, 356 stage IIIC epithelial ovarian cancer patients underwent resection of all visible disease before systemic platinum-based combination chemotherapy. Forty-nine (13.8%) required a splenectomy due to metastatic disease. Survival was analyzed (log rank) on the basis of whether splenectomy was necessary. The frequency of performing other procedures, operative time, blood loss, transfusion rate, and hospitalization, was compared (Chi-square test; discrete and binomial data, t test; continuous data) on the basis of whether a splenectomy was required. Survival was not influenced (log rank) by the requirement of splenectomy (required; median 56.4 months, estimated 5-year survival of 48% vs. not required; median 76.8 months, estimated 5-year survival of 58% P = 0.4). The splenectomy subgroup more commonly required en-bloc resection of reproductive organs with rectosigmoid (89.8% vs. 55.7%, P < 0.001), diaphragm stripping (63.3% vs. 33.6%, <0.001)), full-thickness diaphragm resection (28.6% vs. 9.4%, P < 0.001), and resection of grossly positive retroperitoneal nodes (67.3% vs. 46.3%, P = 0.006). The splenectomy group had a longer operative time (238 min vs. 192 min, P = 0.004), estimated blood loss (1663 ml vs. 1167 ml, P = 0.001), transfusion rate (5.3 units prbc vs. 3.2 units prbc, P = 0.002), and hospitalization (16.1 vs. 12.2 days P = 0.001). The need for splenectomy to achieve complete cytoreduction is a reflection of advanced disease but is not a manifestation of tumor biology precluding long-term survival.


Assessment of therapeutic effect in patients with secondary hyperparathyroidism using bone scintigraphy.
The semi-quantitative method of bone scintigraphy [bone to soft tissue (B/ST) ratio] has been used in diagnosing and evaluating systemic metabolic bone diseases. The aim of this study is to evaluate of the therapeutic effect of secondary hyperparathyroidism (SHP). The subjects were ten hemodialysis patients with SHP. Seven patients underwent parathyroidectomy (PTX), and 22-Oxacalcitoriol (derivative of 1,25-dihydroxyvitamin D3) (OCT) was given to three patients. Bone scintigraphy and blood tests [intact parathyroid hormone (PTH), alkaline phosphatase (ALP), calcium (Ca), phosphorus (P), bone alkaline phosphatase (BALP), and deoxypridinoline (DPYD)] were performed before and after treatment. Regions of interest were drown around cranium, lumbar vertebrae, femoral neck and soft tissue of left medial thigh to calculate the B/ST ratio. The B/ST ratios of cranium, lumbar vertebrae, and femoral neck were reduced significantly after PTX (cranium, p = 0.0079, lumbar vertebrae, p = 0.0282, femoral neck, p = 0.0252). Intact PTH, ALP, Ca, P, BALP and DPYD levels were reduced significantly after PTX (intact PTH, p = 0.003, Ca, p = 0.0005, P, p = 0.0393, ALP, p = 0.0051, DPYD, p = 0.0232, BALP, p = 0.0324). After OCT administration, the B/ST ratio of each bony region showed tendency to diminish, although not significantly. Intact PTH levels were reduced significantly, although ALP, BALP, and DPYD levels were not. Ca and P levels were increased significantly because of the medicinal action of OCT. The B/ST ratio of cranium may be non-invasive method and have potential in evaluating the therapeutic effect of SHP.


Ultrasonographic splanchnic arterial flow measurement in severe acute pancreatitis.
Duplex ultrasonographic technology is now capable of detecting flow signals in the various splanchnic vessels and calculating the concomitant flow velocities using fast-Fourier transformation. To use Doppler sonography to investigate how splanchnic hemodynamics vary during the early stage of severe acute pancreatitis. Six patients with severe acute pancreatitis (age, 59.0 +/- 6.57 years; four men, two women) and seven with mild to moderate acute pancreatitis (age, 60.1 +/- 7.41 years; five men, two women) were examined with Doppler sonography immediately after disease onset. The maximum velocity, minimum velocity, mean velocity, pulsatility index, and resistive index were determined from the Doppler spectra from the proper hepatic artery, celiac artery, and superior mesenteric artery. We also examined 15 healthy subjects (age, 59.3 +/- 4.60 years; 10 men, five women) as controls. The maximum velocity of the proper hepatic artery in patients with severe acute pancreatitis was significantly higher than that in patients with mild to moderate acute pancreatitis (p = 0.011) and in control subjects (p = 0.0047). Similarly, significant increases in both the minimum velocity and the mean velocity of the proper hepatic artery were observed in patients with severe acute pancreatitis. Neither pulsatility index nor resistive index of the proper hepatic artery showed a significant difference among the three groups. There were no significant differences among the three groups with respect to the flow velocity of the superior mesenteric artery. In contrast, the pulsatility index of the superior mesenteric artery in patients with severe acute pancreatitis was significantly lower than that in patients with mild to moderate acute pancreatitis (p = 0.0058) or in control subjects (p = 0.0024). For patients with acute pancreatitis, a significant inverse correlation was obtained between the maximum velocity of the proper hepatic artery and the pulsatility index of the superior mesenteric artery (r = -0.658, p = 0.0145). The increase in the hepatic arterial flow velocity and the decrease in the superior mesenteric arterial pulsatility index may represent early events of the severe type of acute pancreatitis.


Long-lasting effects of chronic rTMS to treat chronic rodent model of depression.
Repetitive transcranial magnetic stimulation (rTMS) has been demonstrated in the pre-clinical and clinical settings to have an antidepressant effect. However, studies on the long-lasting effect of rTMS, especially when the effect is measured after treatment has ceased for a few weeks is lacking. We examined this question in a chronic unpredicted mild stress (CUMS) rat model of depression. We gave 3 weeks of high frequency (15 Hz) rTMS, venlafaxine, or these two treatments combined to a modified CUMS paradigm, and then investigated the prolonged effect of treatments. Behavioral testing (sucrose preference test, open field test, forced swimming test, novelty suppressed feeding test), plasma hormone level, hippocampal BrdU labeling, and amount of related neurotropic factors were used to assess the effects of stress and treatments. Long-term chronic rTMS significantly reversed andehonic-like behavior, increased hippocampus cell proliferation, BDNF protein level, phosphorylation of ERK1/2 compared with CUMS rats two weeks after the cessation of rTMS treatment. However, the changes in plasma hormone level were not sustained for that amount of time. Venlafaxine had no interaction with the physical stimulation. Our results suggest that high frequency rTMS has long-lasting effects, which may have some relationship with neuroplasticity.


Characterization of phospholipases C beta and gamma and their possible roles in Chaetopterus egg activation.
Intracellular calcium release from the endoplasmic reticulum is a hallmark at egg activation of both vertebrates and invertebrates. This fertilization-associated calcium release results from generation of the second messenger inositol 1,4,5-trisphosphate (IP(3)) by one or more phospholipases C (PLC). We characterized Chaetopterus PLCbeta and gamma by reverse transcription/degenerate oligonucleotide primed PCR and rapid amplification of cDNA end PCR. Phylogenetic analyses suggested that the deduced PLCbeta protein shared the greatest homology with mammalian PLCbeta4; the deduced PLCgamma protein shared the greatest homology with starfish PLCgamma and diverged from mammalian PLCgamma before mammalian the PLCgamma1 and gamma2 isoforms diverged. Western blot analyses with specific anti-PLCbeta and gamma antibodies, respectively, revealed that 135 and 150 kDa proteins were expressed in eggs. The general PLC antagonist U-73122 blocked fertilization-induced egg activation; however, the inactive analog, U-73343, had no effect on egg activation. We further tested whether egg activation was G protein-PLCbeta and/or protein tyrosine kinase-PLCgamma dependent. Cholera and pertussis toxins, well-known effectors of G proteins, had no effect on egg activation; while two antagonists of PTK, genistein and tyrphostin B42, inhibited both fertilization-induced and artificial egg activation. Taken together, our studies suggested that PLC activity from eggs contributes to Chaetopterus egg activation and PLCgamma might play an important role during this biological process.


Optimal fermentation parameters for processing high quality African locust bean condiments.
Fermented African locust bean (ALB) condiments are widely used to enhance the aroma and the taste of various dishes in West Africa. They are a good source of proteins. Sonru is one of the ALB condiments processed in Benin using a traditional starter called yanyanku. The variability in sonru processing unit operations (e.g. fermentation) presumably affects the quality (microbiological, biophysical and sensorial) of the final product. This study aimed at optimizing the fermentation step of sonru based on response surface methodology including three-factors [i.e. proportion of yanyanku, fermentation duration and thickness/depth of the layer of ALB (TALB)] and three-level factorial Box Behnken design with four central point replicates. The pH, softness of fermented cotyledons, Bacillus spp. and aerobic mesophilic bacteria count of sonru were evaluated. In addition, consumer acceptability was assessed by 7-hedonic box scale and Just About Right analysis. The pH had an upward trend with the increasing of all factors, and particularly Bacillus spp. count had similar trend with the fermentation duration and TALB whereas maximal penetration force (referred as the softness) had a downward trend with the fermentation duration. The optimal fermented ALB condiment resulted from processing conditions set at 1‰ of yanyanku, 24 h of fermentation and 8.5 cm for TALB. The optimized sonru appeared to be ideal in color, softness and taste. These findings can be used to improve fermented ALB condiments processing and better control the product quality in African countries. Further studies are needed to improve the odor of sonru.


Utility of Contrast-enhanced Ultrasonography with Perflubutane for Determining Histologic Grade in Hepatocellular Carcinoma.
The purpose of this study was to clarify the diagnostic value of contrast-enhanced ultrasonography (CEUS) with perflubutane in determining the histologic grade in hepatocellular carcinoma (HCC). A total of 147 surgically resected HCCs were dichotomized as well differentiated HCC (wd-HCC) and moderately- or poorly-differentiated HCC (mp-HCC). CEUS findings were evaluated during the arterial phase (vascularity, level and shape of enhancement), portal phase (presence or absence of washout) and post-vascular phase (echo intensity and shape). Receiver operating characteristic (ROC) curve analysis for the diagnosis of mp-HCC yielded area under the ROC curve (Az) values for arterial phase vascularity and portal phase washout of 0.910 and 0.807, respectively. The Az value for the combination of vascularity and washout for the diagnosis of mp-HCC was 0.956 (95% confidence interval, 0.910-0.979), corresponding to high diagnostic value. In conclusion, CEUS can provide high-quality imaging assessment for determining the histologic grade of HCCs.


Use of stents for correction of pulmonary artery branch stenosis.
We present a patient with tetralogy of Fallot who developed bilateral branch pulmonary artery stenosis following surgical repair that was refractory to balloon dilatation. Simultaneous stenting of both pulmonary arteries produced a good result.


Impact of comorbid conditions on asthmatic adults and children.
Comorbid conditions (comorbidities) can complicate the diagnosis and management of asthma. In different age groups, comorbid conditions can present varying challenges, including diagnostic confusion due to mimicking asthma symptoms, exacerbation of asthma symptoms, therapy for comorbid conditions affecting asthma or therapy for asthma affecting these conditions. This review aims to summarise some common comorbid conditions with asthma, such as rhinitis, vocal cord dysfunction, gastro-oesophageal reflux, psychiatric disorders, obesity and obstructive sleep apnoea, and discuss their prevalence, symptoms, diagnosis and treatment, highlighting any differences in how they impact children and adults. Overall, there is a lack of data on the impact of treating comorbid conditions on asthma outcomes and further studies are needed to guide age-appropriate asthma management in the presence of these conditions.


ABC-Type, Bola-Form Giant Surfactants: Synthesis and Self-Assembly.
Due to the fast phase separation kinetics and small feature size, the self-assembly of giant molecules has attracted lots of attention. However, there is not much study on multicomponent giant surfactants. In this work, through a modular synthetic strategy, different polyhedral oligomeric silsesquioxane (POSS)-based molecular nanoparticles are installed with diverse functionalities (hydrophobic octavinyl POSS (VPOSS), hydrophilic dihydroxyl-functionalized POSS (DPOSS), and omniphobic perfluoroalkyl-chain-functionalized POSS (FPOSS)) on the ends of one polystyrene (PS) chain to build up a series of triblock bola-form giant surfactants denoted as XPOSS-PSn -FPOSS (X represents V or D). The target molecules are prepared by a combination of atom transfer radical polymerization (ATRP), esterification, as well as Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and thiol-ene "click" reactions. These macromolecules are thoroughly characterized by combined technologies including nuclear magnetic resonance (NMR), size exclusion chromatography (SEC), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analyses. It is revealed by small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) that VPOSS-PSn -FPOSS adopts a two-phase separation scenario where VPOSS and POSS are segregated in one phase. DPOSS-PSn -FPOSS with a third hydrophilic DPOSS shows a three-phase separation scenario, where highly ordered phase structures are difficult to develop owing to the competition of mutual phase separation processes and may be trapped in kinetically metastable states.


How the threshold of a neuron determines its capacity for coincidence detection.
Coherent oscillatory activity of a population of neurons is thought to be a vital feature of temporal coding in the brain. We focus on the question of whether a single neuron can transform a spike code into a rate code. More precisely, how does a neuron vary its mean output firing rate, if its input changes from random to coherent? We investigate the coincidence detection properties of an integrate-and-fire neuron in dependence upon internal parameters and input statistics. In particular, we show how coincidence detection depends on the membrane time constant and the threshold. Furthermore, we demonstrate that there is an optimal threshold for coincidence detection and that there is a broad range of near-optimal threshold values. Fine-tuning is not necessary.


Evaluation systems for anti-HCV drugs.
Development of therapeutics for chronic hepatitis C has been hampered by the lack of an efficient cell culture system and a small animal model for the hepatitis C virus (HCV). An RNA replicon system, in which the HCV genome replicates autonomously in cells, and replication competent viruses derived from an HCV genotype 2a JFH1 strain efficiently propagating in Huh7 cells have been developed, and these systems have contributed to the evaluation of anti-HCV drugs targeted to viral and host proteins involved in the replication of HCV. Several compounds counteracting the viral enzymes, such as RNA polymerase and proteases, and host proteins involved in the lipid synthesis and protein folding are reported to have anti-HCV activities based on assessments using these in vitro systems. Furthermore, a mouse model transplanted with human liver fragments was shown to be capable of replicating HCV and has been used to evaluate the efficacy of antiviral drugs in vivo. In this review, we summarize information regarding systems for studying the HCV life cycle and potential new targets for therapeutic intervention for chronic hepatitis C.


[Arthrodeses of the small finger joints. Clinical studies of results with Kirschner's wire and tension arthrodeses].
An analysis of a series of 41 consecutive arthrodeses of finger-joints on 39 patients is given. Functional and cosmetic results were satisfactory. We prefer the tension band arthrodesis for its uncomplicated aftercare, the brief period of morbidity and the short period of absence from work.


Topical Vancomycin Powder and Dilute Povidone-Iodine Lavage Reduce the Rate of Early Periprosthetic Joint Infection After Primary Total Knee Arthroplasty.
Vancomycin powder and dilute povidone-iodine lavage (VIP) was introduced to reduce the incidence of periprosthetic joint infection (PJI) in high-risk total knee arthroplasty (TKA) patients. We hypothesize that VIP can reduce the incidence of early PJI in all primary TKA patients, regardless of preoperative risk. An infection database of primary TKAs performed before a VIP protocol was implemented (January 2012-December 2013), during a time when only high-risk TKAs received VIP (January 2014-December 2015), and when all TKAs received VIP (January 2016-September 2019) at an urban, university-affiliated, not-for-profit orthopedic hospital was retrospectively reviewed to identify patients with PJI. Criteria used for diagnosis of PJI were the National Healthcare Safety Network and Musculoskeletal Infection Society guidelines. VIP reduced early primary TKA PJI incidence in both the high-risk and all-risk cohorts compared with the pre-VIP cohort by 44.6% and 56.4%, respectively (1.01% vs 0.56% vs 0.44%, P = .0088). In addition, after introducing VIP to all-risk TKA patients, compared with high-risk TKA patients, the relative risk of PJI dropped an additional 21.4%, but this finding did not reach statistical significance (0.56% vs 0.44%, P = .4212). There were no demographic differences between the 3 VIP PJI cohorts. VIP is associated with a reduced early PJI incidence after primary TKA, regardless of preoperative risk. With the literature supporting its safety and cost-effectiveness, VIP is a value-based intervention, but given the nature of this historical cohort study, a multicenter randomized controlled trial is underway to definitively confirm its efficacy.


Yet another improved silver staining method for the detection of proteins in polyacrylamide gels.
Silver staining is very sensitive for detection of proteins in polyacrylamide gels and different procedures have been published. By combining and modifying some of the recipes, a very reproducible method, which is based upon staining with diamine complexes of silver, has been developed. The background staining is negligible and reduced silver does not precipitate on the gel surface. The technique works very well for sodium dodecyl sulfate-polyacrylamide gel electrophoresis in both homogeneous and in gradient gels as well as for two-dimensional (2-D) PAGE. It was possible to detect 1-10 ng of protein corresponding to approximately 50 pg/mm2, provided that a discontinuous buffer system was used, which gives sharp bands.


Robot-assisted laparoscopic prostatectomy: a single-institutions learning curve.
To evaluate the results of robot-assisted laparoscopic prostatectomy (RALP) at a high-volume conventional laparoscopic radical prostatectomy (LRP) center, to determine whether a learning curve still exists. A total of 293 consecutive men underwent RALP between May 2000 and November 2006. We prospectively collected and reviewed patient data including the preoperative prostate-specific antigen (PSA) and Gleason score, operative duration, and blood loss, duration of hospitalization, and pathologic Gleason score and margin status. Mean operative duration for the entire group was 158 +/- 50 minutes, blood loss was 533 +/- 416 mL, hospital duration was 5 days, and mean age was 61 years. Operative time showed a statistically significant decline at 2 different breakpoints: after the first 12 cases, and after 189 cases, dividing the patients into 3 groups. Operative times were 242 +/- 64, 165 +/- 43, and 134 +/- 45 minutes, respectively, for each group. We also evaluated margin status in the 3 groups. The positive margin rate in each group was 7/12 (58%), 41/180 (23%), and 10/89 (9%), which was statistically significant. Foley catheter duration was also statistically significant among groups. Age, preoperative Gleason score, and PSA were statistically significant between the second and third groups. There was no statistical significance demonstrated in blood loss, postoperative Gleason score, and length of hospital stay. Urologists who are proficient in laparoscopic radical prostatectomy will still have a learning curve when first performing an RALP. Experienced laparoscopic surgeons demonstrated continued improvement in operative and pathologic parameters with regard to operative duration and positive margin rate as their experience grew.


A brain-coral-inspired metal-carbon hybrid synthesized using agarose gel for ultra-fast charge and discharge supercapacitor electrodes.
A brain coral-like supercapacitor electrode containing 3D carbon and metal bicontinuous structures was synthesized by a simple method using agarose gel. This bulk electrode can supply excellent power with ultrahigh-rate capability (~1000 V s(-1)).


Effect of Busulfan and Treosulfan on Gonadal Function after Allogeneic Stem Cell Transplantation in Children and Adolescents with Nonmalignant Diseases Is Not Exposure-Dependent.
With an increasing number of young patients surviving into adulthood after hematopoietic stem cell transplantation (HSCT), gonadal dysfunction becomes an important late effect with significant impact on quality of life. In this retrospective study, we evaluated the exposure of busulfan (Bu) and treosulfan (Treo) in relation to gonadal function in pediatric patients who underwent HSCT for a nonmalignant disease between 1997 and 2018. In the Bu group, 56 patients could be evaluated, and gonadal dysfunction was found in 35 (63%). Lower Bu exposure (ie, cumulative area under the curve [AUC] <70 mg*h/L) was not associated with a reduced risk of gonadal dysfunction (odds ratio [OR], .92; 95% confidence interval [CI], .25 to 3.49; P = .90). In the Treo cohort, 32 patients were evaluable and gonadal insufficiency occurred in 9 patients (28%). Lower Treo exposure (AUC <1750 mg*h/L on day 1) was not associated with a reduced risk of gonadal dysfunction (OR, 1.6; 95% CI, .16 to 36.6; P = .71). Our data do not support the premise that reduced-intensity Bu-based conditioning reduces the risk for gonadal toxicity, and it is unlikely that therapeutic drug monitoring-based reduced treosulfan exposure will further limit the risk of gonadal dysfunction.


1-(4-Methyl-phen-yl)-2-[4-(trifluoro-methyl)phen-yl]-1H-phenanthro[9,10-d]imida-zole.
In the title compound, C29H19F3N2, the tetra-cyclic ring system is essentially planar [maximum deviation from the best plane = 0.076 (1) Å] and makes dihedral angles of 78.10 (5) and 33.71 (4)° with the methyl-phenyl and fluoro-phenyl rings, respectively. An intra-molecular C-H⋯π inter-action occurs. In the crystal, pairs of C-H⋯π inter-actions link inversion-related mol-ecules.


Induction of apoptotic DNA fragmentation by nonsteroidal anti-inflammatory drugs in cultured rat gastric mucosal cells.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to cause apoptosis in several cell lines including transformed chicken embryo fibroblasts and human colon cancer cells. We herein report the apoptotic effect of NSAIDs in a non-transformed cell line derived from the rat gastric mucosa, RGMI (rat gastric mucosa cell first). 1-[p-Chlorobenzoyl]-5-methoxy-2-methylindole-3-acetic acid (indomethacin) and sodium 2-(2,6-dichloroanilino)phenylacetate (sodium diclofenac), potent and non-selective inhibitors of cyclooxygenase, were found to induce DNA fragmentation in RGM1 cells in a time- and concentration-dependent manner. The expression of mRNA for cyclooxygenase-2 was hardly detected in the intact cells but was clearly enhanced when the cells were incubated with the two NSAIDs. In contrast, the expression of mRNA for cyclooxygenase-1 was constitutive and was never affected by NSAIDs. The effect of [3,4-di(4-methoxyphenyl)-5-isoxazolyl] acetic acid (mofezolac), a potent and highly preferential inhibitor of cyclooxygenase-1, and N-[2-(cyclohexyloxy)-4-nitrophenyl]methanesulphonamide (NS-398), a selective inhibitor of cyclooxygenase-2, on DNA fragmentation and cyclooxygenase-2 mRNA expression was weak compared to the effect of indomethacin or sodium diclofenac. The DNA fragmentation induced by sodium diclofenac was hardly affected by the exogenous addition of 16,16-dimethyl prostaglandin E2 but was inhibited by caspase inhibitors such as Ac-YVAD-CHO and Ac-DEVD-CHO. The present data provide the first evidence that NSAIDs, such as indomethacin and sodium diclofenac, cause apoptotic DNA fragmentation in cultured gastric mucosal cells, and also indicate the involvement of caspases rather than the inhibition of cellular prostaglandin synthesis in the apoptotic process.


Complete response of stage IV anal mucosal melanoma expressing KIT Val560Asp to the multikinase inhibitor sorafenib.
A 79-year-old man presented to his primary care physician with a 2-month history of pruritus ani and a pigmented nodular lesion was discovered in the posterior rectum. The patient had no other symptoms, or any family history of malignancy. Physical examination; excisional biopsy; CT scan of the chest, abdomen and pelvis; lung biopsy; blood tests; tumor immunohistochemistry for KIT, vascular endothelial growth factor platelet-derived growth factor receptor alpha and beta, and mismatch-repair proteins MLH1, MSH2, and MSH6; and KIT and BRAF tumor genotyping. Stage IV M1b metastatic anal mucosal melanoma. Wide local excision with mucosal advancement of the rectal wall, external-beam radiation, and sorafenib-temozolomide therapy.


Presence of human immunodeficiency virus (HIV) and T-lymphotropic virus type I and II (HTLV-I/II) in a haemophiliac population in Belo Horizonte, Brazil, and correlation with additional serological results.
The aim of this study was to determine the prevalence of human immunodeficiency virus type 1 (HIV-1) and human T lymphotropic virus types I and II (HTLV-I/II) infections in 226 haemophiliac patients treated at Fundação Hemominas in Belo Horizonte, Minas Gerais State, Brazil, and to verify association with other serological results. Patients positive for HTLV-I/II had also a neurological, haematological and ophthalmological evaluation. Fundação Hemominas offers comprehensive care for all haemophiliac patients in Minas Gerais. Thirty-six (15.9%) of the 226 patients showed reactive results to HIV-1 [ELISA, Abbott, USA, confirmed by Western blot (WB), Cambridge Biotech, USA, and/or immunofluorescence, Fiocruz, Brazil] and 16 (7.1%) had reactive sera to HTLV-I/II (ELISA, Ortho). Eleven of these 16 (4.9%) were positive, 3/16 (1.3%) were indeterminate and 2/16 (0.9%) were negative in the HTLV WB (Cambridge Biotech). Neurological, haematological and ophthalmological examination of 9/16 patients revealed no abnormality suggestive of HTLV disease. Of the 16 patients reactive to HTLV-I/II ELISA test, six (37.5%) were also positive to HIV-1 (chi 2 = 5.92; P = 0.01). Seropositivity for HTLV-I/II and HIV-1 was associated with advancing age and positive results for hepatitis C virus (HCV), Chagas' disease (T. cruzi infection) and syphilis. No association between the presence of HTLV with type and severity of haemophilia and hepatitis B results was detected. The prevalence of antibodies against HIV-1 is approximately three times that of HTLV-I/II and a patient positive for HTLV-I/II had a significantly increased risk of being positive for HIV-1, HCV and T. cruzi.