Recipient vessels for free flaps in advanced facial oncologic defects.
To prospectively compare the results of microvascular flap reconstruction of midface and scalp advanced oncologic defects using superficial temporal versus cervical as recipient vessels. This is a parallel group clinical trial with 1:1 allocation ratio of patients who underwent midface and scalp oncologic reconstruction with free tissue flap from April 2018 to April 2022 in a tertiary oncologic center. Two groups were analyzed: those in whom superficial temporal vessels were used as the recipient vessels (Group A) and those in whom cervical vessels were used as the recipient vessels (Group B). Patient gender and age, cause and localization of the defect, flap choice for reconstruction, recipient vessels, intraoperative outcome, postoperative course, and complications were recorded and analyzed. A Fisher's exact test was used to compare outcomes between the 2 groups. On the basis of the different recipient vessels, 32 patients were randomized into 2 groups, and of these 27 patients completed the study: Group A with superficial temporal recipient vessels (n = 12) and Group B with cervical recipient vessels (n = 15). There were 18 male and 09 female patients with an average age of 53.92 ± 17.49 years. The overall flap survival rate was 88.89%. The overall complication rate for vascular anastomosis was 14.81%. The total flap loss rate in patients with superficial temporal recipient vessels was higher than the complication rate in those with cervical recipient vessels but with no statistical significance (16.67% vs. 6.66%, p = 0.569). Minor complications occurred in 05 patients without statistical significance between the groups (p = 0.342). In the group with superficial temporal recipient vessels, the postoperative rate of free flap complications was similar than the cervical recipient vessel group. Therefore the use of superficial temporal recipient vessels for midface and scalp oncologic reconstruction could be a reliable option.


Dosage balance acts as a time-dependent selective barrier to subfunctionalization.
Gene duplication is an important process for genome expansion, sometimes allowing for new gene functions to develop. Duplicate genes can be retained through multiple processes, either for intermediate periods of time through processes such as dosage balance, or over extended periods of time through processes such as subfunctionalization and neofunctionalization. Here, we built upon an existing subfunctionalization Markov model by incorporating dosage balance to describe the interplay between subfunctionalization and dosage balance to explore selective pressures on duplicate copies. Our model incorporates dosage balance using a biophysical framework that penalizes the fitness of genetic states with stoichiometrically imbalanced proteins. These imbalanced states cause increased concentrations of exposed hydrophobic surface areas, which cause deleterious mis-interactions. We draw comparison between our Subfunctionalization + Dosage-Balance Model (Sub + Dos) and the previous Subfunctionalization-Only (Sub-Only) Model. This comparison includes how the retention probabilities change over time, dependent upon the effective population size and the selective cost associated with spurious interaction of dosage-imbalanced partners. We show comparison between Sub-Only and Sub + Dos models for both whole-genome duplication and small-scale duplication events. These comparisons show that following whole-genome duplication, dosage balance serves as a time-dependent selective barrier to the subfunctionalization process, by causing an overall delay but ultimately leading to a larger portion of the genome retained through subfunctionalization. This higher percentage of the genome that is ultimately retained is caused by the alternative competing process, nonfunctionalization, being selectively blocked to a greater extent. In small-scale duplication, the reverse pattern is seen, where dosage balance drives faster rates of subfunctionalization, but ultimately leads to a smaller portion of the genome retained as duplicates. This faster rate of subfunctionalization is because the dosage balance of interacting gene products is negatively affected immediately after duplication and the loss of a duplicate restores the stoichiometric balance. Our findings provide support that the subfunctionalization of genes that are susceptible to dosage balance effects, such as proteins involved in complexes, is not a purely neutral process. With stronger selection against stoichiometrically imbalanced gene partners, the rates of subfunctionalization and nonfunctionalization slow; however, this ultimately leads to a greater proportion of subfunctionalized gene pairs.


Synthesis of Allenes by Catalytic Coupling of Propargyl Carbonates with Aryl Iodides in the Presence of Diboron Species.
Bimetallic copper-/palladium-catalyzed multicomponent reaction of propargyl carbonates, aryl iodides, and diboron species was studied. This procedure can be used for synthesis of di-, tri-, and tetra-substituted allenes. Using diboronic acid, the reaction is supposed to proceed via allenylboronic acid intermediate.


Feasibility and Safety of Remazolam versus Propofol When Inserting Laryngeal Masks Without Muscle Relaxants During Hysteroscopy.
This study aimed to evaluate the efficacy and safety of remazolam compared with propofol in patients who underwent laryngeal mask airway (LMA) insertion without the use of muscle relaxant agents during hysteroscopic surgery. A total of 72 patients undergoing hysteroscopy with LMA insertion were assigned to two groups. The patients in the remazolam group received 0.3 μg/kg sufentanil, 0.3 mg/kg remazolam and 1.2 mg/kg remifentanil, whereas the patients in the propofol group received 0.3 μg/kg sufentanil, 2.0 mg/kg propofol and 1.2 mg/kg remifentanil for insertion of the LMA. The primary endpoint was the summed score of the insertion conditions. The secondary endpoints included hemodynamics, the duration of induction, the duration of insertion, tidal volume, plateau pressure and adverse events. No difference was identified between the propofol group and remazolam group in the median summed score [18.0 (18.0, 18.0), 18.0 (17.0, 18.0), respectively, P > 0.05]. The induction duration was significantly longer (P < 0.05) in the remazolam group than propofol group. The cost of dopamine (P < 0.05) was significantly lower in the remazolam group compared with the patients in the propofol group, while the plateau pressure (P < 0.05) and the incidence of transient mild laryngospasm (P < 0.05) were significantly higher in the remazolam group. No differences were identified between the two groups in terms of heart rate, tidal volume, injection pain or hiccups (P > 0.05). Remazolam provided similar insertion conditions and better hemodynamic stability than propofol during LMA insertion without the use of muscle relaxant agents. However, a higher incidence of transient mild laryngospasm was found in the remazolam group, which should be considered.


Effects of comorbidities on the outcomes of manipulation under anesthesia for primary stiff shoulder.
Studies on the effects of manipulation under anesthesia (MUA) for primary stiff shoulder when different comorbidities are present are lacking. Our aim was to assess how comorbidities influence the recovery speed and clinical outcomes after MUA. Between April 2013 and September 2018, 281 consecutive primary stiff shoulders in the frozen phase treated with MUA were included in this study. We investigated the comorbidities of patients and divided them into the control (n = 203), diabetes mellitus (DM) (n = 32), hyperlipidemia (n = 26), and thyroid disorder (n = 20) groups. The range of motion (ROM) and clinical scores for each group before MUA and 1 week, 6 weeks, and 3 months after MUA were comparatively analyzed. We identified the ROM recovery time after MUA and the responsiveness to MUA. Then, subjects were subdivided into early and late recovery groups based on their recovery time and into successful and nonsuccessful MUA groups based on their responsiveness to MUA. Significant improvements in ROM and clinical scores at 3 months after MUA were observed in all groups. Significant differences in ROM among the 4 groups were also observed during follow-up (P < .05). The DM group had significantly lower ROM values, even at 3 months after MUA, compared with the control group. The ROM recovery speed after MUA was slowest in the DM group, followed by the thyroid disorder, hyperlipidemia, and control groups. Most (90.6%) of the DM group experienced late recovery. The proportion of nonsuccessful MUA was higher in the DM and thyroid disorder groups than that in the control and hyperlipidemia groups (P = .004). During follow-up, there were no differences among groups regarding the visual analog scale, University of California at Los Angeles shoulder, and Constant scores. The ROM recovery speed and responsiveness to MUA for primary stiff shoulder were poorer for the DM and thyroid disorder groups than for the control group. In particular, compared with any other disease, outcomes were poorer when the comorbidity was DM. If patients have comorbidities, then they should be informed before MUA that the comorbidity could affect the outcomes of treatment.


Psychopathology in dual diagnosis and non-addicted schizophrenics--are there differences?
In a previous publication we reported lifetime and 3-month prevalence estimates for substance use in two large samples of schizophrenic inpatients (Soyka et al. 1993). A subsequent analysis of psychopathological findings assessed by means of the AMDP Manual (Guy and Ban 1982) in schizophrenic in-patients of the Haar Mental State Hospital (N=447), in whom a lifetime prevalence for substance use of 42.9% (3-month prevalence 29%) had been reported, was performed. While the overall differences between substance using (dual diagnosis) and nonusing schizophrenics were small, dual diagnosis patients in general reported more positive symptoms, especially more intense hallucinations. These differences could basically be demonstrated in patients with current (3-month) substance use on admission but not on discharge possibly as a result of substance use. Most marked and highly significant results were found with respect to previous suicide attempts and delinquency which were more prevalent in dual diagnosis schizophrenics. Results of this study indicate that dual diagnosis patients compared to other schizophrenics represent a more disturbed patient group. Implications for the self-medication hypothesis for substance use in schizophrenia and future research in this area are discussed.


Recognition of psychiatric disorders, and self-perceived problems. A follow-up study from age 8 to age 18.
To study the rate of, and factors associated with, recognition of psychiatric disorders and self-perceived problems among 18-year-old adolescent boys. The study population consisted of 2347 Finnish boys born during 1981 attending military call-up (79.7% of the original sample). At age 8, the boys were evaluated by parental and teacher Rutter scales and by self-reports using the Child Depression Inventory (CDI). At military call-up 10 years later, the boys filled in the Young Adult Self-Report (YASR). Information about psychiatric disorders recognized at the military call-up health examination was obtained from the national military register. About 4.6% of boys were recognized as having a psychiatric disorder at the military call-up medical examination. In addition, 23.1% of boys reported emotional, behavioral or relational difficulties but were not recognized as having an ICD 10 psychiatric diagnosis at the military call-up medical examination. A higher level of psychopathology, problems across different life domains and early onset of problems were more strongly associated with recognition of psychiatric disorder than with self-reports of difficulties without a recognized psychiatric disorder. All informant sources, parents, teachers and children themselves at age 8, independently predicted recognition of psychiatric disorders and perceived difficulties 10 years later. Only a minority of adolescents with psychiatric problems are recognized as having a psychiatric disorder in the health services. Efforts to prevent psychiatric disturbance in early life are emphasized. The use of screening methods in school health settings to detect children in need of child mental health services is justified.


Music Appreciation of Cochlear Implant Users versus Normal Hearing Individuals.
Cochlear implants (CI) provide speech perception for patients with sensorineural hearing impairment; nonetheless, listening to music is a daunting challenge for them. The present study aimed to compare Iranian CI users and normal hearing (NH) controls in terms of musical habits and appreciation and investigate the possible effect of background variables. A total of 37 CI users who underwent surgery at least 18 months before the study and 59 NH listeners were enrolled in this study. The participants were assigned to two age groups: group A (patients ≥15 years old) and group B (patients <15 years old). They were asked to complete the questionnaires to assess their music engagement. In group A, the mean score of music importance was significantly higher in CI users (8.7±2.1), as compared to that in NH subjects (5.8±2.3) (P=0.005). Participation in professional musical training and singing with music was not significantly different between the groups. In group B, the mean score of desire for music was not significantly different between CI users (8.2±1.8) and NH subjects (7.7±2.0). They participated in professional musical training and had a reaction to music almost equally. Singing with music was significantly less common in the CI group (CI 16[61.5%], NH (40[85.1%]) (P=0.023). Selected background variables had no significant effect on the music tendency and habits of CI users. Iranian CI users tended to have a high level of music appreciation in both adult and children groups. Moreover, CI users and NH controls did not significantly differ in the importance of music, devoted time, participation in musical activities, and musical habits.


Machine-learning-facilitated prediction of heavy metal contamination in distiller's dried grains with solubles.
Excessive heavy metal contamination often occurs in feed due to natural or anthropogenic activity, leading to poisoning and other health problems in animals. In this study, a visible/near-infrared hyperspectral imaging system (Vis/NIR HIS) was used to reveal the different characteristics of spectral reflectance of Distillers Dried Grains with Solubles (DDGS) doped with various heavy metals and to effectively predict metal concentrations. Two types of sample treatment were used, namely tablet and bulk. Three quantitative analysis models were constructed based on the full wavelength, and through comparison the support vector regression (SVR) model was found to show the best performance. As typical heavy metal contaminants, copper (Cu) and zinc (Zn) were used for modeling and prediction. The prediction set accuracy of the tablet samples doped with Cu and Zn was 94.9% and 86.2%, respectively. In addition, a novel characteristic wavelength selection model based on SVR (SVR-CWS) was proposed to filter characteristic wavelengths, which improved the detection performance. The regression accuracy of the SVR model on the prediction set of tableted samples with different Cu and Zn concentrations was 94.7% and 85.9%, respectively. The accuracy of bulk samples with different Cu and Zn concentrations was 81.3% and 80.3%, respectively, which indicated that the detection method can reduce the pretreatment steps and verify its practicability. The overall results suggested the potential of Vis/NIR-HIS in the detection of feed safety and quality.


Systemic hypertension: an overview of the problem.
Hypertension is growing in prevalence and most of this growth represents isolated systolic hypertension in the elderly. Attempts at prevention are critical but likely are ineffectual. Therefore, the delivery and acceptance of current medical regimens must be improved.


An interpretive review of women's experiences of gestational diabetes mellitus: proposing a framework to enhance midwifery assessment.
Gestational diabetes mellitus (GDM) affects almost 5% of pregnancies in Australia, and within 15 years, 25% of affected women will go on to develop Type 2 Diabetes Mellitus (T2DM). The adoption of preventive health behaviours may be influenced by women's experiences of GDM. This review sought to understand women's beliefs, values, perceptions and experiences following diagnosis of GDM. Peer reviewed and professional journals were searched for primary research, published between January 1991 and December 2011 that explored the beliefs, values, perceptions and experiences of peripartum or postpartum women with a diagnosis or history of GDM. Nineteen studies met the inclusion criteria and the majority of these studies were qualitative (n=15). Each study was reviewed and synthesis revealed three emergent themes and core concepts related to each theme: Responses (initial reaction to GDM diagnosis, negative thoughts following diagnosis, struggle to manage GDM, feelings of 'loss of control', changes to identity and adapting to change), Focus of Concern (concern for baby's health, mother's concern for her own health, perceived seriousness of GDM, perceived fear of T2DM) and Influencing Factors (cultural roles and beliefs, social stigmas, social support, professional support, adequate and appropriate information, social roles and barriers to self-care). The experiences of women with GDM are unique and personal however this review highlights common experiences evident in the existing research. The proposed framework may be used by midwives in clinical assessment and care of women diagnosed with GDM.


Risk factors and mortality in patients with listeriosis and end-stage renal disease.
End-stage renal disease (ESRD) is a known immunocompromising status that predisposes patients to developing infections. Disease from Listeria monocytogenes may affect any host but tends to be more severe in the immunocompromised. We used a large population of patients with ESRD to identify risk factors for listeriosis and mortality. Patients with a diagnosis of Listeria and other risk factors for listeriosis were identified using claims data from the United States Renal Data System database from 2004-2015. Demographic parameters and risk factors associated with Listeria were modeled using logistic regression while association with mortality was assessed with Cox Proportional Hazards modeling. A diagnosis of Listeria was identified in 291 (0.01%) of a total 1,071,712 patients with ESRD. Cardiovascular disease, connective tissue disease, upper gastrointestinal ulcerative disease, liver disease, diabetes, cancer, and human immunodeficiency virus were all associated with an increased risk of Listeria. Patients with Listeria had an increased risk of death relative to patients without Listeria (adjusted hazard ratio=1.79; 95% confidence interval 1.52-2.10). Incidence of listeriosis in our study population was over 7 times higher than what has been reported for the general population. The independent association of a Listeria diagnosis with increased mortality is also consistent with the disease's high mortality in the general population. Due to limitations with diagnosis, providers should maintain high clinical suspicion for listeriosis when patients with ESRD present with a compatible clinical syndrome. Further prospective study may help precisely quantify the increased risk of listeriosis in patients with ESRD.


Integrative sediment assessment at Atlantic Spanish harbours by means of chemical and ecotoxicological tools.
This study refers to the integrative assessment of sediment quality in three harbour areas at the Spanish Atlantic Coast: Vigo (Northwestern Spain), Bilbao and Pasajes (Northern Spain). At each site, two lines of evidence have been considered: chemical analyses (metal, PAH and PCB concentrations in sediments and ammonia concentration in bioassays) and toxicity tests (Microtox®, Corophium sp. marine amphipod and Paracentrotus lividus sea urchin larvae). Chemical and ecotoxicological results have been integrated by means of a tabular matrix and a multivariate factorial analysis (FA). Highly toxic samples have been characterised in Vigo and Pasajes harbours while Bilbao samples present toxicity levels ranging from non-toxic to moderately toxic. High toxicity is associated with high levels of contaminants whereas confounding factors (ammonia, organic matter and mud) have been identified to be the main cause of low to moderate toxicity. Based on the obtained results, it can be concluded that deriving potential toxicity of sediments based on comparison with Sediment Quality Guidelines (SQGs) is in agreement to toxicity results in areas presenting high levels of contaminants. However, at lower levels of toxicity (low to moderate), the mismatch between the potential toxicity (SQG approach) and the toxicity measured by bioassays is greater, as the former only accounts for chemical concentrations, without considering the interaction between contaminants and the effect of confounding factors. Contrarily, the multivariate analysis seems to be a robust tool for the integration and interpretation of different lines of evidence in areas affected by different sources of contamination.


Dental extractions related to head and neck radiotherapy: ten-year experience of a single institution.
This study evaluates the frequency of osteoradionecrosis associated with dental extractions. A total of 405 patients submitted to radiotherapy and had dental extractions were evaluated. The patients were divided into 3 groups. In group 1, 316 patients were submitted to 1.647 dental extractions (mean 5.2 teeth per patient) and in another 47 patients the number of teeth removed was not clearly reported. Group 2 comprised 5 patients who had 33 teeth extracted (mean 6.6 each). In group 3, 55 patients had 290 teeth removed (mean 5.3 each) and in another 2 patients the number of dental extractions could not be established. In general, only 3 cases of osteoradionecrosis related to dental extractions were observed: 2 related to exodontias performed before and 1 after radiotherapy. The low prevalence of osteoradionecrosis found in this work suggests the possibility of performing exodontias after radiotherapy by experienced dentists in the management of head and neck cancer.


Proteome-wide Mendelian randomization in global biobank meta-analysis reveals multi-ancestry drug targets for common diseases.
Proteome-wide Mendelian randomization (MR) shows value in prioritizing drug targets in Europeans but with limited evidence in other ancestries. Here, we present a multi-ancestry proteome-wide MR analysis based on cross-population data from the Global Biobank Meta-analysis Initiative (GBMI). We estimated the putative causal effects of 1,545 proteins on eight diseases in African (32,658) and European (1,219,993) ancestries and identified 45 and 7 protein-disease pairs with MR and genetic colocalization evidence in the two ancestries, respectively. A multi-ancestry MR comparison identified two protein-disease pairs with MR evidence in both ancestries and seven pairs with specific effects in the two ancestries separately. Integrating these MR signals with clinical trial evidence, we prioritized 16 pairs for investigation in future drug trials. Our results highlight the value of proteome-wide MR in informing the generalizability of drug targets for disease prevention across ancestries and illustrate the value of meta-analysis of biobanks in drug development.


More than just a pool.
An intricate stem cell niche boundary formed by finger-like extensions generates asymmetry in stem cell divisions.


Five familial hypercholesterolemic kindreds in Japan with novel mutations of the LDL receptor gene.
In the course of investigations of familial coronary artery disease in Hokkaido, the northern island of Japan, we identified five families in which multiple members showed elevated plasma levels of low-density lipoprotein (LDL) cholesterol. To determine the genetic etiology of their lipoprotein abnormalities, we screened DNA samples from these families for mutations in all 18 exons and the exon-intron boundaries of the LDL receptor (LDLR) gene. Novel point mutations were identified in each family: (1) a C-to-A transversion at nucleotide 285, causing a nonsense mutation at codon 74, in eight members of family A; (2) a G-to-A transition at nucleotide 1136, causing substitution of Tyr for Cys at codon 358, in six members of family B; (3) a C-to-T transition at nucleotide 1822, causing substitution of Ser for Pro at codon 587, in five members of family C; (4) a one-base insertion of G to a five-G stretch at nucleotides 1774-1778 (codons 571-572), causing a frameshift, in six members of family D; and (5) a one-base deletion of T at nucleotide 1963-1964 (codon 634), causing a frameshift, in three members of family E. Through the molecular genetic approach a total of 28 individuals in these families were diagnosed unequivocally as heterozygous for the respective LDLR mutations. This method also helped us to diagnose familial hypercholesterolemia, or to exclude from carrier status, 11 children with borderline high cholesterol levels.


Campylobacter jejuni pancolitis mimicking idiopathic ulcerative colitis.
Campylobacter jejuni is the most common cause of community-acquired acute bacterial diarrhea. Campylobacter diarrhea is usually accompanied by fever and abdominal pain. Campylobacter diarrhea is usually watery. Nausea, vomiting, headache, and myalgias may also be present. Tenesmus is a common feature. The majority of patients with Campylobacter diarrhea have some component of segmental colitis, usually beginning in the small bowel and progressing distally to the cecum and colon. C. jejuni is a rare cause of pancolitis. Community-acquired colitis may be caused by C. jejuni or other enteric pathogens, for example, Shigella, Entamoeba, Yersinia, Escherichia coli 0157:H7, Clostridium difficile colitis, ischemic colitis, or idiopathic ulcerative colitis. We present a case of C. jejuni pancolitis in an elderly woman. Differential diagnosis is included in the discussion. The patient's C. jejuni pancolitis was successfully treated with a 7-day course of oral moxifloxacin.


Concentrations of cytokines in peritoneal fluid after abdominal surgery.
To assess the role of concentrations of cytokines in peritoneal fluid in estimating the severity of the host's response to the stress of abdominal operations. Prospective study. University hospital, Japan. 49 patients who underwent various abdominal operations. Main outcome measures--Correlations between concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) in peritoneal fluid measured on the first postoperative day on the one hand, and peritoneal bacterial count, length of operation, and operative blood loss, on the other. The concentrations of all three peritoneal cytokines correlated significantly with length of operation; those of TNF-alpha and IL-1 beta also correlated significantly with peritoneal bacterial count, and that of IL-1 beta with operative blood loss. There were significant correlations between the concentrations of the three cytokines. These correlations suggest that monitoring of the peritoneal concentrations of TNF-alpha, IL-1 beta, and IL-6 may be helpful in estimating the severity of stress caused by abdominal operations.


Immunoglobulin G dimer: an idiotype-anti-idiotype complex.
Immunoglobulin G (IgG) prepared from pooled human plasma contains variable amounts (up to 40%) of IgG dimer whereas IgG isolated from the plasma of a single individual is essentially monomeric. The amount of dimer increases with the number of donors contributing to the plasma pool from which the IgG is prepared. Dimerization is reversed by increasing the temp or decreasing the pH. Two intact antibody-combining sites (paratopes) are required for optimal dimer formation; the Fc region is unnecessary. These findings strongly suggest that IgG dimer consists of idiotype-anti-idiotype pairs formed between molecules of IgG from different individuals, and that a mechanism exists for suppressing idiotype-anti-idiotype formation in vivo.


Comprehensive analysis of synthetic cannabinoids and metabolites in oral fluid by online solid-phase extraction coupled to liquid chromatography-triple quadrupole-mass spectrometry.
The class of novel psychoactive substances known as synthetic cannabinoids (SC) includes illicit compounds that are sprayed on plant material and smoked or sold as liquids to be vaporized in e-cigarettes. In toxicological analysis of SC, fast analytical methods are needed for the detection and confirmation of parent drugs and metabolites at very low levels. While various analytical methods have been developed for SC in blood and urine, few are available for alternative matrices such as oral fluid (OF). There are numerous advantages to using OF as a sample matrix for SC analysis, including non-invasive collection, lesser risk of adulteration, and presence of both parent drug and metabolites. Here we report a validated online solid-phase extraction (online SPE) method coupled to LC-QqQ-MS for rapid confirmation and quantitation of 72 structurally diverse SC parent drugs and metabolites in OF with 2.5 min of preconcentration time and a total elution time of < 10 min. The use of online SPE for sample pretreatment facilitates rapid and consistent processing and greatly increases sample throughput. The method was fully validated according to relevant guidelines (ANSI/ASB Standard 036). Bias and precision values were within ± 20% for all compounds in human OF matrix. Method detection and quantitation limits ranged from 0.4 to 3.8 ng/mL and from 1.1 to 11.6 ng/mL, respectively. Recovery, matrix effects, process efficiency, carryover, and stability were also within acceptable limits for the majority of compounds. Successful application of the method was demonstrated using blank human OF fortified with SC in addition to a set of authentic OF specimens previously tested by another laboratory. Graphical abstract.


Rejuvenating views of the ageing process.
Commonly held assumptions about the ageing process have guided and directed research in this important area over many years. Recent evidence, however, from disciplines as diverse as molecular genetics, clinical epidemiology and demography, provide a direct challenge to the validity of many of these assumptions. So, the time is ripe to re-examine these assumptions about the ageing process and to rethink the scientific foundations of the field.


The role of leukotriene inhibition using a 5-lipoxygenase (5-LO) inhibitor in a joint contracture model.
Arthrofibrosis is a common inflammatory complication of joint trauma and surgery. 5lipoxygenase (5-LO) is a key enzyme involved in inflammation. Inhibition of 5-LO has been shown to reduce inflammation in heart and lung models but has not been examined in a joint contracture model. Twenty-six rats underwent joint contracture. Six rats served as non-surgical controls. A 5-LO inhibitor, caffeic acid (CA), suspended in 10% ethanol was orally administered to 14 rats and ethanol without CA to the remaining 12 rats daily for 21 days. Leukotriene B4 (LTB4) levels were measured, both systemically and locally. 5-LO levels in the posterior capsule were quantified by measuring the ratio of the length of the posterior capsule demonstrating 5-LO immunostaining to the total length of the capsule. Joint contracture was successfully achieved in all rats who underwent manipulation. Levels of 5- LO measured in the posterior capsule were significantly increased in the animals who underwent surgery (56%/44-64) compared to the non-surgical control animals (7%/4-9). LTB4 levels were found to be significantly lower in the non-surgical control animals (107.79 ± 34.08 pg/ml) compared to all surgical animals (157.6 ± 55.3 pg/ml). Surgical intervention resulted in increased 5-LO activity of the synovial surface of the posterior capsule and increased LTB4 levels in the patellar tendon-fat pad. Oral administration of the 5LO inhibitor, CA, was ineffective at reducing systemic and local LTB4 levels and preventing knee joint contracture. Inhibiting 5-LO activity may still be effective in preventing arthrofibrosis and warrants further investigation.


Retreatment of the spinal cord with palliative radiotherapy.
We conducted this retrospective review of patients whose spinal cord was irradiated twice to evaluate the outcome in terms of palliation and long-term side effects. Eight patients (4 females, 4 males; median age: 67 years) were identified whose spinal cord had been irradiated twice between July 1990 and July 1997, usually for the management of bone metastases. All patients were followed up until their death from progressive disease. The Karnofsky performance score at the time of retreatment ranged from 20% to 90%. Total dose for the first treatment ranged from 29 to 50 Gy (median: 38 Gy) with single doses 1.25-3 Gy; the total dose for the retreatment ranged from 29 to 38 Gy (median: 30 Gy) with a single dose 1.8-4 Gy. The cumulative dose ranged from 59 to 88 Gy (median: 67.5 Gy). The overlap in the site of retreatment consisted of 1-3 segments, whereas in one patient, 2 single segments were treated twice. The outcome in terms of progressive disease, the palliative effects, and the development of myelopathy was assessed retrospectively. The median interval to reirradiation was 30 months (range: 6-63 months), and the median follow-up after the last treatment was 16 months (range: 5-44 months). After reirradiation, 4/7 patients experienced complete pain relief, 2/7 patients experienced minor pain relief, and only 1 patient showed no change. Two patients with paraparesis experienced complete recovery. All patients tolerated retreatment very well. No serious acute side effects requiring any therapy were seen. During follow-up, no patient showed treatment-induced neurologic abnormalities affecting motor and sensory function, and all patients were able to walk and were continent for stool and urine. On the basis of the findings in this limited number of patients, it is not possible to give clear and general recommendations concerning the optimal total dose and fraction size that will have maximal palliative effects and minimal side effects. However, for the purpose of palliation, retreatment within the dose range used at our institution should be considered, taking the patient's expected life span and clinical symptoms into account.


[Long term observations after irradiation of the iris by the argon laser (author's transl)].
Eleven pigmented rabbit irides were irradiated with the argon laser and were examined electron-microscopically at several intervals between 15 minutes and 256 days after exposure. It was shown that cells start to migrate into the area of the lesion already on the fourth day. After 32 days the area of the lesion is completely closed. 256 days after exposure only a slight impression remained on the anterior surface of the iris.


Structural model of the collagen-like region of C1q comprising the kink region and the fibre-like packing of the six triple helices.
A detailed three-dimensional model of the collagenous part of C1q was derived by model building and computer-aided energy refinement calculations. The proposed structure is based on the collagen-like (-Gly-Xaa-Yaa-) repeating sequence of 78 to 81 residues in the N-terminal regions of the constituent A, B and C chains, on the mode of disulphide linkage between the 18 chains of C1q, and on its electron microscopically derived gross structure. It is demonstrated that the interruptions of the repeating sequence about half-way along the length of the collagenous regions (Gly36-Ile37-Arg38-Thr39 in the A chain and Ala36-Ile37-Hy138 in the C chain) do not lead to a disruption of the triple helical conformation but rather to a bend of about 60 degrees in an otherwise continuous triple helix. These features are consistent with a flexibility comparable with that of regular triple helices and with the observed low proteolytic susceptibility of the kink region. The azimuthal orientation of the kink is defined approximately by ArgA38 being located in the cap of the knee. Because of this extra residue between two glycine residues, a bad contact that would arise between the methyl group of AlaC36 and the peptide carbonyl of IleA37 in a straight triple helix is relaxed. The model features also a cluster of hydrophobic contacts between large hydrophobic side-chains in the interaction edges between the six collagen triple helices aligned with their about 10 nm long N-terminal regions in the fibril-like endpiece of C1q. The azimuthal orientations of the triple helices were derived by energy calculations of side-chain interactions previously applied to fibre-forming collagens. Independently, the same orientations and interaction edges were derived from the azimuthal orientation of the kink and the electron microscopically observed orientations of the triple helical arms that emerge from the endpiece, and which carry the C-terminal globular binding domains. The structural model has a number of implications for the assembly of the first component of complement from C1q and the zymogen complex C1r2C1s2 and possible mechanisms of its activation.


Bio-Inspired High Sensitivity of Moisture-Mechanical GO Films with Period-Gradient Structures.
Moisture actuators can accomplish humidity-triggered energy-conversion process, through material screening and structural design. Inspired by natural caterpillars and the hydrophilic properties of graphene oxide (GO), this work proposes a geometrical design of period-gradient structures in GO films for fabricating moisture actuators. These novel period-gradient-structured GO films exhibit excellent dynamic performance that they could deform at 1000° with a small radius in several seconds at a high relative humidity (RH ≈ 80%). The properties of fast actuating speed and high response to deformation are achieved through the structural designing of the sole GO film by a one-step formation process. A mechanics-based theoretical model combined with the finite element simulation is presented to demonstrate the actuating mechanism in geometry, moisture, and mechanics, which lays the foundation for potential applications of GO films in remote control, environmental monitoring, and man-machine interactions.


Oligosaccharides from "standardized intermediates". Synthesis of a branched tetrasaccharide glycoside isomeric with the blood-group B, type 2 determinant.
Building block derivatives of the component monosaccharides were used to construct the tetrasaccharide glycoside 15, in which an alpha-D-Galp-(1 leads to 4)-D-Gal linkage replaces the alpha-(1 leads to 3) linkage of the human blood-group B, type 2, determinant structure. The initial coupling of 2-O-benzoyl-3,6-di-O-benzyl-4-O-(tetrahydropyran-2-yl)-alpha-D-galactopyranosyl chloride to allyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-beta-D-glucopyranoside was followed by selective deprotection of the disaccharide product, either at O-4' (to give 8) or O-2' (to give 3). The conversion of 8 into 15 involved successive coupling with tetra-O-benzyl-alpha-D-galactopyranosyl bromide (8 leads to 11), O-debenzoylation at O-2' (11 leads to 12), coupling with tri-O-benzyl-alpha-L-fucopyranosyl bromide (12 leads to 14), and O-debenzylation by hydrogenolysis (14 leads to 15). Alternatively, 3 was alpha-L-fucosylated to give 6, and 6 was selectively deprotected at O-4' to give 7. However, attempts to alpha-D-galactosylate 7 were unsuccessful. The unsubstituted forms of the intermediate disaccharide (8) and trisaccharide (12) glycosides were obtained by appropriate deblocking procedures.


A molecular component of the arterial baroreceptor mechanotransducer.
Baroreceptor nerve endings detect acute fluctuations in arterial pressure. We tested the hypothesis that members of the DEG/ENaC family of cation channels, which are responsible for touch sensation in Caenorhabditis elegans, may be components of the baroreceptor mechanosensor. We found the gamma subunit of ENaC localized to the site of mechanotransduction in baroreceptor nerve terminals innervating the aortic arch and carotid sinus. A functional role for DEG/ENaC members was suggested by blockade of baroreceptor nerve activity and baroreflex control of blood pressure by an amiloride analog that inhibits DEG/ENaC channels. These data suggest that ENaC subunits may be components of the baroreceptor mechanotransducer and pave the way to a better definition of mechanisms responsible for blood pressure regulation and hypertension.


Photodynamic therapy of vascular stenosis: results from cell culture studies on human endothelial cells.
Experimental results from human cell culture studies have shown that smooth muscle cells derived from human atherosclerotic plaques react more sensitively to photoactivated dihematoporphyrin-ester and -ether (DHE) than smooth muscle cells from human nonatherosclerotic arteries. A therapeutic concept of photodynamic therapy of vascular stenosis appears, therefore, to be promising. The prerequisite for an intravascular application is a relatively harmless application of the photosensitizing agent to the luminal lining of endothelial cells. The effect of DHE with and without photoactivation was examined on endothelial cell cultures from human saphenous veins. The cellular uptake of DHE in relation to the serum content of the culture medium was evaluated, as well as its effect on proliferative activity, cell size, cell volume, and cellular viability. Intracellular uptake of DHE decreased significantly when higher serum concentrations were present in the culture medium. Incubation of cells with the photosensitizer for 9 days in the dark without light activation resulted in a significant decrease of endothelial cell proliferation only at concentrations higher than 2.5 micrograms/mL (= 2.5 mg/kg body weight for systemic application in vivo). Additional photoactivation caused no reduction of cell viability at DHE concentrations of 1 microgram/mL, but at 2.5 micrograms/mL and 5 micrograms/mL, a reduction of viable cells within 24 hours was observed in relation to the energy densities used for irradiation. Because smooth muscle cells from atherosclerotic plaques are, however, much more sensitive to photodynamic treatment, the concept of a photodynamic therapy of vascular stenosis may provide a good tool in the reduction of restenosis rates after recanalization of severely stenosed or even occluded arteries.


Solubility of heavy metals added to MSW.
This paper aims to investigate the six heavy metal levels (Cd, Cr, Cu, Pb, Ni and Zn) in municipal solid waste (MSW) at different pHs. It intends to provide the baseline information of metals solubility in MSW co-disposed or co-digested with MSW incinerator ashes in landfill or anaerobic bioreactors or heavy metals contaminated in anaerobic digesters. One milliliter (equal to 1mg) of each metal was added to the 100ml MSW and the batch reactor test was carried out. The results showed that higher HNO3 and NaOH were consumed at extreme pH of 1 and 13 compared to those from pH 2 to 11 due to the comparably higher buffer capacity. Pb was found to have the least soluble level, highest metal adsorption (%) and highest partitioning Kd (lg(-1)) between pH 3 and 12. In contrast, Ni showed the highest soluble level, lowest metal adsorption (%) and lowest Kd (lg(-1)) between pH 4 and 12. Except Ni and Cr, other four metals seemed to show the amphibious properties as comparative higher solubility was found in the acidic and basic conditions.


Density functional theory, comparative vibrational spectroscopic studies, NBO, HOMO-LUMO analyses and thermodynamic functions of N-(bromomethyl)phthalimide and N-(chloromethyl)phthalimide.
Quantum mechanical calculations of energies, geometries, and vibrational wavenumbers of N-(bromomethyl)phthalimide and N-(chloromethyl)phthalimide are carried out using density functional theory (DFT/B3LYP) method with 6-31G and 6-311G(d,p) basis sets. The optimized geometrical parameters obtained by B3LYP method show good agreement with experimental data. The difference between the observed and scaled wavenumber values of most of the fundamentals is very small. A detailed interpretation of the infrared and Raman spectra of N-(bromomethyl)phthalimide and N-(chloromethyl)phthalimide was also reported. The calculated HOMO and LUMO energies show that charge transfer occurs in the molecules. The thermodynamic functions of N-(bromomethyl)phthalimide and N-(chloromethyl)phthalimide have been performed at B3LYP/6-31G and B3LYP/6-311G(d,p) basis sets. The theoretical spectrograms for FT-IR and FT-Raman spectra of N-(bromomethyl)phthalimide and N-(chloromethyl)phthalimide have also been constructed.


Ability of six Latin American antivenoms to neutralize the venom of mapaná equis (Bothrops atrox) from Antioquia and Chocó (Colombia).
This investigation compared the ability of six Latin American antivenoms (monovalent antibothropic INS, Santafé de Bogotá; polyvalent INS; polyvalent probiol, Santafé de Bogotá; antibothropic Instituto Butantan, IB, São Paulo, Brazil; polyvalent Instituto Clodomiro Picado, ICP, San José, Costa Rica; polyvalent MYN, Mexico) to neutralize various pharmacological and enzymatic effects of Bothrops atrox venom from Antioquia and Chocó, north-west of Colombia. Our results demonstrated conspicuous differences in the ability of the six antivenoms. In terms of neutralization of lethality, the highest efficacy was observed in the polyvalent INS and the lowest in the polyvalent MYN antivenom. All antivenoms were highly effective in the neutralization of hemorrhage, polyvalent INS and probiol being the highest. In the neutralization of edema-forming activity, the most effective antivenom was the polyvalent (ICP); monovalent (INS) and polyvalent (MYN) were the least effective. All antivenoms were effective in the neutralization of the myotoxic activity of B. atrox venom, the most effective being the polyvalent (INS) and antibothropic (IB). Defibrinating activity was neutralized by all antivenoms; polyvalent (MYN) showed the lowest efficiency. Polyvalent (ICP) antivenom had the highest neutralizing ability against the indirect hemolytic effect of B. atrox venom; polyvalent (MYN) did not neutralize this enzymatic activity. Overall, the polyvalent antivenom (INS) showed the highest neutralizing ability.


Follow-up study of 14 oral granular cell tumors.
The granular cell tumor is an uncommon benign lesion with a predilection for the oral cavity. Fourteen tumors from 13 patients have been reviewed with a follow-up period ranging from 7 months to 21 years with an average of 7.1 years. Women were affected twice as often as men, and the age of the patients varied from 14 to 75 years. Eleven of the lesions were located on the tongue, the remaining on the lower lip, sublingual papilla, and the buccal mucosa. Multiple lesions were found in one patient.The tumors varied in size from 3 to 25 mm in diameter and were all firm to hard in consistency. All the lesions were treated by local excision. Pseudoepitheliomatous hyperplasia of the overlying epithelium was seen in four patients. In spite of a possible inadequate removal of 10 of the lesions where granular cells extended to the margin of excision, no recurrence was seen. A simple but deep local excision is the recommended treatment.


Development of a robust crystallization platform for immune receptor TREM2 using a crystallization chaperone strategy.
TREM2 has been identified by genomic analysis as a potential and novel target for the treatment of Alzheimer's disease. To enable structure-based screening of potential small molecule therapeutics, we sought to develop a robust crystallization platform for the TREM2 Ig-like domain. A systematic set of constructs containing the structural chaperone, maltose binding protein (MBP), fused to the Ig domain of TREM2, were evaluated in parallel expression and purification, followed by crystallization studies. Using protein crystallization and high-resolution diffraction as a readout, a MBP-TREM2 Ig fusion construct was identified that generates reproducible protein crystals diffracting at 2.0 Å, which makes it suitable for soaking of potential ligands. Importantly, analysis of crystal packing interfaces indicates that most of the surface of the TREM2 Ig domain is available for small molecule binding. A proof of concept co-crystallization study with a small library of fragments validated potential utility of this system for the discovery of new TREM2 therapeutics.


New Ontarians With Disabilities Act finally adopted.
After several false starts, Ontario has passed legislation designed to remove barriers faced by disabled persons, including the barrier of stigma.


Prevalence, epidemiological and clinical correlates of genital Chlamydia trachomatis infection.
To evaluate the prevalence of genital infection with Chlamydia trachomatis in different groups of patients in the region of Plovdiv, Bulgaria, over a period of four years (1992-1995) and to establish epidemiological and clinical correlates of infection. Five groups were enrolled in the study: group A-990 symptomatic male sexually transmitted disease (STD) patients, group B-1023 symptomatic female STD patients, group C-253 gynaecological patients, and asymptomatic groups D-276 men and group E-231 women. Urethral samples from men and cervical and urethral samples from women were examined for C. trachomatis antigen by direct immunofluorescence assay (DFA) or enzyme immunoassay (EIA) confirmed by DFA at the STD outpatient clinic of the Medical Institute in Plovdiv. The prevalence rates for genital infection with Chlamydia trachomatis were 25.1% in group A, 21.8% in group B, 15.4% in group C, 4.3% in group D and 6.1% in group E. Infection with C. trachomatis was more common in patients who were < or = 25 years of age, unmarried, and with risk sexual behaviour, as well as in those who had signs and symptoms suggestive of infection. The study shows a relatively high prevalence of infection with C. trachomatis in STD and gynaecological patients. Symptoms and signs correlated with C. trachomatis infection, but were not specific or reliable indicators of infection. C. trachomatis detection should be included in standard STD and gynaecological examination.


Supporting the integration of technology into contemporary nursing education.
This article provides an overview of the challenges and strategies faced by educational administrators in planning, delivering, and evaluating technology services to today's nursing students and faculty. Academic technology uses, examples, and support suggestions are provided so that educational administrators can effectively choose appropriate technologies geared to meet their educational objectives. The challenge comes with deciding the intended educational outcomes, and designing the appropriate educational milieu. Administrators are reminded to look to central administration to coordinate and participate in technology planning.


Absolute configuration and total synthesis of a novel antimalarial lipopeptide by the de novo preparation of chiral nonproteinogenic amino acids.
The absolute configuration (via degradation and Marfey's derivatization studies) and the total synthesis of a novel antimalarial lipid-peptide isolated from Streptomyces sp. (IC(50) = 0.8 μM, Plasmodium falciparum 3D7) is disclosed. To this end, versatile stereocontrolled routes to nonproteinogenic amino acids (via catalytic Mannich, Sharpless methods) and enantiomeric trans fatty acids (via Evans alkylation, Kocienski-Julia olefination) have been developed.


Synergistic between autotrophic and heterotrophic microorganisms for denitrification using bio-S as electron donor.
In recent years, biological sulfur (bio-S) was employed in sulfur autotrophic denitrification (SAD) in which autotrophic Thiobacillus denitrificans and heterotrophic Stenotrophomonas maltophilia played a key role. The growth pattern of T.denitrificans and S.maltophilia exhibited a linear relationship between OD600 and CFU when OD600 < 0.06 and <0.1, respectively. When S.maltophilia has applied alone, the NorBC and NosZ were undetected, and denitrification was incomplete. The DsrA of S.maltophilia could produce sulfide as an alternative electron donor for T.denitrificans. Even though T.denitrificans had complete denitrification genes, its efficiency was low when used alone. The interaction of T.denitrificans and S.maltophilia reduced nitrite accumulation, leading to complete denitrification. A sufficient quantity of S.maltophilia may trigger the autotrophic denitrification activity of T.denitrificans. When the colony-forming units (CFU) ratio of S.maltophilia to T.denitrificans was reached at 2:1, the highest denitrification performance was achieved at 2.56 and 12.59 times higher than applied alone. This research provides a good understanding of the optimal microbial matching for the future application of bio-S.


Optimizing efficiency and safety in a radiation oncology department through the use of ARIA 11 Visual Care Path.
Visual Care Path (VCP) is a workflow tool within the ARIA 11 Record and Verify System. The purpose of this study was to quantify the impact of VCP implementation on the metrics of efficiency, safety, and staff satisfaction. Our multidisciplinary quality improvement team reviewed the entire process of patient care and constructed VCP modules to chart serial and parallel events from consultation to treatment completion. A failure mode and effects analysis was performed to identify high-risk tasks within existing patient care workflow. Data on timeliness of task completion were collected for 612 patients (6560 tasks) in 3 time phases: pre-VCP, transition, and post-VCP. Errors detected during a physics plan check were also monitored. A survey about the VCP was distributed to all staff to evaluate the impact of the VCP on the department. Descriptive statistics were calculated for the metrics of efficiency, safety, and staff satisfaction. Notable improvements in efficiency and safety were observed. Radiation oncologists' compliance with timely completion of the Simulation Preparation VCP tasks increased from 45.9% ± 14.3% during the pre-VCP phase to 85.8% ± 10.9% during the post-VCP phase. Compliance with Treatment Planning VCP tasks also increased from 52.6% ± 9.9% during the pre-VCP phase to 76.0% ± 9.7% during the post-VCP phase. The monthly defect rate (ratio of plans with errors to the total number of plans checked by a physicist) decreased from 19.1% ± 1.3% during the pre-VCP phase to 5.2% ± 4.1% during the post-VCP phase. Ninety-four percent of staff members responded to the VCP survey; more than 80% of respondents found the VCP to have a favorable impact. Implementation of the VCP in our department improved workflow efficiency, reduced the number of errors, and was very well received within the department.


Applying a nanocomposite hydrogel electrode to mitigate electrochemical polarization and focusing effect in electrokinetic remediation of a Cu- and Pb-contaminated loess.
Inappropriate handling of copper (Cu) and lead (Pb)-containing wastewater resulting from metallurgical and smelting industries in Northwest China encourages their migration to surrounding environments. Their accumulation causes damage to liver and kidney function. The electrokinetic (EK) technology is considered to be an alternative to traditional remediation technologies because of its great maneuverability. The EK remediation is accompanied by the electrode polarization and the focusing effect toward affecting removal efficiency. In this study, a nanocomposite hydrogel (NCH) electrode was proposed and applied to the EK remediation of Cu- and Pb-contaminated loess. The mechanical, adsorption capacity, adsorption kinetics, and electrochemical properties of the NCH electrode were investigated in detail, followed by microscopic analyses of Scanning Electron Microscope (SEM), Energy Dispersive X-ray Spectroscopy (EDS), and Raman spectrometer. Results showed that the enhancement of the mechanical properties of the NCH electrode was attributed to the crosslinks of graphene nanoparticles, calcium alginate, and hydrogen bonds, while the Cu or Pb adsorption by the NCH electrode was in a chemisorption manner. The second layer formation might address the increase in adsorption capacity with increasing temperature. These results highlight the relative merits of the NCH electrode and verify the potential of applying the NCH electrode to the EK remediation of Cu- and Pb-contamianted loess.


A method to identify pulmonary intersegmental planes with intravenous vitamin B2 injection.
The present study investigated whether the pulmonary intersegmental planes could be identified with the intravenous injection of vitamin B2 using a fluorescent camera and whether this method can be used instead of the inflation-deflation technique or the intravenous indocyanine green (ICG) method. In experiment 1, the vitamin B2 was intravenously injected to visualize the pulmonary intersegmental plane and perform segmentectomy, and the visualized pulmonary intersegmental line was then compared to the inflation-deflation line in six pigs. In experiment 2, using six pigs, the fluorescent area and duration of fluorescence were compared after the intravenous injection of vitamin B2 and ICG in the same animals. In all animals in experiment 1, it was possible to clearly detect yellow-green fluorescence in the lung, in segments other than the one intended for resection, for at least 60 min. Moreover, the line visualized with vitamin B2 fluorescence matched the inflation-deflation line in all animals. In experiment 2, the area of vitamin B2 fluorescence corresponded to the area of ICG fluorescence in each animal. The visualization of fluorescence after the intravenous injection of vitamin B2 using a fluorescent camera was a simple, safe, and accurate method for detecting intersegmental planes in a pig model. This method can be an alternative to the inflation-deflation technique and the intravenous ICG method.


Brain oxygenation declines in elite Kenyan runners during a maximal interval training session.
The purpose of this study was to characterise the cerebral oxygenation (Cox) response during a high-intensity interval training session in Kenyan runners, and to examine any relationship with running performance. 15 Kenyan runners completed a 5-km time trial (TT) and a Fatigue Training Test on a treadmill (repeated running bouts of 1-km at a pace 5% faster than their mean 5-km TT pace with a 30-s recovery until exhaustion). Changes in Cox were monitored via near-infrared spectroscopy through concentration changes in oxy- and deoxy-haemoglobin (Δ[O2Hb] and Δ[HHb]), tissue oxygenation index (TOI), and total hemoglobin index (nTHI). The number of 1-km repetitions achieved by the participants was 5.5 ± 1.2 repetitions at a mean pace of 20.5 ± 0.7 km h-1. Δ[O2Hb] measured at the end of each running repetition declined progressively over the course of the trial (p = 0.01, ES = 4.59). Δ[HHb] increased during each running bout until the end of the Fatigue Training Test (p < 0.001; ES = 6.0). TOI decreased significantly from the beginning of the test (p = 0.013, ES = 1.83), whereas nTHI remained stable (ES = 0.08). The Cox decline in the Fatigue Training Test was negatively correlated with the speed at which the test was completed (p = 0.017; r = -0.61), suggesting that the best performers were able to defend their Cox better than those of lower running ability. In conclusion, this study suggests that elite Kenyan runners cannot defend cerebral oxygenation when forced to exercise to their physiological limits. This emphasises the critical importance of pacing in their racing success.


Octahedral ruthenium complexes selectively stabilize G-quadruplexes.
A series of octahedral Ru(ii) complexes with an x-y planar tetradentate and two trans-z-axis ammonia ligands were synthesized. High stabilization of G-quadruplexes was achieved upon π-stacking with aromatic planar ligands. Unique interaction from z-axis ligands bestowed both excellent binding resistance to duplex DNA and selectivity towards the antiparallel topology.


Beta oscillations in freely moving Parkinson's subjects are attenuated during deep brain stimulation.
Investigations into the effect of deep brain stimulation (DBS) on subthalamic (STN) beta (13-30 Hz) oscillations have been performed in the perioperative period with the subject tethered to equipment. Using an embedded sensing neurostimulator, this study investigated whether beta power was similar in different resting postures and during forward walking in freely moving subjects with Parkinson's disease (PD) and whether STN DBS attenuated beta power in a voltage-dependent manner. Subthalamic local field potentials were recorded from the DBS lead, using a sensing neurostimulator (Activa(®) PC+S, Medtronic, Inc., Food and Drug Administration- Investigational Device Exemption (IDE)-, institutional review board-approved) from 15 PD subjects (30 STNs) off medication during lying, sitting, and standing, during forward walking, and during randomized periods of 140 Hz DBS at 0 V, 1 V, and 2.5/3 V. Continuous video, limb angular velocity, and forearm electromyography recordings were synchronized with neural recordings. Data were parsed to avoid any movement or electrical artifact during resting states. Beta power was similar during lying, sitting, and standing (P = 0.077, n = 28) and during forward walking compared with the averaged resting state (P = 0.466, n = 24), although akinetic rigid PD subjects tended to exhibit decreased beta power when walking. Deep brain stimulation at 3 V and at 1 V attenuated beta power compared with 0 V (P < 0.003, n = 14), and this was voltage dependent (P < 0.001). Beta power was conserved during resting and forward walking states and was attenuated in a voltage-dependent manner during 140-Hz DBS. Phenotype may be an important consideration if this is used for closed-loop DBS.


Combined use of conventional and clumped carbonate stable isotopes to identify hydrothermal isotopic alteration in cave walls.
Alteration of conventional carbonate stable isotopes (δ18O, δ13C) in cave walls has been shown to be a useful tool to identify cave formation driven by deep-seated processes, i.e., hypogene karstification. If combined with a prior information on the paleowater stable isotope composition, further insights can be obtained on the temperature and the source of the paleowater. Clumped isotope composition (Δ47) of carbonates is an independent measurement of temperature, and if combined with the conventional stable isotopes, can provide information on the paleowater stable isotope composition. On the example of Provalata Cave (N. Macedonia), we apply for the first time, both conventional and clumped stable isotope analysis, and identify two different isotope alteration trends, reflecting two distinct hydrothermal events: an older, hotter one, where isotope alteration was likely related to isotope diffusion, lowering the δ18O values of the carbonate; and a younger one, related to the cave formation by low-temperature CO2-rich thermal waters, with dissolution-reprecipitation as the alteration mechanism, causing decrease in δ18O values, and unexpected increase in δ13C values. The findings are further corroborated by additional insight from optical petrography and cathodoluminescence microscopy, as well as fluid inclusion analysis of secondary calcite crystals related to the cave forming phase.


Contagious equine metritis: artificial reproduction changes the epidemiologic paradigm.
Recent CEM outbreak reports reflect a novel epidemiologic manifestation with a markedly different risk association for transmission via artificial reproduction and subsequent to inadvertent importation of unapparent carrier stallions. Artificial breeding has an increased association with horizontal or fomite-associated transmission. Reported risk factors include inadequate biosecurity protocols at centralised breeding facilities associated with stallion management and methods of semen collection, processing and transport. Detection of carriers is based on traditional bacteriology from genital swabs and despite limitations inherent to Taylorella equigenitalis is currently the gold standard applied in all international trade and movement protocols. These limitations are reported to be overcome by PCR assays improving diagnostic sensitivity and specificity, practicality, turn-around times, through-put and cost efficacy. Molecular methods have increased understanding of the Taylorelleae, facilitate epidemiologic surveillance and outbreak control strategies. Validation and international regulatory acceptance of a robust PCR-based assay and the undefined risks in association with cryopreserved semen and embryos are future areas warranting further investigation.


Immunotherapy Moves to the Early-Stage Setting in Non-Small Cell Lung Cancer: Emerging Evidence and the Role of Biomarkers.
Despite numerous advances in targeted therapy and immunotherapy in the last decade, lung cancer continues to present the highest mortality rate of all cancers. Targeted therapy based on specific genomic alterations, together with PD-1 and CTLA-4 axis blocking-based immunotherapy, have significantly improved survival in advanced non-small cell lung cancer (NSCLC) and both therapies are now well-established in this clinical setting. However, it is time for immunotherapy to be applied in patients with early-stage disease, which would be an important qualitative leap in the treatment of lung cancer patients with curative intent. Preliminary data from a multitude of studies are highly promising, but therapeutic decision-making should be guided by an understanding of the molecular features of the tumour and host. In the present review, we discuss the most recently published studies and ongoing clinical trials, controversies, future challenges and the role of biomarkers in the selection of best therapeutic options.


Effect of salinity changes on olfactory memory-related genes and hormones in adult chum salmon Oncorhynchus keta.
Studies of memory formation have recently concentrated on the possible role of N-methyl-d-aspartate receptors (NRs). We examined changes in the expression of three NRs (NR1, NR2B, and NR2C), olfactory receptor (OR), and adrenocorticotropic hormone (ACTH) in chum salmon Oncorhynchus keta using quantitative polymerase chain reaction (QPCR) during salinity change (seawater→50% seawater→freshwater). NRs were significantly detected in the diencephalon and telencephalon and OR was significantly detected in the olfactory epithelium. The expression of NRs, OR, and ACTH increased after the transition to freshwater. We also determined that treatment with MK-801, an antagonist of NRs, decreased NRs in telencephalon cells. In addition, a reduction in salinity was associated with increased levels of dopamine, ACTH, and cortisol (in vivo). Reductions in salinity evidently caused NRs and OR to increase the expression of cortisol and dopamine. We concluded that memory capacity and olfactory imprinting of salmon is related to the salinity of the environment during the migration to spawning sites. Furthermore, salinity affects the memory/imprinting and olfactory abilities, and cortisol and dopamine is also related with olfactory-related memories during migration.


Translocation t(6;9)(p22.3;q34) in myelodysplastic syndrome--refractory anemia with excess blasts.
A 69-year-old male patient with refractory anemia with excess blasts (RAEB) was found to have a consistent chromosomal abnormality, t(6;9)(p22.3;q34), in the bone marrow and unstimulated peripheral blood cells. Twenty patients with t(6;9) and leukemia have been reported; some of them had a myelodysplastic syndrome (MDS) before developing overt ANLL. Our patient was still in the MDS stage when the t(6;9) was found. This result suggests that t(6;9) represents one of the pathways from MDS to leukemia in patients with ANLL.


Costs of female odour in males of the parasitic wasp Lariophagus distinguendus (Hymenoptera: Pteromalidae).
The display of female traits by males is widespread in the animal kingdom. In several species, this phenomenon has been shown to function adaptively as a male mating strategy to deceive sexual rivals (female mimicry). Freshly emerged males of the parasitic wasp Lariophagus distinguendus (Hymenoptera: Pteromalidae) are perceived by other males as if they were females because of a very similar composition of cuticular hydrocarbons which function as a sex pheromone in this species inducing courtship behaviour in males. Within 32 h, however, males deactivate the pheromone and are no longer courted by other males. In this paper, behavioural experiments were performed to test hypotheses on potential costs and benefits associated with the female odour in young males. We did not find any benefits, but demonstrated that young males were significantly more often outrivaled in male-male contests when competing with two older males for a female. Also, young males were significantly more often mounted in homosexual courtship events during these contests. Thus, display of female traits by males is not necessarily beneficial, and in fact, can be disadvantageous. We suggest that these costs have favoured the evolution of the pheromone deactivation mechanism in L. distinguendus males. The function of cuticular hydrocarbons as a female courtship pheromone in L. distinguendus might have evolved secondarily from a primary function relevant for both genders, and the deactivation of the signal in males might have caused a shift of specificity of the chemical signal from the species level to the sex level.


Relation between fractional flow reserve value of coronary lesions with deferred revascularization and cardiovascular outcomes in non-diabetic and diabetic patients.
FFR of deferred PCI lesions can predict future cardiovascular events. However, the prognostic utility of FFR remains unclear in diabetic patients in view of the potential impact of the diffuse nature of vascular disease process. We aimed to study the relation between fractional flow reserve (FFR) values and long-term outcomes of diabetic and non-diabetic patients with deferred percutaneous coronary intervention (PCI). Patients with FFR assessment and deferred PCI (n=630) were enrolled and stratified according to diabetes mellitus (DM) status and FFR values. Patients were followed over a median of 39months. Cox proportional hazard regression models were used to analyze the association between clinical endpoints and clinical factors such as DM and FFR. In non-diabetics (n=450), higher FFR values were associated with less cardiovascular events (hazard ratio (HR) for death and myocardial infarction (MI) [95% confidence interval (CI)], 0.61[0.44 to 0.86] per 0.1 increase in FFR, p=0.007; HR for revascularization [95%CI], 0.66[0.49 to 0.9] per 0.1 increase in FFR, p=0.006). In diabetics (n=180), there was no difference in death and MI across the range of FFR values. Among those patients with an FFR >0.85, diabetics had a more than two-fold higher risk of death and MI than non-diabetics (HR [95% CI], 2.20 [1.19 to 4.01], p=0.015). Among non-diabetic patients with deferred PCI, a higher FFR was associated with lower rates of death, MI and revascularization. On the contrary in diabetic patients with deferred revascularization, FFR was not able to differentiate the risk of cardiovascular events.


Current radiosurgery practice: results of an ASTRO survey. Task Force on Stereotactic Radiosurgery, American Society for Therapeutic Radiology and Oncology.
Although there is increasing interest in radiosurgery, little quantitative data regarding current patterns of radiosurgery practice are available. We developed a radiosurgery questionnaire to obtain information on radiosurgery practice. We distributed the questionnaire to the entire membership of the American Society of Therapeutic Radiology and Oncology in early 1993. Responses were obtained from 74 facilities that practice radiosurgery, corresponding to over 6000 treatments carried out since 1983 by 135 radiation oncologists and 130 physicists. Most respondents were found to work within a multidisciplinary team, consisting of the following specialists (average hours devoted per patient on day of treatment in parentheses): radiation oncologist (3.8), neurosurgeon (3.2), physicist (6.1), radiologist (0.7), nurse (2.7), other (3.0). On average, neurosurgeons and nurses who perform Gamma Knife radiosurgery devote significantly more time-per-patient on the day of treatment than their peers who perform linac radiosurgery. On average, less experienced radiation oncologists and physicists (< or = 24 months experience, or < or = 50 patients treated) devote significantly more time-per-patient on the day of treatment than their more experienced peers. Although there are many more linac radiosurgery facilities than Gamma Knife facilities, on average the number of patients treated per month per facility is significantly larger at the latter. On average, follow-up responsibilities are nearly equally shared by radiation oncologists and neurosurgeons, except at Gamma Knife facilities, where neurosurgeons assume a larger percentage of follow-up responsibility. The percentages of patients treated at linac facilities for metastases or primary CNS malignancy are larger than the corresponding percentages at Gamma Knife facilities; the opposite is true for arteriovenous malformation, acoustic neuroma, and meningioma. Current radiosurgery practice usually involves a team approach, with participation of specialists from radiation oncology, neurosurgery, physics, radiology, and nursing. The average number of M.D. and Ph.D. hours required per treatment on the day of radiosurgery is high.


Prognostic value of bone marrow 18F-FDG uptake on PET/CT in lymphoma patients with negative bone marrow involvement.
The study evaluated the significance of 18F fluorodeoxyglucose (18F-FDG) uptake of bone marrow (BM) for predicting progression-free survival (PFS) in lymphoma patients without BM involvement. Ninety-five patients with histopathologically proven lymphoma, 7 Hodgkin's lymphoma and 88 non-Hodgkin's lymphoma, who underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) and BM biopsy for staging work-up and 40 normal subjects were retrospectively enrolled. Maximal 18F-FDG uptake of lymphoma (Lmax), mean 18F-FDG uptake of BM (BM SUV) and BM-to-liver uptake ratio (BLR) were measured. Prognostic value of BM SUV and BLR for predicting PFS were assessed. Of the 95 patients, 35 (36.8%) were histopathologically or clinically diagnosed with BM involvement of lymphoma. There were significant differences of BLR among lymphoma patients with/without BM involvement and normal subjects (P<0.05). For all patients, high risk indicated by International Prognostic Index (IPI) score and Lmax were significantly associated with PFS on multivariate analysis (P<0.05). For 60 patients without BM involvement, BM SUV and BLR were independent prognostic factors for PFS along with performance status and Lmax (p<0.05). Among patients without BM involvement, high 18F-FDG uptake of BM was associated with significantly worse PFS than low 18F-FDG uptake of BM, with no significant difference in PFS apparent compared to patients with BM involvement. In lymphoma patients without BM involvement, 18F-FDG uptake of BM was significantly associated with worse PFS. Patients with high 18F-FDG uptake of BM showed similar prognosis to those with BM involvement.


Collaborative neural processes predict successful cognitive-motor performance.
Psychomotor efficiency is achieved by expert performers who exhibit refined attentional strategies and efficient motor program execution. Further understanding of the psychomotor efficiency hypothesis requires examination of the co-activation of key electroencephalographic (EEG) indices, including frontal theta (Fθ) power, left temporal alpha (T3α) power, the sensory-motor rhythm (SMR), and frontocentral alpha power (FCα). This study examined the relationship between these selected neural processes and the odds of successful cognitive-motor performance. EEG indices of successful and failed putts observed in twenty-seven skilled golfers were subjected to mixed-effects logistic regression analysis. The results revealed that concurrent elevations of Fθ and T3α were associated with increased odds of successful performance. The co-activation from motoric processes indicated by SMR and FCα also elevated the odds. Overall, the findings emphasize that refined attention allocation and effective motor program processing are essential cognitive features of superior cognitive-motor performance for skilled golfers.


Binding of 125I-labeled granulocyte colony-stimulating factor to normal murine hemopoietic cells.
The binding of granulocyte colony-stimulating factor (G-CSF) to murine bone marrow cells was investigated using a radioiodinated derivative of high specific radioactivity which retained full biological activity. The binding was time- and temperature-dependent, saturable and highly specific. The apparent dissociation constant for the reaction was 60-80 pM at 37 degrees C and 90-110 pM at 4 degrees C, similar to that found for the binding of G-CSF to murine leukemic cells (WEHI-3B D+) and significantly higher than the concentration of G-CSF required to stimulate colony formation in vitro. Autoradiographic analysis confirmed the specificity of binding since granulocytic cells were labeled but lymphocytes, erythroid cells and eosinophils were not. Blast cells and monocytic cells were partially labeled, the latter at low levels. In the neutrophilic granulocyte series, grain counts increased with cell maturity, polymorphs being the most heavily labeled but all cells showed considerable heterogeneity in the degree of labeling. Combination of Scatchard analysis of binding with autoradiographic data indicated that mature granulocytes from murine bone marrow exhibited 50-500 G-CSF receptors per cell.


Exploring breast cancer response prediction to neoadjuvant systemic therapy using MRI-based radiomics: A systematic review.
MRI-based tumor response prediction to neoadjuvant systemic therapy (NST) in breast cancer patients is increasingly being studied using radiomics with outcomes that appear to be promising. The aim of this study is to systematically review the current literature and reflect on its quality. PubMed and EMBASE databases were systematically searched for studies investigating MRI-based radiomics for tumor response prediction. Abstracts were screened by two reviewers independently. The quality of the radiomics workflow of eligible studies was assessed using the Radiomics Quality Score (RQS). An overview of the methodologies used in steps of the radiomics workflow and current results are presented. Sixteen studies were included with cohort sizes ranging from 35 to 414 patients. The RQS scores varied from 0 % to 41.2 %. Methodologies in the radiomics workflow varied greatly, especially region of interest segmentation, features selection, and model development with heterogeneous outcomes as a result. Seven studies applied univariate analysis and nine studies applied multivariate analysis. Most studies performed their analysis on the pretreatment dynamic contrast-enhanced T1-weighted sequence. Entropy was the best performing individual feature with AUC values ranging from 0.83 to 0.85. The best performing multivariate prediction model, based on logistic regression analysis, scored a validation AUC of 0.94. This systematic review revealed large methodological heterogeneity for each step of the MRI-based radiomics workflow, consequently, the (overall promising) results are difficult to compare. Consensus for standardization of MRI-based radiomics workflow for tumor response prediction to NST in breast cancer patients is needed to further improve research.


Impact of a national beta-thalassemia carrier screening program on the birth rate of thalassemia major.
In Taiwan, the prevalence of beta-thalassemia trait is at least 1.1%. The Taiwan government initiated a National Screening Program in 1993. Herein we examine the differences before and after the initiation of this program. Data consisting of the total number of patients and the birth prevalence beta-thalassemia major were collected. Ninety-one patients with transfusion-dependent thalassemia treated in our hospitals were included for analysis. DNA analysis was performed for 86 patients. In Taiwan 361 patients exist. The birth prevalence of per 100,000 births was 5.6% in 1994 and declined to 1.21 in 2002. Fourteen patients were born after the program's initiation. DNA analysis of them revealed a new mutation (IVS-1-5 (G-C)), which was introduced through an inter-racial marriage. Otherwise, the remainder was the common beta-thalassemia mutations found in Taiwan. Despite how successful the National Screening Program is, a few doctors still failed to detect parents at risk. In addition, we are concerned about the emerging problem of the increase of interracial marriages where parents may not have appropriate screening. Hence, postgraduate education programs for physicians, health education for the general population, and timely screening of inter-racial marriage should become a priority.


Effects of nanometer-thick passivation layers on the mechanical response of thin gold films.
The mechanical behavior of freestanding gold membranes 0.5 micron thick with and without passivation layers was studied with a membrane deflection experiment. Membrane width was varied from 2.5 to 20 microns to investigate size effects. The presence of the passivation layer had the effect of reducing the membrane strength. Yield stress, as well as fracture strain and stress, were all found to be significantly lower for the passivated specimens. The residual stress state was found to be significantly larger with passivation, to the degree of generating prestressed cracks at micromachined notches. Membrane width had the greatest effect on the residual stress state with smaller widths having larger residual stress.


Gender and age differences in blood utilization and length of stay in radical cystectomy: a population-based study.
Radical cystectomy is a major surgical procedure associated with significant blood loss and lengthy hospital stays. This surgical procedure is more challenging in women than men due to anatomical-based differences. We evaluated resource utilization and complication rates of patients undergoing radical cystectomy or exenteration using the Texas Hospital In-Patient Discharge Data Collection. This was a retrospective study of 1,493 patients, 35 years of age or older, who underwent radical cystectomy for bladder cancer from January 2000 to December 2003. We evaluated blood product charges, length of stay, and complication rates during hospitalization. In this sample, 24% of the patients (n = 356) were women. Overall, women had significantly increased blood product charges and length of stay compared to men, $1,392.87 vs. $718.21 (P < 0.001) and 12.72 vs. 11.64 (P = 0.03), respectively. During hospitalization, 26 of the patients died. No differences in mortality or complication rates were observed between men and women. Multivariate analysis showed that female sex (P < 0.001) and age (P = 0.003) were independent predictors of increased blood product charges. Multivariate analysis showed that female sex (P = 0.015), age (P = 0.003), and Charlson's comorbidity index >1 (P = 0.05) were predictors of longer length of stay. Women and older patients with bladder cancer are at risk of increased blood products utilization and length of hospital stay after a radical cystectomy. Appropriate postoperative care and referrals should improve postoperative outcomes for these vulnerable patients.


Treatment outcome of regenerative endodontic procedures in mature permanent teeth compared to nonsurgical endodontic treatment: A systematic review and meta-analysis.
Regenerative endodontic procedures (REP) have the advantage of restoring root canal's native defense ability by re-establishing vital pulp-like tissue. This review aims to determine the overall clinical and/or radiographic success rate (O) of REP (I) in mature permanent teeth (P) and to compare it (C) with nonsurgical endodontic treatment (NSET). Sources: PubMed, Web of Science, Embase, EBSCO, Cochrane Central Register of Controlled trials, ClinicalTrials.gov, Clinical Trials Registry-India and OpenGrey. Inclusion: Randomized clinical trials and single-arm prospective studies evaluating the treatment outcomes of REP in mature permanent teeth. Exclusion: Incomplete trials/studies, in vitro studies, animal studies, case reports/series, conference proceedings. Cochrane ROB2.0 and ROBINS-I tools were used to assess the risk of bias. Risk difference (R.D.) between NSET and REP was determined by meta-analysis of the randomized clinical trials. The overall success rate of REP was calculated using data from both randomized clinical trials and single-arm prospective studies. Sensitivity analysis and subgroup analysis were performed. Ten studies (n = 552) were included. R.D between REP and NSET was 0.032 (95% C.I: 0.023-0.087; P = 0.258). Overall success rate of REP was 96.0% (95% confidence interval: 94%-98%). No significant difference was found in sensitivity analysis (P = 0.551), or any of the subgroup analysis (P > 0.05). A limited number of randomized clinical trials were available, and only two of them had a low risk of bias. Consistent results were obtained in both types of included studies. Based on a limited number of comparative studies, REP has a similar success rate to NSET in mature permanent teeth. Funding: Nil. Registration: PROSPERO (CRD42020204882).


Vertebral body and splenic irradiation are associated with lymphopenia in localized pancreatic cancer treated with stereotactic body radiation therapy.
The purpose of this study was to determine if vertebral body and splenic dosimetry was associated with the development of lymphopenia in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiation therapy (SBRT). Patients with BRPC/LAPC who were treated with SBRT and who had lymphocyte counts and radiation treatment plans available for review were included in the study. Vertebral body levels T11-L3 and the spleen were retrospectively contoured for each patient. Univariate (UVA) and multivariable analyses (MVA) were performed to identify associations between vertebral body and splenic dosimetric parameters with absolute lymphocyte count (ALC) and grade ≥ 2 lymphopenia. Receiver operator characteristic curves were generated to identify dose-volume thresholds in predicting grade ≥ 2 lymphopenia. A total of 132 patients were included in the study. On UVA and MVA, vertebral V15 (regression coefficient [β]: - 0.026, 95% CI - 0.044 to - 0.009, p = 0.003), vertebral V2.5 (β: - 0.011, 95% CI - 0.020 to - 0.002, p = 0.015), and log10PTV (β: - 0.15, 95% CI - 0.30 to - 0.005, p = 0.042) were associated with post-SBRT ALC. On UVA and MVA, vertebral V15 (odds ratio [OR]: 3.98, 95% CI 1.09-14.51, p = 0.027), vertebral V2.5 (OR: 1.04, 95% CI 1.00-1.09, p = 0.032), and spleen V10 (OR: 1.05, 95% CI 1.09-1.95, p = 0.004) were associated with development of grade ≥ 2 lymphopenia. Development of grade ≥ 2 lymphopenia was more likely in patients with vertebral V15 ≥ 5.84% (65.5% vs 34.0%, p = 0.002), vertebral V2.5 ≥ 48.36% (48.9% vs 23.8%, p = 0.005), and spleen V10 ≥ 4.17% (56.2% vs 26.9%, p < 0.001). Increasing radiation dose to vertebral bodies and spleen were associated with the development of lymphopenia in BRPC/LAPC treated with SBRT. Optimization of vertebral body and splenic dosimetry may reduce the risk of developing lymphopenia and improve clinical outcomes in this population.


Minimally invasive surgical adjuncts to upper blepharoplasty.
A variety of surgical adjuncts can be added to upper eyelid blepharoplasty with the goal of enhancing surgical results and patient satisfaction. All of these procedures are minimally invasive and most are performed through a standard eyelid crease incision. These procedures can be added to stabilize or conservatively lift the outer brow, prevent the stigmata of postoperative volume loss, improve the brow-eyelid transition and contour, and reposition a prolapsed lacrimal gland. The procedures are generally straightforward, easily learned, and complication free. Familiarity with these techniques provides the aesthetic eyelid surgeon with added options to improve surgical results.


Medication synchronization adoption and pharmacy performance.
While medication synchronization programs are becoming a staple in community pharmacies, a standard process needs to be identified to provide consistent positive outcomes. Many studies demonstrate how medication synchronization affects individual level patients but have not examined how medication synchronization affects the pharmacy's performance. Because community pharmacies are calibrated based on performance to adherence measures for all patients, it is important to understand whether resource-intensive interventions, such as medication synchronization, lead to improved performance. The aims of this study were to 1) examine pharmacy characteristics associated with medication synchronization adoption and 2) examine whether medication synchronization is associated with pharmacy-level performance on select medication adherence and utilization measures. This study used a cross-sectional design. Community pharmacies participating in the North Carolina Community Pharmacy Enhanced Services Network (NC CPESN℠) program were included in this study. Pharmacy performance was measured as summary score of pharmacy's performance on seven risk-adjusted measures which were used to measure pharmacy's performance in the program. Adoption of medication synchronization was measured as a binary variable capturing whether the pharmacy offered med sync at the time the survey was administered. Surveys were received from 160 out of 268 participating pharmacies (59.7% response rate) with a total of 155 pharmacies being included in the analytic sample. Pharmacies that adopted medication synchronization were more likely to have a clinical pharmacist on staff (c = 5.4, p = 0.019). Holding all else constant, medication synchronization adoption was not significantly associated with total medication adherence performance (p = 0.371). Medication synchronization has proven successful in improving individual patient level adherence but may not change a pharmacy's overall performance in adherence for all patients. Further research is needed to examine how effective implementation might contribute to whether a medication synchronization program leads to meaningful gains in adherence for all patients.


Can Local Enhancement in Earthworms Affect the Outcome of the Standard Earthworm Avoidance Test?
Earthworms exhibit clumping behaviour in and out of the soil. However, it remains unknown if such social behaviour ultimately influences the outcome of ecotoxicological experiments in the laboratory. We performed several overnight avoidance tests to determine whether social behaviour (i.e., local enhancement) is a factor in pollution avoidance behaviour in the earthworm Eisenia fetida. The results showed that there was no clear influence of social behaviour on the choice or avoidance of Cd contaminated soils, although we suspect that 50 mg Cd/kg might not have been high enough to elicit a significant avoidance response. Nevertheless, when offered a choice between clean undisturbed soil and previously inhabited soil, the worms preferred the previously inhabited soil (p < 0.01). While the level of metal pollution investigated in this study did not disrupt or help predict social dynamics, local enhancement, perhaps driven by some sort of habitat imprinting, was successfully documented in Eisenia fetida.


Transaction processing using remote procedure calls (RPC) for a heterogeneous distributed clinical information system.
The Johns Hopkins Hospital is developing a distributed clinical information system that integrates functionally several UNIX, IBM MVS/CICS and MUMPS computer systems. Distributed application development is accomplished by interprocess communications across Ethernet using remote procedure calls. The remote procedure call (RPC) protocol provides a standard approach to the development of distributed applications using the metaphor of a subroutine call. The Sun Microsystems RPC and XDR (external data representation) protocols have been implemented in these environments. The systems, the distributed model, RPC implementations and applications examples are discussed.


Age-related retinal degeneration in animal models of aging: possible involvement of taurine deficiency and oxidative stress.
There is strong evidence that the retina degenerates with age. Electroretinogram deficits and photoreceptor cell death and structural abnormalities have been observed in both animal and human studies of aging. The mechanism behind this phenomenon is a very interesting area for scientific and medical study. Current data support the link between retinal degeneration and increased oxidative stress. Taurine is a free amino acid found in high millimolar concentrations in the retina, and age-related deficiency in retinal levels of taurine may contribute to the retinal degeneration associated with age. Taurine acts as an antioxidant and taurine replenishment is known to alleviate oxidative stress in the retina. Thus taurine supplementation may be useful in the treatment of age-related retinal dysfunction.


[Femur reconstruction using combined autologous fibula transfer and humeral allograft].
Wide resection far into the femoral metaphysis may be required to treat malignant bone tumors in the pediatric and adolescent patient population. Biological reconstruction using a free, vascularized fibular graft is a well-established surgical technique. A short remaining femoral medullary canal and a relatively small fibula diameter can make fixation of the vascularized bone transfer difficult. Stable fixation and short fusion times, however, can be achieved with the use of an additional humeral allograft and plate osteosynthesis.


Health-related quality of life in the Anthrax Vaccination Program for workers in the Laboratory Response Network.
In 2002 CDC initiated the Anthrax Vaccination Program (AVP) to provide voluntary pre-exposure vaccination with Anthrax Vaccine Adsorbed (AVA) for persons at high risk of exposure to Bacillus anthracis spores. There has been concern that AVA could be associated with long term impairment of physical and/or mental health. To ascertain whether physical and mental functional status, as measured by the SF-36v2 health survey (Medical Outcomes Trust, Boston, MA), of AVA recipients and controls changed differently over time. We enrolled 437 exposed (received AVA) and 139 control subjects. The exposed group received AVA under then-current Advisory Committee on Immunization Practices (ACIP) recommendations. SF-36v2 surveys were completed at 0, 12, and 30 months. SF-36v2 physical and mental scores both range from 0 to 100 with an estimated national average of 50 points. For physical scores, the average change from baseline was -0.53 for exposed vs. -0.67 for controls at 12 months (p=0.80) and -1.09 for exposed vs. -1.97 for controls at 30 months (p=0.23). For mental scores, the average change from baseline was -1.50 for exposed vs. -1.64 for controls at 12 months (p=0.86) and -2.11 for exposed vs. -0.24 for controls at 30 months (p=0.06). In multivariable analysis, the difference in mental score change between exposed vs. controls at 30 months was less pronounced (p=0.37) but other findings were similar to univariate analyses. These results do not favor an association between receipt of AVA and an altered health related quality of life over a 30-month period.


On the role of enzyme kinetic parameters in determining the effectiveness with which channelling can decrease the size of a metabolite pool.
Recently, it has been argued that the phenomenon of direct transfer of intermediate metabolites between adjacent enzymes, also known as metabolic channelling, would not decrease the concentration of those intermediates in the 'bulk' solution. However, this conclusion has been drawn by extrapolation from the results of simulations with a rather restricted set of parameters. We show that, for a number of kinetic cases, the existence of metabolic channelling can decrease the size of the soluble pool of intermediates. When the enzyme(s) 'downstream' of the channel have a catalytic capacity that is large relative to the enzymes 'upstream' of the channel, the decrease of concentration can be substantial (3 orders of magnitude).