Inter-trial Coherence of Medial Frontal Theta Oscillations Linked to Differential Feedback Processing in Youth and Young Adults with Autism.
Impairment in prediction and appreciation for choice outcomes could contribute to several core symptoms of ASD. We examined electroencephalography (EEG) oscillations in 27 youth and young adults diagnosed with autism spectrum disorder (ASD) and 22 IQ-matched neurotypical controls while they performed a chance-based reward prediction task. We re-analyzed our previously published ERP data (Larson et al., 2011) and examined theta band oscillations (4-8 Hz) at frontal midline sites, within a timing window that overlaps with the feedback-related negativity (FRN). We focused on event-related changes after presentation of feedback for reward (WIN) and punitive (LOSE) outcomes, both for spectral power and inter-trial phase coherence. In our reward prediction task, for both groups, medial frontal theta power and phase coherence were greater following LOSE compared to WIN feedback. However, compared to controls, inter-trial coherence of medial frontal theta was significantly lower overall (across both feedback types) for individuals with ASD. Our results indicate that while individuals with ASD are sensitive to the valence of reward feedback, comparable to their neurotypical peers, they have reduced synchronization of medial frontal theta activity during feedback processing. This finding are consistent with previous studies showing neural variability in ASD and suggest that the processes underlying decision-making and reinforcement learning may be atypical and less efficient in ASD.


Studies on the role of glycosylation in the functions and antigenic properties of influenza virus glycoproteins.
The biological and antigenic roles of glycosylation were investigated in the influenza hemagglutinin (HA) glycoprotein using the glycosylation inhibitor tunicamycin (TM). Under conditions where only the nonglycosylated form of HA was detected by immunoprecipitation and gel electrophoresis, the migration of glycoproteins to the cell surface was observed by immunofluorescence using either monospecific or monoclonal antibody to the HA polypeptide. Analysis of the surface fluorescence in TM-treated infected cells by a fluorescence-activated cell sorter (FACS) showed that all cells exhibited fluorescence in the complete absence of glycosylation. The relative amount of HA antigen on cell surfaces was found to be reduced by only 30-40% in TM-treated cells, and this reflected a similar reduction in intracellular synthesis. Electron microscopic studies using ferritin labeling also demonstrated that the nonglycosylated HA glycoprotein was present in significant amounts on surfaces of infected cells. Virions with nonglycosylated glycoproteins were purified, and were found to have an approximate 30-fold decrease in both hemagglutinin and neuraminidase specific activities. The possible role of oligosaccharides in antigenic variation among various H1N1 strains was investigated. Immunoprecipitation reactions involving five different monoclonal antibodies and five antigenic variants of A/USSR/90/77 revealed no major antigenic differences between the glycosylated and nonglycosylated forms of HA.


Three new Prototapirella species, Opisthotrichum janus, and Troglocorys cava add to Entodiniomorphida (Ciliophora, Trichostomatia) diversity in mountain gorillas in Rwanda.
Recently, a high number of Entodiniomorphida species was discovered in Virunga mountain gorillas (Gorilla beringei beringei) in Rwanda compared to other primates. Thirteen species of five genera (Troglocorys, Gorilloflasca, Prototapirella, Troglodytella, and Opisthotrichum) were identified with 10 species in Gorilloflasca, Prototapirella, and Troglodytella being host-specific, to our current knowledge. The remaining three species have been described for other herbivorous mammals; Prototapirella gorillae for western lowland gorillas; Troglocorys cava for western lowland gorillas, chimpanzees, and guinea baboons; Opisthotrichum janus in the family Ophryoscolecidae is regarded as specific to African antelopes. Here, we show the first indication that wild herbivorous hindgut fermenting mammals might have rumen ophryoscolecids in the intestine sympatric with their native intestinal ciliates. We also describe three new Prototapirella species, P. sabyinyo, P. sulcata, and P. curiosa. The somatic ciliary zones of the three new species are atypical of Prototapirella while their buccal infraciliature is not different from that of other Prototapirella species.


Centromere Tension Measurement in Budding Yeast Mitosis.
During budding yeast mitosis, duplicated chromosomes are aligned at the center of the metaphase mitotic spindle, and the centromeres are stretched by forces generated within the mitotic spindle. In response to these stretching forces, mechanical tension builds up in the centromeric chromatin. The magnitude of this tension is detected by the cell to signal the attachment configuration of the sister chromosomes: a high tension signal would indicate that sister chromosomes are properly attached to opposite spindle poles, while a low tension signal could indicate the lack of a bipolar attachment. A low tension signal drives the cell to correct improper attachments in metaphase, thus preventing potential errors in anaphase chromosome segregation. In this paper, we describe a microscopy-based method to directly measure the magnitude of centromere tension in budding yeast metaphase spindles. The advantage of this method is that quantitative tension estimates are obtained without perturbing spindle and/or chromosome structure and as cells progress normally through mitosis.


Phytoplankton and the Macondo oil spill: A comparison of the 2010 phytoplankton assemblage to baseline conditions on the Louisiana shelf.
The Macondo oil spill was likely the largest oil spill to ever occur in United States territorial waters. We report herein our findings comparing the available baseline phytoplankton data from coastal waters west of the Mississippi River, and samples collected monthly from the same sampling stations, during and after the oil spill (May-October, 2010). Our results indicate that overall, the phytoplankton abundance was 85% lower in 2010 versus the baseline, and that the species composition of the phytoplankton community moved towards diatoms and cyanobacteria and away from ciliates and phytoflagellates. The results of this study reaffirm the view that phytoplankton responses will vary by the seasonal timing of the oil spill and the specific composition of the spilled oil. The trophic impacts of the purported lower abundance of phytoplankton in 2010 coupled with the observed assemblage shift remain unknown.


Solitary liver metastasis of chromophobe renal cell carcinoma 20 years after nephrectomy treated by hepatic resection.
A small proportion of patients with metastatic renal cell carcinoma have operable liver metastases, as there is often multiple dissemination within the liver and to other organs. We present a case of a solitary liver metastasis found incidentally 20 years after radical nephrectomy for a chromophobe renal cell carcinoma. The patient underwent a liver resection with tumor-free margins and recovered uneventfully. Time will tell if this was oncologically successful.


Anthropometry of the patellar tendon in Chinese.
To assess the length of the patellar tendon in Chinese and its correlation with patient age, gender, and operated side. 109 men and 11 women aged 15 to 45 (mean, 25) years underwent arthroscopic bone-tendon-bone reconstruction for anterior cruciate ligament (ACL) insufficiency. 55 (46%) injured the left side, and 65 (54%) the right side. Each patient's age, gender, and operated side were recorded. The length of the patellar tendon harvested was measured. The mean length of the patellar tendon graft was 42.6 (standard deviation, 4.6; range, 30-54) mm. There was no correlation between the length of the patellar tendon and patient's age (p=0.147), gender (p=0.076), or operated side (p=0.466). The length of the patellar tendon in the Chinese is comparable to that in Caucasians. Because of the shorter ACL but similar patellar tendon length, graft-tunnel mismatch may be more common in Chinese than Caucasian patients.


Gene expression of adiponectin and adiponectin receptor 1 in type 2 diabetic rats and the relationship with the parameters of glucose and lipid metabolism.
In order to confirm whether the mRNA levels of adiponectin in adipose tissue and mRNA levels of AdipoR1 in the skeletal muscles were correlated with the serum parameters of glucose and lipid metabolism and to clarify the regulation of adiponectin receptor gene expression in diabetic states, serum adiponectin, mRNA levels of adiponectin in adipose tissue and mRNA levels of AdipoR1 in the skeletal muscles were examined in type 2 diabetic rats. The model of type 2 diabetes was prepared by feeding high fat diet and injecting low dosage of streptozotocin (STZ). The diabetic rats were screened out by oral glucose tolerance test. One group of type 2 diabetic rats received rosiglitazone. The serum adiponectin concentration was detected by using ELISA and mRNA levels were examined by RT-PCR. The serum adiponectin levels and mRNA levels of adiponectin in adipose tissue of type 2 diabetic rats were significantly decreased as compared with the normal control rats (P<0.05, P<0.01 respectively). No siglificant changes were observed in the expression of adiponectin receptor 1 in the skeletal muscle of type 2 diabetic rats. The mRNA levels of adiponectin in adipose tissue were reversely correlated with serum insulin (r=-0.66, P<0.05), triglyceride (r= -0.58, P<0.05), cholesterol (r=-0.49, P<0.05), interleukin-6 (r=-0.49, P<0. 05) and tumor necrosis factor (r= -0.43, P<0.05). The expression of adiponectin receptors was not altered in the skeletal muscle of Type 2 diabetic rats. The decreased serum adiponectin was caused by the decreased expression of adiponectin mRNA in adipose tissue rather than the adiponectin receptors in the skeletal muscle, which could be improved by rosiglitazone.


Amino acids and derivatives of thiazole-4-carboxylic acid as constituents of thiopeptin B.
L-Alanine, L-threonine, L-valine, D-cystine and three derivatives of thiazole-4-carboxylic acid (thiostreptin, 1-aminomethylthiazole-4-carboxylic acid and thiostreptoic acid) were isolated from the acid-hydrolysate of thiopeptin B. In addition, the presence of dehydrobutyrine and dehydroalanine residues in the antibiotic was determined. Other components remain unidentified.


Impaired coronary flow reserve after a recent myocardial infarction: correlation with infarct size and extent of microvascular obstruction.
The exact relationship between the coronary flow reserve (CFR) and infarct size remains unknown. In this prospective study the relationship between the CFR both in the infarcted and remote myocardium and infarct size was investigated. Furthermore, the diagnostic value of the CFR to predict the extent of microvascular obstruction (MO) was evaluated. In thirty patients the CFR was measured with a Doppler guide wire 6 ± 3 days after a first myocardial infarction (MI) in the infarct related and in a reference coronary artery. MO and infarct size were determined with magnetic resonance imaging. The CFR was inversely related to infarct size in the infarcted and remote myocardium (respectively, r=-0.60, p<0.01 and r=-0.62, p<0.01). In the infarcted myocardium the extent of MO was strongly related to the infarct size and was in a multivariate analysis the single significant determinant of the CFR and the hyperaemic flow. In the remote myocardium no relationship was present between infarct size and hyperaemic flow, but the baseline flow increased as the infarct size became larger (r=0.58, p<0.01). In a receiver operator characteristic (ROC) analysis, a CFR value ≤ 2 in the infarct related coronary artery offered the best sensitivity (65%) and specificity (71%) to detect the presence of MO (p<0.05). After MI, the CFR both in the infarcted and remote myocardium is inversely related to infarct size. In the infarcted myocardium, a CFR value ≤ 2 predicts the presence of MO with moderate sensitivity and specificity.


Chemical profiling and simultaneous quantification of major bioactive constituents from Cocculus hirsutus by UPLC-QqQ-MS.
Cocculus hirsutus is a widely used herb in traditional systems of medicine for the treatment of various diseases. In the present study, five alkaloids (1-5), two flavonoids (6-7), one triterpenoid (8), and three steroids (9-10) were isolated from the roots of Cocculus hirsutus and further crude extract was analyzed by LC-Q-Tof-MS/MS in positive ionization mode leading to the identification of ten metabolites through comparison of exact molecular masses from their MS/MS spectra, mass fragmentation studies and with literature data. In addition, a method was developed and validated for the quantification of four bio-active compounds [Sinococuline (1), Magnoflorine (2), (E)-N-feruloyltyramine (3), and 20-Hydroxyecdysone (10)] using UPLC-QqQ-MS in multiple reaction monitoring (MRM) mode for the first time. The method has shown good linearity with correlation coefficients (r2) higher than 0.9916 for all four compounds. The intra- and inter-day precision were in the range of 0.3-6.1% and from 0.7% to 8.8%, respectively. The matrix effects of all the four analytes were found in the range of 94.7 ± 2.8-112.7 ± 3.7%. Overall, our study provides a reliable and rapid approach by hyphenated LC-MS/MS using high-resolution mass spectrometers for identification and quantification of bioactive constituents from the root extracts of Cocculus hirsutus.


mtDNA mutations and common neurodegenerative disorders.
The incidence and prevalence of Alzheimer's disease (AD) and Parkinson's disease (PD) are increasing as the population ages. Both disorders have been associated with oxidative stress and mitochondrial dysfunction, and it has been proposed that mutations in the mitochondrial genome have a key role in neurodegeneration in AD and PD patients. Two recent publications propose that heteroplasmic mtDNA mutations are involved in AD and PD. However, when these new studies are considered in relation to the sum of previous evidence, the role of mtDNA mutations in the development of either AD or PD still remains to be established.


The Importance of Technical and Non-technical Skills in Robotic Surgery Training.
We discuss the differences in cognitive (thinking) and other non-technical skills (NTS) in robotic surgery training compared to other approaches to surgery. Recognition of the importance of NTS and cognitive training will aid the development of robotic surgery curricula.


Seasonal and sex differences in the fission-fusion dynamics of spider monkeys (Ateles geoffroyi yucatanensis) in Belize.
Spider monkeys (Ateles sp.) are characterized by high fission-fusion dynamics, meaning their social grouping pattern is fluid and consists of subgroups that vary in size, composition, and spatial cohesion over time. In this study, we quantify the fission-fusion dynamics of a group of spider monkeys at Runaway Creek Nature Reserve in Belize by measuring subgroup size, spatial cohesion, and stability using data spanning 5 years. We then test whether variation in these three subgroup measures differ according to season, subgroup sex composition, and the reproductive status of female subgroup members. Our results show that subgroups were larger in size and less stable in membership during the wet season compared to the dry season. All-female subgroups were less spatially cohesive but more stable in membership than all-male subgroups. Finally, we report that subgroups with one or more non-lactating females (i.e., without nursing young) were smaller on average than subgroups containing lactating females with nursing young. These data contribute to a growing body of research documenting the ecological and social dimensions along which grouping patterns might vary.


Impact of early initiation of sodium-glucose cotransporter 2 inhibitor on cardiovascular outcomes in people with diabetes and known or at risk of atherosclerotic cardiovascular disease: Propensity score matched analysis.
We aimed to evaluate the impact of early initiation of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cardiovascular (CV) outcomes in people with type 2 diabetes (T2D) with known or at risk of atherosclerotic cardiovascular disease (ASCVD). T2D with first prescription of SGLT2i (Dx-to-Rx time) ≤12 months were matched with >12 months using propensity score derived from logistic regression. T2D were divided into 3 groups: (i) known ASCVD; (ii) additional CV risk factor(s) and; (iii) without ASCVD or additional CV risk factors. Incidence rates of 3-point major adverse cardiovascular events (MACE, including non-fatal stroke, non-fatal myocardial infarction and CV death) were compared between Dx-to-Rx time ≤12 months and >12 months across 3 subgroups. Median follow-up was 2.8 years (IQR 2.2 to 3.4). Among 29,309 T2D (mean age 57.6±11.4 years, 59.0% men), 23.6% had established ASCVD and 66.6% had additional CV risk factors. Overall, 19.0% of patients had Dx-to-Rx time ≤12 month which was associated with lower rates of MACE [hazard ratio (HR) = 0.27, 95%CI: 0.17-0.42]. Benefits of early initiation of SGLT2i was observed in patients with additional CV risk factors or known ASCVD but not in those without CV risk factors or ASCVD (P for interaction = 0.001). Early initiation of SGLT2 inhibitor was associated with lower MACE rates in T2D with known or at risk of ASCVD.


Expanding undergraduate dietetic education through a health promotion internship program.
The Lifestyle Assistant Program is a health promotion internship offered by the University of Wisconsin-Stevens Point Health Service. Students majoring in health-related disciplines (e.g., dietetics) gain skills in promoting the six dimensions of wellness: social, occupational, spiritual, physical, intellectual, and emotional. Thirteen competencies provide the basis for training Lifestyle Assistants, who develop, market, present, and evaluate wellness sessions for the university and residential communities. Assistants earn academic credit or a wage. Of particular benefit to assistants majoring in dietetics are studying and operating a self-testing physical assessment unit, which approximates body composition, cardiovascular endurance, muscular strength, and flexibility; using a health hazard appraisal; assisting the University's Nutrition Task Force with its education campaign in the campus cafeterias; and presenting programs on popular nutrition topics (e.g., the athlete's diet). Program evaluation reveals that 84% of participants in programs conducted by assistants gained information of personal benefit. The Lifestyle Assistant competencies support The American Dietetic Association Plan IV minimum competencies in such areas as communication and education. The Lifestyle Assistant experience is in accordance with The American Dietetic Association's Dietetic Manpower Study recommendations: to provide student learning experiences in wellness programs and fitness settings.


The efficacy of iso- and hyperosmotic fluids as volume expanders in fixed-volume and uncontrolled hemorrhage.
Rapid blood volume expansion is the goal in prehospital hemorrhage resuscitation. A comparison was made for fixed volume and uncontrolled hemorrhage between three fluid regimes: Ringer's lactate (RL), Macrodex (MD), or a small volume of a hyperosmotic solution (HSD, 7.5% NaCl/6% dextran 70) followed by RL. A mathematical model was developed to simulate blood volume restoration for these given hemorrhage and resuscitation situations. Model predictions for a fixed hemorrhage (35%) and reinfusion of each fluid regime (1 mL.min-1.kg-1) were found to agree with hematocrit and osmolality changes from experiments on anesthetized rabbits. HSD gave the quickest volume expansion after the controlled hemorrhage, which is a useful experimental model; however, it is not realistic of many trauma injuries. The model suggests for severe uncontrolled hemorrhage that HSD/RL initially hastens the bleed, yet the blood volume expansion is still more effective than RL alone for the first 20 minutes, making it an effective prehospital expander for most urban trauma situations.


Triple fixation suture in operative gynecology.
A secure three-point fixation suture for large tissue pedicles is described. It is particularly applicable to vaginal hysterectomy but is also useful during abdominal hysterectomy.


Ser68 phosphoregulation is essential for CENP-A deposition, centromere function and viability in mice.
Centromere identity is defined by nucleosomes containing CENP-A, a histone H3 variant. The deposition of CENP-A at centromeres is tightly regulated in a cell-cycle-dependent manner. We previously reported that the spatiotemporal control of centromeric CENP-A incorporation is mediated by the phosphorylation of CENP-A Ser68. However, a recent report argued that Ser68 phosphoregulation is dispensable for accurate CENP-A loading. Here, we report that the substitution of Ser68 of endogenous CENP-A with either Gln68 or Glu68 severely impairs CENP-A deposition and cell viability. We also find that mice harboring the corresponding mutations are lethal. Together, these results indicate that the dynamic phosphorylation of Ser68 ensures cell-cycle-dependent CENP-A deposition and cell viability.


Insemination at the second of two induced oestrous periods in anoestrous dairy cows increases conception rates to first service.
To determine whether mating previously anoestrous cows on their second, rather than first, oestrus post pm-turn could increase conception rates to that service. Cows diagnosed as anovulatory anoestrus were allocated to two groups, starting treatment on Day -17 (OES2) or on Day -7 (OESI) where the date of the planned start of mating = Day 0. All cows were treated with intravaginal progesterone (CIDR device) for 6 days and an injection of 1 mg oestradiol benzoate 24 h after removal of the device. Cows in the OES2 group were also injected with prostaglandin F2alpha on Day 0. During the first 7 days of mating, 61.8% (207/335) and 88.2% (328/372) of cows in the OES2 and OESl groups, respectively, were inseminated on detection of oestrus (p <0.001). Oestrus without ovulation occurred in 1.5% of cows in the OES2 group and 6.2% of cows in the OESl group during this period (p <0.01). Of those cows inseminated in the first week of mating, conception rates were 54.0% in the OES2 group and 45.5% in the OESl group (p = 0.05). There was no significant difference in median interval from start of mating to conception between the two groups (24 and 22 days for OES2 and OESl, respectively, p >0.05). Mating previously anoestrous cows on their second, rather than first oestrus post partum increased conception rates to that service. However, median intervals from start of mating to conception were not altered.


On the effects of the modularity of gene regulatory networks on phenotypic variability and its association with robustness.
Biological adaptations depend on natural selection sorting out those individuals that exhibit characters fit to their environment. Selection, in turn, depends on the phenotypic variation present in a population. Thus, evolutionary outcomes depend, to a certain extent, on the kind of variation that organisms can produce through random genetic perturbation, that is, their phenotypic variability. Moreover, the properties of developmental mechanisms that produce the organisms affect their phenotypic variability. Two of these properties are modularity and robustness. Modularity is the degree to which interactions occur mostly within groups of the system's elements and scarcely between elements in different groups. Robustness is the propensity of a system to endure perturbations while preserving its phenotype. In this paper, we used a model of gene regulatory networks (GRNs) to study the relationship between modularity and robustness in developmental processes and how modularity affects the variation that random genetic mutations produce in the expression patterns of GRNs. Our results show that modularity and robustness are correlated in multifunctional GRNs and that selection for one of these properties affects the other as well. We contend that these observations may help to understand why modularity and robustness are widespread in biological systems. Additionally, we found that modular networks tend to produce new expression patterns with subtle changes localized in the expression of a few groups of genes. This effect in the phenotypic variability of modular GRNs may bear important consequences for adaptive evolution: it may help to adjust the expression of one group of genes at a time, with few alterations on other previously evolved expression patterns.


Pancreatic injury: an unusual complication of laparoscopic cholecystectomy.
Laparoscopic cholecystectomy is a popular method for managing symptomatic gallstone disease. Decreased morbidity and mortality rates make this procedure an attractive alternative to conventional cholecystectomy. However, unusual complications still occur. We report a case of pancreatic injury that occurred during laparoscopic cholecystectomy. The case was complicated with posttraumatic pancreatic inflammation and bowel necrosis.


How acceptable is a weight maintenance programme for healthy weight young women who are at increased risk of breast cancer?
Objective: To determine if a weight gain prevention intervention is acceptable to young women with a normal Body Mass Index and a moderately increased or high risk of breast cancer. Design: Qualitative semi-structured interview study involving 14 women aged 26-35 years who were registered with a Family History Clinic in Manchester, UK, due to family history of breast cancer. Participants' views were analysed thematically. Results: Four themes were produced: (1) perceptions of a healthy lifestyle: women's perceptions included health-related behaviours and subjective wellbeing; (2) construing a healthy weight: women rely on appearance, feelings and others opinions to construe weight instead of quantitative indicators; (3) configuring a useful programme: the idea of a programme that is remotely accessible; provides a point of contact; and promotes general wellbeing was appealing. Women believed information explaining the link between lifestyle and breast cancer would facilitate behaviour change; (4) the importance of will(power): women recognised that commitment to a programme is affected by time, money and readiness to change. Conclusion: A weight gain prevention intervention that focuses on wellbeing and behaviour change appears acceptable to many healthy weight women. Future research should examine whether women's expressed acceptability translates into actual acceptability of such a programme.


SUMOylation of Dorsal attenuates Toll/NF-κB signaling.
In Drosophila, Toll/NF-κB signaling plays key roles in both animal development and in host defense. The activation, intensity, and kinetics of Toll signaling are regulated by posttranslational modifications such as phosphorylation, SUMOylation, or ubiquitination that target multiple proteins in the Toll/NF-κB cascade. Here, we have generated a CRISPR-Cas9 edited Dorsal (DL) variant that is SUMO conjugation resistant. Intriguingly, embryos laid by dlSCR mothers overcome dl haploinsufficiency and complete the developmental program. This ability appears to be a result of higher transcriptional activation by DLSCR. In contrast, SUMOylation dampens DL transcriptional activation, ultimately conferring robustness to the dorso-ventral program. In the larval immune response, dlSCR animals show an increase in crystal cell numbers, stronger activation of humoral defense genes, and high cactus levels. A mathematical model that evaluates the contribution of the small fraction of SUMOylated DL (1-5%) suggests that it acts to block transcriptional activation, which is driven primarily by DL that is not SUMO conjugated. Our findings define SUMO conjugation as an important regulator of the Toll signaling cascade, in both development and host defense. Our results broadly suggest that SUMO attenuates DL at the level of transcriptional activation. Furthermore, we hypothesize that SUMO conjugation of DL may be part of a Ubc9-dependent mechanism that restrains Toll/NF-κB signaling.


Transcarotid Transcatheter Aortic Valve Replacement in an Octogenarian With Complex Type B Aortic Dissection and Aneurysm: A Case Report.
We report the case of an octogenarian with severe aortic valve stenosis, chronic kidney disease (CKD) and heart failure. Due to advanced CKD, we used a 3-dimensional transesophageal echocardiogram for sizing the device before transcatheter aortic valve replacement (TAVR). Noncontrast computed tomography found complex aortic dissection involving the arch, descending thoracic aorta, and abdominal aorta. TAVR was approached via the right carotid artery using a CoreValve. There was no cerebral vascular event. Renal function was well preserved. Transcarotid TAVR can be performed safely with complex type B aortic dissection. Three-dimensional transesophageal echocardiogram provides an alternative sizing solution in advanced CKD.


Macrolides and airway inflammation in children.
For more than 20 years macrolide antibiotics have been used to treat chronic inflammatory airway diseases based on their immunomodulatory activity. Macrolide antibiotics down-regulate damaging prolonged inflammation as well as increase mucus clearance, decrease bacterial virulence and prevent biofilm formation. Initially shown to decrease morbidity and mortality in diffuse panbronchiolitis and in steroid-dependent asthma, long-term macrolide therapy has now been shown to significantly reduce exacerbations and improve lung function and quality of life in children with cystic fibrosis. They have also proven beneficial in Japanese children and adults with chronic sinobronchitis especially when there is nasal polyposis. Long-term macrolides have also proven clinically beneficial in some patients with plastic bronchitis. Adverse reactions are few and generally self-limited when used at the recommended dosage for immunomodulation.


Topical and systemic antifungal agents.
Superficial fungal infections are frequent and can cause considerable morbidity. Many topical agents are available that are effective against most of these infections. Systemic fungal infections are increasing in frequency, especially among immunocompromised hosts. Amphotericin B remains the most important therapeutic agents but is associated with significant acute and chronic toxicities.


The occurrence of three different proteoglycan species in chick embryo cartilage. Isolation and characterization of a second proteoglycan (PG-Lb) and its precursor form.
Three different molecular species of proteoglycan (designated PG-H, PG-Lb, and PG-Lt) have been isolated from chick embryo epiphyseal cartilage. PG-H is a major proteoglycan of the tissue and identical, or nearly identical, with so-called cartilage-characteristic proteoglycan previously described in mammalian and avian cartilages. The third proteoglycan, PG-Lt, differs from the other two in containing disulfide-bonded collagenous polypeptides (Noro, A., Kimata, K., Oike, Y., Shinomura, T., Maeda, N., Yano, S., Takahashi, N., and Suzuki, S. (1983) J. Biol. Chem. 258, 9323-9331). The second proteoglycan, PG-Lb, consists of a core protein with Mr congruent to 52,000 dermatan sulfate copolymer chains with glucuronic acid/iduronic acid residues. Upon chondroitinase ABC digestion, the proteoglycan yields a protein-enriched core fraction of Mr congruent to 43,000. Its amino acid composition, tryptic peptide profile, and immunochemical properties indicate that PG-Lb is distinctly different from PG-H and PG-Lt in core protein structure. PG-Lb shows no specific binding with hyaluronic acid. Pulse-chase experiments with [3H]serine indicate that PG-Lb is first synthesized as a precursor form (pro-PG-Lb) that can be distinguished from PG-Lb by the production of a core molecule of Mr congruent to 52,000 after chondroitinase ABC digestion. This core molecule is labeled when [2-3H]mannose is used as a precursor, suggesting that it contains a glycoprotein type oligosaccharide. Since the core molecule from pro-PG-Lb is significantly larger in molecular weight than that from PG-Lb, the conversion of pro-PG-Lb to PG-Lb should involve scission of the polypeptide or possibly removal of mannose-containing oligosaccharide chain.


[A different approach to the care of patients with MS].
Therapeutic patient education comprises multi-disciplinary support to help patients accept and manage a chronic pathology. Nurses are at the heart of this team approach. Two nurses from Brest military teaching hospital share their experience in this field with patients with multiple sclerosis, which provides benefits for the patient as well as added value for a reflexive nursing practice.


Fractal dynamics in circadian cardiac time series of corticotropin-releasing factor receptor subtype-2 deficient mice.
Non-linear fractal analysis of circadian 24 hr heartbeat interval time series was performed in corticotropin releasing factor receptor-subtype 2 (CRFR2) deficient mice. We hypothesized that, as a result of its central as well as its peripheral expression, CRFR2 would mediate or interfere with the circadian rhythmicity. The dynamical properties of cardiac interbeat intervals were expected to be different between CRFR2 (+/+) and CRFR2 (-/-) mice when studied over an extended circadian 24 hr cycle. The dynamics of neurocardiac control were found to remain remarkably stable throughout the circadian cycle. In disagreement with the initial hypothesis, the dynamical properties underlying the cardiac control process were common to both CRFR2 (+/+) and CRFR2 (-/-) mice suggesting that control of heart rate does not rely on the elaborate interaction of the CRFR2-sensor and its intrinsic feedback arrangement. Lack of expression of CRFR2 would not compromise cardiac control and its dynamical output or is subserved by other, unknown mechanisms. Functional integrity of CRFR2 would not constitute an indispensable requirement of physiologic cardiac control. The circadian rhythm of heart rate is generated centrally and is independent of expression of CRFR2. While 'normal' strain C57BL/6N mice exhibit a circadian dark/light cycle of heart rate, absence of circadian fluctuations in transgenic CRFR2-mice (both +/+ and -/-) and 'normal' strain C57BL/6J mice points at the importance of other deficiencies that may be related to a common genetic background. Mutant mice that share a common 129SvJ- or C57BL/6J-derived genetic background may not present an optimal model for physiological studies of cardiovascular control.


Experimental medication treatment approaches for depression.
Depression is one of the most common psychiatric conditions. Symptoms can lead to significant disability, which result in impairments in overall quality of life. Though there are many approved antidepressant treatments for depression-including selective serotonin reuptake inhibitors, tricyclic antidepressants and monoamine oxidase inhibitors-about a third of patients do not respond to these medications. Therefore, it is imperative for drug discovery to continue towards the development of novel and rapidly acting compounds, especially for patients with treatment-resistant depression. After a brief review of the efficacy of approved antidepressant therapies, we will discuss experimental medication treatments for depression. Specifically, we examine novel medications that are thought to primarily modulate the glutamatergic, cholinergic and opioid systems to achieve antidepressant efficacy. We also give examples of anti-inflammatories, neurokinin-1 modulators, vasopressin antagonists and neurogenesis enhancers that may have a therapeutic role in treatment-resistant depression. The current pipeline of antidepressant treatments is shifting towards medications with novel mechanisms, which may lead to important, life-changing discoveries for patients with severe disease.


Coexistent myelodysplastic syndrome and non-Hodgkin lymphoma. Report of a case and review of the literature.
The patients with a hematopoietic neoplasm can develop myelodysplastic syndrome following chemotherapy. We report herein a case of non-Hodgkin B-cell lymphoma and refractory anemia with ringed sideroblasts. Absence of the preceding chemotherapy establishes the true coincidence of the two disorders. We review 25 similar cases reported in the last 11 years and discuss the possible etiology of coexistence.


Exercise for Men with Prostate Cancer: A Systematic Review and Meta-analysis.
Exercise could be beneficial for prostate cancer survivors. However, no systematic review across cancer stages and treatment types addressing potential benefits and harms exists to date. To assess the effects of exercise on cancer-specific quality of life and adverse events in prostate cancer trials. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, AMED, CINAHL, PsycINFO, SPORTDiscus, and PEDro. We also searched grey literature databases, including trial registers. Searches were from database inception to March 2015. Standardised mean differences (SMDs) were calculated for meta-analysis. We included 16 randomised controlled trials (RCTs) involving 1574 men with prostate cancer. Follow-up varied from 8 wk to 12 mo. RCTs involved men with stage I-IV cancers. A high risk of bias was frequently due to problematic intervention adherence. Seven trials involving 912 men measured cancer-specific quality of life. Pooling of the data from these seven trials revealed no significant effect on this outcome (SMD 0.13, 95% confidence interval [CI] -0.08 to 0.34, median follow-up 12 wk). Sensitivity analysis of studies that were judged to be of high quality indicated a moderate positive effect estimate (SMD 0.33, 95% CI 0.08-0.58; median follow-up 12 wk). Similar beneficial effects were seen for cancer-specific fatigue, submaximal fitness, and lower body strength. We found no evidence of benefit for disease progression, cardiovascular health, or sexual function. There were no deaths attributable to exercise interventions. Other serious adverse events (eg, myocardial infarction) were equivalent to those seen in controls. These results support the hypothesis that exercise interventions improve cancer-specific quality of life, cancer-specific fatigue, submaximal fitness, and lower body strength. This review shows that exercise/physical activity interventions can improve quality of life, fatigue, fitness, and function for men with prostate cancer.


Antibody response in humans after administration of whole-virion and split vaccine prepared from two different influenza A/swine viruses.
Previous findings with sera of several different animal species had indicated a close antigenic similarity between the X53 recombinant (possessing both surface antigens of A/Swine/New Jersey/76 virus) and the A/Swine/Ann Arbor/31 (AA) virus (1). Since the latter virus grows much better in chick embryos than the former, we examined the possibility of using the Ann Arbor virus instead of X53 for inactivated vaccine production. The present paper describes our findings in sera of subjects immunized with either whole-virus or split vaccine prepared from AA virus.


High doses of methylene blue/light treatment crosslink the A-alpha-subunit of fibrinogen: influence of this photooxidization on fibrinogen binding to platelets.
Irradiation in the presence of 1 microM methylene blue (MB) inactivates enveloped viruses in human plasma. This method is a useful tool to enhance the safety of human fresh-frozen plasma in blood donor banks. Via a photooxidative mechanism, viral structures as well as plasma proteins, especially fibrinogen, can be damaged. We investigated the effect of MB/light-induced photooxidative modification on the structure of fibrinogen and its function in the interaction with platelets in the concentration range of 150 microM MB. Densitometric scanning of reduced SDS-PAGE showed a decrease in the Aalpha-subunit of fibrinogen as well as an increase in high-molecular-weight (HMW) aggregates with increasing MB concentrations. The HMW aggregates may be due to covalent crosslinking of single Aalpha-subunits via photooxidation induced by MB/light treatment. Fibrinogen treated with high doses of MB (50 microM) showed a weaker binding to the fibrinogen receptor (GP IIb/IIIa) on the platelet surface and a decrease in platelet aggregation after stimulation with ADP and photooxidized fibrinogen. These effects were not detected in fibrinogen isolated from virus-inactivated plasma (1 microM MB). This was in agreement with normal binding of fibrinogen to GP IIb/IIIa on platelets.


Transient severe distributive shock due to early dumping syndrome: a case report.
Early dumping syndrome characterized by palpitation, dizziness, cold sweat, feebleness, and abdominal symptoms, occurs within 30 minutes after meals in patients who have undergone gastrectomy. This case report describes the case of a patient who presented with severe distributive shock due to early dumping syndrome; he recovered within a few hours after massive fluid infusion and vasopressor administration. Our patient was a 68-year-old Japanese man who underwent total gastrectomy for gastric cancer and was diagnosed as having late dumping syndrome. On admission, he developed severe shock and was treated with massive fluid administration. Based on the history of the present illness, past medical history, normal findings of blood chemistry test, transient course, and Sigtad score, which helps diagnose dumping syndrome, early dumping syndrome was considered the cause of severe distributive shock. Early dumping syndrome can cause severe shock requiring massive fluid infusion and vasopressor administration. It should be considered a cause of severe distributive shock in patients who have undergone gastrectomy.


Temporary anterior cervical plating in a child with traumatic cervical ligamentous instability.
Application of anterior cervical plates in children is problematic because of the growing spine, and thus has been reported only rarely in the medical literature. In this case report, a 7-year-old with traumatic C(2-3) and C(3-4) ligamentous instability was treated surgically by limited-duration anterior cervical plating. The plate was removed in a second operation, as the osseous union occurred 1 year after the primary operation. Limited-duration anterior cervical plating is an alternative for stabilization operations of the growing cervical spine in children.


The appointment of an anaesthetist. Edinburgh Royal Infirmary 1900-12.
This is an historical vignette about a stage in the evolution of specialist anaesthesia in the capital city of Scotland. Ignorant management decisions delayed development in Edinburgh by 25 years.


Adult age differences in binding actors and actions in memory for events.
Three experiments provide evidence for an age-related deficit in the binding of actors with their actions. Young and older adults were tested on their memory for a series of events, each involving an actor performing a simple action. Older adults had greater difficulty than did young adults at discriminating old events from novel conjunctions of familiar actors and actions, even when the two groups were equated on memory for each of those features in isolation by using a longer retention interval for young adults. These results are consistent with an age-related associative deficit linked to declines in hippocampal and prefrontal cortical functioning. They further provide evidence that age differences in source monitoring are not limited to speech acts but, rather, generalize to more complex actions. Finally, they provide evidence for age differences in susceptibility to conjunction memory errors, stemming from decreased reliance on recollection and increased reliance on familiarity with increased age. Example videos may be downloaded from www.psychonomic.org/archive.


Identification of the characteristic amino-acid sequence for human alpha-amylase encoded by the AMY2B gene.
Human salivary and pancreatic alpha-amylases (HSA and HPA) are the respective gene products of the AMY1 and AMY2A genes. AMY2B is a newly found human alpha-amylase gene. The presence of the AMY2B gene product (HXA) in the urine of healthy humans was examined. A mixture of alpha-amylases that seemed to contain HXA, judging from the substrate specificity, was purified from urine of healthy volunteers by affinity adsorption on starch and then by ion-exchange chromatography. The mixture was reduced and S-alkylated, and the product was digested with trypsin. The digest was separated by reversed-phase HPLC. LVGLLDLALEKDYVR and LVGLLDLALEK, which were found in the digest, are peptides of HXA, but not of HSA and HPA. The detection of these characteristic peptides of HXA demonstrates the presence of HXA in the urine of healthy humans.


Guidelines for a psychiatric hospital intake staff meeting.
Guidelines are presented that help to make psychiatric intake conferences more efficient and productive. The emphasis is placed on having designated personnel meet individually with the patient as well as review the patient's chart prior to the formal intake conference. Thus, the personnel is able to spend more time on formulating a diagnosis and treatment plan than on reviewing the past history of the patient. Information presented at such conferences should consist more of unique contributions from the personnel (e.g., observations, impressions, testing, etc.) than of redundant material commonly known by the personnel assigned to the patient.


The relationship between serum uric acid and cognitive function in patients with chronic heart failure.
Evidence has shown that serum uric acid (UA) is associated with cognitive function, but this finding remains debatable. Serum UA is commonly elevated in patients with chronic heart failure (CHF), especially in men. However, the relationship between serum UA and cognitive function in CHF populations and stratified by sex are unclear. We aimed to examine whether serum UA was independently associated with cognitive function in CHF populations after controlling for demographic, medical and psychological variables and whether there was a sex difference in the association between serum UA and cognitive function among male and female CHF patients. One hundred ninety-two hospitalized patients with CHF underwent an assessment of cognitive function using the Montreal Cognitive Assessment (MoCA) and the determination of serum UA. Hyperuricemia was defined as serum UA ≥7 mg/dl in men and ≥ 6 mg/dl in women. Multiple linear hierarchical regression analyses were conducted to examine the independent association between serum UA and cognitive function in CHF populations and stratified by sex. The mean serum UA concentration of participants was 7.3 ± 2.6 mg/dL. The prevalence of hyperuricemia was 54.7% (105 of 192) in CHF patients, 52.9% (64 of 121) in men, and 57.7% (41 of 71) in women. In the total sample, higher serum UA was associated with poorer cognitive function independent of demographic, medical and psychological variables (β = - 0.130, ΔR2 = 0.014, p = 0.015). In sex-stratified groups, elevated serum UA was independently associated with worse cognitive function in men (β = - 0.247, ΔR2 = 0.049, p = 0.001) but not in women (β = - 0.005, ΔR2 = 0.000, p = 0.955). Higher serum UA is independently associated with poorer cognitive function in CHF populations after adjusting for confounding variables. Furthermore, elevated serum UA is independently related to worse performance on cognitive function in men but not in women. More longitudinal studies are needed to examine the association between serum UA and cognitive function in CHF populations and stratified by sex.


Clinicopathological significance of mitochondrial D-Loop mutations in head and neck carcinoma.
Mitochondrial DNA mutations have been reported in several types of tumours, including head and neck squamous cell carcinoma (HNSCC). The noncoding region of the Displacement-Loop (D-Loop) has emerged as a mutational hotspot and we recently found that they were associated with prognosis and response to 5 fluorouracil (5FU) in colon cancers. In order to evaluate the frequence of D-Loop mutations in a large series of HNSCC and establish correlations with clinicopathologic parameters, we sequenced the D-Loop of 109 HNSCC before a treatment by neoadjuvant 5FU-cisplatin-based chemotherapy and surgery. Then, we correlated these mutations with prognosis and response to chemotherapy. A D-Loop mutation was identified in 21% of the tumors, the majority of them were located in a C-tract (D310). The prevalence of D310 mutations increased significantly with the number of cytosines in the matched normal tissue sequence (P=0.02). Hypopharyngeal cancer was significantly more frequent (P=0.03) and tobacco consumption more important (P=0.01) in the group of patients with D-Loop mutation. The presence of D-Loop mutation was not associated with prognosis or with response to neoadjuvant chemotherapy. These results suggest that D-Loop mutations should be considered as a cancer biomarker that may be useful for the early detection of HNSCC in individuals at risk of this cancer.


A new diaryheptanoid from the bark of Myrica rubra.
A new diarylheptanoid, (11 xi)-3,5-dimethoxy-11,17-dihydroxy-4,19-diketo-[7,0]-metacyc- lophane, named as rubanol 1, was isolated from the bark of Myrica rubra along with four known compounds (2-5). Their structures were determined by spectroscopic methods including 1D, 2D NMR or comparison with authentic samples. Compound 1 exhibited cytotoxicity against Lun-06, Neu-04, and Bre-04 cell lines with GI50 values of 16.03-32.58 microg mL(-1).


Co-encapsulation of collagen peptide and astaxanthin in WG/OG/W double emulsions-filled alginate hydrogel beads: Fabrication, characterization and digestion behaviors.
The double emulsions-filled hydrogel beads delivery systems with controlled lipolysis and sustained-release property of co-encapsulated bioactive substances will be highly desired. Herein, the water-in-oil-in-water emulsion with gelled inner water phase and oil phase (WG/OG/W) filled hydrogel beads as a novel co-delivery system were developed with varied concentrations of rice bran wax and W/O emulsions to achieve effectively controlled release of lipolysis and nutraceuticals. Interestingly, the gelation of oil phase triggered by rice bran wax could enhance the storage stability of WG/OG/W emulsions due to the enhanced viscoelastic property. Increasing the mass fractions of W/O emulsions improved the stability of double emulsions due to increased viscosity and decreased particle size. Cryo-SEM observation showed that the double emulsion droplets were scattered in the three-dimensional network of alginate gel beads. Increased the addition of rice bran wax or W/O emulsions, the encapsulation efficiency of collagen peptide and astaxanthin was significantly improved. The in vitro digestion results indicated that increasing the concentrations of rice bran wax and W/O emulsion fractions in WG/OG/W emulsion-filled gel beads could effectively delay the release extent of free fatty acids and encapsulated nutraceuticals. The presence of rice bran wax contributed to increase the bioaccessibility of collagen peptide and astaxanthin.


Changes in autonomic responding to stress after practice at controlling heart rate.
Subjects in this experiment viewed a stressful film and then received one of five treatments: (a) practice at increasing heart rate without feedback, (b) practice at decreasing heart rate without feedback, (c) practice at increasing heart rate with feedback, (d) practice at decreasing heart rate with feedback, or (e) a control condition. Subjects then returned on the following day, practiced controlling heart rate again (or sat quietly, for subjects in the control condition), and then viewed the stressful film again. Heart-rate results indicated that subjects in both feedback groups manifested tonic decreases in heart rate from the first viewing of the film to the second, whereas subjects in both of the no-feedback groups manifested no changes in heart rate between viewings, and subjects in the control condition manifested increases in heart rate between viewings. However, all five groups of subjects displayed phasic increases in heart rate during specific stressors in the film during both viewings. The tonic changes in heart rate noted between viewings of the film for the feedback groups were not accompanied by parallel changes in electrodermal activity or respiration rate. Self-report ratings of subjects' beliefs about ability to control heart rate were significantly correlated with the tonic changes in heart rate that were noted between viewings of the stressful film.


Removing barriers to appropriate migraine treatment: formulary limitations and triptan package size.
The main goals in the pharmacologic management of migraine headache are to avert or relieve debilitating pain, prevent escalating acute medication use, and improve day-to-day functioning. This review will examine the evidence supporting the early use of acute medication, usually when pain is mild, to enhance patient outcomes. We will also discuss imposed quantity limits as a practical impediment to the implementation of this strategy in the managed care setting, and will identify strategies for overcoming this barrier to effective care. Quantity limits imposed on triptan therapy by health plans can hinder the optimal acute treatment of migraine. A standard triptan quantity limit sufficient to permit early migraine treatment and a movement by manufacturers to provide blister packs consistent with a standard quantity limit should reduce patients costs, permit brand mobility when appropriate, and bolster long-term cost effectiveness by removing an important impediment to the use of triptans when they are most effective, early in the migraine attack when pain is often still mild.


Freeze-thaw cycle and abrasion resistance of alkali-activated FA and POFA-based mortars: Role of high volume GBFS incorporation.
Alkali-activated binders made from various waste products can appreciably reduce the emission of CO2 and enhance the waste recycling efficiency, thus making them viable substitutes to ordinary Portland cement (OPC)-based binders. Waste materials including fly ash (FA), palm oil fuel ash (POFA), and granulated blast furnace slag (GBFS) reveal favorable effects when applied to alkali-activated mortars (AAMs) that are mainly related to the high contents of silica, alumina, and calcium. Therefore, fifteen AAM mixes enclosing FA, POFA with high volume of GBFS were designed. The obtained GBFS/FA/POFA-based AAMs were subjected wet/dry and freeze/thaw cycles. The impact of various GBFS contents on the microstructures, freeze-thaw cycle, abrasion resistance, mechanical and durability features of the proposed AAMs were evaluated. The results showed that presence of Ca can significantly affect the AAMs durability features and long-term performance. The abrasion resistance of the AAMs was decreased with the decrease of CaO contents. Furthermore, the abrasion depth of 70% AAMs (0.8 mm) was lower in comparison to the mix made by replacing 50 wt% of FA with GBFS (1.4 mm). Generally, increase in the GBFS contents from 50 to 70% could largely impact the AAMs properties under aggressive environmental exposure. The expansion and physical impacts during the freezing-thawing cycles was argued to destroy the bonds in C-S-H and paste-aggregates, causing the formation of large cracks. It is asserted that the AAM mixes made from FA, POFA and high volume of GBFS may offer definitive mechanical, durable, and environmental benefits with their enhanced performance under aggressive environments.


The potential mechanisms of piRNA to induce hepatocellular carcinoma in human.
The hepatocellular carcinoma, as one of the most frequently happened types of cancer in the world, has very complicated intracellular and extracellular molecular underlying pathogenic mechanisms. The role of genome and proteome in the proliferation and metastasis of the hepatocellular carcinoma has been thoroughly investigated, and many theories have been proposed. The subsequent developments, such as the targeted anti-cancer medicine or the treatment strategy, has profoundly influenced the prognosis of patients with hepatocellular carcinoma. As for the transcriptome, it is undeniable that the function of mRNA, rRNA even the long non-coding RNA have been discussed, while as a particular type of RNA-piRNA is not paid enough attention by the academy. piRNA is named because it always interacts with the piwi protein to achieve its physiological functions, with a length that is no more than 30 nucleotides. It is widely distributed in the reproductive organs such as the testis, the ovarian, and the stem cells. Previous studies have elucidated that the piRNA is closely closely related to the maturation of the sperms or the oocytes, even the progression of lung cancer. While the role and underlying molecular mechanisms of piRNA in the proliferation of hepatocellular carcinoma is not thoroughly researched and remained unknown. The authors in this article proposed potential mechanisms of piRNA to initiate the proliferation of hepatocellular carcinoma. We are hoping to provide a unique perspective to the academy and the following researches.


Epidemiology of melanoma and nonmelanoma skin cancer--the role of sunlight.
Melanoma and nonmelanoma skin cancer (NMSC) are now the most common types of cancer in white populations. Both tumor entities show an increasing incidence rate worldwide but a stable or decreasing mortality rate. The rising incidence rates of NMSC are probably caused by a combination of increased sun exposure or exposure to ultraviolet (UV) light, increased outdoor activities, changes in clothing style, increased longevity, ozone depletion, genetics and in some cases, immune suppression. A dose-dependent increase in the risk of squamous cell carcinoma (SCC) of the skin was found associated with exposure to Psoralen and UVA irradiation. An intensive UV exposure in childhood and adolescence was causative for the development of basal cell carcinoma (BCC) whereas for the aetiology of SCC a chronic UV exposure in the earlier decades was accused. Cutaneous malignant melanoma is the most rapidly increasing cancer in white populations. The frequency of its occurrence is closely associated with the constitutive colour of the skin and depends on the geographical zone. The highest incidence rates have been reported from Queensland, Australia with 56 new cases per year per 100,000 for men and 43 for women. Mortality rates of melanoma show a stabilisation in the USA, Australia and also in European countries. The tumor thickness is the most important prognostic factor in primary melanoma. There is an ongoing trend towards thin melanoma since the last two decades. Epidemiological studies have confirmed the hypothesis that the majority of all melanoma cases are caused, at least in part, by excessive exposure to sunlight. In contrast to squamous cell carcinoma, melanoma risk seems not to be associated with cumulative, but intermittent exposure to sunlight. Therefore campaigns for prevention and early detection are necessary.


Differential outcomes of outpatient only versus combined inpatient/outpatient treatment in early intervention for adolescent borderline personality disorder.
Clinical guidelines for adults with borderline personality disorder (BPD) recommend outpatient psychotherapy as first-line treatment. Little is known whether this recommendation is also applicable to adolescents. The current study examined the relationship between treatment setting and the outcome of early intervention for adolescents with BPD pathology. One-hundred and seventy-eight adolescents from a specialized outpatient clinic were assessed at baseline, and at 1- and 2-year follow-up. Sixty-three participants who received inpatient treatment during the first year were assigned to the "combined inpatient/outpatient group", 115 participants to the "outpatient only group". Generalized linear and mixed models with inverted probability weights to adjust for baseline differences were applied to examine the impact of group on clinical changes over time. Both groups demonstrated a significant decrease in BPD features, depressive symptoms, psychopathological distress, non-suicidal self-injury (NSSI), suicidal thoughts, suicide attempts, and overall illness severity, and a significant increase in quality of life and psychosocial functioning from baseline to follow-up 2. The decrease in NSSI and overall illness severity, and the increase in psychosocial functioning from baseline to follow-up 1 were greater in the outpatient only group, with comparable improvements between groups from follow-up 1 to follow-up 2. Both outpatient treatment and combined outpatient/inpatient treatment resulted in clinical improvements over time, with some indication for faster changes in the outpatient only setting. The findings provide preliminary evidence that the recommendation of outpatient psychotherapy as the first-line treatment for BPD also holds true for adolescents.


Clinically Available Software for Automatic Brain Volumetry: Comparisons of Volume Measurements and Validation of Intermethod Reliability.
To compare two clinically available MR volumetry software, NeuroQuant® (NQ) and Inbrain® (IB), and examine the inter-method reliabilities and differences between them. This study included 172 subjects (age range, 55-88 years; mean age, 71.2 years), comprising 45 normal healthy subjects, 85 patients with mild cognitive impairment, and 42 patients with Alzheimer's disease. Magnetic resonance imaging scans were analyzed with IB and NQ. Mean differences were compared with the paired t test. Inter-method reliability was evaluated with Pearson's correlation coefficients and intraclass correlation coefficients (ICCs). Effect sizes were also obtained to document the standardized mean differences. The paired t test showed significant volume differences in most regions except for the amygdala between the two methods. Nevertheless, inter-method measurements between IB and NQ showed good to excellent reliability (0.72 < r < 0.96, 0.83 < ICC < 0.98) except for the pallidum, which showed poor reliability (left: r = 0.03, ICC = 0.06; right: r = -0.05, ICC = -0.09). For the measurements of effect size, volume differences were large in most regions (0.05 < r < 6.15). The effect size was the largest in the pallidum and smallest in the cerebellum. Comparisons between IB and NQ showed significantly different volume measurements with large effect sizes. However, they showed good to excellent inter-method reliability in volumetric measurements for all brain regions, with the exception of the pallidum. Clinicians using these commercial software should take into consideration that different volume measurements could be obtained depending on the software used.


Alteration in autonomic function and cardiovascular regulation in amyotrophic lateral sclerosis.
Autonomic function mediating cardiovascular regulation was evaluated in amyotrophic lateral sclerosis (ALS) in comparison with Shy-Drager syndrome. The subjects were 14 normal controls and 9 patients each with ALS and Shy-Drager syndrome. To evaluate the autonomic function in detail, a new series of quantitative autonomic function tests was conducted, in conjunction with conventional tests. In patients with ALS, the data indicated subclinical sympathetic hyperfunction and parasympathetic (vagal) hypofunction, probably resulting in cardiovascular dysfunction.


Angiotensin converting enzyme 2 abrogates bleomycin-induced lung injury.
Despite substantial progress, mortality and morbidity of the acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI), remain unacceptably high. There is no effective treatment for ARDS/ALI. The renin-angiotensin system (RAS) through Angiotensin-converting enzyme (ACE)-generated Angiotensin II contributes to lung injury. ACE2, a recently discovered ACE homologue, acts as a negative regulator of the RAS and counterbalances the function of ACE. We hypothesized that ACE2 prevents Bleomycin (BLM)-induced lung injury. Fourteen to 16-week-old ACE2 knockout mice-male (ACE2(-/y)) and female (ACE2(-/-))-and age-matched wild-type (WT) male mice received intratracheal BLM (1.5U/kg). Male ACE2(-/y) BLM injured mice exhibited poorer exercise capacity, worse lung function and exacerbated lung fibrosis and collagen deposition compared with WT. These changes were associated with increased expression of the profibrotic genes α-smooth muscle actin (α-SMA) and Transforming Growth Factor ß1. Compared with ACE2(-/y) exposed to BLM, ACE2(-/-) exhibited better lung function and architecture and decreased collagen deposition. Treatment with intraperitoneal recombinant human (rh) ACE2 (2 mg/kg) for 21 days improved survival, exercise capacity, and lung function and decreased lung inflammation and fibrosis in male BLM-WT mice. Female BLM WT mice had mild fibrosis and displayed a possible compensatory upregulation of the AT2 receptor. We conclude that ACE2 gene deletion worsens BLM-induced lung injury and more so in males than females. Conversely, ACE2 protects against BLM-induced fibrosis. rhACE2 may have therapeutic potential to attenuate respiratory morbidity in ALI/ARDS.


Prednisone treatment inhibits the differentiation of B lymphocytes into plasma cells in MRL/MpSlac-lpr mice.
A number of evidence shows that the differentiation of B lymphocytes into plasma cells plays an important role in lupus pathogenesis. In this study we investigated how prednisone, a classical therapeutic drug for autoimmune diseases, regulated plasma cell differentiation in MRL/MpSlac-lpr mice. MRL/lpr mice were treated with prednisone (2.5 or 5 mg·kg(-1)·d(-1), ig) for 13 weeks, and the proteinuria levels and survival times were monitored. After the mice were euthanized, blood sample, spleen and thymus were collected. The serum levels of anti-dsDNA antibody, anti-nuclear antibody, IL-21, and IL-10 were detected using ELISA kits. Subsets of splenic B and T lymphocytes were quantified with flow cytometry. Transcription factor Blimp-1 and Bcl-6 expression was determined using qPCR and Western blot. Prednisone treatment dose-dependently attenuated the lupus symptoms in MRL/lpr mice with decreased proteinuria levels, prolonged survival times, decreased serum anti-nuclear antibody levels, and reduced spleen and thymus indices. Prednisone treatment also significantly decreased the elevated percentages of plasma cells and plasma cell precursors, decreased the percentages of activated T cells, and increased the frequency of CD4(+)CD62L(+) cells, demonstrated that decreased anti-nuclear antibodies and improvements in lupus symptoms were associated with decreased plasma cells. Furthermore, prednisone treatment decreased serum IL-21 and IL-10 levels and reduced the expression of splenic Blimp-1 and Bcl-6 (two key regulatory factors for plasma cell differentiation) in MRL/lpr mice. Prednisone treatment restricts B lymphocyte differentiation into plasma cells in MRL/lpr mice, which may be correlated with the inhibition of IL-21 production and the restoration of the balance between Blimp-1 and Bcl-6.


An external focus of attention compared to an internal focus of attention improves anticipatory postural adjustments among people post-stroke.
People after stroke often have postural impairments that can increase their risk of falling. Anticipatory postural adjustments (APAs) are changes in the activity of postural muscles prior to a voluntary movement in order to maintain vertical equilibrium. Previous research suggests that improving APAs leads to better postural control and reduces the risk of falls. Despite the importance of APAs and their impairment among people post-stroke, studies that aim to investigate methods for improving APAs are limited. Consistent evidence supports that an external focus of attention compared to an internal focus of attention, yields superior performance of motor skills that include postural control. What are the effects of adopting different foci of attention on measures of APAs and movement parameters when performing a lower extremity Fitts' task among people post-stroke? Twelve individuals post-stroke performed a lower extremity stepping movement (Fitts' task) while adopting an external focus or an internal focus of attention in a within-subject design. A motion capture system was used to record participants' movement data. Custom software derived movement time (MT), peak velocity (PV), time to peak velocity (ttPV) and variability at endpoint (SDT). Electromyography was used to measure muscle activity and determine APAs onset and magnitude. For all dependent variables separate repeated measures ANOVAs were conducted to compare performance between foci of attention. The results showed that an external focus of attention yielded significantly better performance on all outcome measures. The improvement in performance was seen in shorter MT, higher PV, shorter ttPV, smaller SDT, earlier APAs onset and more efficient APAs magnitude. The changes in outcome measures suggest that adopting an external focus of attention during postural tasks could be an effective strategy for improving balance control among people post-stroke.


The Impact of COVID-19 on Breast Surgery Fellowships.
Across the world, medical training has been affected by the COVID-19 virus and this has changed the way physicians are educated. What is less clear is the effect of the pandemic on breast surgical oncology fellows who were in training during this time. This review discusses the experience of breast surgical oncology fellows during the pandemic and how fellowships adapted to preserve the educational experience and conserve the quality of training. The challenges and changes experienced by breast surgery fellows during the COVID-19 pandemic have proved to be sudden shifts in not only fellowship training, but future patient care and research opportunities, all while confronting the global impact of a deadly pandemic. While experiences between fellowships varied, the similarities and differences encountered highlight the regional and temporal differences in how fellowships responded to the pandemic. Breast surgical oncology fellowship is one year long, with every day allocated to ensure the surgeon has a deep understanding of the multidisciplinary approach to this ever-evolving field. As the pandemic spread and affected different regions with varying severity, elective cases were canceled, resources were re-allocated, and uncertainty abounded. At the same time, novel approaches to fellowship training were rapidly implemented. It will take time and additional research to fully understand the long-term consequences for trainees affected during their breast surgery fellowship.


A medial linkage orthosis to assist ambulation after spinal cord injury.
A "proof of concept" prototype of a new device to link bilateral knee-ankle-foot orthoses, the Mooring Medial Linkage Orthosis (Moorong MLO), is presented. The device consists of an arcuate sliding link centred on the hip joints with rolling element bearings to minimise friction. A single repeated-measures case study is reported in which a woman with an incomplete C6 tetraplegia ambulated over different surfaces and gradients using both the Moorong MLO and the Walkabout orthosis. Results demonstrated a slight increase in gait velocity in the Moorong MLO (between 0.36-1.02 m/min faster) and a consistently lower oxygen cost across all conditions (between 18-61% reduction) compared to the Walkabout orthosis. The reduction was most noticeable on sloping surfaces. These preliminary results suggest an improved efficiency of ambulation in this new device.


Imaging and surgical management of congenital heart diseases.
Congenital heart disease affects approximately 1% of live births per year. In recent years, there has been a decrease in the morbidity and mortality of these cases due to advances in medical and surgical care. Imaging plays a key role in the management of these children, with chest radiography, echocardiography and chest ultrasound the first diagnostic tools, and cardiac computed tomography, catheterization and magnetic resonance imaging reserved to assess better the anatomy and physiology of the most complex cases. This article is a beginner's guide to the anatomy of the most frequent congenital heart diseases (atrial and ventricular septal defects, abnormal pulmonary venous connections, univentricular heart, tetralogy of Fallot, transposition of the great arteries and coarctation of the aorta), their surgical management, the most common postsurgical complications, deciding which imaging modality is needed, and when and how to image gently.


Genetic diversity within the species Arachis duranensis Krapov. &W.C. Gregory, a possible progenitor of cultivated peanut.
Eighteen accessions of a diploid wild peanut species (Arachis duranensis) were analyzed using morphological, intercrossing, cytological, and RFLP data. Abundant variation was found for morphological characters and for RFLP patterns both between and within accessions, and each accession could be uniquely identified by RFLP pattern. Several plants were found to be F1 hybrids between different accessions, indicating that intercrossing had occurred when these were planted for seed increase. Patterns of RFLP diversity were found to correspond with geographic distribution. Analysis of the number of RFLP fragments observed per accession indicates that additional field collections of this complex of taxa will yield additional genetic variability.


Hepatitis B and hepatitis C virus infections in dermatological patients in west Sicily: a seroepidemiological study.
To evaluate the relative frequencies and molecular epidemiological features of viral hepatitis types B and C in dermatological patients in our geographical area. We determined the hepatitis B virus (HBV) and hepatitis C virus (HCV) antibodies and the hepatitis B virus surface antigen (HBsAg) in a cohort of 677 dermatological patients admitted to the Department of Dermatology of Palermo. An 8-mL blood sample was taken from all subjects. The following assays were used: HBsAg, anti-HB core (antigen) (anti-HBc), anti-HB surface (antigen) (anti-HBs), anti-HB early (antigen) (anti-Hbe) and anti-HCV antibodies using enzyme-linked immunosorbent assay. One hundred and eighty-nine (27.91%) of the 677 dermatological patients were positive for anti-HBc, anti-HBs, anti-HBe and/or anti-HCV antibodies. In particular 22% (149 patients) were anti-HBc, anti-HBs or anti-HBe positive, reflecting exposure to HBV, and six patients (0.88%) were chronic carriers of HBsAg; 2.36% of the dermatological patients (16 persons) were anti-HCV positive. Tests showed that 24 subjects (3.52%) were infected with hepatitis B or C. The peaks in the age bands were in the 55-80-year-old age groups. This study confirms a high rate of HBV and HCV exposure with chronic carriers in our dermatological patients. We assume that the high prevalence of HCV and HBV in dermatological patients is more likely to be age related than to represent a true and direct association with dermatological diseases in general. Definite conclusions will only be available after large epidemiological studies that can establish or refute an aetiological and pathogenetic role of HBV and HCV in certain skin diseases associated with liver infection.


[Malignant interstitial cell tumor of testis with a marker enzyme (author's transl)].
Metastatic interstitial cell tumor of the testis is one of the rarest human neoplasms. This is the nineteenth case to be reported. While most of these tumors are combined with hormonal dysfunction, the present tumor, apart from its uncommon hormonal profile, is remarkable because of its capacity of producing and secreting a marker enzyme, alkaline phosphatase. No response was seen after cytostatic therapy with new antineoplastic agents, such as a combination of adriamycin and cis-diamminedichloride-platinum (II), and ifosfamide. Considering the lack of radiosensitivity, surgery is the primary modality of treatment.


The silent loss of neuronavigation accuracy: a systematic retrospective analysis of factors influencing the mismatch of frameless stereotactic systems in cranial neurosurgery.
Neuronavigation has become an intrinsic part of preoperative surgical planning and surgical procedures. However, many surgeons have the impression that accuracy decreases during surgery. To quantify the decrease of neuronavigation accuracy and identify possible origins, we performed a retrospective quality-control study. Between April and July 2011, a neuronavigation system was used in conjunction with a specially prepared head holder in 55 consecutive patients. Two different neuronavigation systems were investigated separately. Coregistration was performed with laser-surface matching, paired-point matching using skin fiducials, anatomic landmarks, or bone screws. The initial target registration error (TRE1) was measured using the nasion as the anatomic landmark. Then, after draping and during surgery, the accuracy was checked at predefined procedural landmark steps (Mayfield measurement point and bone measurement point), and deviations were recorded. After initial coregistration, the mean (SD) TRE1 was 2.9 (3.3) mm. The TRE1 was significantly dependent on patient positioning, lesion localization, type of neuroimaging, and coregistration method. The following procedures decreased neuronavigation accuracy: attachment of surgical drapes (DTRE2 = 2.7 [1.7] mm), skin retractor attachment (DTRE3 = 1.2 [1.0] mm), craniotomy (DTRE3 = 1.0 [1.4] mm), and Halo ring installation (DTRE3 = 0.5 [0.5] mm). Surgery duration was a significant factor also; the overall DTRE was 1.3 [1.5] mm after 30 minutes and increased to 4.4 [1.8] mm after 5.5 hours of surgery. After registration, there is an ongoing loss of neuronavigation accuracy. The major factors were draping, attachment of skin retractors, and duration of surgery. Surgeons should be aware of this silent loss of accuracy when using neuronavigation.


HLA antigens and progression of multiple sclerosis. Part II.
The HLA-A, -B, -C and -D were determined in 200 multiple sclerosis (MS) patients, 64 of whom underwent a CSF examination. Their frequencies were correlated with the rate of disease progression and with factors thought to influence disease progression, including onset age, type of clinical course and intrathecal IgG synthesis. No correlation was found between HLA haplotypes and progression rate or type of disease course. Patients starting MS after age 31 years carried the DR2 determinant more frequently (P = 0.016) than patients with onset before this median age. Although the greatest proportion of patients with an IgG index greater than 1.5 or more than 15 oligoclonal bands in their CSF were DR2 carriers, no statistical difference was found in the intrathecal IgG synthesis of HLA-DR2 (+) and (-) patients.


Myalgia in outpatient surgery: comparison of atracurium and succinylcholine.
We studied 60 outpatients randomly divided into two groups. Anesthesia was induced with fentanyl 1.5 micrograms.kg-1 plus thiopentone 5-7 mg.kg-1. Patients in Group I were intubated with the aid of succinylcholine 1.5 mg.kg-1 after pre-treatment with d-tubocurarine 0.05 mg.kg-1. Group II received atracurium 350 micrograms.kg-1 three minutes after a priming dose of 50 micrograms.kg-1. Anesthesia was maintained with isoflurane 1-2 per cent in a mixture of nitrous oxide 60 per cent and oxygen 40 per cent. No supplemental doses of fentanyl or atracurium were given. Intubation conditions were satisfactory for all patients in both groups. There was no significant difference in intubation score between the two groups. The incidence of myalgia was 76 per cent in the succinylcholine group compared to 23 per cent in the atracurium group (p less than 0.005). Fifty per cent of the patients in the succinylcholine group had myalgia necessitating bed rest or analgesics compared to 23 per cent in the atracurium group (p less than 0.05). We conclude that atracurium is a suitable neuromuscular relaxant for outpatient surgery and that myalgia is a major morbidity factor in this population that can be reduced by the use of atracurium instead of succinylcholine.


Bacterial signal peptide recognizes HeLa cell mitochondrial import receptors and functions as a mitochondrial leader sequence.
Phage display was used to identify new components of the mammalian mitochondrial receptor complex using Tom20 as a binding partner. Two peptides were identified. One had partial identity (SMLTVMA) with a bacterial signal peptide from Toho-1, a periplasmic protein. The other had partial identity with a mitochondrial inner membrane glutamate carrier. The bacterial signal peptide could carry a protein into mitochondria both in vivo and in vitro. The first six residues of the sequence, SMLTVM, were necessary for import but the two adjacent arginine residues in the 30-amino-acid leader were not critical for import. The signal peptides of Escherichia coli beta-lactamase and Bacillsus subtilis lipase could not carry proteins into mitochondria. Presumably, the Toho-1 leader can adopt a structure compatible for recognition by the import apparatus.


Radiation therapy for triple-negative breast cancer: emerging role of microRNAs as biomarkers and radiosensitivity modifiers. A systematic review.
Radiation therapy (RT) for triple-negative breast cancer (TNBC) treatment is currently delivered in the adjuvant setting and is under investigation as a booster of neoadjuvant treatments. However, TNBC radioresistance remains an obstacle, so new biomarkers are needed to select patients for any integration of RT in the TNBC therapy sequence. MicroRNAs (miRs) are important regulators of gene expression, involved in cancer response to ionizing radiation (IR) and assessable by tumor tissue or liquid biopsy. This systematic review aimed to evaluate the relationships between miRs and response to radiation in TNBC, as well as their potential predictive and prognostic values. A thorough review of studies related to miRs and RT in TNBC was performed on PubMed, EMBASE, and Web of Science. We searched for original English articles that involved dysregulation of miRs in response to IR on TNBC-related preclinical and clinical studies. After a rigorous selection, 44 studies were chosen for further analysis. Thirty-five miRs were identified to be TNBC related, out of which 21 were downregulated, 13 upregulated, and 2 had a double-side expression in this cancer. Expression modulation of many of these miRs is radiosensitizing, among which miR-7, -27a, -34a, -122, and let-7 are most studied, still only in experimental models. The miRs reported as most influencing/reflecting TNBC response to IR are miR-7, -27a, -155, -205, -211, and -221, whereas miR-21, -33a, -139-5p, and -210 are associated with TNBC patient outcome after RT. miRs are emerging biomarkers and radiosensitizers in TNBC, worth further investigation. Dynamic assessment of circulating miRs could improve monitoring and TNBC RT efficacy, which are of particular interest in the neoadjuvant and the high-risk patients' settings.


The effect of erenumab on brain network function in episodic migraine patients: a randomized, placebo-controlled clinical trial (RESET BRAIN).
We aimed to explore whether erenumab, a monoclonal antibody targeting the calcitonin gene-related peptide receptor, could exert a central effect on brain network function in migraine, and investigate the persistence of such an effect following treatment discontinuation. This was a randomized, double-blind, placebo-controlled, multicenter trial with a crossover design performed in adult episodic migraine patients with previous treatment failure. Patients were randomized (1:1) to 12 weeks of erenumab 140 mg or placebo, followed by a 12-week crossover. Resting state (RS) functional connectivity (FC) changes of brain networks involved in migraine were investigated using a seed-based correlation approach. Sixty-one patients were randomized to treatment. In each treatment sequence, 27 patients completed the visit at week 12. Forty-four enrolled patients, 22 in each treatment sequence, completed the study procedures with no major protocol violations. We observed a carry-over effect of erenumab during the placebo treatment and therefore data analysis was performed as a parallel comparison of erenumab vs placebo of the first 12 weeks of treatment. From baseline to week 12, compared to placebo, patients receiving erenumab showed RS FC changes within the cerebellar, thalamic and periaqueductal gray matter networks, significantly associated with clinical improvement. Compared to non-responders, patients achieving a 50% reduction in migraine days had distinct patterns of thalamic and visual network RS FC. Brain RS FC changes reversed when erenumab was stopped. A lower baseline RS FC of the pontine network identified patients responding to erenumab. Erenumab modulates RS FC of networks involved in migraine pathophysiology. In line with clinical response, erenumab-induced brain RS FC changes tend to reverse when treatment is stopped.


Cornell Scale for Depression in Dementia.
The Cornell Scale for Depression in Dementia is introduced. This is a 19-item clinician-administered instrument that uses information from interviews with both the patient and a nursing staff member, a method suitable for demented patients. The scale has high interrater reliability (kw = 0.67), internal consistency (coefficient alpha: 0.84), and sensitivity. Total Cornell Scale scores correlate (0.83) with depressive subtypes of various intensity classified according to Research Diagnostic Criteria.


Inhibition of tumor growth by RGD peptide-directed delivery of truncated tissue factor to the tumor vasculature.
Selective activation of blood coagulation in tumor vessels with subsequent tumor infarction is a promising anticancer strategy. To this end, a fusion protein consisting of the extracellular domain of tissue factor [truncated tissue factor (tTF)] was fused to the peptide GRGDSP selectively targeting alpha(v)-integrins on tumor endothelial cells. tTF-RGD retained its thrombogenic and integrin-binding activity in vitro. In vivo studies in mice bearing human adenocarcinomas (CCL185), melanoma (M21), and fibrosarcoma (HT1080) revealed that i.v. administration of tTF-RGD induced thrombotic occlusion of tumor vessels resulting in tumor growth retardation or regression in all three types of solid tumors. No apparent side effects, such as thrombosis, in other organs or other treatment-related toxicities were observed. Reduced tumor blood flow in tTF-RGD-treated animals as determined by contrast-enhanced magnetic resonance imaging underlines the proposed mechanism. In conclusion, we consider RGD peptide-directed delivery of tTF as alternative to previously used antibody fusion proteins. Small peptide-directed delivery of coaguligands does not cause immunologic side effects and those caused by accumulation in the reticuloendothelial system. This is the first report to describe the induction of selective thrombosis in tumor vessels by RGD peptide-directed delivery of tTF, which may be a promising strategy for the treatment of cancer.


Factors Associated with Mortality in Immunocompetent Patients with Hospital-acquired Pneumonia.
The aim of the study is to determine the factors associated with 28-day mortality in immunocompetent patients with hospital-acquired pneumonia (HAP). This was a 42-month retrospective cohort study in Chiang Kham Hospital. Patients with HAP diagnosed between January 2013 and June 2016 who did not have an immunocompromised status were recruited into the study. Univariable and multivariable binary logistic regression analyses were performed to determine the factors associated with mortality in patients with HAP. A total of 181 HAP patients. The most causative pathogens were nonfermenting Gram-negative bacilli. Fifty-two (28.7%) patients had died within 28 days after HAP diagnosis. Multivariable analysis demonstrated that mechanical ventilation (MV) dependency (adjusted odds ratio [OR] = 3.58, 95% confidence interval [CI] 1.53-8.37, P = 0.003), antibiotic duration (adjusted OR = 0.79, 95% CI 0.70-0.88, P < 0.001), acute kidney injury (adjusted OR = 5.93, 95% CI 1.29-27.22, P = 0.022), and hematologic diseases (adjusted OR = 11.45, 95% CI 1.61-81.50, P = 0.015) were the significant factors associated with 28-day mortality. The factors associated with mortality were MV dependency, HAP duration of treatment, acute kidney injury, and hematologic disease. Early recognition of these factors in immunocompetent patients with HAP and treatment with intensive care may improve the outcome.


Fat emulsions for parenteral nutrition. I: Evaluation of microscopic and laser light scattering methods for the determination of the physical stability.
Droplet size distribution was studied as a measure of the physical stability of fat emulsions. Test emulsions with increasing fractions of larger particles were prepared and investigated by conventional light microscopy and laser light scattering techniques (Photon Correlation Spectroscopy (PCS), Laser Diffractometer). Light microscopy proved to be most sensitive for detecting a few single large particles. All the techniques placed the test emulsions in the same order of increasing content of larger droplets. The application of a two time window analysis for PCS markedly improved the ability to differentiate between emulsions which were very similar in size distribution. In contrast to the applied semi-quantitative microscopic method, the laser techniques characterise the emulsion in absolute figures. Additional zeta potential measurements by Laser Doppler Anemometry (LDA) can quantify reduced electrostatic repulsion as a possible cause for increased formation of larger droplets.


Early menopause in mothers of children with Down syndrome?
To investigate whether having a Down syndrome pregnancy at a relatively young age is associated with lower ovarian reserve as reflected by lower antimüllerian hormone (AMH) levels and the occurrence of earlier menopause. Retrospective, case control study. Not applicable. Two hundred twenty mothers (118 trisomy cases, 102 controls). Questionnaire and serum AMH measurement. Serum AMH levels and menopause, defined as not having a menstrual cycle for at least 1 year. The participant response rate was 93%. After applying the exclusion criteria, 144 women were evaluable (73 trisomy cases, and 71 controls). The baseline characteristics of the women were not statistically significantly different. More women with a Down syndrome pregnancy had an AMH level below 0.5 μg/L, a difference that was statistically significant. Eleven women (15.1%) in the Down syndrome group had reached menopause compared with 9 (12.7%) of the controls. Women who have had a Down syndrome pregnancy at a younger age show signs of limited ovarian reserve, as evidenced by their frequently having lower AMH levels. The study has found no obvious signs of early menopause thus far. Whether their age at menopause is within the normal range remains to be determined.


Supplements as a source of micronutrient intake in middle-aged men in southern Germany: results of the MONICA dietary survey 1994/95.
Survey data on contemporary supplement intake in Germany are scarce, and the contribution of supplements to nutrient intake is especially unclear. In the MONICA Project Augsburg a dietary survey using 7-day weighed records was carried out in a subsample of 607 eligible men aged 45-64 years from the city of Augsburg (participation 430 men = 71%) in 1994/95. Participants also reported their intake of supplements. The German national food data base BLS (version 2.1), which was used to code the records and calculate the nutrients, had to be complemented by nutrient data of supplements and fortified foods. On a group level the maximum mean percentage contribution of supplements to the intake of a micro nutrient was 4.0% (vitamin C). On an individual level, however, up to 4.0% of the men were found to receive more than 50% of their intake of selected micronutrients from supplements. It is, therefore, recommended to ask for supplement intake in future dietary surveys within Germany.


A case control study on psychopharmacotherapy before suicide committed by 61 psychiatric inpatients.
The pharmacotherapy of 61 suicide victims (0.24 % of 27,078 admissions from January 1, 1980 to December 31, 1999) was compared to that of a control group matched for age, gender and diagnosis at the time of discharge. Both groups were also comparable regarding stay in hospital, history of psychiatric disease, and frequency of hospitalisations during the year preceding the index evaluation. Multiple but not single suicide attempts were significantly more frequent in patients who were later to complete the suicide than in controls. Schizophrenia (ICD-9, ICD-10) was the most frequent diagnosis among suicide victims (44.3 %). Affective psychosis (ICD-9, ICD-10) bore the highest relative risk (0.8 %). 50 % of the schizophrenic patients in the suicide group had been continuously treated with full-dose tricyclic antidepressants. The CPZ-equivalents in the patients treated with antipsychotics were not of discriminating value. Four of 27 schizophrenic patients in the suicide group had been off neuroleptics for ten days or more; this was never observed among the controls. Lorazepam applied in 40% of the schizophrenic and in 25 % of the affective psychosis suicide victims had more often been withdrawn or reduced during the ten days preceding suicide than among controls. No schizophrenic suicide victims but five controls had been on mood stabilisers. The use of antipsychotics (classical and atypical) and a recent change in tricyclic drug or drug dose were more frequent in suicide victims with affective psychosis. Lithium had been given to one patient, but it had also been administered to six controls; this difference is significant. Mood stabilisers, especially lithium, should be considered more often in patients with previous suicide attempt(s). When changing antidepressants in affective psychosis, benzodiazepines might be given more deliberate consideration. Patients in all diagnostic categories should be closely guided by means of intensified psychotherapeutic interventions while undergoing a benzodiazepine reduction. The treatment of patients suffering from schizophrenia with full-dose tricyclic regimens should be considered as possibly enhancing the acute suicide risk in some individuals.


Benefits of thymol supplementation on performance, the hepatic antioxidant system, and energetic metabolism in grass carp.
Thymol is an herbal food additive used to improve animal performance. Thymol acts via its potential to enhance productive and reproductive performance, and by improving bioavailability of nutrients in fish. Nevertheless, the exact mechanisms associated with these phenomena remain poorly understood, although recent evidence has suggested the involvement of the phosphotransfer network and antioxidant status. Therefore, the aim of this study was to determine whether the improvement of the antioxidant/oxidant status and the phosphoryl transfer network may be involved in enhanced growth performance in grass carp (Ctenopharyngodon idella) fed with various levels of thymol (100, 200, and 300 mg/kg feed). Thymol-supplementation (100 mg/kg feed) produced higher body weight and weight gain for 60-day post-feeding compared to the control group. Specific growth rate was higher; while feed conversion ratio was lower in fish that consumed 100 mg of thymol/kg compared to other groups. Hepatic lactate dehydrogenase activity and lipid peroxidation levels were lower in the thymol-supplemented group (100 mg/kg feed) than in the control group, while reactive oxygen species were lower in all supplemented groups than in the control group. Hepatic superoxide dismutase (300 mg/kg feed) and glutathione peroxidase (100, 200, and 300 mg/kg feed) activities, as well as antioxidant capacity against peroxyl radicals (100 mg/kg feed) were higher in these groups than in the control group. Based on these data, we conclude that 100 mg thymol/kg dietary supplementation increased growth performance of fingerling grass carp. Finally, hepatic adenylate kinase activity was lower in the thymol supplemented group (100 mg/kg feed) than in the control group. Thymol supplementation (100 mg/kg feed) improved hepatic energy metabolism, while practically all tested concentrations of thymol enhanced hepatic antioxidant status, all of which may be pathways involved in increased growth performance in fingerling grass carp.


Scar cancer of the lung: increase over a 21 year period.
In a review of 1,186 cases of lung cancer found amoung 7,629 autopsied cases over a 21 year period a total of 82 peripheral cancers related to scars were found, constituting 1% of the autopsied cases and 7% of the lung tumors. 15% of all lung tumors were peripheral (vs. bronchogenic) and the percentage rose from less than 7 in the time period of 1955 to 1960 to a little more than 23 in the 1970 to 1976 time period. 45% of all peripheral lung cancers originated in a scar. Less than 2% of all lung cancers were found associated with scars in the 1955 through 1959 time period. This increased to nearly 16% in the 1970 through 1975 time period. 72% of the scar cancers were adenocarcinomas and 18% were of squamous cell type. The rest were large cell undifferentiated carcinomas and none was oat cell or small cell type. Over three-quarters of these scar cancers were found in the upper lobes and more than half were related to infarcts. Less than a quarter were related to tuberculosis scars. No relationship was found between smoking habits and scar cancer.