Crossed Cerebellar Diaschisis: Risk Factors and Correlation to Functional Recovery in Intracerebral Hemorrhage.
The purpose of this study is to investigate predictors of crossed cerebellar diaschisis (CCD), and the effects of CCD on functional outcomes including motor function, activities of daily living, cognitive function, and ambulation 6 months after onset in patients with intracerebral hemorrhage (ICH). A total of 74 patients experiencing their first ICH were recruited. If the asymmetric index was more than 10% using single photon emission computed tomography (SPECT), a diagnosis of CCD was confirmed. Clinical factors were retrospectively assessed by reviewing medical records. Radiologic factors encompassed the concomitance of intraventricular hemorrhage, side and location of the lesion, and hemorrhage volume. Functional outcomes were evaluated using the Fugl-Meyer Assessment, the Korean version of the Mini-Mental State Examination, the Korean version of the Modified Barthel Index, and measurement of the Functional Ambulatory Category at the time of SPECT measurement and 6 months post-ICH. Lesion location, especially in the basal ganglia (odds ratio [OR]=6.138, p=0.011), and hemorrhagic volume (OR=1.055, p=0.046) were independent predictors for CCD according to multivariate logistic regression analysis. In addition, the presence of CCD was significantly related to the improvement in Fugl-Meyer Assessment score after 6 months (adjusted R2=0.152, p=0.036). Lesion location and hemorrhagic volume were the predisposing factors for CCD, and the CCD was associated with poor motor recovery over 6 months in patients with hemorrhagic stroke.


Accuracy of Pediatric Risk of Mortality (PRISM) III Score in Predicting Mortality Outcomes in a Pediatric Intensive Care Unit in Karachi.
Background With the advancements in medicine and increasing access to modern technology, pediatric intensive care units (PICU) are becoming a vital part of any health care setting. PICUs play a key role in saving the life of young patients. Various scales have been designed by researchers to aid in predicting the mortality of a patient admitted in PICU. Pediatric Risk of Mortality (PRISM) and Pediatric Index of Mortality (PIM) are among the most commonly used scales. Calculating the risk of mortality enables the physicians to classify the patients and helps in identifying which patients require more urgent care and resources. Methods A hospital-based prospective study was carried out at PICU in a tertiary care hospital in Karachi from December 2017 to June 2019. All patients between the age of one month and 12 years were included in our study after informed consent from parents/guardians. A standard questionnaire was used and the PRISM III score was calculated at 24 hours of admission. All necessary investigations were carried out, and all statistical analyses were carried out using SPSS v.23 (IBM, Armonk, NY). Results A total of 407 patients were included in our study with the majority being males (54.5%). The mean age was 27±33 months. The mean duration of stay of patients in PICU was 80.15±36.58 hours. The mortality rate in our study was 37.35 % (n=152). The need for mechanical ventilation, use of inotropic drugs, higher temperatures, and low Glasgow Coma Scale scores were associated with poor survival. It was noted that as the PRISM III score increased, the mortality rate also increased. In our study, we found that PRISM III had good predictive power in our population. The area under the curve was 0.903±0.016 (p<0.001, 95% confidence interval: 0.872-0.934). Conclusions PRISM III score showed excellent accuracy and predictive ability in our population. There was no significant difference in observed and expected mortality rates in our study. In a resource-limited setting, the prediction models highlight the cases where more medical attention is required and also enable the physicians to assess the prognosis of the patient so adequate measures can be taken beforehand.


Music and preoperative anxiety: a randomized, controlled study.
Music may decrease the anxiety experienced by patients before surgery. Previous studies of this issue were hindered with multiple methodological problems. In this investigation, we examined this hypothesis while using a rigorous study design and objective outcome measures. Adult patients undergoing anesthesia and surgery were randomly assigned to two study groups. Subjects in Group 1 (n = 48) listened to a 30-min patient-selected music session, and subjects in Group 2 (n = 45) received no intervention. By using self-report validated behavioral (State-Trait Anxiety Inventory) and physiological measures of anxiety (heart rate, blood pressure, and electrodermal activity and serum cortisol, epinephrine, and norepinephrine), patients were evaluated before, during, and after administration of the intervention. We found that after intervention, subjects in the Music group reported significantly lower anxiety levels as compared with the Control group (F(1,91) = 15.4, P = 0.001). That is, the postintervention anxiety level of subjects in the Music group decreased by 16% as compared with the preintervention level, whereas the anxiety level of the Control group did not change significantly. Two-way repeated-measures analysis of variance performed for the electrodermal activity, blood pressure, heart rate, cortisol, and catecholamine data demonstrated no group difference and no time x group interaction (P = not significant). In conclusion, under the conditions of this study, patients who listened to music before surgery reported lower levels of state anxiety. Physiological outcomes did not differ, however, between the two study groups. Patients who listen to music of their choice during the preoperative period report less anxiety.


On the feasibility of resolving the organ shortage.
Debates concerning the feasibility of resolving the organ shortage from the potential pool of deceased donors have suffered from both conceptual and empirical problems. Conceptually, several authors mistakenly have viewed recipient waiting lists as a measure of the magnitude of the shortage. And empirically, the number of deaths that would qualify for potential organ donation has proven difficult to estimate. While the latter problem appears to have been substantially lessened by recent work, the former, definitional, problem remains. This paper offers the economically correct definition of a shortage and applies that definition to the new data on potential supply.


Ampicillin susceptibilities of vaginal and placental isolates of group B streptococcus and Escherichia coli obtained between 1992 and 1994.
Vaginal group B streptococcus (GBS) and Escherichia coli isolates were tested for their susceptibilities to ampicillin. All 414 GBS isolates tested were susceptible to ampicillin; the MIC at which 90% of the isolates were inhibited (MIC90) was 0.125 microg/ml, and the range was 0.06 to 0.25 microg/ml. The MIC50 for the 342 E. coli isolates tested was 4.0 microg/ml, and 27% were resistant to ampicillin.


Cancer-selective, single agent chemoradiosensitising gold nanoparticles.
Two nanometre gold nanoparticles (AuNPs), bearing sugar moieties and/or thiol-polyethylene glycol-amine (PEG-amine), were synthesised and evaluated for their in vitro toxicity and ability to radiosensitise cells with 220 kV and 6 MV X-rays, using four cell lines representing normal and cancerous skin and breast tissues. Acute 3 h exposure of cells to AuNPs, bearing PEG-amine only or a 50:50 ratio of alpha-galactose derivative and PEG-amine resulted in selective uptake and toxicity towards cancer cells at unprecedentedly low nanomolar concentrations. Chemotoxicity was prevented by co-administration of N-acetyl cysteine antioxidant, or partially prevented by the caspase inhibitor Z-VAD-FMK. In addition to their intrinsic cancer-selective chemotoxicity, these AuNPs acted as radiosensitisers in combination with 220 kV or 6 MV X-rays. The ability of AuNPs bearing simple ligands to act as cancer-selective chemoradiosensitisers at low concentrations is a novel discovery that holds great promise in developing low-cost cancer nanotherapeutics.


Arthropods are kin: Operationalizing Indigenous data sovereignty to respectfully utilize genomic data from Indigenous lands.
Indigenous peoples have cultivated biodiverse agroecosystems since time immemorial. The rise of metagenomics and high-throughput sequencing technologies in biodiversity studies has rapidly expanded the scale of data collection from these lands. A respectful approach to the data life cycle grounded in the sovereignty of indigenous communities is imperative to not perpetuate harm. In this paper, we operationalize an indigenous data sovereignty (IDS) framework to outline realistic considerations for genomic data that span data collection, governance, and communication. As a case study for this framework, we use arthropod genomic data collected from diversified and simplified farm sites close to and far from natural habitats within a historic Kānaka 'Ōiwi (Indigenous Hawaiian) agroecosystem. Diversified sites had the highest Operational Taxonomic Unit (OTU) richness for native and introduced arthropods. There may be a significant spillover effect between forest and farm sites, as farm sites near a natural habitat had higher OTU richness than those farther away. We also provide evidence that management factors such as the number of Polynesian crops cultivated may drive arthropod community composition. Through this case study, we emphasize the context-dependent opportunities and challenges for operationalizing IDS by utilizing participatory research methods, expanding novel data management tools through the Local Contexts Hub, and developing and nurturing community partnerships-all while highlighting the potential of agroecosystems for arthropod conservation. Overall, the workflow and the example presented here can help researchers take tangible steps to achieve IDS, which often seems elusive with the expanding use of genomic data.


Validation of high-resolution melting analysis as a diagnostic tool for endothelin receptor B mutation in American Paint horses and allele frequency estimation.
Overo lethal white foal syndrome (OLWFS) is a genetic disorder caused by a dinucleotide mutation in the endothelin receptor type B (EDNRB) gene leading to the death of affected foals shortly after birth. The use of rapid and reliable genetic testing is imperative for the early diagnosis of the mutation avoiding, therefore, either additional suffering or the production of affected animals. In the present study, we developed and validated a high-resolution melting (HRM) genotyping assay to detect the OLWFS causative mutation, and we also determined the frequency of heterozygotes among American Paint horses in Brazil. The HRM genotyping assay resulted in a high sensitivity, specificity, and positive and negative predictive values. The overall estimated frequency of heterozygotes was 21.6%; however, this frequency increased to 89.5% when considering only overo horses. The HRM assay optimized here was a reliable and suitable method for the detection of the dinucleotide mutation observed in the EDNRB gene resulting in a fast, accurate, and precise diagnostic tool. The causative gene mutation of OLWFS is present in heterozygosity in the American Paint Horse population in Brazil and is highly frequent among overo horses.


Endoscopic removal of a pedunculated early duodenal cancer: diagnostic value of endoscopic ultrasound.
A 79-year-old Japanese woman was admitted to our hospital for evaluation of a polypoid lesion in the second portion of the duodenum. Radiographic and endoscopic examinations of the upper gastrointestinal tract indicated that this mass was pedunculated and had a nodular surface. Endoscopic ultrasonography demonstrated a hypoechoic tumor limited to the mucosa without lymph node involvement. Endoscopic polypectomy was performed. Histologic examination showed a tubular adenocarcinoma arising in an adenoma with invasion limited to the mucosa. Findings were consistent with complete endoscopic resection. Follow-up over a 12-month period has disclosed no evidence of tumor recurrence. Endoscopic polypectomy using information from endoscopic ultrasonography would appear to be a safe and effective method for diagnosis and treatment of pedunculated early duodenal cancers.


Layer frustration, polar order and chirality in liquid crystalline phases of silyl-terminated achiral bent-core molecules.
A novel class of bent-core molecules with oligo(siloxane) or carbosilane units at both ends was synthesized and the self-organization of these molecules was investigated by polarizing microscopy, DSC, X-ray scattering, dielectric and electrooptical methods. Depending on the size of the silicon-containing segments, smectic and columnar liquid crystalline phases are formed. Most smectic phases are low birefringent and composed of macroscopic domains of opposite handedness (dark conglomerate phases). The switching process in these smectic phases is surface stabilized ferroelectric and, depending on the conditions, two distinct slow relaxation processes to nonpolar structures were observed. It is proposed that the smectic phases are built up by chiral and polar SmCsPF layer stacks which are separated by anticlinic interfaces. If the size of these layer stacks is sufficiently large a coupling to the substrate surfaces takes place and ferroelectric switching is observed. It is also suggested that the sponge-like layer distortion, occurring in the low birefringent mesophases, is due to an escape from the local polar order within these SmCsPF layer stacks. For compounds with larger silylated units a steric frustration arises, which leads to layer modulation (columnar ribbon phases) and this is associated with a transition from ferroelectric to antiferroelectric switching. All compounds show a switching of the molecules around the long axis which reverses the layer chirality.


Comparison of glacial and non-glacial-fed streams to evaluate the loading of persistent organic pollutants through seasonal snow/ice melt.
The release of persistent organic pollutants (PCBs, HCB, HCHs and DDTs) accumulated in Alpine glaciers, was studied during spring-summer 2006 on the Frodolfo glacial-fed stream (Italian Alps). Samples were also taken on a non-glacial stream in the same valley, to compare POP contribution from different water sources (glacier ice, recent snow and spring). In late spring and early summer (May, June) recent snow melting is the most important process. POP contamination is more affected by local emissions and transport, and comparable levels have been measured in both streams for all studied compounds. In late summer and autumn (July-October), the contribution of ice melting strongly increases. In the glacial-fed stream the concentration of chlorinated pesticides (HCHs and DDTs) is about one order of magnitude higher than in the non-glacial-fed. A different behaviour was observed for PCBs, characterised by a peak in June showing, in both streams, concentrations three orders of magnitude higher than the background levels measured in May and in October. This result should be attributed to local emissions rather than long range atmospheric transport (LRAT). This hypothesis is supported by the PCB congener profile in June strictly comparable to the most commonly used Aroclor technical mixtures. The different seasonal behaviour observed for the different groups of chemicals indicates the POP loading in glacial streams is a combined role of long range atmospheric transport and local emission.


Alveolar bone regeneration around immediate implants using an injectable nHAC/CSH loaded with autogenic blood-acquired mesenchymal progenitor cells: an experimental study in the dog mandible.
Lack of osseointegration between a dental implant and the walls of the alveolar bone is a common problem in immediate implantation. Injectable tissue-engineered bone (ITB) may be an effective and minimally invasive solution to the problem. In this study, an injectable bone cement, nHAC/CSH, which consists of nano-hydroxyapatite/collagen (nHAC) and calcium sulfate hemihydrate (CaSO4 .½H2 O; CSH) was investigated as a tissue-engineered scaffold material with blood-acquired mesenchymal progenitor cells (BMPC) as seeding cells. The aim of the study was to assess the new bone formation around immediate dental implants using nHAC/CSH loaded with dog blood-acquired mesenchymal progenitor cells (dBMPC) in a canine model. dBMPC were first isolated from peripheral blood of healthy adult dogs. Alizarin red and oil red O staining were then used to evaluate the potential of dBMPC to differentiate into bi-lineage mesenchymal tissues in vitro. Four healthy mongrel dogs were used in this study. The alveolar bone defects around immediate implants of dogs were created. Each defect was randomly assigned to one of the following three groups: (1) the ITB group (dBMPC+nHAC/CSH); (2) injectable bone cement nHAC/CSH; or (3) no materials (controls). Methylene blue staining was used to examine the bone formation after 3 months. Studies in vitro revealed that dBMPC could be induced to osteoblasts and adipocytes. The ITB group (dBMPC+nHAC/CSH) showed significantly more bone-implant contact and bone density than either nHAC/CSH or control groups in the areas with peri-implant defects 3 months after implantation. The results indicate that the ITB composed of nHAC/CSH and dBMPC may represent a useful strategy for the clinical reconstruction of bone defects around immediate implantation. However, further investigation is needed involving the use of human BMPC as well as possible use of stem cells.


Partnering against cancer today: a blueprint for coordinating efforts through communication science.
One of the hallmarks of the communication revolution over the past decade has been its support for participation, whether that be in the active engagement of patients searching the Web for answers to vital health questions, or in the collective energies of self-organizing communities through social media. At the same time, some of the major obstacles to achieving a full and equitable reach of evidence-based cancer control knowledge have been traced back to discontinuities in communication either within clinical care or the broader public awareness system. Communication scientists from the National Cancer Institute, the Centers for Disease Control and Prevention, and the American Cancer Society joined forces in 2010 to investigate ways in which communication science can be used to improve coordination and enhance participation in cancer control for the nation. From 2010 to 2013, the three organizations worked together in 1) convening two meetings designed to assess the status of funded research in communication science, 2) completing a systematic review of literature published over the previous 10 years, and 3) authoring a blueprint for coordinated efforts using the implications of communication science. The blueprint consists of three major goals: first, to identify high-yield targets of opportunity using the health impact pyramid articulated by Centers for Disease Control and Prevention Director, Thomas Frieden; second, to leverage opportunities within the new communication environment, including the opportunities catalyzed by national efforts to create an infrastructure for evidence implementation through health information technology; and third, to assist in coordinating efforts across collaborative entities through participative media.


Efficacy and Safety of Nivolumab in Patients with Advanced Non-small-cell Lung Cancer and Poor Performance Status.
Background: Nivolumab efficacy in patients with non-small-cell lung cancer (NSCLC) and performance status (PS) of 2-4 is unclear. We aimed to compare survival, treatment efficacy, and safety in patients with NSCLC with poor PS who received nivolumab plus best supportive care (BSC) with those in patients who received BSC alone in a palliative care unit (PCU). Patients and methods: This retrospective study included 99 consecutive patients with NSCLC who received nivolumab plus BSC or BSC alone between December 2015 and March 2018. Results: In total, 43 patients with PS of 0-1 (good PS group) and 20 patients with PS of 2-4 (poor PS group) received nivolumab plus BSC; the remaining 36 patients received BSC alone in the PCU (PC group). Median overall survival was 32 days [95% confidence interval (CI), 21-43] in the poor PS group and 31 days (95% CI, 25-37) in the PC group (hazard ratio, 0.653; 95% CI, 0.368-1.158; P = 0.137). Moreover, median overall survival in patients with PS of 3 or 4 among the poor PS group was not significantly longer than that in the PC group (HR, 1.235; 95% CI, 0.646-2.360; P = 0.516). The frequency of severe pneumonitis in the poor PS group was significantly higher than that in the good PS group (25% vs. 2%, P = 0.010). Conclusion: Survival benefit of nivolumab in patients with NSCLC with poor PS, especially 3 or 4, was not confirmed. Further studies with larger numbers of patients are required to confirm our results.


Effects of Rearfoot Eversion on Foot Plantar Pressure and Spatiotemporal Gait Parameters in Adolescent Athletes.
Foot malalignment can augment the risk of lower-extremity injuries and lead to musculoskeletal disorders. This study aimed to clarify the contribution of rearfoot alignment to plantar pressure distribution and spatiotemporal parameters during gait in healthy adolescent athletes. This retrospective study included 39 adolescent athletes who were divided into the rearfoot eversion and control groups according to a leg heel angle of 7°. A total of 78 legs were analyzed (45 and 33 legs in the rearfoot eversion [women, 53.3%] and control groups [women, 48.5%], respectively). Gait was assessed using an in-shoe plantar pressure measuring system and a wearable inertial sensor. The foot plantar pressure distribution in the hallux was higher in the rearfoot eversion group than that in the control group (p = 0.034). Spatiotemporal parameters showed that the foot pitch angle at heel strike was significantly larger in the rearfoot eversion group than that in the control group (24.5° vs. 21.7°; p = 0.015). Total sagittal range of motion of the ankle during the stance phase of gait was significantly larger in the rearfoot eversion group than that in the control group (102.5 ± 7.1° vs. 95.6 ± 15.8°; p = 0.020). Logistic regression analysis revealed that plantar pressure at the hallux and medial heel and foot pitch angle at heel strike were significantly associated with rearfoot eversion. Our findings suggest that rearfoot eversion affects the gait patterns of adolescent athletes. Notably, leg heel angle assessment, which is a simple and quick procedure, should be considered as an alternative screening tool for estimating plantar pressure and spatiotemporal gait parameters to prevent sports-related and overuse injuries in adolescent athletes.


Ischaemic preconditioning for the reduction of renal ischaemia reperfusion injury.
Ischaemia reperfusion injury can lead to kidney dysfunction or failure. Ischaemic preconditioning is a short period of deprivation of blood supply to particular organs or tissue, followed by a period of reperfusion. It has the potential to protect kidneys from ischaemia reperfusion injury. This review aimed to look at the benefits and harms of local and remote ischaemic preconditioning to reduce ischaemia and reperfusion injury among people with renal ischaemia reperfusion injury. We searched Cochrane Kidney and Transplant's Specialised Register to 5 August 2016 through contact with the Information Specialist using search terms relevant to this review. We included all randomised controlled trials measuring kidney function and the role of ischaemic preconditioning in patients undergoing a surgical intervention that induces kidney injury. Kidney transplantation studies were excluded. Studies were assessed for eligibility and quality; data were extracted by two independent authors. We collected basic study characteristics: type of surgery, remote ischaemic preconditioning protocol, type of anaesthesia. We collected primary outcome measurements: serum creatinine and adverse effects to remote ischaemic preconditioning and secondary outcome measurements: acute kidney injury, need for dialysis, neutrophil gelatinase-associated lipocalin, hospital stay and mortality. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. We included 28 studies which randomised a total of 6851 patients. Risk of bias assessment indicated unclear to low risk of bias for most studies. For consistency regarding the direction of effects, continuous outcomes with negative values, and dichotomous outcomes with values less than one favour remote ischaemic preconditioning. Based on high quality evidence, remote ischaemic preconditioning made little or no difference to the reduction of serum creatinine levels at postoperative days one (14 studies, 1022 participants: MD -0.02 mg/dL, 95% CI -0.05 to 0.02; I2 = 21%), two (9 studies, 770 participants: MD -0.04 mg/dL, 95% CI -0.09 to 0.02; I2 = 31%), and three (6 studies, 417 participants: MD -0.05 mg/dL, 95% CI -0.19 to 0.10; I2 = 68%) compared to control.Serious adverse events occurred in four patients receiving remote ischaemic preconditioning by iliac clamping. It is uncertain whether remote ischaemic preconditioning by cuff inflation leads to increased adverse effects compared to control because the certainty of the evidence is low (15 studies, 3993 participants: RR 3.47, 95% CI 0.55 to 21.76; I2 = 0%); only two of 15 studies reported any adverse effects (6/1999 in the remote ischaemic preconditioning group and 1/1994 in the control group), the remaining 13 studies stated no adverse effects were observed in either group.Compared to control, remote ischaemic preconditioning made little or no difference to the need for dialysis (13 studies, 2417 participants: RR 0.85, 95% CI 0.37 to 1.94; I2 = 60%; moderate quality evidence), length of hospital stay (8 studies, 920 participants: MD 0.17 days, 95% CI -0.46 to 0.80; I2 = 49%, high quality evidence), or all-cause mortality (24 studies, 4931 participants: RR 0.86, 95% CI 0.54 to 1.37; I2 = 0%, high quality evidence).Remote ischaemic preconditioning may have slightly improved the incidence of acute kidney injury using either the AKIN (8 studies, 2364 participants: RR 0.76, 95% CI 0.57 to 1.00; I2 = 61%, high quality evidence) or RIFLE criteria (3 studies, 1586 participants: RR 0.91, 95% CI 0.75 to 1.12; I2 = 0%, moderate quality evidence). Remote ischaemic preconditioning by cuff inflation appears to be a safe method, and probably leads to little or no difference in serum creatinine, adverse effects, need for dialysis, length of hospital stay, death and in the incidence of acute kidney injury. Overall we had moderate-high certainty evidence however the available data does not confirm the efficacy of remote ischaemic preconditioning in reducing renal ischaemia reperfusion injury in patients undergoing major cardiac and vascular surgery in which renal ischaemia reperfusion injury may occur.


Can the Veterans Affairs health care system continue to care for the poor and vulnerable?
Can the Veterans Affairs (VA) health care system, long an important part of the safety net for disabled and poor veterans, survive the loss of World War II veterans--once its largest constituency and still its most important advocates? A recent shift in emphasis from acute hospital-based care to care of chronic illness in outpatient settings, as well as changes in eligibility allowing many more nonpoor and nondisabled veterans into the VA system, will be key determinants of long-term survivability. Although allowing less needy veterans into the system runs the risk of diluting services to those most in need, the long-run effect may be to increase support among a larger and younger group of veterans, thereby enhancing political clout and ensuring survivability. It may be that the best way to maintain the safety net for veterans is to continue to cast it more widely.


Surface Electromyography Thresholds as a Measure for Performance Fatigability During Incremental Cycling in Patients With Neuromuscular Disorders.
In healthy persons, there is an excellent relation between the timing of the (two) surface electromyography (sEMG) thresholds and the (two) ventilatory thresholds during exercise. The primary aim of this study was to determine the relative timing of both sEMG and ventilatory thresholds in patients with neuromuscular disorders compared with healthy subjects during a maximal ergospirometry cycling test. We hypothesized that in patients with neuromuscular disorders, the sEMG thresholds would occur relatively earlier in time than the ventilatory thresholds, compared to healthy subjects, because performance fatigability occurs more rapidly. In total, 24 healthy controls and 32 patients with a neuromuscular disorder performed a cardiopulmonary exercise test on a bicycle using a 10-min ramp protocol, during which we collected ergospirometry data: power at both ventilatory and sEMG thresholds, and sEMG data of lower leg muscles. In line with our hypothesis, normalized values for all thresholds were lower for patients than healthy subjects. These differences were significant for the first ventilatory (p = 0.008) and sEMG threshold (p < 0.001) but not for the second sEMG (p = 0.053) and ventilatory threshold (p = 0.238). Most parameters for test-retest reliability of all thresholds did not show any fixed bias, except for the second ventilatory threshold. The feasibility of the sEMG thresholds was lower than the ventilatory thresholds, particularly of the first sEMG threshold. As expected, the sEMG thresholds, particularly the first threshold, occurred relatively earlier in time than the ventilatory thresholds in patients compared with healthy subjects. A possible explanation could be (a combination of) a difference in fiber type composition, disuse, and limited muscle-specific force in patients with neuromuscular disorders. sEMG measurements during submaximal dynamic exercises are needed to generalize the measurements to daily life activities for future use in prescribing and evaluating rehabilitation interventions.


Acute myeloid leukemia: novel mutations and their clinical implications.
Acute myeloid leukemia (AML) is a heterogenous and challenging hematological malignancy with suboptimal outcomes. The implications of advanced technologies in the genetic characterization of AML have enhanced the understanding of individualized patient risk, which has also led to the development of new therapeutic strategies. A comprehensive study of novel mutations is essential to moderate the complicacies in patient management and achieve optimal outcomes in AML. In this review, we summarized the clinical relevance of important novel mutations, including TET2, ETV6, SATB1, EZH2, PTPN11, and U2AF1, which impact the prognosis of AML. TET2 mutation can lead to DNA hypermethylation, and gene fusion, and mutation in ETV6 disrupts hematopoietic transcription machinery, SATB1 downregulation aggravates the disease, and EZH2 mutation confers resistance to chemotherapy. PTPN11 mutation influences the RAS-MAPK signaling pathway, and U2AF1 alters the splicing of downstream mRNA. The systemic influence of these mutations has adverse consequences. Therefore, extensive research on novel mutations and their mechanism of action in the pathogenesis of AML is vital. This study lays out the perspective of expanding the apprehension about AML and novel drug targets. The combination of advanced genetic techniques, risk stratification, ongoing improvements, and innovations in treatment strategy will undoubtedly lead to improved survival outcomes in AML.


Upconversion emission of BaTiO3:Er3+ nanocrystals: influence of temperature and surrounding medium.
Here, we report the role of crystallite size and surrounding medium on the upconversion emission of Er3+ in BaTiO3 oxide nanocrystals. The samples were prepared by sol-emulsion-gel method and heat-treated at two different temperatures yielding powders containing nanoparticles of different sizes. Green (550 nm) and red (660 nm) upconversion emission were observed at room temperature from the 4S3/2 and 4F9/2 levels of BaTiO3:Er3+ nanocrystals. The pump power dependence study confirms that all these upconversion emission lines are a two-photon absorption process. We observed that the luminescence lifetime is shorter for the sample containing smaller particles. Optical thermometry experiments were performed in air, water and glycerol in a temperature range from 27.1 up to 47.1 degrees C aiming to use this material as a biological temperature sensor.


Physiological aspects of seed recalcitrance: a case study on the tree Aesculus hippocastanum.
Recalcitrant seeds are typical of some tropical and subtropical trees. Their post-shedding life activity proceeds in humid air and wet litter. They are desiccation sensitive and, for this reason, have a short life span and need some special procedures for cryopreservation. This review is devoted to the post-shedding life strategy of recalcitrant seeds, which includes the maintenance of high hydration status, metabolic readiness and ability to rapidly germinate before desiccation-induced damage exerts a lethal effect. The main physiological aspects of recalcitrant seeds are considered starting from mature seeds, followed during dormancy if occurs and resulting in germination. The collected data embrace the metabolic processes in embryonic axes and whole seeds. The up-to-date results are integrated covering the main metabolic processes, namely water status and transport, protein and carbohydrate metabolism, antioxidant defense, axis-cotyledon relations, hormonal control and germination. Among the representatives of various taxa, the seeds of which exhibit recalcitrance, attention was given to horse chestnut seeds as one of most studied recalcitrants.


Phenotypic heterogeneity can enhance rare-cell survival in 'stress-sensitive' yeast populations.
Individual cells within isogenic microbial cultures exhibit phenotypic heterogeneity, an issue that is attracting intense interest. Heterogeneity could confer benefits, in generating variant subpopulations that may be better equipped to persist during perturbation. We tested this hypothesis by comparing the survival of wild-type Saccharomyces cerevisiae with that of mutants which are considered stress-sensitive but which, we demonstrate, also have increased heterogeneity. The mutants (e.g. vma3, ctr1, sod1) exhibited the anticipated sensitivities to intermediate doses of nickel, copper, alkaline pH, menadione or paraquat. However, enhanced heterogeneity meant that the resistances of individual mutant cells spanned a broad range, and at high stress occasional-cell survival in most of these populations overtook that of the wild type. Green fluorescent protein (GFP) reporter studies showed that this heterogeneity-dependent advantage was not related to perturbation of buffered gene expression. Deletion strain screens combined with other approaches revealed that vacuolar alkalinization resulting from loss of Vma-dependent vacuolar H(+)-ATPase activity was not the cause of vma mutants' net stress sensitivities. An alternative Vma-dependent resistance mechanism was found to suppress an influence of variable vacuolar pH on the metal resistances of individual wild-type cells. In addition to revealing new mechanisms of heterogeneity generation, the results demonstrate experimentally a benefit under adverse conditions that arises specifically from heterogeneity, and in populations conventionally considered to be disadvantaged.


Vibrational Circular Dichroism Absolute Configuration of 9,12-Cyclomulin-13-ol, a Diterpene from Azorella and Laretia Species.
The absolute configuration of the diterpenoid 9,12-cyclomulin-13-ol (1), a constituent of Azorella and Laretia species, has been established by vibrational circular dichroism spectroscopy in combination with density functional theory calculations. The obtained normal diterpene absolute configuration confirms that of azorellanol (2), which was determined by single crystal X-ray diffraction.


Natural-abundance isotope ratio mass spectrometry as a means of evaluating carbon redistribution during glucose-citrate cofermentation by Lactococcus lactis.
The cometabolism of citrate and glucose by growing Lactococcus lactis ssp. lactis bv. diacetylactis was studied using a natural-abundance stable isotope technique. By a judicious choice of substrates differing slightly in their 13C/12C ratios, the simultaneous metabolism of citrate and glucose to a range of compounds was analysed. These end-products include lactate, acetate, formate, diacetyl and acetoin. All these products have pyruvate as a common intermediate. With the objective of estimating the degree to which glucose and citrate metabolism through pyruvate may be differentially regulated, the delta13C values of the products accumulated over a wide range of concentrations of citrate and glucose were compared. It was found that, whereas the relative accumulation of different products responds to both the substrate concentration and the ratio between the substrates, the delta13C values of the products primarily reflect the availability of the two substrates over the entire range examined. It can be concluded that in actively growing L. lactis the maintenance of pyruvate homeostasis takes precedence over the redox status of the cells as a regulatory factor.


Influence of genetic factors (HLA class II genes, insulin-gene region polymorphisms) and metabolic control on the development of diabetic nephropathy.
Both metabolic and genetic factors may contribute to the etiology of diabetic nephropathy. We selected 2 different groups of Type I diabetic patients in an attempt to evaluate both factors. HbA1c values and urinary albumin excretion were examined in 114 selected Type I diabetes patients with disease duration of more than 15 yr. We found signs of late renal complications in 28% of these patients. A clear difference in blood glucose control appeared between the 2 groups; the mean HbA1c value during the last 3 yr was 9.5% in the group with microalbuminuria or nephropathy, compared to 8.5% in the normoalbuminuric group (p < 0.0001). With the aim of studying genetic markers alone, we selected a group of 30 Type I diabetes patients with microalbuminuria and a control group of patients without microalbuminuria, but with very similar blood glucose control (e.g. similar mean 1 yr HbA1c values), age and disease duration. All individuals in both patient groups were genomically typed for HLA-DR, -DQ genes and insulin-gene region (INS) polymorphisms. We found no association between HLA class II alleles and microalbuminuria. Neither did we find any association with particular INS polymorphisms. This data indicates that neither genes in the HLA nor in the insulin region are of importance for development of diabetic microalbuminuria. However, all 11 patients with overt nephropathy carried a given INS polymorphism, suggesting an influence of this region for progression to overt nephropathy.


Completion of colorectal cancer screening in women attending screening mammography.
The American Cancer Society (ACS) and the United States Preventive Services Task Force (USPSTF) recommend colorectal cancer (CRC) screening to begin at age 50 in individuals at average risk for CRC. To estimate rate at which women eligible for CRC screening at the time of screening mammography attendance later completed in CRC screening, we retrospectively evaluated CRC screening utilization in women who underwent screening mammography at our institution. We retrospectively identified 3357 women between the ages of 50 to 75 who received screening mammography in 1998 at a single academic medical center using the institution's Radiology Information System (RIS). Additional information collected from the institution's Health System Data Warehouse and the Radiology department's mammography quality assurance data included mammography results, Breast Imaging Reporting and Database System (BI-RADS) classification of mammography findings, recommendation for screening mammography follow-up, insurance status, and CRC screening utilization after screening mammography. After excluding women who were current with CRC screening at the time of mammography, we determined the proportion of eligible women who completed CRC screening after mammography. Age, insurance type, BI-RADS code, and recommendation code were evaluated as potential predictors of CRC screening completion in eligible women. Of the 3357 women between the ages of 50 and 75 who received screening mammography in 1998, only 414 (12.3%) were current with CRC screening at the time of screening mammography. Of the remaining 2943 women who were eligible for CRC screening at the time of screening mammography, 142 (4.8%) subsequently completed CRC screening. Average time to completion of CRC screening after screening mammography is 35.4 months (range, 0.27-64.9). Managed care insurance was the only significant predictor of CRC screening completion after screening mammography in eligible women after adjusting for other variables (adjusted OR 1.73, 95% CI 1.21-2.47, P < .0001). Neither BI-RADS classification nor postmammography recommendations were significantly associated with CRC screening completion. Prevalence studies have demonstrated that women who were compliant with screening mammography were more compliant with CRC screening. Our data suggest that despite this increased compliance, overall incidence of CRC screening is low in the screening mammography population.


Reverse Radial Forearm Flap to Provide Arterial Inflow to a Toe Transfer.
Background: Toe-to-thumb transfer has become the gold standard for thumb reconstruction, but in badly mutilated hands, additional soft tissue coverage may be required or a suitable recipient artery may not be available. There are only 3 case reports describing the successful use of a reverse radial forearm flap for coverage of a soft tissue defect around the thumb as well as providing arterial inflow for a toe transfer, performed either simultaneously or secondarily. Methods: A single surgeon's experience of all toe-to-hand transfers performed in conjunction with a reverse radial forearm flap between 1995 and 2014 was reviewed, including patient demographics, type of toe transfer and vascular pedicle, whether immediate or secondary, follow-up, and complications. Results: Eight toe-to-hand transfers were performed in 7 patients-3 children (age range, 3-15 years) and 4 adults (age range, 19-39 years). Three patients underwent primary toe-to-thumb transfer simultaneously with a reverse radial forearm flap, and 5 patients underwent secondary toe-to-hand transfer between 4 months and 2½ years after an initial reverse radial forearm flap. All toe transfers survived completely. Average follow-up was 5.1 years. All patients were satisfied with the function and appearance of their reconstructed thumb. Conclusion: The reverse radial forearm flap is a very reliable procedure as a "Sister" or "Siamese" flap to provide immediate arterial inflow to a simultaneous toe-to-thumb transfer, or to provide primary soft tissue coverage on the radial aspect of the hand and subsequently provide a recipient arterial inflow for a secondary toe transfer.


Electron transfer-initiated Diels-Alder cycloadditions of 2'-hydroxychalcones.
An efficient approach to cyclohexenyl chalcones employing highly electron rich 2'-hydroxychalcone dienophiles via electron transfer-initiated Diels-Alder cycloaddition is described. Using the methodology, the total synthesis of nicolaiodesin C has been accomplished.


Nanoparticles in Medicine: Selected Observations and Experimental Caveats.
Medically useful nanoparticles measure 1-100 nm in at least one dimension and are engineered and manufactured for specific diagnostic and treatment applications. Most nanoparticles used currently used in medicine are engineered and manufactured for specific purposes. Medically significant nanoparticles are composed of a 1) central core that is usually the medically active component, 2) one or more layers of organic or inorganic materials that forms a capsule (corona) covering the core and 3) an outer surface layer that interacts with the environment and/or targeted cells and tissues. Effective nanoparticle function in the living, intact animal or human requires electrochemical stability necessary to bypass the reticuloendothelial system (RES) and avoid filtration through the renal glomerulus into the urine. Nanoparticles are present in "natural" as well as the manufacturing and clinical environments thus could pose as significant toxins because of their small sizes, their chemical and drug content and potential effect of causing long term disease including allergies, chronic inflammation and cancer. Currently published studies have focused on the effects of nanoparticles on cells in the extremely artificial environments of cell cultures. More clinical and preclinical studies documenting the short term and long term effects nanoparticle in the intact experimental animal and human are needed.


Anthropometry of Brazilian Air Force pilots.
Anthropometric data are essential for the design of military equipment including sizing of aircraft cockpits and personal gear. Currently, there are no anthropometric databases specific to Brazilian military personnel. The aim of this study was to create a Brazilian anthropometric database of Air Force pilots. The methods, protocols, descriptions, definitions, landmarks, tools and measurements procedures followed the instructions outlined in Measurer's Handbook: US Army and Marine Corps Anthropometric Surveys, 2010-2011 - NATICK/TR-11/017. The participants were measured countrywide, in all five Brazilian Geographical Regions. Thirty-nine anthropometric measurements related to cockpit design were selected. The results of 2133 males and 206 females aged 16-52 years constitute a set of basic data for cockpit design, space arrangement issues and adjustments, protective gear and equipment design, as well as for digital human modelling. Another important implication is that this study can be considered a starting point for reducing gender bias in women's career as pilots. Practitioner Summary: This paper describes the first large-scale anthropometric survey of the Brazilian Air Force pilots and the development of the related database. This study provides critical data for improving aircraft cockpit design for ergonomics and comprehensive pilot accommodation, protective gear and uniform design, as well as digital human modelling.


[Two cases of mediastinitis as a complication of odontogenic infection and tonsillitis].
We experienced two cases of descending necrotizing mediastinitis with different etiology. Case 1: A 59-year-old woman presented with chief complaints of dyspnea and swallowing disturbance. She had been diagnosed as having tonsillitis one week before. She was very pyrexic, and laboratory examination indicated acute inflammation. Chest X-ray and CT-scan showed enlargement of the mediastinum and pleural effusion. We diagnosed the mediastinitis to be a complication of tonsillitis. Case 2: A 54-year-old man had a tooth extracted 3 weeks prior to admission. His chief complaints were craniomandibular disturbance and neck swelling. Laboratory examination disclosed multiple organ failure and DIC. Chest X-ray and CT-scan showed enlargement of the mediastinum and pleural effusion. We diagnosed the mediastinitis in this case to be a consequence of an odontogenic infection following tooth extraction. Both patients received continuous drainage and irrigation of the abscesses and recovered in about 2 months. Case 1 showed an impaired glucose tolerance after recovery from mediastinitis. Although the main causes of mediastinitis are cardiac surgery and esophageal perforation, our cases demonstrate that mediastinitis may occur as a complication of deep neck infection.


Successful pregnancy and follow-up after in vitro fertilization of a kidney transplant patient with systemic lupus erythematosus, primary biliary cholangitis, and hypothyroidism.
This report describes the case of a female kidney transplant patient with systemic lupus erythematosus, primary biliary cholangitis, and postsurgical hypothyroidism due to Grave's disease who had a healthy newborn after in vitro fertilization (IVF). Cases of successful pregnancy involving women who underwent IVF after kidney transplantation have been reported. Normal and stable renal function, adequate immunosuppressant therapy, and well-managed blood pressure are requirements to be eligible for IVF and pregnancy. Primary biliary cholangitis without cirrhosis does not seem to worsen during pregnancy and IVF must be individualized in patients with systemic lupus erythematosus. There are no similar case reports involving kidney transplant patients or individuals with autoimmune disorders, so the decision to perform IVF had to be individualized in order to avoid complications for the mother and fetus.


Thin film bulk acoustic wave filter.
Thin film bulk acoustic wave (BAW) resonators (FBAR) are fabricated on a silicon nitride bridge using a ZnO piezolayer on a glass substrate and surface micromachining by standard thin film technology. These resonators exhibit a coupling constant k(t)2 = 7.8% at the first thickness extensional wave mode and are used as impedance elements in a ladder filter in the 1-GHz frequency band of mobile telecommunications. An electrical equivalent circuit is used to characterize the properties of the resonators and to show how the performance of the filter depends on the parameters of the resonators. 2.5% bandwidth, 2.8-dB insertion loss, and 35-dB selectivity are obtained in a filter with six resonators. The technology can be used to manufacture miniature microwave filters without any additional inductances.


[Antioxidant activity of blood plasma of mountain Altai's aborigines Russian and Kazakh nationality of low and medium height altitude areas].
Due to the points about dependence antioxidant activity of organism of human on a nationality, climatic conditions, quality of nutrition are scanty under study a estimate antioxidant activity of blood plasma of Altai's low and medium height altitude aborigines. As a result there has been discovered a dependence of antioxidant activity of blood plasma more upon age and at least geographical and climatic conditions, sex and quality of nutrition.


Redundancy of human ATG4 protease isoforms in autophagy and LC3/GABARAP processing revealed in cells.
Macroautophagy/autophagy is a cellular degradation pathway that delivers cytoplasmic material to lysosomes via double-membrane organelles called autophagosomes. Lipidation of ubiquitin-like LC3/GABARAP proteins on the autophagosome membrane is important for autophagy. The cysteine protease ATG4 executes 2 LC3/GABARAP processing events: priming of newly synthesized pro-LC3/GABARAP to enable subsequent lipidation, and delipidation/deconjugation of lipidated LC3/GABARAP (the exact purpose of which is unclear in mammals). Four ATG4 isoforms (ATG4A to ATG4D) exist in mammals; however, the functional redundancy of these proteins in cells is poorly understood. Here we show that human HAP1 and HeLa cells lacking ATG4B exhibit a severe but incomplete defect in LC3/GABARAP processing and autophagy. By further genetic depletion of ATG4 isoforms using CRISPR-Cas9 and siRNA we uncover that ATG4A, ATG4C and ATGD all contribute to residual priming activity, which is sufficient to enable lipidation of endogenous GABARAPL1 on autophagic structures. We also demonstrate that expressing high levels of pre-primed LC3B in ATG4-deficient cells can rescue a defect in autophagic degradation of the cargo receptor SQSTM1/p62, suggesting that delipidation by human ATG4 is not essential for autophagosome formation and fusion with lysosomes. Overall, our study provides a comprehensive characterization of ATG4 isoform function during autophagy in human cells. Abbreviations: Atg: autophagy-related; baf A1: bafilomycin A1; CASP3: caspase 3; CLEM: correlative light and electron microscopy; CMV: cytomegalovirus; CRISPR: clustered regularly interspaced short palindromic repeats; DKO: double knockout; EGFP: enhanced green fluorescent protein; GABARAP: GABA type A receptor-associated protein; GABARAPL1: GABA type A receptor-associated protein like 1; GABARAPL2: GABA type A receptor-associated protein like 2; GFP: green fluorescent protein; HB: homogenization buffer; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LIR: LC3 interacting region; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MFN2: mitofusin 2; N.A.: numerical aperture; NEM: N-ethylmaleimide; PDHA1: pyruvate dehydrogenase E1 alpha 1 subunit; PLD: phospholipase D; PE: phosphatidylethanolamine; RLUC: Renilla luciferase; SQSTM1: sequestosome 1; TEM: transmission electron microscopy; TKO: triple knockout; ULK1: unc-51 like autophagy activating kinase 1; VCL: vinculin; WT: wild-type.


[Lived experience and management of the every-day life after lower-limb amputation caused by vascular diseases].
A lower limb amputation seriously restricts people's lives. Suddenly, they lose a crucial part of their body and their usual mobility. The main reason of lower-limb amputation is diabetes mellitus. People living with a chronic illness have to face permanent uncertainty. There is little knowledge about the experience of living with a chronic illness, and suffering from a lower-limb amputation. This study examines how people with a lower-limb amputation caused by vascular diseases experience and manage their every-day life. Grounded Theory approach has been used to examine the research question. Qualitative interviews have been conducted with nine amputees, and data analysis has been done by using the method of Grounded Theory as well. As a result of an amputation, people have to cope with severe loss: the loss of a part of their body with consequences on their body image, the loss of mobility, a following dependency on means such as wheelchairs and prostheses, and the loss of the ability to manage daily activities. In order to be able to manage their daily activities again, amputees need to regain their mobility. At the same time, this regained mobility enables them to perform activities of individual importance within their disability. The results of this study help to understand the challenge of every-day live after a lower limb amputation caused by vascular diseases, which should serve for a basis of support for these people.


Optogenetic Approaches to Restoring Vision.
Severe loss of photoreceptor cells in inherited or acquired retinal degenerative diseases can result in partial loss of sight or complete blindness. The optogenetic strategy for restoration of vision utilizes optogenetic tools to convert surviving inner retinal neurons into photosensitive cells; thus, light sensitivity is imparted to the retina after the death of photoreceptor cells. Proof-of-concept studies, especially those using microbial rhodopsins, have demonstrated restoration of light responses in surviving retinal neurons and visually guided behaviors in animal models. Significant progress has also been made in improving microbial rhodopsin-based optogenetic tools, developing virus-mediated gene delivery, and targeting specific retinal neurons and subcellular compartments of retinal ganglion cells. In this article, we review the current status of the field and outline further directions and challenges to the advancement of this strategy toward clinical application and improvement in the outcomes of restored vision.


Detection of antibodies to Candida albicans germ tube as a possible aid in diagnosing systemic candidiasis in bone marrow transplant patients.
Indirect immunofluorescence assays to detect antibodies to Candida albicans blastospore and germ tube were performed in sera of 29 bone marrow transplant patients. Antibodies to germ tube were present in the sera of six patients, in four of whom a Candida albicans infection was highly probable, while in the other two patients it was not possible to determine the previous course. No healthy blood donors had these antibodies. On the other hand, detection of antibodies to Candida albicans blastospore showed low specificity in the diagnosis of systemic candidiasis. These preliminary findings suggest that the detection of antibodies to Candida albicans germ tube may be an important aid in the diagnosis of systemic candidiasis in bone marrow transplant patients.


Discontinuous low-dose flutamide-metformin plus an oral or a transdermal contraceptive in patients with hyperinsulinaemic hyperandrogenism: normalizing effects on CRP, TNF-alpha and the neutrophil/lymphocyte ratio.
Low-dose flutamide-metformin (Flu-Met) with an oral contraceptive is a therapeutic option for women with hyperinsulinaemic hyperandrogenism. We questioned (i) whether Flu-Met maintains efficacy if given discontinuously; (ii) how the efficacy of discontinuous Flu-Met plus a transdermal contraceptive compares with Flu-Met plus oral contraceptive; and (iii) whether these treatments also lower circulating C-reactive protein (CRP) and tumour necrosis factor alpha (TNF-alpha) and the high neutrophil/lymphocyte ratio. Non-obese, young patients (n = 31) with hyperinsulinaemic hyperandrogenism were started on Flu-Met (21/28 days) and randomized to receive in addition either a drospirenone oral contraceptive or a transdermal contraceptive for 6 months. The effects of Flu-Met were similar whether combined with oral or transdermal contraceptive. In both groups, CRP and TNF-alpha levels fell and the high neutrophil/lymphocyte ratio normalized (P < 0.001). Lean body mass increased (P < 0.001) in both groups but, in contrast to earlier experience with continuous Flu-Met, fat mass failed to decrease in either group. Flu-Met seems less lipolytic, if given for only 21 days in every 28-day period. The efficacy of Flu-Met is comparable when combined with an oral contraceptive or a transdermal contraceptive. The range of Flu-Met effects may henceforth include lower levels of CRP and TNF-alpha, and a normalization of the neutrophil/lymphocyte ratio.


[Study of cognitive function and brain volume in type 2 diabetic patients].
To investigate the differences of cognitive function and brain volume between patients with type 2 diabetes mellitus (DM) and healthy controls. Multi-dimensional neuropsychological tests were employed to evaluated cognitive function in 21 type 2 DM patients and 19 healthy controls, and voxel-based morphometry method was applied to measure volume of whole and regional gray matter in brain of these subjects. Compared to healthy controls [(7.3 +/- 1.4), (22.7 +/- 1.2), (9.5 +/- 2.5) respectively], significantly impaired performance of Auditory Verbal Learning Test (AVLT)-Delay Recall, [(5.7 +/- 1.8)] AVLT-Recognition [(20.8 +/- 2.6)] and Clock Drawing Test (CDT) [(8.0 +/- 1.1)] and extensive atrophy of gray matter (after corrected by total intracranial volume) were observed in type 2 DM patients (P < 0.05). In addition, whole gray matter/Total Intracranial Volume (TIV) was significantly negatively correlated with BMI (r = -0.352, P = 0.013). And negative correlations existed between whole gray matter vs HbA1c (r = -0.309, P = 0.026); the performance of AVLT-Delay Recall and AVLT-Recognition vs BMI (r = -0.398, P = 0.011; r = -0.4, P = 0.011)and HbA1c (r = -0.354, P = 0.025; r = -0.323, P = 0.042) and CDT vs HbA1c (r = -0.322, P = 0.043). Multi-cognitive impairment was associated with the reduced volume of whole and regional gray matter in brain of type 2 DM patients, which indicated that "accelerated brain ageing" might present in type 2 DM patients.


The two faces of avoidance: Time-frequency correlates of motivational disposition in blood phobia.
Contrary to other phobias, individuals with blood phobia do not show a clear-cut withdrawal disposition from the feared stimulus. The study of response inhibition provides insights into reduced action disposition in blood phobia. Twenty individuals with and 20 without blood phobia completed an emotional go/no-go task including phobia-related pictures, as well as phobia-unrelated unpleasant, neutral, and pleasant stimuli. Behavioral results did not indicate a phobia-specific reduced action disposition in the phobic group. Time-frequency decomposition of event-related EEG data showed a reduction of right prefrontal activity, as indexed by an increase in alpha power (200 ms), for no-go mutilation trials in the phobic group but not in controls. Moreover, theta power (300 ms) increased specifically for phobia-related pictures in individuals with, but not without, blood phobia, irrespective of go or no-go trial types. Passive avoidance of phobia-related stimuli subtended by the increased alpha in the right prefrontal cortex, associated with increased emotional salience indexed by theta synchronization, represents a possible neurophysiological correlate of the conflicting motivational response in blood phobia. Through the novel use of time-frequency decomposition in an emotional go/no-go task, the present study contributed to clarifying the neurophysiological correlates of the overlapping motivational tendencies in blood phobia.


Evaluation of the hematologic system as a marker of subclinical inflammation in hyperemesis gravidarum: a case control study.
Current evidence suggests that subclinical inflammation plays a significant role in the development of hyperemesis gravidarum (HEG). Simple hematological markers, such as mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), have been shown to reflect inflammatory burden and disease activity in several disorders. This study aimed to determine the diagnostic value of these hematological parameters for HEG. A total of 54 HEG patients and 58 age- and gestational-age-matched control subjects were studied. NLR, MPV, PLR, platelet distribution width (PDW), and red cell distribution width (RDW) values in all patients were calculated and recorded from complete blood cell counts. For HEG patients, the median NLR was 3.2 (1.6-7.1), and the median PLR was 143.7 (78.1-334.6); for control subjects, the values were 2.1 (1.0-4.7) and 93.1 (47.3-194.7), respectively. Although both the NLR and PLR of HEG patients were found to be significantly higher than in the controls, no significant difference was found between the study groups in terms of MPV, RDW, or PDW. Correlation analysis revealed a significant correlation between NLR and CRP (r = 0.872, p < 0.001). Our results show that peripheral blood NLR and PLR values can reflect inflammatory burden in HEG patients and can be used as markers for HEG.


A Health Literate Approach to Address Health Disparities: a Virtual Program for Parents of Children with Sickle Cell Trait.
Approximately 8% of African Americans born annually have sickle cell trait (SCT), a public health concern that may contribute to health disparities if individuals with SCT do not know it and lack access to understandable information about reproductive implications. Pre-pandemic, Ohio offered in-person SCT education for parents of SCT-affected children but many did not attend. Those with limited health literacy (HL) were less likely to achieve high knowledge. We used a HL-focused evaluation of this education to develop a virtual program (SCTaware) to communicate clear, actionable information and promote knowledge retention. Seven English-speaking parents, three with limited HL, were recruited in 2019 for in-person session videotaping and SCT knowledge assessments. Clinicians, HL experts, educators, genetic counselors, and parent stakeholders (evaluators) reviewed sessions, assessments, and accompanying visuals. Evaluators: observed parents asked few questions; noted undefined technical terms, closed questions, key concept omission, and limited explanation of visuals scoring low for understandability, actionability, and clarity; and developed SCTaware for individual videoconference delivery (knowledge objectives; plain language guide; HL-informed communication strategies; new visuals scoring highly for understandability, actionability, and clarity; narrated post-education version; standardized educator training). Using a HL-focused evaluation, our diverse team created a promising virtual SCT education program addressing a common issue affecting populations at risk for disparities. Given virtual education will likely continue post-pandemic and limited HL is common, this approach may be essential and replicable for other public health education programs, especially those transitioning to virtual formats, to convey clear, actionable information and promote health equity.


Injectable Poly-L-Lactic Acid: Understanding Its Use in the Current Era.
A survey of Sculptra® Aesthetic injectors was conducted to understand how the product is being currently reconstituted and injected. Questions were asked of injectors to understand their reasons for choice and volume of diluent(s), additions, and time for the reconstitution process. These results are discussed in the context of the past history of the product over the last decade, with a focus on adverse events such as papules and nodules.

 J Drugs Dermatol. 2016;15(6):759-762.


Estimation of bilirubin using BiliChektrade mark, a transcutaneous bilirubin measurement device: Effects of gestational age and use of phototherapy.
Heel puncture to obtain bilirubin measurements is painful for infants and distressing for parents. Transcutaneous bilirubin measurement using BiliChek (Respironics, USA) is easily performed in any setting. Reliable transcutaneous testing should decrease the number of painful procedures in otherwise well infants, reduce the volume of phlebotomy losses in ill newborns, and reduce the need for hospital or specialized clinic visits after discharge. To correlate bilirubin measurements using the transcutaneous device BiliChek with 'gold standard' serum measurements in well term infants, and in ill term and preterm infants admitted to the authors' neonatal intensive care unit. The study consisted of two phases. In phase 1, informed consent was obtained from mothers of 99 healthy, full-term infants not receiving phototherapy to perform both serum and transcutaneous bilirubin measurements at the time of heel puncture for routine neonatal screening. In phase 2, 56 infants in the neonatal intensive care unit had a total of 99 transcutaneous readings performed at the time serum bilirubin measurements were ordered for clinical reasons by the attending staff. The operators of the transcutaneous device, who were unaware of the serum bilirubin levels, performed readings within 1 h of the heel puncture. Using a Bland-Altman comparison in the well term infants, the transcutaneous measurements were -32.2 mumol/L to +31.2 mumol/L (1.96 SD); however, 79 (79.8%) of the transcutaneous measurements were within 15 mumol/L of the serum measurements. The variation in preterm infants was greater at -69.6 mumol/L to +62.0 mumol/L, and only 49 (49.5%) were within 15 mumol/L. For infants receiving phototherapy, the variation was -76.3 mumol/L to +49.5 mumol/L, but improved to -40.4 mumol/L to +31.0 mumol/L if an area of skin was patched for testing, approximating the group not receiving phototherapy. Transcutaneous bilirubin measurements obtained with the BiliChek instrument were accurate for measuring bilirubin levels in term jaundiced infants not receiving phototherapy and in those receiving phototherapy if an area of skin was patched. The instrument was not as sensitive in the small sample of preterm infants, and a larger study is required before recommending the use of this instrument in this population.


Cytokines and soluble receptors of the interleukin-1 family in Schnitzler syndrome.
Schnitzler syndrome (SchS) is an autoinflammatory disorder characterized by chronic urticaria, fever, and monoclonal gammopathy. The success of interleukin-1 (IL-1) blocking therapies suggests a crucial role for IL-1 in disease induction. The aim of this study is to perform a comprehensive analysis of IL-1 family cytokines and soluble receptors in a group of SchS patients. Three patients fulfilling the criteria for the diagnosis of SchS were recruited; 80 blood donors formed the control group. IL-1 family cytokines (IL-1α, IL-1β, IL-33, IL-18), soluble receptors (sIL-1R1, sIL-1R2, sIL-1R3, sIL-1R4), and antagonists [IL-1Ra, IL-18 binding protein (IL-18BP)] were measured by a multiarray enzyme-linked immunosorbent assay. Free IL-18 was calculated as the amount of IL-18 not inhibited by IL-18BP. Cytokine levels were compared by the Mann-Whitney test. IL-18 and free IL-18 were increased in patients compared with controls (p = 0.005 and p = 0.0082, respectively), while IL-18BP levels were not different. IL-1α, IL-1β, and IL-33 were undetectable in both patients and controls. The soluble receptors sIL-1R1, sIL-1R2, and ST2/sIL-1R4, and the IL-1 antagonist IL-1Ra were all within normal ranges; sIL-1R3 was significantly lower in patients than in controls (p = 0.039). The data indicate that SchS is characterized by increased circulating levels of free IL-18, possibly leading to a higher activation of innate/inflammatory effector cells. At variance with other inflammatory diseases, the lack of increase in sIL-1R1 and sIL-1R2 and the decreased levels of sIL-R3 imply a failure in the counterbalancing mechanism aimed at inhibiting excessive IL-1β in tissues.


Quantification of phytoplankton bloom dynamics by citizen scientists in urban and peri-urban environments.
Freshwater ecosystems are severely threatened by urban development and agricultural intensification. Increased occurrence of algal blooms is a main issue, and the identification of local dynamics and drivers is hampered by a lack of field data. In this study, data from 13 cities (250 water bodies) were used to examine the capacity of trained community members to assess elevated phytoplankton densities in urban and peri-urban freshwater ecosystems. Coincident nutrient concentrations and land use observations were used to examine possible drivers of algal blooms. Measurements made by participants showed a good relationship to standard laboratory measurements of phytoplankton density, in particular in pond and lake ecosystems. Links between high phytoplankton density and nutrients (mainly phosphate) were observed. Microscale observations of pollution sources and catchment scale estimates of land cover both influenced the occurrence of algal blooms. The acquisition of environmental data by committed and trained community members represents a major opportunity to support agency monitoring programmes and to complement field campaigns in the study of catchment dynamics.


When things don't talk: knowledge and belief in the inter-war humanism of Charles Singer (1876-1960).
The science historian Charles Singer might seem to have shared with positivists a widely held commitment to observation as the foundation of knowledge. Yet in fact Singer's historiography was peculiarly unconcerned with instruments, models and other artefacts. Such tools might have been expected to present crucial empirical evidence for the historical arguments and ideal material for the didactics which pioneers such as Singer associated with their mission of a 'scientific humanism'. In their hands, physical things did not translate into epistemic things. This was deliberate. Yet while the configuration of science history which would distance it from material objects seems to speak of a shift from the visual to texts, the ocular technologies deployed in Singer's histories rather point to a co-existence of different kinds of visuality in that period's scholarship. As the academic and the museological aspects of science history pulled apart, the visuality of the museum came to be complemented by texts that vitally relied on images. The function of such images was to create proximity with the cognitive desires around whose traffic these histories became paper theatres of knowing. In bypassing material theatres and crafting realities that he understood to be empirically undemonstrable, Singer purposefully developed the story of understanding nature not as entailing obedience to its established results, but instead as embodying an attitude of continuing enquiry.


Promoting evidence-based practice through anintegrated model ofcare: patient case studiesas a teaching method.
This paper intends to encourage debate on how evidence-based practice may be achieved through developing an integrated approach to teaching clinical practice skills by using case study as a teaching method. This is achieved by examining societal, social, and political changes as well as the changes that have occurred in nurse education over the past 15 years. What evidence-based nursing is, the processes required to practice it effectively and how case study as a teaching method can support these processes are described. Finally, the paper describes how, as educationalists involved in curriculum development, the introduction of an integrated approach to teaching clinical skills may be a way forward in resolving the concerns highlighted by the recent Department of Health (DoH) publications.


Correlation between static radiographic measurements and intersegmental angular measurements during gait using a multisegment foot model.
Radiographic examination is a widely used evaluation method in the orthopedic clinic. However, conventional radiography alone does not reflect the dynamic changes between foot and ankle segments during gait. Multiple 3-dimensional multisegment foot models (3D MFMs) have been introduced to evaluate intersegmental motion of the foot. In this study, we evaluated the correlation between static radiographic indices and intersegmental foot motion indices. One hundred twenty-five females were tested. Static radiographs of full-leg and anteroposterior (AP) and lateral foot views were performed. For hindfoot evaluation, we measured the AP tibiotalar angle (TiTA), talar tilt (TT), calcaneal pitch, lateral tibiocalcaneal angle, and lateral talcocalcaneal angle. For the midfoot segment, naviculocuboid overlap and talonavicular coverage angle were calculated. AP and lateral talo-first metatarsal angles and metatarsal stacking angle (MSA) were measured to assess the forefoot. Hallux valgus angle (HVA) and hallux interphalangeal angle were measured. In gait analysis by 3D MFM, intersegmental angle (ISA) measurements of each segment (hallux, forefoot, hindfoot, arch) were recorded. ISAs at midstance phase were most highly correlated with radiography. Significant correlations were observed between ISA measurements using MFM and static radiographic measurements in the same segment. In the hindfoot, coronal plane ISA was correlated with AP TiTA (P < .001) and TT (P = .018). In the hallux, HVA was strongly correlated with transverse ISA of the hallux (P < .001). The segmental foot motion indices at midstance phase during gait measured by 3D MFM gait analysis were correlated with the conventional radiographic indices. The observed correlation between MFM measurements at midstance phase during gait and static radiographic measurements supports the fundamental basis for the use of MFM in analysis of dynamic motion of foot segment during gait.


Solid-state NMR meets electron diffraction: determination of crystalline polymorphs of small organic microcrystalline samples.
A combination of solid-state NMR (ssNMR) and electron diffraction (ED) has been used to determine the crystalline polymorphs in small-organic microcrystalline molecules. Although 13C cross-polarization magic angle spinning (CPMAS) is a widely used method for determining crystalline polymorphs, even in a mixture, it sometimes fails if the molecular conformations are similar. On the other hand, ED can, in principle, differentiate crystalline forms with different lattice parameters, even when they have very similar molecular conformations. However, its application is usually limited to inorganic molecules only. This is because the ED measurements of organic molecules are very challenging due to degradation of the sample by electron irradiation. We overcame these difficulties by the use of 1H double-quantum/single-quantum correlation experiments at very fast magic angle spinning, together with ED observations under mild electron irradiation. The experiments were demonstrated on L-histidine samples in L-histidine·HCl·H2O, orthorhombic L-histidine and monoclinic L-histidine.


Onset of arterial 'steal' following proximal angioaccess: immediate and delayed types.
Critical hand ischaemia following angioaccess is a potentially devastating complication and timely surgical repair is necessary to prevent permanent sequelae. However, the duration of the post-operative surveillance needed to exclude its occurrence has not been determined. A retrospective review conducted over a 10-year period revealed 28 patients with critical hand ischaemia following access and surgical repair. The initial access that resulted in the limb-threatening 'steal' included 10 autologous brachiocephalic arteriovenous (AV) fistulae and 18 AV bridge grafts. The two groups of patients, those with autologous AV fistulae and those with AV bridge grafts, were compared regarding the time elapsed from the initial access to the correction procedure, the systolic pressure index between the two forearms and the existence of tissue loss. There was a highly significant difference in the time elapsed from the creation of the initial access to the revision procedure among the two groups, the median time being 2 days in the AV graft group and 165 days in the autologous group (P < 0.00001). The method of treatment was the distal revascularization-interval ligation (DRIL) procedure in the majority of patients (23 of 28), with immediate relief of ischaemic symptoms in all and a mid-term 1 year patency of 69%. Severe steal develops immediately following AV bridge grafting and patients should be closely monitored during the first 24 h; surveillance is not indicated beyond 1 month. In contrast, steal following formation of proximal autogenous fistulae may be either of immediate or of 'late' onset, months or years after the creation of the fistulae, and lifelong monthly surveillance is recommended. Close monitoring is also recommended after any subsequent surgical or interventional correcting procedure for all access types. DRIL is the procedure of choice in limb-threatening severe steal.


Initial Displacement Does Not Affect Loss of Reduction After Lisfranc Fracture Dislocations.
We sought to determine whether significantly displaced Lisfranc injuries had a higher rate of loss of reduction after fixation compared to those with low displacement. Forty-five patients who had fixation of an acute Lisfranc injury from 2005 to 2014 were retrospectively reviewed. All patients underwent subsequent hardware removal at 3 to 15 months after their index procedure. Radiographs were reviewed from the time of injury, 2 weeks, and 6 months postoperative. Lisfranc joint reduction was assessed using criteria previously described in the literature and graded as malreduced if displacement was >2 mm. We used a cutoff of 4 mm for high initial displacement. Those patients with ≥4 mm of initial displacement did not have an increased rate of loss of reduction after hardware removal compared to those patients with <4 mm initial displacement (40% and 27%, respectively; P = .362). Anatomic reduction was achieved immediately postoperative in 89% of cases. A high degree of displacement in Lisfranc injuries does not preclude achievement and maintenance of adequate reduction after fixation of these injuries. Levels of Evidence: Prognostic study, Level II: Retrospective.


The Levels of DAHP Synthase, the First Enzyme of the Shikimate Pathway, Are Related to Free Aromatic Amino Acids and Glutamine Content in Nicotiana plumbaginifolia Cell Cultures.
Aromatic amino acid homeostasis was investigated in cell suspension cultures of Nicotiana plumbaginifolia and was related to the activity of the first enzyme in aromatic biosynthesis, 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) synthase. An inverse relationship was found between the intracellular content of free phenylalanine, tyrosine and tryptophan and enzyme specific activity levels, suggesting the occurrence of end-product control mechanisms. Two DAHP synthase isogenes are present in wild tobacco that showed a different expression pattern during the culture growth cycle. Intracellular levels of aromatic amino acids were increased or decreased by adding the culture medium with phenylalanine, tyrosine and tryptophan, or with sublethal doses of the shikimate pathway inhibitor glyphosate, respectively. As a consequence, enzyme levels varied in the opposite direction. The concomitant exogenous supply of glutamine further reduced enzyme activity in mid-log cells, suggesting induction by both aromatic amino acid depletion and nitrogen starvation.


[Stress and inflammatory bowell disease (I.B.D). Therapeutic strategies].
Clinical and animal studies indicate that stress can contribute to the onset and/or the worsening of the course of inflammatory bowel diseases (IBD). In a model (inmobilisation stress for 6 h.) in rats it has been demonstrated that stress increases colonic inflammatory damage, as well as antiinflammatory prostaglandins and of the nuclear receptor PPARgamma. This inflammation is followed by an increase in the permeability of the colonic mucosa barrier and a decrease in IgA levels. All these parameters contribute to the bacterial traslocation to other organs. PPARgamma agonists drugs prevent these inflammatory changes as well as the disfunction of the mucosal colonic barrier, which suggests its use in the worsening episodes of IBD produced by stress.


Junctional complexes and cell polarity in the urinary tubule.
In this review, we demonstrate how differentiated membrane domains can be detected in epithelial cells using conventional light and electron microscopy, freeze-fracture electron microscopy and the immuno- and cytochemical detection of membrane components. Using specific examples from the kidney, we show how the polarized insertion of these components into either apical or basolateral plasma membrane regions on either side of the tight junction barrier is related to specific functions of principal and intercalated cells in the collecting duct. In addition, distinct basal and lateral membrane domains have been revealed in some cells that are maintained in the absence of a tight junctional barrier in the plane of the membrane. This suggests that other factors, possibly related to cytoskeletal elements, may be involved in the functional segregation of these membrane areas. We propose that epithelial cell plasma membranes should be subdivided into apical, lateral and basal regions, and that the term "basolateral" may be an oversimplification.


Endoscopic ultrasound guided biliary and pancreatic duct interventions.
When endoscopic retrograde cholangio-pancreatography fails to decompress the pancreatic or biliary system, alternative interventions are required. In this situation, endosonography guided cholangio-pancreatography (ESCP), percutaneous radiological therapy or surgery can be considered. Small case series reporting the initial experience with ESCP have been superseded by comprehensive reports of large cohorts. Although these reports are predominantly retrospective, they demonstrate that endoscopic ultrasound (EUS) guided biliary and pancreatic interventions are associated with high levels of technical and clinical success. The procedural complication rates are lower than those seen with percutaneous therapy or surgery. This article describes and discusses data published in the last five years relating to EUS-guided biliary and pancreatic intervention.


Nonlinear absorbance amplification using a diffuse reflectance cell: total organic carbon monitoring at 214 nm.
We present an absorption spectrometric method using a polytetrafluoroethylene (PTFE) cell as a diffuse reflector. The system was used for monitoring ultrapure water. All compounds absorb to some degree at low UV wavelengths, and the absorption at 214 nm from a zinc lamp source was monitored using a charge-coupled device (CCD) spectrometer. The absorption was interpreted in terms of total organic carbon present. The cell acts as a nonlinear absorbance amplifier, improving both the limit of detection (LOD) and the dynamic range. Potassium hydrogen phthalate (KHP) and glucose were used to evaluate the system and provided respective LODs of 46.5 ng/L and 4.5 mg/L as carbon. Although the physical path length was 25 cm, a maximum effective path length of 280 cm was observed at the lowest tested KHP concentrations. The system is intended for real-time monitoring of ultrapure water.


Real-world cohort study of adult and pediatric patients treated for hereditary angioedema in the United States.
Background: There is limited real-world evidence on hereditary angioedema (HAE) patient characteristics and health-care resource utilization (HCRU); in addition, pediatric patients have been described in small cohorts. Objective: To describe patient characteristics, treatment patterns, and HCRU among adult and pediatric patients treated for HAE in a large U.S. cohort. Methods: This retrospective cohort study used an administrative claims data base (January 2006 to September 2015). Eligible patients with either ≥1 pharmacy claim for HAE-indicated therapies (C1 inhibitors, ecallantide, icatibant) or ≥2 medical claims with codes associated with HAE (per medical billing codes), and ≥1 claim for androgens, fresh frozen plasma, tranexamic acid, or ε-aminocaproic acid formed a "treated cohort." Three nonexclusive treated cohorts were assessed: overall, pediatric, and HCRU (≥2 years of continuous enrollment during 2010-2015). Results: Overall, 1429 patients received treatment (mean ± standard deviation [SD] age, 38.8 ±15.7 years; 62.4% female patients; mean ± SD Charlson Comorbidity Index of 1.4 ± 2.4). Common comorbidities were allergy or anaphylaxis (51.4%) and anxiety or depression (35.8%). Diagnoses indicative of HAE attacks included swelling and/or angioedema (78.5%), abdominal pain (55.6%), and asphyxiation (27.2%). Use of HAE-indicated medication rose between 2006 and 2015 to 81.8%, whereas androgen use declined (from 91.5% to 24.9%). Similar trends were observed in the pediatric treated cohort (n = 143). In the HCRU treated cohort (n = 538), HAE-related claims for emergency department and inpatient admissions were observed for 36.6% and 22.3% of patients, respectively. Conclusion: In a large U.S. cohort of adult and pediatric patients who received treatments indicated or used for HAE, common comorbidities and trends in resource use denoted the substantial burden of attacks, which reflected a continued need that recently approved long-term prophylactic treatments may help to address.


A meta-analysis of reflux genome-wide association studies in 6750 Northern Europeans from the general population.
Gastroesophageal reflux disease (GERD), the regurgitation of gastric acids often accompanied by heartburn, affects up to 20% of the general population. Genetic predisposition is suspected from twin and family studies but gene-hunting efforts have so far been scarce and no conclusive genome-wide study has been reported. We exploited data available from general population samples, and studied self-reported reflux symptoms in relation to genome-wide single nucleotide polymorphism (SNP) genotypes. We performed a GWAS meta-analysis of three independent population-based cohorts from Sweden, Finland, and UK. GERD cases (n=2247) and asymptomatic controls (n=4503) were identified using questionnaire-derived symptom data. Upon stringent quality controls, genotype data for more than 2.5M markers were used for association testing. Bioinformatic characterization of genomic regions associated with GERD included gene-set enrichment analysis (GSEA), in silico prediction of genetic risk effects on gene expression, and computational analysis of drug-induced gene expression signatures using Connectivity Map (cMap). We identified 30 GERD suggestive risk loci (P≤5×10-5 ), with concordant risk effects in all cohorts, and predicted functional effects on gene expression in relevant tissues. GSEA revealed involvement of GERD risk genes in biological processes associated with the regulation of ion channel and cell adhesion. From cMap analysis, omeprazole had significant effects on GERD risk gene expression, while antituberculosis and anti-inflammatory drugs scored highest among the repurposed compounds. We report a large-scale genetic study of GERD, and highlight genes and pathways that contribute to further our understanding of its pathogenesis and therapeutic opportunities.


Regional differences in adrenoceptor binding and fat cell lipolysis in obese, postmenopausal women.
In women there is an increase in visceral obesity, subcutaneous abdominal adipocyte lipolysis, and risk of cardiovascular disease (CVD) associated with weight gain after menopause. The mechanisms underlying this increase in adrenoreceptor (AR)-agonist catecholamine-stimulated lipolysis and abdominal obesity in postmenopausal women were studied in intact adipocytes isolated from the abdominal and gluteal subcutaneous fat depots in 19 obese (48% +/- 1% body fat, mean +/- SE) women with a mean +/- SE age of 58 +/- 1 years. The fat cell size and adipose tissue lipoprotein lipase (ATLPL) activity were similar in both sites. The maximal lipolytic responsiveness and sensitivity to isoproterenol were higher (P < .05) in abdominal compared with gluteal adipocytes, but maximal lipolytic response to a post-AR agent was similar. Abdominal adipocytes had a higher beta-AR ([3H]-CGP-12177) and alpha2-AR ([3H]-yohimbine) affinity than gluteal cells (P < .05), lower alpha2-AR density (P < .05), but similar beta-AR density as gluteal cells. Both abdominal and gluteal cell size correlated with alpha2-AR density (P < .01), but not with beta-AR density. Thus, a higher beta-AR affinity and lower alpha2-AR relative to beta-AR density may explain the higher in vitro catecholamine-mediated lipolysis in abdominal compared with gluteal adipocytes in obese, postmenopausal women.


From sedentary to active: Shifting the movement paradigm in workplaces.
Increased sedentary behavior and reduced physical activity are risk factors for morbidity and mortality. As adults spend a significant portion of their time at work where the default is to spend the majority of the day sitting, shifting workplace norms to decrease sedentary time and increase active time could have a public health impact. Workplaces offer a unique setting for multi-level interventions that can reach diverse populations. Traditional worksite wellness initiatives have produced equivocal results in terms of increasing physical activity. One reason for this may be the focus on corporate-fitness type programs and health education with little change in workplace culture. More innovative approaches combining theory-based worksite wellness components with behavioral economics approaches promoting incidental physical activity at the workplace to make activity the default may be necessary. This article discusses strategies to shift the workplace paradigm from being sedentary to more active using a range of approaches.


Anthropometric survey of high-altitude Bolivian porters.
This paper presents the results of an anthropometric survey of 138 rural Aymaran high-altitude males who were working as porters in La Paz, Bolivia (3700 m). All subjects were measured for stature, weight, upper arm circumference, and triceps skinfolds. The body size and composition of the porters were then compared to an Aymaran rural population from the Bolivian highlands, and urban mestizo labourers from La Paz. The porters were smaller than the urban sample, but appeared to be generally representative of rural Aymaran natives with respect to body size and composition, and nutritional status. It is suggested that towards one extreme of nutritional variability, some degree of undernutrition may be indicated, which should be considered in future studies of adaptation to hypoxia among these Andean highlanders.


The Effect of Teriparatide Treatment on the Risk of Fragility Fractures in Postmenopausal Women with Osteoporosis: Results from the Asian and Latin America Fracture Observational Study (ALAFOS).
The Asian and Latin America Fracture Observational Study (ALAFOS) is a prospective, observational, single-arm study conducted in 20 countries across Asia, Latin America and the Middle East. ALAFOS evaluated new clinical vertebral and non-vertebral fragility fractures in relation to time on teriparatide, in postmenopausal women with osteoporosis in real-life clinical practice. Clinical fragility fractures, back pain, and health-related quality of life (HRQoL) were recorded in 6-month intervals for ≤ 24 months during teriparatide treatment and up to 12-months post-treatment. Data were analysed with piecewise exponential regression with inverse probability weighting for time to event outcomes and mixed-model repeated measures for back pain and HRQoL. 3054 postmenopausal women started teriparatide and attended ≥ one follow-up visit (mean [SD] age 72.5 [10.4] years). The median (95% CI) time to treatment discontinuation was 22.0 months (21.2, 22.8). During the treatment period, 111 patients (3.6%) sustained 126 clinical fractures (2.98 fractures/100 patient-years). Rates of new clinical fragility fractures were significantly decreased during the > 6-12, > 12-18, and > 18-24-month periods, as compared with the first 6 months of treatment (hazard ratio [HR] 0.57; 95% CI 0.37, 0.88; p = 0.012; HR 0.35; 95% CI 0.19, 0.62; p < 0.001; HR 0.43; 95% CI 0.23, 0.83; p = 0.011; respectively). Patients also reported an improvement in back pain and HRQoL (p < 0.001). These results provide data on the real-world effectiveness of teriparatide in the ALAFOS regions and are consistent with other studies showing reduction of fractures after 6 months of teriparatide treatment. These results should be interpreted in the context of the noncontrolled design of this observational study.


Recombinant Spider Silk: Promises and Bottlenecks.
Spider silk threads have exceptional mechanical properties such as toughness, elasticity and low density, which reach maximum values compared to other fibre materials. They are superior even compared to Kevlar and steel. These extraordinary properties stem from long length and specific protein structures. Spider silk proteins can consist of more than 20,000 amino acids. Polypeptide stretches account for more than 90% of the whole protein, and these domains can be repeated more than a hundred times. Each repeat unit has a specific function resulting in the final properties of the silk. These properties make them attractive for innovative material development for medical or technical products as well as cosmetics. However, with livestock breeding of spiders it is not possible to reach high volumes of silk due to the cannibalistic behaviour of these animals. In order to obtain spider silk proteins (spidroins) on a large scale, recombinant production is attempted in various expression systems such as plants, bacteria, yeasts, insects, silkworms, mammalian cells and animals. For viable large-scale production, cost-effective and efficient production systems are needed. This review describes the different types of spider silk, their proteins and structures and discusses the production of these difficult-to-express proteins in different host organisms with an emphasis on plant systems.


Quantitative EEG Correlates of Outcome in Older Psychiatric Patients: Part I: Cross-Sectional and Longitudinal Assessment of Patients With Dementia.
Using quantitative electroencephalographic coherence (a measure of synchronized electrical activity between brain regions) the authors examined heterogeneity in clinical presentation and outcome inpatients with dementia. Patients (N = 114) with mild-to-moderate dementia of the Alzheimer's type (DAT) or multi-infarct dementia (MID) were examined for coherence from the left hemisphere. More than 70% diagnostic accuracy in distinguishing between DAT and MID subjects was achieved using coherence measures alone. Also, decreased coherence measured across the Rolandic fissure in the left hemisphere was significantly associated with poorer functional status of subjects at 2-year follow-up, despite similar levels of cognitive impairment at baseline. These findings suggest that coherence is a useful measure for assessment and for prediction of the course of illness inpatients with dementia.


[Not Available].
The rising cost of health and long term care for the elderly is a major issue in any discussion of the future of the welfare state. This article proposes a long term perspective on the historical relationship between medicine, social policy, and old people. What impact did the changing nature of old age have on the health system from the mid nineteenth century to the present? The thesis is posited that the health needs of the aging were rather neglected or even marginalized in the second half of the nineteenth century, whereas they slowly gained recognition and formed the very core of the modern welfare state since the 1950s. Evidence points up (1) the varying attention paid to geriatric subjects in the medical sciences, (2) the gradual inclusion of pensioners and poor old people in health insurance and social services, and (3) the radical change in the age and gender profile of hospital patients in the course of the twentieth century. From this overview emerges a tentative model of a transition in the allocation of medical services to the different age and sex groups. Like the demographic and the epidemiologic transition, these fundamental changes have created challenges for medicine and social policy which still await responses.