The importance of the AMPK gamma 1 subunit in metformin suppression of liver glucose production.
Metformin has been used to treat patients with type 2 diabetes for over 60 years, however, its mechanism of action is still not completely understood. Our previous reports showed that high-fat-diet (HFD)-fed mice with liver-specific knockout of both AMPK catalytic α1 and α2 subunits exhibited significantly higher fasting blood glucose levels and produced more glucose than floxed AMPK catalytic α1 and α2 mice after long-term metformin treatment, and that metformin promotes the formation of the functional AMPK αβγ heterotrimeric complex. We tested the importance of each regulatory γ subunit isoform to metformin action in this current study. We found that depletion of γ1, but not γ2 or γ3, drastically reduced metformin activation of AMPK. HFD-fed mice with depletion of the γ1 subunit are resistant to metformin suppression of liver glucose production. Furthermore, we determined the role of each regulatory cystathionine-β-synthase (CBS) domain in the γ1 subunit in metformin action and found that deletion of either CBS1 or CBS4 negated metformin's effect on AMPKα phosphorylation at T172 and suppression of glucose production in hepatocytes. Our data indicate that the γ1 subunit is required for metformin's control of glucose metabolism in hepatocytes. Furthermore, in humans and animal models, metformin treatment leads to the loss of body weight, we found that the decrease in body weight gain in mice treated with metformin is not directly attributable to increased energy expenditure.


[X-ray diffraction Fourier Pattern Analysis of the Chinese materia medica "shannai" (Kaempferia Galanga L.)].
Every Chinese materia medica consists of dozens of ingredients. It is a multiingredient system. X-ray diffraction provides a way to determine Chinese materia medica in diffraction space which can reflect the general structural characteristics of Chinese materia medica and quantitative changes of partial ingredients. Considering the influence of varieties, growing places, growing periods, collecting seasons and other phenological factors, we selected 6 samples of Kaempferia galanga L. and Kaempferia marginata Carey, collected in different seasons from different growing places for X-ray diffraction Fourier Pattern Analysis. We have obtained characteristic peaks and diffraction fuzzy figures for distinguishing purposes. The result shows that X-ray diffraction Fourier Pattern Analysis can be used for distinguishing Chinese materia medica with similar shape and properties, similar tissue texture or similar chemical composition.


Improving the Efficiency and Effectiveness of Parent Education in the Neonatal Intensive Care Unit.
March of Dimes partners with hospitals across the country to implement NICU Family Support (NFS) Core Curriculum, a program providing education to parents in neonatal intensive care units (NICUs) across the country. This NFS project's goal was to increase the efficiency and effectiveness of NICU parent education by establishing consistency, improving quality, and identifying best practices. A 5 topic curriculum was developed and implemented across NFS program sites. The project studied 4 main outcomes of interest related to efficiency and effectiveness: increase in parenting confidence, parent learning, knowledge change, and satisfaction. Data were collected from speakers and attendees immediately following educational sessions. Analytical approaches included descriptive statistics such as frequency, percentage, and response rate, and inferential approaches such as t test, χ, and analysis of variance. Findings suggest that the NFS Core Curriculum improved both program efficiency and effectiveness. Sessions fully implemented according to recommended strategies had better outcomes than sessions not fully implemented according to recommended strategies (P < .0001). Across the 3648 attendees at 41 sites, 77% of parents reported learning "a lot" at the session they attended and 85% of attendees reported increased confidence. Attendees also reported positive knowledge change and high satisfaction. Parent education best practices identified through this initiative can be utilized for future NFS Core Curriculum topics and potentially generalized to all NICU parent education and family education in other hospital intensive care units. Content and best practices identified through this project will require regular review to ensure medical accuracy and appropriateness of best practices as the physical design of NICUs evolves.


Dimethyladenosine Transferase 1 Homolog Promotes Human Gastric Carcinoma Cell Proliferation and Inhibits Apoptosis via the AKT Pathway.
Our previous work identified the dimethyladenosine transferase 1 homolog as a novel prognostic factor for detecting human gastric carcinoma with high sensitivity and specificity. The high expression of dimethyladenosine transferase 1 is closely associated with the occurrence and progression of gastric carcinoma. However, the underlying mechanism of dimethyladenosine transferase 1 for the occurrence and development of gastric carcinoma is not well elucidated yet. In our present study, the biological role of dimethyladenosine transferase 1 on cell proliferation, apoptosis, and cell cycle progression in human gastric carcinoma cells was investigated through in vitro and in vivo assays by the overexpression and knockdown of dimethyladenosine transferase 1 2-way authentication method. We found that the overexpression of dimethyladenosine transferase 1 significantly promotes cell proliferation (P < .001) and inhibition of cell apoptosis (P < .01) in SGC-7901 cells. However, the in vivo experiment results of the knockdown dimethyladenosine transferase 1 using small interfering RNAs in the MKN-45 are just the opposite. Reverse-transcriptase polymerase chain reaction and western blotting analysis revealed that overexpressed dimethyladenosine transferase 1 in SGC-7901 cells significantly activated the AKT pathway compared to control cells. In contrast, we found that apoptosis genes such as Caspase-3 and Caspase-9 were downregulated in those cells. The xenograft nude mice model exhibited increased tumor growth (P < .01) and weight loss (P < .01), with the overexpression of dimethyladenosine transferase 1 homolog in the SGC-7901 cells. These results have been further confirmed through backward verification in dimethyladenosine transferase 1 knockdown cells. Taken together, our results indicated that the dimethyladenosine transferase 1 plays a crucial role in stimulating cancer cell proliferation and contributes to apoptosis resistance in human gastric carcinoma. Meanwhile, it provides a potential therapeutic target for gastric carcinoma treatment and is worthy of further studies.


Dry coating of solid dosage forms: an overview of processes and applications.
Dry coating techniques enable manufacturing of coated solid dosage forms with no, or very limited, use of solvents. As a result, major drawbacks associated with both organic solvents and aqueous coating systems can be overcome, such as toxicological, environmental, and safety-related issues on the one hand as well as costly drying phases and impaired product stability on the other. The considerable advantages related to solventless coating has been prompting a strong research interest in this field of pharmaceutics. In the article, processes and applications relevant to techniques intended for dry coating are analyzed and reviewed. Based on the physical state of the coat-forming agents, liquid- and solid-based techniques are distinguished. The former include hot-melt coating and coating by photocuring, while the latter encompass press coating and powder coating. Moreover, solventless techniques, such as injection molding and three-dimensional printing by fused deposition modeling, which are not purposely conceived for coating, are also discussed in that they would open new perspectives in the manufacturing of coated-like dosage forms.


A multifunctional nanoparticle constructed with a detachable albumin outer shell and a redox-sensitive inner core for efficient siRNA delivery to hepatocellular carcinoma cells.
Successful delivery of small interfering RNA (siRNA) into the cytoplasm of target cells relies on biocompatible and efficient vectors. In this study, a novel multifunctional core/shell nanoparticle [CS-SS-9R/BSA-c(RGDyK)] was developed to effectively deliver siVEGF to hepatocellular carcinoma cells (Bel-7402 cells). To improve the gene payload and transfection efficiency, a positively charged inner core (CS-SS-9R) was constructed by grafting nona-arginine (9R) onto chitosan (CS) using disulphide bonds. The negatively charged outer shell [BSA-c(RGDyK)] assembled on the surface of the inner core by electrostatic forces that shielded high cationic charges and provided improved targeting. The protein outer shell gradually detached from the inner core in the acidic lysosomal environment, leaving the cationic inner core exposed in order to escape from lysosomes. The nanoparticles were capable of delivering siVEGF into Bel-7402 cells via integrin receptor-mediated endocytosis. Successful lysosomal escape of the inner core and the rapid release of siVEGF into the cytoplasm resulted in a 78.9% decrease in VEGF expression and 81.2% inhibition of tumour cell proliferation. In conclusion, this nanoparticle is responsive to the intracellular environment and accurately delivered siRNA into the cytoplasm, providing a safe and highly efficient gene delivery strategy for cancer therapy.


Prevalence, awareness, treatment, and control of hypertension in older people: results from the population-based KORA-age 1 study.
Hypertension remains a significant modifiable risk factor for cardiovascular diseases and a major determinant of morbidity and mortality. We aimed to describe sex-stratified age-standardized estimates of prevalence, awareness, treatment and control of hypertension, and their associated factors in older adults. The KORA-Age1 is a population-based cross-sectional survey carried out in 2008/2009 on individuals aged 65-94 years in Augsburg region, Germany. Blood pressure measurements were available for 1052 out of 1079 persons who participated in the physical examination. Factors associated with prevalence, awareness and control of hypertension were investigated by multivariable logistic regression. The overall prevalence of hypertension (≥140/90 mmHg) was 73.8% [95% confidence interval (CI), 69.3-77.9], representing 74.8% (95% CI, 68.4-80.2) in men and 73.5% (95% CI, 66.8-79.3) in women. Among those with hypertension, 80.2% (95% CI, 75.3-84.4) were aware of their hypertensive condition and 74.4% (95% CI, 69.2-79.1) were on treatment for hypertension. Among those aware of their hypertension status, 92.8% (95% CI, 88.8-95.6) were on treatment and 53.7% (95% CI, 47.0-60.1) had their blood pressure controlled. Hypertension was more frequent in individuals who were older, obese, or had diabetes. Higher education attainment or presence of comorbidities was associated with higher level of hypertension awareness. Individuals taking three antihypertensive drug classes were more likely to have controlled hypertension compared with those taking one antihypertensive drug class, odds ratio (OR), 1.85 (95% CI, 1.14-2.99). Our findings identified high prevalence of hypertension and relevant health gaps on awareness, treatment and suboptimal control of hypertension in older adults in Germany. Screening for hypertension should especially target older adults with low educational attainment and 'healthy' elderly with less contact to physicians.


Association of antibodies to the NR1 subunit of N-methyl-D-aspartate receptors with neuropsychiatric systemic lupus erythematosus.
To determine epitope reactivity of autoantibodies to N-methyl-D-aspartate (NMDA) receptor NR1 subunit and their association with neuropsychiatric systemic lupus erythematosus (NPSLE). Paired serum and CSF specimens were obtained from 41 patients with NPSLE (22 with diffuse psychiatric/neuropsychological syndromes [diffuse NPSLE] and 19 with neurologic syndromes or polyneuropathy [focal NPSLE]), 21 patients with various rheumatic diseases other than SLE (non-SLERD). Sera were also obtained from 27 SLE patients without neuropsychiatric manifestations (non-CNS SLE). Antibodies to murine NR1 (mNR1) or to 4 different preparations of synthetic 25-amino-acid (AA) peptides of human NR1 were measured by enzyme-linked immune sorbent assay (ELISA). Serum anti-mNR1 levels were significantly higher in NPSLE than in non-SLERD. Sera from NPSLE patients bound efficiently to the AA residues 19-44 from the N-terminus of NR1 (NR1-A) or 56-81 (NR1-C). Accordingly, serum anti-NR1-A and anti-NR1-C were also elevated in NPSLE compared with non-SLERD. Of note, anti-NR1-A as well as anti-NR1-C levels in CSF, but not in sera, were significantly elevated in diffuse NPSLE compared with focal NPSLE or with non-SLERD. These results suggest that autoantibodies to NMDA receptor NR1, especially to the AA residues 19-44 and 56-81 from the N-terminus play a pivotal role in the pathogenesis of diffuse NPSLE.


Role of cell cycle molecules in the pathophysiology of glomerular epithelial cells.
The postmitotic characteristics of podocytes are the basis for the structural assembly and central function (filtration) of the glomeruli. Persistent cell cycle quiescence is required for stability in these cells. In cells of the podocyte lineage, transdifferentiation from the metanephric mesenchyme to mature podocytes is closely associated with tight regulation of the expression of cell cycle molecules. This cell cycle control in podocytes acts as a safeguard for the glomeruli; however, deregulation of this system might result in structural deterioration. This article focuses on the expression of cell cycle molecules in podocyte differentiation and pathology.


Conjoint Analysis of Telemedicine Preferences for Hypertension Management Among Adult Patients.
Background: Telemedicine has been differentially utilized by different demographic groups during COVID-19, exacerbating inequities in health care. We conducted conjoint and latent class analyses to understand factors that shape patient preferences for hypertension management telemedicine appointments. Methods: We surveyed 320 adults, oversampling participants from households that earned <$50K per year (77.2%) and speak a language other than English at home (68.8%). We asked them to choose among 2 hypothetical appointments through 12 conjoint tasks measuring 6 attributes. Individual utilities for attributes were constructed using logit estimation, and latent classes were identified and compared by demographic and clinical characteristics. Results: Respondents preferred in-person visits (0.353, standard error [SE] = 0.039) and video appointments conducted through a secure patient portal (0.002, SE = 0.040). Respondents also preferred seeing a clinician with whom they have an established relationship (0.168, SE = 0.021). We found four latent classes: "in-person" (26.5% of participants) who strongly weighted in-person appointments, "cost conscious" (8.1%) who prioritized the lowest copay ($0 to $10), "expedited" (19.7%) who prioritized getting the earliest appointment possible (same/next day or at least within the next week), and "comprehensive" (45.6%) who had preferences for in-person care and telemedicine appointments through a secure portal, low copayments, and the ability to see a familiar clinician. Conclusions: Appointment preferences for hypertension management can be segmented into four groups that prioritize (1) in-person care, (2) low copayments, (3) expedited care, and (4) balanced preferences for in-person and telemedicine appointments. Evidence is needed to clarify whether aligning appointment offerings with patients' preferences can improve care quality, equity, and efficiency.


Deformability- and size-based microcapsule sorting.
Biomedical applications often require to sort cells according to their physical properties, such as size, density or deformability. In recent years, microfluidics has provided a variety of tools to sort micro-objects. We present here a simple microfluidic device consisting of a channel containing a semi-cylindrical obstacle against which capsules are squeezed by the flow, followed by a diverging chamber where streamlines separate. We demonstrate that this basic system is capable of sorting elastic microcapsules according to their size at low flow strength, and according to the stiffness of their membrane at high flow strength. Contrary to most existing sorting devices, we show that the present one is very sensitive and capable of discriminating between capsules with differences in membrane elasticity of order unity.


Pharmacokinetics, Safety, and Dosing of Novel Pediatric Levofloxacin Dispersible Tablets in Children with Multidrug-Resistant Tuberculosis Exposure.
This study characterized the pharmacokinetics of novel 100-mg levofloxacin dispersible tablets in 24 children aged <5 years who had household multidrug-resistant tuberculosus (MDR-TB) exposure. The current data were pooled with previously published data from children (n = 109) with MDR-TB receiving adult (250-mg) levofloxacin tablets, using nonlinear mixed-effects modelling. The adult tablets had 41% lower bioavailability than the novel dispersible tablets, resulting in much higher exposures with the dispersible tablets with the same dose.


The impact of anemia on quality of life in human immunodeficiency virus-infected patients.
Anemia is the most commonly encountered hematologic abnormality in human immunodeficiency virus (HIV)-positive patients, occurring with increasing frequency as the disease progresses. Several factors play a role in the development of anemia in patients with HIV, including chronic disease, opportunistic infections, and certain nutritional deficiencies. Despite the high prevalence of anemia in this population, the symptoms of anemia are frequently overlooked, although anemia can significantly affect a patient's ability to carry on even normal activities of daily living. Therefore, approaches--including the treatment of causative infections, discontinuation of certain drugs, or use of recombinant human erythropoietin (epoetin alfa)--aimed at increasing hemoglobin levels to normal or near-normal levels would be expected to improve quality of life (QOL). The purpose of this article is to describe the effects of anemia on QOL and to provide an overview of several studies showing that QOL improves with the alleviation of anemia.


Massive hematuria due to iliac artery-ureteral fistula. Case report.
Massive hematuria in a 73-year-old man, who 17 years previously had undergone aorto-iliac-femoral thrombendarterectomy, was found to originate from an iliac artery-ureteral fistula due to a false aneurysm. Fistula formation should be kept in mind when investigating such hematuria in patients with a history of vascular surgery in the iliac segment.


The efficacy of hydroxychloroquine in altering pregnancy outcome in women with antiphospholipid antibodies. Evidence and clinical judgment.
The use of low-dose aspirin and heparinoids has improved the pregnancy outcome in obstetric antiphospholipid syndrome (APS). However, current treatment fails in 20-30% of APS pregnancies, raising the need to explore other treatments to improve obstetrical outcome. Hydroxychloroquine (HCQ) is widely used in patients with autoimmune diseases, mainly systemic lupus erythematous (SLE), due to its anti-inflammatory, anti-aggregant and immune-regulatory properties. Evidence from in vitro and animal models suggests a potential protective effect of HCQ in obstetric APS. Pending the availability of prospective trials, we aimed to systematically review the available evidence and to assess the clinical judgment of a panel of experts regarding the use of HCQ in improving pregnancy outcome in women with antiphospholipid antibodies (aPL). Clinical data on the ability of HCQ to improve pregnancy outcome in women with aPL are very limited in the available literature. Only one cohort study evaluating maternal and fetal outcome of pregnancy in patients with SLE who were exposed to HCQ was identified. Four of 14 (29%) treated with HCQ patients had pregnancy failure, compared with six of 24 (25%) of patients not treated with HCQ. However, the effect of HCQ was not adjusted for the use of other medications such as aspirin, heparins or steroids. Selected experts were contacted by e-mail and asked to review the summary of the evidence provided by the working group and to briefly answer each of the proposed questions. Overall, the panel of experts agreed that adding HCQ could be considered in selected cases or after failure of standard treatment with aspirin and a heparin agent. Specifically, the majority of experts considered adding HCQ in specific scenarios, such as women with previous thrombosis (either arterial and/or venous), and/or with previous ischaemic placenta-mediated complications. Prospective studies are necessary before the use of HCQ during pregnancy in women with aPL should be routinely recommended for clinical practice.


Protective functions of salvianolic acid B in PC-12 cells against hydrogen peroxide-triggered damage by mediation of microRNA-26a.
Spinal cord injury (SCI) can lead to varying degrees of sensory and motor dysfunction. Salvianolic acid B (Sal-B) is the dominating bioactive constituent of Danshen, which has been reported to alleviate liver fibrosis and exert neuroprotective effects. But, the influence of Sal-B in SCI remains mysterious. The research planned to delve the protective function of Sal-B in hydrogen peroxide (H2O2)-caused PC-12 cell injury. H2O2-caused PC-12 cells injury model was built, CCK-8, Transwell and flow cytometry experiments were enforced to assess cell proliferation, migration and apoptosis. The microRNA (miR)-26a plasmid and the matching control were transfected into PC-12 cells, subsequently, the influence of miR-26a inhibition in H2O2-corrupted PC-12 cells was evaluated. The cell growth-correlated factors and PI3K/AKT and MEK/ERK pathways were assayed through western blot assay. Results corroborated that Sal-B eased H2O2-evoked injury in PC-12 cells. Ascended miR-26a was monitored in Sal-B and H2O2-exposed cells. MiR-26a inhibition annulled the protective action of Sal-B in H2O2-corrupted cells. The protective function of Sal-B was enabled through activating PI3K/AKT and MEK/ERK pathways. These findings delineated that Sal-B protected PC-12 cells against H2O2-caused injury through ascending miR-26a via initiating PI3K/AKT and MEK/ERK pathways. Highlights H2O2 causes PC-12 cell injury; Sal-B eases H2O2-caused PC-12 cell injury; Sal-B protects PC-12 cells against H2O2-caused injury via elevating miR-26a; Sal-B activates AKT and MEK/ERK pathways via modulating miR-26a.


Natural flavonoids as potential multifunctional agents in prevention of diabetic cataract.
Cataract is one of the earliest secondary complications of diabetes mellitus. The lens is a closed system with limited capability to repair or regenerate itself. Current evidence supports the view that cataractogenesis is a multifactorial process. Mechanisms related to glucose toxicity, namely oxidative stress, processes of non-enzymatic glycation and enhanced polyol pathway significantly contribute to the development of eye lens opacity under conditions of diabetes. There is an urgent need for inexpensive, non-surgical approaches to the treatment of cataract. Recently, considerable attention has been devoted to the search for phytochemical therapeutics. Several pharmacological actions of natural flavonoids may operate in the prevention of cataract since flavonoids are capable of affecting multiple mechanisms or etiological factors responsible for the development of diabetic cataract. In the present paper, natural flavonoids are reviewed as potential agents that could reduce the risk of cataract formation via affecting multiple pathways pertinent to eye lens opacification. In addition, the bioavailability of flavonoids for the lens is considered.


Genetics, cross-resistance and synergism of indoxacarb resistance in Helicoverpa armigera (Lepidoptera: Noctuidae).
The cotton bollworm Helicoverpa armigera is a global pest of field and horticultural crops and has developed resistance to insecticides from many chemical classes. Indoxacarb is an important option for selective control of H. armigera in a range of crops that play host to this species. A strain of H. armigera resistant to indoxacarb (designated GY7-39) was detected from the field by F2 screening and characterised by comparison with a near-isogenic indoxacarb-susceptible laboratory strain to determine inheritance, cross-resistance profile and synergism of indoxacarb resistance. The level of indoxacarb resistance in the GY7-39 strain was 139-198-fold compared with the susceptible strain. Genetic analysis showed that resistance was autosomal, incompletely dominant and conferred by one or a few closely linked loci. Indoxacarb resistance in the GY7-39 strain did not confer cross-resistance to chlorantraniliprole. The GY7-39 strain was more susceptible to emamectin benzoate, fenvalerate, Cry1Ac and Cry2Ab compared with the susceptible strain. Indoxacarb resistance was synergised by the metabolic inhibitor PBO. Rapid selection of indoxacarb resistance in the GY7-39 strain indicates the potential risk of resistance development to indoxacarb in field populations of H. armigera. Lack of cross-resistance indicates that resistance could be managed effectively by the use of rotational strategies that incorporate transgenic technologies. Synergism studies indicate the potential involvement of metabolic detoxification enzymes as the mechanism of resistance to indoxacarb. © 2016 Society of Chemical Industry.


Diagnostic Testing for Zika Virus: a Postoutbreak Update.
Since the emergence and dissemination of Zika virus (ZIKV) in late 2015, our understanding of the biology, transmission, clinical disease, and potential sequelae associated with infection has markedly expanded. Over the past 2 years, the number of diagnostic assays for ZIKV has increased from none in 2015 to 5 serological assays and 14 molecular assays in 2017, all with emergency use authorization granted through the U.S. Food and Drug Administration. Here we provide an update on ZIKV, addressing what we have collectively learned since the outbreak began, including a summary of currently available diagnostic assays for this virus.


Polyethylene thickness does not influence aseptic revision rate with highly cross-linked liners in THA with 36-mm femoral heads.
To reduce the risk of dislocation, larger head size can be used in total hip arthroplasty (THA). However, larger head size leads to thinner acetabular liners. With conventional polyethylene, thickness of >8 mm has been advocated to reduce stress and wear rate of the polyethylene. Modern polyethylene has become more wear-resistant. In this study, we investigated if the thickness of sequentially cross-linked polyethylene (XLPE) liners is associated with failure of THA in the medium term. 3654 THAs were included (2009-2016), in which THA was performed with a XLPE liner in combination with a 36-mm femoral head. Patient and surgical characteristics were collected. We compared implant survival of THA with thin liners (<7.9 mm) and thick liners (⩾7.9 mm) with a Kaplan Meier survival analysis at 5 years, median follow-up and 10 years of follow-up with and point aseptic loosening and performed a multivariate analysis to estimate hazard ratios (HR). Median follow-up was 7.7 years (IQR 5.6-9.8). In total, 179 revision procedures were performed, where 82 revisions (46%) were performed for aseptic loosening. The survival rate at 5 years, median and 10 years of follow-up showed no statistically significant difference in implant survival. The survival rate at 10 years follow-up was for thin liners 97.1% (95% CI, 96.3-97.9) and for thick liners 98.2% (95% CI, 97.4-99.0) in the aseptic loosening group (chi-square 2.55; p = 0.11).The adjusted HR for thick liners (⩾7.9 mm) was 0.65 (95% CI, 0.38-1.08) compared with the thin liners (<7.9 mm), which was not significantly different. From this single-centre retrospective study it appears that thinner polyethylene liners are well tolerated when using second-generation highly cross-linked polyethylene. Thickness of the XLPE liners did not influence the risk of aseptic loosening of the implants in the medium term.


A mental health survey of the Vietnamese refugee in Japan.
A mental health survey was conducted using the Cornell Medical Index (CMI) on Vietnamese refugees who have resettled in Japan. 64.5% of the females and 37.2% of the males displayed emotional disturbance. The refugees with life-threatening and/or concentration camp experience had significantly higher CMI scores than those without it (t test, P less than 0.05). CMI scores of the group residing in Japan for 4-5 years are markedly lower than the group residing there for 2-3 years (F test, P less than 0.05).


Knee effusion-synovitis volume measurement and effects of vitamin D supplementation in patients with knee osteoarthritis.
To develop a measure of knee joint effusion-synovitis volume and to examine the effect of vitamin D supplementation on effusion-synovitis in people with knee osteoarthritis (OA) and low vitamin D levels over 24 months. Symptomatic knee OA patients with low 25-(OH)D levels (12.5-60 nmol/l) were recruited for a multi-centre, randomised, placebo-controlled and double-blind trial. Participants (age 63 ± 7 years, 208 females) were allocated to either 50,000 IU monthly vitamin D3 (n = 209) or placebo (n = 204) for 24 months. Knee effusion-synovitis volume in suprapatellar and other regions was measured on magnetic resonance imaging (MRI) using OsiriX software. The intra-class correlation coefficients (ICCs) were used to test inter- and intra-rater reliabilities. The least significant change criterion was used to define the increase/decrease in effusion-synovitis volume. The reproducibilities of effusion-synovitis volume measurement were high with ICCs ranging from 0.93 to 0.99. Over 24 months, effusion-synovitis volume remained stable in the vitamin D group but increased in placebos with a significant between-group difference (-1.94 ml, 95% confidence interval (CI): -3.54, -0.33). This effect was evident in those with baseline effusion-synovitis and with suprapatellar effusion-synovitis. The proportion with an increase in effusion-synovitis volume was lower in the vitamin D group than placebo (risk ratio (RR): 0.87, 95% CI: 0.77, 0.97). This highly reproducible effusion-synovitis volume measurement could be a promising outcome measure in OA trials. Vitamin D supplementation could retard the progression of effusion-synovitis which can potentially benefit people with an inflammatory OA phenotype.


Advances in percutaneous electrode systems.
In the past eight years, developing a percutaneous electrode system has advanced to a successful, yet simple, method to transmit electrical signals, overcoming the serious problems of excessive mechanical irritation at the skin interface. Experience with over 50-74% in the clinical applications of 1) chronic pain relief; 2) contracture correction; and 3) sensory feedback.


Outcomes of Pediatric Osteogenesis Imperfecta Patients Requiring Port-a-Cath Placement for Long-Term Vascular Access.
Intravenous (iv) bisphosphonates are widely used to treat the skeletal manifestations of osteogenesis imperfecta (OI). Obtaining peripheral iv access in pediatric patients with OI is often difficult and traumatic. Although this may be mitigated with surgically placed iv ports (port-a-caths), surgeons may be hesitant to perform this procedure on these children because of the lack of safety data. This study aims to gain better insight into the safety and efficacy of port-a-cath use in this population and identify risk factors for port-a-cath complications. In the present study, we conducted a retrospective cohort analysis of patient characteristics and the incidence of port-a-cath-related complications in children with OI. Fifty-three port-a-caths were placed in 29 children (21 males and 8 females). Of the 29 patients, most are OI type III (n = 18), followed by type I (n = 4), type IV (n = 4), and type V (n = 3). At the time of initial port-a-cath placement, the median age was 52 months (10-191 months), and the median weight was 7.9 kg (5.1-41.1 kg). Most patients (n = 20) weighed less than 10 kg during initial placement. Weight correlated significantly with OI type (p = 0.048), sex (p = 0.03), and vessel used (p = 0.02). Median initial port-a-cath longevity was 43 months (1-113 months), and we found no significant difference in port-a-cath longevity between sexes, OI types, or vessels used. Most patients (n = 19) required multiple port-a-cath placements. There is a significant difference (p = 0.02) between the number of placements and OI type, with type IV having more than type III. Port-a-cath removal was almost always due to mechanical complications (n = 19) but also for infection (n = 1) and malposition (n = 1). Eight patients still had their initial port-a-caths in place at the conclusion of this study. These findings indicate that complications associated with port-a-cath placement are mild and can be used to safely deliver iv bisphosphonates to pediatric OI patients. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.


Decrease in pH strongly enhances binding of native, proteolyzed, lipolyzed, and oxidized low density lipoprotein particles to human aortic proteoglycans.
Binding of low density lipoprotein (LDL) to proteoglycans and modification of LDL are key processes in atherogenesis. Recently, it has been demonstrated that during atherogenesis the extracellular pH of atherosclerotic lesions decreases. We have examined the effect of the decreased pH on the binding of LDL to human aortic proteoglycans. The binding of native, oxidized, proteolyzed (alpha-chymotrypsin-treated), or lipolyzed (sphingomyelinase- or phospholipase A(2)-treated) LDL particles to proteoglycans were measured in microtiter well assays at pH 5.5-7.5. We found that the lower the pH, the higher the amount of binding of LDL to proteoglycans. At the lowest pH tested (pH 5.5), the amounts of proteoglycan-bound native, proteolyzed, sphingomyelinase-, and phospholipase A(2)-treated LDL were 20-, 23-, 30-, and 37-fold higher, respectively, than at pH 7.5. Interestingly, although oxidized LDL failed to bind to proteoglycans at neutral pH, there was significant binding at acidic pH. Binding of native and modified LDL to proteoglycans at pH 5.5 was blocked by 1 m NaCl, indicating that at neutral pH LDL binds to proteoglycans via ionic interactions. Inhibition of this binding by acetylation and cyclohexanedione treatment of LDL showed that the positively charged amino acids of apolipoprotein B-100, lysine, and arginine, respectively, mediated the ionic interaction. Taken together, our results suggest that in areas of atherosclerotic arterial intima where the extracellular pH decreases, retention of LDL by proteoglycans is enhanced, leading to extracellular accumulation of LDL and progression of the disease.


Cancer-related coagulopathy (Trousseau's syndrome): review of the literature and experience of a single center of internal medicine.
Venous thromboembolism (VTE) occurs roughly in one out of five cancer patients and is the second cause of death in this population. When all cancer patients are considered together, a sevenfold increased risk for VTE has been calculated. Over the last 20 years, a number of risk factors have been recognized. These have been used in several risk assessment models aimed at identifying high-risk patients who are therefore candidates for thromboprophylaxis. An easily applicable and reliable risk score is based on the cancer site, hemoglobin levels, pre-chemotherapy platelet and leukocyte counts as well as body mass index. The additional measurement of two biomarkers, namely D-dimer and soluble P-selectin, may improve estimates of the cumulative VTE probability. A variable incidence of VTE has been determined in patients with specific types of malignancy, with the highest odds in those with pancreatic cancer followed by head and neck tumors. In terms of histotype, the risk of VTE is significantly higher in patients with adenocarcinoma than in those with squamous cell carcinoma and in patients with high-grade versus low-grade tumors. Cancer therapy may also be responsible for VTE; specifically, the presence of an indwelling central venous catheter, immunomodulatory drugs such as thalidomide and lenalidomide, monoclonal antibodies, such as bevacizumab, erythropoiesis-stimulating agents and hormonal therapy with tamoxifen place patients at higher risk. The pathogenesis of cancer-related VTE is poorly understood but is likely to be multifactorial. "Virchow's triad," comprising stasis consequent to a decreased blood flow rate, an enhanced blood clotting tendency such as accompanies inflammation and growth factor expression, and structural modifications in blood vessel walls, is thought to play a central role in the induction of VTE. The prophylaxis and treatment of VTE are based on well-established drugs such as vitamin K antagonists and unfractionated and low-molecular-weight heparins as well as on an expanding group of new oral anticoagulants, including fondaparinux, rivaroxaban, apixaban and dabigatran. Furthermore, aspirin has been shown to prevent arterial thrombosis and to reduce the rate of major vascular events. Guidelines for the general management of VTE in cancer patients and in those with an indwelling central venous catheter have been recently developed with the aim of selecting the most rational therapeutic approach for each clinical situation. The main features of VTE based on our own observations of 92 cancer patients and 159 patients with non-neoplastic disease are briefly described herein.


Comparison of postoperative phacoemulsification results in dogs with and without diabetes mellitus: 153 cases (1991-1992).
Data were collected from the medical records of 123 nondiabetic dogs (182 eyes) and 30 diabetic dogs (57 eyes) in which phacoemulsification surgery was performed. Pre- and postoperative comparisons, including signalment, initial ophthalmic examination findings, surgical variables, and postoperative findings for the short-term follow-up period (mean, 5.75 weeks), between nondiabetic and diabetic dogs revealed that the complication rate was not greater in the diabetic group. Postoperative uveitis was evident with nearly equal frequency (in nondiabetic dogs, 90% or 164 of 182 eyes and in diabetic dogs, 88% or 50 of 57 eyes). In nondiabetic dogs, 1% prednisolone ophthalmic solution and prednisone were administered pre- and postoperatively, and amoxicillin and dichlorphenamide postoperatively. In diabetic dogs, the same treatment regimen, except for treatment with flunixin meglumine IV at surgery and substitution of aspirin for prednisone, was used. When nondiabetic and diabetic dogs were treated according to their respective pre- and postoperative medical regimens, clinical differences in postoperative findings were not apparent.


Formation and modulation of multi-pulse femtosecond laser-induced periodic surface structures by electromagnetic and partial differential equation simulations.
In order to demonstrate the formation of laser-induced periodic surface structures (LIPSS), simulations were performed to investigate the effect of multiple femtosecond laser pulses with different laser energy densities on a Ti6Al4V surface. In this work, a set of partial differential equations calculating the electron and lattice temperature variations, followed by coupling with an electric field, is used to analyze the evolution of the periodic surface structure induced by the interaction of the femtosecond laser with the material. As the number of pulses increases, the surface structure of the material changes from none to produce LIPSS structure and from low spatial frequency LIPSS (LSFL) structure to high spatial frequency LIPSS (HSFL) structure. In order to compare the results, single-point laser scanning ablation experiments were carried out at femtosecond laser energy. The experimental results are consistent with the simulation results.


Evaluation of Sensor Technology to Detect Fall Risk and Prevent Falls in Acute Care.
Sensor technology that dynamically identifies hospitalized patients' fall risk and detects and alerts nurses of high-risk patients' early exits out of bed has potential for reducing fall rates and preventing patient harm. During Phase 1 (August 2014-January 2015) of a previously reported performance improvement project, an innovative depth sensor was evaluated on two inpatient medical units to study fall characteristics. In Phase 2 (April 2015-January 2016), a combined depth and bed sensor system designed to assign patient fall probability, detect patient bed exits, and subsequently prevent falls was evaluated. Fall detection depth sensors remained in place on two medicine units; bed sensors used to detect patient bed exits were added on only one of the medicine units. Fall rates and fall with injury rates were evaluated on both units. During Phase 2, the designated evaluation unit had 14 falls, for a fall rate of 2.22 per 1,000 patient-days-a 54.1% reduction compared with the Phase 1 fall rate. The difference in rates from Phase 1 to Phase 2 was statistically significant (z = 2.20; p = 0.0297). The comparison medicine unit had 30 falls-a fall rate of 4.69 per 1,000 patient-days, representing a 57.9% increase as compared with Phase 1. A fall detection sensor system affords a level of surveillance that standard fall alert systems do not have. Fall prevention remains a complex issue, but sensor technology is a viable fall prevention option.


Locating the central sulcus: comparison of MR anatomic and magnetoencephalographic functional methods.
To compare MR anatomic and magnetoencephalographic (MEG) functional methods in locating the central sulcus. Eleven healthy subjects and five patients with focal cerebral lesions were studied. The central sulcus was located anatomically with MR by two independent observers using axial vertex and sagittal (midline and lateral) images. Locations via the MEG functional method were based on detecting the somatosensory-evoked magnetic fields elicited by painless tactile stimuli. The axial method yielded the most consistent interrater results, with complete agreement in 76% of sections in both control subjects and patients. The intermethod discordance of the sagittal midline and lateral methods was 32% in control subjects and 33% in patients. The concordance of MR and MEG methods ranged from 55% to 84% in control subjects and 65% to 67% in patients. MR anatomic techniques can usually identify the central sulcus, but in the presence of anatomic distortion, the MEG functional method adds significant information.


Bortezomib-mediated down-regulation of telomerase and disruption of telomere homeostasis contributes to apoptosis of malignant cells.
Bortezomib inhibits the ubiquitin/proteasome pathway to achieve its anti-cancer effect and its well characterized activity is the NF-κB inhibition through which the anti-apoptotic bcl-2 expression is down-regulated and apoptosis is subsequently induced. However, the downstream molecular targets of bortezomib are still incompletely defined. Because telomere stabilization via activation of telomerase, induction of telomerase reverse transcriptase (hTERT) and appropriate expression of shelterin proteins is essential to cancer development and progression, we investigated the effect of bortezomib on telomere homeostasis/function in malignant cells. The bortezomib treatment of leukemic (HEL) and gastric cancer cells (BGC-823) led to significant inhibition of hTERT and telomerase expression, widespread dysregulation of shelterin protein expression, and telomere shortening, thereby triggering telomere dysfunction and DNA damage. hTERT over-expression attenuated bortezomib-induced telomere shortening, abnormal shelterin expression and telomere dysfunction. Importantly, bortezomib-mediated apoptosis of malignant cells was partially prevented by hTERT over-expression. Mechanistically, hTERT first robustly enhances bcl2 expression and maintains significantly high residual levels of bcl2 even in bortezomib-treated HEL cells. Second, hTERT protects against bortezomib-induced DNA damage. Our findings collectively reveal a profound impact of bortezomib on telomere homeostasis/function. Down-regulation of hTERT expression and telomere dysfunction induced by bortezomib both contribute to its cancer cell killing actions. It is evident from the present study that hTERT can confer resistance of malignant cells to bortezomib-based target cancer therapy, which may have important clinical implications.


Large cell neuroendocrine tumor of the cervix and human papillomavirus 16: a case report.
Large cell neuroendocrine cancer of the cervix is a rare entity. Most cervical cancers are high-risk human papillomavirus (HPV)-related neoplasms. A 31-year-old woman presented with pelvic pain and daily vaginal bleeding for 6 months. Uterine curettage revealed an undifferentiated malignancy. A total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic, common iliac, and periaortic lymphadenectomy and peritoneal cytology were performed. The pathological findings revealed a poorly differentiated large cell neuroendocrine carcinoma of the cervix with metastasis to 1 right obturator lymph node. Nonisotopic in situ hybridization stains were positive for high-risk HPV in the cervical tumor and in the lymph node metastasis in virtually every tumor cell indicative of viral integration into the host genome. Specific HPV typing by polymerase chain reaction was positive for HPV-16. Integration of high-risk HPV, in particular type 16, is associated with this uncommon variant of cervical carcinoma.


Synthesis of 3-Functionalized 4-Quinolones from Readily Available Anthranilic Acids.
We report herein an efficient synthesis of 3-functionalized 4-quinolones, a class of privileged pharmacophores found in numerous biologically and pharmaceutically active compounds. Our synthetic strategy features a telescoped two-step sequence starting from readily available anthranilic acids and functionalized methane derivatives bearing an electron-withdrawing group, such as methyl sulfones, methyl ketones, and acetonitrile. The method delivers good to excellent yields for a variety of structurally diverse substrates, showing good functional group tolerability. We believe that the disclosed method offers a highly efficient and practical entry to functionalized 4-quinolones under mild conditions that is amenable to preparative-scale synthesis.


Enhancing nonclassical properties of quantum states of light using linear optics.
In this Letter, we present a simple and versatile scheme for enhancing the nonclassical properties of light states using only linear optics and photodetectors. By combining a coherent state |α〉 and an arbitrary pure state of light |ϕ〉 (excluding coherent states) at two beam splitters, we show that the amplitude α of the coherent state can be tuned to filter out specific Fock components and generate states of light with increased nonclassical features. We provide two examples of input states and demonstrate the effectiveness of our scheme in enhancing the sub-Poissonian statistics or the quadrature squeezing of the output states.


[Evaluation of the community integration of persons with lateralised post-acute acquired brain injury].
INTRODUCTION. Hemispheric specialization is a topic of interest that has motivated an enormous amount of research in recent decades. After a unilateral brain injury, the consequences can affect various areas of specialization, leading, depending on the location of the injury, impairment in quality of life and community integration. PATIENTS AND METHODS. Cross-sectional study with a sample of 58 patients, 28 traumatic brain injury (TBI) and 30 cerebrovascular accidents, both lateralized. The level of integration in the community is measured by the Community Integration Questionnaire. RESULTS. There were three groups analyzed by considering unilateral injury (full sample, stroke sample, and TBI sample). Results showed a significantly high community integration of people with right hemisphere injury. However, to measure the level of community integration between TBI and stroke, the results showed no significant differences. CONCLUSION. According to the results of the study people with brain injury in the right hemisphere have a better community integration than people with lesions in the left hemisphere regardless of the origin of the lesions (vascular or traumatic). We discussed the reasons that may motivate the differences and clinical implications.


Cost-effectiveness analysis of endometrial cancer prevention strategies for obese women.
It is unknown whether obese women would benefit from oral contraceptives or screening as endometrial cancer prevention strategies. We estimated the net health benefits and cost-effectiveness of these strategies in a hypothetical cohort of obese women. A Markov decision-analytic model evaluated 4 strategies: 1) no prevention (reference strategy); 2) oral contraceptive pills (OCPs) for 5 years; 3) annual screening with endometrial biopsy from age 30; 4) biennial screening from age 30. Net health benefit was life expectancy and primary outcome was the incremental cost-effectiveness ratio. Baseline and transition probabilities were obtained from published literature and the Surveillance Epidemiology and End Results database, and costs were from the U.S. Department of Health and Human Services and Agency for Healthcare Research and Quality. Sensitivity analyses were performed for uncertainty around various measures. Average life expectancy for all strategies ranged from 74.52 to 74.60 years. None of the strategies had an incremental cost-effectiveness ratio less than $50,000 per year of life saved relative to the next best strategy. Endometrial cancer risk in obese women had to be 13 times greater than the general population risk before OCPs were a cost-effective intervention. Oral contraceptives and current screening methods are not cost-effective endometrial cancer prevention strategies for obese women. Risk factors such as morbid obesity and longstanding anovulation may define a subgroup at highest risk of endometrial cancer for whom OCPs may be a cost-effective strategy. Interventions that reduce endometrial cancer risk further or those with additional health benefits are needed in this population. III.


Characteristic long-chain fatty acid of Pleurocybella porrigens.
As part of an investigation on the chemical constituents and contaminants of the basidiomycete Pleurocybella porrigens (Japanese name: Sugihiratake), we analyzed the UV-detected constituents of this mushroom using HPLC. One of the major UV peaks detected was isolated and identified as a-eleostearic acid, a long-chain fatty acid with a conjugated triene moiety, based on the results of spectroscopic methods. alpha-Eleostearic acid was concluded to be a characteristic fatty acid of P. porrigens, because it was not detected in eight other edible mushrooms examined. Free long-chain fatty acids in P. porrigens and other edible mushrooms were analyzed by HPLC after derivatization with acidic 2-nitrophenylhydrazine hydrochloride. Oleic acid was the main fatty acid in P. porrigens, and saturated long-chain fatty acids such as linoleic acid, palmitic acid, and stearic acid, together with a-eleostearic acid, were also detected.


CIN2 is a much less reproducible and less valid diagnosis than CIN3: results from a histological review of population-based cervical samples.
We wished to compare the relative reproducibility and validity of cervical intraepithelial neoplasia (CIN) 2 and CIN3 diagnoses. In a population-based cohort study (1993-2001) of human papillomavirus (HPV) and cervical neoplasia in Costa Rica, we compared community pathologists' diagnoses with those of the 2 independent reviewers from the United States (total, n = 357). As measures of validity, we correlated primary and review diagnoses with HPV positivity and cytological interpretations. Two review pathologists agreed with 84% and 81%, respectively, of initial diagnoses of CIN3 compared with 13% and 31% of CIN2. The CIN3 diagnoses made by review pathologists were 94% oncogenic HPV positive, compared with 72% of CIN2 diagnoses. Eighty-one percent of CIN3 diagnoses versus 61% of CIN2 were correlated with high-grade cytological interpretations. The CIN3 is a substantially more reproducible diagnosis that can be validated more frequently with HPV tests and cytological interpretations than CIN2.


Predictive Factors of Survival and 6-Month Favorable Outcome of Very Severe Head Trauma Patients; a Historical Cohort Study.
Very severe head trauma cases, defined as Glasgow Coma Scale (GCS) scores of less than 6, have a higher mortality rate and poorer outcome. The purpose of this study was to recognize factors associated with survival and 6-month favorable outcome of very severe head trauma patients presenting to emergency department. In this historical cohort study, the authors retrospectively reviewed medical records of head trauma patients who were admitted to the emergency department with post-resuscitation GCS scores of less than 6. Both univariate and multivariate analyses were used to test the association between various parameters with survival and 6-month outcome. 103 cases with the mean age of 39 ± 16.5 years were studied (80% male). The overall survival rate was 41.7% and the rate of 6-month favorable outcome was 28.2%. In multivariate analysis, brisk pupil light reaction on admission and patent basal cistern on brain computed tomography (CT) scan were significant factors associated with both survival (OR 5.20, 95% CI 1.57-17.246, p = 0.007 and OR 3.65, 95% CI 1.22-10.91, p=0.02 respectively) and favorable outcome (OR 4.07, 95% CI 1.35-12.24, p=0.01 and OR 3.54, 95% CI 1.22-10.26, p 0.02), respectively. Based on the results of present study, the survival rate of patients with very severe head trauma (GCS < 6) was 41.7%. The strong predictors of survival and 6-month favorable outcome of these patients were brisk pupillary reactivity and patent cistern on brain CT scan. It seems that very severe head trauma patients still have a reasonable chance to survive and aggressive management should be continued.


Microperimetric changes and fixation stability status after half-dose photodynamic therapy for chronic central serous chorioretinopathy.
The aim of this study was to evaluate the effect of half-dose verteporfin photodynamic therapy on central retinal sensitivity, status of fixation stability, and choroidal thickness in patients with chronic central serous chorioretinopathy. In total, 22 eyes of 22 patients with chronic central serous chorioretinopathy were enrolled, and all the eyes received indocyanine green angiography-guided half-dose verteporfin photodynamic therapy. Best-corrected visual acuity, contrast sensitivity, and retinal sensitivity in the central 10° and status of the fixation stability are assessed by MAIA microperimetry, and optical coherence tomography findings (central macular thickness and subfoveal choroidal thickness) were evaluated at baseline and 1, 3, and 6 months after the half-dose verteporfin photodynamic therapy. Subretinal fluid was completely resolved in 9 eyes at 1 month and in 17 eyes at 3 months. There was recurrence in two eyes at 6 months and five of the eyes had a persistent subretinal fluid through all the time points. Best-corrected visual acuity, contrast sensitivity, and retinal sensitivity improved significantly 6 months after half-dose verteporfin photodynamic therapy. Fixation stability did not change in either follow-up visit. Central macular thickness and subfoveal choroidal thickness decreased significantly at 6 months of the visits compared to baseline. There was not any systemic and ocular side effect after the treatment. This study shows that there is significant improvement in best-corrected visual acuity, contrast sensitivity, and retinal sensitivity after half-dose verteporfin photodynamic therapy. The status of fixation stability remained unchanged in the eyes with chronic central serous chorioretinopathy after half-dose verteporfin photodynamic therapy. Furthermore, half-dose verteporfin photodynamic therapy is also effective in decreasing central macular thickness and subfoveal choroidal thickness.


Combinatorial Pairwise Assembly Efficiently Generates High Affinity Binders and Enables a "Mix-and-Read" Detection Scheme.
We show that a combinatorial library constructed by random pairwise assembly of low affinity binders can efficiently generate binders with increased affinity. Such a library based on the Sso7d scaffold, from a pool of low affinity binders subjected to random mutagenesis, contained putative high affinity clones for a model target (lysozyme) at higher frequency than a library of monovalent mutants generated by random mutagenesis alone. Increased binding affinity was due to intramolecular avidity generated by linking binders targeting nonoverlapping epitopes; individual binders of KD ∼ 1.3 μM and 250 nM produced a bivalent binder with apparent KD ∼ 2 nM. Furthermore, the bivalent protein retained thermal stability (TM = 84.5 °C) and high recombinant expression yields in E. coli. Finally, when binders comprising the bivalent protein are fused to two of the three fragments of tripartite split-green fluorescent protein (GFP), target-dependent reconstitution of fluorescence occurs, thereby enabling a "mix-and-read" assay for target quantification.


Comparative study of the effect of teicoplanin and vancomycin upon the phagocytic process of peritoneal macrophages.
The effect of Teicoplanin and Vancomycin upon the phagocytic process was compared by evaluating the different activities of the peritoneal macrophage phagocytic function from mice treated with these antibiotics. The results indicated that teicoplanin and vancomycin increased both the substrate adherence and chemotaxis of peritoneal macrophages and that neither antibiotic, at the concentrations of 10, 25, 50, 75 and 100 mg/l, had any chemoattractant capacity for peritoneal macrophages. There was an increase in the attachment of Candida albicans only in the macrophages from mice treated with vancomycin. The phagocytosis of C. albicans, Staphylococcus aureus, Escherichia coli and inert particles as well, as the nitroblue tetrazolium reduction capacity (microbicide capacity) increased in the presence of both antibiotics. The C. albicans digestion capacity increased only in the peritoneal macrophages from mice treated with teicoplanin.


A nucleolar targeting signal in PML-I addresses PML to nucleolar caps in stressed or senescent cells.
The promyelocytic leukemia (PML) tumour suppressor is the organiser of PML nuclear bodies, which are domains the precise functions of which are still disputed. We show that upon several types of stress, endogenous PML proteins form nucleolar caps and eventually engulf nucleolar components. Only two specific PML splice variants (PML-I and PML-IV) are efficiently targeted to the nucleolus and the abundant PML-I isoform is required for the targeting of endogenous PML proteins to this organelle. We identified a nucleolar targeting domain within the evolutionarily conserved C-terminus of PML-I. This domain contains a predicted exonuclease III fold essential for the targeting of the PML-I C-terminus to nucleolar fibrillar centres. Furthermore, spontaneous or oncogene retrieval-induced senescence is associated with the formation of very large PML nuclear bodies that initially contain nucleolar components. Later, poly-ubiquitin conjugates are found on the outer shell or within most of these senescence-associated PML bodies. Thus, unexpectedly, the scarcely studied PML-I isoform links PML bodies, nucleolus, senescence and proteolysis.


Characterization of the oxygen tolerance of a hydrogenase linked to a carbon monoxide oxidation pathway in Rubrivivax gelatinosus.
A hydrogenase linked to the carbon monoxide oxidation pathway in Rubrivivax gelatinosus displays tolerance to O2. When either whole-cell or membrane-free partially purified hydrogenase was stirred in full air (21% O2, 79% N2), its H2 evolution activity exhibited a half-life of 20 or 6 h, respectively, as determined by an anaerobic assay using reduced methyl viologen. When the partially purified hydrogenase was stirred in an atmosphere containing either 3.3 or 13% O2 for 15 min and evaluated by a hydrogen-deuterium (H-D) exchange assay, nearly 80 or 60% of its isotopic exchange rate was retained, respectively. When this enzyme suspension was subsequently returned to an anaerobic atmosphere, more than 90% of the H-D exchange activity was recovered, reflecting the reversibility of this hydrogenase toward O2 inactivation. Like most hydrogenases, the CO-linked hydrogenase was extremely sensitive to CO, with 50% inhibition occurring at 3.9 microM dissolved CO. Hydrogen production from the CO-linked hydrogenase was detected when ferredoxins of a prokaryotic source were the immediate electron mediator, provided they were photoreduced by spinach thylakoid membranes containing active water-splitting activity. Based on its appreciable tolerance to O2, potential applications of this hydrogenase are discussed.


Systematic exploration of a decade of publications on psychiatric genetics in Latin America.
Psychiatric disorders have a great impact in terms of mortality, morbidity, and disability across the lifespan. Considerable effort has been devoted to understanding their complex and heterogeneous genetic architecture, including diverse ancestry populations. Our aim was to review the psychiatric genetics research published with Latin American populations from 2010 to 2019, and classify it according to country of origin, type of analysis, source of funding, and other variables. We found that most publications came from Brazil, Mexico, and Colombia. Also, local funds are generally not large enough for genome-wide studies in Latin America, with the exception of Brazil and Mexico; larger studies are often done in collaboration with international partners, mostly funded by US agencies. In most of the larger studies, the participants are individuals of Latin American ancestry living in the United States, which limits the potential for exploring the complex gene-environment interaction. Family studies, traditionally strong in Latin America, represent about 30% of the total research publications. Scarce local resources for research in Latin America have probably been an important limitation for conducting bigger and more complex studies, contributing to the reduced representation of these populations in global psychiatric genetics studies. Increasing diversity must be a goal to improve generalizability and applicability in clinical settings.


Incidentaloma on Staging CT Revealed to Be Breast to Renal Tumour-to-Tumour Metastasis.
Tumour-to-tumour metastases (TTM) are a rare phenomenon in which a primary tumour has metastasised within another distant primary tumour. We present the case of a 63-year-old female who presented with right-sided breast cancer. An incidental left-sided renal mass was detected on staging CT of the thorax, abdomen, and pelvis (CT-TAP). The patient had no evidence of metastases below the diaphragm. Histology following a radical left nephrectomy revealed metastatic breast cancer within a renal cell carcinoma (RCC). The patient underwent chemotherapy and surgery for right-sided breast cancer. Follow-up imaging demonstrated the metastatic spread of the breast cancer. This is an unusual case of TTM from breast to an initially occult RCC primary.


Lipid synthesis, intracellular transport, storage, and secretion. I. Electron microscopic radioautographic study of liver after injection of tritiated palmitate or glycerol in fasted and ethanol-treated rats.
A time sequence study of intracellular movement of labeled lipid in the liver was carried out on fasted and ethanol-treated rats injected with either palmitate-(3)H or glycerol-(3)H by electron microscopic radioautography. The elimination of water-soluble lipid precursors during specimen preparation was checked and found to be complete. The labeled lipid product in the tissue was identified as mostly triglyceride. A dehydration procedure was adapted to minimize the loss of lipid during specimen preparation. At 2 min after injection, the earliest time interval studied, both precursors were found to have penetrated the liver cells, and the label was found over both rough and smooth elements of the endoplasmic reticulum, which is the site of glyceride esterification. From 5 min on, in fasted and especially in ethanol-treated rats, the label was seen also over lipid droplets 0.5-2.0 micro in diameter, which represent "storage lipid" (slowly turning over compartment). Mitochondria became labeled mostly at later time intervals after injection. From 10 min on, concentration of label was seen over the Golgi apparatus, containing small osmiophilic particles. Association of label with groups of particles in smooth-surfaced vesicles and vacuoles in and near the Golgi apparatus and in the vicinity of the sinusoidal border was seen, both after palmitate-(3)H and glycerol-(3)H. It is proposed that these particles represent lipoproteins which are formed in the endoplasmic reticulum, "processed" in the Golgi apparatus, and transported in vacuoles to the sinusoid surface to be discharged into the circulation.


Sulfated N-Myristoyl Chitosan as a Surface Modifier of Liposomes.
Sulfated N-myristoyl chitosan (S-M-chitosan), which is strongly electrolytic and water soluble as well as partly hydrophobic due to long alkyl chains, was synthesized to be used as a liposome-surface modifier. The effects of the treatment with an aqueous S-M-chitosan solution on the stability of the liposome suspension prepared from hydrogenated egg yolk lecithin were examined on several points. A suspension of large liposomes prepared by the Bangham method was precipitated by standing for a day, but the precipitation was restrained when the sample was treated with S-M-chitosan solution. The turbidity of a small liposome suspension was changed greatly after the suspension was freeze-thawed, but the change was small in the treated sample. A similar result was obtained when the suspension was freeze-dried following the addition of water. These results come from the facts that the surface of the liposome was coated with S-M-chitosan and negatively charged as ascertained by the measurement of zeta potential and the electron microscopic observation. The repulsive force between charges was considered to be the origin of the stabilization. It was also shown from an ESR experiment that the treatment suppressed the elution rate of the material incorporated into the liposomes.


Identification of key genes in prostate cancer gene expression profile by bioinformatics.
The aim of this study was to identify key candidate genes in prostate cancer. The gene expression profiles of GSE32448, GSE45016, GSE46602 and GSE104749 were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between prostate cancer and normal samples were identified by R language. The gene ontology functional and pathway enrichment analyses of DEGs were performed by the Database for Annotation, Visualization and Integrated Discovery software followed by the construction of protein-protein interaction network. Hub gene identification was performed by the plug-in cytoHubba in Cytoscape software. The 217 DEGs were significantly enriched in biological processes including epithelial cell differentiation, response to estradiol and several pathways, mainly associated with protein digestion and absorption pathway in prostate cancer. Epithelial cell adhesion molecule, twist family basic helix-loop-helix transcription factor 1, CD38 molecule and vascular endothelial growth factor A were identified as hub genes. The expression levels of hub genes were consistent with data obtained in The Cancer Genome Atlas for prostate adenocarcinoma. These hub genes may be used as potential targets for prostate cancer diagnosis and treatment.


Biomechanics of the Proximal Radius Following Drilling of the Bicipital Tuberosity to Mimic Cortical Button Distal Biceps Repair Technique.
A fracture through the proximal radius is a theoretical concern after cortical button distal biceps fixation in an active patient. The permanent, nonossified cortical defect and medullary tunnel is at risk during a fall eliciting rotational and compressive forces. We hypothesized that during simulated torsion and compression, in comparison with unaltered specimens, the cortical button distal biceps repair model would have decreased torsional and compressive strength and would fracture in the vicinity of the bicipital tuberosity bone tunnel. Sixteen fourth-generation composite radius Sawbones models were used in this controlled laboratory study. A bone tunnel was created through the bicipital tuberosity to mimic the exact bone tunnel, 8 mm near cortex and 3.2 mm far cortex, made for the BicepsButton distal biceps tendon repair. The radius was then prepared and mounted on either a torsional or compression testing device and compared with undrilled control specimens. Compression tests resulted in average failure loads of 9015.2 N in controls versus 8253.25 N in drilled specimens ( P = .074). Torsional testing resulted in an average failure torque of 27.3 Nm in controls and 19.3 Nm in drilled specimens ( P = .024). Average fracture angle was 35.1° in controls versus 21.1° in drilled. Gross fracture patterns were similar in compression testing; however, in torsional testing all fractures occurred through the bone tunnel in the drilled group. There are weaknesses in the vicinity of the bone tunnel in the proximal radius during biomechanical stress testing which may not be clinically relevant in nature. In cortical button fixation, distal biceps repairs creates a permanent, nonossified cortical defect with tendon interposed in the bone tunnel, which can alter the biomechanical properties of the proximal radius during compressive and torsional loading.


A phase II trial of ISIS 3521 in patients with metastatic colorectal cancer.
This phase II study was designed to characterize the clinical activity of ISIS 3521 in patients with metastatic colorectal cancer (CRC). Sixteen patients with pretreated or refractory CRC were treated with ISIS 3521. Eleven patients were given a dose of 2.0 mg/kg per day, and 5 patients received 3.0 mg/kg per day given over 21 days followed by a 7-day rest period. Patients continued with study until evidence of disease progression or unacceptable toxicity was detected. Patients underwent baseline tumor biopsies followed by a second biopsy during the last week of the first 21-day infusion. All 16 patients underwent baseline tumor biopsies, and 12 of the 16 patients underwent on-study tumor biopsies. No evidence of tumor response was observed. One patient had stable disease after 2 cycles and remained on for 1 additional cycle only to demonstrate progression of disease at that time. No dose-limiting or other significant toxicities were observed at both dosages, which could not be explained by progression of disease. Fatigue was common in all patients treated but was not dose limiting, and there was no evidence of coagulopathy. Analysis of the tumor biopsies obtained from the 11 evaluable samples showed marked uptake of ISIS 3521 in the normal liver parenchyma. However, there was minimal uptake within the tumor cells. In addition, no evidence of any alteration in protein kinase C-a within the tumors or any downstream effects leading to apoptosis were observed. ISIS 3521 demonstrated no clinical activity or target modulation in refractory metastatic CRC.


Role of intestinal mucins in innate host defense mechanisms against pathogens.
Gastrointestinal mucins produced by goblet cells comprise the main structural components of the mucus layer. Mucins play a critical role in the maintenance of mucosal homeostasis and are responsible for the differential effector and regulatory responses against a plethora of microorganisms, including commensals and pathogens. In this review, we present a comprehensive overview on mucin biology, its properties, classification and gene assembly. We also consider the structure of the mucin gene, its proteins and its role in innate host defenses. We compare the various mucin secretagogues and the differential regulatory pathways involved in mucin biosynthesis and secretion during normal and diverse pathogenic conditions. Finally, we summarize the putative uncharted aspects of mucin-derived innate host defenses, whose exploration will help drug developers to identify factors that can strengthen mucosal integrity and will facilitate basic science research into curative treatments for gastrointestinal diseases.


Urease-aided calcium carbonate mineralization for engineering applications: A review.
Inducing calcium carbonate precipitation is another important function of urease in nature. The process takes advantage of the supply of carbonate ions derived from urea hydrolysis and of an increase in pH generated by the reaction, effects that in the presence of Ca2+ ions lead to the precipitation of CaCO3. Further to its importance in nature, if performed in a biomimetic manner, the urease-aided CaCO3 mineralization offers enormous potential in innovative engineering applications as an eco-friendly technique operative under mild conditions, to be used for remediation and cementation/deposition in field applications in situ. These include among others, the strengthening and consolidation of soil/sand, the protection and restoration of stone and concrete structures, conservation of stone cultural heritage materials, cleaning waste- and groundwater of toxic metals and radionuclides, and plugging geological formations for the enhancement of oil recovery and geologic CO2 sequestration. In view of the potential of this newly emerging interdisciplinary branch of engineering, this article presents the principles of urease-aided calcium carbonate mineralization apposed to other biomineralization processes, and reviews the advantages and limitations of the technique compared to the conventional techniques presently in use. Further, it presents areas of its existing and potential applications, notably in geotechnical, construction and environmental engineering, and its future perspectives.


KiSS-1 messenger ribonucleic acid expression in the hypothalamus of the ewe is regulated by sex steroids and season.
The KiSS-1 gene encodes a family of peptides called kisspeptins, which are endogenous ligands for the G protein-coupled receptor GPR54. Kisspeptin function appears to be critical for GnRH secretion and the initiation of puberty. To test the hypothesis that steroid hormones regulate KiSS-1 mRNA expression in the ewe, we examined the brains of ovary-intact (luteal phase) and ovariectomized (OVX) ewes, as well as OVX ewes that received estradiol (E) or progesterone (P) replacement. KiSS-1 mRNA-expressing cells were predominantly located in the arcuate nucleus (ARC). Here, expression was increased after OVX but returned to the level of gonad-intact animals with E treatment. Treatment with P partially restored KiSS-1 expression toward gonad-intact levels. Double-label immunohistochemistry revealed that approximately 86% of kisspeptin-immunoreactive cells in the ARC are also P-receptor positive. Finally, we tested the hypothesis that KiSS-1 mRNA is lower during anestrus, due to a non-steroid-dependent seasonal effect. In OVX ewes, expression in the ARC was lower at the time of year corresponding to anestrus. We conclude that KiSS-1 expression in the ARC of the ewe brain is negatively regulated by chronic levels of E and P, suggesting that both steroids may exert negative feedback control on GnRH secretion through altered kisspeptin signaling. Furthermore, a seasonal alteration in KiSS-1 expression in the ARC of OVX ewes strongly suggests that kisspeptin is fundamentally involved in the control of seasonal changes in reproductive function.


Influence of matricial molecules on growth and differentiation of entrapped chondrocytes.
Primary cultures of rabbit articular chondrocytes have been cultivated normally and within three-dimensional systems using different alginate matrices. The in vitro proliferation capacity of the cells immobilized in the calcium alginate beads was investigated. The growth curve showed that chondrocytes are able to grow and to divide for several days inside the beads; in parallel an increase in protein contents was also measured. The differentiated phenotype of rabbit articular chondrocytes consists of cartilage-specific proteoglycans. During serial monolayer cultures this phenotype was lost and replaced by a low level of proteoglycan synthesis. On the contrary when cultivated in beads, entrapped cells maintained their differentiated phenotype over time; the rates of proteoglycan were similar to those of primary chondrocytes. All these parameters were tested comparatively using different substrata in monolayer cultures and in alginate gels. Assays were carried out to assess the influence of type I collagen, type IV collagen, and of fibronectine on the growth as well as on the differentiation phenotype. The encapsulation methodology is readily applicable to the culture of chondrocytes in single beads, in multiwell dishes, or to mass culture for a bioproduction of extracellular matrix components.


[How we can learn better and more safely from serious incidents; translation of 'Just Culture' and 'Safety-II' into clinical practice].
After a serious incident, all involved expect it will provide an opportunity to learn and that improvements will follow. However, 'safe' learning is often threatened due to a primary focus on accountability. Focus should, instead, be on the needs of both patients and care providers, with the goal of repairing damage and restoring trust in the wider sense - a culture of justice ('Just Culture'). Common daily practice is a more realistic focus for further investigation, with active involvement of healthcare professionals ('Safety-II'). This means that an event is no longer reduced to 'human failure' but that complex work processes and interdependencies are thoroughly investigated, as to understand how things mostly go well but sometimes also go wrong. Deeper insight into the context of a serious incident and its relation to daily practice could ensure that plans for improvement are more closely aligned with this daily practice. Primary focus on the needs of those involved, and appreciation of the complex context, can allow for a safe and realistic approach to learning from undesirable events, such as serious incidents.


Characteristics of HIV Seroconverters Identified in an Emergency Department HIV Screening Program.
The emergency department (ED) may represent a missed opportunity to proactively intervene upon patients at "high risk" for HIV. We sought to describe characteristics of ED HIV seroconverters (individuals who screened positive in the ED for HIV who had either (1) a previous prior negative HIV test in the electronic health record (EHR) or who (2) self-reported a prior negative HIV test) to identify a "high-risk" phenotype for pre-infection engagement. A retrospective chart-review was performed of HIV seroconverters at an academic, urban ED. General demographics, mental health illness comorbidities, and Centers for Disease Control and Prevention (CDC)-identified "high risk" factors, including intravenous drug use (IVDU) and history of sexually transmitted infection (STI) were noted. One hundred thirty total patients were identified, 48 (36.9%) with prior HER-negative test and 82 (63.1%) with self-reported previous negative test. Of total seroconverters: 100 (76.9%) were male and 77 (59.2%) were between the ages of 13-34, comparable to national rates of new HIV diagnoses. Ninety-two patients (70.8%) were Black and 16 (12.3%) had a history of IVDU, significantly increased compared with regional and national new HIV rates (p < 0.05). Fifty-two patients (40%) had an STI within 1 year before HIV-positive screen, 67 (51.5%) had a history of mental health illness, and 77 (59.2%) were uninsured. This review revealed an HIV seroconversion population disproportionately affected by race, IVDU, mental health comorbidities, and additional social factors. The ED may represent a unique opportunity for at-risk, pre-HIV exposure intervention, particularly for vulnerable populations.


Increased Serum Insulin Exposure Does Not Affect Age or Stage of Pancreatic Adenocarcinoma Diagnosis in Patients With Diabetes Mellitus.
In considering whether medications that increase insulin levels accelerate pancreatic adenocarcinoma (PC) development, we hypothesized that PC patients with diabetes mellitus (DM) who used exogenous insulin or insulin-stimulating medications should have an earlier age at diagnosis or present with more advanced disease. Patients enrolled in our PC registry from June 1, 2003, to May 31, 2012, were stratified according to treatment solely with insulin, insulin-stimulating medications, or insulin-independent medications. Age at PC diagnosis, PC stage, and years between DM and PC diagnoses were analyzed among the cohorts. Of 122 DM patients (mean age, 67.4 ± 10.2 years), the mean ages at PC diagnosis within the insulin-only (n = 40), insulin-stimulating (n = 11), insulin-independent (n = 71), and non-DM (n = 321) cohorts were 68.7 ± 10.5, 69.6 ± 10.8, 66.3 ± 9.7, and 65.5 ± 10.5 years, respectively. No significant difference among the age at PC diagnosis was observed based on duration or type of DM treatment. There was no correlation between PC stage and increased insulin exposure. Anti-DM medications that increase exposure to insulin do not appear to accelerate PC development using outcomes of mean age at PC diagnosis, PC stage, or duration between DM and PC diagnoses.


Degradation mechanism and development of detection technologies of ATP-related compounds in aquatic products: recent advances and remaining challenges.
The degradation of ATP-related compounds is an important biochemical process that reflects the freshness of aquatic products after death. There has been considerable interest in investigating the factors affecting the degradation of ATP-related compounds in aquatic products and in developing techniques to detect them. This review provides the latest knowledge on the degradation mechanisms of ATP-related compounds during the storage of aquatic products and discusses the latest advances in ATP-related compound detection techniques. The degradation mechanisms discussed include mainly degradation pathways, endogenous enzymes, and microbial mechanisms of action. Microbial activity is the main reason for the degradation of IMP and related products during the mid to late storage of aquatic products, mainly through the related enzymes produced by microorganisms. Further elucidation of the degradation mechanisms of ATP-related compounds provides new ideas for quality control techniques in raw aquatic products during storage. The development of new technologies for the detection of ATP-related compounds has become a significant area of research. And, biosensors further improve the efficiency and accuracy of detection and have potential application prospects. The development of biosensor back-end modalities (test strips, fluorescent probes, and artificial intelligence) has accelerated the practical application of biosensors for the detection of ATP-related compounds.


Catalytic significance of binary enzyme-aldehyde complexes in the liver alcohol dehydrogenase reaction.
The interaction of liver alcohol dehydrogenase with NADH and aldehyde substrates has been characterized with respect to ternary-complex formation by the apparently non-preferred pathway which involves intermediate formation of binary enzyme X aldehyde complexes. Rate constant estimates are reported for dimethylaminocinnamaldehyde (DACA) binding to free enzyme and for NADH binding to the enzyme X DACA complex. The rate of NADH (or NAD+) association to liver alcohol dehydrogenase is not detectably affected by DACA binding to the enzyme, but the NADH dissociation rate decreases approximately by a factor of 6. The NADH-induced increase in affinity of the enzyme for DACA is similarly attributable to a decreased dissociation rate rather than an increased association rate of the aldehyde. DACA dissociates much more rapidly than coenzyme from the enzyme X NADH X aldehyde complex and shows a higher association rate constant than NADH in its interaction with free enzyme. It is concluded from these results that the enzymic reduction of typical aldehyde substrates will conform to a rate equation which is experimentally indistinguishable from that of a compulsory-order mechanism with coenzyme binding preceding substrate binding, and that this rate equation will obtain irrespective of which pathway for ternary-complex formation is actually preferred. Rate equations provide no reliable information about the order of ligand binding in ternary-complex systems. A flow analysis is presented which indicates that coenzyme and substrate are actually bound in random order to liver alcohol dehydrogenase during the enzymic reduction of aldehydes by NADH. The enzyme X aldehyde pathway for ternary-complex formation is fully kinetically competent, and reaction flow via this pathway may predominate when aldehyde concentrations exceed those required for half-saturation of free enzyme. Binary enzyme X aldehyde complexes are seemingly insignificant with respect to the rate behaviour of the enzyme, but may provide most significant and even predominant contributions to the catalytic reaction flow.


NF-κB-DICER-miRs Axis Regulates TNF-α Expression in Responses to Endotoxin Stress.
Unbalanced tumor necrosis factor (TNF)-α production is associated with pathogenesis of a variety of human diseases. However, the molecular pathways maintaining TNF-α homeostasis remain elusive. Here, we report that NF-κB/p65-DICER-miRs axis negatively regulates TNF-α production. We demonstrated that NF-κB bound to DICER promoter and transcriptionally regulated DICER expression. In addition, the NF-κB/DICER signaling suppresses TNF-α expression by generating mature forms of miR-125b and miR-130a which negatively regulate TNF-α mRNA. Furthermore, we showed that the hepatocyte-specific depletion of Dicer in mice resulted in TNF-α overproduction and sensitized the mice to endotoxin, which could be corrected by administration of miR-125b mimics. These data suggest that NF-κB/p65-DICER-miRs axis involved in maintaining of TNF-α homeostasis, and injection of miR-125b as a potential therapeutic method for septic shock.


Characterization of corneal tangent modulus in vivo.
Intraocular pressure (IOP) measured using Goldmann Applanation Tonometry (GAT) changes with individual's corneal properties, but the method to measure the in vivo corneal material properties to account for individual variation in GAT IOP is not available. In this study, a new method to measure the IOP-dependent corneal tangent modulus in vivo is developed to address this research gap. Instrumented indentation and analysis were developed to measure the corneal tangent modulus. The validity of the method and procedure was verified using model silicone eye pressurized to different IOP. In addition, 15 porcine eyes and 3 rabbit eyes were tested using the corneal indentation at different set intraocular pressure and different indentation rates. The results from silicone eye showed that the measured tangent modulus is in good agreement with the standard silicone rubber modulus. The results on the porcine eyes and rabbit eyes showed that the method can be used to measure corneal tangent modulus in vivo in the human range of intraocular pressure from 10 to 40 mmHg. An indentation method to measure the corneal tangent modulus in vivo was developed, and the IOP dependence of the corneal tangent modulus was characterized. The developed indentation method provides a new means to measure the in vivo corneal tangent modulus to account for individual and pressure variations in measurement of intraocular pressure.


[The Use of Arginine Vasopressin and PhosphodiesteraseIII Inhibitor for Circulatory Shock after the Resection of a Massive Adrenal Pheochromocytoma].
A 72-year-old man developed hypertensive crisis five month previously, and was diagnosed with massive adrenal pheochromocytoma, with a diameter of 14.5 cm. Preoperative echocardiography revealed normal cardiac function. The open abdominal surgery was performed under general anesthesia. During manipulation of the tumor he developed hypertension and tachycardia. Severe hypotension (50/25 mmHg) and mild bradycardia (70 beats x min(-1)) followed the resection of the tumor. In addition to volume replacement noradrenaline and adrenaline were administered, but the systolic blood pressure rose only to 60-70 mmHg. In order to treat vasodilatory shock, we started to administer arginine vasopressin infusion at 0.03 units x min(-1). His systolic blood pressure rose to 90 mmHg. The patient was transferred to the intensive care unit (ICU) postoperatively. The echocardiography revealed diffuse hypokinetic cardiac function. In order to treat cardiogenic shock, we started to administer olprinone (phosphodiesteraseIII inhibitor, infusion of 0.1 μg x kg(-1) x min(-1)). On postoperative day 2, circulatory shock improved and the patient was discharged from the ICU. In conclusion, circulatory shock after the resection of a massive pheochromocytoma was due to the down regulation of α and β adrenergic receptors. The non-adrenergic vasoconstrictor and inotrope were useful for this situation.


Asymptotic-based bootstrap approach for matched pairs with missingness in a single arm.
The issue of missing values is an arising difficulty when dealing with paired data. Several test procedures are developed in the literature to tackle this problem. Some of them are even robust under deviations and control type-I error quite accurately. However, most of these methods are not applicable when missing values are present only in a single arm. For this case, we provide asymptotic correct resampling tests that are robust under heteroskedasticity and skewed distributions. The tests are based on a meaningful restructuring of all observed information in quadratic form-type test statistics. An extensive simulation study is conducted exemplifying the tests for finite sample sizes under different missingness mechanisms. In addition, illustrative data examples based on real life studies are analyzed.


A Double-Chambered Protein Nanocage Loaded with Thrombin Receptor Agonist Peptide (TRAP) and γ-Carboxyglutamic Acid of Protein C (PC-Gla) for Sepsis Treatment.
New protein nanocages are designed bearing two functional proteins, γ-carboxyglutamic acid of protein C (PC-Gla) and thrombin receptor agonist peptide (TRAP), and have an anti-septic response. These nanoparticles reduce sepsis-induced organ injury and septic mortality in vivo. Noting that there are currently no medications for severe sepsis, these results show that novel nanoparticles can be used to treat sepsis.


Immunological functions of the gut--role of the mucosal immune system.
This review summarizes recent information about immune responses in the intestinal mucosa with emphasis on the role of orally-administered antigens from the external environment. The intestinal mucosa provides an extensive surface for potential absorption of pathogenic environmental antigens, such as microbes, chemicals, and food. The intestinal mucosa is densely populated by IgA-producing plasma cells. The humoral immune responses to antigens in the intestinal mucosa are largely of the IgA class in secretory form (sIgA). This sIgA provides an immunological barrier to absorption of antigens on the mucosal epithelium and to penetration into the body. The cell-mediated immune mechanism is also equipped in the mucosal sites. In addition, the mucosal immune response induces hyporesponsiveness of nonmucosal (systemic) immune reactions, and the liver is an integral part of the mucosal immune system. Thus we consider that the mucosal immune system plays a central role in the maintenance of the homeostasis of the total immune system.


Re-visiting the six-item Stanford presenteeism scale (SPS-6) and its psychometric properties.
Presenteeism has often been considered as the correlate of absenteeism and associated to productivity loss. This study sought to re-examine the psychometric properties of the 6-item Stanford Presenteeism Scale (SPS-6), a popular measure which has been translated in a number of languages. The study adopted a cross-sectional design with 268 participants aged 18 - 65 working in a multinational IT company with headquarters based in Poland. The respondents participated willingly in an online questionnaire on a presenteeism health-related productivity measure (SPS-6), job resources (peer support), job demands (work-to-family conflict), engagement and burnout. Their responses were subjected to statistical analyses. Confirmatory Factor Analysis revealed that the SPS-6 is better represented by two singular and independent components, namely completing work and avoiding distractions, rather than an aggregated measure of health-related productivity. In fact, the aggregated measure had convergent and discriminant validity issues. We also assessed, via Structural Equation Modeling (SEM), the explanatory role of the SPS-6 within the wider well-being discourse by subjecting its' factors as outcomes using the JD-R framework. Here, burnout was better at explaining its relationship to avoiding distractions and completing work compared to engagement, while avoiding distractions was more dominant than completing work in explaining indirect pathways. Given the convergent and discriminant validity of its two-dimensional measures, we argue that the SPS-6 is a better assessment of health-related productivity in the light of presenteeism when keeping both components separate rather than adding the scores from both dimensions to provide a global score as has been the practice so far. In addition, the SEM findings suggest that both SPS-6 components may require different theoretical explanations. This study supports a growing chorus of scholars who argue the need to look deeper into the presenteeism phenomenon, not least its measures.


Rapid Active Sampling Surveys as a Tool to Evaluate Factors Associated with Acute Gastroenteritis and Norovirus Infection among Children in Rural Guatemala.
We examined burden and factors associated with norovirus (NoV) acute gastroenteritis (AGE) among children in rural Guatemala. Children age 6 weeks to 17 years were enrolled into three AGE surveillance groups, using two-stage cluster sampling: a prospective participatory syndromic surveillance (PSS) cohort and two cross-sectional rapid active sampling (RAS) surveys, conducted from April 2015 to February 2016. Epidemiologic and NoV testing data were used to identify factors associated with NoV infection, AGE, and NoV+ AGE. The three cross-sectional surveys (PSS enrollment visit, RAS Survey 1, and RAS Survey 2) enrolled 1,239 children, who reported 134 (11%) AGE cases, with 20% of AGE and 11% of non-AGE samples positive for NoV. Adjusted analyses identified several modifiable factors associated with AGE and NoV infection. The cross-sectional RAS surveys were practical and cost-effective in identifying population-level risk factors for AGE and NoV, supporting their use as a tool to direct limited public health resources toward high-risk populations.


[Hyperbaric chamber].
The purpose of this article is to describe a hyperbaric chamber, to expound on the physiology of oxygen dissolved in plasma, state the effects of hyperbaric oxygen therapy and the clinical uses of this therapy. The role of nurses during this entire procedure which this treatment calls for shall also be highlighted in this article.


Emotional reactivity and regulation in individuals with psychopathic traits: Evidence for a disconnect between neurophysiology and self-report.
Individuals with psychopathic traits often demonstrate blunted reactivity to negative emotional stimuli. However, it is not yet clear whether these individuals also have difficulty regulating their emotional responses to negative stimuli. To address this question, participants with varying levels of psychopathic traits (indexed by the Triarchic Measure of Psychopathy; Patrick, 2010) completed a task in which they passively viewed, increased, or decreased their emotions to negative picture stimuli while electrocortical activity was recorded. During passive viewing of negative images, higher boldness, but not higher disinhibition or meanness, was associated with reduced amplitude of the late positive potential (LPP), an ERP that indexes reactivity to emotionally relevant stimuli. However, all participants demonstrated expected enhancement of the LPP when asked to increase their emotional response. Participants did not show expected suppression of the LPP when asked to decrease their emotional response. Contrary to the electrophysiological data, individuals with higher boldness did not self-report experiencing blunted emotional response during passive viewing trials, and they reported experiencing greater emotional reactivity relative to other participants when regulating (e.g., both increasing and decreasing) their emotions. Results suggest inconsistency between physiological and self-report indices of emotion among high-bold individuals during both affective processing and regulation.


Microstructural properties at the interfaces of ZnO nanorods and ZnO homo-buffer layers.
Uniformly and vertically well-aligned ZnO nanorods were fabricated in-situ and ex-situ on ZnO films using a catalyst-free metal-organic chemical vapor process. Microstructural properties of the initial growth of ZnO nanorods on ZnO films with different surface roughnesses were investigated. We observed that the ZnO nanorods grown on ZnO films with surface roughness of less than 1.0 nm were well-aligned along the c-axis and in the ab-plane. When the nanorods grew on ZnO films with a large surface roughness, they had three different growth directions of 28 degrees, 62 degrees, and 90 degrees to the film surface. The slant angle of 62 degrees corresponds to the angle between the ZnO(001) and (101) planes. The initial growth direction difference caused structural disorder at the interface of the ZnO nanorod and film, and prevented epitaxial growth and the alignment of the nanorods.