Analysis of Proposed Medicare Part B to Part D Shift With Associated Changes in Total Spending and Patient Cost-Sharing for Prescription Drugs.
The US Department of Health and Human Services (HHS) has proposed to reform drug pricing in Medicare Part B, which primarily covers physician-administered drugs and biologic agents. One HHS proposal would shift coverage of certain drugs from Medicare Part B to Part D, which is administered by private prescription drug plans. To estimate the association of changes of a shift in Medicare Part B to Part D with total drug spending and patient cost-sharing. Retrospective drug cohort study of the 75 brand-name drugs associated with the highest Part B expenditures among fee-for-service Medicare beneficiaries in 2016. Estimated total Medicare spending in Part B and Part D; annual out-of-pocket costs in Part B and under the standard 2018 Part D benefit; and proportion of drugs in Part D's protected drug classes (immunosuppressants for prophylaxis of organ transplant rejection, antidepressants, antipsychotics, anticonvulsants, antiretrovirals, and antineoplastics). At 2018 prices, total Medicare Part B spending for the 75 brand-name drugs with the highest Part B expenditures was estimated to be $21.6 billion annually. Under the proposed policy, total Part D drug spending for these drugs was estimated to range between $17.6 billion and $20.1 billion after rebates, corresponding to a 6.9% to 18.3% decrease in drug spending in Part D compared with Part B. Of the 75 drugs studied, 33 (44.0%) drugs, accounting for $9.5 billion (43.9%) in Part B spending, were in protected Part D classes where plans must cover essentially all drugs. For 67 drugs with available information, the prices for 65 (97.0%) were a median of 45.8% to 59.7% lower in comparator high-income countries than Part B drug prices. Median patient cost-sharing in Part B for all 75 brand-name drugs was $4683 (interquartile range [IQR], $1069-$9282) per year. Shifting Part B drugs to the 2018 standard Part D benefit was projected to decrease out-of-pocket costs by a median of $860 (IQR, -$3884 to $496) among Medicare beneficiaries without Medicaid or Part B supplemental insurance (Medigap). For beneficiaries who would qualify for the low-income subsidy program in Part D, cost-sharing would be lower in Part D than in Part B for all drugs. For beneficiaries with Medigap insurance, estimated Part D out-of-pocket costs exceeded average Medigap premium costs by a median of $1460 for those with Part D coverage and by a median of $1952 for those without Part D coverage. Although the HHS proposal to shift certain drugs from Medicare Part B to Part D may reduce total drug spending, it may increase out-of-pocket costs for some Medicare beneficiaries, including those with Medicare supplement insurance. The Department of Health and Human Services should ensure that the proposed reforms benefit both patients and payers.


A content analysis of Camel Snus advertisements in print media.
Researchers have questioned whether the R.J. Reynolds Tobacco Company is marketing Camel Snus as a product for nontobacco users, smokeless-tobacco users, or cigarette smokers. The objective of this study was to examine advertisements of Camel Snus in print media to determine the most likely audience of intent. A content analysis was conducted among Camel Snus advertisements printed in newspaper and consumer magazines between July 2007 and August 2010. The advertisements (n = 83 distinct; N = 458 total) were identified from a comprehensive search of a proprietary database maintained by TNS Media Intelligence. Results indicated that all advertisements, published between July 2007 and September 2009, were intended to promote a tobacco product for cigarette smokers. A shift in marketing strategy occurred from October 2009 to the present time with publication of the "Break Free" magazine advertisements, characterized by an ambiguous message that could conceivably appeal to any group, including nontobacco users (e.g., adolescents), smokeless-tobacco users, and/or cigarette smokers. However, an examination of the consumer magazines advertising Camel Snus indicated a demographically diverse readership in terms of gender, age, and education, suggesting that the advertisements are less likely to be intended for smokeless-tobacco users. These findings validate other reports and editorials, suggesting that Camel Snus was being marketed as a product for smokers at the time of the product's national debut. The recent shift to the "Break Free" marketing campaign may reflect an attempt to enhance the image of the Camel brand in order to attract a broader spectrum of consumers.


SARS-CoV-2 Nucleocapsid Protein Interacts with RIG-I and Represses RIG-Mediated IFN-β Production.
SARS-CoV-2 is highly pathogenic in humans and poses a great threat to public health worldwide. Clinical data shows a disturbed type I interferon (IFN) response during the virus infection. In this study, we discovered that the nucleocapsid (N) protein of SARS-CoV-2 plays an important role in the inhibition of interferon beta (IFN-β) production. N protein repressed IFN-β production induced by poly(I:C) or upon Sendai virus (SeV) infection. We noted that N protein also suppressed IFN-β production, induced by several signaling molecules downstream of the retinoic acid-inducible gene I (RIG-I) pathway, which is the crucial pattern recognition receptor (PRR) responsible for identifying RNA viruses. Moreover, our data demonstrated that N protein interacted with the RIG-I protein through the DExD/H domain, which has ATPase activity and plays an important role in the binding of immunostimulatory RNAs. These results suggested that SARS-CoV-2 N protein suppresses the IFN-β response through targeting the initial step, potentially the cellular PRR-RNA-recognition step in the innate immune pathway. Therefore, we propose that the SARS-CoV-2 N protein represses IFN-β production by interfering with RIG-I.


Chemical characterization of organic carbon dissolved in natural waters using inorganic adsorbents.
Dissolved organic carbon (DOC) in water samples from Lake Biwa was chemically characterized by two inorganic adsorbents with completely different surface characteristics. The two adsorbents were HIO (hydrous iron oxide) and SG (silica gel). Solutions of reference standard materials were analyzed concerning their adsorption behavior to HIO and SG for bovine serum albumin (BSA), fulvic acid extracted from the bottom sediments of Lake Biwa, phthalic acid, and starch. The adsorption of DOC to HIO was mainly controlled by ligand exchange and electrostatic interaction; that of SG was by electrostatic interaction. It was found that in a weak acid solution of around pH 5, BSA adsorbs to both HIO and SG, but that fulvic acid, phthalic acid and starch only show adsorption to HIO. Using these characteristics, DOC samples in natural water samples were characterized into pro-DOC, which adsorbs to both HIO and SG at pH 5, and car-DOC, which only adsorbs to HIO at pH 5. The DOC samples in Lake Biwa on October 7, 1997, at sampling sites Nb-2 and Nb-5 (south basin of Lake Biwa, the depths were about 2 and 4 m), and Ie-1 (north basin of Lake Biwa, the depth was about 75 m) were characterized. The pro-DOC has different values, depending on their sampling sites and depths, and had the maximum value of 0.42 mg C l(-1) at the surface water of Ie-1, and had the lowest values at middle to deeper water depths (0.18-0.27 mg C l(-1)). The car-DOC showed a relatively stable value at Ie-1 regardless of the depth (0.63-0.83 mg C l(-1)), and the maximum value was observed in Nb-2 and Nb-5 (1.2 and 1.3 mg C l(-1)). The ratios between car-DOC and pro-DOC concentrations were 0.2-0.5, and had different values for different sampling sites and depths. The ratios were significantly different for surface water samples where the biological activities are high and for bottom water samples where decomposition predominates.


Excited-State Dynamics of [Ru(bpy)3 ]2+ Thin Films on Sensitized TiO2 and ZrO2.
The excited state dynamics of Tris(2,2'-bipyridine)ruthenium(II) hexafluorophosphate, [Ru(bpy)3 (PF6 )2 ], was investigated on the surface of bare and sensitized TiO2 and ZrO2 films. The organic dyes LEG4 and MKA253 were selected as sensitizers. A Stern-Volmer plot of LEG4-sensitized TiO2 substrates with a spin-coated [Ru(bpy)3 (PF6 )2 ] layer on top shows considerable quenching of the emission of the latter. Interestingly, time-resolved emission spectroscopy reveals the presence of a fast-decay time component (25±5 ns), which is absent when the anatase TiO2 semiconductor is replaced by ZrO2 . It should be specified that the positive redox potential of the ruthenium complex prevents electron transfer from the [Ru(bpy)3 (PF6 )2 ] ground state into the oxidized sensitizer. Therefore, we speculate that the fast-decay time component observed stems from excited-state electron transfer from [Ru(bpy)3 (PF6 )2 ] to the oxidized sensitizer. Solid-state dye sensitized solar cells (ssDSSCs) employing MKA253 and LEG4 dyes, with [Ru(bpy)3 (PF6 )2 ] as a hole-transporting material (HTM), exhibit 1.2 % and 1.1 % power conversion efficiency, respectively. This result illustrates the possibility of the hypothesized excited-state electron transfer.


The human milk oligosaccharide 2'-fucosyllactose augments the adaptive response to extensive intestinal.
Intestinal resection resulting in short bowel syndrome (SBS) carries a heavy burden of long-term morbidity, mortality, and cost of care, which can be attenuated with strategies that improve intestinal adaptation. SBS infants fed human milk, compared with formula, have more rapid intestinal adaptation. We tested the hypothesis that the major noncaloric human milk oligosaccharide 2'-fucosyllactose (2'-FL) contributes to the adaptive response after intestinal resection. Using a previously described murine model of intestinal adaptation, we demonstrated increased weight gain from 21 to 56 days (P < 0.001) and crypt depth at 56 days (P < 0.0095) with 2'-FL supplementation after ileocecal resection. Furthermore, 2'-FL increased small bowel luminal content microbial alpha diversity following resection (P < 0.005) and stimulated a bloom in organisms of the genus Parabacteroides (log2-fold = 4.1, P = 0.035). Finally, transcriptional analysis of the intestine revealed enriched ontologies and pathways related to antimicrobial peptides, metabolism, and energy processing. We conclude that 2'-FL supplementation following ileocecal resection increases weight gain, energy availability through microbial community modulation, and histological changes consistent with improved adaptation.


[Reconstruction and preparation of lentiviral vector system expressing dual-reporter genes].
This study was aimed to construct, package and purify the recombinant lentivirus vector carrying the firefly luciferase gene (FLUC) and red fluorescent protein gene (RFP) and to transfect the recombinant lentivirus into HeLa cells, so as to observe the expression levels of these two genes. The FLUC and RFP genes were amplified by RT-PCR and inserted in the lentiviral expression vector (pLenti-Bi-cistronic) to construct the lentiviral vector pLenti-FLUC-RFP. The viral particles were generated by cotransfection of 293T cells with pLenti-FLUC-RFP and three packaging vectors, and the virus titer was determined by calculating the percentage of RFP positive cells. After transfection of pLenti-FLUC-RFP into HeLa cells, the expression of RFP was observed by fluorescent microscopy, and the activity of FLUC was determined by luciferase reporter gene assay kit. The results showed that the inserting orientation of the RFP and FLUC genes in the lentiviral vector pLenti-FLUC-RFP were verified by restriction analysis. Targeted RFP and FLUC sequences were confirmed by DNA sequencing. The final titer obtained was 1×10(7)TU/ml. The expressions of RFP and FLUC were observed in the transfected HeLa cells. It is concluded that the pLenti-III-FLUC-RFP recombinant lentivirus vector carrying RFP gene and FLUC gene with high viral titer is constructed and packaged successfully, and provides experimental basis for studying dynamic distribution of mesenchymal stem cells in vivo.


Effectiveness of Iodophor vs Chlorhexidine Solutions for Surgical Site Infections and Unplanned Reoperations for Patients Who Underwent Fracture Repair: The PREP-IT Master Protocol.
The risk of developing a surgical site infection after extremity fracture repair is nearly 5 times greater than in most elective orthopedic surgical procedures. For all surgical procedures, it is standard practice to prepare the operative site with an antiseptic solution; however, there is limited evidence to guide the choice of solution used for orthopedic fracture repair. To compare the effectiveness of iodophor vs chlorhexidine solutions to reduce surgical site infections and unplanned fracture-related reoperations for patients who underwent fracture repair. The PREP-IT (Program of Randomized Trials to Evaluate Pre-operative Antiseptic Skin Solutions in Orthopaedic Trauma) master protocol will be followed to conduct 2 multicenter pragmatic cluster randomized crossover trials, Aqueous-PREP (Pragmatic Randomized Trial Evaluating Pre-Operative Aqueous Antiseptic Skin Solution in Open Fractures) and PREPARE (Pragmatic Randomized Trial Evaluating Pre-Operative Alcohol Skin Solutions in Fractured Extremities). The Aqueous-PREP trial will compare 4% aqueous chlorhexidine vs 10% povidone-iodine for patients with open extremity fractures. The PREPARE trial will compare 2% chlorhexidine in 70% isopropyl alcohol vs 0.7% iodine povacrylex in 74% isopropyl alcohol for patients with open extremity fractures and patients with closed lower extremity or pelvic fractures. Both trials will share key aspects of study design and trial infrastructure. The studies will follow a pragmatic cluster randomized crossover design with alternating treatment periods of approximately 2 months. The primary outcome will be surgical site infection and the secondary outcome will be unplanned fracture-related reoperations within 12 months. The Aqueous-PREP trial will enroll a minimum of 1540 patients with open extremity fractures from at least 12 hospitals; PREPARE will enroll a minimum of 1540 patients with open extremity fractures and 6280 patients with closed lower extremity and pelvic fractures from at least 18 hospitals. The primary analyses will adhere to the intention-to-treat principle and account for potential between-cluster and between-period variability. The patient-centered design, implementation, and dissemination of results are guided by a multidisciplinary team that includes 3 patients and other relevant stakeholders. The PREP-IT master protocol increases efficiency through shared trial infrastructure and study design components. Because prophylactic skin antisepsis is used prior to all surgical procedures and the application, cost, and availability of all study solutions are similar, the results of the PREP-IT trials are poised to inform clinical guidelines and bring about an immediate change in clinical practice. ClinicalTrials.gov Identifiers: NCT03385304 and NCT03523962.


Clinical characteristics in patients with cervicogenic dizziness: A systematic review.
Cervicogenic dizziness (CD) is a clinical syndrome of dizziness associated with neck dysfunction. CD represents a considerable diagnostic challenge since dizziness and neck pain are common symptoms with complex and multifactorial etiologies. Both research and clinical work on CD is limited by the lack of accepted diagnostic criteria. The aim of this study was to review clinical studies on CD and to assess current evidence regarding the clinical characteristics of this syndrome. A comprehensive PubMed and MEDLINE search was conducted from the date of inception of the database, with the last search conducted in September 2018. Included studies had to contain operable diagnostic criteria as well as a comparison between patients considered to have CD and a clinical comparison group. Data extracted were clinical outcomes, diagnostic criteria, age, sex, and sample size. Studies were assessed for methodological quality using the Crowe Critical Appraisal Tool. Out of 2161 screened studies, eight studies comprising 225 patients met the inclusion criteria. Studies were of low to acceptable methodological quality. The most frequent and consistent clinical characteristic in patients classified as having CD, compared with other populations, was reduced posturographic stability. The most consistent diagnostic criteria were based on the concurrence of neck pain with dizziness after exclusion of other possible reasons for dizziness. There are few studies examining clinical characteristics in patients with cervicogenic dizziness. Altered posturography appeared to be the only consistent characteristic used when distinguishing CD from other populations. Diagnostic criteria currently used in research are likely to have low specificity, since they rest on the exclusion of other causes rather than on positive distinctive features. More studies are needed to better understand the clinical interrelations between dizziness and neck pain.


Low back pain (acute).
Low back pain affects about 70% of people in resource-rich countries at some point in their lives. Acute low back pain can be self-limiting; however, 1 year after an initial episode, as many as 33% of people still have moderate-intensity pain and 15% have severe pain. Acute low back pain has a high recurrence rate; 75% of those with a first episode have a recurrence. Although acute episodes may resolve completely, they may increase in severity and duration over time. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral drug treatments for acute low back pain? What are the effects of local injections for acute low back pain? What are the effects of non-drug treatments for acute low back pain? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 49 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, advice to stay active, analgesics (paracetamol, opioids), back exercises, back schools, bed rest, behavioural therapy, electromyographic biofeedback, epidural corticosteroid injections, lumbar supports, massage, multidisciplinary treatment programmes, muscle relaxants, non-steroidal anti-inflammatory drugs (NSAIDs), spinal manipulation, temperature treatments (short-wave diathermy, ultrasound, ice, heat), traction, and transcutaneous electrical nerve stimulation (TENS).


Interference between Triplex and Protein Binding to Distal Sites on Supercoiled DNA.
We have explored the interdependence of the binding of a DNA triplex and a repressor protein to distal recognition sites on supercoiled DNA minicircles using MD simulations. We observe that the interaction between the two ligands through their influence on their DNA template is determined by a subtle interplay of DNA mechanics and electrostatics, that the changes in flexibility induced by ligand binding play an important role and that supercoiling can instigate additional ligand-DNA contacts that would not be possible in simple linear DNA sequences.


Complement activation and stimulation of chemotaxis by Chlamydia trachomatis.
The stimulus for the migration of polymorphonuclear leukocytes (PMNs) in acute chlamydial infection was studied in vitro by examining the chemotaxigenic effect of L2 and DE Chlamydia trachomatis elementary bodies (EB) upon the plasma of three healthy donors. In each individual experiment, chemotactic response was assessed with PMNs and plasma from the same respective donor, and no specific antibodies against C. trachomatis were detected in the plasma of any donor. Chemotaxis was observed in an agarose plate assay and was quantitated as the chemotactic differential, or CD (directed migration of PMNs minus random movement of PMNs). For each donor, the mean CD was significantly greater (P less than 0.005) when plasma preincubated for 2 h with L2 EB was used as the chemoattractant than when (i) plasma alone, (ii) plasma preheated to 56 degrees C for 30 min before incubation with L2 EB, or (iii) L2 EB in phosphate-buffered saline (PBS) was used as the potential chemoattractant. Similarly, in the one donor in whom DE EB were studied, the mean CD was also significantly greater (P less than 0.005) for plasma preincubated with DE EB as compared with (i) plasma alone or (ii) DE EB in PBS. Complement activation by C. trachomatis EB was assessed by radioimmunoassay for C5a des-arginine in all chemoattractant preparations used in the chemotaxis assay. Mean C5a des-arginine levels were high in plasma samples preincubated with L2 EB (171.00 +/- 10.64, 107.00 +/- 4.76, and 89.70 +/- 1.74 ng per ml) or DE EB (37.40 +/- 15.76 ng per ml) but were undetectable (less than 4.0 ng per ml) in (i) plasma alone, (ii) preheated plasma incubated with L2 EB, and (iii) PBS containing L2 EB. Thus, L2 EB and DE EB of C. trachomatis exert a chemotaxigenic effect upon normal antibody-negative plasma, and this effect is at least in part a result of complement activation and generation of the potent chemotaxin C5a.


The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure.
Hypertension is one of the most frequent pathologies in the industrialized world. Although recognized to be dependent on a combination of genetic and environmental factors, its molecular basis remains elusive. Increased activity of the monomeric G protein RhoA in arteries is a common feature of hypertension. However, how RhoA is activated and whether it has a causative role in hypertension remains unclear. Here we provide evidence that Arhgef1 is the RhoA guanine exchange factor specifically responsible for angiotensin II-induced activation of RhoA signaling in arterial smooth muscle cells. We found that angiotensin II activates Arhgef1 through a previously undescribed mechanism in which Jak2 phosphorylates Tyr738 of Arhgef1. Arhgef1 inactivation in smooth muscle induced resistance to angiotensin II-dependent hypertension in mice, but did not affect normal blood pressure regulation. Our results show that control of RhoA signaling through Arhgef1 is central to the development of angiotensin II-dependent hypertension and identify Arhgef1 as a potential target for the treatment of hypertension.


The susceptible-unidentified infected-confirmed (SUC) epidemic model for estimating unidentified infected population for COVID-19.
In this article, we propose the Susceptible-Unidentified infected-Confirmed (SUC) epidemic model for estimating the unidentified infected population for coronavirus disease 2019 (COVID-19) in China. The unidentified infected population means the infected but not identified people. They are not yet hospitalized and still can spread the disease to the susceptible. To estimate the unidentified infected population, we find the optimal model parameters which best fit the confirmed case data in the least-squares sense. Here, we use the time series data of the confirmed cases in China reported by World Health Organization. In addition, we perform the practical identifiability analysis of the proposed model using the Monte Carlo simulation. The proposed model is simple but potentially useful in estimating the unidentified infected population to monitor the effectiveness of interventions and to prepare the quantity of protective masks or COVID-19 diagnostic kit to supply, hospital beds, medical staffs, and so on. Therefore, to control the spread of the infectious disease, it is essential to estimate the number of the unidentified infected population. The proposed SUC model can be used as a basic building block mathematical equation for estimating unidentified infected population.


Assigning lifetime occupation domains for older Mexicans: MHAS-O*NET linkage protocol.
We developed a MHAS (Mexican Health and Aging Study) and O*NET (Occupational Information Network) linkage to allow global researchers using MHAS data to assign lifetime occupation domains for older Mexicans. Three bilingual raters independently matched 440 records with 132 unique occupation codes from the 2012 MHAS. We used a modified Delphi technique to reach agreements. To assess reliability, we compared the distribution of observations between the MHAS file and the MHAS-O*NET linked file across five job categories (upper white collar, lower white collar, upper blue collar, low blue collar, and agriculture/fishing/forestry). The Institutional Review Board at the University of Texas Medical Branch reviewed and approved the research (IRB # 21-0268). Using the developed 1:1 MHAS-ONET linkage, consistency between MHAS and ONET was 97.4% across the five job categories. This MHAS-O*NET linkage will allow researchers to analyze the association between lifetime occupation and multiple dimensions of health, functionality, and retirement determinants for a low-middle income country with a large proportion of workers in the informal sector.


Production of an extracellular matrix as an isotropic growth phase of Penicillium rubens on gypsum.
Indoor mold represents an important environmental concern, but a fundamental knowledge of fungal growth stages is needed to limit indoor fungal proliferation on finishing materials used in buildings. The present study focused on the succession of germination stages of the common indoor fungus Penicillium rubens on a gypsum substrate. This substrate is used as a model system representing porous materials that are widely used in indoor environments. Imaging with cryo-scanning electron microscopy showed that the formation of an extracellular matrix (ECM) is a phase of the isotropic growth of P. rubens that is uniquely related to germinating conidia. Furthermore, the ECM is observed only when a dry-state inoculation of the surface is applied, i.e., applying conidia directly from a 7-day-old colony, mimicking airborne contamination of the surface. When inoculation is done by spraying an aqueous conidial suspension, no ECM is observed. Moreover, it is concluded that the formation of an ECM requires active processes in the fungal cell. The porosity of the substrate proved that the ECM substance has high-viscosity characteristics. The present results stress that studies of indoor fungal growth should consider the method of inoculation, knowing that the common aqueous suspension may obscure specific stages in the initial phases of germination.


Randomized Trials Built on Sand: Examples from COPD, Hormone Therapy, and Cancer.
The randomized controlled trial is the fundamental study design to evaluate the effectiveness of medications and receive regulatory approval. Observational studies, on the other hand, are essential to address post-marketing drug safety issues but have also been used to uncover new indications or new benefits for already marketed drugs. Hormone replacement therapy (HRT) for instance, effective for menopausal symptoms, was reported in several observational studies during the 1980s and 1990s to also significantly reduce the incidence of coronary heart disease. This claim was refuted in 2002 by the large-scale Women's Health Initiative randomized trial. An example of a new indication for an old drug is that of metformin, an anti-diabetic medication, which is being hailed as a potential anti-cancer agent, primarily on the basis of several recent observational studies that reported impressive reductions in cancer incidence and mortality with its use. These observational studies have now sparked the conduct of large-scale randomized controlled trials currently ongoing in cancer. We show in this paper that the spectacular effects on new indications or new outcomes reported in many observational studies in chronic obstructive pulmonary disease (COPD), HRT, and cancer are the result of time-related biases, such as immortal time bias, that tend to seriously exaggerate the benefits of a drug and that eventually disappear with the proper statistical analysis. In all, while observational studies are central to assess the effects of drugs, their proper design and analysis are essential to avoid bias. The scientific evidence on the potential beneficial effects in new indications of existing drugs will need to be more carefully assessed before embarking on long and expensive unsubstantiated trials.


Correlation of Streptococcus agalactiae concentration on immune system and effective dose of inactivated vaccine for Chitralada 3 strain Nile tilapia (Oreochromis niloticus) in Thailand.
The main pathogen in the Nile tilapia (Oreochromis niloticus) culture, Streptococcus agalactiae, causes economic harm. Infected fish's immune systems worked to eliminate of the infection. This study demonstrated the effect of different bacterial concentrations on tilapia immunity and optimal vaccine concentration to induce immunity in Nile tilapia. The experiment was performed at 102, 104, 106, 108, and 1010 CFU/fish of S. agalactiae compared with the control (PBS) through intraperitoneal injection for 72 h. Fish that survived employed to gather blood, and immune responses were assessed through measures of the survival rate include blood smears, antibody titers, and immunoglobulin gene expression. The vaccine experiment investigated formalin-inactivated S. agalactiae vaccination and administered S. agalactiae injections for 14 days. The statistic revealed a significant difference (p < 0.05) in the 108 and 1010 CFU/fish injections with high survival rates (62.22% and 53.33%, respectively). Immunoglobulin gene expression was highly represented in the 1010 CFU/fish injection; antibody titers were significantly improved from the control group, and antibody levels were high in the 1010 CFU/fish injection. The analysis of blood cell types using the blood smear method revealed a progressive increase in leucocytes, particularly lymphocytes, neutrophils, and monocytes, in the treatment group compared to the control group. Moreover, the erythrocyte/leucocyte ratio decreased significantly in response to the high bacterial injection, indicating an increase in leucocytes. Conversely, the erythrocyte level stayed ed within at the 7.03-9.70 × 102 cell/ml and shown no significant difference (p > 0.05). The lymphocytes were almost two-fold in 1010 CFU/fish compared to 108 CFU/fish. As depicted in the lowest concentration of 106 CFU/fish, the vaccine performance had a high relative percent survival (RPS) at 86.67%. This research suggested that the tilapia infected with high S. agalactiae concentrations did not affect the mortality of the tilapia, and vaccine concentration was effective in 106 CFU/fish.


Overview of the Effect of Complementary Medicine on Treating or Mitigating the Risk of Endometriosis.
Endometriosis is a hormone-dependent chronic inflammatory disease with symptoms such as pelvic pain, which affect the physical, emotional, and social health of women in reproductive age. The current overview article aims to explore the effect of complementary medicine on the treatment or in mitigating the risk of endometriosis. This is an overview article done in Iran. Two separate researchers systematically searched 3 databases (Medline, Scopus, and Cochrane Central Register Trials) until September 2020. The methodological quality of each study was assessed using the assessment of multiple systematic reviews (AMSTAR) tool. The results of two reviews suggested that physical activity, tobacco smoking, diet, coffee and caffeine intake had no effect on mitigating the risk of endometriosis or improving its treatment, but acupuncture successfully reduced pain and related marker (serum CA-125) levels. As endometriosis is an annoying disease with many complications and is hard to diagnose and treat, related studies in complementary medicine can help patients with endometriosis. Based on the relevant literature review, among the complementary medicine available for the treatment or to mitigate the risk of endometriosis, only acupuncture seems to alleviate the pain of endometriosis.


Parastomal hernia repair with the Sugarbaker technique using e-PTFE mesh.
Although surgery is commonly used to treat parastomal hernia, it is very difficult and has shown poor results. Recently, repair with prosthetic materials has been thought to be a more promising method. The Sugarbaker technique with e-PTFE mesh (Dualmesh®) performed via open surgery was adopted for seven patients with parastomal hernia. Two of them were recurrent cases. Three of the patients experienced incarceration of the intestine and recovered conservatively before surgery. The median age of the patients at the parastomal hernia repair was 77.6 years old (range 37.7-84.7). The median operative time was 211 min (range 147-256). The median hernia size was 28 cm2 (range 7.5-60 cm2). The median amount of blood loss during the operation was 158 g (range 0-370 g). Surgical site infection was not observed. The postoperative median hospital stay was 17 days (range 13-40) and the median follow-up was 2.4 years (range 1.0-3.7). During the follow-up period, we did not observe recurrence or readmission. The surgical results were satisfactory with minimal morbidity and no recurrences. The Sugarbaker technique for parastomal repair using e-PTFE mesh may be suitable as a standard method for treating parastomal hernia.


A longitudinal study of job strain and ambulatory blood pressure: results from a three-year follow-up.
This study was conducted to investigate the hypothesis that exposure to "job strain" is related to increased ambulatory blood pressure (ABP). Participants were 195 men who wore an ABP monitor for 24 hours on two occasions 3 years apart. Job strain status, evaluated at each assessment, was used to identify four groups: those not having job strain at either assessment (N = 138), those having job strain at both times (N = 15), and two crossover groups. Regression analysis was used to examine the cross-sectional associations of ABP with job strain, controlling for other known risk factors. Repeated-measures analysis of variance was used to examine the association of ABP change with the category of job strain change. The cross-sectional analysis of the Time 2 data yielded almost identical, highly significant effects of job strain on ABP as was shown in our previously published Time 1 analysis. Those in high strain jobs at both times had systolic/diastolic ABPs at work and at home that were, on average, 11/7 mm Hg higher than those with no job strain at both times; the crossover groups had intermediate levels of ABP. The longitudinal analysis showed that those with a high strain job at Time 1, but not at Time 2, had a significant decrease in work and home ABP of approximately 5/3 mm Hg. The previously reported cross-sectional association between job strain and ABP was replicated at follow-up. The group repeatedly exposed to job strain had higher levels of ABP at Time 2 than either crossover group. Furthermore, change in job strain status partially predicted change in ABP. These results provide new evidence supporting the hypothesis that job strain is an occupational risk factor in the etiology of essential hypertension.


Long-term effects of a three-component lifestyle intervention on emotional well-being in women with Polycystic Ovary Syndrome (PCOS): A secondary analysis of a randomized controlled trial.
Many women with Polycystic Ovary Syndrome (PCOS) report high depression rates. The relationship between PCOS and these high depression rates is unclear. Two-component lifestyle interventions have revealed short-term effects on depression scores in this group of women. In general, 3-component interventions including diet, exercise, and cognitive behavioral therapy (CBT) are more effective in the long-term to improve emotional well-being. This has not yet been studied in women with PCOS. This study examined the effect of 20 CBT lifestyle (LS) sessions combined with a healthy diet and physical therapy with or without 9 months additional feedback through Short Message Service (SMS) via mobile phone, compared to care as usual (CAU, involving advice to lose weight). In this secondary analysis, 155 women with PCOS and a BMI above 25 kg/m2 were eligible. Depression scores decreased significantly in the LS programme compared to CAU (P = 0.045). In both the LS programme without SMS (P = 0.036) and the LS programme with SMS (P = 0.011) depression scores decreased while no change was observed in CAU (P = 0.875). Self-esteem scores improved significantly in the LS programme compared to CAU (P = 0.027). No differences in body image scores were observed in LS participants compared to CAU (P = 0.087), although body image improved significantly in both the LS without SMS (P = 0.001) and with SMS (P = 0.008) study arms. We found no significant mediating role by androgens in the relationship between LS participants and emotional well-being. Only weight-loss mediated the relationship between LS and self-esteem. To conclude, a three-component lifestyle intervention programme with or without additional SMS resulted in significant improvements in depression and self-esteem compared to CAU, in women with PCOS, obesity, and a wish to achieve a pregnancy. Testosterone, androstenedione, DHEA, insulin, HOMA-IR, and cortisol did not mediate this effect. Weight loss mediated the effects on self-esteem but not on depression and body-image. This suggests that lifestyle treatment independent of weight loss can reduce depression and body-image, but both lifestyle treatment and weight loss can improve self-esteem. Thus, a three-component lifestyle intervention based on CBT could prove successful in improving mood in women with PCOS who are overweight or obese and attempting to become pregnant.


Caesarean section delivery and childhood obesity in a British longitudinal cohort study.
Several studies reported an association between Caesarean section (CS) birth and childhood obesity. However, there are several limitations in the current literature. These include an inability to distinguish between planned and emergency CS, small study sample sizes and not adjusting for pre-pregnancy body-mass-index (BMI). We examined the association between CS delivery and childhood obesity using the United Kingdom Millennium Cohort Study (MCS). Mother-infant pairs were recruited into the MCS. Use of sampling weights ensured the sample was representative of the population. The exposure was categorised as normal vaginal delivery (VD) [reference], assisted VD, planned CS and emergency CS. Childhood obesity prevalence, at age three, five, seven, eleven and fourteen years was calculated using the International Obesity Taskforce criteria. Mixed-effects linear regression models were fitted with associations adjusted for several potential confounders like maternal age, pre-pregnancy BMI, education and infant macrosomia. Linear regression models were fitted evaluating body fat percentage (BF%), at age seven and fourteen years. Of the 18,116 infants, 3872 (21.4%) were delivered by CS; 9.2% by planned CS. Obesity prevalence was 5.4%, 5.7%, 6.5%, 7.1% and 7.6% at age three, five, seven, eleven and fourteen years respectively. The mixed-effects linear regression model showed no association between planned (adjusted mean difference = 0.00; [95% confidence interval (CI) -0.10; 0.10], p-value = 0.97) or emergency CS (adjusted mean difference = 0.08; [95% CI -0.01; 0.17], p-value = 0.09) and child BMI. At age seven years, there was no association between planned CS and BF% (adjusted mean difference = 0.13; [95% CI -0.23; 0.49]); there was no association at age fourteen years. Infants born by planned CS did not have a significantly higher BMI or BF% compared to those born by normal VD. This may suggest that the association, described in the literature, could be due to the indications/reasons for CS birth or residual confounding.


GPX4 aggravates experimental autoimmune encephalomyelitis by inhibiting the functions of CD4+ T cells.
Multiple sclerosis (MS) is a common autoimmunity disease of the central nervous system (CNS) that mostly happens in young adults. The chronic clinical features of MS include inflammatory demyelination, infiltration of immune cells, and secretion of inflammatory cytokines, which have been proved to be associated with CD4+ T cells. Ferroptosis is a newly discovered programmed cell death mediated by the massive lipid peroxidation and more sensitive to CD4+ T cells. However, the effect of ferroptosis of CD4+ T cells on the occurrence and progression of MS retains unclear. Here, the experimental autoimmune encephalomyelitis (EAE) model was used to investigate the role of GPX4, a leading inhibitor of ferroptosis, which plays in the function of CD4+ T cells. Our results showed that GPX4 was highly expressed in CD4+ T cells of MS patients based on existing databases. Strikingly, conditional knockout of GPX4 in CD4cre mice (cKO mice) significantly alleviated the average symptom scores and immunopathology of EAE. The infiltration of immune cells, including CD4+ T and CD8+ T cells, and the generation of GM-CSF, TNF-α, and IL-17A, were remarkably reduced in the CNS from cKO mice compared with WT mice. These findings further revealed the vital role of GPX4 in the expansion and function of CD4+ T cells. Moreover, GPX4-deficient CD4+ T cells were susceptible to ferroptosis in EAE model. Overall, this study provided novel insights into therapeutic strategies targeting GPX4 in CD4+ T cells for inhibiting CNS inflammation and treating MS.


DFT study of undoped and As-doped Si nanowires approaching the bulk limit.
The electronic properties of pure and As-doped Si nanowires (NWs) with radii up to 9.53 nm are studied using large scale density functional theory (DFT) calculations. We show that, for the undoped NWs, the DFT bandgap reduces with increasing diameter and converges to its bulk value, a trend in agreement with experimental data. Moreover, we show that the atoms closest to the surface of the nanowire (NW) contribute less to the states near the band edges, when compared with atoms close to the centre; this is shown to be due to differences in Si-Si atomic distances, as well as surface passivation effects. When considering As-doped Si NWs we show that dopant placement within the NW plays an important role in deciding electronic properties. We show that a low velocity band is introduced by As doping, in the gap, but close to the conduction band edge. The curvature of this low velocity band depends on the dopant location, with the curvature reducing when the dopant is placed closer to the center. We also show that asymmetry of dopant location with the NW leads to splitting of the valence band edge.


A review of chemotherapy trials for malignant mesothelioma.
Treatment of malignant pleural mesothelioma continues to be frustrating regardless of the modality employed. Numerous trials of chemotherapeutic agents have been performed, but until recently, these studies were small and subject to inaccuracies of disease measurement. To our knowledge, no chemotherapeutic regimen has emerged as a standard of care. A review of the literature reveals that small activity against this disease has been shown by the anthracyclines, platinum compounds, and alkylating agents, whereas higher activity has been reported with the antimetabolites. The plant alkaloids have not demonstrated any activity against mesothelioma. Dose-escalated chemotherapeutic regimens may offer an advantage, whereas combination chemotherapy has not shown any benefit over single-agent therapy. Favorable responses have been reported with the administration of intrapleural biological response modifiers. Further trials and the investigation of new agents in the treatment of this disease are necessary.


The role of vision in academic school performance.
To determine whether presenting distance visual acuity is related to subsequent academic school performance in Singaporean children between 9 to 10 years of age. Singapore children (n = 1143 children) were examined during their visits at ages 9 to 10 years (grades 3 to 4) as part of the Singapore Cohort Study of the Risk Factors for Myopia (SCORM) longitudinal study. Each child underwent an annual comprehensive eye examination, including the assessment of presenting logarithm of the minimum angle of resolution (LogMAR) distance visual acuity (VA). The individual marks of a nation-wide standard examination in grade 4 were used as the outcome measure for academic school performance. Children with any known eye disease, (such as media opacities) were excluded from the analysis. The mean presenting distance VA of the better eye was 0.10 and 0.08 when the children were in grades 3 and 4, respectively. There was a statistically significant difference for mean presenting VA with 9 and 10 year old boys scoring better (0.08 and 0.07) compared to girls (0.12 and 0.09) for the same ages, (p = 0.001 and p = 0.007), respectively. After adjusting for gender, ethnicity, school, reading, intelligence quotient and father's education, no significant relationships were found between average examination marks at the end of grade 4 and presenting VA obtained (better eye and worst eye) in grade 3 (p = 0.38 and p = 0.98) and 4 (p = 0.27 and p = 0.16). In our sample of Singaporean children without ocular disease, distance VA did not play a significant role in predicting academic school performance.


Objective methods in postlingually and prelingually deafened adults for programming cochlear implants: ESR and NRT.
This study compared responses of prelingually and postlingually deafened adult Nucleus 24 cochlear implant users on two objective measures employed to predict programming levels: neural response telemetry (NRT) and electrically evoked stapedial reflexes (eSR). Thirty experienced postlingually and prelingually deafened adult implant users underwent standard behavioural judgements of maximum comfortable loudness levels (C levels) and thresholds (Ts) followed by eSR and NRT measurements. Two different programs were created based on both the subjective judgement and the objective estimates of C levels (eSR thresholds) and these were compared. Relationships between the subjective and the objective measures were statistically analysed. Maximum stimulation levels estimated by both eSR and NRT were highly correlated with C levels. Variability of NRT results was higher than for eSR results. Mean NRT thresholds for postlingually deafened patients were higher than for prelingually deafened patients. A number of prelingually deafened users could distinguish no difference between programs; however, the majority of postlingually deafened users were sensitive to the difference and many reported preference for the program with eSR-estimated C levels. Neural response telemetry thresholds and eSRTs obtained in Nucleus 24 patients are highly correlated with C levels and Ts. Results suggest that estimation of C levels and Ts using NRT or eSR requires different correction factors for prelingually versus postlingually deafened adult subjects.


Genetics of food intake self-regulation in childhood: literature review and research opportunities.
Pediatric obesity results from a daily energy imbalance between intake and expenditure, an imbalance potentially as slight as ~30-50 kcal/day (e.g., a few extra sips of cola or bites of a cookie). That an 'energy gap' so small may be so powerful suggests the importance of understanding mechanisms of food intake self-regulation (FISR). This review focuses on 4 behavioral indices of FISR in childhood: (1) eating in the absence of hunger; (2) eating rate; (3) caloric compensation and satiety responsiveness, and (4) food responsiveness. Evidence from pediatric samples around the world indicates that these traits are associated with body mass index, are heritable, and are linked to polymorphisms in the FTO gene. We review these data, also discussing their relevance to practical issues of parental feeding styles, portion sizes, and health literacy and numeracy. Research gaps and opportunities for future investigation are discussed. Multidisciplinary approaches and study designs that can address gene-environment interactions are needed to advance the science of FISR and stimulate new avenues for childhood obesity prevention.


Interactive Tree Of Life v2: online annotation and display of phylogenetic trees made easy.
Interactive Tree Of Life (http://itol.embl.de) is a web-based tool for the display, manipulation and annotation of phylogenetic trees. It is freely available and open to everyone. In addition to classical tree viewer functions, iTOL offers many novel ways of annotating trees with various additional data. Current version introduces numerous new features and greatly expands the number of supported data set types. Trees can be interactively manipulated and edited. A free personal account system is available, providing management and sharing of trees in user defined workspaces and projects. Export to various bitmap and vector graphics formats is supported. Batch access interface is available for programmatic access or inclusion of interactive trees into other web services.


Heat avoidance is regulated by transient receptor potential (TRP) channels and a neuropeptide signaling pathway in Caenorhabditis elegans.
The ability to avoid noxious extremes of hot and cold is critical for survival and depends on thermal nociception. The TRPV subset of transient receptor potential (TRP) channels is heat activated and proposed to be responsible for heat detection in vertebrates and fruit flies. To gain insight into the genetic and neural basis of thermal nociception, we developed assays that quantify noxious heat avoidance in the nematode Caenorhabditis elegans and used them to investigate the genetic basis of this behavior. First, we screened mutants for 18 TRP channel genes (including all TRPV orthologs) and found only minor defects in heat avoidance in single and selected double and triple mutants, indicating that other genes are involved. Next, we compared two wild isolates of C. elegans that diverge in their threshold for heat avoidance and linked this phenotypic variation to a polymorphism in the neuropeptide receptor gene npr-1. Further analysis revealed that loss of either the NPR-1 receptor or its ligand, FLP-21, increases the threshold for heat avoidance. Cell-specific rescue of npr-1 implicates the interneuron RMG in the circuit regulating heat avoidance. This neuropeptide signaling pathway operates independently of the TRPV genes, osm-9 and ocr-2, since mutants lacking npr-1 and both TRPV channels had more severe defects in heat avoidance than mutants lacking only npr-1 or both osm-9 and ocr-2. Our results show that TRPV channels and the FLP-21/NPR-1 neuropeptide signaling pathway determine the threshold for heat avoidance in C. elegans.


A survey of binge eating and obesity treatment practices among primary care providers.
Obesity is an increasingly prevalent condition and many obese individuals binge eat. It is unclear how much knowledge physicians possess regarding binge eating, but the limited existing data suggest that primary care physicians frequently do not identify obesity as a clinical problem. The objective of this study was to examine physician knowledge and treatment recommendations regarding binge eating and obesity. A survey on binge eating and obesity assessment and treatment was mailed to 700 licensed physicians. The survey was returned by 272 (38.9%) respondents. Greater than 40% of physicians never assessed binge eating. Body mass index (BMI) was calculated "often or always" by 36.2% of physicians and "rarely or never" by 39.7%. The pattern of obesity treatment methods offered by providers was quite different from the pattern of treatment requested by their patients. Physicians who made higher estimates of binge eating prevalence were more likely to make treatment referrals. In this study, physicians frequently did not assess binge eating. Only a minority of physicians utilize BMI in the assessment and management of obesity. Also, physicians report that the obesity treatments they recommend differ from the treatments patients request of them.


Interactive visualization of whole eukaryote genome alignments using NCBI's Comparative Genome Viewer (CGV).
We report a new visualization tool for analysis of whole genome assembly-assembly alignments, the Comparative Genome Viewer (CGV) ( https://ncbi.nlm.nih.gov/genome/cgv/ ). CGV visualizes pairwise same-species and cross-species alignments provided by NCBI using assembly alignment algorithms developed by us and others. Researchers can examine the alignments between the two assemblies using two alternate views: a chromosome ideogram- based view or a 2D genome dotplot. Whole genome alignment views expose large structural differences spanning chromosomes, such as inversions or translocations. Users can also navigate to regions of interest, where they can detect and analyze smaller-scale deletions and rearrangements within specific chromosome or gene regions. RefSeq or user-provided gene annotation is displayed in the ideogram view where available. CGV currently provides approximately 700 alignments from over 300 animal, plant, and fungal species. CGV and related NCBI viewers are undergoing active development to further meet needs of the research community in comparative genome visualization.


Integrating community based research into residency training.
Knowledge of and experience in both community medicine and research are important ingredients in the make-up of modern day family physicians. Although most family practice teachers agree with the statement, many remain in a quandary as to how to integrate these topics in the overall curriculum. This paper presents one possible solution to this dilemma. Two examples are given whereby family practice residents perform community based research projects, thereby fulfilling objectives in both community medicine and research.


Neural mechanisms of surround attenuation and distractor competition in visual search.
Visual attention biases relevant processing in the visual system by amplifying relevant or attenuating irrelevant sensory input. A potential signature of the latter operation, referred to as surround attenuation, has recently been identified in the electromagnetic brain response of human observers performing visual search. It was found that a zone of attenuated cortical excitability surrounds the target when the search required increased spatial resolution for item discrimination. Here we address the obvious hypothesis that surround attenuation serves distractor suppression in the vicinity of the target where interference from irrelevant search items is maximal. To test this hypothesis, surround attenuation was assessed under conditions when the target was presented in isolation versus when it was surrounded by distractors. Surprisingly, substantial and indistinguishable surround attenuation was seen under both conditions, indicating that it reflects an attentional operation independent of the presence of distractors. Adding distractors in the target's surround, however, increased the amplitude of the N2pc--an evoked response known to index distractor competition in visual search. Moreover, adding distractors led to a topographical change of source activity underlying the N2pc toward earlier extrastriate areas. In contrast, the topography of reduced source activity due to surround attenuation remained unaltered with and without distractors in the target's surround. We conclude that surround attenuation is not a direct consequence of the attenuation of distractors in visual search and that it dissociates from attentional operations reflected by the N2pc. A theoretical framework is proposed that links both operations in a common model of top-down attentional selection in visual cortex.


Relationship of physician continuity to type of health problems in primary care.
The objective of this study was to determine if the level of continuity of medical care was related to the type of health problems (chronic or acute) presented by patients at four family health centers during a one-year period. Patients with chronic diagnoses encountered significantly fewer physicians and had a higher mean Continuity Index than patients with acute illness diagnoses, even though these two groups made the same number of health center visits for their respective problems during this period. These findings indicate that the prioritizing of clinical problems (whether planned or fortuitous) with respect to the importance of providing continuous care may already be taking place at these health centers. These activities are appropriate if one accepts the premise that, other things being equal, longer illnesses are treated more effectively if there is a consistent knowledge base about a patient and his/her illness, and that this consistency of knowledge is related to the number of providers encountered by that patient.


Experiences of undergraduate African health sciences students: A hermeneutic inquiry.
While efforts have been made to understand the experiences of African students in predominantly white environments, the experiences of African students in clinical placement areas have rarely been explored. This paper is a report on a study designed to address the gap in educational research on the experiences of African health sciences students in clinical placements in predominantly white environments. Interviews adopting an open approach to conversations were conducted with nine African students from three health disciplines at one metropolitan university in Australia between 2012 and 2013. Interview transcripts were analyzed using philosophical hermeneutics, where shared meanings were arrived at by employing key Gadamerian hermeneutic components. Findings revealed a number of factors that had a direct effect on the meaning students derived from their clinical placement experiences. These, as revealed in the interlinked domains of body, space, relationships, and time included difference, acceptance, resilience, and cultural sensitivity. Insights from this study may lead to the adoption of strategies designed to improve the experiences of African students studying health sciences in predominantly white environments.


Pregnancy, cardiomyopathies, and genetics.
Although familial forms of cardiomyopathy such as hypertrophic or dilated cardiomyopathy have been recognized for decades, it is only recently that much of the genetic basis of these inherited cardiomyopathies has been elucidated. This has provided important insights into the pathophysiological mechanisms underlying the disease phenotype. This increased knowledge and the availability of genetic testing has resulted in increasing numbers of mutation carriers who are being monitored, including many who are now of child-bearing age. Pregnancy is generally well tolerated in asymptomatic patients or mutation carriers with inherited cardiomyopathies. However, since pregnancy leads to major physiological changes in the cardiovascular system, in women with genetic cardiomyopathies or who carry a mutation pre-disposing to a genetic cardiomyopathy, pregnancy entails a risk of developing heart failure and/or arrhythmias. This deterioration of cardiac function may occur despite optimal medical treatment. Advanced left ventricular dysfunction, poor functional class (NYHA class III or IV), or prior cardiac events appear to increase the risk of maternal cardiac complications. However, there are no large series of cardiomyopathy patients who are regularly evaluated for cardiac complications during pregnancy and for certain types of inherited cardiomyopathy, only case reports on individual pregnancies are available. Pre-conception cardiologic evaluation and genetic counselling are important for every woman with a cardiomyopathy or a cardiomyopathy-related mutation who is considering having a family. In this article, we give an overview of the basic clinical aspects, genetics, and pregnancy outcome in women with different types of inherited cardiomyopathies. We also discuss the genetic aspects of pregnancy-associated cardiomyopathy, including peripartum cardiomyopathy.


Vulnerable Populations in Hospital and Health Care Emergency Preparedness Planning: A Comprehensive Framework for Inclusion.
As attention to emergency preparedness becomes a critical element of health care facility operations planning, efforts to recognize and integrate the needs of vulnerable populations in a comprehensive manner have lagged. This not only results in decreased levels of equitable service, but also affects the functioning of the health care system in disasters. While this report emphasizes the United States context, the concepts and approaches apply beyond this setting. This report: (1) describes a conceptual framework that provides a model for the inclusion of vulnerable populations into integrated health care and public health preparedness; and (2) applies this model to a pilot study. The framework is derived from literature, hospital regulatory policy, and health care standards, laying out the communication and relational interfaces that must occur at the systems, organizational, and community levels for a successful multi-level health care systems response that is inclusive of diverse populations explicitly. The pilot study illustrates the application of key elements of the framework, using a four-pronged approach that incorporates both quantitative and qualitative methods for deriving information that can inform hospital and health facility preparedness planning. The conceptual framework and model, applied to a pilot project, guide expanded work that ultimately can result in methodologically robust approaches to comprehensively incorporating vulnerable populations into the fabric of hospital disaster preparedness at levels from local to national, thus supporting best practices for a community resilience approach to disaster preparedness.


Postexercise syncope: Wingate syncope test and effective countermeasure.
Altered systemic haemodynamics following exercise can compromise cerebral perfusion and result in syncope. As the Wingate anaerobic test often induces presyncope, we hypothesized that a modified Wingate test could form the basis of a novel model for the study of postexercise syncope and a test bed for potential countermeasures. Along these lines, breathing through an impedance threshold device has been shown to increase tolerance to hypovolaemia, and could prove beneficial in the setting of postexercise syncope. Therefore, we hypothesized that a modified Wingate test followed by head-up tilt would produce postexercise syncope, and that breathing through an impedance threshold device (countermeasure) would prevent postexercise syncope in healthy individuals. Nineteen recreationally active men and women underwent a 60 deg head-up tilt during recovery from the Wingate test while arterial pressure, heart rate, end-tidal CO2 and cerebral tissue oxygenation were measured on a control day and a countermeasure day. The duration of tolerable tilt was increased by a median time of 3 min 48 s with countermeasure in comparison to the control (P < 0.05), and completion of the tilt test increased from 42 to 67% with the countermeasure. During the tilt, mean arterial pressure was greater (108.0 ± 4.1 versus 100.4 ± 2.4 mmHg; P < 0.05) with the countermeasure in comparison to the control. These data suggest that the Wingate syncope test produces a high incidence of presyncope, which is sensitive to countermeasures such as inspiratory impedance.


The Perspectives of Patients on Health-Care for Co-Morbid Diabetes and Chronic Kidney Disease: A Qualitative Study.
Multi-morbidity due to diabetes and chronic kidney disease (CKD) remains challenging for current health-systems, which focus on single diseases. As a first step toward health-care improvement, we explored the perspectives of patients and their carers on factors influencing the health-care of those with co-morbid diabetes and CKD. In this qualitative study participants with co-morbid diabetes and CKD were purposively recruited using maximal variation sampling from 4 major tertiary health-services from 2 of Australia's largest cities. Separate focus groups were conducted for patients with CKD stages 3, 4 and 5. Findings were triangulated with semi-structured interviews of carers of patients. Discussions were transcribed verbatim and thematically analysed. Twelve focus groups with 58 participants and 8 semi-structured interviews of carers were conducted. Factors influencing health-care of co-morbid diabetes and CKD grouped into patient and health service level factors. Key patient level factors identified were patient self-management, socio-economic situation, and adverse experiences related to co-morbid diabetes and CKD and its treatment. Key health service level factors were prevention and awareness of co-morbid diabetes and CKD, poor continuity and coordination of care, patient and carer empowerment, access and poor recognition of psychological co-morbidity. Health-service level factors varied according to CKD stage with poor continuity and coordination of care and patient and carer empowerment emphasized by participants with CKD stage 4 and 5, and access and poor recognition of psychological co-morbidity emphasised by participants with CKD stage 5 and carers. According to patients and their carers the health-care of co-morbid diabetes and CKD may be improved via a preventive, patient-centred health-care model which promotes self-management and that has good access, continuity and coordination of care and identifies and manages psychological morbidity.


Myeloid Dendritic Cells are Potential Players in Human Neurodegenerative Diseases.
Alzheimer's diseases (AD) and Parkinson's diseases (PD) are devastating neurodegenerative disturbances, wherein neuroinflammation is a chronic pathogenic process with high therapeutic potential. Major mediators of AD/PD neuroimmune processes are resident immune cells, but immune cells derived from periphery may also participate and to some extent modify neuroinflammation. Specifically, blood borne myeloid cells emerge as crucial components of AD/PD progression and susceptibility. Among these, dendritic cells (DCs) are key immune orchestrators and players of brain immune surveillance; we candidate them as potential mediators of both AD and PD and as relevant cell model for unraveling myeloid cell role in neurodegeneration. Hence, we recapitulate and discuss emerging data suggesting that blood-derived DCs play a role in experimental and human neurodegenerative diseases. In humans, in particular, DCs are modified by in vitro culture with neurodegeneration-associated pathogenic factors and dysregulated in AD patients, while the levels of DC precursors are decreased in AD and PD patients' blood, possibly as an index of their recruitment to the brain. Overall, we emphasize the need to explore the impact of DCs on neurodegeneration to uncover peripheral immune mechanisms of pathogenic importance, recognize potential biomarkers, and improve therapeutic approaches for neurodegenerative diseases.


Personality competence in black male adolescents.
This study explores the nature and antecedents of personality competence in Black male adolescents. Community college teachers were first asked to describe, in interview and Q-Sorts, the qualities they believed characterized competent young Black men. There was considerable agreement between Black and White teachers, and the ratings of both correlated highly with the California Q-Sort description of the Optimally Adjusted Personality described by White clinicians. In the second phase of the study, particularly competent young Black males, nominated by these teachers, were compared with average Black students on the same Q-Sort, a vocabulary test, and Offer's Self-Image Questionnaire. In general, the personality qualities of the two groups are more alike than different, though the more competent males are more inner- than outer-directed; more sensitive to personal qualities than to outward appearances and their own acceptability to others. They are more ambitious, more motivated for success, and seem to strive more vigorously, perhaps even to sidestep some moral precepts (indicated by lower Offer Morality score). The competent young Black males differ importantly, although not always significantly, from their more average peers in being earlier and more thoroughly committed to a work ethic; they come from more stable homes; have more social contact with the White culture; and are more likely to be first or only children. Although the study intended to contrast more and less competent adolescents within the Black culture, it is speculated that both the nature and antecedents of competence are probably transracial. Additional analyses show that competence can be empirically distinguished from social desirability, though the two concepts are related.


Expression analysis of MIF4GD in the rat testis.
The difference between transcriptional and translational activities of genes is one of the remarkable features in spermatogenesis. In this study, we characterized MIF4GD (MIF4G domain containing), a possible translational regulator, to uncover the function during rat spermatogenesis. Western blot analysis revealed the presence of two forms of MIF4GD with molecular sizes of 25 and 16 kDa in various tissues including the testis. An additional 20-kDa form of MIF4GD was also found exclusively in the testis. These three proteins were abundantly present in pachytene spermatocytes and haploid spermatids. Importantly, the 16-kDa MIF4GD was distinguished from the 25- and 20-kDa proteins by presence in fractions of 40S subunits and ribosomes of spermatogenic cells according to analysis of subcellular localizations. These results suggest that the 16-kDa MIF4GD may function as a translational regulator in spermiogenesis.


'Dynamics of neuronal interactions' cannot be explained by 'neuronal transients'.
In a recent paper, Vaadia et al. demonstrated that patterns of firing correlation between single neurons in the cortex of behaving monkeys can be modified within a fraction of a second. These changes occur in relation to sensory stimuli and behavioral events, and even without modulations of the neurons' firing rates. These findings call for a revision of prevailing models of neural coding that solely rely on single neuron firing rates. In a defense of these models, Friston put forward an alternative explanation, proposing that the observed correlation dynamics emerge solely from co-modulations of the firing rates of each of the neurons, while the strength of their interaction remains constant. To test this possibility we re-examined the data, adopting Friston's 'neuronal transients' model, and the associated equations and procedures. We found that, to explain the dynamic correlation between a pair of neurons, the alternative interpretation requires that each neuron's response to a single stimulus is composed of a relatively large number of independent components, which co-vary with their counterparts in the companion neuron. This large number of components and their shapes lead us to conclude that, although in principle possible, the neuronal transients model: (i) does not provide a simpler explanation of the experimental results; and (ii) cannot explain these results without itself deviating significantly from most rate code models.


Pathophysiology of Major Depression by Clinical Stages.
The comprehension of the pathophysiology of the major depressive disorder (MDD) is essential to the strengthening of precision psychiatry. In order to determine the relationship between the pathophysiology of the MDD and its clinical progression, analyzed by severity of the depressive symptoms and sleep quality, we conducted a study assessing different peripheral molecular biomarkers, including the levels of plasma C-reactive protein (CRP), serum mature brain-derived neurotrophic factor (mBDNF), serum cortisol (SC), and salivary cortisol awakening response (CAR), of patients with MDD (n = 58) and a control group of healthy volunteers (n = 62). Patients with the first episode of MDD (n = 30) had significantly higher levels of CAR and SC than controls (n = 32) and similar levels of mBDNF of controls. Patients with treatment-resistant depression (TRD, n = 28) presented significantly lower levels of SC and CAR, and higher levels of mBDNF and CRP than controls (n = 30). An increased severity of depressive symptoms and worse sleep quality were correlated with levels low of SC and CAR, and with high levels of mBDNF. These results point out a strong relationship between the stages clinical of MDD and changes in a range of relevant biological markers. This can assist in the development of precision psychiatry and future research on the biological tests for depression.


[Results of the residential cardiac rehabilitation in patients after myocardial infarction treated with percutaneous coronary intervention (PCI)].
Patients after cardiac infarct and primary PCI are mainly people shortly immobilized with slight damage of the heart muscle with good condition and low consciousness of the disease. Development of the cardiology gives new goals for a cardiac rehabilitation. Traditional rehabilitation targets just like preventation results of immobilization and raising of efficiency are now not so important. Main task of modern rehabilitation, except function improvement of life quality, is preventation of progress coronary disease and reduction of mortality by changing health behavior, especially consent to regular physical activity. The purpose of this study was to evaluate physical efficiency and life quality of life in patients after myocardial infarction treated with PCI who participated in residential cardiac rehabilitations according to age and time of beginning this process. 167 patients (male) after myocardial infarction treated with primary PCI in age 33-82 years, mean age 57,1 +/- 8,92 (years). All patients participated in a 20 +/- 2 (days) comprehensive residential cardiac rehabilitation. ECG treadmill exercise test according Bruce protocol was performed after beginning and at the end of rehabilitation process. Quality of life was evaluated according to SF-36 questionnaire completed at the beginning and after rehabilitation programm. Residential cardiac rehabilitation increases physical efficiency and improves quality of life in patients who undergo primary PCI after myocardial infarction. Effects of cardiac rehabilitation dose not depend on age or on time of beginning of rehabilitation. Most significant increase of physical efficiency was observed in patients who were referend to cardiac rehabilitation no longer then 6 weeks after cardiac event.


Cultural and linguistic fairness in the assessment of semantics.
In creating a semantic assessment that will be linguistically and culturally fair, it is important to avoid the bias of acquired vocabulary tests. This article describes techniques to assess children's processing of new words, their lexical organization and retrieval, which may be more significant than the number of words known. Special properties of the quantifier every also give an idea of the child's level of semantic ability. In addition, we examine how the child's performance on each item-type helps the speech-language pathologist determine the sources of children's problems in this domain.


Searching for potential biomarkers of cisplatin resistance in human ovarian cancer using a label-free LC/MS-based protein quantification method.
Platinum-based chemotherapy, such as cisplatin, is the primary treatment for ovarian cancer. However, drug resistance has become a major impediment to the successful treatment of ovarian cancer. To date, the molecular mechanisms of resistance to platinum-based chemotherapy remain unclear. In this study, we applied an LC/MS-based protein quantification method to examine the global protein expression of two pairs of ovarian cancer cell lines, A2780/A2780-CP (cisplatin-sensitive/cisplatin-resistant) and 2008/2008-C13*5.25 (cisplatin-sensitive/cisplatin-resistant). We identified and quantified over 2000 proteins from these cell lines and 760 proteins showed significant expression changes with a false discovery rate of less than 5% between paired groups. Based on the results we obtained, we suggest several potential pathways that may be involved in cisplatin resistance in human ovarian cancer. This study provides not only a new proteomic platform for large-scale quantitative protein analysis, but also important information for discovery of potential biomarkers of cisplatin resistance in ovarian cancer. Furthermore, these results may be clinically relevant for diagnostics, prognostics, and therapeutic improvement for ovarian cancer treatment.


Auditory event-related potentials associated with perceptual reversals of bistable pitch motion.
Previous event-related potential (ERP) experiments have consistently identified two components associated with perceptual transitions of bistable visual stimuli, the "reversal negativity" (RN) and the "late positive complex" (LPC). The RN (~200 ms post-stimulus, bilateral occipital-parietal distribution) is thought to reflect transitions between neural representations that form the moment-to-moment contents of conscious perception, while the LPC (~400 ms, central-parietal) is considered an index of post-perceptual processing related to accessing and reporting one's percept. To explore the generality of these components across sensory modalities, the present experiment utilized a novel bistable auditory stimulus. Pairs of complex tones with ambiguous pitch relationships were presented sequentially while subjects reported whether they perceived the tone pairs as ascending or descending in pitch. ERPs elicited by the tones were compared according to whether perceived pitch motion changed direction or remained the same across successive trials. An auditory reversal negativity (aRN) component was evident at ~170 ms post-stimulus over bilateral fronto-central scalp locations. An auditory LPC component (aLPC) was evident at subsequent latencies (~350 ms, fronto-central distribution). These two components may be auditory analogs of the visual RN and LPC, suggesting functionally equivalent but anatomically distinct processes in auditory vs. visual bistable perception.


[The sodium-potassium pump in hypertension. Mechanisms of action of potassium].
Increasing evidence indicates that sodium ingestion in the face of an inability to excrete it normally causes hypertension by releasing a humoral pressor substance. This substance, which is probably the putative natriuretic hormone, inhibits Na+-K+-ATPase and thereby increases cardiac contractility and blood vessel tone. Potassium may be antihypertensive in part by virtue of its ability to stimulate Na+-K+-ATPase in the vascular smooth muscle cells and in adrenergic nerve endings, thereby causing vasodilation.


Conditional disruption of AMP kinase in dopaminergic neurons promotes Parkinson's disease-associated phenotypes in vivo.
Emerging studies implicate energy dysregulation as an underlying trigger for Parkinson's disease (PD), suggesting that a better understanding of the molecular pathways governing energy homeostasis could help elucidate therapeutic targets for the disease. A critical cellular energy regulator is AMP kinase (AMPK), which we have previously shown to be protective in PD models. However, precisely how AMPK function impacts on dopaminergic neuronal survival and disease pathogenesis remains elusive. Here, we showed that Drosophila deficient in AMPK function exhibits PD-like features, including dopaminergic neuronal loss and climbing impairment that progress with age. We also created a tissue-specific AMPK-knockout mouse model where the catalytic subunits of AMPK are ablated in nigral dopaminergic neurons. Using this model, we demonstrated that loss of AMPK function promotes dopaminergic neurodegeneration and associated locomotor aberrations. Accompanying this is an apparent reduction in the number of mitochondria in the surviving AMPK-deficient nigral dopaminergic neurons, suggesting that an impairment in mitochondrial biogenesis may underlie the observed PD-associated phenotypes. Importantly, the loss of AMPK function enhances the susceptibility of nigral dopaminergic neurons in these mice to 6-hydroxydopamine-induced toxicity. Notably, we also found that AMPK activation is reduced in post-mortem PD brain samples. Taken together, these findings highlight the importance of neuronal energy homeostasis by AMPK in PD and position AMPK pathway as an attractive target for future therapeutic exploitation.


Virtual Planning and 3D Printing in Contemporary Orthognathic Surgery.
Orthognathic surgery is a powerful tool to improve facial balance, form, and function. Virtual planning and three-dimensional printing has improved our ability to visualize complex anatomy, consider various iterations and execute complex movements, and create accurate splints, plates, and cutting guides. This article will outline the distinct advantages of the use of virtual surgical planning over traditional planning, and it will explore the utility of computer-aided design and technology within contemporary orthognathic surgery, including its expanded applications and limitations.


Telomere dynamics in the lower plant Physcomitrella patens.
A comparative approach in biology is needed to assess the universality of rules governing this discipline. In plant telomere research, most of the key principles were established based on studies in only single model plant, Arabidopsis thaliana. These principles include the absence of telomere shortening during plant development and the corresponding activity of telomerase in dividing (meristem) plant cells. Here we examine these principles in Physcomitrella patens as a representative of lower plants. To follow telomerase expression, we first characterize the gene coding for the telomerase reverse transcriptase subunit PpTERT in P. patens, for which only incomplete prediction has been available so far. In protonema cultures of P. patens, growing by filament apical cell division, the proportion of apical (dividing) cells was quantified and telomere length, telomerase expression and activity were determined. Our results show telomere stability and demonstrate proportionality of telomerase activity and expression with the number of apical cells. In addition, we analyze telomere maintenance in mre11, rad50, nbs1, ku70 and lig4 mutants of P. patens and compare the impact of these mutations in double-strand-break (DSB) repair pathways with earlier observations in corresponding A. thaliana mutants. Telomere phenotypes are absent and DSB repair kinetics is not affected in P. patens mutants for DSB factors involved in non-homologous end joining (NHEJ). This is compliant with the overall dominance of homologous recombination over NHEJ pathways in the moss, contrary to the inverse situation in flowering plants.


[Migration as a factor in the genetic heterogeneity of the population of large cities].
The report deals with the influence of migration on genetic heterogeneity of population of big cities. The study of AB0 blood groups frequency distribution in population of Moscow during the period of 50 years shows that the observed genetic heterogeneity is associated with demographic structure of the groups compared. Besides, the evaluation of genetic identity of Moscow population and that of different Russian regions population is related to the migrants part having come to Moscow from these regions.


Early onset of reproductive function in normal female mice treated with leptin.
Numerous studies have revealed an association between nutritional status, adiposity, and reproductive maturity. The role of leptin, a hormone secreted from adipose tissue, in the onset of reproductive function was investigated. Normal prepubertal female mice injected with leptin grew at a slower rate than controls as a result of the hormone's thinning effects, but they reproduced up to 9 days earlier than controls and showed earlier maturation of the reproductive tract. These results suggest that leptin acts as a signal triggering puberty, thus supporting the hypothesis that fat accumulation enhances maturation of the reproductive tract.


Structure and phase behavior of polymer-linked colloidal gels.
Low-density "equilibrium" gels that consist of a percolated, kinetically arrested network of colloidal particles and are resilient to aging can be fabricated by restricting the number of effective bonds that form between the colloids. Valence-restricted patchy particles have long served as one archetypal example of such materials, but equilibrium gels can also be realized through a synthetically simpler and scalable strategy that introduces a secondary linker, such as a small ditopic molecule, to mediate the bonds between the colloids. Here, we consider the case where the ditopic linker molecules are low-molecular-weight polymers and demonstrate using a model colloid-polymer mixture how macroscopic properties such as the phase behavior as well as the microstructure of the gel can be designed through the polymer molecular weight and concentration. The low-density window for equilibrium gel formation is favorably expanded using longer linkers while necessarily increasing the spacing between all colloids. However, we show that blends of linkers with different sizes enable wider variation in microstructure for a given target phase behavior. Our computational study suggests a robust and tunable strategy for the experimental realization of equilibrium colloidal gels.


Analysis of bevacizumab-based preoperative radiochemotherapy in patients with locally advanced rectal cancer on surgery-associated spectrum of complications.
Preoperative radiochemotherapy (RCT) is a standard of care for patients with locally advanced rectal cancer (LARC; stages II and III). Results of our phase II study (BevXelOx-RT) have shown that this regimen is feasible but without a significant improvement of pathological complete response. Whether preoperatively administered bevacizumab, due to its specific toxicity profile, leads to increased rates of surgical complications is currently a subject for debate. This analysis focusses on the surgery-associated spectrum of complications. Data from 62 patients with rectal cancer (uT3-4; N0/1, M0) of the phase II trial were analyzed. Patients received radiotherapy (50.4/1.8 Gy fractions), simultaneous bevacizumab 5 mg/kg (d1, d15, d29), and capecitabine 825 mg/m(2) twice daily (d1-14, d22-35), oxaliplatin 50 mg/m(2) (d1, d8, d22, d29). Four to six weeks after RCT, surgical resection was performed. Overall, 69/69 patients underwent surgery, and 66 (95.7 %) patients had R0 resection. Surgery was mainly conducted (in 66 %) by highly experienced surgeons (>20 resections of rectal cancer/year) with differences between the institutions due to the operative procedures but without effects on the rate of R0 resection or complications. The average duration of surgery was 239 min (±10). Frequency of multivisceral resections (11 %), intraoperative (8 %) and postoperative (43 %) complications were all in the expected range. In particular, we did not observe an increased rate of postoperative bleedings (3 %). The postoperative mortality rate was 0 %. Quantity and the kind of surgery-associated spectrum of complications followed by a preoperative bevacizumab-containing RCT regimen in patients with LARC were in line with comparable trials of bevacizumab-based approaches.


Whole body leptin kinetics and renal metabolism in vivo.
Leptin metabolism was investigated in male Sprague-Dawley rats by use of 125I-labeled leptin plasma kinetic and arteriovenous balance studies. When conscious rats received bolus venous injections of 125I-leptin, intact (precipitable) leptin quickly disappeared from circulation in a biexponential manner during the 2-h experimental period. After substantial delay, most of the injected radioactivity appeared in the urine. The data were described by a two-compartment model, which postulated that plasma leptin exchanged with a nonplasma pool and that all of the tracer cleared from plasma appeared in urine or in a degraded form in plasma. The half-life of leptin was 9.4 +/- 3.0 min, and the leptin production rate was 3.6 +/- 1.2 ng 100 g fat-1.min-1. The left kidney extracted 21 +/- 1.5% of intact arterial 125I-leptin 5 min after femoral venous injection. Endogenous arterial leptin was reduced 21 +/- 8 and 18 +/- 12%, respectively, in simultaneously sampled left and right renal veins. Renal elimination appears to be the major elimination mechanism for leptin in normal rats, and the kinetic studies suggest that uptake of leptin by renal tissue rather than glomerular filtration is the predominant elimination mechanism.


Impact of a risk management plan on Legionella contamination of dental unit water.
The study aimed to assess the prevalence of Legionella spp. in dental unit waterlines of a dental clinic and to verify whether the microbiological parameters used as indicators of water quality were correlated with Legionella contamination. A risk management plan was subsequently implemented in the dental health care setting, in order to verify whether the adopted disinfection protocols were effective in preventing Legionella colonization. The water delivered from syringes and turbines of 63 dental units operating in a dental clinic, was monitored for counts of the heterotrophic bacteria P. aeruginosa and Legionella spp. (22 °C and 37 °C). At baseline, output water from dental units continuously treated with disinfection products was more compliant with the recommended standards than untreated and periodically treated water. However, continuous disinfection was still not able to prevent contamination by Legionella and P. aeruginosa. Legionella was isolated from 36.4%, 24.3% and 53.3% of samples from untreated, periodically and continuously treated waterlines, respectively. The standard microbiological parameters used as indicators of water quality proved to be unreliable as predictors of the presence of Legionella, whose source was identified as the tap water used to supply the dental units. The adoption of control measures, including the use of deionized water in supplying the dental unit waterlines and the application of a combined protocol of continuous and periodic disinfection, with different active products for the different devices, resulted in good control of Legionella contamination. The efficacy of the measures adopted was mainly linked to the strict adherence to the planned protocols, which placed particular stress on staff training and ongoing environmental monitoring.


Differential maturation of murine bone-marrow derived dendritic cells with lipopolysaccharide and tumor necrosis factor-alpha.
Dendritic cells (DCs) play a key role in the interface between the innate and acquired immune systems. In response to both exogenous as well as endogenous signals, DCs undergo a programmed maturation to become an efficient, antigen-presenting cell. Yet little is known regarding the differential responses by endogenous versus exogenous stimuli on DC maturation. In the present report, we have compared the phenotypic, functional, and genome-wide expression responses associated with maturation by bone marrow derived DCs to either an endogenous danger signal, tumor necrosis factor-alpha (TNF-alpha), or a microbial product, bacterial lipopolysaccharide (LPS). Examination of the cell surface expression of DCs as well as cytokine production demonstrated that patterns of DC maturation varied dramatically depending upon the stimulus. Whereas LPS was highly effective in terms of inducing phenotypic and functional maturation, TNF-alpha exposure produced a phenotypically distinct DC. Gene expression patterns in DCs 6 and 24 h after LPS and TNF-alpha exposure revealed that these activation signals produce fundamentally different genomic responses. Supervised analysis revealed that the expression of 929 probe sets discriminated among the treatment groups, and the patterns of gene expression in TNF-alpha stimulated DCs were more similar to unstimulated cells at both 6 and 24 h post-stimulation than to LPS-stimulated cells at the same time points. These findings reveal that DCs are capable of a varying phenotypic response to different antigens and endogenous signals.


Structure of the sinus-lining cells in the popliteal lymph node of the rabbit.
The structure of the sinus walls in the popliteal lymph node of the rabbit was studied with the electron microscope. In the marginal sinus, the endothelial cells are connected by gap junctions, puncta adherentia, and surface specializations characterized by focal approximation of the adjoining membranes without fusion. They possess large numbers of simple and compound uncoated invaginations of the plasma membrane that are closed by a diaphragm with a central thickening. The tissue strands that straddle the lumen of the sinus consist of a fibrous core containing both collagen and elastic fibers, surrounded by endothelial cells identical to those composing the outer sinus wall. Cortical sinuses that run independently of the trabeculae were identified by exploiting the fact that their endothelial cells accumulate lymph-borne ferritin, and their lumen is outlined by horseradish peroxidase administered intravenously. They are lined by a flattened, continuous endothelium and lack luminal strands. The walls of the medullary sinuses consist of endothelial cells and macrophages. The endothelial cells are interconnected by specialized junctions and contain fewer plasmalemmal vesicles than in the cortex; furthermore, dense granules are present in their cytoplasm. Macrophages adhere to the surface of the endothelial cells; typically, none of the junctional specializations that characterize the interface between endothelial cells connect endothelial cells to macrophages. However, at points along the contact region with the endothelium, the plasmalemma of the macrophage is decorated by an attachment plaque of fluffy cytoplasmic material. Sinus endothelial cells slowly accumulate lymph-borne ferritin like vascular endothelial cells elsewhere in the body, whereas macrophages contain both ferritin and engulfed erythrocytes.


Pain Catastrophizing and Pain Health-Related Quality-of-Life in Endometriosis.
To determine if pain catastrophizing is independently associated with pain health-related quality-of-life (HRQoL) in women with endometriosis, independent of potential confounders. Analysis of cross-sectional baseline data from a prospective database at a tertiary referral center for endometriosis/pelvic pain. Referrals to the center were recruited between December 2013 to April 2015, with data collected from online patient questionnaires, physical examination, and review of medical records. The primary outcome was HRQoL as measured by the 11-item pain subscale of the Endometriosis Health Profile-30 questionnaire. The Pain Catastrophizing Scale was the independent variable of interest. Other independent variables (potential confounders) included other psychological measures, pain severity, comorbid pain conditions, and social-behavioral and demographic variables. Multivariable linear regression was used to control for these potential confounders and assess independent associations with the primary outcome. In total, 236 women were included (87% consent rate). The mean age was 35.0±7.3 years, and 98 (42%) had stage I to II endometriosis, 110 (47%) had stage III to IV endometriosis, and 28 (11%) were of unknown stage after review of operative records. Regression analysis demonstrated that higher pain catastrophizing (P<0.001), more severe chronic pelvic pain (P<0.001), more severe dysmenorrhea (P<0.001), and abdominal wall pain (positive Carnett test) (P=0.033) were independently associated with worse pain HRQoL. Higher pain catastrophizing was associated with a reduced pain HRQoL in women with endometriosis at a tertiary referral center, independent of pain severity and other potential confounders.


Local Dynamics of Collaboration for Maternal, Newborn and Child Health: A Social Network Analysis of Healthcare Providers and Their Managers in Gert Sibande District, South Africa.
Accountability for maternal, newborn and child health (MNCH) is a collaborative endeavour and documenting collaboration dynamics may be key to understanding variations in the performance of MNCH services. This study explored the dynamics of collaboration among frontline health professionals participating in two MNCH coordination structures in a rural South African district. It examined the role and position of actors, the nature of their relationships, and the overall structure of the collaborative network in two sub-districts. Cross-sectional survey using a social network analysis (SNA) methodology of 42 district and sub district actors involved in MNCH coordination structures. Different domains of collaboration (eg, communication, professional support, innovation) were surveyed at key interfaces (district-sub-district, across service delivery levels, and within teams). The overall network structure reflected a predominantly hierarchical mode of clustering of organisational relationships around hospitals and their referring primary healthcare (PHC) facilities. Clusters were linked through (and dependent on) a combination of district MNCH programme and line managers, identified as central connectors or boundary spanners. Overall network density remained low suggesting potential for strengthening collaborative relationships. Within cluster collaborative patterns (inter-professional and across levels) varied, highlighting the significance of small units in district functioning. SNA provides a mechanism to uncover the nature of relationships and key actors in collaborative dynamics which could point to system strengths and weaknesses. It offers insights on the level of fragmentation within and across small units, and the need to strengthen cohesion and improve collaborative relationships, and ultimately, the delivery of health services.