Porphyromonas gingivalis fimbriae are pro-inflammatory but do not play a prominent role in the innate immune response to P. gingivalis.
The fimA gene encodes the major fimbrial protein of Porphyromonas gingivalis. It has been shown to stimulate adhesion to salivary proteins and other bacteria. It is also thought to play a major role in invading and stimulating host cells. To determine whether the fimA gene represents one of the principal molecules of P. gingivalis that induces inflammation, we tested purified FimA protein and a mutant P. gingivalis (DPG3) that lacks the fimA gene versus wild-type (WT) P. gingivalis. When injected into connective tissue of the scalp, purified FimA protein induced TNF-alpha and MIP-2 expression confirming that it is pro-inflammatory. WT P. gingivalis induced TNF-alpha expression and recruitment of PMNs in the same model. However, DPG3 P. gingivalis stimulated TNF expression and PMN recruitment to the same extent. The latter was consistent with similar induction of the chemokine MIP-2. Similar results were obtained with diabetic mice that have a more prolonged inflammatory response to bacterial stimulation. These results indicate that FimA is a potent inducer of inflammatory cytokine expression but, in the context of P. gingivalis infection, it is not a principal stimulator of the innate host response.


Determination of minimum inhibitory concentrations of itraconazole, terbinafine and ketoconazole against dermatophyte species by broth microdilution method.
Various antifungal agents both topical and systemic have been introduced into clinical practice for effectively treating dermatophytic conditions. Dermatophytosis is the infection of keratinised tissues caused by fungal species of genera Trichophyton, Epidermophyton and Microsporum, commonly known as dermatophytes affecting 20-25% of the world's population. The present study aims at determining the susceptibility patterns of dermatophyte species recovered from superficial mycoses of human patients in Himachal Pradesh to antifungal agents; itraconazole, terbinafine and ketoconazole. The study also aims at determining the minimum inhibitory concentrations (MICs) of these agents following the recommended protocol of Clinical and Laboratory Standards Institute (CLSI) (M38-A2). A total of 53 isolates of dermatophytes (T. mentagrophyte-34 in no., T. rubrum-18 and M. gypseum-1) recovered from the superficial mycoses were examined. Broth microdilution method M38-A2 approved protocol of CLSI (2008) for filamentous fungi was followed for determining the susceptibility of dermatophyte species. T. mentagrophyte isolates were found more susceptible to both itraconazole and ketoconazole as compared to terbinafine (MIC50: 0.125 µg/ml for itraconazole, 0.0625 µg/ml for ketoconazole and 0.5 µg/ml for terbinafine). Three isolates of T. mentagrophytes (VBS-5, VBSo-3 and VBSo-73) and one isolate of T. rubrum (VBPo-9) had higher MIC values of itraconazole (1 µg/ml). Similarly, the higher MIC values of ketoconazole were observed in case of only three isolates of T. mentagrophyte (VBSo-30 = 2 µg/ml; VBSo-44, VBM-2 = 1 µg/ml). The comparative analysis of the three antifungal drugs based on t-test revealed that 'itraconazole and terbinafine' and 'terbinafine and ketoconazole' were found independent based on the P < 0.005 in case of T. mentagrophyte isolates. In case of T. rubrum, the similarity existed between MIC values of 'itraconazole and ketoconazole' and 'terbinafine and ketoconazole'. The MIC values observed in the present study based on standard protocol M38-A2 of CLSI 2008 might serve as reference for further studies covering large number of isolates from different geographic regions of the state. Such studies might reflect on the acquisition of drug resistance among isolates of dermatophyte species based on MIC values.


Endothelium-targeted delivery of dexamethasone by anti-VCAM-1 SAINT-O-Somes in mouse endotoxemia.
Microvascular endothelial cells play a pivotal role in the pathogenesis of sepsis-induced inflammatory responses and multiple organ failure. Therefore, they represent an important target for pharmacological intervention in the treatment of sepsis. Glucocorticosteroids were widely used in the treatment of sepsis but vast evidence to support their systemic use is lacking. The limited effects of glucocorticoids in the treatment of sepsis may be explained by differential effects of drug initiated NF-κB inhibition in different cell types and insufficient drug delivery in target cells. The current study aimed therefore to investigate the effects of an endothelial targeted delivery of dexamethasone in a mouse model of endotoxemia induced by two consecutive i.p. injections of lipopolysaccharide (LPS). To achieve endothelial cell specific delivery of dexamethasone, we modified SAINT-O-Somes, a new generation of liposomes that contain the cationic amphiphile SAINT-C18 (1-methyl-4-(cis-9-dioleyl) methyl-pyridinium chloride, with antibodies against vascular cell adhesion molecule-1 (VCAM-1). In LPS challenged mice, the systemic administration of free dexamethasone had negligible effects on the microvascular inflammatory endothelial responses. Dexamethasone-loaded anti-VCAM-1 SAINT-O-Somes specifically localized at VCAM-1 expressing endothelial cells in the microvasculature of inflamed organs. This was associated with a marginal attenuation of the expression of a few pro-inflammatory genes in kidney and liver, while no effects in the lung were observed. This study reveals that, although local accumulation of the targeted drug was achieved, endothelial targeted dexamethasone containing anti-VCAM-1 SAINT-O-Somes exhibited marginal effects on inflammatory endothelial cell activation in a model of endotoxemia. Studies with more potent drugs encapsulated into anti-VCAM-1 SAINT-O-Somes will in the future reveal whether this delivery system can be further developed for efficacious endothelial directed delivery of drugs in the treatment of sepsis.


Integrated metabolomics and transcriptomics reveal glyphosate based-herbicide induced reproductive toxicity through disturbing energy and nucleotide metabolism in mice testes.
Glyphosate is a widely used herbicide that has deleterious effects on animal reproduction. However, details regarding the systematic mechanisms of glyphosate-induced reproductive toxicity are limited. This study aimed to investigate the toxic effects of glyphosate-based herbicide (GBH) on reproduction in mice exposed to 0 (control group), 50 (low-dose group), 250 (middle-dose group), and 500 (high-dose group) mg/kg/day GBH for 30 days. Toxicological parameters, metabolomics, and transcriptomics were performed to reveal GBH-induced reproductive toxicity. Our findings demonstrated that GBH exposure damaged mitochondrial pyknosis and the nuclear membrane of spermatogonia. GBH triggered a significant increase in sperm malformations in the high-dose group. Omics data showed that GBH impaired the Krebs cycle and respiratory chain, blocked pyruvate metabolism and glycolysis/gluconeogenesis, and influenced the pentose phosphate pathway and nucleotide synthesis and metabolism. Overall, the multi-omics results revealed systematic and comprehensive evidence of the adverse effects of GBH exposure, providing new insights into the reproductive toxicity of organophosphorus pesticides.


Relationships among three pathways for resource acquisition and their contribution to plant performance in the emergent aquatic Plant Lythrum salicaria (L.).
Three pathways for resource acquisition exist in the emergent aquatic plant, Lythrum salicaria (L.); a subterranean root system, a free-floating adventitious root system, and arbuscular mycorrhiza (AM) fungal hyphae colonizing subterranean roots. This study examined the relationship(s) among these pathways and their contribution to plant performance. If the free-floating adventitious root system and/or AM fungi contribute to plant growth in wetland habitats, we predicted that their absence would result in a significant reduction in plant performance. Furthermore, if a reduction in resource uptake, effected by an absence of free-floating adventitious roots and/or AM fungi, is compensated for by increased allocation to remaining pathway(s) for resource uptake, we predicted altered patterns of resource allocation among shoots and the remaining pathway(s) for resource uptake. Contrary to our predications, plants experiencing adventitious root removal and/or grown in the absence of AM fungi generally had greater biomass and total shoot height than controls. Similarly, while levels of AM colonization and subterranean root biomass displayed a treatment effect, the observed responses did not correspond with our predictions. This was also true for shoot : subterranean root dry weight ratios. Our results indicate that there is interaction among the 3 pathways for resource acquisition in L. salicaria and an effect on plant performance. The adaptive significance of these characteristics is unclear, highlighting the potential difficulties in extrapolating from terrestrial to aquatic plant species and among aquatic plant species with potentially different life history strategies.


Phospholipid fatty acid remodeling and carbonylated protein increase in extracellular vesicles released by airway epithelial cells exposed to cigarette smoke extract.
Cigarette smoke (CS) represents one of the most relevant environmental risk factors for several chronic pathologies. Tissue damage caused by CS exposure is mediated, at least in part, by oxidative stress induced by its toxic and pro-oxidant components. Evidence demonstrates that extracellular vesicles (EVs) released by various cell types exposed to CS extract (CSE) are characterized by altered biochemical cargo and gained pathological properties. In the present study, we evaluated the content of oxidized proteins and phospholipid fatty acid profiles of EVs released by human bronchial epithelial BEAS-2B cells treated with CSE. This specific molecular characterization has hitherto not been performed. After confirmation that CSE reduces viability of BEAS-2B cells and elevates intracellular ROS levels, in a dose-dependent manner, we demonstrated that 24 h exposure at 1% CSE, a concentration that only slight modifies cell viability but increases ROS levels, was able to increase carbonylated protein levels in cells and released EVs. The release of oxidatively modified proteins via EVs might represent a mechanism used by cells to remove toxic proteins in order to avoid their intracellular overloading. Moreover, 1% CSE induced only few changes in the fatty acid asset in BEAS-2B cell membrane phospholipids, whereas several rearrangements were observed in EVs released by CSE-treated cells. The impact of changes in acyl chain composition of CSE-EVs accounted for the increased saturation levels of phospholipids, a membrane parameter that might influence EV stability, uptake and, at least in part, EV-mediated biological effects. The present in vitro study adds new information concerning the biochemical composition of CSE-related EVs, useful to predict their biological effects on target cells. Furthermore, the information regarding the presence of oxidized proteins and the specific membrane features of CSE-related EVs can be useful to define the utilization of circulating EVs as marker for diagnosing of CS-induced lung damage and/or CS-related diseases.


Fine-needle aspiration cytology of a para-aortical solitary plasma-cell tumor.
Extramedullary plasma-cell tumor (EMP) is a very rare disease and mainly arises in the head and neck area. An EMP arising in the paraaortical space was diagnosed by fine needle aspiration cytology and immunocytochemistry, in a 48-year-old male. Smears were cellular and showed dissociated monomorphic plasma cells. Immunocytochemistry demonstrated monoclonal expression of kappa-light immunoglobulin chain and CD38 positivity. Cytomorphology and immunocytochemical profile allowed a definitive diagnosis of plasmacytoma.


HER-2 amplification but not butyrylcholinesterase multability reflects aggressiveness of European-originated ovarian tumors.
Tumorigenic roles were variably suggested for HER-2 and INT-2 oncogene amplifications and the "atypical" aspartate to glycine mutability in the butyrylcholinesterase (BCHE) gene in ovarian adenocarcinomas. To examine this notion we searched for correlations between these three phenomena and ovarian tumor classification and aggressiveness, using quantitative polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and direct PCR sequencing. Our findings revealed no alleles carrying the atypical BCHE mutability in 30 European-originated patients with ovarian tumors compared with 11% (2/18) such alleles in Israeli patients with malignant ovarian tumors. This apparently reflected population diversity rather than disease relationship. INT-2 amplification was observed in 14/94 (15%) of the European patients; however, there was no correlation between this phenomenon and clinicopathological indices in the corresponding patients. In contrast, in 94 tumor samples we found that 40% (38/94) of the cases had HER-2 amplification. Moreover, there was a highly significant correlation (P < 0.008) between the over fivefold HER-2 amplification and ovarian tumor severity. These findings demonstrate an informative value for HER-2 amplification tests in tumor DNA, but not for INT-2 amplification or BCHE mutability, for the assessment of treatment.


A prospective national study of acute renal failure treated with RRT: incidence, aetiology and outcomes.
Acute renal failure (ARF) is a diverse condition with no standardized definition and is managed in several sub-specialty areas within hospitals. Its incidence and aetiology are unknown and studies show a wide range of incidences. ARF is becoming more common as the population ages leading to the hypothesis that the incidence is much higher than previous estimates. This prospective population study investigated the incidence, aetiology and outcomes of ARF based on a standardized classification of ARF treated by renal replacement therapy (RRT) in all sub-specialty areas within hospitals where such treatment takes place. Data were collected prospectively on all patients starting RRT for ARF within three 12-week periods in 2002. Two hundred eighty-six adults per million population (pmp) per year received RRT for ARF. The incidence increased with age and pre-existing comorbid illness. Two hundred twelve adults pmp per year had no evidence of pre-existing chronic kidney disease (CKD) and the remainder had acute on CKD. The median age was 67 years. Fifty-one percent of the patients received their first RRT treatment in a critical care setting. Sepsis was the most common aetiological insult contributing to ARF in 48% of the patients. Mortality was high with 48% dying within 90 days of starting RRT. Age, comorbidity, sepsis and recent surgery were independent risk factors for death in those with no pre-existing CKD. This is the first national study to describe ARF treated with RRT in all hospital locations. The hypothesis that ARF occurs more frequently than previously thought has been confirmed. This study provides data upon which to base effective decision making for prevention, patient care and resource planning for patients with ARF.


An Evaluation on the Role of Non-Coding RNA in HIV Transcription and Latency: A Review.
The existence of latent cellular reservoirs is recognized as the major barrier to an HIV cure. Reactivating and eliminating "shock and kill" or permanently silencing "block and lock" the latent HIV reservoir, as well as gene editing, remain promising approaches, but so far have proven to be only partially successful. Moreover, using latency reversing agents or "block and lock" drugs pose additional considerations, including the ability to cause cellular toxicity, a potential lack of specificity for HIV, or low potency when each agent is used alone. RNA molecules, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are becoming increasingly recognized as important regulators of gene expression. RNA-based approaches for combatting HIV latency represent a promising strategy since both miRNAs and lncRNAs are more cell-type and tissue specific than protein coding genes. Thus, a higher specificity of targeting the latent HIV reservoir with less overall cellular toxicity can likely be achieved. In this review, we summarize current knowledge about HIV gene expression regulation by miRNAs and lncRNAs encoded in the human genome, as well as regulatory molecules encoded in the HIV genome. We discuss both the transcriptional and post-transcriptional regulation of HIV gene expression to align with the current definition of latency, and describe RNA molecules that either promote HIV latency or have anti-latency properties. Finally, we provide perspectives on using each class of RNAs as potential targets for combatting HIV latency, and describe the complexity of the interactions between different RNA molecules, their protein targets, and HIV.


Beef tallow diet decreases uncoupling protein content in the brown adipose tissue of rats.
The effects of dietary fats consisting of different fatty acids on the content of mitochondrial uncoupling protein in the interscapular brown adipose tissue were studied in rats. Sprague-Dawley male rats were meal-fed an isoenergetic diet based on either beef tallow or safflower oil for nine weeks. The gain in body weight during the experimental period did not differ between the two dietary groups. The weight of the brown adipose tissue was similar in the two dietary groups, whereas the weight of the abdominal white adipose tissue was larger in rats fed the beef tallow diet. The content of mitochondrial uncoupling protein in brown adipose tissue was lower in the beef tallow diet group than in the safflower oil diet group without differing mitochondrial mass between the two dietary groups. These results suggest that, in rats, a beef tallow diet reduces the content of uncoupling protein in brown adipose tissue, resulting in lower diet-induced thermogenesis as compared to a safflower oil diet.


Racial/ethnic disparity trends in children's mental health care access and expenditures from 2002 to 2007.
To examine trends in disparities in children's mental health care. 2002-2007 Medical Expenditure Panel Survey. We used the Institute of Medicine (IOM) definition of health care disparities and estimated two-part expenditure models to examine disparity trends in any mental health care use, any outpatient care, and psychotropic drug use, as well as expenditures in these three categories, conditional on use. We used 2-year longitudinal panel data to determine disparities in care initiation among children with unmet need. Assessing trends over time between 2002 and 2007, we identified that disparities persist for blacks and Latinos in receipt of any mental health care, any outpatient care, and any psychotropic drug use. Among those with positive mental health care expenditures, Latino-white disparities in overall mental health care expenditures increased over time. Among children with unmet need, significant disparities in initiation of an episode of mental health care were found, with whites approximately twice as likely as blacks and Latinos to initiate care. Disparities in children's mental health care use are persistent and driven by disparities in initiation, suggesting policies to improve detection or increase initial access to care may be critical to reducing disparities.


Influence of female reproductive anatomy on the outcome of sperm competition in Drosophila melanogaster.
Females as well as males can influence the outcome of sperm competition, and may do so through the anatomy of their reproductive tracts. Female Drosophila melanogaster store sperm in two morphologically distinct organs: a single seminal receptacle and, normally, two spermathecae. These organs have different temporal roles in sperm storage. To examine the association between sperm storage organ morphology and sperm competition, we used a mutant type of female with three spermathecae. Although the common measure of sperm competition, P(2), did not differ between females with two and three spermathecae, the pattern of sperm use over time indicated that female morphology did affect male reproductive success. The rate of offspring production by females with three spermathecae rose and fell more rapidly than by females with two spermathecae. If females remate or die before using up second male sperm, then second male reproductive success will be higher when they mate with females with three spermathecae. The results indicate that temporal patterns of sperm use as well as P(2) should be taken into account when measuring the outcome of sperm competition.


Murine renal cell carcinoma: a suitable human model.
Many models of renal cell carcinoma are available. They have been observed in various species of animals. However, a renal adenocarcinoma which metastasizes, is available for study, and can be serially transplanted in BALB/c mice, appears to be the currently favored model. Our results reported herein describe a study on tumor kinetics, the effects of chemotherapy and other manipulations which appear relevant to the human state. A brief description of other available models is provided.


The Emerging Plasticizer Alternative DINCH and Its Metabolite MINCH Induce Oxidative Stress and Enhance Inflammatory Responses in Human THP-1 Macrophages.
The use of the plasticizer bis(2-ethylhexyl)phthalate (DEHP) and other plasticizers in the manufacture of plastic products has been restricted due to adverse health outcomes such as obesity, metabolic syndrome, and asthma, for which inflammation has been described to be a driving factor. The emerging alternative plasticizer 1,2-cyclohexanedioic acid diisononyl ester (DINCH) still lacks information regarding its potential effects on the immune system. Here, we investigated the effects of DINCH and its naturally occurring metabolite monoisononylcyclohexane-1,2-dicarboxylic acid ester (MINCH) on the innate immune response. Human THP-1 macrophages were exposed to 10 nM-10 μM DINCH or MINCH for 4 h, 16 h, and 24 h. To decipher the underlying mechanism of action, we applied an untargeted proteomic approach that revealed xenobiotic-induced activation of immune-related pathways such as the nuclear factor κB (NF-κB) signaling pathway. Key drivers were associated with oxidative stress, mitochondrial dysfunction, DNA damage repair, apoptosis, and autophagy. We verified increased reactive oxygen species (ROS) leading to cellular damage, NF-κB activation, and subsequent TNF and IL-1β release, even at low nM concentrations. Taken together, DINCH and MINCH induced cellular stress and pro-inflammatory effects in macrophages, which may lead to adverse health effects.


The pathogenesis of Lyme disease.
Lyme disease affects several major organ systems and leads to chronic illness. The pathogenesis of this disease appears to be centered around the long-term persistence of the organisms in tissues. In Lyme disease, isolations of B. burgdorferi are rare. It is thought that few organisms actually invade the host and that host mediators amplify the inflammatory response. Immune and nonimmune phagocytosis leading to bacterial killing occurs in Lyme disease. This organism shows preference for cell surfaces and tissues which may explain the paucity of isolations but also displays characteristic nonspecificity in its adherence to eukaryotic cells. This lack of specificity may explain its capacity to reside and injure vastly different tissues. Autoimmune mechanisms may coincide with spirochetal persistence in the pathogenesis of chronic Lyme disease.


Exercise Intervention: Attrition, Compliance, Adherence, and Progression Following Hematopoietic Stem Cell Transplantation .
Exercise is widely touted as an effective intervention to optimize health and well-being after high-dose chemotherapy and hematopoietic stem cell transplantation. . This article reports attrition, compliance, adherence, and progression from the strength training arm of the single-blind randomized, controlled trial Strength Training to Enhance Early Recovery (STEER). . 37 patients were randomized to the intervention and participated in a structured strength training program introduced during hospitalization and continued for six weeks after release. Research staff and patients maintained exercise logs to document compliance, adherence, and progression. . No patients left the study because of burden. Patients were compliant with completion of exercise sessions, and their adherence was high; they also progressed on their exercise prescription. Because STEER balances intervention effectiveness with patient burden, the findings support the likelihood of successful translation into clinical practice.


Prevalence case-control study of epilepsy in three Burkina Faso villages.
To estimate the association between the prevalence of epilepsy and potential risk factors in three Burkina Faso villages. Three villages were selected based on local reports of high numbers of epilepsy cases and pig-rearing practices. One person aged 7 or older was selected at random from all households of selected concessions for epilepsy screening and blood sampling. Epilepsy was confirmed by a physician using the ILAE definition. The cross-sectional associations between epilepsy and selected factors and seroresponse to the antigens of Taenia solium were estimated using a Bayesian hierarchical logistic regression. Prevalence odds ratios (POR) and their 95% Bayesian Credible Intervals (95% BCI) were estimated. Of 888 individuals interviewed, 39 of 70 screened positive were confirmed to have epilepsy for a lifetime prevalence of 4.5% (95% CI: 3.3; 6.0). The prevalence of epilepsy was associated with a positive reaction to cysticercosis Ag-ELISA serology (POR = 3.1, 95% BCI = 1.0; 8.3), past pork consumption (POR = 9.7, 95% BCI = 2.5; 37.9), and being salaried or a trader compared to a farmer or housewife (POR = 2.9, 95% BCI = 1.2; 6.4). Several factors were associated with prevalent epilepsy, with Ag-ELISA suggesting the presence of neurocysticercosis. The association between epilepsy and some occupations may reflect differences in local attitudes toward epilepsy and should be further explored.


Use of ACE (Angiotensin-Converting Enzyme) Inhibitors and Risk of Lung Cancer: A Nationwide Nested Case-Control Study.
Use of angiotensin-converting enzyme inhibitors (ACEIs)was associated with increased risk of lung cancer in a cohort study from the United Kingdom. We aimed to replicate these findings in a Danish population. We conducted a nested case-control study using data from 4 Danish national health and administrative registries. New users of ACEIs or angiotensin II receptor blockers in Denmark from January 1, 2000 were followed until December 31, 2015, incident lung cancer, death, or emigration. Each lung cancer case was matched with up to 20 controls on age, sex, duration of follow-up, and year of cohort entry using risk-set sampling. Conditional logistic regression was used to estimate odds ratios (ORs) for incident, histologically verified lung cancer with high use of ACEIs defined as a cumulative dose above 3650 defined daily doses. We examined different cumulative doses of ACEI (≤1800, 1801-3650, >3650 defined daily doses), examined whether the association varied with lung cancer histology, and repeated the analyses using thiazides as active comparator. We included 9652 lung cancer cases matched to 190 055 controls. High use of ACEIs was associated with lung cancer (adjusted OR, 1.33 [95% CI, 1.08-1.62]). Lower cumulative doses showed neutral associations (≤1800 defined daily doses OR, 1.01 [95% CI, 0.94-1.09]; 1801-3650 defined daily doses OR, 1.03 [95% CI, 0.90-1.19]). CIs were wide and included the null when stratifying on histology. Using thiazides as active comparator yielded comparable results (OR, 1.34 [95% CI, 0.96-1.88]). Use of high cumulative ACEI doses was associated with modestly increased odds of lung cancer although use of lower doses showed neutral associations. The established benefits of ACEIs should be considered when interpreting these findings.


Epitheliocystis Distribution and Characterization in Brown Trout (Salmo trutta) from the Headwaters of Two Major European Rivers, the Rhine and Rhone.
We present a first description of the distribution and characterization of epitheliocystis infections in brown trout (Salmo trutta) from the upper catchments of two major European rivers, the Rhine and the Rhone. Overall, epitheliocystis was widely distributed, with 70% of the Rhine and 67% of the Rhone sites harboring epitheliocystis positive brown trout. The epitheliocystis agents Candidatus Piscichlamydia salmonis and Candidatus Clavichlamydia salmonicola could be identified in both catchments, although their relative proportions differed from site to site. Additionally, in two rivers in the Rhine catchment, a new species of Candidatus Similichlamydia was identified. Based on the histology, infection intensity, and severity of pathological changes were significantly more pronounced in mixed chlamydial infections, whereas single infections showed only low numbers of cysts and mild pathology. Infections could be found over a wide range of temperatures, which showed no correlation to infection prevalence or intensity.


Tunicate bulb size variation in monocots explained by temperature and phenology.
Plant bulbs are modified shoot systems comprised of short internodes with apical bud(s) surrounded by layers of leaf bases. Bulb diameters can vary greatly, with overall bulb size playing a role in flower formation and resource allocation. Despite the importance of bulb size to the overall fitness of an individual, evolutionary and ecological aspects of this trait have been almost completely neglected. Examining over 2,500 herbarium vouchers for 115 selected species, we analyzed monocot tunicate bulb size within a phylogenetic context in order to investigate its evolutionary significance. We recorded two bulb diameter optima and observed that as bulb size increases taxa inhabit warmer areas with less temperature seasonality. Furthermore, we found that hysteranthous taxa, a habit where leaves emerge separately from flowers, exhibit overall larger bulbs potentially due to reliance upon belowground stored resources to flower rather than on current environmental inputs. This work highlights the importance of including the belowground portion of plants into ecological and evolutionary studies in order to gain a more complete understanding of the evolution of plant forms and functions.


Pesticides reduce symbiotic efficiency of nitrogen-fixing rhizobia and host plants.
Unprecedented agricultural intensification and increased crop yield will be necessary to feed the burgeoning world population, whose global food demand is projected to double in the next 50 years. Although grain production has doubled in the past four decades, largely because of the widespread use of synthetic nitrogenous fertilizers, pesticides, and irrigation promoted by the "Green Revolution," this rate of increased agricultural output is unsustainable because of declining crop yields and environmental impacts of modern agricultural practices. The last 20 years have seen diminishing returns in crop yield in response to increased application of fertilizers, which cannot be completely explained by current ecological models. A common strategy to reduce dependence on nitrogenous fertilizers is the production of leguminous crops, which fix atmospheric nitrogen via symbiosis with nitrogen-fixing rhizobia bacteria, in rotation with nonleguminous crops. Here we show previously undescribed in vivo evidence that a subset of organochlorine pesticides, agrichemicals, and environmental contaminants induces a symbiotic phenotype of inhibited or delayed recruitment of rhizobia bacteria to host plant roots, fewer root nodules produced, lower rates of nitrogenase activity, and a reduction in overall plant yield at time of harvest. The environmental consequences of synthetic chemicals compromising symbiotic nitrogen fixation are increased dependence on synthetic nitrogenous fertilizer, reduced soil fertility, and unsustainable long-term crop yields.


Integrity of the Pericentriolar Material Is Essential for Maintaining Centriole Association during M Phase.
A procentriole is assembled next to the mother centriole during S phase and remains associated until M phase. After functioning as a spindle pole during mitosis, the mother centriole and procentriole are separated at the end of mitosis. A close association of the centriole pair is regarded as an intrinsic block to the centriole reduplication. Therefore, deregulation of this process may cause a problem in the centriole number control, resulting in increased genomic instability. Despite its importance for faithful centriole duplication, the mechanism of centriole separation is not fully understood yet. Here, we report that centriole pairs are prematurely separated in cells whose cell cycle is arrested at M phase by STLC. Dispersal of the pericentriolar material (PCM) was accompanied. This phenomenon was independent of the separase activity but needed the PLK1 activity. Nocodazole effectively inhibited centriole scattering in STLC-treated cells, possibly by reducing the microtubule pulling force around centrosomes. Inhibition of PLK1 also reduced the premature separation of centrioles and the PCM dispersal as well. These results revealed the importance of PCM integrity in centriole association. Therefore, we propose that PCM disassembly is one of the driving forces for centriole separation during mitotic exit.


Drug-associated cardiovascular risks: A retrospective evaluation of withdrawn drugs.
A considerable number of drugs were withdrawn from the world market in the last decades due to safety reasons. A retrospective review of withdrawals is important in determining the adequacy of regulations regarding the safety and efficacy of drugs. The scope of the present study was to focus on cardiovascular adverse reactions of 61 withdrawn medicinal products, as well as 40 additional drugs withdrawn due to non-cardiovascular toxicity, while being cardiovascular agents themselves. A detailed web-based data search was held to draw a list of withdrawn pharmaceutical products from the pharmaceutical market by regulatory authorities between 1950 and 2017 due to safety reasons. A total of 464 medicinal products were withdrawn from the pharmaceutical markets between 1950 and 2017 due to safety reasons. Hepatotoxicity was the most commonly reported adverse drug reaction (ADR) that led to withdrawal, followed by immune-related reactions, neurotoxicity, and cardiovascular toxicity. The underlying mechanisms leading to cardiovascular toxicity should be investigated in depth to avoid the use of risky drugs for long periods, especially in consideration of the fact that some cardiovascular drugs persisted in the market for many decades. Furthermore, improved reporting of suspected adverse reactions and stricter regulations will lead to quicker detection of ADRs, thus emphasizing the importance of this public health problem and highlighting the need for improved "early warning systems" to manage the risks of high-risk drugs.


The role of causal models and beliefs in interpreting health claims.
Health claims on food packaging are regulated to inform and protect consumers; however, many consumers do not accurately interpret the meaning of the claims. Whilst research has shown different types of misinterpretation, it is not clear how those interpretations are formed. The aim of this study was to elicit the causal beliefs and causal models about food and health held by consumers, that is their understanding of the causal relationships between nutrients, health outcomes, and the causal pathways connecting them, and investigate how well this knowledge explains the variation in inferences they draw about health benefits from health claims. A total of 400 participants from Germany, the Netherlands, Spain, Slovenia, and the United Kingdom were presented with seven authorized health claims and drew inferences about the health benefits of consuming nutrients specified in the claim. Then, their personal causal models of health were elicited along with their belief in the truth and familiarity with the claims. The strength of inferences about health benefits that participants drew from the claims was predicted independently by the strength of the relevant causal pathways within the causal model, and belief in the truth of the claim, but not familiarity with the claim. Participants drew inferences about overall health benefits of the nutrients by extrapolating from their causal models of health. Consumers' interpretation of claims is associated with their belief in the claim and their causal models of health. This prior knowledge is used to interpret the claim and draw inferences about overall health benefits that go beyond the information in the claim. Therefore, efforts to improve consumers' understanding and interpretation of health claims must address both their wider causal models of health and their knowledge of specific claims. Statement of Contribution What is already known on this subject? Health claims influence the likelihood of buying a product. But consumers do not accurately understand or interpret health claims. What does this study add? Consumers' interpretation of health claims is mediated by their personal causal model of health. Consumers draw inferences that go beyond what is claimed by extrapolating from their personal causal model of health. Consumers are also influenced directly by their belief in the claim, but not frequency of exposure to it.


Three Decades of Advances in Arabinogalactan-Protein Biosynthesis.
Arabinogalactan-proteins (AGPs) are a large, complex, and highly diverse class of heavily glycosylated proteins that belong to the family of cell wall hydroxyproline-rich glycoproteins. Approximately 90% of the molecules consist of arabinogalactan polysaccharides, which are composed of arabinose and galactose as major sugars and minor sugars such as glucuronic acid, fucose, and rhamnose. About half of the AGP family members contain a glycosylphosphatidylinositol (GPI) lipid anchor, which allows for an association with the outer leaflet of the plasma membrane. The mysterious AGP family has captivated the attention of plant biologists for several decades. This diverse family of glycoproteins is widely distributed in the plant kingdom, including many algae, where they play fundamental roles in growth and development processes. The journey of AGP biosynthesis begins with the assembly of amino acids into peptide chains of proteins. An N-terminal signal peptide directs AGPs toward the endoplasmic reticulum, where proline hydroxylation occurs and a GPI anchor may be added. GPI-anchored AGPs, as well as unanchored AGPs, are then transferred to the Golgi apparatus, where extensive glycosylation occurs by the action of a variety glycosyltransferase enzymes. Following glycosylation, AGPs are transported by secretory vesicles to the cell wall or to the extracellular face of the plasma membrane (in the case of GPI-anchored AGPs). GPI-anchored proteins can be released from the plasma membrane into the cell wall by phospholipases. In this review, we present an overview of the accumulated knowledge on AGP biosynthesis over the past three decades. Particular emphasis is placed on the glycosylation of AGPs as the sugar moiety is essential to their function. Recent genetics and genomics approaches have significantly contributed to a broader knowledge of AGP biosynthesis. However, many questions remain to be elucidated in the decades ahead.


Diabetic retinopathy and inflammation: novel therapeutic targets.
Most anti-vascular endothelial growth factor (VEGF) therapies in diabetic macular edema are not as robust as in proliferative diabetic retinopathy. Although the VEGF appears to be a good target in diabetic macular edema, the anti-VEGF therapies appear to be of transient benefit as the edema recurs within a few weeks, and repeated injections are necessary. There is new evidence that indicates 'retinal inflammation' as an important player in the pathogenesis of diabetic retinopathy. There are common sets of inflammatory cytokines that are upregulated in both the serum and vitreous and aqueous samples, in subjects with diabetic retinopathy, and these cytokines can have multiple interactions to impact the pathogenesis of the disease. The key inflammatory events involved in the blood retinal barrier (BRB) alteration appear to be: (1) Increased expression of endothelial adhesion molecules such as ICAM1, VCAM1, PECAM-1, and P-selectin, (2) adhesion of leukocytes to the endothelium, (3) release of inflammatory chemokines, cytokines, and vascular permeability factors, (4) alteration of adherens and tight junctional proteins between the endothelial cells, and (5) infiltration of leukocytes into the neuro-retina, resulting in the alteration of the blood retinal barrier (diapedesis). VEGF inhibition itself may not achieve neutralization of other inflammatory molecules involved in the inflammatory cascade of the breakdown of the BRB. It is possible that the novel selective inhibitors of the inflammatory cascade (like angiopoietin-2, TNFα, and chemokines) may be useful therapeutic agents in the treatment of diabetic macular edema (DME), either alone or in combination with the anti-VEGF drugs.


The WIG (weighted individual and group) shrinkage estimator.
Regularization, or shrinkage estimation, refers to a class of statistical methods that constrain the variability of parameter estimates when fitting models to data. These constraints move parameters toward a group mean or toward a fixed point (e.g., 0). Regularization has gained popularity across many fields for its ability to increase predictive power over classical techniques. However, articles published in JEAB and other behavioral journals have yet to adopt these methods. This paper reviews some common regularization schemes and speculates as to why articles published in JEAB do not use them. In response, we propose our own shrinkage estimator that avoids some of the possible objections associated with the reviewed regularization methods. Our estimator works by mixing weighted individual and group (WIG) data rather than by constraining parameters. We test this method on a problem of model selection. Specifically, we conduct a simulation study on the selection of matching-law-based punishment models, comparing WIG with ordinary least squares (OLS) regression, and find that, on average, WIG outperforms OLS in this context.


[Patterns of thrombocytopoiesis regulation].
Based on literature data, the main kinds of thrombocytopoiesis regulation are analyzed. It is shown that humoral factors regulate the intensity of proliferation of committed precursors and the mean sizes of mature megakaryocytes. The activity of these factors depends on the numbers of thrombocytes in blood and of megakaryocytes in bone marrow. The evidence presented in the review enables one to give a quantitative description of the relationship between the rate of thrombocytopoiesis and the content of thrombocytes in blood. The fact that the alteration of the time of megakaryocyte maturation does not depend on the duration and strength of the influences points to a non-specificity of this reaction. A scheme for the thrombopoiesis regulation is proposed which can serve as a basis for its mathematic description.


Photon echoes in an amplifying rare-earth-ion-doped crystal.
We report what we believe is the first experimental demonstration of photon echoes in an amplifying rare-earth-ion-doped crystal. Population inversion is achieved by optical pumping, which yields high-power photon echoes, with an energy gain of as much as a factor of 5. Effects of the pump on the photon echo process highlight the advantages of an amplifying crystal. New questions concerning the optical dephasing mechanisms in Er3+:YSO have arisen.


Cloning and characterization of the bovine gene for steroid 21-hydroxylase (P-450c21).
Steroid 21-hydroxylase activity is required for the synthesis of both cortisol and aldosterone. Using two manually synthesized oligonucleotide probes, we screened a bovine genomic DNA library and identified a phage, lambda E11, carrying the gene for the steroid 21-hydroxylase, P-450c21. The identity of lambda E11 was initially proven by initiating dideoxy sequencing from the two oligonucleotides directly on the full-length, uncleaved phage template. Hybridization of total bovine genomic DNA to lambda E11 restriction fragments indicates the presence of repetitive sequences in or near the P-450c21 gene. Northern blots indicate that the mature mRNA exists in two principal forms of about 2.2 and 2.4 kb in length. Southern blots indicate there are two copies of the gene in the bovine genome. Sequence analysis of a 1141-bp Eco RI fragment of the gene shows three complete exons and a portion of a fourth exon, correctly determining the amino acid sequence of 148 amino acids of this important enzyme. This cloned 1141-bp fragment cross-hybridizes to human genomic DNA, indicating it should be a useful probe for studying the human P-450c21 gene in patients having impaired 21-hydroxylase activity.


Mechanically tunable three-dimensional elastomeric network/air structures via interference lithography.
We show how to employ an interference lithographic template (ILT) as a facile mold for fabricating three-dimensional bicontinuous PDMS (poly(dimethylsiloxane)) elastomeric structures and demonstrate the use of such a structure as a mechanically tunable PDMS/air phononic crystal. A positive photoresist was used to make the ILT, and after infiltration with PDMS, the resist was removed in a water-based basic solution which avoided PDMS swelling or pattern collapse occurring during the ILT removal process. Since the period of the structure is approximately 1 microm, the density of states of gigahertz phonons are altered by the phononic PDMS/air crystal. Brillouin light scattering (BLS) was employed to measure phononic modes of the structure as a function of mechanical strain. The results demonstrate that the phononic band diagram of such structures can be tuned mechanically.


A Study of Advanced Practice Provider Staffing Models and Professional Development Opportunities at National Comprehensive Cancer Network Member Institutions.
The National Comprehensive Cancer Network (NCCN) Best Practices Committee created an Advanced Practice Provider (APP) Workgroup to develop recommendations to support APP roles at NCCN Member Institutions. The Workgroup conducted three surveys to understand APP program structure, staffing models, and professional development opportunities at NCCN Member Institutions. The total number of new and follow-up visits a 1.0 APP full-time equivalent conducts per week in shared and independent visits ranged from 11 to 97, with an average of 40 visits per week (n = 39). The type of visits APPs conduct include follow-up shared (47.2%), follow-up independent (46%), new shared (6.5%), and new independent visits (0.5%). Seventy-two percent of respondents utilize a mixed model visit type, with 15% utilizing only independent visits and 13% utilizing only shared visits (n = 39). Of the 95% of centers with APP leads, 100% indicated that leads carry administrative and clinical responsibilities (n = 20); however, results varied with respect to how this time is allocated. Professional development opportunities offered included posters, papers, and presentations (84%), leadership development (57%), research opportunities (52%), writing book chapters (19%), and other professional development activities (12%; n = 422). Twenty percent of APPs indicated that protected time to engage in development opportunities should be offered. As evidenced by the variability of the survey results, the field would benefit from developing standards for APPs. There is a lack of information regarding leadership structures to help support APPs, and additional research is needed. Additionally, centers should continuously assess the career-long opportunities needed to maximize the value of oncology APPs.


Substance Use Patterns and Schizophrenia Spectrum Disorders: A Retrospective Study of Inpatients at a Community Teaching Hospital.
Schizophrenia is one of the chronic mental illnesses, characterized by delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, and cognitive decline. It frequently leads to a lifetime of impairment and disability that span the entire lifespan of the patients. Several epidemiologic studies have shown that schizophrenia spectrum disorders (SSDs) contribute significantly to years lived with disability. Additionally, substance use disorders have been reported to co-occur commonly among patients with SSD (a comorbidity also known as dual diagnosis), attracting notable attention over the past few decades. This dual diagnosis often requires treatment modifications to ensure for best patient outcomes. This study was a retrospective review of the electronic medical charts. The patients included in the study were discharged from the psychiatric unit of our hospital between July 1, 2017 and October 31, 2017. Patients were included in the study using three inclusion criteria: 1) age ≥18 years; 2) had a diagnosis of SSD at discharge; and 3) had urine drug screen performed. Sociodemographic and clinical variables were abstracted. Univariate analysis and summary statistics were performed. Bivariate and multivariate analyses were done via logistic regression models to determine the odds ratios (ORs) and corresponding P values (P). A total of 365 (52.2%) patients had a diagnosis of SSD at discharge. Of these, 349 met the inclusion criteria. The age ranged from 19 to 79 years, with a mean age of 42.2 years, and 76.8% of the patients used substances. Out of the 269 patients who used substances, 199 (74%) used two or more substances. Tobacco use was most prevalent (62.3%), followed by cannabis use (41.5%), alcohol use (40.2%), and cocaine use (27.4%). Patients who reported using tobacco, were more likely to have comorbid alcohol use (OR = 7.24; P = 0.000), cannabis use (OR = 2.80; P = 0.000), cocaine use (OR = 5.00; P = 0.000), and synthetic cannabis (K2) use (OR = 4.62; P = 0.048). Results of the multivariate analyses supported the other findings. Our study found a high association between schizophrenia spectrum disorders and substance use, with three out of four patients with SSD using a substance. This prevalence is higher than previously reported by other studies. Among those who use substances, about three in four use multiple substances. These point to some interaction between the substances and appear to be heavily influenced by significant social determinants of mental health that continue to plague the community. It is important to establish if a patient with schizophrenia has a comorbid substance use disorder, because addressing both generally leads to better patient outcomes.


Bioengineering the ovary to preserve and reestablish female fertility.
Different bioengineering strategies can be presently adopted and have been shown to have great potential in the treatment of female infertility and ovarian dysfunction deriving from chemotherapy, congenital malformations, massive adhesions as well as aging and lifestyle. One option is transplantation of fresh or cryopreserved organs/fragments into the patient. A further possibility uses tissue engineering approaches that involve a combination of cells, biomaterials and factors that stimulate local ability to regenerate/ repair the reproductive organ. Organ transplant has shown promising results in large animal models. However, the source of the organ needs to be identified and the immunogenic effects of allografts remain still to be solved before the technology may enter the clinical practice. Decellularization/ repopulation of ovary with autologous cells or follicles could represent an interesting, still very experimental alternative. Here we summarize the recent advancements in the bioengineering strategies applied to the ovary, we present the principles for these systems and discuss the advantages of these emerging opportunities to preserve or improve female fertility.


Discrepant susceptibility to gentamicin despite amikacin resistance in Klebsiella pneumoniae by VITEK 2 represents false susceptibility associated with the armA 16S rRNA methylase gene.
Because we experienced gentamicin failure in Klebsiella pneumoniae bacteraemia that was susceptible to gentamicin despite amikacin resistance, as determined by VITEK 2, we evaluated the true susceptibility and mechanism of resistance. We screened 2818 K. pneumoniae isolates during a 1-year period at a university hospital and reviewed anti-microbial susceptibility reports using the VITEK 2 system. The minimum inhibitory concentration was substantiated by broth microdilution (BMD), and the presence of 16S rRNA methylase genes and aminoglycoside-modifying enzymes was also investigated. A total of 131 amikacin-resistant isolates from 19 patients were gentamicin non-resistant according to the VITEK 2 system. Among these, we were able to collect isolates from 12 patients (63.2 %), and a single isolate from each patient was tested. Eleven of the gentamicin non-resistant isolates (91.7 %) showed high-level resistance to both amikacin and gentamicin by BMD in association with the armA gene. Gentamicin is not an adequate treatment option for amikacin-resistant K. pneumoniae, even if VITEK 2 reports susceptibility.


Biosynthesis of palladium nanoparticles using Diospyros kaki leaf extract and determination of antibacterial efficacy.
Palladium, the building block of white gold, has been found to exhibit extraordinary properties in nanotechnological products produced in recent years. The most prominent feature of palladium is adsorbing and storing high levels of hydrogen. Therefore, the demand for palladium in the world increased excessively in the 2000s. In the present study, palladium nanoparticles (PdNPs) were biosynthesized by the extract of Diospyros kaki leaves as bio-stimulator. D. kaki, also called persimmon, was collected in a local area in Istanbul Turkey. PdNP formation was screened by analyzing UV-Vis spectrophotometer at 250-550 nm. The nanoparticles were characterized by scanning electron microscope which revealed that the biosynthesized PdNPs were in sizes ranging from 50 to 120 nm. Fourier transform infrared spectroscopy applied on both D. kaki leaf extract and PdNPs was used to decide on the reactive groups managing the reduction of the biosynthesized nanoparticles. Also, the PdNPs showed reasonably proficient antibacterial efficacy for both Escherichia coli and Staphylococcus aureus and the zones of inhibition were found as 18 and 10.5 mm, respectively.


DDM1 binds Arabidopsis methyl-CpG binding domain proteins and affects their subnuclear localization.
Methyl-CpG binding domain (MBD) proteins in Arabidopsis thaliana bind in vitro methylated CpG sites. Here, we aimed to characterize the binding properties of AtMBDs to chromatin in Arabidopsis nuclei. By expressing in wild-type cells AtMBDs fused to green fluorescent protein (GFP), we showed that AtMBD7 was evenly distributed at all chromocenters, whereas AtMBD5 and 6 showed preference for two perinucleolar chromocenters adjacent to nucleolar organizing regions. AtMBD2, previously shown to be incapable of binding in vitro-methylated CpG, was dispersed within the nucleus, excluding chromocenters and the nucleolus. Recruitment of AtMBD5, 6, and 7 to chromocenters was disrupted in ddm1 and met1 mutant cells, where a significant reduction in cytosine methylation occurs. In these mutant cells, however, AtMBD2 accumulated at chromocenters. No effect on localization was observed in the chromomethylase3 mutant showing reduced CpNpG methylation or in kyp-2 displaying a reduction in Lys 9 histone H3 methylation. Transient expression of DDM1 fused to GFP showed that DDM1 shares common sites with AtMBD proteins. Glutathione S-transferase pull-down assays demonstrated that AtMBDs bind DDM1; the MBD motif was sufficient for this interaction. Our results suggest that the subnuclear localization of AtMBD is not solely dependent on CpG methylation; DDM1 may facilitate localization of AtMBDs at specific nuclear domains.


Elevated serum beta-human chorionic gonadotropin in nonpregnant conditions.
Positive serum beta-human chorionic gonadotropin (beta-hCG) in reproductive-age women generally indicates a pregnancy, and to a lesser extent, gestational trophoblastic disease, ovarian or peripheral germ cell tumor. Besides gynecologic conditions, nongynecologic cancers can be associated with beta-hCG positivity as well. The hormone in these tumors varies from detection by the immunohistochemistry studies of the tumor tissue only to a high serum level. This is illustrated by our case report of a 26-year-old woman who was diagnosed with a spindle cell osteosarcoma of the shoulder. The serum beta-hCG became undetectable after chemotherapy. Obstetricians & Gynecologists, Family Physicians Learning After completion of this article, the reader should be able to recall that elevated serum hCG can be related to pregnancy, gestational neoplasias, and ovarian and nongynecologic tumors and explain that it is important to appreciate that the hCG detected in these conditions may differ in type and be a marker of the success of treatment.


Chlorhexidine and silver-sulfadiazine coated central venous catheters in haematological patients--a double-blind, randomised, prospective, controlled trial.
Central venous catheters (CVCs) are essential for the intensive care of patients with haematological illness. Catheter-related infections (CRI) are an important problem in modern medicine, which may lead to life-threatening situations, to prolonged hospitalisation and increased cost. In immunocompromised patients suffering from haemato-oncological diseases, CRI is a significant factor for adverse outcome. Several clinical studies have shown that CVCs coated with antiseptics such as chlorhexidine and silver-sulfadiazine (CHSS) reduce the risk of catheter-related bacteraemia. Most studies, however, were performed on intensive care patients not suffering from chemotherapy-induced immunosuppression. A prospective double-blind, randomised, controlled trial was performed to investigate the effectiveness of CHSS-coated catheters in haemato-oncological patients. A total number of 184 catheters (median duration of placement, 11 days) were inserted into 184 patients (male 115, female 69), of which 90 were antiseptically coated. After removal, all catheters were investigated for bacterial growth. Catheters coated with CHSS were effective in reducing the rate of significant bacterial growth on either the tip or subcutaneous segment (26%) compared to control catheters (49%). The incidence of catheter colonisation was also significantly reduced (12% coated vs 33% uncoated). Data obtained show a significant reduction of catheter colonisation in CHSS catheters. There was no significant difference in the incidence of catheter-related bacteraemia (3% coated vs 7% uncoated). However, due to the overall low rate of CRI, we could not observe a significant reduction in the incidence of catheter-related bacteraemia. Our data show that the use of CHSS catheters in patients with haematological malignancy reduces the overall risk of catheter colonisation and CRI, although the incidence of catheter-related bacteremia was similar in both groups.


Systems Immunology Analysis Reveals the Contribution of Pulmonary and Extrapulmonary Tissues to the Immunopathogenesis of Severe COVID-19 Patients.
As one of the current global health conundrums, COVID-19 pandemic caused a dramatic increase of cases exceeding 79 million and 1.7 million deaths worldwide. Severe presentation of COVID-19 is characterized by cytokine storm and chronic inflammation resulting in multi-organ dysfunction. Currently, it is unclear whether extrapulmonary tissues contribute to the cytokine storm mediated-disease exacerbation. In this study, we applied systems immunology analysis to investigate the immunomodulatory effects of SARS-CoV-2 infection in lung, liver, kidney, and heart tissues and the potential contribution of these tissues to cytokines production. Notably, genes associated with neutrophil-mediated immune response (e.g. CXCL1) were particularly upregulated in lung, whereas genes associated with eosinophil-mediated immune response (e.g. CCL11) were particularly upregulated in heart tissue. In contrast, immune responses mediated by monocytes, dendritic cells, T-cells and B-cells were almost similarly dysregulated in all tissue types. Focused analysis of 14 cytokines classically upregulated in COVID-19 patients revealed that only some of these cytokines are dysregulated in lung tissue, whereas the other cytokines are upregulated in extrapulmonary tissues (e.g. IL6 and IL2RA). Investigations of potential mechanisms by which SARS-CoV-2 modulates the immune response and cytokine production revealed a marked dysregulation of NF-κB signaling particularly CBM complex and the NF-κB inhibitor BCL3. Moreover, overexpression of mucin family genes (e.g. MUC3A, MUC4, MUC5B, MUC16, and MUC17) and HSP90AB1 suggest that the exacerbated inflammation activated pulmonary and extrapulmonary tissues remodeling. In addition, we identified multiple sets of immune response associated genes upregulated in a tissue-specific manner (DCLRE1C, CHI3L1, and PARP14 in lung; APOA4, NFASC, WIPF3, and CD34 in liver; LILRA5, ISG20, S100A12, and HLX in kidney; and ASS1 and PTPN1 in heart). Altogether, these findings suggest that the cytokines storm triggered by SARS-CoV-2 infection is potentially the result of dysregulated cytokine production by inflamed pulmonary and extrapulmonary (e.g. liver, kidney, and heart) tissues.


Construction of a new growth references for China based on urban Chinese children: comparison with the WHO growth standards.
Growth references for Chinese children should be updated due to the positive secular growth trends and the progress of the smoothing techniques. Human growth differs among the various ethnic groups, so comparison of the China references with the WHO standards helps to understand such differences. The China references, including weight, length/height, head circumference, weight-for-length/height and body mass index (BMI) aged 0-18 years, were constructed based on 69,760 urban infants and preschool children under 7 years and 24,542 urban school children aged 6-20 years derived from two cross-sectional national surveys. The Cole's LMS method is employed for smoothing the growth curves. The merged data sets resulted in a smooth transition at age 6-7 years and continuity of curves from 0 to 18 years. Varying differences were found on the empirical standard deviation (SD) curves in each indicator at nearly all ages between China and WHO. The most noticeable differences occurred in genders, final height and boundary centiles curves. Chinese boys' weight is strikingly heavier than that of the WHO at age 6-10 years. The height is taller than that of the WHO for boys below 15 years and for girls below 13, but is significantly lower when boys over 15 years and girls over 13. BMI is generally higher than that of the WHO for boys at age 6-16 years but appreciably lower for girls at 3-18 years. The differences between China and WHO are mainly caused by the reference populations of different ethnic backgrounds. For practitioners, the choices of the standards/references depend on the population to be assessed and the purpose of the study. The new China references could be applied to facilitate the standardization assessment of growth and nutrition for Chinese children and adolescents in clinical pediatric and public health.


Training veterinarians and agricultural advisers on a novel tool for tail biting prevention.
Many health and welfare problems in modern livestock production are multifactorial problems which require innovative solutions, such as novel risk assessment and management tools. However, the best way to distribute such novel - and usually complex - tools to the key applicants still has to be discussed. This paper shares experiences from distributing a novel tail biting prevention tool ('SchwIP') to 115 farm advisers and 19 veterinarians in 23 one-day workshops. Participants gave written and oral feedback at the end of the workshops, which was later analysed together with the number of farms they had visited after the workshops. Workshop groups were categorised into groups showing (a) HIGH, (b) INTermediate or (c) LOW levels of antagonism against SchwIP or parts of it during workshop discussions. Group types did not significantly differ in their evaluation of knowledge transfer. However, HIGH group members evaluated the on-farm usability of the tool significantly lower in the workshop feedback and tended to visit fewer farms. As antagonistic discussion can influence workshop output, future workshop leaders should strive for basic communication training as well as some group leadership experience before setting up and leading workshops.


Simultaneous bilateral-knee MR imaging.
To demonstrate and evaluate the scan time and quantitative accuracy of simultaneous bilateral-knee imaging compared with single-knee acquisitions. Hardware modifications and safety testing was performed to enable MR imaging with two 16-channel flexible coil arrays. Noise covariance and sensitivity-encoding g-factor maps for the dual-coil-array configuration were computed to evaluate coil cross-talk and noise amplification. Ten healthy volunteers were imaged on a 3T MRI scanner with both dual-coil-array bilateral-knee and single-coil-array single-knee configurations. Two experienced musculoskeletal radiologists compared the relative image quality between blinded image pairs acquired with each configuration. Differences in T2 relaxation time measurements between dual-coil-array and single-coil-array acquisitions were compared with the standard repeatability of single-coil-array measurements using a Bland-Altman analysis. The mean g-factors for the dual-coil-array configuration were low for accelerations up to 6 in the right-left direction, and minimal cross-talk was observed between the two coil arrays. Image quality ratings of various joint tissues showed no difference in 89% (95% confidence interval: 85-93%) of rated image pairs, with only small differences ("slightly better" or "slightly worse") in image quality observed. The T2 relaxation time measurements between the dual-coil-array configuration and the single-coil configuration showed similar limits of agreement and concordance correlation coefficients (limits of agreement: -0.93 to 1.99 ms; CCC: 0.97 (95% confidence interval: 0.96-0.98)), to the repeatability of single-coil-array measurements (limits of agreement: -2.07 to 1.96 ms; CCC: 0.97 (95% confidence interval: 0.95-0.98)). A bilateral coil-array setup can image both knees simultaneously in similar scan times as conventional unilateral knee scans, with comparable image quality and quantitative accuracy. This has the potential to improve the value of MRI knee evaluations. Magn Reson Med 80:529-537, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Th2 cells as targets for therapeutic intervention in allergic bronchial asthma.
Th2 cells play a central role in the pathogenesis of allergic bronchial asthma, since each of their characteristic cytokines such as IL-4, IL-5, IL-9 and IL-13 contributes to hallmarks of this disease, including airway eosinophilia, increased mucus production, production of allergen-specific IgE and development of airway hyper-responsiveness. Therefore, these cells are predisposed as target cells for therapeutic intervention. Experimental approaches targeted Th2-type effector cytokines, Th2-cell recruitment and Th2-cell development. Another strategy uses the immunomodulatory potential of tolerance-inducing cytokines such as IL-10 or of cytokines such as IL-12, IL-18 and IFN-gamma that are able to induce a counterbalancing Th1 immune response.


Visiting Friends and Relatives (VFRs) travelers and imported malaria in the Palermo district (Sicily).
Although Italy has been malaria-free since 1970, the infection is commonly introduced into the country by travelers and immigrants from endemic areas. The term VFRs refers to immigrants from malaria-endemic countries who are regularly resident in a malaria-free area, and who travel to their countries of origin to visit friends and relatives (VFRs). This group is at special risk of malaria as they are unaware of having lost their transitory immunity to the disease. We conducted a retrospective study at the International Travelers Department of Palermo (Italy), examining records of malaria cases (67) reported over the period from 1998 to 2013. VFRs represent the highest number of cases (77.6%), followed by workers (16.4%) and tourists (6.0%). All female patients and patients under the age of 18 were VFRs. Plasmodium falciparum was the most frequently-identified species. In all cases, chemoprophylaxis was not taken or was incomplete. VFRs are at high risk of contracting malaria. This is probably related to an inequality in health care available to immigrants, as well as to ethnic and cultural conditions.


Antiemetics added to phenylephrine infusion during cesarean delivery: a randomized controlled trial.
To estimate whether the addition of metoclopramide or its combination with ondansetron to a prophylactic phenylephrine infusion provides improved intraoperative nausea and vomiting prophylaxis compared with phenylephrine infusion alone. Women scheduled for elective cesarean delivery were randomized to one of three groups: placebo (placebo plus placebo); metoclopramide (metoclopramide 10 mg plus placebo); or combination (metoclopramide 10 mg plus ondansetron 4 mg). The first study drug was administered before spinal placement and the second was administered after cord clamping. Spinal anesthesia was standardized. The primary outcome was intraoperative nausea and vomiting. Three-hundred patients completed the study in two centers. Intraoperative nausea and vomiting occurred in 49%, 31%, and 23% of patients in the placebo, metoclopramide, and combination groups, respectively (P<.001). There was a significant difference between the two centers in exteriorization of the uterus (93% compared with 39%; P<.001) and intraoperative nausea and vomiting rates (47% compared with 20%; P<.001). In a multivariable model adjusting for center, exteriorization of the uterus, age, and hypotension, intraoperative nausea and vomiting were significantly lower in the metoclopramide and combination groups compared with placebo (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.24--4.42; P=.001 and OR 4.06, 95% CI 2.06--7.97; P<.001, respectively). Postoperative nausea and vomiting were reduced with the combination compared with placebo at 2 hours (39% compared with 20%; P<.017), but not at 2-6 hours or at 6-24 hours. Metoclopramide with ondansetron reduced intraoperative nausea and vomiting and early postoperative nausea and vomiting compared with placebo. Metoclopramide alone also decreased intraoperative but not postoperative nausea and vomiting. Surgical factors contributed to a significant difference in intraoperative nausea and vomiting between the two centers.


Arterial chemoreflex in conscious normotensive and hypertensive adult rats.
Evidence from human and animal studies suggests that the arterial chemoreflex may be exaggerated in essential hypertension. In the present study, cardiorespiratory responses to peripheral chemoreceptor stimulation were compared in conscious unrestrained spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats (13-14 wk old). Chemoreceptors were stimulated by injections of potassium cyanide (30-125 microgram/kg iv). Chemoreceptor stimulation elicited a pressor response and bradycardia. The peak change in mean arterial pressure evoked during chemoreceptor stimulation was not significantly different between SH (n = 18) and WKY (n = 18) rats but was significantly smaller in SD rats (n = 18). An evaluation of respiratory responses to chemoreceptor stimulation in conscious and anesthetized rats also demonstrated no significant difference between SH and WKY rats, but the response of the SD rats tended to be smaller. These results demonstrate that differences in the arterial chemoreflex response of SH vs. normotensive rats are not linked to hypertension but, rather, to differences between rat strains.


Simplified method of staging hyperplastic rhinosinusitis.
There is a need to both classify and simplify the staging of hyperplastic rhinosinusitis. In essence, this is an extension and modification of the staging system proposed by William Friedman in 1990. It is based primarily on computed tomographic scans, but includes a subclassification that relies on the success or failure of conservative therapy, diagnostic endoscopic findings, and, most important, interval radiographic monitoring. Its basic premise is that not all people with nose and sinus complaints need computed tomographic scans. Four stages are outlined with three letter subclassifications for each stage. These subclassifications, divided into A, B, and C, simply denote the success or failure of conservative therapy as monitored by interval radiographic studies. Examples of each stage are given.


The intergeniculate leaflet partially mediates effects of light on circadian rhythms.
Photic signals affect circadian activity rhythms by both phasic and tonic mechanisms that modulate pacemaker phase and period. In mammals, the effects of light on circadian activity are mediated by the retina, which communicates with the suprahiasmatic nucleus (SCN) by two different anatomical routes: the retino-hypothalamic tract (RHT), originating in the retina, and the geniculo-hypothalamic tract (GHT), arising from a retino-recipient nucleus, the intergeniculate leaflet (IGL). We assessed the roles of these two afferent systems in mediating phasic and tonic effects of light on circadian activity in IGL-lesioned animals. Destruction of the IGL significantly affected phase shifts produced by brief light pulses (phasic effect) and modified the change in period (tau) of the free-running activity rhythm produced by changing the level of constant light (LL) (tonic effect). Phase advances produced by brief light pulses were decreased in amplitude while phase delays were increased in IGL-lesioned animals as compared to controls. The free-running period in constant dark (tau DD) of IGL-lesioned animals was greater than tau DD of controls, and the lengthening of tau normally produced by LL was not observed or was greatly reduced in IGL-lesioned animals. Entrainment to light-dark cycles was unaffected by the lesions, as were other aspects of the circadian activity rhythm that normally change in response to LL (e.g., activity-rest ratio, total activity, splitting). Our data support the interpretation that the IGL plays a significant role in relaying information regarding illumination intensity to the SCN.


Bacterial communities associated with subsurface geochemical processes in continental serpentinite springs.
Reactions associated with the geochemical process of serpentinization can generate copious quantities of hydrogen and low-molecular-weight organic carbon compounds, which may provide energy and nutrients to sustain subsurface microbial communities independently of the photosynthetically supported surface biosphere. Previous microbial ecology studies have tested this hypothesis in deep sea hydrothermal vents, such as the Lost City hydrothermal field. This study applied similar methods, including molecular fingerprinting and tag sequencing of the 16S rRNA gene, to ultrabasic continental springs emanating from serpentinizing ultramafic rocks. These molecular surveys were linked with geochemical measurements of the fluids in an interdisciplinary approach designed to distinguish potential subsurface organisms from those derived from surface habitats. The betaproteobacterial genus Hydrogenophaga was identified as a likely inhabitant of transition zones where hydrogen-enriched subsurface fluids mix with oxygenated surface water. The Firmicutes genus Erysipelothrix was most strongly correlated with geochemical factors indicative of subsurface fluids and was identified as the most likely inhabitant of a serpentinization-powered subsurface biosphere. Both of these taxa have been identified in multiple hydrogen-enriched subsurface habitats worldwide, and the results of this study contribute to an emerging biogeographic pattern in which Betaproteobacteria occur in near-surface mixing zones and Firmicutes are present in deeper, anoxic subsurface habitats.


Digestibility of processed food protein.
An overview is given on the effects of food processing on the protein digestibility. Beneficial effects of food processing are primarily observed in a range of plant foods containing toxic substances and/or anti-nutrients (legumes, cereals, some seed food). Digestibilities improve by heating, soaking, germination and fermentation. These processing steps reduce the amount of active enzyme inhibitors through extraction, inactivation by heat or microorganisms, or by compositional modification through germination. Reduced protein digestibility is primarily associated with excessive heat, exemplified by the comparatively low digestibility of ready-to-eat breakfast cereals. Experiments with model systems indicate that some caution should be observed with the use of alkalis in food processing, and with products prone to the Maillard reaction.


Pairing exercise with activity: new tools for inspiring active lifestyles.
The concept of "fitness personality" has been a topic of growing interest in the past few decades, and recent findings suggest it can be used to open a dialogue with patients about their activity choices. Clinicians who understand how seven personality dimensions (sociability, spontaneity, self-motivation, aggressiveness, competitiveness, aggressiveness, mental focus, and risk taking) relate to various sports can help patients identify more satisfying activities. By using simple tools for matching personality types with activities, physicians may increase patient compliance with exercise prescriptions. Patients who complete a personality assessment may gain insights and additional motivation to pursue regular exercise and fitness for a lifetime.


[Potential for modelling the hemodynamic effects of weightlessness by exposure to increased pressure].
Venous and arterial circulation was investigated by simulating cephalad blood shifts generated by an exposure of test subjects (n = 15) to lower body positive pressure (+25 mm Hg) and head-down tilts (at -8 degrees and -15 degrees). At LBPP and tilt -15 degrees arterial pressure increased by 5-15%. During tilt -8 degrees jugular vein blood filling increased by 8-94% in the course of the first 3 hrs and then decreased reaching the baseline (horizontal position) level. During LBPP the parameter changed in a similar manner (increased by 2-50%). During tilt -15 degrees the parameter grew by 10-110% and remained elevated. The exposures gave rise to bradycardia which was more pronounced during -8 degrees and LBPP. The data obtained give evidence that circulation changes during LBPP and head-down tilts are identical. This suggests that LBPP can be used to simulate the effect of cephalad blood shifts, one of the most important effects of weightlessness on the human body.


Genomic Analysis of Lassa Virus during an Increase in Cases in Nigeria in 2018.
During 2018, an unusual increase in Lassa fever cases occurred in Nigeria, raising concern among national and international public health agencies. We analyzed 220 Lassa virus genomes from infected patients, including 129 from the 2017-2018 transmission season, to understand the viral populations underpinning the increase. A total of 14 initial genomes from 2018 samples were generated at Redeemer's University in Nigeria, and the findings were shared with the Nigerian Center for Disease Control in real time. We found that the increase in cases was not attributable to a particular Lassa virus strain or sustained by human-to-human transmission. Instead, the data were consistent with ongoing cross-species transmission from local rodent populations. Phylogenetic analysis also revealed extensive viral diversity that was structured according to geography, with major rivers appearing to act as barriers to migration of the rodent reservoir.


An augmentation study of MSI-195 (S-adenosylmethionine) in Major Depressive Disorder.
We conducted a 6-week double-blind, placebo-controlled, augmentation study comparing the efficacy and safety of MSI-195 800 mg (a proprietary formulation of S-adenosylmethionine) or placebo added to ongoing antidepressant medication (ADT) in acutely depressed subjects with Major Depressive Disorder (MDD) who had experienced an inadequate response to their ongoing ADT (The Horizon Study, ClinicalTrials.gov NCT01912196). There were 234 eligible subjects randomized to either MSI-195 (n = 118) or placebo (n = 116). There were no overall statistically significant differences found between MSI-195 added to ongoing ADT compared to placebo on any of 3 depression-rating instruments (HamD17, MADRS, IDS-SR30) in the ITT set. MSI-195 was generally safe and well tolerated with predominantly mild gastrointestinal side effects. Post-hoc analyses examined factors that might have affected study outcome. The ITT set was divided into subjects enrolled during the 1st half (first nine months) and 2nd half of the study. MSI-195 added to ongoing ADT was significantly better than placebo on both the HamD17 and MADRS in the 1st half (p = 0.03 and 0.02 respectively), but not in the 2nd half of the study. Several demographic and clinical characteristics were significantly different between the two study segments including body mass index, pre-randomization symptom severity fluctuation, number of lifetime depressive episodes, and anxious depression sub-type. Thus, the characteristics of the enrolled subjects changed between the 1st and 2nd half of the study. These post-hoc findings highlight the inherent challenges encountered for subject selection in double-blind, placebo controlled trials and compel further investigation of enrollment criteria and moderating factors that affect treatment. The favorable safety profile and clinical benefit observed with MSI-195 in the 1st half of this study warrant further investigation in MDD.


[Prenatal origin of parent-child relations. I. Attempt at a schema of development].
All over the world in recent years the increasing awareness of the importance of the relationship between parent and child for the perinatal period has led to changes in the practices of maternity units. Unfortunately, concentrating on the perinatal period has turned attention away from the interaction of the parent with the child over a much longer period before and after birth. We suggest that, under favourable conditions, there is a psychobiological development of the relationship that exists in the perinatal period which has developed in parallel with the physical development of the fetus. This article suggests how the normal process of the antenatal development occurs in this reference and points out certain psycho-social difficulties that can interfere with its progress. Our thesis is that it is essential to understand this process as part of the complete care given in obstetrics.


Income differences in social control of eating behaviors and food choice priorities among southern rural women in the US: A qualitative study.
The role of social influences on rural women's food choice is not well understood. Rural adults experience high rates of obesity and poor diet quality prompting exploration of how social factors influence food choice in this population. Semi-structured qualitative interviews were conducted with 20 women in rural North Central Florida. Women were purposively sampled and stratified by race and income. Lower income was defined as household income at or below 185% of the federal poverty level (FPL). Women at or below 185% poverty level (BPL) experienced direct social control of their eating behaviors, which occurred when social network members explicitly regulated or otherwise sanctioned eating behaviors or food choices. Women above 185% of the federal poverty level (APL) internalized social norms and self-regulated their eating behaviors to maintain healthy habits. APL women described choosing foods for health reasons whereas BPL women offered a variety of reasons including taste, convenience, family history, price, health, and routine. Findings suggest that women in different income groups have different social influences working to help them regulate eating behaviors as well as diverse priorities influencing their food choices. Future interventions to promote healthy eating may be more effective by incorporating social network members and framing intervention messages so they are consistent with priorities.


Toward parsimony in the inpatient community meeting on a short-term unit.
The role of the community meeting on the inpatient psychiatric unit has been continuously transformed by the radical shifts in the practice of inpatient psychiatry over the past 40 years. The current clinical climate of extremely shortened lengths of stay requires the community meeting to directly address the inpatient unit's primary tasks of stabilization, discharge planning, and treatment compliance and to avoid the regressive effects of large, unstructured groups. In these conditions, an interpretive model of the community meeting, which addresses patients' projections onto staff behavior, seems problematic and not widely applicable because it turns patients' attention away from the adaptational challenges they face from their external social environments. It also places heavy demands on staff time, training, and tolerance.


Isocube: exploiting the cubemap hardware.
This paper proposes a novel six-face spherical map, isocube, that fully utilizes the cubemap hardware built in most GPUs. Unlike the cubemap, the proposed isocube uniformly samples the unit sphere (uniformly distributed), and all samples span the same solid angle (equally important). Its mapping computation contains only a small overhead. By feeding the cubemap hardware with the six-face isocube map, the isocube can exploit all built-in texturing operators tailored for the cubemap and achieve a very high frame rate. In addition, we develop an anisotropic filtering that compensates aliasing artifacts due to texture magnification. This filtering technique extends the existing hardware anisotropic filtering and can be applied not only to the proposed isocube, but also to other texture mapping applications.


Childhood adversity trajectories and PTSD in young adulthood: A nationwide Danish register-based cohort study of more than one million individuals.
We examine the association between trajectories of childhood adversities and Post-Traumatic Stress Disorder (PTSD) using a register-based Danish cohort. The DANish LIFE Course (DANLIFE) cohort includes and prospectively follows all individuals born in Denmark from 1980. We estimated the rate of PTSD diagnosed from age 16, according to childhood adversity trajectories from age 0 to 16 (n = 1 277 548). Trajectories were previously defined into 5 groups: Low Adversity, Early Life Material Deprivation, Persistent Material Deprivation, Loss or Threat of Loss, And High Adversity. We then estimated adjusted relative hazard ratios (aHR), and absolute hazards differences of PTSD according to childhood adversity trajectories in adjusted survival analysis. All analyses were stratified by sex. Individuals were followed for a median of 10·1 years a fter their 16th birthday, and 4966 individuals were diagnosed with PTSD. Compared with the low adversity group, children exposed to childhood adversity were more likely to be diagnosed with PTSD. The aHR for PTSD varied from 1·4 (95% CI: 1·3-1·5) in the Early Life Material Deprivation group, to 3·7 (3·3-4·1) in the High Adversity group, which corresponds to 8·3 extra cases of PTSD per 10 000 person years. The relative associations were comparable in men and women, but approximately twice as many women compared with men were affected. We report a clear association between exposure to childhood adversities and PTSD in young adulthood. The highest burden was among women in the high adversity group.


Patterns of genetic structuring at the northern limits of the Australian smelt (Retropinna semoni) cryptic species complex.
Freshwater fishes often exhibit high genetic population structure due to the prevalence of dispersal barriers (e.g., waterfalls) whereas population structure in diadromous fishes tends to be weaker and driven by natal homing behaviour and/or isolation by distance. The Australian smelt (Retropinnidae: Retropinna semoni) is a native fish with a broad distribution spanning inland and coastal drainages of south-eastern Australia. Previous studies have demonstrated variability in population genetic structure and movement behaviour (potamodromy, facultative diadromy, estuarine residence) across the southern part of its geographic range. Some of this variability may be explained by the existence of multiple cryptic species. Here, we examined genetic structure of populations towards the northern extent of the species' distribution, using ten microsatellite loci and sequences of the mitochondrial cyt b gene. We tested the hypothesis that genetic connectivity among rivers should be low due to a lack of dispersal via the marine environment, but high within rivers due to dispersal. We investigated populations corresponding with two putative cryptic species, SEQ-North (SEQ-N), and SEQ-South (SEQ-S) lineages occurring in south east Queensland drainages. These two groups formed monophyletic clades in the mtDNA gene tree and among river phylogeographic structure was also evident within each clade. In agreement with our hypothesis, highly significant overall FST values suggested that both groups exhibit very low dispersal among rivers (SEQ-S FST = 0.13; SEQ-N FST= 0.27). Microsatellite data indicated that connectivity among sites within rivers was also limited, suggesting dispersal may not homogenise populations at the within-river scale. Northern groups in the Australian smelt cryptic species complex exhibit comparatively higher among-river population structure and smaller geographic ranges than southern groups. These properties make northern Australian smelt populations potentially susceptible to future conservation threats, and we define eight genetically distinct management units along south east Queensland to guide future conservation management. The present findings at least can assist managers to plan for effective conservation and management of different fish species along coastal drainages of south east Queensland, Australia.


Normal pressure hydrocephalus: Diagnostic and predictive evaluationon.
In typical cases, normal pressure hydrocephalus (NPH) manifests itself with the triad of gait disturbance, which begins first, followed by mental deterioration and urinary incontinence associated with ventriculomegaly (on CT or MRI) and normal cerebrospinal fluid (CSF) pressure. These cases present minor diagnostic difficulties and are the most likely to improve after shunting. Problems arise when NPH shows atypical or incomplete clinical manifestations (25-50% of cases) or is mimicked by other diseases. In this scenario, other complementary tests have to be used, preferentially those that can best predict surgical outcome. Radionuclide cisternography, intracranial pressure monitoring (ICP) and lumbar infusion tests can show CSF dynamics malfunction, but none are able to confirm whether the patient will benefit from surgery. The CSF tap test (CSF-TT) is the only procedure that can temporarily simulate the effect of definitive shunt. Since the one tap CSF-TT has low sensitivity, it cannot be used to exclude patients from surgery. In such cases, we have to resort to a repeated CSF-TT (RTT) or continuous lumbar external drainage (LED). The most reliable prediction would be achieved if RTT or LED proved positive, in addition to the occurrence of B-waves during more than 50% of ICP recording time. This review was based on a PubMed literature search from 1966 to date. It focuses on clinical presentation, neuroimaging, complementary prognostic tests, and differential diagnosis of NPH, particularly on the problem of selecting appropriate candidates for shunt.


Estimating the Prevalence of Dementia in India Using a Semi-Supervised Machine Learning Approach.
Accurate estimation of dementia prevalence is essential for making effective public and social care policy to support individuals and families suffering from the disease. The purpose of this paper is to estimate the prevalence of dementia in India using a semi-supervised machine learning approach based on a large nationally representative sample. The sample of this study is adults 60 years or older in the wave 1 (2017-2019) of the Longitudinal Aging Study in India (LASI). A subsample in LASI received extensive cognitive assessment and clinical consensus ratings and therefore has diagnoses of dementia. A semi-supervised machine learning model was developed to predict the status of dementia for LASI participants without diagnoses. After obtaining the predictions, sampling weights and age standardization to the World Health Organization (WHO) standard population were applied to generate the estimate for prevalence of dementia in India. The prevalence of dementia for those aged 60 years and older in India was 8.44% (95% CI: 7.89%-9.01%). The age-standardized prevalence was estimated to be 8.94% (95% CI: 8.36%-9.55%). The prevalence of dementia was greater for those who were older, were females, received no education, and lived in rural areas. The prevalence of dementia in India may be higher than prior estimates derived from local studies. These prevalence estimates provide the information necessary for making long-term planning of public and social care policy. The semi-supervised machine learning approach adopted in this paper may also be useful for other large population aging studies that have a similar data structure.


Data Augmentation of Surface Electromyography for Hand Gesture Recognition.
The range of applications of electromyography-based gesture recognition has increased over the last years. A common problem regularly encountered in literature is the inadequate data availability. Data augmentation, which aims at generating new synthetic data from the existing ones, is the most common approach to deal with this data shortage in other research domains. In the case of surface electromyography (sEMG) signals, there is limited research in augmentation methods and quite regularly the results differ between available studies. In this work, we provide a detailed evaluation of existing (i.e., additive noise, overlapping windows) and novel (i.e., magnitude warping, wavelet decomposition, synthetic sEMG models) strategies of data augmentation for electromyography signals. A set of metrics (i.e., classification accuracy, silhouette score, and Davies-Bouldin index) and visualizations help with the assessment and provides insights about their performance. Methods like signal magnitude warping and wavelet decomposition yield considerable increase (up to 16%) in classification accuracy across two benchmark datasets. Particularly, a significant improvement of 1% in the classification accuracy of the state-of-the-art model in hand gesture recognition is achieved.


Exposure-response relationships for inhalant wheat allergen exposure and asthma.
A few studies have investigated exposure-response relationships for sensitisation to wheat, work-related symptoms and wheat allergen exposure. IgG4 is suggested to protect against the development of allergic sensitisation. The main aim of this current study was to explore the nature of exposure-response relationships for a range of clinically relevant endpoints among bakery workers, and to investigate the role of IgG4 in these relationships. A cross-sectional study of 517 supermarket bakery workers in 31 bakeries used a questionnaire, serum-specific IgE and IgG4 to wheat, and methacholine challenge testing. Exposure models were developed previously using job, bakery size, tasks and specific ingredients used. These models were used to predict average personal exposure to wheat allergens. The exposure-response relationships for average exposure followed a linear relationship for sensitisation, but a bell-shaped curve for allergic symptoms and probable occupational asthma, increasing up to 10-15 µg/m(3) wheat allergen concentration after which they plateau off and decrease at higher exposure concentrations. This relationship was modified by atopic status. IgG4 levels were strongly exposure related: a clear increase in prevalence of higher IgG4 with increase in wheat allergen exposure was observed among those sensitised and non-sensitised to wheat, with IgG4 even more strongly associated with exposure than IgE to wheat. The bell-shaped exposure-response relationship in the current study is consistent with the findings of previous studies. IgG4 showed no protective effect for sensitisation, confirming the findings of previous studies, suggesting that the pattern is probably related to a healthy worker effect.


iPSC Modeling of RBM20-Deficient DCM Identifies Upregulation of RBM20 as a Therapeutic Strategy.
Recent advances in induced pluripotent stem cell (iPSC) technology and directed differentiation of iPSCs into cardiomyocytes (iPSC-CMs) make it possible to model genetic heart disease in vitro. We apply CRISPR/Cas9 genome editing technology to introduce three RBM20 mutations in iPSCs and differentiate them into iPSC-CMs to establish an in vitro model of RBM20 mutant dilated cardiomyopathy (DCM). In iPSC-CMs harboring a known causal RBM20 variant, the splicing of RBM20 target genes, calcium handling, and contractility are impaired consistent with the disease manifestation in patients. A variant (Pro633Leu) identified by exome sequencing of patient genomes displays the same disease phenotypes, thus establishing this variant as disease causing. We find that all-trans retinoic acid upregulates RBM20 expression and reverts the splicing, calcium handling, and contractility defects in iPSC-CMs with different causal RBM20 mutations. These results suggest that pharmacological upregulation of RBM20 expression is a promising therapeutic strategy for DCM patients with a heterozygous mutation in RBM20.