Engaging families as experts: collaborative family program development.
This article presents the collaborative family program development (CFPD) model, a collaborative research-based approach to creating community-based programs for families. In this approach, families are viewed as experts on the nature of their challenges and on what they desire in a program. This approach is particularly useful in developing programs for families who have experienced social oppression and who may have been reluctant to participate in programs created for them by professionals without their consultation. In contrast, when professionals adopt the stance of respectful learners, families respond by actively engaging in the program development research and in the program created from it. This article describes the nature and complexities of a collaborative program development stance, the unique contribution to community-based program development offered by a family systems focus, and the 10 steps in the CFPD approach. These 10 steps guide movement from initiating the project and forming collaborative professional partnerships to engaging cultural consultants; conducting in-depth research to understand the problems, resources, contexts, and recommendations from the perspective of families who will receive the program and from the perspective of front-line professionals working with these families; transforming research findings into program contents and formats; and implementing, evaluating, revising, and replicating the program. The approach is illustrated by a program called Fresh Start for Families, developed and replicated for families in New York City who are homeless and attempting to move from welfare to work.


XPA-210: a new proliferation marker determines locally advanced prostate cancer and is a predictor of biochemical recurrence.
XPA-210 is a proliferation marker derived from Thymidine kinase-1. It is of clinical significance in kidney, breast, and bladder cancer. There are no data available for XPA-210 in prostate cancer (PC). Herein, we aim to determine the clinical usefulness of XPA-210 in PC. In a retrospective study, cancer and benign tissue samples of 103 patients (median age 65 years, median PSA 9.04 ng/ml, median Gleason score 6) who underwent prostatectomy were constructed to a tissue micro array and stained for XPA-210. Semi-quantitative results were correlated with pathological and clinical data by Wilcoxon-Kruskall-Wallis and linear regression analysis. Expression levels in PC were correlated between the time of biochemical recurrence and the time to development of metastasis by the Kaplan-Meier method. Multivariate analysis was done to correlate those with the resection status. Mean staining score was 0.51-0.14 for tumor and benign tissue (P < 0.0001). Tumor staining score was significantly associated with Gleason score <6/≥6 (P < 0.0001) and T2/T >2 (P = 0.0007). When dividing the tumor score by the mean value, higher expression of XPA-210 was associated with a shorter time to biochemical recurrence (P = 0.003) and time to development of metastasis (P = 0.0061). Tumor staining (P = 0.0371) was an independent prognostic factor for biochemical relapse regardless of resection status. XPA-210 is a new tissue-based prognostic marker for prostate cancer histopathology. It reliably differentiates tumor and normal prostatic tissue predicting biochemical relapse and onset of metastatic disease. XPA-210 might be clinically useful for individual decision-making in PC-treatment.


Gene regulatory networks by transcription factors and microRNAs in breast cancer.
Gene regulatory networks (GRNs) affect numerous cellular processes and every process of life, and abnormalities of GRN lead to breast cancer. Transcription factors (TFs) and microRNAs (miRNAs) are two of the best-studied gene regulatory mechanisms. However, the architecture and feature of GRNs by TFs and miRNAs in breast cancer and its subtypes were unknown. In this study, we investigated the GRNs by TFs and miRNAs with emphasis on breast cancer classifier genes at system level.


What to do when SSRIs fail: eight strategies for optimizing treatment of panic disorder.
Selective serotonin reuptake inhibitors (SSRIs) are the drug of choice for treatment of patients with panic disorder. Most patients have a favorable response to SSRI therapy; however, 30 percent will not be able to tolerate these drugs or will have an unfavorable or incomplete response. Strategies to improve management of such patients include optimizing SSRI dosing (starting at a low dose and slowly increasing the dose to reach the target dose) and ensuring an adequate trial before switching to a different drug. Benzodiazepines should be avoided but, when necessary, may be used for a short duration or may be used long-term in patients for whom other treatments have failed. Slower-onset, longer-acting benzodiazepines are preferred. All patients should be encouraged to try cognitive behavior therapy. Augmentation therapy should be considered in patients who do not have a complete response. Drugs to consider for use in augmentation therapy include benzodiazepines, buspirone, beta blockers, tricyclic antidepressants, and valproate sodium.


Taxane-based chemotherapy and risk of breast cancer-related lymphedema: Protocol for a systematic review and meta-analysis.
Many studies were performed to explore the correlation between taxane-based chemotherapy and the risk of breast cancer-related lymphedema (BCRL), however, with inconsistent results. Hence, the purpose of this study is to evaluate whether taxane-based chemotherapy is a risk factor for BCRL. A comprehensive systematic search of clinical trials published in the PubMed, Embase and the Cochrane Library databases will be conducted to identify eligible studies up to the date of December 31, 2018. We will employ risk ratios with 95% confidence intervals (95% CIs) to estimate the correlations between taxane-based chemotherapy and BCRL. Meta-analysis will be performed using Stata SE version 12.0 software. The results of this systematic review and meta-analysis will provide a high-quality synthesis of existing evidence of the correlations between taxane-based chemotherapy and the risk of BCRL. The protocol will provide updated evidence for the use of taxane-based chemotherapy in postoperative breast cancer patients. It is not necessary for ethical approval because it is based on published studies. The protocol will be disseminated in a peer-reviewed journal or presented at a topic-related conference. This systematic review protocol has been registered with a number of CRD42019123989.


Apoptotic effects of diosgeninlactoside on oral squamous carcinoma cells in vitro and in vivo.
Diosgenyl saponins possess a variety of biological functions. Herein, we demonstrate a new type of diosgenyl saponin derivatives that inhibit cellular proliferation of oral squamous cell carcinoma (OSCC) cell lines. Thereafter, we analyzed these cells' expression of apoptosis-related proteins. Crucial proteins that participate in apoptosis regulation including caspases 8, 9, and 3, and cleaved Bid were activated and upregulated accompanied by increased concentrations of diosgenyl saponins. Meanwhile, Bcl-2 was downregulated and mitochondrial membrane potential decreased. In our mice model of OSCC, compound 1 showed potent inhibition of solid tumor growth and salient antitumor activity. Diosgenyl β-D-galactopyranosyl-(1→4)-β-D-glucopyranoside might induce OSCC cell line apoptosis through extrinsic and intrinsic pathways, and might provide a mechanistic background for the development of this new type of diosgenylsaponin derivatives into anti-oral cancer agents against OSCC.


Prognostic factors in non-metastatic Ewing's sarcoma tumor of bone: an analysis of 579 patients treated at a single institution with adjuvant or neoadjuvant chemotherapy between 1972 and 1998.
We aimed to identify pretreatment and treatment factors that may influence the outcome of Ewing's sarcoma family tumors of bone and enable customized therapy for future studies with a retrospective analysis of 579 patients with non-metastatic Ewing's sarcoma treated with combined adjuvant or neoadjuvant chemotherapy at a single institution between 1972 and 1998. We evaluated the prognostic significance of gender, age, site and volume of tumor, serum level of LDH, type of local treatment, type of chemotherapy and histologic response to preoperative treatment. The 5- and 10-year disease-free survival rates were 56.9% and 49.2% respectively. Multivariate analyses showed that all the evaluated factors, with exclusion of the tumor site, were significantly correlated with the 5-year disease-free survival. We concluded that the outcome of non-metastatic ESF of bone tumors is influenced by many clinical and treatment-correlated variables. In order to gain the greatest benefit from treatment, while reducing the morbidity, appropriate therapeutic strategies for different risk groups of patients should be selected. Criteria to stratify patients according to the risk of local or systemic relapse should not be based on a single prognostic factor, but should include all the variables that showed prognostic significance.


The autophagic pathway is actively modulated by phase II Coxiella burnetii to efficiently replicate in the host cell.
The etiologic agent of Q fever Coxiella burnetii, is an intracellular obligate parasite that develops large vacuoles with phagolysosomal characteristics, containing multiple replicating bacteria. We have previously shown that Phase II C. burnetii replicative vacuoles generated after 24-48 h post infection are decorated with the autophagic protein LC3. The aim of the present study was to examine, at earlier stages of infection, the distribution and roles of the small GTPases Rab5 and Rab7, markers of early and late endosomes respectively, as well as of the protein LC3 on C. burnetii trafficking. Our results indicate that: (i) Coxiella phagosomes (Cph) acquire the two Rab proteins sequentially during infection; (ii) overexpression of a dominant negative mutant form of Rab5, but not of Rab7, impaired Coxiella entry, whereas both Rab5 and Rab7 dominant negative mutants inhibited vacuole formation; (iii) Cph colocalized with the protein LC3 as early as 5 min after infection; acquisition of this protein appeared to be a bacterially driven process, because it was inhibited by the bacteriostatic antibiotic chloramphenicol and (iv) C. burnetii delayed the arrival of the typical lysosomal protease cathepsin D to the Cph, which delay is further increased by starvation-induced autophagy. Based on our results we propose that C. burnetii transits through the normal endo/phagocytic pathway but actively interacts with autophagosomes at early times after infection. This intersection with the autophagic pathway delays fusion with the lysosomal compartment possibly favouring the intracellular differentiation and survival of the bacteria.


A review of the Personal Orientation Dimensions Inventory.
The Personal Orientation Dimensions Inventory is considered to be an extension and refinement of the concepts measured by the Personal Orientation Inventory. Changes include the elimination of item overlap, an increase in the number of scales and items in the inventory as well as a new theoretical perspective. Significant difficulties still appear to exist in the areas of test construction, theoretical justification, and interpretation. Moreover, the new inventory creates new problems concerning cost for scoring, failure to generate significant amounts of research, as well as a potential loss of relatedness to old research.


Giant Magnetoelastic Effect Enabled Stretchable Sensor for Self-Powered Biomonitoring.
Interfacing with the human body, wearable and implantable bioelectronics are a compelling platform technology for healthcare monitoring and medical therapeutics. However, clinical adoption of these devices is largely shadowed by their weakness in humidity resistance, stretchability, durability, and biocompatibility. In this work, we report a self-powered waterproof biomechanical sensor with stretchability up to 440% using the giant magnetoelastic effect in a soft polymer system. By manipulating the magnetic dipole alignment, the sensor achieved a particularly broad sensing range from 3.5 Pa to 2000 kPa, with a response time of ∼3 ms. To validate the excellent performance of the magnetoelastic sensor in biomonitoring, both ex vivo porcine heart testing and in vivo rat model testing were performed for cardiovascular monitoring and heart disease diagnosis. With the obtained sensing data, we have successfully detected ventricular arrhythmia and ventricular fibrillation in the Sprague-Dawley rat model. Holding a collection of compelling features, including minimal hysteresis, ultrawide sensing range, waterproofness, and biocompatibility, the magnetoelastic sensor represents a unique platform technology for self-powered biomonitoring in both wearable and implantable manners.


Update on myasthenia gravis.
Myasthenia gravis is an autoimmune disorder caused by autoantibodies against the nicotinic acetylcholine receptor on the postsynaptic membrane at the neuromuscular junction and characterised by weakness and fatigability of the voluntary muscles. It has a bimodal peak of incidence with first peak in the third decade and the second peak in the sixth decade. It is probably underdiagnosed in the very old population. Our understanding of the pathogenesis, immunology, and molecular biology of myasthenia gravis has greatly improved in last three decades. It is almost always possible to establish the diagnosis of myasthenia gravis with the current tests. The modern treatment is highly successful and the mortality of treated myasthenia gravis is practically zero. However, there are still important gaps in our knowledge of the origin of myasthenia gravis, the factors that contribute to chronic disease, and the way to cure the disease. In this article the current knowledge of the various aspects of myasthenia gravis are outlined.


Immunological interactions between host cells and mycoplasmas: an introduction.
In addition to eliciting host immune responses, many mycoplasmas interact nonspecifically with host cells. Early reports revealed peculiar inhibitory and stimulatory effects of mycoplasmas on the immune response in vivo; several investigators have now clearly defined nonspecific stimulation of B and T lymphocytes and also a nonspecific immunosuppressive effect on experimental animals and humans. These interactions relate to attachment of mycoplasmas to host cell membranes and perhaps involve sharing of membrane components. The implications of these peculiar effects of mycoplasmas on host cells suggest that much of the disease seen in the infected host is due to a nonspecific, inflammatory response to the mitogenic properties of the organism. Since the organism becomes intimately involved with the host cell membrane, this could enable the organism to evade the immunologic surveillance system and thus achieve the prolonged surface colonization characteristic of many mycoplasmas.


Gastrointestinal involvement in the Ehlers-Danlos syndromes.
Current evidence suggests that an association exists between non-inflammatory hereditary disorders of connective tissue such as the Ehlers-Danlos syndromes (EDS) and gastrointestinal (GI) symptoms. Patients with EDS can present with both structural problems such as hiatus hernias, visceroptosis, rectoceles, and rectal prolapse as well as functional problems such as disordered gut motility. It has recently been demonstrated that patients with hypermobile EDS (hEDS) present with GI symptoms related to the fore and hind-gut and these patients frequently meet the criteria for functional gastrointestinal disorders such as functional dyspepsia and irritable bowel syndrome. Presence of GI symptoms in EDS patients influences their quality of life. Specific evidence based management guidelines for the management of GI symptoms in EDS patients do not exist and these patients are often treated symptomatically. There is, however, recognition that certain precautions need to be taken for those patients undergoing surgical treatment. Future studies are required to identify the mechanisms that lead to GI symptoms in patients with EDS and more specific treatment guidelines are required. © 2017 Wiley Periodicals, Inc.


Temperament and character dimensions assessed in general population, in individuals with psychoactive substance dependence and in young male conscripts.
In this work we consider Cloninger's psychobiological model, which measures two dimensions of personality: character and temperament. Temperament refers to the biological basis of personality and its characteristics, while character refers to an individual's attitudes towards own self, towards humanity and as part of the universe. The Temperament and Character Inventory-Revised-140 (TCI-R-140) was administered to 3 divergent samples: a general population sample, a sample of male conscripts and a sample of individuals attending a substance abuse rehabilitation programme. Score differences among the three samples were assessed controlling for age and gender and reliability coefficients are reported. The latent structure was studied in all samples, using exploratory and confirmatory factor analysis methods (EFA and CFA respectively). The proposed structure was partially replicated via EFA. CFA however indicated less than satisfactory fit, as in previously reported results. To improve the fit, the path diagram was augmented to account for multiple factor complexity, as suggested by the EFA results in all samples. While retaining the original seven-factor structure, the augmented model provided adequate fit. The consistency of the inventory was satisfactory in all samples. Evidence for the construct validity was found in relation to aggression. This is the first study to conclude in adequate fit, after allowing for the indicators to load on more than one factor within each dimension. While cross-national differences apply, our results were similar (when comparable) with previously reported ones in the literature.


Dynamic copper(I) imaging in mammalian cells with a genetically encoded fluorescent copper(I) sensor.
Copper, a key cofactor for many life processes, is toxic at elevated levels, and its availability is strictly controlled inside cells. Therefore, it is a challenge to visualize copper availability in the tight copper-binding environment of the cell. We report a genetically encoded fluorescent copper(I) sensor based on the copper(I)-binding-induced conformational change of a copper-responsive transcriptional regulator, Amt1. The resulting reporter, Amt1-FRET, is ratiometric, highly sensitive (K(d) = 2.5 x 10(-18) M), and selective toward copper(I). Its measured high affinity to copper(I) confirms the extremely low copper availability in yeast since Amt1 senses the upper limit of cellular copper levels in yeast and activates copper detoxification genes. Amt1-FRET operates in the dynamic range of the cellular copper buffer in mammalian cells and can report dynamic fluctuations of the cellular copper availability within minutes of perturbation. Thus, Amt1-FRET visualizes the tightly controlled copper availability in mammalian cells.


Ultrastructural changes of the renal cortex after septic shock in rats.
The purpose of this study was to observe the ultrastructural changes of the renal cortex that occur in septic shock. Twenty male Wistar rats were used. They were divided into 4 groups of five animals each one. A septic shock was caused by intraperitoneal injection of 5 x 10(6) living E. Coli, in a dose of 2ml/100gr B. W., in four rats of each group. The fifth rat of each group was used as control, and was injected by an equal volume of normal saline. A small segment from the right kidney was excised from every rat of each group, respectively 1, 2, 4 and 6 hours after the onset of the shock. Morphologically, alterations of the endothelium of the peritubular and glomerular capillaries were found. The endothelial layer was thick with many cytoplasmic folds. In the glomeruli, the basal lamina as well as the overlying epithelial podocytes and their foot processes were swollen. The urinary space contained erythrocytes and cell debris. Lesions of the proximal and distal tubule epithelium were also observed. The basal infoldings of the cell membrane disappeared in many epithelial cells of the proximal tubule and the brush border showed varying degrees of disruption. Within the tubular lumen much cellular debris was found. The epithelium of the distal tubule was thinner in some portions and in others it was swollen. The lesions were focal during the first hour after the onset of shock, while at the fourth and sixth hours they were most extensive. In conclusion, the ultrastructural findings after septic shock were non-specific and indicated cellular injury.


The Monkeypox Outbreak and Implications for Dental Practice.
Monkeypox (MPX) caused by the MPX virus, is a contagious disease confined mainly to African regions, and is currently making multiple appearances outside of disease-endemic countries. World Health Organization (WHO) very recently declared the current monkeypox outbreak a Public Health Emergency of International Concern. We review here the salient features of MPX and its possible impact on dentistry. The data on the aetiology, transmission modes, signs and symptoms, diagnosis, and management, including the risk of its occupational transmission in dental settings, were garnered from the current literature, mainly from the World Health Organization and Centers for Disease Control and Prevention databases. Over recent months, MPX has reemerged in more than 88 countries in Europe, North America, and Australia, with some 22000 case reports to date (as of July 2022). The initial signs of MPX appear during the prodromal period, in the oral cavity as single or multiple macular lesions on the oral mucosa, accompanied by generalised lymphadenopathy. Subsequently, the characteristic rash appears on the skin and spreads centripetally from the trunk towards the palms and soles. MPX is a self-limiting disease with very low mortality and may last from 2 to 4 weeks. Although MPX is similar to chickenpox, there are a number of differentiating signs, the main element being lymphadenopathy. Strict adherence to standard, contact, and droplet infection control precautions, including wearing N95 masks, FFP3 respirators, fluid-resistant attire, and eye protection, is necessary to prevent its spread. MPX appears to be a significant travel-related disease. Dental care workers should note that premonitory signs of the disease usually appear on the oral mucosa as macules and ulcers prior to the characteristic skin lesions. Implementing standard, contact, and droplet infection control measures, patient isolation, and referral are important, particularly during a local outbreak. A vaccine specific for MPX is under development, although the smallpox vaccine appears to be effective.


Perioperative complications of threaded cylindrical lumbar interbody fusion devices: anterior versus posterior approach.
Few data are available to evaluate approach-related differences in perioperative complications with lumbar interbody fusion devices. Complications occurring in the intraoperative and immediate postoperative period were identified and categorized for 31 consecutive posterior lumbar interbody fusions (PLIFs) and 88 consecutive anterior lumbar interbody fusions (ALIFs). In this study, all lumbar interbody fusions were conducted with threaded cylindrical devices as stand-alone internal fixation devices. Multivariate analysis was used to account for potential covariates and identify factors associated with an increased complication risk. Twenty-two percent of the patients had a perioperative complication. The relative risk of having a perioperative complication was 4.75 times higher for the PLIF group. All intraoperative complications occurred in the PLIF group. The relative risk of having a major postoperative complication was 6.8 times higher in the PLIF group than the ALIF group. Anterior approached patients tended to have visceral (ileus, 6%) and vascular (deep venous thrombosis, 2%) complications. In the posterior group, complications were neurologic and dura related (pseudomeningocele, 16%; epidural hematoma, 3%) and occurred most frequently in patients that had had previous posterior lumbar surgery (31% with major complication).


Risk factors for development of aminoglycoside resistance among gram-negative rods.
Development of scoring systems to predict the risk of aminoglycoside resistance and to guide therapy is described. Infections due to aminoglycoside-resistant gram-negative rods (AR-GNRs) are increasingly common and associated with adverse outcomes; selection of effective initial antibiotic therapy is necessary to reduce adverse consequences and shorten length of stay. To determine risk factors for AR-GNR recovery from culture, cases of GNR infection among patients admitted to 2 institutions in a major academic hospital system during the period 2011-2016 were retrospectively analyzed. Gentamicin and tobramycin resistance (GTR-GNR) and amikacin resistance (AmR-GNR) patterns were analyzed separately. A total of 26,154 GNR isolates from 12,516 patients were analyzed, 6,699 of which were GTR, and 2,467 of which were AmR. In multivariate analysis, risk factors for GTR-GNR were presence of weight loss, admission from another medical or long-term care facility, a hemoglobin level of <11 g/dL, receipt of any carbapenem in the prior 30 days, and receipt of any fluoroquinolone in the prior 30 days (C statistic, 0.63). Risk factors for AmR-GNR were diagnosis of cystic fibrosis, male gender, admission from another medical or long-term care facility, ventilation at any point prior to culture during the index hospitalization, receipt of any carbapenem in the prior 30 days, and receipt of any anti-MRSA agent in the prior 30 days (C statistic, 0.74). Multinomial and ordinal models demonstrated that the risk factors for the 2 resistance patterns differed significantly. A scoring system derived from the developed risk prediction models can be applied by providers to guide empirical antimicrobial therapy for treatment of GNR infections.


Clinical behaviors and skills that faculty from 12 institutions judged were essential for medical students to acquire.
This paper describes a 1988-1989 collaborative mail survey of faculty opinion about clinical behaviors and skills that students should be expected to demonstrate prior to graduation from undergraduate medical school (hereafter called "exit objectives"). Selected faculty from 12 American and Canadian medical schools indicated whether each of 77 objectives was essential for every student to know or demonstrate prior to graduation; useful but not essential at the undergraduate level; or not applicable to their undergraduate program. Their responses provide a glimpse into faculty expectations regarding some of the exit behaviours and skills they deemed essential. Forty-two percent (32) of the 77 objectives were regarded as essential by 75% or more of the faculty members who responded. Essential objectives involved conducting organ system examinations, formulating problems and hypotheses, and gathering fundamental interview, physical, and screening examination data, including emergency examinations of the airway and circulatory systems. Other essential objectives involved collaboration and communication, demonstrating concern for legal and ethical values, and keeping abreast of current information within the discipline. Exit objectives related to the diagnosis and management of specific conditions were regarded as useful but not essential at the undergraduate level. Implications for medical education are discussed.


Mobile Applications to Support Diabetes Self-Management Education: Patient Experiences and Provider Perspectives.
Diabetes self-management education and support (DSMES) is a critical component of diabetes care, but time for it is often limited. Digital tools, such as mobile applications (apps), show promise in extending efforts and supporting self-management education, but have not been fully used. Objectives of this multi-phase study were to (1) evaluate an app designed to support patients with insulin therapy and (2) examine provider perspectives on DSMES apps. Phase 1: Thirty-two adult patients with type 2 diabetes new to or having difficulties with insulin therapy were introduced to the BDTM Diabetes Care App. Three-month app use and satisfaction and changes in hemoglobin A1c (HbA1c) and diabetes distress were assessed. Phase 2: Sixty diabetes providers completed a survey about their experiences with and perspectives on DSMES apps. Phase 1: Patients reported satisfaction with the app, and significant improvements in HbA1c and diabetes distress were observed. Phase 2: Most providers viewed apps as adjuncts to diabetes education. Only 33% had previous app experience; however, 100% would consider recommending apps to their patients. Most would spend 5-15 minutes introducing apps to patients. All respondents agreed that the following DSMES app features-evidence-based educational content, data logging and tracking features, customizable user experience, digital coaching via goal setting or reminders, and ability to share data with providers-are key components to consider. Findings suggest DSMES apps can play a role in self-management support and provide guidance on factors to consider when introducing digital tools into clinical practice. Clinicaltrials.gov, #NCT03999268.


Role of lectin microarrays in cancer diagnosis.
The majority of cell differentiation associated tumor markers reported to date are either glycoproteins or glycolipids. Despite there being a large number of glycoproteins reported as candidate markers for various cancers, only a handful are approved by the US Food and Drug Administration. Lectins, which bind to the glycan part of the glycoproteins, can be exploited to identify aberrant glycosylation patterns, which in turn would help in enhancing the specificity of cancer diagnosis. Although conventional techniques such as HPLC and MS have been instrumental in performing the glycomic analyses, these techniques lack multiplexity. Lectin microarrays have proved to be useful in studying multiple lectin-glycan interactions in a single experiment and, with the advances made in the field, hold a promise of enabling glycomic profiling of cancers in a fast and efficient manner.


Anticoagulation in elderly patients who fall frequently: a therapeutic dilemma.
There is general agreement that patients with persistent atrial fibrillation, who are at risk of having a stroke, need to be anticoagulated. However, clinicians often are in a difficult dilemma when these patients also are at increased risk of falling. Falls can lead to serious injuries in anticoagulated individuals, including intracranial hemorrhages. This case study describes an 88-year-old patient with a history of falling. She received multiple injuries following a fall, including a subdural hematoma. Warfarin was among the patient's many medications. Upon admission to the hospital this patient had a supratherapeutic INR that most likely contributed to her injuries. A question facing the medical team was should she continue to receive warfarin to prevent stroke after discharge from the hospital? Much controversy exists over whether older patients receiving anticoagulation therapy are at increased risk of major hemorrhagic complications. This article discusses the relationship between anticoagulation, falling, and the risks of hemorrhagic events. It also discusses opinions on when to restart anticoagulation following resolution of the subdural hematoma. In addition, the patient was taking multiple medications that are known to contribute to falls in older people. Recommendations for lowering this patient's fall risks are presented.


Rare Incidence of Acute Liver Injury with Potassium Para-Aminobenzoate Introduction.
Acute liver injury is an alarming condition, as it may lead to a devastating outcome. Of the many causes of acute liver injury, review of medications is crucial to identifying the cause of the injury. Some commonly used medications may unpredictably be the underlying cause of liver injury. We present a case of Peyronie's disease treated with potassium para-aminobenzoate that developed acute liver injury. After starting the new treatment, the patient complained of right upper quadrant pain. He was found to have elevated liver enzymes. The condition resolved after stopping potassium para-aminobenzoate use. We report a potassium para-aminobenzoate side effect of liver injury that can be managed conservatively.


Long-term variation in environmental conditions influences host-parasite fitness.
Long-term data on host and parasite fitness are important for predicting how host-parasite interactions will be altered in an era of global change. Here, we use data collected from 1997 to 2013 to explore effects of changing environmental conditions on bird-blowfly interactions in northern New Mexico. The objectives of this study were to examine what climate variables influence blowfly prevalence and intensity and to determine whether blowflies and climate variables affect bird fledging success. We examined how temperature, precipitation, and drought affect two parasitic blowflies and their hosts, Western Bluebirds (Sialia mexicana) and Ash-throated Flycatchers (Myiarchus cinerascens). We found that blowfly prevalence did not change over time. Blowfly intensity increased over time in bluebird nests, but not in flycatcher nests. More blowflies result in slightly higher fledging success in bluebirds, but not flycatchers. There was a significant interaction between blowflies and precipitation on bluebird fledging success. For flycatchers, there was a significant interaction between blowflies and temperature and between blowflies and drought severity on fledging success. Given that the southwest is projected to be hotter and have more frequent and prolonged droughts, we predict that flycatchers may be negatively impacted by blowflies if these trends continue. Future work should focus on investigating the role of both blowflies and climate on fledging success. Climate patterns may negatively impact host fitness through altered parasite pressure.


A computer-based approach to assess the perception of composite odour intensity: a step towards automated olfactometry calibration.
The 2004 Nobel Prize in Physiology or Medicine laureates, Richard Axel and Linda Buck, have made smell a less enigmatic sense to study. In clinical routine, olfactory function is assessed using defined concentrations of a single defined substance, a setting which is uncommon in daily life. The present study was therefore conducted to evaluate the applicability of composite odours. Air was contaminated with different quantities of cyclohexanol, cyclohexanone and cyclohexane to generate 73 gas mixtures (one component: n = 21, two components: n = 40, three components: n = 12). The intensity of perception was estimated for each mixture by an average of 60.3 healthy individuals (4,403 assessments). An artificial neural network (ANN) was trained and validated using the contaminants' concentrations with the corresponding estimated intensities. The inter-rater variability was low, as 75.7% of the assessments did not exceed a difference beyond 0.5 from the corresponding median (considered correct predictions). The ANN correctly estimated 78.1% of the gas mixtures, and in terms of the regression task the ANN demonstrated a sufficient prediction performance (Pearson's correlation coefficient r = 0.883; R(2) = 0.757) and outperformed linear regression (r = 0.770; R(2) = 0.667). Evaluating extra ANNs for gas mixtures comprising one, two or three components, the predictive power did not decrease when complexity increased. The aforementioned results reflect nonlinearity in human perception. ANN technology helps simulate human perception of composite odour intensity which may be applicable to olfactometry calibration and systems biological mathematical modelling. The use of composite odours may represent real-life problems more adequately than single substances.


Plasma glucagon and catecholamines during exhaustive short-term exercise.
Plasma glucagon and catecholamine levels were measured in male athletes before and after exhaustive 15 min continuous running and strenuous intermittent short-term exercise (3 X 300 m). Blood lactate levels were higher after the intermittent exercise (mean 16.7 mmol X 1(-1)) than after the continuous running (mean 7.1 mmol X 1(-1)). Plasma glucagon concentration increased during continuous running and intermittent exercise by 41% and 55%, respectively, and the increases in plasma noradrenaline concentration were 7.7- and 9.1-fold compared with the respective pre-exercise values. Immediately after the exercises plasma cyclic AMP, blood glucose and alanine levels were elevated significantly. The data suggest that the sympathoadrenal system is of major importance for liver glucose production during high-intensity exercises. Catecholamines directly stimulate liver glucose production and may indirectly stimulate it by enhancing the secretion of glucagon.


Diffuse Peritoneal Malignant Mesothelioma Presenting with Abnormal Uterine Bleeding: Case Report.
This report describes a highly unusual case of malignant peritoneal mesothelioma (MPM), who presented with abnormal menstrual bleeding due to diffuse infiltration of the uterus. MPM is a rare entity, which on initial clinical presentation can be indistinguishable from a primary gynecological malignancy such as ovarian cancer. As differential diagnosis is challenging among primary care physicians, gynecologists, gynecological oncologists, and pathologists, misdiagnosis and subsequent mismanagement are not uncommon. Immunohistochemical stains were required in our case to help to make the final diagnosis. We included multiple mesothelial markers such as calretinin, CK5/6, WT-1, and D240 in our analysis, in addition to epithelial markers such as Claudin-4, BerEP4, B72.3, and PAX-8, to exclude metastatic adenocarcinoma.


Diffusion and binding of monoclonal antibody TNT-1 in multicellular tumor spheroids.
Tumor spheroids of HT-29 human colon adenocarcinoma and A375 melanoma were established to investigate the uptake and clearance kinetics of TNT-1, a monoclonal antibody that targets necrotic cells of tumors. Our data reveal that there was rapid uptake of TNT-1 and its F(ab')2 fragment in both spheroid models, whereas an antibody of irrelevant specificity, Lym-1, and its F(ab')2 fragment bound poorly to the spheroids. Unlike previously reported monoclonal antibodies to tumor cell-surface antigens, TNT-1 showed 1) a linear uptake that increased over time without saturation in tumor spheroids and 2) an unexpected uptake by a subpopulation of cells in the viable outer rim of the spheroids. These preclinical studies provide important information concerning the therapeutic potential of TNT monoclonal antibodies for the treatment of cancer and micrometastases.


Increased serum soluble CD147 levels in patients with systemic sclerosis: association with scleroderma renal crisis.
CD147 is a glycosylated membrane protein that belongs to the immunoglobulin superfamily. This study aimed to determine serum soluble CD147 (sCD147) levels and their clinical associations in patients with systemic sclerosis (SSc). Serum sCD147 levels were examined by enzyme-linked immunosorbent assay in 61 SSc patients and 24 healthy individuals. Serum sCD147 levels were significantly elevated in SSc patients compared with healthy individuals (P<0.001). Among patients with SSc, there were no differences in serum sCD147 levels between limited cutaneous (n030) and diffuse cutaneous SSc (n031). Patients with SSc who had elevated sCD147 levels had renal crisis more often than those with normal sCD147 levels (13% vs 0%; P<0.05). Serum sCD147 levels were increased in patients with SSc and associated with the presence of renal crisis. These results suggest that sCD147 may have a role in the development of renal crisis in SSc. Measurement of serum sCD147 may be useful for risk stratification for renal crisis in SSc.


Recurrent WNT pathway alterations are frequent in relapsed small cell lung cancer.
Nearly all patients with small cell lung cancer (SCLC) eventually relapse with chemoresistant disease. The molecular mechanisms driving chemoresistance in SCLC remain un-characterized. Here, we describe whole-exome sequencing of paired SCLC tumor samples procured at diagnosis and relapse from 12 patients, and unpaired relapse samples from 18 additional patients. Multiple somatic copy number alterations, including gains in ABCC1 and deletions in MYCL, MSH2, and MSH6, are identifiable in relapsed samples. Relapse samples also exhibit recurrent mutations and loss of heterozygosity in regulators of WNT signaling, including CHD8 and APC. Analysis of RNA-sequencing data shows enrichment for an ASCL1-low expression subtype and WNT activation in relapse samples. Activation of WNT signaling in chemosensitive human SCLC cell lines through APC knockdown induces chemoresistance. Additionally, in vitro-derived chemoresistant cell lines demonstrate increased WNT activity. Overall, our results suggest WNT signaling activation as a mechanism of chemoresistance in relapsed SCLC.


Effect of Yikou-Sizi powder hot compress on gastrointestinal functional recovery in patients after abdominal surgery: Study protocol for a randomized controlled trial.
Postoperative gastrointestinal dysfunction (PGD) is a common complication of patients who have undergone surgery. The clinical manifestations cause great discomfort to postoperative patients and can severely affect postoperative recovery. However, although various pharmacologic agents have been explored for several years, success has been limited. Because some commonly used drugs have caused adverse reactions and because abdominal surgery patients generally cannot consume food or medication during the perioperative period, we were prompted to try an external Chinese medicine treatment method. Yikou-Sizi powder hot compress is an efficient therapy in our hospital, but there is a lack of rigorous studies to certify the safety and effectiveness of its external use to improve gastrointestinal motility. This study aimed to introduce the clinical trial design and test the ability of Yikou-Sizi powder hot compress treatment to accelerate gastrointestinal functional recovery after abdominal surgery. This study is a randomized controlled clinical trial. The participants will undergo laparoscopic colorectal cancer surgery and laparoscopic total hysterectomy. The primary outcome measure will be the gastrointestinal functional evaluation index, including the time to first passage of flatus, first defecation, first normal bowel sounds, and first consumption of liquid/semigeneral diet foods. According to good clinical practice (GCP), we will evaluate the clinical efficacy and safety of Yikou-Sizi powder hot compress and objectively study the acting mechanism of ghrelin. This pilot trial will be a standard, scientific, and clinical study designed to evaluate the effect of Yikou-Sizi powder hot compress for the recovery of gastrointestinal function after surgery and determine its overall safety. This is the first study to describe the use of Yikou-Sizi powder hot compress to accelerate the recovery of gastrointestinal function after abdominal surgery. The study is designed as a randomized, controlled, clinical, large sample size and pilot trial. Evaluation will consist of combining the primary outcome measures with secondary outcome measures to ensure the objectivity and scientific validity of the study. Due to the observational design and the limited follow-up period, it is not possible to evaluate to what extent the connection between the observed improvement and the interventions represents a causal relationship. Efficient comparison between groups will be analyzed by chi-square test.


Neuropsychiatric symptom clusters and functional disability in cognitively-impaired-not-demented individuals.
Previous research has shown that cognitively-impaired-not-demented (CIND) individuals with at least one neuropsychiatric symptom (NPS) have more functional disability than individuals without any NPSs. The objectives of the present study were to determine whether there are consistent clusters of NPS in CIND individuals and whether certain NPS clusters are more strongly associated with measures of functional disability than other NPS clusters in this population. This was a cross-sectional baseline study of NPS using the Neuropsychiatric Inventory (NPI) in a national clinic-based observational cohort study (the Canadian Cohort Study of Cognitive Impairment and Related Dementias study). The present investigation focuses on a subset of CIND subjects (73%) whose informant endorsed the presence of at least one NPI item. A hierarchical cluster analysis identified two NPS clusters. One consisted of mood factors (i.e., depression, anxiety, apathy, irritability, and problems with sleep) and the other cluster captured frontal symptoms (i.e., aberrant motor behavior, disinhibition, agitation, and problems with appetite). NPSs grouped within the mood cluster were more common than the frontal cluster (95% of subjects had at least one NPS within the mood cluster versus 53% in the frontal cluster). However, the frontal cluster was more strongly associated with functional disability measures even after controlling for cognitive status (i.e., the Mini-Mental State Exam) and the mood cluster score. The frontal cluster of NPSs was more strongly associated with functional disability than the mood cluster.


Impact of the level of sickness on higher mortality in emergency medical admissions to hospital at weekends.
Objective Routine administrative data have been used to show that patients admitted to hospitals over the weekend appear to have a higher mortality compared to weekday admissions. Such data do not take the severity of sickness of a patient on admission into account. Our aim was to incorporate a standardized vital signs physiological-based measure of sickness known as the National Early Warning Score to investigate if weekend admissions are: sicker as measured by their index National Early Warning Score; have an increased mortality; and experience longer delays in the recording of their index National Early Warning Score. Methods We extracted details of all adult emergency medical admissions during 2014 from hospital databases and linked these with electronic National Early Warning Score data in four acute hospitals. We analysed 47,117 emergency admissions after excluding 1657 records, where National Early Warning Score was missing or the first (index) National Early Warning Score was recorded outside ±24 h of the admission time. Results Emergency medical admissions at the weekend had higher index National Early Warning Score (weekend: 2.53 vs. weekday: 2.30, p < 0.001) with a higher mortality (weekend: 706/11,332 6.23% vs. weekday: 2039/35,785 5.70%; odds ratio = 1.10, 95% CI 1.01 to 1.20, p = 0.04) which was no longer seen after adjusting for the index National Early Warning Score (odds ratio = 0.99, 95% CI 0.90 to 1.09, p = 0.87). Index National Early Warning Score was recorded sooner (-0.45 h, 95% CI -0.52 to -0.38, p < 0.001) for weekend admissions. Conclusions Emergency medical admissions at the weekend with electronic National Early Warning Score recorded within 24 h are sicker, have earlier clinical assessments, and after adjusting for the severity of their sickness, do not appear to have a higher mortality compared to weekday admissions. A larger definitive study to confirm these findings is needed.


Outcomes of pathologic stage T3a renal cell carcinoma up-staged from small renal tumor: emphasis on partial nephrectomy.
The prognosis of patients with pathologic stage T3a renal cell carcinoma (RCC) that is up-staged from a small renal tumor remains controversial. We evaluated the prognosis of patients with RCC who were up-staged from clinical stage T1 to pathologic stage T3a. We retrospectively reviewed the data of 3431 patients who were surgically treated for clinical stage T1 RCC. The survival outcomes were compared using Kaplan-Meier and Cox proportional analyses. Among the clinical stage T1 patients, 215 (6.3%) were finally up-staged to pathologic stage T3a. Patient age (HR 1.302, 95% CI 1.018-1.046, p < 0.001), tumor diameter (HR 1.686, 95% CI 1.551-1.834, p < 0.001), and hilar location (HR 1.765, 95% CI 1.147-2.715, p = 0.010) were significantly associated with upstaging. Kaplan-Meier analyses showed significantly shorter recurrence-free, cancer-specific and overall survivals (all p < 0.001) in patients who were up-staged. Multivariate Cox analyses revealed pathologic upstaging as an independent predictor of shorter recurrence-free (HR 2.195, 95% CI 1.459-3.300, p < 0.001), cancer-specific (HR 2.238, 95% CI 1.252-4.003, p = 0.007), and overall survivals (HR 1.632, 95% CI 1.029-2.588, p = 0.037). Subgroup analysis of pathologic stage T3a showed no significant difference in survival of the partial nephrectomy group when compared to the radical nephrectomy group (all p > 0.5). Patients up-staged from clinical stage T1 to pathologic stage T3a RCC showed shorter survival outcomes than those without upstaging. However, partial nephrectomy, compared with radical nephrectomy, showed comparable outcomes in patients who were up-staged.


A comparison between different anti-retroviral therapy regimes on soluble inflammation markers: a pilot study.
Although HIV-related deaths have decreased dramatically following the introduction of antiretroviral therapy (ART), HIV infection itself causes increased morbidity and mortality for both non-AIDS-related events or chronic inflammation and immune activation. The use of certain antiretroviral drugs can contribute to this process. We investigated 26 potential biomarkers in serum samples from HIV-1 infected patients virologically suppressed under ART. The main objective of our study was to evaluate if virological suppression achieved with a triple drug regimen containing tenofovir disoproxil fumarate co-formulated with emtricitabine (TDF/FTC) as backbone, could correlate with a better immunological and inflammatory profile in relation to the third class of antiretroviral drug administered. The eligible patients were then divided into 3 groups in relation to the third drug associated with TDF/FTC: nucleoside reverse transcriptase inhibitors (NNRTI) (Group 1, n = 16), protease inhibitors (PI) (Group 2, n = 17) and integrase inhibitors (INI) (Group 3, n = 16). Inflammatory cytokines and chemokines were more represented in Group 2 than in Group 3 (IL-1Ra, p = 0.013; IL-12p70 p = 0.039; TNF-α p = 0.041; IL-8, p = 0.027; MIP1 β, p = 0.033). Eotaxin showed lower levels in Group 1 compared to Group 2 (p = 0.010), while IP-10 was significantly lower in Group 1 compared to both Group 2 and Group 3 (p = 0.003 and p = 0.007, respectively). Our results seem to discourage the administration of PI as a third drug in a virologically effective antiretroviral regimen, as its use is linked to the detection of higher levels of pro-inflammatory mediators in comparison with INI and NNRTI.


Son Preference and Children's Housework: The Case of India.
We use a nationally representative survey of Indian households (NFHS-3) to conduct the first study that analyzes whether son preference is associated with girls bearing a larger burden of housework than boys. Housework is a non-negligible part of child labor in which around 60 % of children in our sample are engaged. The preference for male offspring is measured by a mother's ideal proportion of sons among her offspring. We show that when the ideal proportion increases from 0 to 1, the gap in the time spent on weekly housework for an average girl compared to that of a boy increases by 2.5 h. We conduct several robustness analyses. First, we estimate the main model separately by caste, religion, and family size. Second, we use a two-stage model to look at participation into housework (as well as other types of work) in addition to hours. Third, we use mother's fertility intentions as an alternative measure of son preference. The analysis confirms that stated differences in male preference translate in de facto differences in girl's treatment.


Severe sulfadiazine hypersensitivity in a child with reactivated congenital toxoplasmic chorioretinitis.
A 7-year-old with congenital toxoplasmosis who took pyrimethamine and sulfadiazine for reactivated chorioretinitis developed fever, severe cutaneous involvement, swelling, abdominal pain and transaminitis, persisting weeks after withholding medicines. Symptoms resolved when systemic corticosteroids were administered. This case underscores problems in clinical management with sulfadiazine hypersensitivity, potential immunosuppression from corticosteroids and selection of medications for recurrences of toxoplasmic chorioretinitis.


An early event in the transport mechanism of LacY protein: interaction between helices V and I.
Helix V in LacY, which abuts and crosses helix I in the N-terminal helix bundle of LacY, contains Arg(144) and Trp(151), two residues that play direct roles in sugar recognition and binding, as well as Cys(154), which is important for conformational flexibility. In this study, paired Cys replacement mutants in helices V and I were strategically constructed with tandem factor Xa protease cleavage sites in the loop between the two helices to test cross-linking. None of the mutants form disulfides spontaneously; however, three mutants (Pro(28) → Cys/Cys(154), Pro(28) → Cys/Val(158) → Cys, and Phe(29) → Cys/Val(158) → Cys) exhibit cross-linking after treatment with copper/1,10-phenanthroline (Cu/Ph) or 1,1-methanediyl bismethanethiosulfonate ((MTS)(2)-1), 3-4 Å), and cross-linking is quantitative in the presence of ligand. Remarkably, with one mutant, complete cross-linking with (MTS)(2)-1 has no effect on lactose transport, whereas quantitative disulfide cross-linking catalyzed by Cu/Ph markedly inhibits transport activity. The findings are consistant with a number of previous conclusions suggesting that sugar binding to LacY causes a localized scissors-like movement between helices V and I near the point where the two helices cross in the middle of the membrane. This ligand-induced movement may act to initiate the global conformational change resulting from sugar binding.


Insecticidal characteristics and mechanism of a promising natural insecticide against saw-toothed grain beetle.
The prevention of grain storage pests is a universal concern all over the world. It is in high demand to explore novel, safe and green insecticidal techniques to address such concerns. In this work, both raw and calcined diatomite were used as a natural insecticide to remove common grain storage pests with improved lethal effect on the saw-toothed grain beetle. Interestingly, the raw diatomite showed higher insecticidal efficiency than the calcined diatomite, and its associated insecticidal properties and preparation conditions were also optimized through orthogonal tests. The optimal conditions for processing the raw diatomite insecticide were identified as follows: the diatomite dust was 500 mesh (A 3), the temperature was 25 °C (B 1), the relative humidity was 65% (C 2), the diatomite dosage was 20 g m-2 (D 2), the influence factor order was C ≥ D > A > B. The observation of surface morphology indicated that the raw diatomite had a complete, multi hole surface morphology and good adsorption performance, whereas the structure of the calcined diatomite was uncomplete with collapsed pores, resulting in poor adsorption performance. The special pore structure and excellent adsorption capacity of diatomite make the stored grain pests lose water to lethal effect. Acute toxicity and long-term toxicity tests in mice showed that diatomite has no harmful effects on mammals. The findings from our work led to a green and effective approach in producing a highly efficient and safe storage grain insecticide.


Investigating the association of toll-like receptor 9 rs5743836, rs352140, and rs187084 gene polymorphisms and their mRNA levels with different hepatic fibrosis stages of non-alcoholic fatty liver patients compared to healthy controls.
Recent studies have shown that the level of hepatocyte-derived mitochondrial DNA is elevated in plasma samples obtained from mice and NASH patients, and it has the ability to toll-like receptor 9 (TLR9) activation resulting in steatosis, hepatocyte injury, and fibrosis. In this study, we explored the association between TLR9 rs5743836, rs352140, and rs187084 polymorphism and its plasma mRNA level in non-alcoholic fatty liver (NAFL) patients with different liver fibrosis scores compared to healthy controls. Seventy Iranian patients diagnosed with NAFL, based on fibroscan testing results, were divided into F0-F1 (N=33), F2-F3 (N=19), and F4 (N=18) hepatic fibrosis groups and compared to 22 healthy controls. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the mRNA expression level of TLR9 was determined using Real-Time PCR analysis. Results showed no significant association between allelic and genotypic distribution frequency of TLR9 rs5743836, rs352140, and rs187084 polymorphisms in NAFL patients with hepatic fibrosis compared to healthy controls (P>0.05). However, the mRNA level of TLR9 was significantly elevated in correlation with hepatic fibrosis progression in NAFL patients compared to healthy controls (P<0.05). As a preliminary study, our data showed a correlative overexpression of TLR9 mRNA with hepatic fibrosis progression in NAFL patients without the effectiveness of TLR9 gene polymorphisms.


Characterization of TLX expression in neural stem cells and progenitor cells in adult brains.
TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ) of adult mouse brains. Then, using a double thymidine analog labeling approach, we showed that almost all of the self-renewing neural stem cells expressed TLX. Interestingly, most of the TLX-positive cells in the SVZ represented the thymidine analog-negative, relatively quiescent neural stem cell population. Using cell type markers and short-term BrdU labeling, we demonstrated that TLX was also expressed in the Mash1+ rapidly dividing type C cells. Furthermore, loss of TLX expression dramatically reduced BrdU label-retaining neural stem cells and the actively dividing neural progenitor cells in the SVZ, but substantially increased GFAP staining and extended GFAP processes. These results suggest that TLX is essential to maintain the self-renewing neural stem cells in the SVZ and that the GFAP+ cells in the SVZ lose neural stem cell property upon loss of TLX expression. Understanding the cellular distribution of TLX and its function in specific cell types may provide insights into the development of therapeutic tools for neurodegenerative diseases by targeting TLX in neural stem/progenitors cells.


Work-family conflict and salespeople deviant behavior: the mediating role of job stress.
The salesperson is a job that is prone to deviant behavior. Prior studies addressed that deviant behavior is a behavioral stress response. Although numerous studies have demonstrated the relationship between job stress and deviant behavior, the clarity of the job stress mechanism remains limited. Drawing from coping theory, we proposed that job stress acts as a critical mechanism in linking the association between work-family conflict and salesperson deviant behavior. The objectives of this study are threefold. First, this study investigates the relationship between work-family conflict and job stress. Second, this study examines how job stress determines the likelihood of a salesperson engaging in deviant behavior. Last, this study investigates the mediating mechanism of work-family conflict and job stress. Using an online survey of salespeople in Indonesia, we received 321 data and employed a partial least square to test our proposed hypotheses. The results of this study confirm all hypotheses. The implications for managers regarding the result of this study is encouraging managers to establish and implement family-friendly policies which can diminish the level of stress and will decrease the likelihood of salespeople engaging in deviant behavior. Our study offers a significant contribution to the body of knowledge by clarifying the mediating role of job stress.


Diastereoselective self-assembly of chiral diamine-chelated aryllithiums to dimeric aggregates.
Aryllithium compounds [LiC6H4(CH2N(Et)CH2CH2NEt2)-2]2 (2b), [LiC6H4(CH(Me)N(Me)CH2CH2NMe2-(R))-2]2 ((R)-3b), and [LiC6H4(CH(Me)N(Me)CH2CH2NMe2-(rac))-2]2 ((rac)-3b) were synthesized and characterized in the solid state and in solution. X-ray crystallographic studies of 2b and (R)-3b and molecular weight determinations of 2b, (R)-3b, and (rac)-3b by cryoscopy in benzene showed that, both in the solid state and in apolar, noncoordinating solvents such as benzene, these compounds exist as discrete dimeric aggregates. For (R)-3b and (rac)-3b the aggregation process of two monomeric aryllithium units to one dimer is highly diastereoselective.


(2-Fluorophenylimino)tri(1-pyrrolyl)phosphorane.
The P atom of the title compound, C(18)H(16)FN(4)P, has a slightly distorted tetrahedral geometry. The P--N bond lengths range from 1.671 (3) to 1.680 (3) A, while the P==N bond is 1.517 (3) A. The pyrrolyl groups are arranged around the P atom in a chiral propeller-like geometry.


Prescribing Silver Chirality with DNA Origami.
Metal nanostructures of chiral geometry interacting with light via surface plasmon resonances can produce tailorable optical activity with their structural alterations. However, bottom-up fabrication of arbitrary chiral metal nanostructures with precise size and morphology remains a synthetic challenge. Here we develop a DNA origami-enabled aqueous solution metallization strategy to prescribe the chirality of silver nanostructures in three dimensions. We find that diamine silver(I) complexes coordinate with the bases of prescribed single-stranded protruding clustered DNA (pcDNA) on DNA origami via synergetic interactions including coordination, hydrogen bonds, and ion-π interaction, which induce site-specific pcDNA condensation and local enrichment of silver precursors that lowers the activation energy for nucleation. Using tubular DNA origami-based metallization, we obtain helical silver patterns up to a micrometer in length with well-defined chirality and pitches. We further demonstrate tailorable plasmonic optical activity of metallized chiral silver nanostructures. This method opens new pathways to synthesize programmable inorganic materials with arbitrary morphology and chirality.


Brain-targeted delivery of paclitaxel using glutathione-coated nanoparticles for brain cancers.
Paclitaxel is not effective for treatment of brain cancers because it cannot cross the blood-brain barrier (BBB) due to efflux by P-glycoprotein (P-gp). In this work, glutathione-coated poly-(lactide-co-glycolide) (PLGA) nanoparticles (NPs) of paclitaxel were developed for brain targeting for treatment of brain cancers. P-gp ATPase assay was used to evaluate the NP as potential substrates. The NP showed a particle size suitable for BBB permeation (particle size around 200 nm) and higher cellular uptake of the NP was demonstrated in RG2 cells. The P-gp ATPase assay suggested that the NP were not substrate for P-gp and would not be effluxed by P-gp present in the BBB. The in vitro release profile of the NP exhibited no initial burst release and showed sustained drug release. The proposed coated NP showed significantly higher cytotoxicity in RG2 cells compared with uncoated NP (p ≤ 0.05). Tubulin immunofluorescent study showed higher cell death by the NP due to increased microtubule stabilization. In vivo brain uptake study in mice showed higher brain uptake of the NP containing coumarin-6 compared with solution. The proposed brain-targeted NP delivery of paclitaxel could be an effective treatment for the brain cancers.


Common under-five morbidity in South-Eastern Nigeria: a study of its pattern in a rural mission general hospital in Imo State.
The under-five children are the most vulnerable group that bears the burden of diseases to a large extent in Nigeria. This study was aimed at describing the common and pattern of under-five morbidity in a rural Mission General Hospital in Imo state, South-Eastern Nigeria. A cross sectional descriptive hospital-based study was carried out from June 2008 to June 2009 on 244 under-five children aged 4 days to 58 months. The under-five children seen within the study period who met the selection criteria were studied. The data collected included age, sex and diagnosis made. One hundred and seven (43.8%) out of a total of 244 under-five children studied were aged 37-60 months, eighty one (33.2%) were aged 13-36 months and fifty six (23.0%) were aged 0-12 months. There were 141 (57.8%)males and 103 (42.2%) females. The three commonest causes of morbidity were malaria infections (80.3%), acute respiratory infections (32.0%) and skin infections (29.1%). The age group 37-60 months bears the greatest burden of malaria infections (49.0%), acute respiratory infections (55.1%) and skin infections (53.5%). This study shows that the three commonest causes of under-five morbidity (malaria, acute respiratory infections and skin infections) are largely preventable and infectious diseases still remaining major causes of morbidity; and similar to the under-five morbidity pattern documented at the beginning of the implementation of Primary Health Care and Child Survival Strategies in Nigeria. Identification, implementation, monitoring and evaluation of multidisciplinary and multisectoral intervention strategies targeted at the common under-five morbidity that are culturally acceptable, scientifically proven, patient-, family- and community-friendly and centred are recommended.


Investigation of serum protein profiles in sheep naturally infected with foot-and-mouth disease virus.
This study was carried out to determine serum protein profiles in naturally infected sheep with foot-and-mouth disease virus (FMDV). The study material consisted of twelve healthy and 36 sheep with foot-and-mouth disease (FMD). FMD had been diagnosed on the basis of clinical findings and results of serological examination. Serotypes serologically detected in the FMDV-infected sheep were as follows: O (n = 11), A (n = 8) and mixed infection with serotypes O, A and Asia-1 (n = 17).The total protein, albumin and globulin concentrations as well as Albumin/Globulin ratio were slightly different among the groups (P < 0.05). Three protein bands of 66 kDa, 45 kDa and 20 kDa were remarkable. Moderate differences were determined between healthy and infected sheep for proportion of distribution in serum proteins. In conclusion, serum protein concentrations and serum protein profiles were slightly changed and no specific serum protein profile occurred in sheep infected with either O or A or in sheep mixed infected with the O and A and Asia-1 serotypes of FMDV compared to healthy ones.


A rare presentation of spontaneous rupture of splenic vein aneurysm as cardiac arrest: A case report.
Splenic vein aneurysm (SVA) is a rare condition associated primarily with portal hypertension. This case highlights a potentially fatal, rare SVA complication in a young patient who presented in cardiac arrest, creating a diagnostic enigma in the emergency department until a POCUS revealed a possible underlying etiology.


[Studies on flavonoids extraction technology from Glycyrrhiza inflata and their bacteriostatic activities].
To study the extraction technique for the flavonoids from Glycyrrhiza inflata and their bacteriostatic bioactivities. It was investigated about comparison of extraction methods such as ultrasonic-assisted extraction (UAE), enzymatic extraction (EE), whisk extraction (WE) and repeat freeze-dissolve extraction (FDE). The UAE conditions were optimized by orthogonal array. The bacteriostatic effect was studied using doubling dilution. The UAE was the most effective method and the optimal UAE conditions were adding 20-fold ethanol (30% v/v), extracting for two times, 20 min each time. Futhermore, the minimal inhibitory concentrations (MIC) of the flavonoids against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Bacillus subtilis were 0.03125, 0.03125, 0.125, 0.03125 mg/ml respectively. UAE is suitable for fast and effective extraction of flavonoids. The flavonoids have obvious bacteriostatic bioactivities against microorganisms mentioned above.


Multi-modality data-driven analysis of diagnosis and treatment of psoriatic arthritis.
Psoriatic arthritis (PsA) is associated with psoriasis, featured by its irreversible joint symptoms. Despite the significant impact on the healthcare system, it is still challenging to leverage machine learning or statistical models to predict PsA and its progression, or analyze drug efficacy. With 3961 patients' clinical records, we developed a machine learning model for PsA diagnosis and analysis of PsA progression risk, respectively. Furthermore, general additive models (GAMs) and the Kaplan-Meier (KM) method were applied to analyze the efficacy of various drugs on psoriasis treatment and inhibiting PsA progression. The independent experiment on the PsA prediction model demonstrates outstanding prediction performance with an AUC score of 0.87 and an AUPR score of 0.89, and the Jackknife validation test on the PsA progression prediction model also suggests the superior performance with an AUC score of 0.80 and an AUPR score of 0.83, respectively. We also identified that interleukin-17 inhibitors were the more effective drug for severe psoriasis compared to other drugs, and methotrexate had a lower effect in inhibiting PsA progression. The results demonstrate that machine learning and statistical approaches enable accurate early prediction of PsA and its progression, and analysis of drug efficacy.


Detecting disease progression in mild, moderate and severe glaucoma.
The purpose of this review is to examine contemporary techniques for detecting the progression of glaucoma. We provide a general overview of detection principles and review evidence-based diagnostic strategies and specific considerations for detecting glaucomatous progression in patients with mild, moderate and severe disease. Diagnostic techniques and technologies for glaucoma have dramatically evolved in recent years, affording clinicians an expansive toolkit with which to detect glaucoma progression. Each stage of glaucoma, however, presents unique diagnostic challenges. In mild disease, either structural or functional changes can develop first in disease progression. In moderate disease, structural or functional changes can occur either in tandem or in isolation. In severe disease, standard techniques may fail to detect further disease progression, but such detection can still be measured using other modalities. Detecting disease progression is central to the management of glaucoma. Glaucomatous progression has both structural and functional elements, both of which must be carefully monitored at all disease stages to determine when interventions are warranted.


The role of antibiotics in the prevention of preterm birth.
THERE ARE MULTIPLE USES FOR ANTIBIOTICS DURING PREGNANCY: treatment of intercurrent bacterial infections such as urinary or respiratory tract infections, maternal treatment to prevent fetal or neonatal disease, prophylactic treatment for surgical procedures, and treatment of puerperal infections. This report will summarize the current recommendations for the use of antibiotics specifically to reduce the risk of preterm birth.


Possible relationship between testosterone and comorbid major depressive episode in male patients with schizophrenia treated with typical antipsychotic medications.
In this cross-sectional study, the author tested the hypothesis that serum testosterone levels were associated with depressive illness in chronic male schizophrenia patients. The subjects were 49 male inpatients meeting DSM-IV criteria for schizophrenia treated with typical antipsychotic medications. The author found that the schizophrenia patients with major depressive episodes (MDE) had been taking significantly higher dosages of antipsychotic medications than those without an MDE. Also, there was a trend for the serum testosterone concentration to be lower in schizophrenia patients with an MDE. It is suggested that we should be aware of testosterone levels when we find depression in chronic male schizophrenia patients, especially those treated with high-dose typical antipsychotic medications.


Arthroscopic stabilization for first-time versus recurrent shoulder instability.
The purpose of this study was to systematically review the evidence on the outcomes of arthroscopic repair for anterior shoulder instability in first-time dislocators when compared with patients with recurrent instability. We designed a systematic review with a specific methodology to investigate the outcomes of surgery for those with only a first-time dislocation versus those who underwent surgery after multiple instability events. We performed a literature search from January 1966 to December 2008 using Medline, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the Cochrane Central Register of Controlled Trials. Key words included the following: first time, primary shoulder, or recurrent shoulder instability, shoulder dislocation, Bankart repair, arthroscopic Bankart repair, and labral repair. The inclusion criteria were cohort studies (Level I to II) that evaluated the outcomes of patients undergoing arthroscopic stabilization after the first dislocation or multiple recurrent episodes. Studies that lacked a comparison group or were retrospective (Level III studies or higher) were excluded. There were 15 studies that met the inclusion criteria and were included in the final analysis: 5 in the first-time dislocation group and 10 in the recurrent instability group. Study design, patient demographics, mean number of dislocations, surgical technique, and rehabilitation protocol, as well as subjective and objective outcome measures, were recorded. There were no differences in recurrence or complication rate among patients undergoing surgery after the primary dislocation when compared with those undergoing surgery after multiple recurrent episodes. Clinical outcome measures significantly improved within all independent studies from preoperatively to postoperatively. However, because of variation in the outcome measurement tools used, no direct comparison between the study groups could be performed. Additional randomized controlled studies are needed to compare the functional outcome, quality of life, and ability to return to preinjury activity level among patients undergoing early versus delayed repair for anterior shoulder instability.


Blood Pressure Measurement: From Cuff-Based to Contactless Monitoring.
Blood pressure (BP) determines whether a person has hypertension and offers implications as to whether he or she could be affected by cardiovascular disease. Cuff-based sphygmomanometers have traditionally provided both accuracy and reliability, but they require bulky equipment and relevant skills to obtain precise measurements. BP measurement from photoplethysmography (PPG) signals has become a promising alternative for convenient and unobtrusive BP monitoring. Moreover, the recent developments in remote photoplethysmography (rPPG) algorithms have enabled new innovations for contactless BP measurement. This paper illustrates the evolution of BP measurement techniques from the biophysical theory, through the development of contact-based BP measurement from PPG signals, and to the modern innovations of contactless BP measurement from rPPG signals. We consolidate knowledge from a diverse background of academic research to highlight the importance of multi-feature analysis for improving measurement accuracy. We conclude with the ongoing challenges, opportunities, and possible future directions in this emerging field of research.


Myosin accumulation and striated muscle myopathy result from the loss of muscle RING finger 1 and 3.
Maintenance of skeletal and cardiac muscle structure and function requires precise control of the synthesis, assembly, and turnover of contractile proteins of the sarcomere. Abnormalities in accumulation of sarcomere proteins are responsible for a variety of myopathies. However, the mechanisms that mediate turnover of these long-lived proteins remain poorly defined. We show that muscle RING finger 1 (MuRF1) and MuRF3 act as E3 ubiquitin ligases that cooperate with the E2 ubiquitin-conjugating enzymes UbcH5a, -b, and -c to mediate the degradation of beta/slow myosin heavy chain (beta/slow MHC) and MHCIIa via the ubiquitin proteasome system (UPS) in vivo and in vitro. Accordingly, mice deficient for MuRF1 and MuRF3 develop a skeletal muscle myopathy and hypertrophic cardiomyopathy characterized by subsarcolemmal MHC accumulation, myofiber fragmentation, and diminished muscle performance. These findings identify MuRF1 and MuRF3 as key E3 ubiquitin ligases for the UPS-dependent turnover of sarcomeric proteins and reveal a potential basis for myosin storage myopathies.


Efficacy and safety of different modes of exercise-based cardiac rehabilitation delivery for patients with heart failure: a protocol for a systematic review and network meta-analysis.
The prevalence of heart failure (HF) is increasing. Exercise-based cardiac rehabilitation (CR) reduces mortality and further improves the prognosis of patients with HF. However, the effect of different modes of CR delivery on HF remains unclear. Thus, the purpose of this study is to find out the relative efficacy and safety of different modes of CR delivery for individuals with HF using a network meta-analysis. We will perform a systematic review and network meta-analysis of randomised controlled trials which compare different modes of exercise-based CR delivery for patients with HF. Databases including Embase, Medline, the Cochrane Central Register of Controlled Trials and Web of Science will be searched up to May 2022. The primary outcomes will focus on the functional capacity and the health-related quality of life (hr-QOL). Functional capacity will be evaluated by peak oxygen consumption (mL/kg/min) and 6 min walking test (metres). The Minnesota Living with Heart Failure questionnaire, Short Form-36, Psychometric properties of the Kansas City cardiomyopathy questionnaire and EuroQol five dimensions questionnaire will serve as measures of hr-QOL. As secondary outcomes, we will assess hospital admissions (all-cause and cardiac) and all-cause mortality, which required a minimum follow-up of 6 months, as well as adverse events during exercise training. The risk of bias for individual studies will be evaluated according to the Cochrane Handbook. The quality of evidence will be assessed by the Grading of Recommendations, Assessment, Development and Evaluation approach. This study does not require ethics approval as it is based on published trials. Results of this systematic review and network meta-analysis will be submitted to a peer-reviewed journal for future publication. CRD42021278351.


Prognostic significance of 18F-FDG PET/CT parameters in IDH-1 wild-type GBM and correlation with molecular markers.
To assess the prognostic role of metabolic parameters on 18F-FDG PET/CT & correlation with molecular markers in IDH-1 wild-type GBM. A total of 129 patients with brain lesions showing equivocal findings on baseline MRI who were referred for fluoro-deoxy-glucose PET/CT were analyzed. Of these, 50 underwent surgery/biopsy and postoperative histopathological diagnosis of IDH-1 wild-type GBM. SUVmax, metabolic tumor volume (MTV), total lesion glycolysis (TLG) & T/w ratio was calculated. Median metabolic parameters were used for stratification. Overall survival was calculated using Kaplan-Meier method and was compared using log rank test. P value < 0.05 was considered significant. Multivariate analysis was done using Cox proportional hazard model. Correlation between metabolic parameters and molecular markers was done using Mann-Whitney U test. Median of SUVmax, T/w ratio, MTV, TLG, 18.3, 2.09, 61, 409. Average overall survival (OS) for T/w ratio >2.08 was 5 months, <2.08 was 18 months (P value 0.001). For MTV >61 was 4 months, <61 was 18 months (P value 0.001). Similarly, for TLG >409 was 5 months while for <409 was 19 months (P value 0.001). SUVmax was not significant for OS. In multivariate analysis, age was the statistically significant independent prognostic factor. Metabolic parameters of fluoro-deoxy-glucose PET/CT help in prognosticating IDH-1 wild-type GBM. Higher MiB-1 index correlates with higher T/w ratio and is associated with poor overall survival.


Adaptation of the mechanisms controlling gastric motility following chronic vagotomy in the ferret.
Changes in gastric motility were studied in the urethane-anaesthetized ferret following acute or chronic (3 weeks) vagotomy. The stomach was divided into the corpus and antrum and the effects of vagotomy on tone, frequency and contraction amplitude were investigated separately in the two gastric regions. In the corpus tone is kept at low levels by vagal activation of nonadrenergic, non-cholinergic (NANC) inhibitory neurones and also tonic sympathetic inhibition of intramural cholinergic activity. Frequency of contractions is also low due to tonic inhibition of cholinergic neurones by the vagus but not the sympathetic nervous system. There appears to be little vagal involvement in contraction amplitude but there is sympathetic inhibition of this parameter again via inhibition of cholinergic neurones. In the antrum there is no vagally driven inhibition of tone but a sympathetic inhibition of cholinergic neurones tends to reduce tone in the intact animal. Frequency of contractions does not appear to be extrinsically modulated. The vagus is tonically excitatory with regard to contraction amplitude in the antrum whereas the sympathetic nervous system is inhibitory, again via inhibition of cholinergic neurones. After chronic vagotomy some adaptation appears to take place within the surviving control systems in both the corpus and the antrum. Changes in cholinergic function have been suggested previously and are corroborated in this study. In addition novel alterations in intrinsic NANC systems and the remaining sympathetic innervation have been demonstrated in both regions of the stomach which tended to reduce the effects of vagotomy and return values for the parameters measured toward those observed in intact animals. The contribution of the cholinergic, adrenergic and NANC neurotransmitter systems to the post-vagotomy motility patterns differed in the corpus and antrum.


[Prognostic value of PCSK9 and blood lipid in patients with sepsis].
To investigate the prognostic value of proprotein convertase subtilisin/kexin type 9 (PCSK9) and blood lipid indexes in patients with sepsis. Patients with sepsis or septic shock who were ≥ 18 years old and met the Sepsis-3.0 diagnostic criteria admitted to the department of critical care medicine of Binzhou Medical University Hospital from January to October 2021 were enrolled. Healthy adults at the same period were selected as healthy control group. Baseline characteristics, acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) score were recorded. Venous blood samples were collected within 24 hours after diagnosis, and serum PCSK9 was determined by enzyme-linked immunosorbent assay (ELISA) at 1, 3 days and 5 days. Meanwhile, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and lipoprotein A were detected. The differences of each index between sepsis group (28-day death group and survival group) and healthy control group were compared. Meanwhile, the indexes of patients with different severity and 28-day prognosis in sepsis group were compared. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of PCSK9 and blood lipid for the prognosis of sepsis. Multivariate Logistic regression was used to analyze the influencing factors for the prognosis of sepsis, and the Kaplan-Meier survival curve at 28th day was drawn. There were 50 patients in sepsis group (including 19 patients with sepsis, 31 patients with septic shock) and 27 patients in healthy control group. In the sepsis group, 19 patients died and 31 patients survived within 28 days. The serum PCSK9 in the sepsis group was significantly higher than that in the healthy control group [μg/L: 223.09 (198.47, 250.82) vs. 188.00 (165.27, 214.90), P < 0.01], and HDL-C, LDL-C, TC and lipoprotein A were significantly lower than those in the healthy control group [HDL-C (mmol/L): 0.82±0.35 vs. 1.45±0.24, LDL-C (mmol/L): 1.53 (1.14, 2.47) vs. 2.89 (2.55, 3.19), TC (mmol/L): 2.03 (1.39, 2.84) vs. 4.24 (3.90, 4.71), lipoprotein A (g/L): 8.80 (5.66, 17.56) vs. 27.03 (14.79, 27.03), all P < 0.01]. PCSK9 in the sepsis death group was higher than that in the survival group [μg/L: 249.58 (214.90, 315.77) vs. 207.01 (181.50, 244.95), P < 0.01], and the HDL-C, LDL-C and TC were lower than those in the survival group [HDL-C (mmol/L): 0.64±0.35 vs. 0.93±0.30, LDL-C (mmol/L): 1.32±0.64 vs. 2.08±0.94, TC (mmol/L): 1.39 (1.01, 2.23) vs. 2.69 (1.72, 3.81), all P < 0.01]. With the progression of the disease, the PCSK9 in the sepsis death group and the survival group was significantly lower than that within 1 day of diagnosis (all P < 0.05). ROC curve analysis showed that PCSK9 had higher predictive value of 28-day death than HDL-C, LDL-C, TC [area under ROC curve (AUC) and 95% confidence interval (95%CI): 0.748 (0.611-0.885) vs. 0.710 (0.552-0.868), 0.721 (0.575-0.867), 0.702 (0.550-0.854)]. Multivariate Logistic regression analysis showed that PCSK9 was an independent risk factor affecting the 28-day prognosis of sepsis (β value was 1.014, P = 0.020). Kaplan-Meier survival curve analysis showed that when PCSK9 ≥ 208.97 μg/L, with the increase of PCSK9, the 28-day survival rate of sepsis patients decreased significantly. PCSK9, HDL-C, LDL-C and TC can all predict the 28-day prognosis of patients with sepsis. The prognostic value of PCSK9 is the highest. PCSK9 is an independent risk factor affecting the prognosis of sepsis. In the early stage of the disease, PCSK9 may have a good predictive value for the prognosis of sepsis. When PCSK9 ≥ 208.97 μg/L, the 28-day survival rate decreased significantly.


Do you know this syndrome?
Bloch-Sulzberger syndrome (incontinentia pigmenti) is a rare genodermatosis that affects predominantly females, since it is generally lethal to male fetuses in utero. It is characterized principally by skin lesions, but may also involve dental, ophthalmological and neurological abnormalities. The skin lesions are present in four different phases: vesicular, verrucous, hyperpigmented and atrophic/hypopigmented. Their sequence is irregular and overlapping of stages is common.


Cardiomyocyte deletion of mitofusin-1 leads to mitochondrial fragmentation and improves tolerance to ROS-induced mitochondrial dysfunction and cell death.
Molecular studies examining the impact of mitochondrial morphology on the mammalian heart have previously focused on dynamin related protein-1 (Drp-1) and mitofusin-2 (Mfn-2), while the role of the other mitofusin isoform, Mfn-1, has remained largely unexplored. In the present study, we report the generation and initial characterization of cardiomyocyte-specific Mfn-1 knockout (Mfn-1 KO) mice. Using electron microscopic analysis, we detect a greater prevalence of small, spherical mitochondria in Mfn-1 KO hearts, indicating that the absence of Mfn-1 causes a profound shift in the mitochondrial fusion/fission balance. Nevertheless, Mfn-1 KO mice exhibit normal left-ventricular function, and isolated Mfn-1 KO heart mitochondria display a normal respiratory repertoire. Mfn-1 KO myocytes are protected from mitochondrial depolarization and exhibit improved viability when challenged with reactive oxygen species (ROS) in the form of hydrogen peroxide (H(2)O(2)). Furthermore, in vitro studies detect a blunted response of KO mitochondria to undergo peroxide-induced mitochondrial permeability transition pore opening. These data suggest that Mfn-1 deletion confers protection against ROS-induced mitochondrial dysfunction. Collectively, we suggest that mitochondrial fragmentation in myocytes is not sufficient to induce heart dysfunction or trigger cardiomyocyte death. Additionally, our data suggest that endogenous levels of Mfn-1 can attenuate myocyte viability in the face of an imminent ROS overload, an effect that could be associated with the ability of Mfn-1 to remodel the outer mitochondrial membrane.


Phenylalanine-arginine β-naphthylamide could enhance neomycin-sensitivity on Riemerella anatipestifer in vitro and in vivo.
Riemerella anatipestifer is an important duck pathogen responsible for septicemia and infectious serositis, which has caused great economic losses to the duck industry. Phenylalanine-arginine β-naphthylamide (PAβN) is an efflux pump inhibitor, which mainly reduces the efflux effect by competing with antibiotics for efflux pump channels. Here, we found that R. anatipestifer strain GD2019 showed resistances to gentamicin, amikacin, kanamycin, and neomycin. Notably, PAβN could significantly reduce the Minimal inhibitory concentrations (MICs) of neomycin on the GD2019 strain. Moreover, PAβN combined with neomycin significantly decreased bacterial loads, relieved pathological injury and increase survival rate (p < 0.05) for the ducks lethally challenged by the GD2019 strain. Therefore, our results suggested, in vitro and in vivo, PAβN could reduce neomycin-resistant of R. anatipestifer. Importantly, finding of this study provide a new approach for treating antibiotic-resistant R. anatipestifer infection.


[Tumor multidrug-resistance and reversing actions of traditional Chinese medicine].
Tumor multidrug-resistance (MDR) is a major factor in chemotherapeutic failure. In recent years, the development of anti-MDR has become an important focus in research. The mechanisms of MDR relate to P-glycoprotein, MRP1, apoptosis, the unusual DNA repair, the organic micro-environment, and so on. This review summarized the advances in MDR mechanism research. At the same time, it summarized the recent research of traditional Chinese medicine in reversing MDR. Furthermore, their mechanisms and major features of actions were also discussed.


The global histone modification pattern correlates with overall survival in metachronous liver metastasis of colorectal cancer.
Post-translational histone modifications are known to be altered in cancer tissues, and differences in the histone modification levels have recently been used to predict the clinical outcome in patients with certain types of cancer. In this study, we evaluated the immunohistochemical staining patterns of histone H3 dimethylation and acetylation in metachronous liver metastasis of colorectal carcinomas and examined its correlation with patient prognosis. Double 2 mm core tissue microarrays were made from 54 paraffin-embedded samples of liver metastasis from colorectal adenocarcinoma, and were examined by an immunohistochemical analysis of histone H3 lysine 4 (H3K4) dimethylation, histone, H3 lysine 9 (H3K9) dimethylation and histone H3 lysine 9 (H3K9) acetylation. Positive tumor cell staining for each histone modification was used to classify patients into low- and high-staining groups, which were then examined for correlations with the clinicopathological parameters and clinical outcome. Dimethylation of H3K4 correlated with the tumor histological type (P=0.043), and acetylation of H3K9 correlated with the tumor histological type (P=0.016). In addition, lower levels of H3K4 dimethylation correlated with a poor survival rate (P=0.035). The multivariate survival analysis showed that the H3K4 dimethylation status is an independent prognostic factor for colorectal cancer patients (P=0.011). We suggest that the pattern of histone modification as detected by immunohistochemistry may be an independent prognostic factor for metachronous liver metastasis of colorectal carcinomas.


[Potential cost reductions for the National Health Service through a telecardiology service dedicated to general practice physicians].
Rising health care costs resulted in increasing pressure on the health care system and stimulated new strategies for improving the efficiency of care. A telecardiology service provides a useful support to general practitioners in the management of cardiac patients and contributes to the optimization of health care costs in terms of appropriateness of hospital admission and diagnostic testing. The aim of our study was to evaluate the reduction in the number of referrals to the Emergency Department and to cardiological evaluation resulting from the employment of a telecardiology service by general practitioners. Eight hundred and ninety-one consecutive calls arrived to the receiving station of the telecardiology service were analyzed. One hundred and fifty general practitioners received a portable electrocardiographer (Card-Guard 7100, Rehovot, Israel) transferring, by a mobile or fixed telephone, a 12-lead ECG to a receiving station, where a cardiologist was available for reporting and for interactive teleconsultation. At the onset of the phone call, a question was asked to the general practitioner: "What would you have done without the telecardiology service?". The possible answers were: "No actions"; "Referral to the Emergency Department"; "Cardiological consultancy"; "Further investigations". Then we collected the history, risk factors, symptoms and therapy of the patients; the general practitioner sent the ECG tracing by phone. Eight hundred and ninety-one patients were enrolled (402 males, 489 females, mean age 59 +/- 19 years); 465 (52%) patients were symptomatic; 36.4% had no evidence of previous cardiac disease, 35.1% had systemic hypertension, 10.6% had ischemic cardiac disease, 3.7% had atrial fibrillation, and 11.9% other diseases. ECG was normal in 55%. The general practitioners would have sent to the Emergency Department 106 patients (11.9%), and requested further investigations in 717 patients (80.5%). The cardiologist of the telecardiology service solved the problems of the general practitioners in 657 cases (73.7%), sent 56 patients (6.3%) to the Emergency Department, and asked for further investigations in 178 patients (20%), with a reduction of 47% of Emergency Department admission (p < 0.001) and of 95% of further investigations (p < 0.0001) respectively. The cost analysis showed a reduction, between the two modalities, varying from Itl 22,760,000 and Itl 140,060,000 for 891 calls. Telemedicine is a useful tool for the support of general practitioners' daily activity, with a possible cost reduction due to increased appropriateness of hospital admission and of diagnostic testing.


Targeted Approach to Enhance the Solubility of Weakly Soluble Drugs by Nanocrystal Technology.
About 90% of the newly discovered drugs are poorly soluble in water, to overcome this problem, nanocrystal technology is used. Nanocrystal technology is a modern technique that is specially used to increase the solubility of less soluble drugs. Production of a nanocrystal on a large scale can be done by techniques like homogenization (high-pressure), precipitation, and milling methods. Using this technique, saturation solubility, the adhesiveness of a drug molecule to the surface cell, and the dissolution velocity is enhanced. This technology is better than the traditional method because it provides certain other benefits like increased drug loading capability, fantastic reproducibility of oral retention, further developed proportionality of portion bioavailability and expanded patient compliance. This audit makes sense of the various kinds of techniques for the arrangement of nanocrystals, benefits, drawbacks, a system of solvency improvement, clinical applications, and future imminent. This review article also provides further guidelines for studies about nanocrystal technology.


Durian (Durio zibethinus Murr.) cultivars as nutritional supplementation to rat's diets.
The properties of Mon Thong, Chani and Kan Yao durian (Durio zibethinus Murr.) cultivars were compared in vitro and in vivo studies in order to find the best one as a supplement to antiatherosclerotic diet. Total polyphenols (361.4+/-35.3 mgGAE/100g FW), flavonoids (93.9+/-8.9 mgCE/100g FW) and total antioxidant capacity determined by DPPH and beta-carotene-linoleic acid assays (261.3+/-25.3 microMTE/100g FW and 77.8+/-7.8% of inhibition) were maximal in Mon Thong in comparison with Chani and Kan Yao and showed a good correlation between these three variables (R(2)=0.9859). Five groups of rats were fed diets supplemented with cholesterol and different durian cultivars. Diets supplemented with Mon Thong and to a lesser degree with Chani and Kan Yao significantly hindered the rise in the plasma lipids (TC - 8.7%, 16.1% and 10.3% and (b) LDL-C - 20.1%, 31.3% and 23.5% for the Chol/Kan Yao, Chol/Mon Thong and Chol/Chani, respectively) and the decrease in plasma antioxidant activity (P<0.05). Nitrogen retention remained significantly higher in Chol/Mon Thong than in other diet groups. Diet supplemented with Mon Thong affected the composition of plasma fibrinogen in rats and showed more intensity in protein bands around 47 kDa. No lesions were found in the examined tissue of heart and brains. Mon Thong cultivar is preferable for the supplementation of the diet as positively influenced the lipid, antioxidant, protein and metabolic status. The durian fruit till now was not investigated extensively, therefore based on the results of this study durian cultivars can be used as a relatively new source of antioxidants.