[Immunopathogenesis and appropriate use of monoclonal antibody agents in multiple myeloma].
Multiple myeloma (MM) involves the immune dysregulation not only of B cells but also of NK, T, and dendritic cells. Furthermore, the number of regulatory T and myeloid-derived immunosuppressive cells, which are associated with disease progression, also increases. Immunomodulatory drugs (IMiDs) such as lenalidomide and pomalidomide exhibit an antimyeloma effect and improve the immune status. Thus, IMiD-enhanced antibody-dependent cell cytotoxicity increases the cytotoxic activity of monoclonal antibody treatment. Among many antibodies, anti-SLAMF7 elotuzumab and anti-CD38 daratumumab have been approved in Japan, and their targeted antigens are responsible for functions that may influence clinical efficacy. Daratumumab exerts various mechanisms of antitumor activity and enhances T-cell immunity by inhibiting immunosuppressive cells. New monoclonal antibodies, including the anti-CD38 antibody isatuximab and anti-BCMA antibody-drug conjugate, are being developed and are expected to demonstrate clinical efficacy. To improve long-term prognosis and achieve cure for MM, immunotherapies such as IMiD-intensified antibody treatment, which resulted in better response rates and longer survival in refractory/relapsed MM, are essential.


[Social competence evaluated by patients on methadone maintenance treatment program].
Social competence were analysed using the origin Polish Questionnaire of Social Competence questionnaire (KKS). The competence gained during the life span are dependent on age, temperament, personality and partially on intelligence. There were 66 drug users (22 females, and 44 males) from methadone maintenance treatment programme conducted in Rydygier's Hospital. Social Exposure Scale, Scale of Assertiveness, Scale of Direct Interpersonal Contacts separately as well as the sum of information were used for estimation of the competence. The patient age at narcotic initiation, duration of being in methadone substitution programme, means of support were a statistically significant factors. A significant differences between two group as regard the psychopathology the drug abuse alone or coincidence with psychiatric diagnosis were also noted.


Civil money penalties: procedures for investigations, imposition of penalties, and hearings--extension of expiration date. Final rule.
An interim final rule establishing procedures for the imposition, by the Secretary of Health and Human Services, of civil money penalties on entities that violate standards adopted by the Secretary under the Administrative Simplification provisions of the Health Insurance Portability and Accountability Act of 1996 (HIPAA) was published on April 17, 2003. The interim final rule expires on September 16, 2005. This regulatory action extends the expiration date to March 16, 2006 to avoid the disruption of ongoing enforcement actions while HHS completes with rulemaking to develop a more comprehensive enforcement rule.


An update on epistaxis.
Epistaxis is one of the most common ear, nose and throat (ENT) emergencies to present to general practitioners (GPs). The management of epistaxis has evolved significantly in recent years, including the use of nasal cautery and packs. Successful treatment requires knowledge of nasal anatomy, and potential risks and complications of treatment. Epistaxis is often a simple and readily treatable condition. However, given the potential consequences of a significant bleed, GPs should have an understanding of the causes, potential risks and emergency management. Epistaxis can be classified into anterior or posterior bleeds, the former being the most common. Anterior bleeds can often be treated with cauterisation with silver nitrate sticks, provided there is good preparation, correct equipment and assistance close at hand. If there is a lack in any of these aspects, prompt use of nasal packing and referral to an emergency department or a specialist ENT service is recommended.


The Chronic Diseases Clinic of Ifakara (CDCI)-Establishing a Model Clinic for Chronic Care Delivery in Rural Sub-Saharan Africa.
The rollout of antiretroviral drugs in sub-Saharan Africa to address the huge health impact of the HIV pandemic has been one of the largest projects undertaken in medical history and is an unprecedented medical success story. However, the path has been and still is characterized by many far reaching implementational challenges. Here, we report on the building and maintaining of a role model clinic in Ifakara, rural Southwestern Tanzania, within a collaborative project to support HIV services within the national program, training for staff and integrated research to better understand local needs and improve patients' outcomes.


Computational discovery of gene modules and regulatory networks.
We describe an algorithm for discovering regulatory networks of gene modules, GRAM (Genetic Regulatory Modules), that combines information from genome-wide location and expression data sets. A gene module is defined as a set of coexpressed genes to which the same set of transcription factors binds. Unlike previous approaches that relied primarily on functional information from expression data, the GRAM algorithm explicitly links genes to the factors that regulate them by incorporating DNA binding data, which provide direct physical evidence of regulatory interactions. We use the GRAM algorithm to describe a genome-wide regulatory network in Saccharomyces cerevisiae using binding information for 106 transcription factors profiled in rich medium conditions data from over 500 expression experiments. We also present a genome-wide location analysis data set for regulators in yeast cells treated with rapamycin, and use the GRAM algorithm to provide biological insights into this regulatory network


The radiology of the superior intercostal veins.
The superior intercostal veins define the pleural reflections of the caudad extent of the posterior junction line. They are paired structures which drain the first three intercostal spaces and join the azygous on the right and the accessory hemiazygous on the left. Because of their location posterior and lateral to the esophagus and trachea, their pleural reflections may be altered early in the course of a focal nodal disease of the posterior mediastinum.


The sexually exploited child.
Sexual exploitation of children (under 14 years of age) is a common occurrence, although actual numbers are unknown. There are three major forms of sexual abuse: (1) incest, ie, sexual activity between consanguineous family members; (2) sexual assault, such as rape or molestation by adults not related to the child; and (3) habitual sexual exploitation for purposes of financial reward or perverse sexual satisfaction. Brother-sister incest has the highest incidence in the middle and upper socioeconomic levels and is probably the least damaging, psychologically, to sexual adjustment later in life. Father-daughter incest is more common in the lower socioeconomic levels and is thought to produce major disorders in the psychosexual area. Sexual assault of children, if handled supportively and with understanding by the surrounding adults, including parents, physicians, teachers, law enforcement officers, and others, can result in minimal sequelae; however, often the situation is handled with emotional reactions ranging from disgust to hysteria which result in the child's being victimized and traumatized unnecessarily. These latter situations lead to sexual acting-out in adolescence, promiscuity, perversions, or frigidity in adult sexual life. Teachers, physicians, and child welfare workers need to be attuned to the possibility to sexual abuse in the children they serve.


ABC transporters in human lymphocytes: expression, activity and role, modulating factors and consequences for antiretroviral therapies.
ATP-binding cassette (ABC) transporters are a superfamily of efflux pumps that transport numerous compounds across cell membranes. These transporters are located in various human tissues including peripheral blood cells, in particular lymphocytes, and present a high variability of expression and activity. This variability may affect the intracellular concentrations and efficacy of drugs acting within lymphocytes, such as antiretroviral drugs. This review focuses on the current knowledge about the expression, activity, roles and variability of ABC drug transporters in human lymphocytes. The identified modulating factors and their impact on the intracellular pharmacokinetics and efficacy of antiretroviral drugs are also detailed. Controversial data regarding the expression, activity and sources of variability of ABC transporters in lymphocytes are discussed. The modulating factors and their pharmacological consequences regarding antiretroviral therapies are also provided. Numerous studies have reported conflicting results regarding the expression and activity of ABC drug transporters in lymphocytes. Despite these discrepancies, which may partly result from heterogeneous analytical methods, ABCC1 appears to have the highest expression in lymphocytes and may thus play a predominant role in the resistance to antiretroviral drugs, particularly to protease inhibitors.


Machine learning and density functional theory simulation of the electronic structural properties for novel quaternary semiconductors.
In order to accelerate the application of quaternary optoelectronic materials in the field of luminescence, it is crucial to develop new quaternary semiconductor materials with excellent properties. However, faced with vast alternative quaternary semiconductors, traditional trial-and-error methods tend to be laborious and inefficient. Here, we combined machine learning (ML) with density functional theory (DFT) calculation to predict the bandgaps of 2180 quaternary semiconductors, most of which were undeveloped but environmentally friendly. The evaluation coefficient (R2) of the model using a random forest algorithm was up to 0.93 in ML. Four novel quaternary semiconductors with direct bandgaps: Ag2InGaS4, AgZn2InS4, Ag2ZnSnS4, and AgZn2GaS4, were selected from the ML model. Then their electronic structures and optical properties were further verified and studied by DFT calculations, which demonstrated that the four quaternary semiconductors had direct bandgaps, a small effective mass, and a large exciton binding energy and Stokes shift. Our calculation could significantly speed up the discovery of novel optoelectronic semiconductors and has a certain reference value for the study of luminescent materials and devices.


Possibility of simplification of APACHE II scoring system in the prediction of the outcome in critically ill patients with perforative peritonitis.
Simplification of APACHE II scoring system in the prediction of the outcome in critically ill patients with perforative peritonitis can be a useful and a cheaper model than the standard APACHE II system. We tested APACHE II and SAPS I scoring systems and variables of arterial pH, pO2, pCO2 and HCO3, cholesterol and albumin in the prediction of the outcome in these patients. The prospective study involved 145 patients of both sexes with perforative peritonitis. The main outcome of this study was peritonitis-related death. APACHE II and SAPS I scoring systems were calculated on the admission (during the first 24 hours). Cutoff points were specified and all values greater than the cut-off points were taken to predict death. Sensitivity and specificity are graphically shown for the different values of cut-off points. They are presented with the ROC curve. Variables of arterial pH, pO2, pCO2 and HCO3 were tested with Feed-Forward Artificial Neural Network which had 4 hidden layers with 8 neurons in the layer. We used Levenberg-Marquardt method for training, and 16 variables for the entrance in the network. We tested correlation between cholesterol and albumin levels with the patient outcome. APACHE II ROC curve demonstrated that its discriminatory ability was better than the SAPS ROC curve. The area under the curve was 0.86 for APACHE II score in comparison to 0.83 for SAPS score. This illustrated that APACHE II is significantly better (P < 0.01) at determining of outcome. Use of FeedForward Artificial Neural Network (ANN) for analysis of variables such as arterial pH, pO2, pCO2 and HCO3, showed that withdrawal of these variables lead to the decreased power of prediction of APACHE II scoring system. Measurement of the correlation between the cholesterol and albumin levels and the patient outcome revealed that there was no significance between these parameters, as the level of correlation for cholesterol and albumin was -, 1, and -, 14, respectively. APACHE II has better prognostic power than SAPS scoring system. Withdrawal of variables such as arterial pH, pO2, pCO2 and HCO3, reduces the prognostic power of APACHE II system.


Calpain: the regulatory point of myocardial ischemia-reperfusion injury.
Calpain is a conserved cysteine protease readily expressed in several mammalian tissues, which is usually activated by Ca2+ and with maximum activity at neutral pH. The activity of calpain is tightly regulated because its aberrant activation will nonspecifically cleave various proteins in cells. Abnormally elevation of Ca2+ promotes the abnormal activation of calpain during myocardial ischemia-reperfusion, resulting in myocardial injury and cardiac dysfunction. In this paper, we mainly reviewed the effects of calpain in various programmed cell death (such as apoptosis, mitochondrial-mediated necrosis, autophagy-dependent cell death, and parthanatos) in myocardial ischemia-reperfusion. In addition, we also discussed the abnormal activation of calpain during myocardial ischemia-reperfusion, the effect of calpain on myocardial repair, and the possible future research directions of calpain.


Primary structure elements responsible for the conformational switch in the envelope glycoprotein gp120 from human immunodeficiency virus type 1: LPCR is a motif governing folding.
The ability to undergo a particular conformational switch on moving from a polar to a less polar environment has been shown to be conserved at the CD4-binding domain of the envelope glycoprotein gp120 from human immunodeficiency virus type 1 despite considerable variability in primary structure and is essential for the process of binding to the T-cell receptor CD4. The elements necessary to the expression of this behavior have been examined in synthetic peptides using circular dichroism and have been found to include a tetrad, LPCR, plus a tryptophan at a position 8 residues C-terminal to it. In the absence of the tryptophan the conformational change from beta-sheet to alpha-helix as medium polarity decreases does not occur abruptly but, rather, in a linear fashion. In the absence of the LPCR tetrad, no transition to alpha-helix occurs even at 100% trifluoroethanol. These two domains interact to control not only the beta-->alpha transition but also both its cooperativity and the critical point on the polar-->apolar gradient at which it occurs. Sequence similarity searches of the protein data banks suggest that an LPCR tetrad, governing the folding behavior of subsequent residues, may occur as a conserved motif in proteins in general. Synthetic peptides with the sequence of non-gp120 proteins that contain the tetrad do in fact display a similar pattern of folding response to decreasing polarity, with a sharp, cooperative transition from beta-sheet to alpha-helix. The LPCR tetrad appears to be a motif that controls secondary structure in a manner supplementary to that predicted by folding algorithms.


[Isolation and cultivation of a swine rotavirus].
A swine rotavirus capable of inducing the cytopathic effect was isolated in a roller culture of Macaca rhesus kidney cells (line MA-104) after two preliminary passages in gnotobiotic piglets and colostrum-free piglets, and the isolate was designated strain K. For virus isolation, fecal specimens were treated with trypsin, and besides, trypsin was added into the maintenance medium. After 20 passages in MA-104 cell culture the swine rotavirus was adapted to pig embryo kidney cell cultures (SPEV line) in which the maximum virus accumulation, 8.0 log TCD50/ml, was achieved within 24 hours after inoculation. The virus accumulation was most marked in the presence of 10 micrograms/ml trypsin in the maintenance medium. In the roller culture, the virus multiplied to a much higher titre (approximately 100-fold) than in the stationary culture. In the course of passages the virus was shown to lose its pathogenic properties. A scheme of swine rotavirus virion structure is suggested on the basis of ultramicroscopic studies.


Expression of CDC42 in cervical squamous cell carcinoma and its correlation with clinicopathologic characteristics.
The high expression of cell division cycle 42 protein (CDC42) may be involved in the occurrence and progression of several tumors. However, the expression and function of CDC42 in cervical squamous cell carcinoma remains unclear. This study aimed to investigate the expression of CDC42 in cervical squamous cell carcinoma and its correlation with clinicopathologic characteristics. The expression of CDC42 in 162 cervical squamous cell carcinoma tissue samples and 33 normal cervical tissue samples was investigated by immunohistochemistry. The CDC42 mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR). The cervical squamous cell carcinoma group showed a significantly higher CDC42 positive rate, compared to the normal cervical tissues (P<0.05). Furthermore, the tissues of stage II-IV carcinoma patients showed higher CDC42 expression levels compared to stage I patients (P=0.05). In addition, the expression of CDC42 was not correlated to age of patients, differentiation degree of cancer cells, or lymph node metastasis (P>0.05). Furthermore, compare with normal cervical tissues, the CDC42 mRNA expression in cervical cancer had no significant difference. CDC42 was up-regulated at protein level, but not mRNA level, in cervical squamous cell carcinoma. The high expression of CDC42 was correlated to the clinical stage of the patients, indicating that CDC42 might contribute to the progression of cervical squamous cell carcinoma.


Practicality of performing medical procedures in chemical protective ensembles.
To determine whether certain life saving medical procedures can be successfully performed while wearing different levels of personal protective equipment (PPE), and whether these procedures can be performed in a clinically useful time frame. We assessed the capability of eight medical personnel to perform airway maintenance and antidote administration procedures on manikins, in all four described levels of PPE. The levels are: Level A--a fully encapsulated chemically resistant suit; Level B--a chemically resistant suit, gloves and boots with a full-faced positive pressure supplied air respirator; Level C--a chemically resistant splash suit, boots and gloves with an air-purifying positive or negative pressure respirator; Level D--a work uniform. Time in seconds to inflate the lungs of the manikin with bag-valve-mask, laryngeal mask airway (LMA) and endotracheal tube (ETT) were determined, as was the time to secure LMAs and ETTs with either tape or linen ties. Time to insert a cannula in a manikin was also determined. There was a significant difference in time taken to perform procedures in differing levels of personal protective equipment (F21,72 = 1.75, P = 0.04). Significant differences were found in: time to lung inflation using an endotracheal tube (A vs. C mean difference and standard error 75.6 +/- 23.9 s, P = 0.03; A vs. D mean difference and standard error 78.6 +/- 23.9 s, P = 0.03); time to insert a cannula (A vs. D mean difference and standard error 63.6 +/- 11.1 s, P < 0.001; C vs. D mean difference and standard error 40.0 +/- 11.1 s, P = 0.01). A significantly greater time to complete procedures was documented in Level A PPE (fully encapsulated suits) compared with Levels C and D. There was however, no significant difference in times between Level B and Level C. The common practice of equipping hospital and medical staff with only Level C protection should be re-evaluated.


Mental health and health care utilization in geriatric primary care patients.
This study examines the effect of mental health factors on health care utilization in a group of community dwelling elderly subjects followed in a primary care setting. Data on utilization was obtained prospectively from computerized billing records for a one-year period following completion of a structured survey. Relationships between variables were characterized by Spearman's rank correlation. Multivariate linear regression modeling was employed to relate health care utilization, as measured by total cost, to the baseline variables. No significant relationship was found between mental health measures and health care utilization as measured by total costs in this elderly population. However, total costs were found to be related to medical comorbidity and total daily medication use. The present study did not find the relationship of psychiatric distress and increased use of health care services to apply to a group of community dwelling elderly. Future research will need to focus on larger data sets and improvement of models that attempt to examine the relationships between mental health and health care utilization in the elderly.


Accuracy Requirements for Cost-effective Suicide Risk Prediction Among Primary Care Patients in the US.
Several statistical models for predicting suicide risk have been developed, but how accurate such models must be to warrant implementation in clinical practice is not known. To identify threshold values of sensitivity, specificity, and positive predictive value that a suicide risk prediction method must attain to cost-effectively target a suicide risk reduction intervention to high-risk individuals. This economic evaluation incorporated published data on suicide epidemiology, the health care and societal costs of suicide, and the costs and efficacy of suicide risk reduction interventions into a novel decision analytic model. The model projected suicide-related health economic outcomes over a lifetime horizon among a population of US adults with a primary care physician. Data analysis was performed from September 19, 2019, to July 5, 2020. Two possible interventions were delivered to individuals at high predicted risk: active contact and follow-up (ACF; relative risk of suicide attempt, 0.83; annual health care cost, $96) and cognitive behavioral therapy (CBT; relative risk of suicide attempt, 0.47; annual health care cost, $1088). Fatal and nonfatal suicide attempts, quality-adjusted life-years (QALYs), health care sector costs and societal costs (in 2016 US dollars), and incremental cost-effectiveness ratios (ICERs) (with ICERs ≤$150 000 per QALY designated cost-effective). With a specificity of 95% and a sensitivity of 25%, primary care-based suicide risk prediction could reduce suicide death rates by 0.5 per 100 000 person-years (if used to target ACF) or 1.6 per 100 000 person-years (if used to target CBT) from a baseline of 15.3 per 100 000 person-years. To be cost-effective from a health care sector perspective at a specificity of 95%, a risk prediction method would need to have a sensitivity of 17.0% or greater (95% CI, 7.4%-37.3%) if used to target ACF and 35.7% or greater (95% CI, 23.1%-60.3%) if used to target CBT. To achieve cost-effectiveness, ACF required positive predictive values of 0.8% for predicting suicide attempt and 0.07% for predicting suicide death; CBT required values of 1.7% for suicide attempt and 0.2% for suicide death. These findings suggest that with sufficient accuracy, statistical suicide risk prediction models can provide good health economic value in the US. Several existing suicide risk prediction models exceed the accuracy thresholds identified in this analysis and thus may warrant pilot implementation in US health care systems.


Outcomes of a Modular Intercalary Endoprosthesis as Treatment for Segmental Defects of the Femur, Tibia, and Humerus.
Resection of diaphyseal bone tumors for local tumor control and stabilization often results in an intercalary skeletal defect and presents a reconstructive challenge for orthopaedic surgeons. Although many options for reconstruction have been described, relatively few studies report on the functional outcomes and complications of patients treated with modular intercalary endoprostheses. The objectives of this study were to examine clinical outcomes after reconstruction with a modular intercalary endoprosthesis with a specific focus on (1) the rate of complication or failure; (2) differences in complication rates by anatomic site; (3) functional results as assessed by the Musculoskeletal Tumor Society System (MSTS); and (4) differences in complication rate between patients treated with cemented versus noncemented fixation. We conducted a retrospective chart review of patients treated with a modular intercalary endoprosthesis from three musculoskeletal oncology centers from 2008 to 2013. The indication for use of this intercalary endoprosthesis was segmental bone loss from aggressive or malignant tumor with sparing of the joint above and below and deemed unsuitable for biologic reconstruction. No other implant was used for this indication during this period. During this period, 41 patients received a total of 44 intercalary implants, which included 18 (40%) humeri, 5 (11%) tibiae, and 21 (48%) femora. There were 27 (66%) men and 14 (34%) women with a mean age of 63 years (range, 18–91 years). Eight patients (20%) had primary bone tumors and 33 (80%) had metastatic lesions. Thirty-five (85%) patients were being operated on as an initial treatment and six (15%) for revision of a previous reconstruction. Twenty-nine (66%) procedures had cemented stem fixation and 15 (34%) were treated with noncemented fixation. The overall mean followup was 14 months (range, 1–51 months). Patients with primary tumors had a mean followup of 19 months (range, 4–48 months) and patients with metastatic disease had a mean followup of 11 months (range, 1–51 months). Causes of implant failure were categorized according to Henderson et al. [19] into five types as follows: Type I (soft tissue failure), Type II (aseptic loosening), Type III (structural failure), Type IV (infection), and Type V (tumor progression). At 2 years of followup, 38 (93%) of these patients were accounted for with three (7%) lost to followup. MSTS functional assessment was available for 39 of 41 patients (95%). At latest followup of these 41 patients, 14 (34%) patients were dead of disease, two patients (5%) dead of other causes, seven (17%) are continuously disease-free, one (2%) shows no evidence of disease, and 17 (41%) are alive with disease. There were 12 (27%) nononcologic complications. Five (11%) of these were Type II failures occurring in noncemented implants between the stem and bone, and six (14%) were Type III failures occurring in cemented implants at the clamp-rod implant interface. One patient developed a deep infection (2%, Type IV failure) and underwent removal of the implant. Additionally, one patient (2%, Type V failure) was treated by amputation after local progression of his metastatic disease. Complications were more common in femoral reconstructions than in tibial or humeral reconstructions. Twelve of 21 patients (57%) with femoral reconstructions had complications versus 0% of tibial or humeral reconstructions (0 of 23; odds ratio [OR], 62; 95% confidence interval [CI], 3–1154; p < 0.0001). The mean overall MSTS score was 77%. Implants with cemented fixation (29) had higher mean MSTS scores when compared with implants with noncemented (15) fixation (84% versus 66%, p = 0.0017). The complication rate was 33% in noncemented cases and 21% in cemented cases (p = 0.39); however, Type II failure at the bone-stem interface was associated with noncemented fixation and Type III failure at the clamp-rod interface was associated with cemented fixation (OR, 143; 95% CI, 2.413–8476; p = 0.0022). The results of this study indicate that this modular intercalary endoprosthesis yields equivalent results to other studies of intercalary endoprostheses in terms of MSTS scores. We found that patients treated with intercalary endoprostheses in the femur experienced more frequent complications than those treated for lesions in either the humerus or tibia and that the femoral complication rate of this endoprosthesis is higher when compared with other studies of intercalary endoprostheses for femoral reconstruction. Further studies are still needed to determine the long-term outcomes of this endoprosthesis in patients with primary tumors where longevity of the implant is of more importance than in the metastatic setting. We recommend cemented fixation for this intercalary modular endoprostheses because this provides improved MSTS scores and allows immediate return to weightbearing, which is of advantage to metastatic patients with limited lifespans. Level of Evidence: Level III, therapeutic study.


Short-term rhythmic proliferation of human breast cancer cell lines: surface effects and fractal growth patterns.
Kinetic studies of cell proliferation rates shed light on the growth dynamics of cancer. Most such studies are based on measurements of cell numbers that were evaluated in time intervals of about 12 h. Studies of the initial tumour growth with short measuring intervals are rare. This study was therefore designed with 1 h measuring intervals over a 24 h period. Human breast cancer cell lines (ZR-75-1, SK-BR-3, MCF-7) and a benign cell line (HBL-100) were used to study the hourly thymidine uptake as a measure of cells in synthesis. In parallel experiments, the same cell lines were also exposed to tumour necrosis factor alpha (TNF-alpha) to explore the effect of an apoptosis-inducing substance on initial tumour growth kinetics. In time-evolution plots, there was an oscillation of the labelling index of thymidine uptake for all investigated cell lines, with and without TNF-alpha. Based on the results obtained, a mathematical model was developed mimicking the real experiment. To describe the system dynamically a cellular automaton model was studied. The growth kinetics revealed by the simulation were in accordance with our experimental data. Two- and three-dimensional growth simulations of this computer model yielded objects morphologically similar to real images of human breast cancer. Almost identical fractal dimensions of the virtual and real tumours further supported this visual similarity. The cellular automata models could, therefore, be seen as a bridge towards realistic in vivo scenarios. From a clinical point of view, the results obtained may be applicable not only to primary tumours, but even to tumour cell microfoci and small metastases, which are a major concern in early metastasizing tumours such as breast cancer.


Consensus guidelines for coordinated outpatient oral anticoagulation therapy management. Anticoagulation Guidelines Task Force.
To provide primary and referring healthcare practitioners with guidelines for the provision of safe and effective anticoagulation management in any venue to standardize and improve quality of care and to permit negotiation for reimbursement from third-party payers. Data on the current practice of anticoagulation providers and outcomes related to anticoagulation clinic care were obtained through the literature, interviews with anticoagulation providers, and a focus group meeting of anticoagulation clinic stakeholders. This information collation process revealed that an anticoagulation service consists of three separate areas for which guidelines should be developed. Based on the consensus opinions of the committee members, the literature review, and the current practice of anticoagulation services providers, a draft guideline was developed and reviewed by an independent multidisciplinary panel of anticoagulation services providers whose comments were incorporated into the final guideline. Systematic outpatient anticoagulation services are systems of care designed to coordinate and optimize the delivery of anticoagulation therapy by (1) evaluating patient-specific risks and benefits to determine the appropriateness of therapy; (2) facilitating the management of anticoagulation dosages and prescription pick up or delivery; (3) providing ongoing education of the patient and other caregivers about warfarin and the importance of self-care behavior leading to optimal outcomes; (4) providing continuous systematic monitoring of patients, international normalized ratio results, diet, concomitant drug therapy, and disease states; and (5) communicating with other healthcare practitioners involved in the care of the patient. To create a reproducible framework for the provision of these services, guidelines for structure, process, and outcomes of coordinated outpatient anticoagulation management services were developed. Guidelines for organization and management include (1) qualifications for personnel, (2) supervision, (3) care management and coordination, (4) communication and documentation, and (5) laboratory monitoring. Guidelines for the process of patient care include (6) patient selection and assessment, (7) initiation of therapy, (8) maintenance and management of therapy, (9) patient education, and (10) management and triage of therapy-related and unrelated problems. Guidelines for the evaluation of patient outcomes include (11) organizational components and (12) patient outcomes. The impact of these 12 guidelines on patient care and reimbursement procurement will depend on their implementation and the perceived value of their use.


Cutting edges: deconstructive inquiry and the mission of the border ethnographer.
Research is an activity nursing 'cannot not want'. Such an imperative compels me to sketch out some theoretical borders of a hybrid postmodern methodological framework that I have called 'border' ethnography. It is a methodology suspended between a still authoritative modernity and an as yet only partially legitimate postmodernity. At one level this position is somewhat uncomfortably in a post-methodological terrain. The text that issues from such a tension-laden research space is, I argue, intensely autobiographical, inescapably ethnographic and inherently deconstructive. Ethno(autobio) graphy is a method 'on the run'; it destabilizes while it authorizes, it represents while it misrepresents, and it threatens to disintegrate as it comes into view. But, most importantly, it is the creature of a praxis-oriented endeavour not only to better understand a culture, but to actively intervene in its (re) production.


[Effect of a couple of stimulants on the gastric motility (author's transl)].
The effects of the stimulants such as antral distention, administration of gastrin and insulin on the gastric motility were investigated in the dogs with innervated antral pouches. The results were as follows: 1. The gastric motility was markedly increased by these stimulants and characteristic motility patterns were recognized in each stimulants. 2. Antral distention stimulated strongly the contraction pressure but not in the frequency of the gastric contractions. 3. Gastrin produced regular and higher frequency contractions and the decrease in contraction pressure of the stomach. 4. Insulin stimulated both of the contraction pressure and the frequency of the gastric contractions. 5. The tests of compound stimulation by each two of these stimuli demonstrated that gastrin constantly produced an increase in frequency and a decrease in contraction pressure and that antral distention always increased the contraction pressure of the stomach.


Rational design and development of radiation-sensitizing histone deacetylase inhibitors.
Histone deacetylases (HDACs) offer potentially attractive molecular targets for sensitizing cancers to treatment with radiation therapy. By affecting patterns of gene expression, differentiation, apoptosis, and enhanced responses to therapeutic agents may be induced in cancer cells. Here, we review the drug characteristics underlying design and screening of HDAC inhibitors with a focus on radiation-sensitizing properties. Radiation-sensitizing capacities have been observed in three model systems, squamous carcinoma of head and neck origin (SQ-20B), prostate adenocarcinoma (PC-3), and breast adenocarcinoma (MCF7). Cell-type specificities in radiation-sensitizing properties have been observed. Mechanisms underlying specificity are under investigation.


[Characteristics of Enterococcus strains isolated from neutropenic patients at the National Bone-Marrow Transplantation Center of Tunis].
The frequency of digestive colonization of neutropenic patients by Enterococci during the phase of pre-transplant and post-transplant of bone marrow is important indeed as 441 Enterococcus spp strains have been isolated from stool-cultures and other specimens whithin a period of 35 months in 80 patients. A quantitative stool culture was done on appropriate media. Simple bile-esculine agar (BE) and bile esculine-agar additionned with 6 mg/l of vancomycine (BEV) were used for detecting Enterococci. These organisms were taken into account, when then numeration was > 10(3) UFC/g of fecal sample on BE and in all cases on BEV. Species isolated were essentially Enterococcus faecalis (39.4%), Enterococcus faecium (34.4%) and Enterococcus casseliflavus (17%). These strains were characterized by a high frequency of high-level resistance to gentamicin (40.8%). Resistance to amoxicillin concerns 40% of E. faecium strains. Seventeen multiresistant strains of E. faecium isolated from 7 patients (colonized during a long period and receiving a gut decontamination treatment) were the subject of a phenotypic analysis (biotyping, antibiotyping and determination of MICs to beta-lactam, aminoglycosides and glycopeptides). This analysis showed that these strains are distinguishable, endogenic and specific for each patient, the common multiresistance trait resulted from the selective pressure of decontamination treatment used for our patient.


Cytoskeletal asymmetry in Zea mays subsidiary cell mother cells: a monopolar prophase microtubule half-spindle anchors the nucleus to its polar position.
Double labeling of microtubules and actin filaments revealed that in prophase subsidiary mother cells of Zea mays a monopolar prophase microtubule "half-spindle" is formed, which lines the nuclear hemisphere distal to the inducing guard mother cell. The nuclear hemisphere proximal to the guard mother cell is lined by an F-actin cap, consisting of a cortical F-actin patch and actin filaments originating from it. The microtubules of the "half-spindle" decline from the nuclear surface and terminate to the preprophase microtubule band. After disintegration of the latter, a bipolar metaphase spindle is organized. The polar F-actin cap persists during mitosis and early cytokinesis, extending to the chromosomes and the subsidiary cell daughter nucleus. In oryzalin treated subsidiary mother cells the prophase nuclei move away from the polar site. Cytochalasin B and latrunculin-B block the polar migration of subsidiary mother cell nuclei, but do not affect those already settled to the polar position. The prophase nuclei of latrunculin-B treated subsidiary mother cells are globally surrounded by microtubules, while the division plane of latrunculin-B treated subsidiary mother cells is misaligned. The prophase nuclei of brick 1 mutant Zea mays subsidiary mother cells without F-actin patch are also globally surrounded by microtubules. The presented data show that the prophase microtubule "half-spindle"-preprophase band complex anchors the subsidiary mother cell nucleus to the polar cell site, while the polar F-actin cap stabilizes the one metaphase spindle pole proximal to the inducing guard mother cell.


Modulation of carcinogenesis with selected GRAS nutraceuticals via Keap1-Nrf2 signaling pathway.
Keap1-Nrf2 is a fundamental signaling cascade known to promote or prevent carcinogenesis. Extensive studies identify the key target of modulatory aspects of Keap1-Nrf2 signaling against cancer. Nutraceuticals are those dietary agents with many health benefits that have immense potential for cancer chemoprevention. The nutritional supplements known as nutraceuticals are found to be one of the most promising chemoprevention agents. Upon investigating the dual nature of Nrf2, it became clear that, in addition to shielding normal cells from numerous stresses, Nrf2 may also promote the growth of tumors. In the present review, we performed a systematic analysis of the role of 12 different nutraceuticals like curcumin, sulforaphane, resveratrol, polyunsaturated fatty acids (PUFA) from fish oil, lycopene, soybean, kaempferol, allicin, thymoquinone, quercetin, gingerol, and piperine in modulating the Nrf2/Keap1 signaling mechanism. Among these, 12 Generally Recognized As Safe (GRAS) certified nutraceuticals, sulforaphane is the most extensively studied compound in modulating Keap1-Nrf signaling. Even though there is much evidence at preclinical levels, further high-quality research is still required to validate the potential role of these nutraceuticals in Keap1-Nrf2 modulation.


Obesity. Part I--Pathogenesis.
Obesity--defined by a body mass index above 30 kg per m2--is a major problem for affluent nations. Its prevalence is higher in North America than in Europe--between 9% and 12% of the population. Reduced energy expenditure from exercise or metabolism or both may be an important contributory factor in the development of obesity because of a failure to reduce food intake sufficiently to maintain energy balance. A high ratio of abdominal circumference relative to gluteal circumference carries a twofold or greater risk of heart attack, stroke, hypertension, diabetes mellitus, gallbladder disease, and death. The effect of increased quantities of abdominal fat is greater than that of a similar increase in total body fat on the risks of ill health associated with obesity. Genetic factors appear to contribute about 25% to its etiology.


Affordability of essential medicines: The case of fluoride toothpaste in 78 countries.
Fluoride toothpaste (FT) has recently been included in the WHO Model List of Essential Medicines. Whereas it is essential for preventing dental caries, its current affordability around the globe remains unclear. This study aimed to analyse the affordability of FT in as many as possible countries worldwide, to capture the extent of variations in FT affordability between high-, middle- and low-income countries. A standardized protocol was developed to collect country-specific information about the characteristics of the cheapest available FT at a regular point of purchase. 82 members of the WHO Global Oral Health Network of Chief Dental Officers (CDOs), directors of WHO Collaborative Centres and other oral health experts collected data using mobile phone technology. In line with established methodologies to assess affordability, the Fluoride Toothpaste Affordability Ratio (FTAR) was calculated as the expenditure associated with the recommended annual consumption of FT relative to the daily wage of the lowest-paid unskilled government worker (FTAR >1 = unaffordable spending on fluoride toothpaste). There are significant differences in the affordability of FT across 78 countries. FT was strongly affordable in high-income countries, relatively affordable in upper middle-income countries, and strongly unaffordable in lower middle-income and low-income countries. The affordability of FT across WHO Regions was dependent upon the economic mix of WHO Regions' member states. FT is still unaffordable for many people, particularly in low-income settings. Strategies to improve the universal affordability of FT should be part of health policy decisions in order to contribute to reducing dental caries as a global public health problem.


Oral Subcutaneous Midline Leiomyomatous Hamartoma Presenting as Congenital Incisive Papilla Overgrowth in a Toddler.
Congenital soft-tissue tumors of oral cavity are mostly hyperplastic and benign in nature. This article presents an unusual case of congenital subcutaneous hamartoma of incisive papilla in a 2-year-old female child causing feeding and breathing difficulty. Total excisional biopsy was done under local anesthesia. Histopathology of tissue in reticulin-stained slide showed the presence of immature muscle fibers whereas Masson's trichrome stain revealed collagen fibers and smooth muscles confirming the diagnosis of oral midline subcutaneous smooth muscle (leiomyomatous) hamartoma of incisive papilla. It is important for dental professionals to be aware of this oral lesion present from birth mimicking overgrowth of incisive papilla, by its presentation, differential diagnosis, histopathology, and management.


The production of red blood cell alloantibodies in mice transfused with blood from transgenic Fyb-expressing mice.
A murine model would be useful to identify which immune mechanisms could be manipulated to treat or prevent red blood cell (RBC) alloimmunization in patients who become sensitized to multiple or widely expressed antigens. Transgenic mice (B6CBAF1/J-Tg-Fy(b)) expressing the human Fy(b) antigen of the Duffy (Fy) blood group were donors. Recipient B6CBA-F1 mice received four weekly intravenous (IV) transfusions: either 0.3 mL of washed buffy coat-depleted RBCs or 0.3 mL of RBCs with spleen cells. Titers of immunoglobulin M (IgM) and immunoglobulin G (IgG) were measured in recipient serum samples by flow cytometry with RBCs from donor mice as target cells. Recipient serum samples were also tested against human RBCs of various Fy phenotypes. Additionally, RBC survival studies were performed in alloimmunized mice utilizing biotin-labeled Fy(b) transgenic mouse RBCs. B6CBA-F1 mice receiving washed buffy coat-depleted RBCs first made IgM, followed by IgG alloantibodies to transgenic mouse Fy(b)-positive RBCs. Recipients of Fy(b)-positive RBCs mixed with spleen cells also produced IgM and IgG alloantibodies, but at a slower rate than recipients of washed buffy coat-depleted RBCs. Serum samples showed specificity for Fy3, Fy(b), and Fy6. Decreased survival of transfused RBCs was evident at 24 hours after transfusion. It is possible to elicit the formation of anti-Fy alloantibodies by IV transfusion in mice that lack Fy antigens. The transfusion of RBCs alone was adequate to stimulate alloantibody production in B6CBA-F1 recipient mice. The survival of transfused Fy(b)-positive RBCs is diminished in sensitized mice. This model will be useful in further studies of RBC alloimmunization.


Influence of olive oil on alveolar bone response during orthodontic retention period: rabbit model study.
This study attempted to evaluate clinically and histologically the effects of olive oil (Ol) consumption on orthodontic relapse after the retention period. Thirty apparently healthy female albino rabbits, weight more than 1000 g each was used in this study. The animals were grouped randomly into six groups of five animals each: two control and four experimental groups. In control groups, the relapse was estimated either at zero day, or at the end of the fourth week after orthodontic retention period. In the experimental groups, the animals' groups received Ol, 7.7, or 15.4 ml/kg b.w. per day during the orthodontic retention period. The relapse was estimated either at zero day, or at the end of the fourth week after orthodontic retention period for each concentration. Modified fixed orthodontic appliances were attached to the rabbits' lower central incisors. Each rabbit received orthodontic intervention for one week, followed by six weeks retention period. At the end of the experiments, the clinical and histological investigations were conducted. Data analyses were performed at the level of p < .05 for the statistically significant difference. Clinically, Ol high concentration four weeks group showed a significantly lower relapse tendency than control four weeks group. Histologically, Ol low concentration zero time group showed significantly higher osteoblasts numbers than control zero time group. Olive oil low and high concentrations four weeks group showed significantly lower fibroblasts count. Moreover, Ol high concentration four weeks group revealed significantly higher bone mineralization, osteoblasts and osteocytes counts than control four weeks study group. Supplementation with Ol during an orthodontic retention period, especially at 15.4 ml/kg b.w. per day concentration, clinically reduced orthodontic relapse on rabbit model. Histologically, Ol increased osteoblasts and osteocytes counts and the relative amount of bone mineralization of connective tissue layer forming alveolar bone (AB) at the end of four weeks after the orthodontic retention period.


Melanin-like pigment in the human prostate.
Twenty surgical specimens of prostate [1 histologically normal, 8 with benign hyperplasia (BPH), and 11 with cancer (PCa)] were examined by histochemical staining methods for the presence of a melanin-like pigment that we first observed in organ culture. Fontana-Masson-positive pigment was observed in epithelial cells of the normal specimen, of five BPH and of eight PCa. The distribution of pigment in BPH was unpredictable and patchy. The pigment was consistently absent in neoplastic epithelia. Silver-positive stromal cells also were observed in a number of the specimens. The epithelial pigment reacted to histochemical stains in part like melanin, in part like lipofuscin. It probably represents an endogenous pigment similar to other types of noncutaneous melanins.


Impact of a Music Intervention on Quality of Life in Breast Cancer Patients Undergoing Chemotherapy: A Randomized Clinical Trial.
Background: Music can influence human behavior and may be used as a complementary therapy in health care. Objectives: To assess the effect of music interventions on symptoms, adverse events, and quality of life (QoL) of breast cancer patients undergoing chemotherapy (CT). Design: Nonblinded, randomized clinical trial. Women with breast cancer undergoing adjuvant CT were randomized into 2 groups-Group Music (GM) or Group Control (GC)-and followed during the first 3 cycles of treatment. Measurements: Sociodemographic data, WHOQOL-BREF, BDI-II, BAI, and Chemotherapy Toxicity Scale were assessed. Patients were evaluated after each session of the first 3 CT cycles. GM underwent a 30-minute musical intervention before CT. There was no intervention in the GC. Continuous data were analyzed by Student's t test, and χ2 test was used to compare qualitative variables. Results: Higher QoL scores on functional scales were observed for the GM in comparison to the GC after the first and third sessions of CT. Depression (P < .001) and anxiety scores (P < .001) and vomiting (P < .01) incidence were lower for the GM in the third session of CT. All the participants in the GM reported positive changes in life in the Subjective Impression of the Subject questionnaire, as well as improvement in fatigue and reduced stress levels. Conclusions: Improvements in QoL, anxiety, depression, and incidence of vomiting were associated with the music intervention, suggesting a positive effect of the music intervention on adverse events of cancer CT.


DNA typing from vaginal smear slides in suspected rape cases.
In an investigation of suspected rape, proof of sexual assault with penetration is required. In view of this, detailed descriptions of the genitalia, the thighs and pubic region are made within the forensic medical service. In addition, vaginal swabs are taken from the rape victim and some of the biological material collected is then transferred to glass slides. In this report, we describe two rape cases solved using DNA typing from cells recovered from vaginal smear slides. In 1999, two young women informed the Rio de Janeiro Police Department that they had been victims of sexual assaults. A suspect was arrested and the victims identified him as the offender. The suspect maintained that he was innocent. In order to elucidate these crimes, vaginal smear slides were sent to the DNA Diagnostic Laboratory for DNA analysis three months after the crimes, as unique forensic evidence. To get enough epithelial and sperm cells to perform DNA analysis, we used protocols modified from the previously standard protocols used for DNA extraction from biological material fixed on glass slides. The quantity of cells was sufficient to perform human DNA typing using nine short tandem repeat (STR) loci. It was 3.3 billion times more probable that it was the examined suspect who had left sperm cells in the victims, rather than any other individual in the population of Rio de Janeiro.


[Electrolyte- and urea concentration profiles of the kidney in experimental asymmetric glomerulonephritis (author's transl)].
Bilateral studies on kidney function concerning the electrolyte and urea concentration-profiles in renal medulla were performed in experimental unilateral acute glomerulonephritis in rabbits. 1. Both in the intact and in the glomerulonephritic kidneys sodium is concentrated mainly in the outer medulla and urea in the inner medulla. 2. In the glomerulonephritic kidneys the reduction of the filtered load seems to impair the regions of mainly passive concentrating mechanisms more than those of mainly active transport mechanisms. 3. Potassium gradients are not involved, the tissue concentrations of the glomerulonephritic kidneys however are diminished by 20 %. 4. According to the decreasing interstital electrolyte and urea gradients the osmolarity of the collecting ducts of the glomerulonephritic kidneys are diminished. These results support the conclusion, that the urinary concentrating defect in Masuginephritis is due mainly to the unability to concentrate urea.


Rogue athletes and recombinant DNA technology: challenges for doping control.
The quest for athletic excellence holds no limit for some athletes, and the advances in recombinant DNA technology have handed these athletes the ultimate doping weapons: recombinant proteins and gene doping. Some detection methods are now available for several recombinant proteins that are commercially available as pharmaceuticals and being abused by dopers. However, researchers are struggling to come up with efficient detection methods in preparation for the imminent threat of gene doping, expected in the 2008 Olympics. This Forum article presents the main detection strategies for recombinant proteins and the forthcoming detection strategies for gene doping as well as the prime analytical challenges facing them.


Sedation/analgesia techniques for nonoperating room anesthesia: new drugs and devices.
The purpose of this article is to review new drugs and devices for nonoperating room anesthesia (NORA). Remimazolam is an ultra-short-acting, water-soluble intravenous benzodiazepine with a fast onset and offset that has been approved recently for use in procedural sedation. Phase III trials have established the effectiveness of remimazolam sedation compared with placebo and midazolam in gastrointestinal endoscopy and bronchoscopy. More research is required investigating remimazolam in real-world NORA settings, including comparisons with propofol sedation. Oliceridine is a μ-agonist with selectivity for the G protein pathway and low potency for β-arrestin recruitment. As such it may be associated with less nausea, vomiting and respiratory depression than traditional opioids used. Although no studies have been published about oliceridine use in NORA to date, results from surgical studies indicate a potential place in nonoperating room practice. Research continues into alternative methods of drug delivery, such as patient-controlled sedation but no new devices are described. Further studies are required before these new drugs and devices are embraced in NORA.


Targeting of aequorin for calcium monitoring in intracellular compartments.
We have recently developed a new method for monitoring Ca2+ concentrations in defined cell compartments. The cDNA encoding the Ca(2+)-sensitive photoprotein aequorin has been modified in order to include specific targeting sequences and expressed in eukaryotic cells; the recombinant protein, specifically located inside the cells, has allowed the direct study of mitochondrial and nuclear Ca2+ concentrations in living cells. The principles, and the application, of this new methodology are discussed in this article.


Resident Arterial Cells and Circulating Bone Marrow-Derived Cells both Contribute to Intimal Hyperplasia in a Rat Allograft Carotid Transplantation Model.
Neointimal formation following vascular injury remains a major mechanism of restenosis, whereas the precise sources of neointimal cells are still uncertain. We tested the hypothesis that both injured arterial cells and non-arterial cells contribute to intimal hyperplasia. Following allograft transplantation of the balloon-injured carotid common artery (n = 3-6), the cellular composition of the transplant grafts and the origins of neointimal cells were measured by immunohistochemistry and immunofluorescence staining. Smooth muscle actin (SMA)-positive and CD68-positive cells were clearly observed 14 days later in the neointima after allograft transplantation of the balloon-injured carotid common artery, where re-endothelialization was not yet complete. Green fluorescent protein (GFP) and wild-type (WT) allograft transplantation revealed that the majority of the neointima cells were apparently from the recipient (≈85%) versus the donor (≈15%). Both monocyte chemotactic protein-1 (MCP-1)/CCR2 and stromal cell-derived factor-1 (SDF-1)/CXCR4 signaling were involved in intimal hyperplasia, with bone marrow-derived cells also playing a role. These data support the hypothesis that intimal hyperplasia could develop in our novel rat allograft transplantation model of arterial injury, where neointima is attributable not only to local arterial cells but also non-arterial cells including the bone marrow.


Spectrally Sharp Near-Field Thermal Emission: Revealing Some Disagreements between a Casimir-Polder Sensor and Predictions from Far-Field Emittance.
Near-field thermal emission largely exceeds blackbody radiation, owing to spectrally sharp emission in surface polaritons. We turn the Casimir-Polder interaction between Cs(7P_{1/2}) and a sapphire interface into a sensor sharply filtering, at 24.687 THz, the near-field sapphire emission at ∼24.5 THz. The temperature evolution of the sapphire mode is demonstrated. The Cs sensor, sensitive to both dispersion and dissipation, suggests the polariton to be redshifted and sharper, as compared, up to 1100 K, to predictions from far-field sapphire emission, affected by birefringence and multiple resonances.


Pulmonary telerehabilitation vs. conventional pulmonary rehabilitation - a secondary responder analysis.
Home-based pulmonary telerehabilitation (PTR) has been proposed to be equivalent to supervised outpatient pulmonary rehabilitation (PR) but available randomised trials have failed to reach the minimal important changes (MIC). The purpose of this study was to analyse the proportion of MIC responders and non-responders on short-term (10 weeks from baseline) and long-term (62 weeks from baseline) in total and between groups in 134 patients with COPD randomised (1:1) to either home-based PTR or traditional hospital-based outpatient PR. Difference between PTR and PR on 6MWD response proportion could not be shown at 10 (OR=0.72, CI=0.34 to 1.51, p=0.381) or 62 weeks (OR=1.12, CI=0.40 to 3.14, p=0.834). While the evidence and knowledge of PTR accumulate, outpatient supervised PR for now remains the standard of care, with home-based PTR as a strong secondary option for those unable to attend out-patient programmes.


Emerging roles of non-coding RNAs in brain evolution, development, plasticity and disease.
Novel classes of small and long non-coding RNAs (ncRNAs) are being characterized at a rapid pace, driven by recent paradigm shifts in our understanding of genomic architecture, regulation and transcriptional output, as well as by innovations in sequencing technologies and computational and systems biology. These ncRNAs can interact with DNA, RNA and protein molecules; engage in diverse structural, functional and regulatory activities; and have roles in nuclear organization and transcriptional, post-transcriptional and epigenetic processes. This expanding inventory of ncRNAs is implicated in mediating a broad spectrum of processes including brain evolution, development, synaptic plasticity and disease pathogenesis.


Joint Community Health Needs Assessments as a Path for Coordinating Community-Wide Health Improvement Efforts Between Hospitals and Local Health Departments.
To examine the association between hospital-local health department (LHD) collaboration around community health needs assessments (CHNAs) and hospital investment in community health. We combined 2015 National Association of County and City Health Officials (NACCHO) Forces of Change, 2013 NACCHO Profile, and 2014-2015 Area Health Resource File data to identify a sample of LHDs (n = 439) across the United States. We included data on hospitals' community benefit from their 2014 tax filings (Internal Revenue Service Form 990, Schedule H). We used bivariate and multivariate regression analyses to examine LHDs' involvement in hospitals' CHNAs and implementation strategies and the relationship with hospital investment in community health. The LHDs that collaborated with hospitals around CHNAs were significantly more likely to be involved in joint implementation planning activities than were those that did not. Importantly, LHD involvement in hospitals' implementation strategies was associated with greater hospital investment in community health improvement initiatives. Joint CHNAs may improve coordination of community-wide health improvement efforts between hospitals and LHDs and encourage hospital investment in community health improvement activities. Public Health Implications. Policies that strengthen LHD-hospital collaboration around the CHNA may enhance hospital investments in community health.


Assessment of Patients with a DePuy ASR Metal-on-Metal Hip Replacement: Results of Applying the Guidelines of the Spanish Society of Hip Surgery in a Tertiary Referral Hospital.
The prognosis associated with the DePuy ASR hip cup is poor and varies according to the series. This implant was withdrawn from use in 2010 and all patients needed to be assessed. We present the results of the assessment of our patients treated with this device, according to the Spanish Society of Hip Surgery (SECCA) algorithm published in 2011. This retrospective study evaluates 83 consecutive ASR cups, followed up at a mean of 2.9 years. Serum levels of chromium and cobalt, as well as the acetabular abduction angle, were determined in order to assess their possible correlation with failure, defined as the need for revision surgery. The mean Harris Hip Score was 83.2 (range 42-97). Eight arthroplasties (13.3%) required revision due to persistent pain and/or elevated serum levels of chromium/cobalt. All the cups had a correct abduction angle, and there was no correlation between elevated serum levels of metal ions and implant failure. Since two previous ASR implants were exchanged previously to the recall, the revision rate for ASR cups in our centre is 18.2% at 2.9 years.


Laparoscopic treatment of small bowel strangulation caused by an intramesosigmoid hernia and review of literature.
An internal hernia is defined as a protrusion of an abdominal viscera through the defects of the gastrointestinal mesentery or peritoneum-lined fossa. Sigmoid mesocolic hernias are an uncommon type of internal hernias, accounting for only 6% of all internal hernias. Furthermore, intramesosigmoid hernia is one of the three subtypes of the sigmoid mesocolic hernias. Internal hernias are potentially fatal conditions with diagnostic challenges. Patients presenting with acute obstruction, no surgical history and no external hernia should receive an urgent CT scan to facilitate early surgery and to minimise the risk of strangulation and bowel resection. Here, we report a case of strangulated small bowel obstruction secondary to an intramesosigmoid hernia with a successful laparoscopic repair. We also present a literature review of all reported cases so far and give an up-to-date perspective on intramesosigmoid hernia.


Adaptive potential of maritime pine (Pinus pinaster) populations to the emerging pitch canker pathogen, Fusarium circinatum.
There is a concern on how emerging pests and diseases will affect the distribution range and adaptability of their host species, especially due to different conditions derived from climate change and growing globalization. Fusarium circinatum, which causes pitch canker disease in Pinus species, is an exotic pathogen of recent introduction in Spain that threatens its maritime pine (P. pinaster) stands. To predict the impact this disease will have on the species, we examine host resistance traits and their genetic architecture. Resistance phenotyping was done in a clonal provenance/progeny trial, using three-year-old cuttings artificially inoculated with the pathogen and maintained under controlled environmental conditions. A total number of 670 ramets were assessed, distributed in 10 populations, with a total of 47 families, 2 to 5 half-sibs per family, and 3-7 ramets per clone. High genetic variation was found at the three hierarchical levels studied: population, family and clone, being both additive and non-additive effects important. Narrow-sense and broad-sense heritability estimates were relatively high, with respective values of 0.43-0.58 and 0.51-0.8, depending on the resistance traits measured (lesion length, lesion length rate, time to wilting, and survival). These values suggest the species' high capacity of evolutionary response to the F. circinatum pathogen. A population originated in Northern Spain was the most resistant, while another from Morocco was the most susceptible. The total number of plants that did not show lesion development or presented a small lesion (length<30 mm) was 224 out of 670, indicating a high proportion of resistant trees in the offspring within the analyzed populations. We found large differences among populations and considerable genetic variation within populations, which should allow, through natural or artificial selection, the successful adaptation of maritime pine to pitch canker disease.


Technology-Assisted Hip and Knee Arthroplasty in Orthopaedic Residency Training: A National Survey.
The adoption of technology-assisted total joint arthroplasty (TA-TJA) is increasing; however, the extent to which TA-TJA is used among orthopaedic trainees is unknown. The purpose of this study was to assess the current use of TA total knee arthroplasty (TKA) and total hip arthroplasty (THA) by orthopaedic residents and to evaluate resident perceptions toward TA-TJA in their surgical training. In this cross-sectional study, an anonymous electronic survey was sent to all Accreditation Council for Graduate Medical Education-accredited orthopaedic surgery residency program coordinators to distribute to their PGY-2 to PGY-5 residents. The survey consisted of 24 questions, including resident demographics, utilization of TA-TJA in their training, and perceptions regarding TA-TJA. A total of 103 orthopaedic residents completed the survey, of whom 68.0% reported using TA-TJA at their institution. Of the residents using TA-TJA, 28.6% used TA for total TKA only, 71.4% used TA for both TKA and THA, and none used TA solely for THA. One-third of residents (33.3%) use TA for more than half of all TKAs conducted, whereas 57.0% use TA for <10% of all THAs conducted. Approximately half of all residents (49.5%) thought that training in TA-TJA should be required during residency, with no significant differences between junior and senior level residents ( P = 0.24). Most (82.0%) thought that trainees should be required to learn conventional TJA before learning TA-TJA. 63.0% thought that technology had a positive effect on their primary TJA training experience; however, 26.0% reported concern that their training conducting conventional TJA may be inadequate. This study demonstrates that most orthopaedic residents currently conduct TA-TJA and highlights notable differences in TJA training experiences. These results provide a platform for future work aimed at further optimizing TJA training in residency, particularly as technology continues to rapidly evolve and utilization of TA-TJA is projected to grow exponentially. N/A, survey-based study.


[The development of a new multi-functional translumbar epidural space intracrandial pressure monitor].
This paper presents work principle and structure characteristic of a new translumbar pressure monitor. The monitor had the device of microduct with ball bladder and probe filled with liquid for making pressure. The clinical practice indicated that the monitor had the advantages of simply operating, small injury and good stability.


Evaluation of gallbladder motility in patients with irritable bowel syndrome.
Abnormalities involving smooth muscle function in different systems of the body have been reported in irritable bowel syndrome (IBS). There are a few studies on gallbladder function in this disorder with conflicting results. To investigate the motility of gallbladder in patients with IBS. Forty-eight patients (15 male and 33 female) with IBS and 48 healthy volunteers (15 male and 33 female) were included into the study. Thirty-four patients (70.8%) had constipation predominant and 14 patients (29.2%) had diarrhoea predominant type of IBS. Fasting and postprandial gallbladder volumes were studied using real time ultrasonography and ejection fraction (EF) of gallbladder was calculated. While fasting gallbladder volume (FGV) was similar between IBS and control groups (18.0 +/- 4.0 ml vs. 17.8 +/- 4.9 ml, p >0.05), postprandial gallbladder volume (PGV) was lower in IBS group than in the control group (5.5 +/- 1.4 ml vs. 6.2 +/- 1.9 ml, p = 0.03). Accordingly, the mean EF of gallbladders was found to be higher in IBS group than in the control group (69.1% vs. 64.1%, p = 0.0001). There were no difference in FGV, PGV and EF of gallbladders between constipation predominant and diarrhoea predominant IBS patients (p >0.05). The results of this study indicated that IBS patients have increased emptying of gallbladder compared to healthy subjects.


Recent Advances of Flexible Data Storage Devices Based on Organic Nanoscaled Materials.
Following the trend of miniaturization as per Moore's law, and facing the strong demand of next-generation electronic devices that should be highly portable, wearable, transplantable, and lightweight, growing endeavors have been made to develop novel flexible data storage devices possessing nonvolatile ability, high-density storage, high-switching speed, and reliable endurance properties. Nonvolatile organic data storage devices including memory devices on the basis of floating-gate, charge-trapping, and ferroelectric architectures, as well as organic resistive memory are believed to be favorable candidates for future data storage applications. In this Review, typical information on device structure, memory characteristics, device operation mechanisms, mechanical properties, challenges, and recent progress of the above categories of flexible data storage devices based on organic nanoscaled materials is summarized.


The anatomy of the tympanic sinus.
The tympanic sinus is one of the most important structures of the human temporal bone. Located in its vicinity are the round window, posterior semicircular canal and facial nerve. The study was performed on 30 temporal bones taken from adult cadavers of both sexes. After the tympanic sinus had been identified, its morphological features were evaluated. The sinus was then measured using a graticule with an accuracy of 0.05 mm. Also measured were the shortest distances from the tympanic sinus to the neighbouring structures (the lateral and posterior semicircular canal, the facial nerve canal and the jugular fossa). The measurements were performed under a surgical microscope with eye-piece graduation of 0.05 mm accuracy. Four main morphological types of fossa of the tympanic sinus and two main developmental forms, a deep sinus and a shallow sinus, were distinguished. The existence of a deep sinus was associated with absence of the bridge and the sinus was shallower when the bridge was prominent. The very deep sinuses were located close to the facial canal, in some cases penetrating deep in its vicinity (in some cases even going beyond two thirds of the canal's circumference), which poses a real risk of facial nerve damage during surgical removal of a lesion located in close proximity to the nerve. In most cases the tympanic sinus is elliptical in shape and its long diameter lies in the vertical plane (mean value: 2.73 x 2.23 mm). The mean distances from the tympanic sinus to the facial nerve canal, lateral semicircular canal, posterior semicircular canal and jugular fossa were 1.5 mm, 2.1 mm, 1.59 mm and 5.5 mm respectively. No correlation was observed between the measurement results and either sex or side.


Eco-Friendly Epoxy-Terminated Polyurethane-Modified Epoxy Resin with Efficient Enhancement in Toughness.
Polyurethane is widely used to toughen epoxy resins due to its excellent comprehensive properties and compatibility. However, some demerits of polyurethanes limit their applications, such as the harsh storage condition of isocyanate-terminated polyurethane (ITPU), the limited amount of ITPU in epoxy resin, and using solvents during the preparation of polyurethane-modified epoxy resins. To address these issues, in this study, we reported a facile and green approach for preparing epoxy-terminated polyurethane (EPU)-modified epoxy resins with different EPU contents. It was found that the toughness of the epoxy resin was significantly improved after the addition of EPU. When the EPU content was 30 wt%, the elongation at break and toughness were improved by 358.36% and 73.56%, respectively. In comparison, the toughening effect of EPU outperformed that of ITPU. Moreover, the high content of EPU did not significantly decrease the glass transition temperature and had little effect on the thermal stability of the epoxy resin.


Hereditary pancreatitis in a family of Aboriginal descent.
Hereditary pancreatitis is an autosomal dominant condition characterized by recurrent episodes of acute pancreatitis, usually starting in childhood. We present a family who was ascertained when an 11-year-old girl presented with an episode of acute pancreatitis. Her father and other family members had also had recurrent bouts of acute pancreatitis. Genetic testing revealed a pathogenic mutation in the cationic trypsinogen gene in the proband, her father and her paternal grandmother. As far as we are aware, this is the first Aboriginal kindred with mutation-proven hereditary pancreatitis. Hereditary pancreatitis is an important differential diagnosis to consider in a patient with recurrent episodes of acute pancreatitis with no obvious precipitating cause. This family is of Aboriginal descent and the implications of the family's background are also discussed when considering the aetiology of the condition. We emphasize the need to ascertain a full family history from patients with a history of repeated episodes of acute pancreatitis and also emphasize the need to avoid ethnic stereotypes when assessing patients.


Development of a qualitative dose indicator for gamma radiation using lyophilized Deinococcus.
The feasibility of using Deinococcus showing strong resistance to both desiccation and ionizing radiation as a dose indicator of gamma radiation exposure was evaluated. Three Deinococcus strains having different levels of radiation resistance, Deinococcus radiodurans (DRD), Deinococcus radiopugnans (DRP), and the DRD pprI mutant (DRM), were selected to develop an appropriate dose indicator for a broad range of exposures. DRD, DRP, and DRM cultures with different numbers of cells [~10(7) to 10(3) colony forming units (CFU)/100 microliter] were lyophilized and subjected to various doses of gamma radiation to determine a critical dose that inhibited bacterial growth completely. Finally, a combination of DRD at ~10(7) and ~10(6) CFU, DRP at ~10(5) CFU, and DRM at ~10(4) CFU successfully indicated exposure to 5, 10, 20, and 30 kGy of gamma radiation, respectively. This study shows the possibility of developing a qualitative indicator of radiation exposure using Deinococcus.


Harnessing phosphonate antibiotics argolaphos biosynthesis enables a synthetic biology-based green synthesis of glyphosate.
Glyphosate is a widely used herbicide with an annual production of more than one million tons globally. Current commercialized production processes of glyphosate are generally associated with manufacturing hazards and toxic wastes. Recently, many countries have strengthened environmental supervision and law enforcement on glyphosate manufacturing. Therefore, a green source of glyphosate is required. Here, we characterize the genes required for producing aminomethylphosphonate (AMP), one of the intermediates in the biosynthesis of the potent antibiotics argolaphos. We apply a synthetic biology strategy to improve AMP production in Streptomyces lividans, with fermentation titers of 52 mg L-1, a 500-fold improvement over the original strain. Furthermore, we develop an efficient and practical chemical process for converting AMP to glyphosate. Our findings highlight one greenness-driven alternative in the production of glyphosate.


Sex and litter effects on anxiety and DNA methylation levels of stress and neurotrophin genes in adolescent rats.
Maternal care variations associate with DNA methylation of the glucocorticoid receptor gene, Nr3c1, in hippocampus at a nerve-growth factor-inducible protein 1 binding site. Epigenetic regulation of brain-derived neurotrophin factor is affected by early stress. These systems contribute to anxiety and fear. Early stress has sex-dependent effects perhaps reflecting sex differences in maternal care. Altering litter gender composition affects maternal behavior and DNA methylation levels of another gene in hippocampus and nucleus accumbens (NAc). We now test if DNA methylation levels of Nr3c1, Egr1, and Bdnf differ by litter composition or sex. Rats from mixed- or single-sex litters were tested for anxiety and fear on postnatal day 35. Brain tissues were collected and analyzed using direct sequencing methods. Females showed hypermethylation of Nr3c1 of hippocampal DNA and litter composition modified sex effects on methylation of Egr1 in NAc. Few differences were seen for Bdnf. LGC modified some sex differences in behavior.


Citrate milling of oxides: from poly-dispersed micron scale to nearly mono-dispersed nanoscale.
Complex (multivalent/mixed valent) oxides involving two or more cations (e.g. ABO3, AB2O4 and A2B2O7) exhibit the most fascinating range of physical and chemical properties amongst the family of materials systems. There is growing interest in nanoscale forms of such oxides which emanates from the novel changes in their properties with size. To obtain nanomaterials with a high degree of crystallinity it is desirable to first make crystalline oxide powders by high temperature processing and then mill them down to nanometer size. In this paper we show that simple citric acid treatment of BiFeO3 and Bi2O3 powders leads to the desired micron-scale to nanoscale transformation, yielding nearly monodispersed nanoparticles. Importantly, these are highly dispersible and stable in water. By performing similar experiments on Fe3O4 and Fe2O3 we have elucidated the possible mechanism, which hinges on valence-controlled dissolution and ripening phenomena.


[Expression of signaling pathway of mammalian target of rapamycin in articular cartilage cell induced by interleukin 1β].
Objective: To observe effect of interleukin(IL)-1β on the expression of signaling pathway of mammalian target of rapamycin(mTOR) of articular cartilage. Methods: Articular cartilage of rats was isolated under sterile technique, cells were digested by type Ⅱ collagenase and trypsin and cultured in vitro, pre-culture the Ⅱ cells for three days, different concentrations of IL-1β were added for 24 hours.The cells were stained with toluidine blue and HE, to observe morphological changes of cells.RT-PCR was used to detect the mRNA expression of typeⅡcollagen gene, aggrecan gene, mTOR gene and P70S6K gene, Western blotting was used to detect the expression of protein related to mTOR. Results: With increasing concentrations of IL-1β, the phenotype of cells appeared polygon into a spindle, the mRNA expression of gene of type Ⅱ collagen (the control group: 0.821±0.014; 1 ng/ml: 0.614±0.014; 10 ng/ml: 0.549±0.009; 100 ng/ml: 0.520±0.008), aggrecan(0.867±0.005; 0.857±0.001; 0.554±0.008; 0.538±0.004) and mTOR(0.845±0.015; 0.785±0.009; 0.569±0.025; 0.518±0.014) reduced, but P70S6K(0.465±0.024; 0.566±0.022; 0.663±0.022; 0.896±0.015) increased by PCR .Expression of protein detected by Western blotting was similar to the trend of PCR. Conclusion: mTOR signaling pathway may play an important role on the degeneration of articular cartilage, regulating mTOR signaling pathway may provides a new idea of delaying the degeneration process of cells.


Four danger response programs determine glomerular and tubulointerstitial kidney pathology: clotting, inflammation, epithelial and mesenchymal healing.
Renal biopsies commonly display tissue remodeling with a combination of many different findings. In contrast to trauma, kidney remodeling largely results from intrinsic responses, but why? Distinct danger response programs were positively selected throughout evolution to survive traumatic injuries and to regenerate tissue defects. These are: (1) clotting to avoid major bleeding, (2) immunity to control infection, (3) epithelial repair and (4) mesenchymal repair. Collateral damages are acceptable for the sake of host survival but causes for kidney injury commonly affect the kidneys in a diffuse manner. This way, coagulation, inflammation, deregulated epithelial healing or fibrosis contribute to kidney remodeling. Here, I focus on how these ancient danger response programs determine renal pathology mainly because they develop in a deregulated manner, either as insufficient or overshooting processes that modulate each other. From a therapeutic point of view, immunopathology can be prevented by suppressing sterile renal inflammation, a useless atavism with devastating consequences. In addition, it appears as an important goal for the future to promote podocyte and tubular epithelial cell repair, potentially by stimulating the differentiation of their newly discovered intrarenal progenitor cells. By contrast, it is still unclear whether selectively targeting renal fibrogenesis can preserve or bring back lost renal parenchyma, which would be required to maintain or improve kidney function. Thus, renal pathology results from ancient danger responses that evolved because of their evolutional benefits upon trauma. Understanding these causalities may help to shape the search for novel treatments for kidney disease patients.


Phage Targeting Neonatal Meningitis E. coli K1 In Vitro in the Intestinal Microbiota of Pregnant Donors and Impact on Bacterial Populations.
Escherichia coli K1 is a leading cause of neonatal meningitis. The asymptomatic carriage of these strains in the maternal intestinal microbiota constitutes a risk of vertical transmission to the infant at birth. The aim of this work was to evaluate the efficacy of phage therapy against E. coli K1 in an intestinal environment and its impact on the intestinal microbiota. For this purpose, three independent experiments were conducted on the SHIME® system, the first one with only the phage vB_EcoP_K1_ULINTec4, the second experiment with only E. coli K1 and the last experiment with both E. coli K1 and the phage. Microbiota monitoring was performed using metagenetics, qPCR, SCFA analysis and the induction of AhR. The results showed that phage vB_EcoP_K1_ULINTec4, inoculated alone, was progressively cleared by the system and replicates in the presence of its host. E. coli K1 persisted in the microbiota but decreased in the presence of the phage. The impact on the microbiota was revealed to be donor dependent, and the bacterial populations were not dramatically affected by vB_K1_ULINTec4, either alone or with its host. In conclusion, these experiments showed that the phage was able to infect the E. coli K1 in the system but did not completely eliminate the bacterial load.


Mean Organ Doses Resulting From Non-Human Primate Whole Thorax Lung Irradiation Prescribed to Mid-Line Tissue.
Multi-organ dose evaluations and the effects of heterogeneous tissue dose calculations have been retrospectively evaluated following irradiation to the whole thorax and lung in non-human primates (NHP). A clinical-based approach was established to evaluate actual doses received in the heart and lungs during whole thorax lung irradiation. Anatomical structure and organ densities have been introduced in the calculations to show the effects of dose distribution through heterogeneous tissue. Mean organ doses received by non-human primates undergoing whole thorax lung irradiations were calculated using a treatment planning system that is routinely used in clinical radiation oncology. The doses received by non-human primates irradiated following conventional dose calculations have been retrospectively reconstructed using computerized tomography-based, heterogeneity-corrected dose calculations. The use of dose volume descriptors for irradiation to organs at risk and tissue exposed to radiation is introduced. Mean and partial-volume doses to lung and heart are presented and contrasted. The importance of exact dose definitions is highlighted, and the relevance of precise dosimetry to establish organ-specific dose response relationships in NHP models of acute and delayed effects of acute radiation exposure is emphasized.


In situ Growth of Cu2O/CuO Nanosheets on Cu Coating Carbon Cloths as a Binder-Free Electrode for Asymmetric Supercapacitors.
Cu2O/CuO nanosheets in-situ grown on Cu-Carbon cloths (Cu-CCs), namely Cu2O/CuO@Cu-CCs, are constructed by a simple strategy with electroless copper plating, chemical etching, and thermal dehydration. The as-prepared material is directly used as binder-free electrodes for supercapacitors (SCs). CCs coated with Cu, as the current collector, can effectively promote the charge collection and electron transfer, while the hierarchical Cu2O/CuO nanosheets provide massive active sites for fast faradic reactions. The composite electrode exhibits high specific capacitance [1.71 F cm-2, equivalent to 835.2 F g-1, at the current density of 10 mA cm-2 (3.57 A g-1)]. The asymmetric supercapacitor device using Cu2O/CuO@Cu-CCs as the positive electrode and activated carbon as the negative electrode, achieves a superior energy density up to 60.26 Wh kg-1 at a power density of 299.73 W kg-1 and an excellent long-term cycling stability (9.65% loss of its initial capacitance after 5,000 cycles). The excellent electrochemical performance is mainly ascribed to the unique hierarchical structure of Cu2O/CuO@Cu-CCs, making it attractive as a potential electrode material for high performance SCs.


Clear cell sarcoma of the kidney in a 4-month-old infant: a case report.
A case of clear cell sarcoma of the kidney is described in a 4-month-old male infant. The tumor had a typical histological pattern, consisting of sheets of tumor cells possessing "empty" nuclei set within a delicate capillary network. There was extensive necrosis and tumor cell cytoplasm contained vimentin. This tumor occurs only rarely in infants less than six months of age. The different renal neoplasms of childhood have diverse prognoses and demand specific therapy so that accurate diagnosis is mandatory. The present case illustrates that clear cell sarcoma, a highly malignant neoplasm, must be considered in the differential diagnosis of a renal mass occurring in this age group.


The impact of iron on the bleaching efficacy of hydrogen peroxide in liquid whey systems.
Whey is a value-added product that is utilized in many food and beverage applications for its nutritional and functional properties. Whey and whey products are generally utilized in dried ingredient applications. One of the primary sources of whey is from colored Cheddar cheese manufacture that contains the pigment annatto resulting in a characteristic yellow colored Cheddar cheese. The colorant is also present in the liquid cheese whey and must be bleached so that it can be used in ingredient applications without imparting a color. Hydrogen peroxide and benzoyl peroxide are 2 commercially approved chemical bleaching agents for liquid whey. Concerns regarding bleaching efficacy, off-flavor development, and functionality changes have been previously reported for whey bleached with hydrogen peroxide and benzoyl peroxide. It is very important for the dairy industry to understand how bleaching can impact flavor and functionality of dried ingredients. Currently, the precise mechanisms of off-flavor development and functionality changes are not entirely understood. Iron reactions in a bleached liquid whey system may play a key role. Reactions between iron and hydrogen peroxide have been widely studied since the reaction between these 2 relatively stable species can cause great destruction in biological and chemical systems. The actual mechanism of the reaction of iron with hydrogen peroxide has been a controversy in the chemistry and biological community. The precise mechanism for a given reaction can vary greatly based upon the concentration of reactants, temperature, pH, and addition of biological material. In this review, some hypotheses for the mechanisms of iron reactions that may occur in fluid whey that may impact bleaching efficacy, off-flavor development, and changes in functionality are presented. Cheese whey is bleached to remove residual carotenoid cheese colorant. Concerns regarding bleaching efficacy, off-flavor development, and functionality changes have been reported for whey proteins bleached with hydrogen peroxide and benzoyl peroxide. It is very important for the dairy industry to understand how whey bleaching can impact flavor and functionality of dried ingredients. Proposed mechanisms of off-flavor development and functionality changes are discussed in this hypothesis paper.


Barriers and facilitators to mental health promotion for Mexican immigrants in the U.S. through the Ventanillas de Salud program.
Mental health promotion and screenings are recommended as part of standard preventive care. Mexican immigrants in the U.S. are at high risk for mental health illness especially after the COVID-19 pandemic, however access to mental health prevention for this population has been limited, which results in important implementation and equity gaps. The Ventanilla de Salud (VDS) program provides preventive services through Mexican consulates in the U.S. The objective of this study was to assess capability, opportunity, and motivation for promotores to implement mental health programming through the VDS, leveraging early experiences of ongoing mental health prevention efforts. This was a qualitative study using the Capability, Opportunity, and Motivation for Behavior Change model (COM-B). We conducted 9 focus groups with 40 VDS promotores and 6 semi-structured interviews with program stakeholders. Data were analyzed using inductive and deductive coding. We found high levels of interest from the leadership, partners, and promotores to provide mental health services through the VDS. Early implementation of a mental health strategy that included training sessions for promotores and mental health promotion, screenings and referrals for VDS users was ongoing. We identified facilitators and barriers that could affect capability, opportunity, and motivation to provide mental health services. Facilitators included promotores' extensive knowledge about the importance of mental health, promotores service mindset and commitment to provide services to VDS users, and general support from the VDS network and partners. Barriers included promotores' turnover, need for additional economic compensation, burnout, competing priorities, and lack of mental health professionals to provide clinical services or supervision. Additional investments are recommended to support promotores' well-being. The main lesson learned from this study was that investing in VDS promotores' training, resources, and well-being is key to their capability, opportunity and motivation to provide mental health services for Mexican immigrants in the US. Results from this study can be applied to improve the ongoing VDS mental health strategy and increase its impact on the mental health of Mexican immigrants.


Recognition of the phenotype of thalidomide embryopathy in countries endemic for leprosy: new cases and review of the main dysmorphological findings.
Thalidomide is the best-known teratogen worldwide. It was first marketed as a sedative in the late 1950s, but the birth of ~10 000 children with birth defects resulted in the withdrawal of thalidomide from the market in 1962. Thalidomide embryopathy affects almost all organs but the main defects are concentrated in the limbs, eyes, ears, and heart. Shortly after the withdrawal of thalidomide from the market, its effectiveness in the treatment of erythema nodosum leprosum, an inflammatory condition resulting from leprosy, was reported and since the mid-1990s, the drug has been used widely in the treatment of cancers and autoimmune diseases, among other conditions. 40 000 new cases of leprosy are diagnosed every year in Brazil. Although there is a strict legislation for the prescription and use of thalidomide in Brazil, cases of thalidomide embryopathy have continued to be reported. Here, we present two new cases of thalidomide embryopathy identified in 2011 and review the major clinical findings in the literature that can aid the identification of the embryopathy.


Gas chromatography-mass spectrometry analysis of 4-O-methylpyridoxine (MPN) in the serum of patients with ginkgo seed poisoning.
The 4-O-methylpyridoxine (MPN) present in the seeds of the Ginkgo biloba (maidenhair tree) has anti-vitamin B6 actions, and ginkgo seed poisoning can induce convulsions. We developed a specific quantitative method using gas chromatography-mass spectrometry for the analysis of MPN in human serum. The trifluoroacyl (TFA) derivative of MPN was obtained by treating MPN with trifluoroacetic anhydride at 50 degrees C for 5 min and remained stable for 6 h. The calibration curve of standard MPN obtained in the selective ion mode using the base ion (m/z 343) was linear between 100 pg and 10 ng, and the detection limit was 50 pg. The full mass spectrum of 100 pg of the TFA derivative of MPN was obtained easily. MPN was extracted from the serum with the use of a C18 solid-phase extraction cartridge. The recovery rate of MPN added to the serum at a concentration of 0.1 microg/mL was 90.0%.


Discovery of cell-type specific DNA motif grammar in cis-regulatory elements using random Forest.
It has been observed that many transcription factors (TFs) can bind to different genomic loci depending on the cell type in which a TF is expressed in, even though the individual TF usually binds to the same core motif in different cell types. How a TF can bind to the genome in such a highly cell-type specific manner, is a critical research question. One hypothesis is that a TF requires co-binding of different TFs in different cell types. If this is the case, it may be possible to observe different combinations of TF motifs - a motif grammar - located at the TF binding sites in different cell types. In this study, we develop a bioinformatics method to systematically identify DNA motifs in TF binding sites across multiple cell types based on published ChIP-seq data, and address two questions: (1) can we build a machine learning classifier to predict cell-type specificity based on motif combinations alone, and (2) can we extract meaningful cell-type specific motif grammars from this classifier model. We present a Random Forest (RF) based approach to build a multi-class classifier to predict the cell-type specificity of a TF binding site given its motif content. We applied this RF classifier to two published ChIP-seq datasets of TF (TCF7L2 and MAX) across multiple cell types. Using cross-validation, we show that motif combinations alone are indeed predictive of cell types. Furthermore, we present a rule mining approach to extract the most discriminatory rules in the RF classifier, thus allowing us to discover the underlying cell-type specific motif grammar. Our bioinformatics analysis supports the hypothesis that combinatorial TF motif patterns are cell-type specific.