Male sex workers in Moscow, Russia: a pilot study of demographics, substance use patterns, and prevalence of HIV-1 and sexually transmitted infections.
The Russian federation has been undergoing a concentrated epidemic of HIV-1 with high rates of infection among injecting drug users. Less is known about the relative risk and contribution to the country's HIV epidemic by other at-risk populations including sex workers and men who have sex with men. The goals of this project were to explore demographic characteristics, substance use patterns, and estimate the prevalence of sexually transmitted infections (STIs) and high-risk behaviors among male sex workers (MSW) in Moscow and to assess the feasibility of prospective cohort recruitment and retention among this population. Research design was a longitudinal study of 50 men with a six-month follow-up period. Participants were recruited through venue-based and snowball sampling methods. Results revealed an HIV prevalence at baseline of 16%; one MSW seroconverted during the follow-up period, yielding an incidence estimate of 4.8/100PY (95%CI 0.0-11.2). Twenty-four percentage were diagnosed with at least one STI: 12% had syphilis; 8% had Human Papilloma Virus (HPV); and 4% had Herpes Simplex Virus (HSV)-2. Three (6%) of the study participants had evidence of previous Hepatitis C Virus (HCV) exposure at baseline. Retention rates were poor with higher retention significantly associated with older men (OR: 13.1, 95% CI 3.3-52.5). This was the first study to evaluate baseline demographics, substance use patterns, and prevalence of infectious disease among MSW in Moscow. Identification and recruitment of this population appears to be feasible, but retention a challenge. While the sample size in the current study was small, the results also suggested that this is a population at considerable high risk for HIV. MSW in Moscow may be an important at-risk population in the Russian HIV epidemic and further research is urgently required to address their needs and explore prevention strategies.


Comparative effectiveness research in the United States: a progress report.
The United States, with vast resources devoted to medical care, is investing in a new approach designed to improve health care efficiency. The conduct and reporting of comparative effectiveness research (CER) promises to help clinicians, payers, patients and other stakeholders make better and more informed decisions. Expectations for CER are high and public and private investments are sizeable. This paper discussions the evolution of CER in the US and gives a brief report on its progress and challenges.


Transglutaminase IgA antibodies in a celiac disease mass screening and the role of HLA-DQ genotyping and endomysial antibodies in sequential testing.
The aim of this study was to evaluate hypothetical screening strategies in a Swedish celiac disease (CD) mass screening. Of 10,041 Swedish sixth graders born in 1993 invited to a population-based CD mass screening, 7208 participated. Anti-tissue transglutaminase (tTG) immunoglobulin (Ig) A were analyzed in all children and total serum IgA (s-IgA) in 7161 children. Additional analyses of tTG-IgG, endomysial antibodies (EMA) IgA and IgG, and human leukocyte antigen (HLA) alleles were performed according to a standardized protocol. Children with elevated levels of serological markers were recommended to undergo a small intestinal biopsy to verify diagnosis, and 153 children with CD were thus identified. Sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs) were calculated and receiver operating characteristic curves were plotted. By lowering the cutoff for tTG-IgA, 17 additional cases of CD were identified at the cost of 32 biopsies. All children with tTG-IgA >50 U/mL (10 times the recommended upper limit of normal) had gluten enteropathy. Area under the receiver operating characteristic curve for tTG-IgA was 0.988. All cases carried HLA-DQ2 or HLA-DQ8, as did 53% of the controls. For different hypothetical screening strategies, sensitivity, specificity, PPV, and NPV ranged between 87.6% and 100%, 99.5% and 99.9%, 79.7% and 89.7%, and 99.7% and 100%, respectively. Efforts to increase sensitivity by lowering tTG-IgA cutoff would result in increased number of small intestinal biopsies and lower PPV. Sequential testing for both EMA and HLA-DQ genotyping would reduce the number of negative small intestinal biopsies. tTG-IgA is a robust marker when used in CD mass screening and its performance can be enhanced by sequential testing for EMA or HLA-DQ genotyping.


Valine 375 and phenylalanine 109 confer affinity and specificity for pyruvate as donor substrate in acetohydroxy acid synthase isozyme II from Escherichia coli.
Acetohydroxy acid synthase (AHAS) is a thiamin diphosphate-dependent enzyme that catalyzes the condensation of pyruvate with either another pyruvate molecule (product acetolactate) or 2-ketobutyrate (product acetohydroxybutyrate) as the first common step in the biosynthesis of branched-chain amino acids in plants, bacteria, algae, and fungi. AHAS isozyme II from Escherichia coli exhibits a 60-fold higher specificity for 2-ketobutyrate (2-KB) over pyruvate as acceptor, which was shown to result from a stronger hydrophobic interaction of the ethyl substituent of 2-KB with the side chain of Trp464 in multiple, apparently committed steps of catalysis. Here, we have elucidated the molecular determinants conferring specificity for pyruvate as the sole physiological donor substrate. Structural studies and sequence alignments of the POX subfamily of ThDP enzymes that act on pyruvate indicate that a valine and a phenylalanine hydrophobically interact with the methyl substituent of pyruvate. Kinetic and thermodynamic studies on AHAS isozyme II variants with substitutions at these positions (Val375Ala, Val375Ile, and Phe109Met) were carried out. While Val375 variants exhibit a slightly reduced k(cat) with a moderate increase of the apparent K(M) of pyruvate, both substrate affinity and k(cat) are significantly compromised in AHAS Phe109Met. The specificity for 2-ketobutyrate as acceptor is not altered in the variants. Binding of acylphosphonates as analogues of donor substrates was analyzed by circular dichroism spectroscopy and stopped-flow kinetics. While binding of the pyruvate analogue is 10-100-fold compromised in all variants, Val375Ala binds the 2-KB analogue better than the wild type and with higher affinity than the pyruvate analogue, suggesting steric constraints imposed by Val375 as a major determinant for the thermodynamically favored binding of pyruvate in AHAS. NMR-based intermediate analysis at steady state reveals that a mutation of either Val375 or Phe109 is detrimental for unimolecular catalytic steps in which tetrahedral intermediates are involved, such as substrate addition to the cofactor and product liberation. This observation implies Val375 and Phe109 to not only conjointly mediate substrate binding and specificity but moreover to ensure a proper orientation of the donor substrate and intermediates for correct orbital alignment in multiple transition states.


The Yin and the Yang of Prediction: An fMRI Study of Semantic Predictive Processing.
Probabilistic prediction plays a crucial role in language comprehension. When predictions are fulfilled, the resulting facilitation allows for fast, efficient processing of ambiguous, rapidly-unfolding input; when predictions are not fulfilled, the resulting error signal allows us to adapt to broader statistical changes in this input. We used functional Magnetic Resonance Imaging to examine the neuroanatomical networks engaged in semantic predictive processing and adaptation. We used a relatedness proportion semantic priming paradigm, in which we manipulated the probability of predictions while holding local semantic context constant. Under conditions of higher (versus lower) predictive validity, we replicate previous observations of reduced activity to semantically predictable words in the left anterior superior/middle temporal cortex, reflecting facilitated processing of targets that are consistent with prior semantic predictions. In addition, under conditions of higher (versus lower) predictive validity we observed significant differences in the effects of semantic relatedness within the left inferior frontal gyrus and the posterior portion of the left superior/middle temporal gyrus. We suggest that together these two regions mediated the suppression of unfulfilled semantic predictions and lexico-semantic processing of unrelated targets that were inconsistent with these predictions. Moreover, under conditions of higher (versus lower) predictive validity, a functional connectivity analysis showed that the left inferior frontal and left posterior superior/middle temporal gyrus were more tightly interconnected with one another, as well as with the left anterior cingulate cortex. The left anterior cingulate cortex was, in turn, more tightly connected to superior lateral frontal cortices and subcortical regions-a network that mediates rapid learning and adaptation and that may have played a role in switching to a more predictive mode of processing in response to the statistical structure of the wider environmental context. Together, these findings highlight close links between the networks mediating semantic prediction, executive function and learning, giving new insights into how our brains are able to flexibly adapt to our environment.


Flux driven automatic centerline extraction.
We present a fast, robust and automatic method for computing centerline paths through tubular structures for application to virtual endoscopy. The key idea is to utilize a skeletonization algorithm which exploits properties of the average outward flux of the gradient vector field of a Euclidean distance function from the boundary of the structure. The algorithm is modified to yield a collection of 3D curves, each of which is locally centered. The approach requires no user interaction, is virtually parameter free and has low computational complexity. We validate the method quantitatively on a number of synthetic data sets with known centerlines and qualitatively on colon and vessel data segmented from CT and CRA images.


E-cadherin expression: a diagnostic utility for differentiating breast carcinomas with ductal and lobular morphologies.
The objective of this study was to evaluate the diagnostic utility of the E-Cadherin (EC) expression in differentiating between an infiltrating ductal carcinoma (IDC) and an infiltrating lobular carcinoma (ILC), the two most common forms of invasive breast carcinomas. The authors evaluated the E-Cadherin expression by doing immunohistochemistical studies of all the cases of invasive lobular carcinomas (ILC) which were diagnosed in the pathology laboratory during a 3 year period and they compared the expression of E-Cadherin in an equal number of invasive ductal carcinomas (IDC) of the breast. A moderate to strong inter-membranous E-Cadherin expression on immunohistochemistry was seen in all the cases of IDC, while only 1 case of ILC showed a moderate E-Cadherin expression. Hence, the E-cadherin expression can be reliably used as a marker to differentiate IDC and ILC. However, an aberrant cytoplasmic expression of E-Cadherin may be seen in some cases of ILC, which should be interpreted with caution.


Thymus capitatus from Tunisian arid zone: chemical composition and in vitro anthelmintic effects on Haemonchus contortus.
The increasing prevalence of anthelmintic resistant strains of helminths, the drug residues in animal products and the high cost of conventional anthelmintics has created an interest in studying medicinal plants as an alternative source of anthelmintics. Thymus capitatus (Lamiales: Lamiaceae) is used traditionally by people as spices and reported to possess some biological effects. The objective of this study is to evaluate the anthelmintic efficacy of T. capitatus in comparison to albendazole against the gastrointestinal nematodes of sheep. To fulfil the objectives, in vitro anthelmintic activities of crude aqueous and crude ethanolic extracts of aerial parts of T. capitatus were investigated on the eggs and adults of the nematode parasite Haemonchus contortus. Both extract types of T. capitatus completely inhibited egg hatching at a concentration close to 2 mg/ml. LC₅₀ of ethanolic extract of T. capitatus was 0.368 mg/ml while that of aqueous extract was 6.344 mg/ml (p<0.05). The ethanolic extract showed higher in vitro activity against adult parasites than the aqueous one in terms of the paralysis and/or death of the worms at different hours post-treatment. Dose dependent effect was observed for both extracts. Chemical analyses revealed that the overall profile of both extracts was dominated by oxygenated constituents. In addition, ethanolic extract is mainly composed of phenols among which thymol (71.22%) and camphor (17.18%). As far as the literature could be ascertained, this is the first publication on anthelmintic activity of T. capitatus. The results of the present study suggest that T. capitatus extracts are a promising alternative to the commercially available anthelmintics like albendazole for the treatment of small ruminants' gastrointestinal nematodes.


Rh-PIP2;1, a rose aquaporin gene, is involved in ethylene-regulated petal expansion.
Aquaporins are water channel proteins that facilitate the passage of water through biological membranes and play a crucial role in plant growth. We showed that ethylene treatment significantly reduced petal size, inhibited expansion of petal abaxial subepidermal cells, and decreased petal water content in rose (Rosa hybrida 'Samantha'). Here, we report the isolation of a plasma membrane aquaporin (PIP) gene, Rh-PIP2;1, and characterized its potential role in ethylene-inhibited petal expansion. Rh-PIP2;1 is mainly localized on the plasma membrane and belongs to the class 2 subfamily of PIP proteins. We show that Rh-PIP2;1 is an active water channel. The transcripts of Rh-PIP2;1 are highly abundant in petal epidermal cells, especially in the abaxial subepidermal cells. The expression of Rh-PIP2;1 is highly correlated with petal expansion and tightly down-regulated by ethylene. Furthermore, we demonstrate that in Rh-PIP2;1-silenced flowers, petal expansion was greatly inhibited and anatomical features of the petals were similar to those of ethylene-treated flowers. We argue that Rh-PIP2;1 plays an important role in petal cell expansion and that ethylene inhibits petal expansion of roses at least partially by suppressing Rh-PIP2;1 expression.


Bacterial contamination of the vitreous cavity associated with transconjunctival 25-gauge microincision vitrectomy surgery.
To evaluate differences in the bacterial contamination rates of the vitreous cavity between patients undergoing transconjunctival 25-gauge microincision vitrectomy surgery (MIVS) and conventional 20-gauge pars plana vitrectomy (PPV). Prospective, comparative, consecutive, interventional case series. Eighty-one eyes of 81 patients who underwent primary vitrectomy and completed perioperative sample collection. Patients were randomly assigned to 25-gauge MIVS or 20-gauge PPV. Conjunctival swabs were obtained from each patient before and after preoperative administration of topical 0.5% moxifloxacin. Vitreous samples were collected at the beginning and end of surgery. All 4 consecutive specimens from each eye were cultured using direct culturing techniques under aerobic and anaerobic conditions. The primary outcome measure was the incidence of bacterial contamination of the vitreous cavity at the start and end of vitrectomy. The secondary measures were the incidence of bacterial contamination of the ocular surface and the disinfection rate with preoperative moxifloxacin. Of the 81 eyes (40 eyes in the 25-gauge MIVS group; 41 eyes in the 20-gauge PPV group), the incidences of positive bacterial isolation at the 4 time points of sample collection were 77.5%, 62.3%, 22.5%, and 0% in the former group and 82.9%, 63.4%, 2.4%, and 0% in the latter group. Although the rate of bacterial contamination of the ocular surface significantly (P<0.001) decreased after preoperative moxifloxacin administration in both groups, transconjunctival 25-gauge MIVS had a significantly (P = 0.007) higher incidence of vitreous contamination at the beginning of surgery compared with conventional 20-gauge PPV. The multivariate model showed that 25-gauge MIVS (odds ratio, 11.27; P = 0.027; 95% confidence interval, 1.31-96.79) was the factor prognostic of vitreous contamination at the beginning of surgery. Propionibacterium acnes was identified most often in the vitreous samples (80% of cases), which was consistent with the commensal bacteria isolated from the ocular surface. The higher incidence of bacterial contamination of the vitreous cavity at the beginning of 25-gauge MIVS suggests the increasing risk of direct inoculation of ocular surface flora into the vitreous cavity through the transconjunctival trocar-cannula system compared with conventional 20-gauge PPV. However, vitreous cavity contamination can be eliminated during vitrectomy in most cases. Proprietary or commercial disclosure may be found after the references.


Unintended consequences of being proactive? Linking proactive personality to coworker envy, helping, and undermining, and the moderating role of prosocial motivation.
Drawing upon social comparison theory, we developed and tested a model to examine potential negative coworker reactions toward proactive employees. We theorized that a focal employee's proactive personality is positively related with his or her high relative standing in the group, which in turn exposes him or her to being the target of coworker envy. This may then reduce the focal employee's received help from coworkers and give rise to coworker undermining. We further reasoned that employee prosocial motivation moderates the serial mediated relationships. Our hypotheses were generally supported in 3 field studies involving a total of 1,069 employees from 223 groups. Proactive personality was negatively and indirectly related to received help from coworkers, via relative leader-member exchange (RLMX) and relative job performance, and then via being envied by coworkers (Study 1). Results also generally supported the positive and indirect effect of proactive personality on coworker undermining via the same set of sequential mediators (e.g., RLMX and then being envied, Study 2). The indirect effects of proactive personality on coworker helping and undermining (e.g., via relative job performance and coworker envy) were only significant when employees' prosocial motivation was low (Study 3). This research contributes to a more complete and balanced theorization of the influences of proactive personality in organizations. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Salmonella enterica serovar-specific transcriptional reprogramming of infected cells.
Despite their high degree of genomic similarity, different Salmonella enterica serovars are often associated with very different clinical presentations. In humans, for example, the typhoidal S. enterica serovar Typhi causes typhoid fever, a life-threatening systemic disease. In contrast, the non-typhoidal S. enterica serovar Typhimurium causes self-limiting gastroenteritis. The molecular bases for these different clinical presentations are incompletely understood. The ability to re-program gene expression in host cells is an essential virulence factor for typhoidal and non-typhoidal S. enterica serovars. Here, we have compared the transcriptional profile of cultured epithelial cells infected with S. Typhimurium or S. Typhi. We found that both serovars stimulated distinct transcriptional responses in infected cells that are associated with the stimulation of specific signal transduction pathways. These specific responses were associated with the presence of a distinct repertoire of type III secretion effector proteins. These observations provide major insight into the molecular bases for potential differences in the pathogenic mechanisms of typhoidal and non-typhoidal S. enterica serovars.


Potency testing of up to twenty cannabinoids by liquid chromatography diode array detector with optional electrospray ionization time-of-flight mass spectrometry.
The growing popularity of Cannabis sativa L. and its widespread use for medical and recreational purposes have created an urgent demand of accurate and reliable analytical methods to identify and quantify a growing number of cannabinoids. To meet this demand, a liquid chromatography diode array detector (LC-DAD) method has been developed, validated, and applied in analysis of cannabinoids in nine samples of plant materials of marijuana, six samples of marijuana cigarettes, five samples of hemp flowers, one sample of hemp cigarette, and two samples of Δ8-tetrahydrocannabinol (Δ8-THC) fortified hemp flowers. The method has achieved significant improvements over published methods, which was characterized of 20 targeted cannabinoids, 18 quantified cannabinoids, baseline resolution among quantified cannabinoids, a low limit of quantification (0.02 μg mL-1), a wide linear range (0.02-25 μg mL-1 or 0.04-50% (w/w)), a unique experiment to track the recovery of sample preparation in real time by spiking abnormal cannabidiol (CBD), and a well-assessed specificity by electrospray ionization time-of-flight mass spectrometry (ESI/TOFMS). Precision and accuracy were assessed using quality control (QC) samples at three concentration levels, i.e., 0.02, 0.5, and 12.5 μg mL-1, in triplicates with inter-day and intra-day precision of less than 15% relative standard deviation (RSD) and accuracy of less than ±15% relative error, therefore meeting the requirements by the ISO 17025 standards. Additionally, ESI/TOFMS has discovered seven unknown cannabinoids, including one structural isomer of cannabigerol (CBG), one structural isomer of cannabinolic acid (CBNA), four structural isomers of Δ9-THC, and one structural isomer of Δ9-THC acetate. Furthermore, it uncovered that one of the two samples of Δ8-THC fortified hemp flowers contained 5.16% (w/w) Δ9-THC, an alarm to the current Δ8-THC craze by the public.


Correlation among smartphone addiction, craniovertebral angle, scapular dyskinesis, and selected anthropometric variables in physiotherapy undergraduates.
Smartphone addiction has been indicated to reduce the craniovertebral angle, thereby causing a forward head posture and increasing scapular dyskinesis. This study determined the correlation among smartphone addiction level, craniovertebral angle, scapular dyskinesis, and selected anthropometric variables in physiotherapy undergraduates. Seventy-seven participants were recruited from the Department of Physiotherapy, College of Medicine, University of Lagos, through a purposive sampling technique. The smartphone addiction level was assessed with the short version Smartphone Addiction Scale (English version). Craniovertebral and scapular dyskinesis were assessed using the photographic method. Descriptive and inferential statistics were used to analyse the data at an alpha level of 0.05. The analysis in this study revealed that many undergraduates are addicted to using smartphones. There was no significant difference in the addiction level (p = 0.367) and in scapular dyskinesis (p = 0.129) between male and female participants. However, there was a significant difference in craniovertebral angle (p = 0.032) between male and female participants. There was a significant relationship among smartphone addiction, craniovertebral angle (r = 0.306, p = 0.007), and scapular dyskinesis (r = 0.363, p = 0.007) in male and female participants. A high level of smartphone addiction reduces the craniovertebral angle and increases scapular dyskinesis. Therefore, the smartphone addiction level should be assessed in all patients with neck and shoulder pain to plan appropriate management.


Cervical cancer: Can it be prevented?
Cervical cancer prevention requires a multipronged approach involving primary, secondary and tertiary prevention. The key element under primary prevention is human papilloma virus (HPV) vaccination. So far, only prophylactic HPV vaccines which prevent HPV infection by one or more subtypes are commercially available. Therapeutic HPV vaccines which aid in clearing established infection are still under trial. Secondary prevention entails early detection of precancerous lesions and its success is determined by the population coverage and the efficacy of the screening technique. A number of techniques are in use, including cytology, visual inspection (using the naked eye, magnivisualizer, acetic acid and Lugol's iodine), HPV testing and a combination of these methods. Updated screening guidelines have been advocated by the American Cancer Society in light of the role of HPV on cervical carcinogenesis. Recent research has also focussed on novel biomarkers that can predict progression to cancer in screen positive women and help to differentiate those who need treatment from those who can be left for follow-up. Last but not the least, effective treatment of precancerous lesions can help to reduce the incidence of invasive cervical cancer and this constitutes tertiary prevention. A combination of these approaches can help to prevent the burden of cervical cancer and its antecedent morbidity and mortality, but all of these are not feasible in all settings due to resource and allocation constraints. Thus, all countries, especially low and middle income ones, have to determine their own cocktail of approaches that work before we can say with certainty that yes, cervical cancer can be prevented.


Theories of Change and Mediators of Psychotherapy Effectiveness in Adolescents With Externalising Behaviours: A Systematic Review.
Externalising behaviours are becoming a remarkably prevalent problem during adolescence, often precipitating both externalising and internalising disorders in later adulthood. Psychological treatments aim to increase the social functioning of adolescents in order for them to live a more balanced life and prevent these negative trajectories. However, little is known of the intervening variables and mediators involved in these treatments' change mechanisms. We conducted a systematic review, exploring the available evidence on mediators of psychological treatments for externalising behaviours and symptoms amongst adolescents (10 to 19 years old). A systematic search was performed on Medline and PsycINFO databases, which identified studies from inception to February 23, 2020. Eligible studies included randomised controlled trials that enrolled adolescents with externalising symptoms and behaviours as, at least, one of the primary outcomes. A group of 20 reviewers from the COST-Action TREATme (CA16102) were divided into 10 pairs. Each pair independently screened studies for inclusion, extracted information from the included studies, and assessed the methodological quality of the included studies and the requirements for mediators, following Kazdin's criteria. Risk of bias of RCTs was assessed by the Mixed Methods Appraisal Tool. Extracted data from the included studies were reported using a narrative synthesis. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA), after removing duplicates, 3,660 articles were screened. Disagreements were resolved by consensus. In a second stage, 965 full-text articles were assessed for eligibility. A total of 14 studies fulfilled all inclusion criteria. The majority were related to systemic psychological treatment approaches. Two types of mediators were identified as potentially being involved in the mechanisms of change for better social improvements of adolescents: to increase healthier parent-adolescent relationships and parental discipline. However, there were significant and non-significant results amongst the same mediators, which led to discussing the results tentatively. Family variables were found to be the largest group of investigated mediators, followed by relational, behavioural, and emotional variables. No cognitive or treatment-specific mediators were identified. Both adequate behavioural control of adolescents' peer behaviour and a better positive balance in their relationships with their parents seemed to buffer the effects of externalising behaviours in adolescents. Several methodological limitations concerning mediation testing design, outcome measures, and mediator selection have been identified. Ethical approval was not required. PROSPERO registration number: CRD42021231835.


Association between industry sponsorship and author conflicts of interest with outcomes of systematic reviews and meta-analyses of interventions for opioid use disorder.
Author conflicts of interest (COI) and industry sponsorship may lead to biased research results and conclusions. Considering the direct influence that systematic reviews have on patient care, including the management of patients being treated for opioid use disorders (OUD), these studies should be free of industry bias. Thus, we sought to determine whether a relationship exists between COI and the favorability of systematic review outcomes using a sample of systematic reviews regarding OUD interventions. We searched MEDLINE and Embase for systematic reviews and meta-analysis related to OUD treatment. The study team performed all data extraction in a masked duplicate fashion. We searched for undisclosed COI for each systematic review author in 3 databases--the CMS Open Payments database, Dollars for Profs, and the United States Patent and Trademark Office (USPTO). The research team quantified results using descriptive statistics. We evaluated associations between review characteristics using Fisher's exact tests, when possible. This article includes seventeen systematic reviews and meta-analyses with 81 authors. We found that 25 authors (30.9%) had some form of COI, and 22 (of 25, 88.0%) authors had an undisclosed COI. However, no significant association existed between COI and favorability of results and conclusions. Notably, two systematic reviews (of 17; 11.76%) were industry-sponsored. Similarly, we found no association between the study sponsor source and the favorability of systematic review results and conclusions. Our results suggest the favorability of systematic review results and conclusions are not influenced by author COI or industry sponsorship. However, nearly one-fourth of authors had an undisclosed COI, further emphasizing the need for standardization and adherence to COI disclosure policies within addiction medicine literature.


A dual-component carrier with both non-enzymatic and enzymatic antioxidant activity towards ROS depletion.
While ROS display crucial functions in many physiological processes, elevated ROS levels are also related to the initiation and progression of many severe diseases such as cancer, cardiovascular conditions or neurologic disorders. Research approaches to diminish ROS levels during disease progression are currently being focused on the therapeutic administration of antioxidant enzymes. However, enzyme administration suffers from several limitations including their fast elimination from blood upon administration, thus making crucial the development of enzyme encapsulating platforms. We have recently reported a multicompartment architecture constituted by two inherently different types of materials, i.e., polymeric microgels and liposomes. Poly(N-isopropylacrylamide-co-acrylic acid) microgels decorated with liposomes and subsequently coated by a protective poly(dopamine) shell (PDA) combine the benefits of both systems while minimizing some of their drawbacks. Herein, we exploit this dual-component platform as a microreactor for ROS depletion. We combine the intrinsic PDA's antioxidant properties with the encapsulation of the catalase enzyme within the liposomal compartments. The surface of the carrier is further functionalised with a poly(ethylene glycol) layer and the low fouling properties are demonstrated in terms of reduction of protein adsorption and cellular uptake. The potential of the carrier as an antioxidant microreactor is shown by its ability to deplete superoxide radicals and hydrogen peroxide, which can also take place in the presence of the two relevant cell lines.


Utilisation of intramyocellular lipids (IMCLs) during exercise as assessed by proton magnetic resonance spectroscopy (1H-MRS).
Recently, a 1H-MRS method became available to quantify intramyocellular lipids (IMCL) non-invasively. Currently, little is known about the regulation of this lipid pool. During prolonged exercise of moderate intensity, non-plasma-derived fatty acids play an important role as an energy source; lipids located within the skeletal muscle are considered to be a major source for these fatty acids. To see whether IMCL are reduced by exercise, 12 male runners were studied before and after exercising at different workloads and duration. Six subjects participated in a non-competitive run (NCR), three runners in a competitive half marathon (HM, 21 km) and another three in a competitive marathon (M, 42 km). Intra- and extramyocellular lipids were quantified by 1H-MR spectroscopy in the tibialis anterior (TA) and soleus (SOL) muscles prior to and after the exercise bout. Moderate intensity (MI; 60-70% VO2max in NCR) with a mean exercise time (MET) ranging between 105-110 min decreased IMCL by 10 - 36% in both muscles. Prolonged MI exercise (MET 210-240 min; 68-70% VO2max in M) reduced IMCL by 42-57% in TA and 27 - 56% in SOL. In contrast, high intensity exercise (HI; MET 80-120 min; 83-85% VO2max in HM) did not alter IMCL in either muscle. Extramyocellular lipids (EMCL) did not show any significant change in any group. The data show that one bout of moderate-intensity (60-70% VO2max) aerobic exercise markedly reduces the IMCL in TA and SOL muscles in a time-dependent fashion as assessed by 1H-MRS. However, exercise of similar duration but higher workload (> 80% VO2max) does not reduce IMCL. These data suggest that both exercise duration and workload are important factors in determining the reduction of IMCL.


Rapid determination of quaternary protein structures in complex biological samples.
The understanding of complex biological systems is still hampered by limited knowledge of biologically relevant quaternary protein structures. Here, we demonstrate quaternary structure determination in biological samples using a combination of chemical cross-linking, high-resolution mass spectrometry and high-accuracy protein structure modeling. This approach, termed targeted cross-linking mass spectrometry (TX-MS), relies on computational structural models to score sets of targeted cross-linked peptide signals acquired using a combination of mass spectrometry acquisition techniques. We demonstrate the utility of TX-MS by creating a high-resolution quaternary model of a 1.8 MDa protein complex composed of a pathogen surface protein and ten human plasma proteins. The model is based on a dense network of cross-link distance constraints obtained directly in a mixture of human plasma and live bacteria. These results demonstrate that TX-MS can increase the applicability of flexible backbone docking algorithms to large protein complexes by providing rich cross-link distance information from complex biological samples.


Corticotropin-releasing hormone (CRH) downregulates the function of its receptor (CRF1) and induces CRF1 expression in hippocampal and cortical regions of the immature rat brain.
In addition to regulating the neuroendocrine stress response, corticotropin-releasing hormone (CRH) has been implicated in both normal and pathological behavioral and cognitive responses to stress. CRH-expressing cells and their target neurons possessing CRH receptors (CRF1 and CRF2) are distributed throughout the limbic system, but little is known about the regulation of limbic CRH receptor function and expression, including regulation by the peptide itself. Because CRH is released from limbic neuronal terminals during stress, this regulation might play a crucial role in the mechanisms by which stress contributes to human neuropsychiatric conditions such as depression or posttraumatic stress disorder. Therefore, these studies tested the hypothesis that CRH binding to CRF1 influenced the levels and mRNA expression of this receptor in stress-associated limbic regions of immature rat. Binding capacities and mRNA levels of both CRF1 and CRF2 were determined at several time points after central CRH administration. CRH downregulated CRF1 binding in frontal cortex significantly by 4 h. This transient reduction (no longer evident at 8 h) was associated with rapid increase of CRF1 mRNA expression, persisting for >8 h. Enhanced CRF1 expression-with a different time course-occurred also in hippocampal CA3, but not in CA1 or amygdala, CRF2 binding and mRNA levels were not altered by CRH administration. To address the mechanisms by which CRH regulated CRF1, the specific contributions of ligand-receptor interactions and of the CRH-induced neuronal stimulation were examined. Neuronal excitation without occupation of CRF1 induced by kainic acid, resulted in no change of CRF1 binding capacity, and in modest induction of CRF1 mRNA expression. Furthermore, blocking the neuroexcitant effects of CRH (using pentobarbital) abolished the alterations in CRF1 binding and expression. These results indicate that CRF1 regulation involves both occupancy of this receptor by its ligand, as well as "downstream" cellular activation and suggest that stress-induced perturbation of CRH-CRF1 signaling may contribute to abnormal neuronal communication after some stressful situations.


Selectively Patterning Polymer Opal Films via Microimprint Lithography.
Large-scale structural color flexible coatings have been hard to create, and patterning color on them is key to many applications, including large-area strain sensors, wall-size displays, security devices, and smart fabrics. To achieve controlled tuning, a micro-imprinting technique is applied here to pattern both the surface morphology and the structural color of the polymer opal films (POFs). These POFs are made of 3D ordered arrays of hard spherical particles embedded inside soft shells. The soft outer shells cause the POFs to deform upon imprinting with a pre-patterned stamp, driving a flow of the soft polymer and a rearrangement of the hard spheres within the films. As a result, a patterned surface morphology is generated within the POFs and the structural colors are selectively modified within different regions. These changes are dependent on the pressure, temperature, and duration of imprinting, as well as the feature sizes in the stamps. Moreover, the pattern geometry and structural colors can then be further tuned by stretching. Micropattern color generation upon imprinting depends on control of colloidal transport in a polymer matrix under shear flow and brings many potential properties including stretchability and tunability, as well as being of fundamental interest.


Thymus transplantation, a critical factor for correction of autoimmune disease in aging MRL/+mice.
MRL/MP-+/+ (MRL/+) mice develop pancreatitis and sialoadenitis after they reach 7 months of age. Conventional bone marrow transplantation has been found to be ineffective in the treatment of these forms of apparent autoimmune disease. Old MRL/+ mice show a dramatic thymic involution with age. Hematolymphoid reconstitution is incomplete when fetal liver cells (as a source of hemopoietic stem cells) plus fetal bone (FB; which is used to recruit stromal cells) are transplanted from immunologically normal C57BL/6 donor mice to MRL/+ female recipients. Embryonic thymus from allogeneic C57BL/6 donors was therefore engrafted along with either bone marrow or fetal hematopoietic cells (FHCs) plus fragments of adult or fetal bone. More than seventy percent of old MRL/+ mice (> 7 months) that had been given a fetal thymus (FT) transplant plus either bone marrow or FHCs and also bone fragments survived more than 100 days after treatment. The mice that received FHCs, FB, plus FT from allogeneic donors developed normal T cell and B cell functions. Serum amylase levels decreased in these mice whereas they increased in the mice that received FHCs and FB but not FT. The pancreatitis and sialoadenitis already present at the time of transplantations were fully corrected according to histological analysis by transplants of allogeneic FHCs, FB and FT in the MRL/+ mice. These findings are taken as an experimental indication that perhaps stem cell transplants along with FT grafts might represent a useful strategy for treatment of autoimmune diseases in aged humans.


Age bias in physicians' recommendations for physical activity: a behavioral model of healthcare utilization for adults with arthritis.
To examine whether age bias exists in physicians' recommendations for physical activity among individuals with arthritis. A cross-sectional sample with 33,071 U.S. adults, 45 years or older with physician-diagnosed arthritis was obtained from 2007 Behavioral Risk Factor Surveillance System Survey. We used logistic regression to examine physicians' recommendations for physical activity as a function of age controlling for gender, race, education, marital status, employment, income, health insurance, personal physician, emotional support, body mass index, activity limitations, health status, and comorbidities. Majority of individuals were females (65%), White (85%), had annual household income < $50,000 (67%), and with comorbidities (86%). Respondents were approximately equal across age groups: middle-aged group (53%) and older group (47%). About 36% were obese and 44% had activity limitations, and 44% did not receive any physicians' recommendations for physical activity. Results from logistic regression indicated older adults (≥ 65 years old) were less likely (OR = 0.87; 95% CI, 0.82-0.92) to receive physicians' recommendations for physical activity compared with the middle-aged group (45-64 years old). This study indicates that although the benefits associated with the physical activity is well recognized, there is age bias in physicians' recommendations for physical activity.


Intravitreal triamcinolone acetonide combined with subthreshold grid laser treatment for macular oedema in branch retinal vein occlusion: a pilot study.
To compare the effectiveness of subthreshold grid laser treatment (SGLT) with infrared micropulse diode laser alone or in combination with intravitreal triamcinolone injection (SGLT-IVTJ) for the treatment of macular oedema (MO) secondary to branch retinal vein occlusion (BRVO). Pilot randomised clinical trial including 24 patients (24 eyes) who were randomised either to the SGLT (13 eyes) or to SGLT-IVTJ (11 eyes). Complete ophthalmic examinations, including Early Treatment of Diabetic Retinopathy Study visual acuity, OCT and fluorescein angiography, were performed at the moment of the study entry and at 3-month intervals, with a planned follow-up of 12 months. Main outcome measures were the decrease in mean foveal thickness (MFT) on OCT, and the proportion of eyes that gained at least 10 letters (approximately two or more lines of visual acuity gain) at the 12-month examination. Secondary outcomes were the decrease in mean total macular volume on OCT, and the timing of MO resolution. The change in MFT from the initial values was statistically significant for the SGLT-IVTJ from the 3-month examination and for the SGLP from the 6-month examination (p<0.001). At the 12-month evaluation, 10 patients of the SGLT-IVTJ group (91%) and eight of the SGLT group (62%) gained at least 10 letters (two lines) in visual acuity. The mean number of lines gained was 3.4 and 1.3 in the SGLT-IVTJ and in the SGLT group, respectively. The combined SGLT-IVT treatment of MO secondary to BRVO allows a significant visual acuity improvement, when compared with simple grid laser treatment.


How exposure to chronic stress contributes to the development of type 2 diabetes: A complexity science approach.
Chronic stress contributes to the onset of type 2 diabetes (T2D), yet the underlying etiological mechanisms are not fully understood. Responses to stress are influenced by earlier experiences, sex, emotions and cognition, and involve a complex network of neurotransmitters and hormones, that affect multiple biological systems. In addition, the systems activated by stress can be altered by behavioral, metabolic and environmental factors. The impact of stress on metabolic health can thus be considered an emergent process, involving different types of interactions between multiple variables, that are driven by non-linear dynamics at different spatiotemporal scales. To obtain a more comprehensive picture of the links between chronic stress and T2D, we followed a complexity science approach to build a causal loop diagram (CLD) connecting the various mediators and processes involved in stress responses relevant for T2D pathogenesis. This CLD could help develop novel computational models and formulate new hypotheses regarding disease etiology.


A review of the drug events reported by 12,917 patients treated with cephalexin.
This paper reviews the adverse events reported by 12,917 patients treated with cephalexin in formal clinical trials. Six percent of all patients reported adverse events, and in 3% the association with the drug was thought to be definite or probable. In the remaining 3%, the relationship was uncertain. The gastrointestinal system was most commonly involved, with diarrhoea being reported by 164 patients. Patients in the upper and lower age ranges reported more events than those in the middle range, and most events were reported 6-15 days after treatment started. Patients who received cephalexin 4 times a day reported more events than those who were treated twice daily. Four hundred and sixty-two patients had a known sensitivity to penicillin, and all except 21 of these were treated with cephalexin without developing a sensitivity reaction.


Medicolegal issues and ergogenic aids: trade, tragedy, and public safety, the example of ephedra and the Dietary Supplement Health and Education Act.
On February 6, 2004, the US Food and Drug Administration banned dietary supplements containing ephedrine alkaloids (ephedra) pending Congressional review. The ban culminates a 7-year regulatory process, the first of its kind under the Dietary Supplement Health and Education Act (DSHEA). This paper reviews that process, and the governing rules of DSHEA, within the contexts of modern science and the history of food and drug legislation. The example of ephedra reflects a longstanding conflict between trade and safety and suggests inherent weaknesses within DSHEA that place the public at risk.


[Utility of the Abeona Health® app for patient participation in the identification of chemotherapy-induced toxicity according to the CTCAE classification].
Since 2003, the National Cancer Institute (NCI) of the United States of America has been one of the world leaders in classifying adverse effects (AEs). Currently, smartphones allow, among many other things, the monitoring of these AEs of chemotherapy from home to improve the safety and quality of life of patients. The aim was to perform a descriptive comparative analysis of the AEs content of the Abeona Health® app and the latest version of the CTCAE (Common Terminology Criteria for Adverse Events). The Abeona Health® app and the CTCAE v5 guide were used. Subsequently, the most recurrent AEs in the existing chemotherapy treatment were analysed according to the NCI and the Spanish Society of Medical Oncology (SEOM) and finally, whether patients could identify them. The CTCAE v5 (collects 837 AEs), where two hundred and twenty-five are signs and symptoms. The NCI classifies fifty-five signs and symptoms as the most recurrent, and the SEOM sixteen, of which fifteen coincide with the NCI. The Abeona Health® application has seven AEs, all included in the CTCAE v5. Of these seven, six appear in the NCI lists of most recurrent AEs and four in the SEOM list, all identifiable by the patient. The Abeona Health® app is considered adequate for the patient participation in their self-care, although some fields could be expanded.


Personality disorders in cluster headache: a study using the Millon Clinical Multiaxial Inventory-III.
A great deal of studies suggests that cluster headache (CH) patients are usually comorbid to anxiety-mood spectrum disorders and psychopathological symptoms; however, the personality profiles reported in the literature strictly depend on type of assessment used. Psychiatric comorbidities have been extensively studied in migraine and they are recognized to represent a major risk factor associated with poorer outcome, playing a role in the headache chronification process at once as cause and consequence of it. By contrast the incidence and role of psychopathological aspects in CH is still not clarified, insufficiently explored as the striking severity of such a physical pain apparently leaves no room to psychological explanations. The aim of the present study is to describe psychopathological aspects of CH patients by means of the Millon Clinical Multiaxial Inventory-III (MCMI-III), a psychological assessment tool compatible to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) that correlates personality disorders (PDs) and clinical syndromes. We included all consecutive inward patients with CH between January 2014 and December 2016. Patients were evaluated using the MCMI-III a validated inventory assessing 14 PDs Scales (coordinate with DSM-IV Axis II disorders) and ten Clinical Syndrome Scales (coordinate with DSM-IV Axis I disorders). Twenty-six CH patients (24 chronic CH) were tested. Personality disorders were present in 92% of the patients. The most frequent PDs were: obsessive-compulsive (30.8%), histrionic (26.9%), narcissistic (11.5%), paranoid (11.5%) and avoidant (11.5%). According to the MCMI-III, patients with CH showed a high prevalence of personality disorders (Axis II-DSM-IV). PDs in CH patients can play an important role in determining CH course toward chronification. These preliminary results suggest that behavioral treatments can find room to support more conventional drug and neurostimulation therapies in these patients. In addition, the very high prevalence of PDs in our patients suggests that CH could in some cases be considered among the spectrum of somatoform and pain syndromes in patients with PDs.


Impact of lower atmospheric carbon dioxide on tropical mountain ecosystems
Carbon-isotope values of bulk organic matter from high-altitude lakes on Mount Kenya and Mount Elgon, East Africa, were 10 to 14 per mil higher during glacial times than they are today. Compound-specific isotope analyses of leaf waxes and algal biomarkers show that organisms possessing CO2-concentrating mechanisms, including C4 grasses and freshwater algae, were primarily responsible for this large increase. Carbon limitation due to lower ambient CO2 partial pressures had a significant impact on the distribution of forest on the tropical mountains, in addition to climate. Hence, tree line elevation should not be used to infer palaeotemperatures.


Joint quantification of transmission dynamics and diagnostic accuracy applied to influenza.
The influenza A (H1N1) pandemic 2009 posed an epidemiological challenge in ascertaining all cases. Although the counting of all influenza cases in real time is often not feasible, empirical observations always involve diagnostic test procedures. This offers an opportunity to jointly quantify transmission dynamics and diagnostic accuracy. We have developed a joint estimation procedure that exploits parsimonious models to describe the epidemic dynamics and that parameterizes the number of test positives and test negatives as a function of time. Our analyses of simulated data and data from the empirical observation of interpandemic influenza A (H1N1) from 2007-08 in Japan indicate that the proposed approach permits a more precise quantification of the transmission dynamics compared to methods that rely on test positive cases alone. The analysis of entry screening data for the H1N1 pandemic 2009 at Tokyo-Narita airport helped us quantify the very limited specificity of influenza-like illness in detecting actual influenza cases in the passengers. The joint quantification does not require us to condition diagnostic accuracy on any pre-defined study population. Our study suggests that by consistently reporting both test positive and test negative cases, the usefulness of extractable information from routine surveillance record of infectious diseases would be maximized.


Analysis of Screening Electrocardiogram for the Subcutaneous Defibrillator in Adults with Congenital Heart Disease.
Candidates for the subcutaneous implantable cardioverter-defibrillator (S-ICD) are screened using an electrocardiogram (S-ECG) tool to measure appropriate detection. We sought to define the S-ICD candidacy of congenital heart disease patients using the S-ECG tool. We also analyzed the reliability of the (S-ECG) tool between measurers in this population. Patients above the age of 12 and with a diagnosis associated with either a higher incidence of cardiac arrest or vascular access challenges were asked to undergo screening. S-ECGs were then analyzed by a pediatric electrophysiologist, an S-ICD device engineer, and an S-ICD clinical representative for candidacy. Results were compared for interobserver variability and S-ECGs were analyzed by t test to determine variables that differ among passing and failing leads. Thirty-one patients underwent screening. Two of the 31 (6.5%) patients failed S-ICD screening. Analysis of the screening leads demonstrated the highest passing rates using lead III at a 5 mm/mV amplitude setting with 71 and 62% pass rate in the supine and standing positions, respectively. Interobserver analysis correlated well among the three measurers. There was a higher amplitude difference between QRS and T waves among passing versus failing S-ECG. Congenital heart disease patients have acceptable passage rates utilizing the S-ECG algorithm. Interobserver measurements were well correlated and these data suggest that the proximal coil to device (lead III) vector would be best utilized in this patient population. A larger difference between QRS and T wave amplitudes was associated with a higher S-ECG passing rate.


Describing Racial Disparity in Hypertension Control in a Large Minnesota Outpatient Practice.
This analysis is a part of ongoing quality improvement efforts aiming at improving hypertension control among various racial minority groups seen in a large outpatient practice with a special focus on two war refugee populations, the Hmong and the Somali populations. Deidentified medical records were reviewed for adult hypertensive patients who had an outpatient encounter with a hypertension diagnosis during the years 2015 through 2019. The study outcome was the rate of uncontrolled hypertension, defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, and stratified by race, age, and gender. There were 752,504 patient records representing 259,824 unique patients (mean age 61 ± 13 years) with 49.1% women, 82.1% white 8.3% African American, 4% Asian, 1.6% Hispanic, Somali 0.6%, and 0.2% Hmong. Hmong men had the highest rate of uncontrolled HTN (33.6%) followed by African American (31.3%) then Somali (29.2%). Among women, African Americans had the highest rate (28.6%) followed by Hmong (28.5%) then Somali (25.7%). In all races except Somali, the rate of uncontrolled hypertension was highest in the 18-29 age group, decreased progressively over the next several decades, then increased again in the ≥70 age group. Hmong, African American, and Somali groups have the highest rates of uncontrolled hypertension. Efforts to address hypertension management need to be tailored to the specific characteristics of each racial group and to target young adults.


The Role of Palliative Medicine in Assessing Hereditary Cancer Risk.
Hereditary cancer assessment and communication about family history risks can be critical for surviving relatives. Palliative care (PC) is often the last set of providers before death. We replicated a prior study of the prevalence of hereditary cancer risk among patients with cancer receiving PC consultations, assessed the history in the electronic medical record (EMR), and explored patients' attitudes toward discussions about family history. This study was conducted at an academic urban hospital between June 2016 and March 2017. The average age of the 75 adult patients with cancer was 60 years, 49 (55%) male and 49 (65%) white. A total of 19 (25%) patients had no clear documentation of family history in the EMR, sometimes because no family history was included in the admission template or an automatically imported template lacked content. In all, 24 (32%) patients had high-risk pedigrees that merited referral to genetic services. And, 48 (64%) patients thought that PC was an appropriate venue to discuss the implications of family history. The mean comfort level in addressing these questions was high. At an academic center, 25% of patients had no family history documented in the EMR. And, 32% of pedigrees warranted referral to genetic services, which was rarely documented. There is substantial room for quality improvement for oncologists and PC specialists-often the last set of providers-to address family cancer risk before death and to increase use and ease of documenting family history in the EMR. Addressing cancer family history could enhance prevention, especially among high-risk families.


Intracellular processing and activation of membrane type 1 matrix metalloprotease depends on its partitioning into lipid domains.
The integral membrane type 1 matrix metalloprotease (MT1-MMP) is a pivotal protease in a number of physiological and pathological processes and confers both non-tumorigenic and tumorigenic cell lines with a specific growth advantage in a three-dimensional matrix. Here we show that, in a melanoma cell line, the majority (80%) of MT1-MMP is sorted to detergent-resistant membrane fractions; however, it is only the detergent-soluble fraction (20%) of MT1-MMP that undergoes intracellular processing to the mature form. Also, this processed MT1-MMP is the sole form responsible for ECM degradation in vitro. Finally, furin-dependent processing of MT1-MMP is shown to occur intracellularly after exit from the Golgi apparatus and prior to its arrival at the plasma membrane. It is thus proposed that the association of MT1-MMP with different membrane subdomains might be crucial in the control of its different activities: for instance in cell migration and invasion and other less defined ones such as MT1-MMP-dependent signaling pathways.


The efficacy of acupressure at the Sanyinjiao point in the improvement of women's general health.
This study's objective was to examine the effectiveness of Sanyinjiao point (SP6) acupressure on women's general health. This was a randomized, single-blind clinical trial. The setting for this trial was at Medical University, Bojnoord University of Medical Science, Bojnoord, Iran. Eighty-six (86) university students were recruited for this study. Their demographic characteristics were gathered before the intervention commenced. Participants completed General Health Questionnaires (GHQ) prior to participation. Next, they were randomly assigned to either the acupressure-receiving group or the sham-pressure-receiving group. The study group received acupressure at the Sanyinjiao point, while the control group received sham pressure. Both groups completed GHQ after both the first and second months of intervention. Data analysis was carried out using SPSS version 13.5 for Windows. The mean age of those who completed the study was 20.84±1.64 years. Mean scores of GHQs were similar between groups before intervention (p>0.05). The general health of participants in both groups improved after intervention, and the amelioration in four domains was significant in the groups (p<0.05 within group). It was found that acupressure was more effective than sham pressure. In addition, there was a statistically significant difference between the two groups in the four domains of their general heath after the first month of the intervention (p<0.0001). Furthermore, the general health status of the participants changed much more after the second month in both the acupressure intervention and the sham pressure groups; nevertheless, acupressure was more effective than sham pressure (p<0.05). Both acupressure and sham pressure were effective in promoting women's general health; nevertheless, the efficacy of acupressure was more than that of sham pressure. SP6 acupressure could be regarded as a self-manageable approach to improve women's general health.


Large-Area WS2 Film with Big Single Domains Grown by Chemical Vapor Deposition.
High-quality WS2 film with the single domain size up to 400 μm was grown on Si/SiO2 wafer by atmospheric pressure chemical vapor deposition. The effects of some important fabrication parameters on the controlled growth of WS2 film have been investigated in detail, including the choice of precursors, tube pressure, growing temperature, holding time, the amount of sulfur powder, and gas flow rate. By optimizing the growth conditions at one atmospheric pressure, we obtained tungsten disulfide single domains with an average size over 100 μm. Raman spectra, atomic force microscopy, and transmission electron microscopy provided direct evidence that the WS2 film had an atomic layer thickness and a single-domain hexagonal structure with a high crystal quality. And the photoluminescence spectra indicated that the tungsten disulfide films showed an evident layer-number-dependent fluorescence efficiency, depending on their energy band structure. Our study provides an important experimental basis for large-area, controllable preparation of atom-thick tungsten disulfide thin film and can also expedite the development of scalable high-performance optoelectronic devices based on WS2 film.


Feasibility and Effectiveness of Telelactation Among Rural Breastfeeding Women.
To evaluate the feasibility and impact of telelactation via personal electronic devices on breastfeeding duration and exclusivity among rural women. The Tele-MILC trial, a pragmatic, parallel design trial, recruited 203 women during their postpartum hospitalization in a critical access hospital in Pennsylvania and randomized them to receive telelactation (n = 102) or usual care (n = 101). We used intent-to-treat (ITT) and instrumental variable (IV) approaches to analyze study data for the 187 participants who completed follow-up. The primary outcomes were any breastfeeding and exclusive breastfeeding at 12 weeks postpartum. Among participants in the telelactation arm, 50% (47/94) reported participating in video calls. At 12 weeks, 71% of participants in the telelactation arm versus 68% of control participants were breastfeeding in the ITT model (3% difference, P = .73), whereas 73% of participants in the telelactation arm versus 68% of control participants were breastfeeding in the IV model (5% difference, P = .74). Among participants who were still breastfeeding at 12 weeks, 51% participants in the telelactation arm were breastfeeding exclusively versus 46% of control participants in the ITT model (5% difference, P = .47), whereas 56% of participants in the telelactation arm were breastfeeding exclusively versus 45% of control participants in the IV model (11% difference, P = .48). In all models, participants in the telelactation arm were breastfeeding at higher rates; however, differences were not statistically significant. This trial demonstrated that telelactation can be implemented with a rural underserved population. Though this trial was not powered to detect differences in breastfeeding duration and exclusivity, and none were observed, telelactation remains a promising approach for further investigation. ClinicalTrials.gov Identifier: NCT02870413.


Metabolomic profile in pancreatic cancer patients: a consensus-based approach to identify highly discriminating metabolites.
pancreatic adenocarcinoma is the fourth leading cause of cancer related deaths due to its aggressive behavior and poor clinical outcome. There is a considerable variability in the frequency of serum tumor markers in cancer' patients. We performed a metabolomics screening in patients diagnosed with pancreatic cancer. Two targeted metabolomic assays were conducted on 40 serum samples of patients diagnosed with pancreatic cancer and 40 healthy controls. Multivariate methods and classification trees were performed. Sparse partial least squares discriminant analysis (SPLS-DA) was used to reduce the high dimensionality of a pancreatic cancer metabolomic dataset, differentiating between pancreatic cancer (PC) patients and healthy subjects. Using Random Forest analysis palmitic acid, 1,2-dioleoyl-sn-glycero-3-phospho-rac-glycerol, lanosterol, lignoceric acid, 1-monooleoyl-rac-glycerol, cholesterol 5α,6α epoxide, erucic acid and taurolithocholic acid (T-LCA), oleoyl-L-carnitine, oleanolic acid were identified among 206 metabolites as highly discriminating between disease states. Comparison between Receiver Operating Characteristic (ROC) curves for palmitic acid and CA 19-9 showed that the area under the ROC curve (AUC) of palmitic acid (AUC=1.000; 95% confidence interval) is significantly higher than CA 19-9 (AUC=0.963; 95% confidence interval: 0.896-1.000). Mass spectrometry-based metabolomic profiling of sera from pancreatic cancer patients and normal subjects showed significant alterations in the profiles of the metabolome of PC patients as compared to controls. These findings offer an information-rich matrix for discovering novel candidate biomarkers with diagnostic or prognostic potentials.


Dietary SFAs and ω-6 Fatty Acids Alter Incorporation of ω-3 Fatty Acids into Milk Fat of Lactating CD-1 Mice and Tissues of Offspring.
Methods to increase the amount of omega-3 (n-3) PUFAs in milk are desirable for neonatal health. The n-3 PUFA, α-linolenic acid (18:3n-3), can be elongated to EPA (20:5n-3) and DHA (22:6n-3). n-6 PUFAs suppress tissue n-3 PUFA incorporation, but the effect of SFAs is not clear. In this study, we compared the effects of SFAs and n-6 PUFAs on n-3 PUFA incorporation into milk and tissues of lactating mice and tissues of their offspring. Female CD-1 mice were bred at 8 wk of age. All experimental diets included 3% flaxseed oil and were begun on day 8 of lactation: low-fat diet (LFD); high-SFA diet (SAT), with an additional 12% saturated oil; or high-linoleic-acid diet (HLA), with 12% high-linoleic-acid oil (% kcal, carbohydrates:fat:protein: LFD, 49:24:27; both SAT and HLA, 35:46:19; n = 5/treatment). After 5 d, pup stomach milk clot FA profiles, tissue FA profiles in dams and pups, and mammary and hepatic expression of lipid metabolism genes in dams were analyzed. Data were analyzed by ANOVA with treatment diet as a fixed effect. Dams in all groups had similar total milk fat concentrations, but both SAT and HLA decreased the concentration of n-3 PUFAs (SAT: -23%; HLA: -31%) compared with LFD, and HLA increased milk n-6 FAs by 347% compared with SAT. SAT pups had n-3 PUFA tissue concentrations similar to LFD, but HLA pups had lower n-3 PUFAs than SAT pups in multiple tissues (liver, -32%; kidney, -29%; heart, -28%; muscle, -18%). Mammary expression of lipid metabolism genes was mostly unchanged, but hepatic expression of elongases and desaturases was decreased with SAT compared with LFD [elongation of very-long-chain fatty acid (Elov)5, -42%; Elov6, -64%; fatty acid desaturase (Fads)1, -33%; Fads2, -44%]. HLA decreased n-3 PUFA concentrations across multiple pup tissues compared with SAT. This suggests that high dietary n-6 PUFAs suppress n-3 PUFA incorporation in neonates.


Automated segmentation of the knee for age assessment in 3D MR images using convolutional neural networks.
Age assessment is used to estimate the chronological age of an individual who lacks legal documentation. Recent studies indicate that the ossification degree of the growth plates in the knee joint correlates with chronological age of adolescents and young adults. To verify this hypothesis, a high number of datasets need to be analysed. An approach which enables an automated detection and analysis of the bone structures may be necessary to handle large datasets. The purpose of this study was to develop a fully automatic 2D knee segmentation based on 3D MR images using convolutional neural networks. A total of 76 datasets were available and divided into a training set (74%), a validation set (13%) and a test set (13%). Multiple preprocessing steps were applied to correct image intensity values and to reduce the image size. Image augmentation was employed to virtually increase the dataset size for training. The proposed architecture for the segmentation task resembles the encoder-decoder model type used for the U-Net. The trained network achieved a dice similarity coefficient score of 98% compared to the manual segmentations and an intersection over union of 96%. The precision and recall of the model were balanced, and the error was only 1.2%. No overfitting was observed during training. As a proof of concept, the predicted segmentations were used for the age estimation of 145 subjects. Initial results show the potential of this approach attaining a mean absolute error of 0.48 ± 0.32 years for a test set of 14 subjects. The proposed automated segmentation can contribute to faster, reproducible and potentially more reliable age estimation in the future.


DNA endoreplication in the brain neurons during body growth of an adult slug.
Endoreplication is DNA synthesis without cell division. Giant neurons observed in the brains of mollusks are thought to be generated as a result of DNA endoreplication. It has been hypothesized that neuronal size becomes larger in parallel with an increase in body size and that DNA endoreplication is involved in this process to meet the increasing demand for macromolecules in neurons. There is, however, no experimental evidence for this hypothesis to date. In the present study, we investigated the following quantitatively: (1) the size of the brain and each ganglion, (2) the size of identified neurons, (3) the total number of neurons undergoing DNA endoreplication, (4) the total number of the neurons containing a cardioexcitatory peptide, and (5) the gene expression level per neuron, using terrestrial slugs whose body growth was regulated through the amount of food supplied in the laboratory. The body growth was accompanied by increases in the sizes of both neurons and ganglia and triggered more frequent DNA endoreplication events in each ganglion of the growth-promoted slugs, without increasing the total number of neurons. Increase in the neuronal size also involved the increase in the amount of transcripts expressed in a single neuron. This is the first quantitative evidence showing that the DNA endoreplication, neuronal size, and gene expression are increased concomitantly with body growth in adult mollusks.


Insulin resistance is associated with gestational hypertension and not with preeclampsia: a population-based screening study.
To investigate the relationship between insulin resistance (IR) and subsequent gestational hypertension (GH) or preeclampsia (PE) in normoglycemic and in gestational diabetic pregnant women. Furthermore, we tested whether this association was independent of the prepregnancy body mass index (BMI). Each participant underwent a 75-gram oral glucose tolerance test (OGTT) according to World Health Organization recommendation criteria with determination of serum glucose and C-peptide concentrations. IR was determined as a C-peptide-to-glucose ratio at the fasting (FCGR) state and at 2 h (2CGR) after load. A total of 2,954 women were included with a singleton pregnancy, delivery at term, no chronic hypertension, and data on both glucose and C-peptide. Of these women, 183 (6.2%) developed GH and 49 (1.7%) PE. Gestational diabetes mellitus (GDM) was diagnosed in 6.0% of the participants. The FCGR and 2CGR were significantly higher in all women with GH, irrespective of their BMI, compared to the normotensive group; however, the PE and the normotensive groups had similar FCGR and 2CGR values. The present study suggests that IR at the OGTT is associated with the later development of GH; on the other hand, it is not associated with PE. These relationships are independent of the maternal BMI.


Adding fossil occupancy trajectories to the assessment of modern extinction risk.
Besides helping to identify species traits that are commonly linked to extinction risk, the fossil record may also be directly relevant for assessing the extinction risk of extant species. Standing geographical distribution or occupancy is a strong predictor of both recent and past extinction risk, but the role of changes in occupancy is less widely assessed. Here we demonstrate, based on the Cenozoic fossil record of marine species, that both occupancy and its temporal trajectory are significant determinants of risk. Based on extinct species we develop a model on the additive and interacting effects of occupancy and its temporal changes on extinction risk. We use this model to predict extinction risk of extant species. The predictions suggest a moderate risk for marine species on average. However, some species seem to be on a long-term decline and potentially at a latent extinction risk, which is not considered in current risk assessments.


Compensation of rotation effect in a combination of retarders.
In a cascaded system comprising a combination of oblique retarders, the effect of optical rotation is observed in addition to the overall retardation. This shows that the combined system does not behave as a pure oblique retarder. Analyzing such a general system using Pauli Spin matrices, it is shown that the effect of optical rotation may be completely annulled through the use of a suitably oriented retarder at the output of the cascaded system. The analysis assumes monochromaticity of the illuminating light beam.


Nestin and CD146 expression in metaplastic breast cancer: stem-cell therapy in need? Lessons reported from a male patient.
Metaplastic breast carcinomas represent a rare subtype of breast cancer exhibiting aggressive clinical features. They appear as highly chemoresistant tumors, therefore showing poor outcome and high rates of local recurrence or distant metastasis. A 37-year-old greek man was referred to our hospital for evaluation of a locally advanced, ulcerated, fixed, irregular and hard in consistency mass covering his left breast and chest wall. Further work out with CT and biopsy of the tumor revealed a triple negative metaplastic breast cancer classified as cT4cN3cM1. The patient received first line chemotherapy and afterward a palliative resection of the tumor. The histology revealed the presence of a combined triple negative adenocarcinoma with a predominant metaplastic squamous carcinoma and a spindle cell (sarcomatoid) carcinoma of the breast. In the tissue sample stem cell markers, nestin and CD146 (MCAM) were expressed, enhancing the theory that cancer cells of this tumor could possibly harbor stem cell properties. The patient received several chemotherapy regimens but died 6 months after the initiation of treatment. Metaplastic breast cancer consists of cells with stem cell properties. New targeted therapies are warranted in the view of the tumor's high resistance to conventional chemotherapy. Targeting nestin and CD146 might be a promising therapy as they seem to be implicated in the EMT pathway.


HuD RNA recognition motifs play distinct roles in the formation of a stable complex with AU-rich RNA.
Human neuron-specific RNA-binding protein HuD belongs to the family of Hu proteins and consists of two N-terminal RNA recognition motifs (RRM1 and -2), a hinge region, and a C-terminal RRM (RRM3). Hu proteins can bind to AU-rich elements in the 3' untranslated regions of unstable mRNAs, causing the stabilization of certain transcripts. We have studied the interaction between HuD and prototype mRNA instability elements of the sequence UU(AUUU)(n)AUU using equilibrium methods and real-time kinetics (surface plasmon resonance using a BIACORE). We show that a single molecule of HuD requires at least three AUUU repeats to bind tightly to the RNA. Deletion of RRM1 reduced the K(d) by 2 orders of magnitude and caused a decrease in the association rate and a strong increase in the dissociation rate of the RNA-protein complex, as expected when a critical RNA-binding domain is removed. In contrast, deletion of either RRM2 or -3, which only moderately reduced the affinity, caused marked increases in the association and dissociation rates. The slower binding and stabilization of the complex observed in the presence of all three RRMs suggest that a change in the tertiary structure occurs during binding. The individual RRMs bind poorly to the RNA (RRM1 binds with micromolar affinity, while the affinities of RRM2 and -3 are in the millimolar range). However, the combination of RRM1 and either RRM2 or RRM3 in the context of the protein allows binding with a nanomolar affinity. Thus, the three RRMs appear to cooperate not only to increase the affinity of the interaction but also to stabilize the formed complex. Kinetic effects, similar to those described here, could play a role in RNA binding by many multi-RRM proteins and may influence the competition between proteins for RNA-binding sites and the ability of RNA-bound proteins to be transported intracellularly.


Automatically parcellating the human cerebral cortex.
We present a technique for automatically assigning a neuroanatomical label to each location on a cortical surface model based on probabilistic information estimated from a manually labeled training set. This procedure incorporates both geometric information derived from the cortical model, and neuroanatomical convention, as found in the training set. The result is a complete labeling of cortical sulci and gyri. Examples are given from two different training sets generated using different neuroanatomical conventions, illustrating the flexibility of the algorithm. The technique is shown to be comparable in accuracy to manual labeling.


Dental caries and oral hygiene status: Survey of schoolchildren in rural communities, Southwest Nigeria.
Dental caries and poor oral hygiene cause pain and have an effect on activities of children such as playing, sleeping, eating and school attendance. Previous studies on the prevalence of dental caries and poor oral hygiene have focused more on urban than rural communities in the developing countries. The objective of the study was to assess dental caries and oral hygiene status of schoolchildren in rural communities. It was a cross-sectional study involving 778 schoolchildren from 12 public primary schools. A pre-tested, semi-structured interviewer-administered questionnaire was used to obtain information on socio-demographics and oral health practice. Dental caries was assessed using the decayed, missing and filled teeth (DMFT) index and oral hygiene status by the simplified oral hygiene and gingival indices. The mean age of the children was 11.0 ± 1.8 years, and the prevalence of dental caries was 12.2% with a mean DMFT/dmft of 0.2 ± 0.7. Children aged 10-12 years were 3 times more likely to have caries on ≥1 tooth (P = 0.01, confidence interval = 1.3-6.7). Herbal remedies were more often (35.3%) used to manage dental problems. The mean simplified oral hygiene and gingival indices were 1.7 ± 0.9 and 1.1 ± 0.5, respectively. The occurrence of dental caries appears to be increasing in rural Nigerian schoolchildren, but still within WHO limits. Oral hygiene status was poor and gingivitis was common.


Genetic parameters of calf morbidity and stayability for US organic Holstein calves.
The objectives of this study were to estimate genetic parameters of calf health in organic US Holstein calves. Calves were born on farms across the United States from 2006 to 2019. Three calf health traits were evaluated in the study: calf respiratory disease until 365 d of age, calf scours until 60 d of age, and heifer stayability until 365 d of age. For respiratory disease and scours, animals were assigned a phenotype of 0 if they were healthy and a phenotype of 1 if they were diseased. For stayability, animals were assigned a phenotype of 0 if they were removed from the herd by 365 d of age and 1 if they remained in the herd at 365 d of age. Genetic parameters were estimated from threshold models that included the fixed effects of mean, year-season of birth, and dam age (respiratory disease and scours only) as well as the random effects of herd-year of birth and additive genetics. Heritability estimates were 0.100, 0.075, and 0.085 for respiratory disease, scours, and stayability, respectively. Solutions for estimated breeding values for respiratory disease and scours were transformed from disease risk to disease resistance by reversing the signs before calculating genetic correlations such that higher values of scours, respiratory disease, and stayability were favored. There was a moderate favorable genetic correlation estimate between respiratory disease resistance and stayability of 0.675. However, genetic correlation estimates between respiratory disease resistance and scours resistance (0.148) and between scours resistance and stayability (0.165) were low. Estimated breeding value correlations between calf health traits and other traits evaluated nationally were generally low in magnitude. The strongest correlation estimates were with longevity, particularly between stayability and heifer livability (0.217) and between stayability and cow livability (0.288); respiratory disease resistance was also favorably correlated with heifer (0.190) and cow (0.178) livability. Correlations with cow health traits were generally low and unfavorable. Linear models including the random effect of herd-by-sire indicated that herd-by-sire accounted for approximately 2% of phenotypic variance for scours and stayability, which may indicate a genotype by environment interaction effect for these traits. In conclusion, there is significant genetic variation in organic calf health, and there was evidence of genotype by environment interaction.


Changing Patient Expectations Decreases Length of Stay in an Enhanced Recovery Program for THA.
The implementation of care pathways in hip arthroplasty programs has been shown to result in a decreased length of stay (LOS), but often multiple elements of a care pathway are implemented at the same time. As a result, it is difficult to understand the impact each of the individual modifications has made to the patient's prepathway care. In particular, it is unknown what the role of patient expectations pertaining to anticipated LOS alone is on the LOS after primary THA. (1) Does changing the patient's expectations regarding his or her anticipated LOS, without intentionally changing the rest of the care pathway, result in a change in the patient's LOS after primary THA? (2) Is the resultant LOS associated with the patient's age, gender, or day of the week the surgery was performed? We retrospectively compared the LOS in 100 consecutive patients undergoing THA immediately after the implementation of a 4-day care pathway (4-day Group) with 100 consecutive patients, 3 months later, who were also in the same pathway but were told by their surgeon preoperatively and in the hospital to expect a LOS of 2 days (2-day Group). Aside from reeducation by the surgeon, there was no difference in the surgery or intentional changes to the intraoperative or postoperative management of the two groups. Only the patient and the surgeon were made aware of the accelerated discharge plan. We compared the LOS between the two groups and the number of patients who met their discharge goal. As well, the ability to meet the discharge goal for each group was further determined based on age, gender, and day of the week the surgery was performed. Overall, patients in the 2-day Group had a shorter LOS than those in the 4-day Group (2.9 ± 0.88 days versus 3.9 ± 1.71 days; mean difference 1 day; 95% confidence interval [CI], 0.60-1.36; p = 0.001). In the 2-day Group, the LOS was 2 days in 32% compared with 8% in the 4-day Group (odds ratio, 4.0; 95% CI, 1.76-9.11; p < 0.001). Men in the 4-day Group had a shorter LOS than women (3.4 ± 1.22 days versus 4.2 ± 1.89 days; mean difference 0.8 days; 95% CI, 0.17-1.78; p = 0.019), but there was no difference in LOS by gender in the 2-day Group (2.8 ± 0.81 days versus 3.1 ± 0.93 days; mean difference 0.3 days; 95% CI, -0.14 to 0.61; p = 0.219). For all patients > 40 years and < 90 years of age, a greater percentage of patients in the 2-day Group went home by postoperative day 2 than those in the 4-day Group (32% compared with 7%; odds ratio, 4.6; p < 0.001). In both groups, there was no difference in the LOS if the surgery was on Friday compared with an earlier day of the week (4-day Group: 3.4 ± 0.67 days versus 4.0 ± 1.80 days; p = 0.477 and 2-day Group: 2.8 ± 0.62 days versus 3.0 ± 0.93 days; p = 0.547). We found that a surgeon who sets a clear expectation in terms of LOS could achieve a reduction in this parameter. Although it is impossible to be certain in the context of a retrospective study whether other caregivers adjusted the pathway in response to the surgeon's preferences, and we suspect this probably did occur, this still points to an opportunity on the topic of expectations setting that future studies should explore. This study highlights the influence patient education and expectations has on the effectiveness of care pathways in THA as well as the importance of continuous reinforcement of discharge planning both preoperatively and in the hospital. Level III, therapeutic study.


Shared genome analyses of notable listeriosis outbreaks, highlighting the critical importance of epidemiological evidence, input datasets and interpretation criteria.
The persuasiveness of genomic evidence has pressured scientific agencies to supplement or replace well-established methodologies to inform public health and food safety decision-making. This study of 52 epidemiologically defined Listeria monocytogenes isolates, collected between 1981 and 2011, including nine outbreaks, was undertaken (1) to characterize their phylogenetic relationship at finished genome-level resolution, (2) to elucidate the underlying genetic diversity within an endemic subtype, CC8, and (3) to re-evaluate the genetic relationship and epidemiology of a CC8-delimited outbreak in Canada in 2008. Genomes representing Canadian Listeria outbreaks between 1981 and 2010 were closed and manually annotated. Single nucleotide variants (SNVs) and horizontally acquired traits were used to generate phylogenomic models. Phylogenomic relationships were congruent with classical subtyping and epidemiology, except for CC8 outbreaks, wherein the distribution of SNV and prophages revealed multiple co-evolving lineages. Chronophyletic reconstruction of CC8 evolution indicates that prophage-related genetic changes among CC8 strains manifest as PFGE subtype reversions, obscuring the relationship between CC8 isolates, and complicating the public health interpretation of subtyping data, even at maximum genome resolution. The size of the shared genome interrogated did not change the genetic relationship measured between highly related isolates near the tips of the phylogenetic tree, illustrating the robustness of these approaches for routine public health applications where the focus is recent ancestry. The possibility exists for temporally and epidemiologically distinct events to appear related even at maximum genome resolution, highlighting the continued importance of epidemiological evidence.


Assessment of health risks resulting from early-life exposures: Are current chemical toxicity testing protocols and risk assessment methods adequate?
Abstract Over the last couple of decades, the awareness of the potential health impacts associated with early-life exposures has increased. Global regulatory approaches to chemical risk assessment are intended to be protective for the diverse human population including all life stages. However, questions persist as to whether the current testing approaches and risk assessment methodologies are adequately protective for infants and children. Here, we review physiological and developmental differences that may result in differential sensitivity associated with early-life exposures. It is clear that sensitivity to chemical exposures during early-life can be similar, higher, or lower than that of adults, and can change quickly within a short developmental timeframe. Moreover, age-related exposure differences provide an important consideration for overall susceptibility. Differential sensitivity associated with a life stage can reflect the toxicokinetic handling of a xenobiotic exposure, the toxicodynamic response, or both. Each of these is illustrated with chemical-specific examples. The adequacy of current testing protocols, proposed new tools, and risk assessment methods for systemic noncancer endpoints are reviewed in light of the potential for differential risk to infants and young children.


Expression of beta-defensins in gingival health and in periodontal disease.
Human beta-defensins (HBDs) are epithelial-derived antimicrobial peptides. The expression of three HBDs (HBD-1, HBD-2, and HBD-3) has been reported in oral mucosa, gingiva, and salivary glands. However, their role in protection against oral infections is not well understood. This study examined the expression of HBD-1, HBD-2, and HBD-3 mRNAs in gingival health and periodontal disease. Gingival tissue discarded from periodontal procedures was obtained from 20 periodontally healthy and 29 periodontally diseased sites. Total RNA was isolated, and expression of beta-defensins was analyzed by both 35-cycle and semiquantitative (25-cycle) reverse transcription-polymerase chain reaction (RT-PCR). The level of expression was assigned ordinal scores of no expression, low expression, or high expression. mRNA expression was compared between healthy and diseased groups using exact tests of homogeneity and Cochran-Mantel-Haenszel tests; associations among the variables were assessed using exact tests and Kendall's tau-b statistic. All 49 samples demonstrated basal mRNA expression of HBD-1, HBD-2, and HBD-3. Significantly higher levels of HBD-3 (P = 0.012) expression were found in the healthy tissues as compared to the diseased ones. There was also a suggestion of higher expression of HBD-2 in the healthy tissues (P = 0.12). Levels of HBD-1, HBD-2, and HBD-3 mRNA expression were correlated with one another (P < 0.001). High levels of HBD-3 mRNA expression in healthy tissues suggest a potentially important protective role for defensins in the host immune response to infection by periodontal pathogens.


In situ hematopoiesis: a regulator of TH2 cytokine-mediated immunity and inflammation at mucosal surfaces.
Hematopoiesis refers to the development of blood cells in the body through the differentiation of pluripotent stem cells. Although hematopoiesis is a multifocal process during embryonic development, under homeostatic conditions it occurs exclusively within the bone marrow. There, a limited number of hematopoietic stem cells differentiate into a rapidly proliferating population of lineage-restricted progenitors that serve to replenish circulating blood cells. However, emerging reports now suggest that under inflammatory conditions, alterations in hematopoiesis that occur outside of the bone marrow appear to constitute a conserved mechanism of innate immunity. Moreover, recent reports have identified previously unappreciated pathways that regulate the egress of hematopoietic progenitor cells from the bone marrow, alter their activation status, and skew their developmental potential. These studies suggest that progenitor cells contribute to inflammatory response by undergoing in situ hematopoiesis (ISH). In this review, we highlight the differences between homeostatic hematopoiesis, which occurs in the bone marrow, and ISH, which occurs at mucosal surfaces. Further, we highlight factors produced at local sites of inflammation that regulate hematopoietic progenitor cell responses and the development of TH2 cytokine-mediated inflammation. Finally, we discuss the therapeutic potential of targeting ISH in preventing the development of inflammation at mucosal sites.


Biofeedback and pelvic floor exercises for the rehabilitation of urinary stress incontinence.
We investigated the effectiveness of pelvic floor muscle (PFM) exercises or biofeedback for the treatment of urinary stress incontinence (USI). Fifty patients with USI were included in this randomized, controlled, prospective study. Twenty patients were taught PFM exercises via digital palpation and instructed to perform regularly as home program. The second group of 20 patients had PFM exercises via biofeedback three times a week for 2 months. The third group of 10 patients did not have any exercises. The patients were evaluated via pad test, perineometry, digital palpation based PFM strength, incontinence frequency, and visual analog scale based social activity index prior to and 8 weeks after the treatment. The first two groups had significant improvement in USI with respect to the control group (p < 0.001). The rise in PFM strength with perineometry of the biofeedback group was higher than in the digital palpation group after treatment (p < 0.001). PFM exercises are effective for the treatment of USI; the biofeedback method revealed better PFM strength results with respect to digital palpation.


Diagnostic utility of letter fluency, category fluency, and fluency difference scores in Alzheimer's disease.
Word generation tasks, specifically letter fluency and category fluency, are a standard part of most test protocols used by clinical neuropsychologists to measure aspects of language and executive retrieval functions. Given the reliance on these measures as clinical tools, it is important to understand the diagnostic implications of patients' performances. In Alzheimer's disease (AD), category fluency has generally been found to be disproportionately impaired, whereas letter fluency is usually more mildly impaired. It has been proposed that this performance pattern occurs because access to temporal-lobe semantic stores is necessary for category fluency but not letter fluency. In this study, the diagnostic utility of category fluency, letter fluency, and difference scores (letter fluency minus category fluency) in AD were examined. Forty AD patients and 221 normal control subjects took category fluency and letter fluency tests. Traditional t-test comparisons revealed that the groups differed significantly on the two test tasks and in terms of mean difference scores. However, using sensitivity and specificity to calculate predictive values, only category fluency and letter fluency (but not difference scores) were useful in predicting AD in individuals. Furthermore, category fluency was superior to letter fluency in this regard. Likelihood ratio tables are provided for use in calculating the odds of AD for specific category fluency and letter fluency scores generated by individual patients.


Assessing the impact of cancer among Dutch non-Hodgkin lymphoma survivors compared with their American counterparts: a cross-national study.
To understand cultural differences in the impact of cancer (IOC) by (i) performing an independent psychometric evaluation of the Dutch version of the Impact of Cancer Scale version 2 (IOCv2) in a non-Hodgkin lymphoma (NHL) sample and (ii) examining differences between Dutch and American NHL survivors in perceived IOC and identifying associations with socio-demographic and clinical characteristics. Data collected from 491 Dutch and 738 American NHL survivors were used in this study. IOCv2 responses were obtained from all survivors; the Dutch survivors also completed the European Organization for Research and Treatment of Cancer Quality of Life Core questionnaire, which measures quality of life. Exploratory factor analysis of the Dutch version yielded a factor solution similar to the American structure but with some subscales merging into single factors. Internal consistency was good; Cronbach's alpha was 0.88 for the Positive and 0.94 for the Negative summary scales. Large differences were observed between survivors, whereby Dutch survivors reported fewer Positive (Δ -0.4, p < 0.001, effect size: 0.27) and more Negative (Δ 0.2, p ≤ 0.001, effect size: 0.13) impacts of cancer independent of socio-demographic and clinical characteristics. Similar impact domains of the IOCv2 were observed in the Dutch sample, providing evidence that IOCv2 scales measure common and important survivor concerns across two different Western nations. Higher positive impacts for US survivors might be explained by more personal control and availability of supportive services. Future research should focus on determinants of the IOC in both Dutch and American survivors to gain better understanding of the factors that might improve it and suggest how health care may be modified toward that end.