Prominent expression of the selenoprotein thioredoxin reductase in the medullary rays of the rat kidney and thioredoxin reductase mRNA variants differing at the 5' untranslated region.
The mammalian selenoprotein thioredoxin reductase is a central enzyme in protection against oxidative damage or the redox control of cell function. Previously a neuroblastoma-cell-derived 2193 bp cDNA for rat thioredoxin reductase 1 (TrxR1) was characterized [Zhong, Arnér, Ljung, Aslund and Holmgren (1998) J. Biol. Chem. 273, 8581-8591]. Here, the major rat TrxR1 mRNA was determined as 3.5 kb by Northern blotting. A corresponding full-length 3360 bp liver-derived cDNA was cloned and sequenced, being extended in the 3' untranslated region (3' UTR) compared with the previous clone. Among tissues examined, lowest TrxR1 mRNA levels were found in spleen and testis and highest in liver and kidney. High expression in kidney was unexpected and in situ hybridization of adult rat kidney was performed. This revealed a highly structured expression pattern with the mRNA being prominently synthesized in the proximal tubules of the medullary rays. Analysing rat kidney cDNA, a 5' UTR domain of TrxR1 was found that was different from that in liver- or neuroblastoma-derived cDNA clones. The kidney-derived 5' UTR mRNA domain was instead highly similar to kidney-derived cDNA variants of murine apolipoprotein E. By sequence determination of the rat genomic sequence upstream of the open reading frame for TrxR1, an exon was encountered that encoded a third alternative 5' UTR domain that could also be expressed, as confirmed by its presence in a mouse skin TrxR1 cDNA clone. It can therefore be concluded that TrxR1 mRNA is expressed in at least three different variants that differ at their 5' UTRs.


Patient perspective on telemedicine replacing physical consultations in urology during the COVID-19 lockdown in Denmark.
In March-April 2020, during the coronavirus disease 2019 (COVID-19) pandemic lockdown in Denmark, the Danish Health Authorities recommended that, where possible, face-to-face patient-physician consultations be replaced by telephone consultations. The aim of this study was to obtain patients' evaluation of their telemedicine experience. Patients who were candidates for telemedicine consultations were recruited based on their urological ailment, necessity for follow-up and comorbidity. New referrals including patients with suspicion of cancer were not candidates for telemedicine. In total, 548 patients had their appointment altered during the period from 13 March to 30 April 2020. Postal questionnaires were sent to 548 patients and 300 (54.7%) replied. In total, 280 patient answered, 224 (80%) men and 56 (20%) women, mean age 69 years (range 18-91) of whom 180 (64.3%) had a benign and 100 (35.7%) a malignant diagnosis. Twenty (6.7%) respondents did not remember their telephone consultation and were therefore excluded. Telephone consultation satisfaction was reported by 230 (85.0%) patients, but they would not prefer video consultations over telephone consultations, and only 102 (36.4%) would prefer telephone consultations in the future. Patients' age, sex and distance to the hospital did not seem to be associated with telephone consultation satisfaction (age p = 0.17; sex p = 0.99; distance p = 0.27, respectively). In total, 226 (80.7%) were medically assessed as being at risk for COVID, but 74 (26.4%) subjectively evaluated themselves as being at risk. In general (85.0%), urological patients were satisfied with telephone consultations.


Influenza vaccination and vitamin K antagonist treatment: a placebo-controlled, randomized, double-blind crossover study.
Among millions of persons vaccinated against influenza virus each year, many are older patients treated with several drugs, including vitamin K antagonists (VKAs), among which warfarin is the most commonly used. Due to high interpatient and intrapatient variability, the therapeutic dose of VKA has to be individualized by monitoring of international normalized ratio (INR) values. The objectives of this study were to evaluate variation in the INR and warfarin weekly dose variation after influenza vaccination administration and to follow up patients for related hemorrhagic and thrombotic events to evaluate the safety of the influenza vaccine and to assess the immunogenicity of the influenza vaccination in patients receiving VKAs. One hundred four patients on a stable VKA regimen and with an indication for influenza vaccination were randomized to receive influenza vaccination and subsequent placebo administration, or vice versa. All patients were tested for coagulation variables, clinical events, and antibody response against vaccine components. Similar mean prothrombin times, expressed as the INR and VKA weekly dose, were found in patients after receiving vaccine or placebo. The absence of any vaccination effect on VKA treatment was confirmed using a linear mixed-effects model. The percentages of time that patients were in therapeutic range were 70.7% after receiving vaccine and 72.4% after receiving placebo (P = .57). There were no fatal or major bleeding events and 11 minor mucocutaneous hemorrhagic events. After vaccination, the percentage of seroprotected patients ranged from 92.0% to 100.0% depending on the vaccine antigen examined. Influenza vaccination had no significant effect on INR values or warfarin sodium weekly doses. Close monitoring of INR values is not required after influenza vaccination in patients on stable long-term VKA regimens. clinicaltrials.gov Identifier: NCT00222638.


[Ontogeny-specific interaction of psychophysiological mechanisms of emotional perception and educational achievement in students].
In order to explore the process of adaptation of children to school environment psychophysiological characteristics of perception of emotional speech information and school progress were experimentally studied. Forty-six schoolchildren of three age groups (7-10, 11-13, and 14-17 years old) participated in the study. In experimental session, a test sentence was presented to a subject through headphones with two emotional intonations (joy and anger) and without emotional expression. A subject had to recognize the type of emotion. His/her answers were recorded. School progress was determined by year grades in Russian, foreign language, and mathematics. Analysis of variance and linear regression analysis showed that ontogenetic features of a correlation between psychophysiological mechanisms of emotion recognition and school progress were gender- and subject-dependent. This correlation was stronger in 7-13-year-old children than in senior children. This age boundary was passed by the girls earlier than by the boys.


Left Ventricular Diastolic Dysfunction (LVDD) & Cardiovascular Autonomic Neuropathy (CAN) in Type 2 Diabetes Mellitus (DM): A Cross-Sectional Clinical Study.
Cardiovascular autonomic neuropathy (CAN) is one of the major complications of Diabetes Mellitus (DM) seen in a significant number of patients, which is often ignored and is also least frequently diagnosed. It can be diagnosed by performing five standard non-invasive bedside autonomic function tests based on Cardiovascular reflexes, which are quite cumbersome. Studies have revealed an increase in mortality in the diabetic patients with CAN due to silent cardiac ischemia, sudden cardiac death, arrhythmias. The precursor of diabetic cardiomyopathy is Left ventricular diastolic dysfunction (LVDD). In the present study we are studying the association between LVDD and CAN, in order to identify high mortality risk patients by performing 2D Echo and looking at LVDD instead of performing the cumbersome bedside cardiovascular autonomic function tests. To study the association between LVDD and CAN in patients with Type 2 DM. This study is a cross-sectional observational study with a sample size of 100. Both outpatients and inpatients between 35 y and 65 y of age with Type 2 DM coming to Department of General Medicine, KIMS hospital, Bangalore were studied from November 2011 to October 2013.Patients with macrovascular complications, Hypertension, congenital & acquired heart diseases etc. were excluded from the study. The standard five autonomic function tests based on cardiovascular reflexes and 2D Echo were performed. Individual scores for each of the five tests were added to produce Ewing's score. Ewing's score of >2.5 is positive for CAN. Chi-square/ Fisher Exact test has been. There was a significant association between individual non-invasive bedside tests of Ewing's score and LVDD. Significant association was also seen between LVDD and positive Ewing's score. Positive Ewing's score is strongly associated with LVDD in patients with Type 2 DM in this study .This suggests that patients with LVDD have CAN and hence, are at increased risk of sudden cardiac death. As bedside tests are cumbersome, patients with LVDD on 2D Echo can be concluded to have CAN.


Lateral shear interferometer for infrared and visible light.
An infrared wavefront is recorded holographically on a dynamic recording medium consisting of a thin oil film on a glass substrate. The phase hologram obtained may restore the information of the infrared wavefront or alternatively play the role of a diffraction grating for a visible reconstruction beam. On this basis, the principle of a lateral shear interferometer for the simultaneous testing of infrared or visible optical components is described and physically implemented. A theoretical discussion explains the operation of the interferometer and points out experimental restrictions due to recording medium nonuniformities, holographic aberrations, and the curvature of the reconstructed wavefronts. The interferometer is easy to set up and confirms its usefulness with experimental results that include collimation tests for both visible and infrared afocal assembly, as well as quality tests for visible components.


Beta-caryophyllene is a dietary cannabinoid.
The psychoactive cannabinoids from Cannabis sativa L. and the arachidonic acid-derived endocannabinoids are nonselective natural ligands for cannabinoid receptor type 1 (CB(1)) and CB(2) receptors. Although the CB(1) receptor is responsible for the psychomodulatory effects, activation of the CB(2) receptor is a potential therapeutic strategy for the treatment of inflammation, pain, atherosclerosis, and osteoporosis. Here, we report that the widespread plant volatile (E)-beta-caryophyllene [(E)-BCP] selectively binds to the CB(2) receptor (K(i) = 155 +/- 4 nM) and that it is a functional CB(2) agonist. Intriguingly, (E)-BCP is a common constituent of the essential oils of numerous spice and food plants and a major component in Cannabis. Molecular docking simulations have identified a putative binding site of (E)-BCP in the CB(2) receptor, showing ligand pi-pi stacking interactions with residues F117 and W258. Upon binding to the CB(2) receptor, (E)-BCP inhibits adenylate cylcase, leads to intracellular calcium transients and weakly activates the mitogen-activated kinases Erk1/2 and p38 in primary human monocytes. (E)-BCP (500 nM) inhibits lipopolysaccharide (LPS)-induced proinflammatory cytokine expression in peripheral blood and attenuates LPS-stimulated Erk1/2 and JNK1/2 phosphorylation in monocytes. Furthermore, peroral (E)-BCP at 5 mg/kg strongly reduces the carrageenan-induced inflammatory response in wild-type mice but not in mice lacking CB(2) receptors, providing evidence that this natural product exerts cannabimimetic effects in vivo. These results identify (E)-BCP as a functional nonpsychoactive CB(2) receptor ligand in foodstuff and as a macrocyclic antiinflammatory cannabinoid in Cannabis.


Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials.
Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition. Pegloticase, monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase, was developed to fulfill this need. To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout. Two replicate, randomized, double-blind, placebo-controlled trials (C0405 and C0406) were conducted between June 2006 and October 2007 at 56 rheumatology practices in the United States, Canada, and Mexico in patients with severe gout, allopurinol intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or greater. A total of 225 patients participated: 109 in trial C0405 and 116 in trial C0406. Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion (biweekly treatment group), pegloticase alternating with placebo at successive infusions (monthly treatment group), or placebo (placebo group). Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6. In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group (47%; 95% CI, 31%-62%), 8 of 41 patients in the monthly group (20%; 95% CI, 9%-35%), and in 0 patients treated with placebo (0/20; 95% CI, 0%-17%; P < .001 and <.04 for comparisons between biweekly and monthly groups vs placebo, respectively). Among patients treated with pegloticase in trial C0406, 16 of 42 in the biweekly group (38%; 95% CI, 24%-54%) and 21 of 43 in the monthly group (49%; 95% CI, 33%-65%) achieved the primary end point; no placebo-treated patients reached the primary end point (0/23; 95% CI, 0%-15%; P = .001 and < .001, respectively). When data in the 2 trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group (42%; 95% CI, 32%-54%), 29 of 84 patients in the monthly group (35%; 95% CI, 24%-46%), and 0 of 43 patients in the placebo group (0%; 95% CI, 0%-8%; P < .001 for each comparison). Seven deaths (4 in patients receiving pegloticase and 3 in the placebo group) occurred between randomization and closure of the study database (February 15, 2008). Among patients with chronic gout, elevated serum uric acid level, and allopurinol intolerance or refractoriness, the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months resulted in lower uric acid levels compared with placebo. clinicaltrials.gov Identifier: NCT00325195.


MEDICAL EXPERIMENTS IN THE LIGHT OF THE AMENDMENT OF THE ACT ON THE PROFESSION OF A PHYSICIAN AND A DENTIST.
On the 1st of January 2021 the new legal regulations to the Act of 5 December 1996 on the professions of a physician and a dentist came into force. The aim of this article is to present the new legal regulations of conducting medical experiments and to clarify the regulations already applicable. Under the amended regulations, the legislator, comprehensively regulated the legal conditions and rules to conduct the medical experiments, both research experiments and therapeutic ones, by imposing the new restrictions on a person who conducts medical experiments. The most significant change is that examination of biological material, including genetic material collected from a person for scientific purposes, is also regarded as a medical experiment. The purpose of the article is therefore to familiarize medical community with the new legal regulations concerning the principles of conducting all kind of medical experiments and to point out what interpretation doubts and legal dilemmas may arise while their conducting.


Distribution of Bemisia tabaci (Hemiptera: Aleyrodidae) biotypes in North America after the Q invasion.
After the 2004 discovery of the Bemisia tabaci (Gennadius) (Hemiptera Aleyrodidae) Q biotype in the United States, there was a vital need to determine the geographical and host distribution as well as its interaction with the resident B biotype because of its innate ability to rapidly develop high-level insecticide resistance that persists in the absence of exposure. As part of a coordinated country-wide effort, an extensive survey of B. tabaci biotypes was conducted in North America, with the cooperation of growers, industry, local, state, and federal agencies, to monitor the introduction and distribution of the Q biotype. The biotype status of submitted B. tabaci samples was determined either by polymerase chain reaction amplification and sequencing of a mitochondrial cytochrome oxidase I small subunit gene fragment and characterization of two biotype discriminating nuclear microsatellite markers or esterase zymogram analysis. Two hundred and eighty collections were sampled from the United States, Bermuda, Canada, and Mexico during January 2005 through December 2011. Host plants were split between ornamental plant and culinary herb (67%) and vegetable and field crop (33%) commodities. The New World biotype was detected on field-grown tomatoes (Solanum lycopersicum L.) in Mexico (two) and in commercial greenhouses in Texas (three) and represented 100% of these five collections. To our knowledge, the latter identification represents the first report of the New World biotype in the United States since its rapid displacement in the late 1980s after the introduction of biotype B. Seventy-one percent of all collections contained at least one biotype B individual, and 53% of all collections contained only biotype B whiteflies. Biotype Q was detected in 23 states in the United States, Canada (British Columbia and Ontario territories), Bermuda, and Mexico. Forty-five percent of all collections were found to contain biotype Q in samples from ornamentals, herbs and a single collection from tomato transplants located in protected commercial horticultural greenhouses, but there were no Q detections in outdoor agriculture (vegetable or field crops). Ten of the 15 collections (67%) from Canada and a single collection from Bermuda contained biotype Q, representing the first reports of biotype Q for both countries. Three distinct mitochondrial haplotypes of B. tabaci biotype Q whiteflies were detected in North America Our data are consistent with the inference of independent invasions from at least three different locations. Of the 4,641 individuals analyzed from 517 collections that include data from our previous work, only 16 individuals contained genetic or zymogram evidence of possible hybridization of the Q and B biotypes, and there was no evidence that rare hybrid B-Q marker co-occurrences persisted in any populations.


Wearable Haptic Device Presenting Sensations of Fingertips to the Forearm.
Several existing haptic displays used in virtual reality (VR) environments present haptic sensations generated by the fingertips in the VR to actual fingertips. However, these devices face certain challenges, such as physical interference between the devices, particularly when multi-degree-of-freedom (DOF) force needs to be presented to multiple fingers. To address this issue, we propose a haptic presentation method that transmits haptic sensations generated by the fingertips in the VR, including the direction of the force, to the forearm. We previously proposed a method to present both magnitude and direction of the force applied to the index finger using a five-bar linkage mechanism, which transmits the force sensation with two DOF to the forearm. In this study, the forces in the downward and left-right directions were obtained from the kinematics of a five-bar linkage mechanism for accurate force presentation. Additionally, we conducted a user study evaluating user grasping an object in the VR and performing task. The results verified the haptic sensation of the force transmitted by the proposed prototype to the user's forearm provides a sufficient comfort level. Furthermore, the task execution time and comfort level were comparable to those of a vibrotactile presentation presented directly to the fingertips.


WhatsApp in mHealth: an overview on the potentialities and the opportunities in medical imaging.
WhatsApp as many other Messaging Apps or "Messengers" enables messaging and exchanging documents and/or multimedia element (images, movies, music) through chat like tools; these last characteristics makes WhatsApp useful for the remote-image exchanging in mHealth for teleconsulting. Among the other potentialities of this App there are (I) the possibility to create groups, the so called WhatsApp Groups and (II) the possibility of this App to be installed into a platform based on a personal computer through the version for pc named WhatsApp Web; these potentialities allow both the creation of protected groups for cooperative teleconsulting and the creation of client-server architectures in telemedicine and e-Health. Scholars have recently shown the usefulness of WhatsApp in several mHealth applications. Recent important studies are highlighting, for example, the wide-range opportunities of WhatsApp as an adjunctive tool in mHealth in medical imaging or in specific applications such as in oral medicine in orthopedics and tele-education. In this contribution we share our alignment with these scholars and presents our polarities of research in the use of WhatsApp. These polarities range from the institutional surveillance of the spontaneous phenomena of WhatsApp groups in the families for the monitoring of the fragile patient up to the test of use of WhatsApp in digital-pathology and digital-radiology static imaging and recently in cardiologic dynamic imaging.


Documentation of screening for perpetration of intimate partner violence in male veterans with PTSD.
Men seeking care for posttraumatic stress disorder (PTSD) are believed to have high rates of relationship conflict and intimate partner violence (IPV). But little is known about screening for IPV perpetration in this population. In phase one of a two-phase study of male veterans treated for PTSD, the primary objective was to determine how many veterans' records showed documentation that they'd been screened for IPV perpetration. The secondary objective was to count the total number of screenings and to determine whether an initial screening affected future screenings. For this retrospective cohort study, a stratified random sample of 10% (N = 507) of all male veterans receiving treatment for PTSD at a U.S. Department of Veterans Affairs health care facility in a five-year period (November 2002 to November 2007) was selected and more than 70,000 progress notes were reviewed. The presence or absence of a documented screening for IPV perpetration in each record was noted and a Spearman rank correlation test to determine the relationship between the documentation of a first screening and future screenings was performed. Of the 507 records examined, 120 (24%) showed documentation of screening for IPV perpetration. Of those, 73 (61%) showed positive results for IPV perpetration, and 61 (51%) showed more than one screening. Documentation of screening was most likely to have occurred at the veteran's initial appointment (71%) and in an outpatient mental health setting (72%); IPV perpetration was determined most often as the result of a provider's inquiry (45%). There was a total of 415 screenings, including 356 in records in which there was more than one screening. The documentation of a single screening for IPV perpetration was significantly correlated with the documentation of subsequent screenings and with IPV perpetration determination (Spearman rank correlation = 0.611, P < 0.001). Also, veterans with documented IPV perpetration and high rates of relationship conflict accessed the health care system twice as often as those without such documentation. In the sample analyzed, fewer than a quarter of male veterans with PTSD had a documented screening for IPV perpetration. Also, because those identified as IPV perpetrators accessed the health care system at a higher rate than those not so identified and repeated screenings were associated with a higher rate of IPV perpetrator determinations, health care providers should be made more aware of opportunities for screening for IPV in this population.


The impact of limb deficiency impairment on Para swimming performance.
Swimmers with limb deficiency are a core population within Para Swimming, accordingly this study examined the contribution of limb segments to race performance in these swimmers. Data were obtained for 174 male Para swimmers with limb deficiency. Ensemble partial least squares regression showed accurate predictions when using relative limb segment lengths to estimate Para swimmers' personal best race performances. The contribution of limb segments to performance in swim events was estimated using these regression models. The analysis found swim stroke and event distance to influence the contributions of limb segments to performance. For freestyle swim events, these changes were primarily due to the increased importance of the hand, and decreased importance of the foot and shank, as the distance of the event increased. When comparing swim strokes, higher importance of the thigh and shank in the 100 m breaststroke compared with other swim strokes confirms the separate SB class. Varied contributions of the hand, upper arm and foot suggest that freestyle could also be separated from backstroke and butterfly events to promote fairer classification. This study shows that swim stroke and event distance influence the activity limitation of Para swimmers with limb deficiency suggesting classification should account for these factors.


Bloodstream infection following 217 consecutive systemic-enteric drained pancreas transplants.
Combined kidney pancreas transplantation (PTx) evolved as excellent treatment for diabetic nephropathy. Infections remain common and serious complications. 217 consecutive enteric drained PTxs performed from 1997 to 2004 were retrospectively analyzed with regard to bloodstream infection. Immunosuppression consisted of antithymocyteglobuline induction, tacrolimus, mycophenolic acid and steroids for the majority of cases. Standard perioperative antimicrobial prophylaxis consisted of pipercillin/tazobactam in combination with ciprofloxacin and fluconazole. One year patient, pancreas and kidney graft survival were 96.4%, 88.5% and 94.8%, surgical complication rate was 35%, rejection rate 30% and rate of infection 59%. In total 46 sepsis episodes were diagnosed in 35 patients (16%) with a median onset on day 12 (range 1-45) post transplant. Sepsis source was intraabdominal infection (IAI) (n = 21), a contaminated central venous line (n = 10), wound infection (n = 5), urinary tract infection (n = 2) and graft transmitted (n = 2). Nine patients (4%) experienced multiple episodes of sepsis. Overall 65 pathogens (IAI sepsis 39, line sepsis 15, others 11) were isolated from blood. Gram positive cocci accounted for 50 isolates (77%): Coagulase negative staphylococci (n = 28, i.e. 43%) (nine multi-resistant), Staphylococcus aureus (n = 11, i.e. 17%) (four multi-resistant), enterococci (n = 9, i.e. 14%) (one E. faecium). Gram negative rods were cultured in twelve cases (18%). Patients with blood borne infection had a two year pancreas graft survival of 76.5% versus 89.4% for those without sepsis (p = 0.036), patient survival was not affected. Sepsis remains a serious complication after PTx with significantly reduced pancreas graft, but not patient survival. The most common source is IAI.


Dog and owner demographic characteristics and dog personality trait associations.
The aim of this study was to analyze the relationships between four personality traits (calmness, trainability, dog sociability and boldness) of dogs (Canis familiaris) and dog and owner demographics on a large sample size with 14,004 individuals. German speaking dog owners could characterize their dog by filling out a form on the Internet. There were five demographic variables for dogs and nine for owners. Two statistical methods were used for investigating the associations between personality and demographic traits: the more traditional general linear methods and regression trees that are ideal for analyzing non-linear relationships in the structure of the data. The results showed that calmness is influenced primarily by the dog's age, the neutered status, the number of different types of professional training courses (e.g. obedience, agility) the dog had experienced and the age of acquisition. The least calm dogs were less than 2.5 years old, neutered and acquired after the first 12 weeks of age, while the calmest dogs were older than 6.9 years. Trainability was affected primarily by the training experiences, the dog's age, and the purpose of keeping the dog. The least trainable dogs had not received professional training at all and were older than 3 years. The most trainable dogs were those who participated in three or more types of professional training. Sociability toward conspecifics was mainly determined by the age, sex, training experience and time spent together. The least sociable dogs were older than 4.8 years and the owners spent less than 3h with the dog daily. The most sociable dogs were less than 1.5 years old. Males were less sociable toward their conspecifics than females. Boldness was affected by the sex and age of the dog and the age of acquisition. The least bold were females acquired after the age of 1 year or bred by the owner. The boldest dogs were males, acquired before the age of 12 weeks, and were younger than 2 years old. Other variables, including the owner's gender, age, education, previous experience with dogs, the number of people and dogs in the household, and purpose of keeping the dogs had minor, but detectable effects. The results suggest that on-line questionnaires are a very effective means for collecting data about dog behavior, especially if owners are motivated by instant feedback. However, note that the characteristics of dogs in the present study were reported by the owners, and the associations with the traits do not necessarily represent a causal relationship.


An appendix to the 2012 IOF-ECTS guidelines for the management of glucocorticoid-induced osteoporosis.
The use of glucocorticoids in the treatment of medical disorders can lead to rapid bone loss and increased risk of fragility fracture. Updated clinical guidelines are needed that accommodate recent advances in fracture risk assessment and new pharmacological interventions to reduce fracture risk. This document serves as an appendix to the 2012 IOF-ECTS guidelines for the management of glucocorticoid-induced osteoporosis.


What are the 5-year survivorship outcomes of compressive endoprosthetic osseointegration fixation of the femur?
Aseptic complications such as stress shielding leading to bone loss are major problems associated with revision of cemented and uncemented long-stem tumor endoprostheses. Endoprosthetic reconstruction using compressive osseointegration fixation is a relatively new limb salvage technology designed to enhance osseointegration, prevent stress shielding, and provide fixation for short end-segments. (1) What is the survivorship of this technique at minimum 5-year followup? (2) Were patient factors (age, sex, body mass index), oncological factors, or anatomic locations associated with implant failure? (3) Were there any prosthesis-related variables associated with failure? A single-center, retrospective review of patients with a minimum 5-year followup (mean, 8 years; range, 5-12 years) treated with an osseointegration compressive device for endoprosthetic fixation of proximal and distal femoral limb salvage reconstructions was performed. We have previously published the implant survivorship of this patient cohort with a minimum 2-year followup and are now reporting on the 5-year survivorship data. From 2002 to 2008, we performed 22 such procedures in 22 patients. Four patients died of their disease within 5 years of surgery and all surviving patients (n = 18) had complete followup data at a minimum of 5 years. General indications for this device during that time were pediatric and adult patients requiring primary endoprosthetic reconstructions of the proximal or distal femur for benign and malignant bone lesions. The primary outcome was reoperations for mechanical (aseptic) failures. Secondary outcomes included implant removal for nonmechanical failures and any patient-, oncological-, or implant-related variables associated with implant removal. At a minimum of 5 years followup, overall mechanical (aseptic) implant survivorship was 16 of 18. Survivorship for all modes of failure (oncological failure, infection, arthrofibrosis, and mechanical failure) was 12 of 18. All mechanical failures occurred early, within the first 30 months. We identified no patient-, oncological-, or implant-related features predictive of failure. Our intermediate-term experience with compressive osseointegration fixation for endoprosthetic limb reconstructions demonstrates with longer clinical followup, no additional mechanical failures were observed as compared with our early analysis. Our experience with this fixation at a minimum of 5-years followup adds to a very limited but increasing body of literature demonstrating that after a transient period of increased risk for implant failures, survivorship stabilizes. Assessment of this fixation strategy beyond 10 years of clinical followup is needed. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Adrenalectomy reduces neuropeptide Y-induced insulin release and NPY receptor expression in the rat ventromedial hypothalamus.
Chronic central administration of neuropeptide Y (NPY) causes hyperphagia, hyperinsulinemia, and obesity, a response that is prevented by prior adrenalectomy (ADX) in rats. The basis of NPY's effect and how the acute responses to this peptide are affected by ADX remain unknown. This study investigates the role of glucocorticoids in acute NPY-stimulated food intake, acute NPY-induced insulin release, and hypothalamic NPY-receptor mRNA expression levels. NPY-induced food intake was similar in ADX and control rats after acute intracerebroventricular injection of NPY. Injection of NPY caused a significant increase in plasma insulin in control rats, but this effect was completely absent in ADX rats in which basal plasma insulin levels were also lower than controls. In addition, ADX significantly reduced the number of neurons expressing NPY receptor Y(1) and Y(5) mRNAs in the ventromedial hypothalamus (VMH), without affecting Y(1)- or Y(5)-mRNA expression in the paraventricular hypothalamus or the arcuate nucleus. These data indicate that glucocorticoids are necessary for acute NPY-mediated insulin release and suggest that the mechanisms involve glucocorticoid regulation of Y(1) and Y(5) receptors specifically within the VMH nucleus.


Beta-adrenoreceptors in rat brown adipose tissue: proportions of beta 1- and beta 2-subtypes.
Binding of (-)-[3H]dihydroalprenolol [( 3H]DHA) to isolated brown adipose tissue (BAT) microsomal membranes was used to estimate beta-adrenoreceptor density, and this was found to be saturable, reversible, and stereospecific. Scatchard analysis indicated a single class of binding sites of equilibrium dissociation constant 2.2 nM, with a maximum number of binding sites of 160-170 fmol/mg protein. These values were unaffected by the age or sex of the animals, and similar Kd values were obtained for binding to heart and lung membranes. The kinetically derived Kd from forward and reverse reactions was 1.4 nM for BAT. Hofstee analysis of displacement of [3H]DHA produced linear plots for propranolol but curvilinear plots for atenolol and ICI 118,551. Atenolol showed 50-fold selectivity for beta 1-receptors and ICI 118,551 50-fold selectivity for beta 2-receptors in heart, lung, and BAT membranes. These plots indicated beta 1:beta 2-receptor ratios of 59:41 for BAT and heart and 25:75 for lung. It is possible that both beta-adrenoreceptor subtypes in BAT may be involved in the activation of thermogenesis in the tissue.


Inner ear and kidney anomalies caused by IAP insertion in an intron of the Eya1 gene in a mouse model of BOR syndrome.
A spontaneous mutation causing deafness and circling behavior was discovered in a C3H/HeJ colony of mice at the Jackson Laboratory. Pathological analysis of mutant mice revealed gross morphological abnormalities of the inner ear, and also dysmorphic or missing kidneys. The deafness and abnormal behavior were shown to be inherited as an autosomal recessive trait and mapped to mouse chromosome 1 near the position of the Eya1 gene. The human homolog of this gene, EYA1, has been shown to underly branchio-oto-renal (BOR) syndrome, an autosomal dominant disorder characterized by hearing loss with associated branchial and renal anomalies. Molecular analysis of the Eya1 gene in mutant mice revealed the insertion of an intracisternal A particle (IAP) element in intron 7. The presence of the IAP insertion was associated with reduced expression of the normal Eya1 message and formation of additional aberrant transcripts. The hypomorphic nature of the mutation may explain its recessive inheritance, if protein levels in homozygotes, but not heterozygotes, are below a critical threshold needed for normal developmental function. The new mouse mutation is designated Eya1(bor) to denote its similarity to human BOR syndrome, and will provide a valuable model for studying mutant gene expression and etiology.


A randomized, controlled trial to evaluate topical anesthetic for 15 minutes before venipuncture in pediatrics.
The aim of the study was to assess the differences in reported pain from venipuncture comparing liposomal 4% lidocaine with placebo cream in a pediatric population. Other factors assessed were patient anxiety, difficulty of venipuncture, and history of venipuncture. A prospective, randomized, double-blind, placebo control study design was used in which subjects were assigned to receive either liposomal 4% lidocaine or placebo cream. The study population consisted of pediatric patients aged 5 to 18 years old who presented to 1 site of a multisite, academic, community emergency department. Once subjects had consented and randomized, the liposomal 4% lidocaine or placebo cream was applied for 15 minutes under occlusion. A 6-point validated FACES pain scale was used to evaluate each patient's level of pain during venipuncture. Patient anxiety was evaluated using a 100-mm visual analogue scale before, during, and after the venipuncture. Heart rate was captured as an indirect measurement of pain. There were no significant differences between the study and placebo groups (P > .05) in mean levels of patient ratings of anxiety, patient heart rate, or the patient's mean rating of pain before, during, or after the venipuncture procedure. There was an association between increased anxiety with an increase in venipuncture pain and an inverse association between age and pain. Topical liposomal 4% lidocaine cream in this case did not prove to be effective with a 15-minute dwell time under occlusion because there were no differences in pain between study groups.


Sow postural changes, responsiveness to piglet screams, and their impact on piglet mortality in pens and crates.
Free farrowing pens (pens) improve the welfare of sows but may increase sow activity and negatively influence piglet production. The aim of this study was to assess the effect of pens and crates on sow postural changes, piglet trapping, sow responses to piglet screams, piglet mortality, and piglet BW gain. It was predicted that provision of greater space (in pens) would increase not only the frequency of sow postural changes and the probability of trappisng but also sow responses to the screams of piglets; thus, the outcome would be no differences in fatal piglet crushing or overall mortality between the housing systems. Sows were randomly moved to either a farrowing pen (n = 20) or farrowing crate (n = 18). Sow behavior was recorded and analyzed for 72 h from the birth of the first piglet (BFP). Sow postural changes included rolling from a ventral to lateral position and vice versa and going from standing to sitting, standing to lying, and sitting to lying. Occurrences of piglet trapping and sow responsiveness to real crushing situations were analyzed. Sow responsiveness was assessed in response to audio playbacks (PB) of piglet screams on d 3 postpartum (48 to 72 h after BFP; PB crush calls) and real piglet crushing during the first 72 h after BFP (real crush calls). Piglet BW gain was estimated 24 h after BFP, piglet BW was recorded at weaning, and piglet crushing and piglet mortality were recorded during the 72 h after BFP. Data were analyzed using PROC MIXED and PROC GENMOD of SAS. Sows in pens showed more postural changes (P = 0.04) and tended to have greater incidences of piglet trapping (P = 0.07) than those in crates. Sow response to PB crush calls was greater in pens (P = 0.04) but did not differ for real crush calls between pens and crates (P = 0.62). There was no effect on the probability of piglet crushing (P = 0.38) and mortality (P = 0.41) during the 72 h after BFP nor in piglet mortality at weaning (P = 0.81) between pens and crates. Piglet BW gain at 24 h after BFP (P = 0.01) and piglet BW at weaning (P = 0.02) were greater in pens. Sows in pens showed more postural changes and tended to trap more piglets; however, the response to real crush calls did not differ between the two housing systems. Despite this, there was no increase in piglet crushing or mortality in pens, which might be influenced by the better piglet body condition observed in pens, which in turn could influence their ability to avoid crushing by the sow.


Radiographic case definitions and prevalence of osteoarthrosis of the hip: a survey of 4 151 subjects in the Osteoarthritis Substudy of the Copenhagen City Heart Study.
The diagnosis of osteoarthrosis (OA) is founded on radiographic evidence of joint degeneration and characteristic subjective symptoms. Due to the lack of consensus radiographic case definitions, the prevalence and incidence of OA reported in the literature varies. The aims of the current study were to establish an accurate and workable radiographic definition of OA in hip joints and to examine the association of OA (thus defined) with self-reported pain. Radiographic features of hip OA were classified in pelvic radiographs of 3 807 subjects (1448 males and 2 359 females) according to the OA classifications of Kellgren and Lawrence (1957) and Croft (1990), and according to minimum joint space width (JSW) of 2.0 mm regardless of other radiographic features of OA. The relationships between these radiographic discriminators and self-reported hip pain were investigated. Formation of cysts, osteophytes and subchondral sclerosis was significantly more frequent in men. Average minimum JSW was narrower in women than in men (p < 0.001). In both sexes, minimum JSW decreased after the fourth decade of life, but progressively more so in women. Women reported hip pain more frequently than men (p < 0.001). When the cut-off JSW value of 2.0 mm was applied regardless of other radiographic features of OA, prevalences of hip OA ranged from 4.4% to 5.3% in subjects > or = 60 years of age. The radiographic discriminator with the strongest association with self-reported hip pain in men and women > or = 60 years of age was minimum JSW < or = 2.0 mm; OR = 3.3 (95% CI 1.9-5.7) for men, and OR = 3.2 (95% CI 1.9-5.2) for women. We found that minimum JSW < or = 2.0 mm was the radiographic criterion having the closest association with self-reported hip pain. Using composite OA scores emphasizing the relatively inconsequential formation of cysts, osteophytes and subchondral sclerosis runs the risk of over-inflating the prevalence of hip OA in men and of underestimating hip OA prevalence in women.


Regulation of the cardiomyocyte population in the developing heart.
During fetal life the myocardium expands through replication of cardiomyocytes. In sheep, cardiomyocytes begin the process of becoming terminally differentiated at about 100 gestation days out of 145 days term. In this final step of development, cardiomyocytes become binucleated and stop dividing. The number of cells at birth is important in determining the number of cardiomyocytes for life. Therefore, the regulation of cardiomyocyte growth in the womb is critical to long term disease outcome. Growth factors that stimulate proliferation of fetal cardiomyocytes include angiotensin II, cortisol and insulin-like growth factor-1. Increased ventricular wall stress leads to short term increases in proliferation but longer-term loss of cardiomyocyte generative capacity. Two normally circulating hormones have been identified that suppress proliferation: atrial natriuretic peptide (ANP) and tri-iodo-L-thyronine (T₃). Atrial natriuretic peptide signals through the NPRA receptor that serves as a guanylate cyclase and signals through cGMP. ANP powerfully suppresses mitotic activity in cardiomyocytes in the presence of angiotensin II in culture. Addition of a cGMP analog has the same effect as ANP. ANP suppresses both the extracellular receptor kinases and the phosphoinositol-3 kinase pathways. T₃ also suppresses increased mitotic activity of stimulated cardiomyocytes but does so by increasing the cell cycle suppressant, p21, and decreasing the cell cycle activator, cyclin D1.


Access of torsinA to the inner nuclear membrane is activity dependent and regulated in the endoplasmic reticulum.
TorsinA (also known as torsin-1A) is a membrane-embedded AAA+ ATPase that has an important role in the nuclear envelope lumen. However, most torsinA is localized in the peripheral endoplasmic reticulum (ER) lumen where it has a slow mobility that is incompatible with free equilibration between ER subdomains. We now find that nuclear-envelope-localized torsinA is present on the inner nuclear membrane (INM) and ask how torsinA reaches this subdomain. The ER system contains two transmembrane proteins, LAP1 and LULL1 (also known as TOR1AIP1 and TOR1AIP2, respectively), that reversibly co-assemble with and activate torsinA. Whereas LAP1 localizes on the INM, we show that LULL1 is in the peripheral ER and does not enter the INM. Paradoxically, interaction between torsinA and LULL1 in the ER targets torsinA to the INM. Native gel electrophoresis reveals torsinA oligomeric complexes that are destabilized by LULL1. Mutations in torsinA or LULL1 that inhibit ATPase activity reduce the access of torsinA to the INM. Furthermore, although LULL1 binds torsinA in the ER lumen, its effect on torsinA localization requires cytosolic-domain-mediated oligomerization. These data suggest that LULL1 oligomerizes to engage and transiently disassemble torsinA oligomers, and is thereby positioned to transduce cytoplasmic signals to the INM through torsinA.


A plant biodiversity effect resolved to a single chromosomal region.
Despite extensive evidence that biodiversity promotes plant community productivity, progress towards understanding the mechanistic basis of this effect remains slow, impeding the development of predictive ecological theory and agricultural applications. Here, we analysed non-additive interactions between genetically divergent Arabidopsis accessions in experimental plant communities. By combining methods from ecology and quantitative genetics, we identify a major effect locus at which allelic differences between individuals increase the above-ground productivity of communities. In experiments with near-isogenic lines, we show that this diversity effect acts independently of other genomic regions and can be resolved to a single region representing less than 0.3% of the genome. Using plant-soil feedback experiments, we also demonstrate that allelic diversity causes genotype-specific soil legacy responses in a consecutive growing period, even after the original community has disappeared. Our work thus suggests that positive diversity effects can be linked to single Mendelian factors, and that a range of complex community properties can have a simple cause. This may pave the way to novel breeding strategies, focusing on phenotypic properties that manifest themselves beyond isolated individuals; that is, at a higher level of biological organization.


[Pericardiocentesis and Pericardial Drainage].
Peicardiocentesis and surgical pericardial drainage are essential treatment and diagnostic modality for pericardial effusion. Though it theoretically is a simple therapeutic method, accurate diagnosis, correct decision, and safe procedure are not always easy. Thoracic and cardiovascular surgeons are required to have high level of expertise in pericardial drainage as surgeons who specialize this anatomical part of the body. The presence of pericardial effusion does not always require drainage. Accurate diagnosis is essential to determine correct indication. Echocardiography and computed tomography are useful tools for accurate diagnosis. The percutaneous drainage has become much safer in these 2 decades with the aid of imaging technology, especially echocardiography and fluoroscopy. Surgical pericardial window still has its role and is considered one of the standard treatment methods with minimal chance to require repeat procedure compared to percutaneous drainage.


Severity of mental health impairment and trajectories of improvement in an integrated primary care clinic.
To model typical trajectories for improvement among patients treated in an integrated primary care behavioral health service, multilevel models were used to explore the relationship between baseline mental health impairment level and eventual mental health functioning across follow-up appointments. Data from 495 primary care patients (61.1% female, 60.7% Caucasian, 37.141 ± 12.21 years of age) who completed the Behavioral Health Measure (Kopta & Lowry, 2002) at each primary care appointment were used for the analysis. Three separate models were constructed to identify clinical improvement in terms of number of appointments attended, baseline impairment severity level, and the interaction of these 2 variables. The data showed that 71.5% of patients improved across appointments, 56.8% of which (40.5% of the entire sample) was clinically meaningful and reliable. Number of appointments and baseline severity of impairment significantly accounted for variability in clinical outcome, with trajectories of change varying across appointments as a function of baseline severity. Patients with more severe impairment at baseline improved faster than patients with less severe baseline impairment. Patients treated within an integrated primary care behavioral health service demonstrate significant improvements in clinical status, even those with the most severe levels of distress at baseline.


Test-enhanced learning in medical education.
In education, tests are primarily used for assessment, thus permitting teachers to assess the efficacy of their curriculum and to assign grades. However, research in cognitive psychology has shown that tests can also directly affect learning by promoting better retention of information, a phenomenon known as the testing effect. Cognitive psychology laboratory studies show that repeated testing of information produces superior retention relative to repeated study, especially when testing is spaced out over time. Tests that require effortful retrieval of information, such as short-answer tests, promote better retention than tests that require recognition, such as multiple-choice tests. The mnemonic benefits of testing are further enhanced by feedback, which helps students to correct errors and confirm correct answers. Medical educational research has focused extensively on assessment issues. Such assessment research permits the conclusion that clinical expertise is founded on a broad fund of knowledge and effective memory networks that allow easy access to that knowledge. Test-enhanced learning can potentially strengthen clinical knowledge that will lead to improved expertise. Tests should be given often and spaced out in time to promote better retention of information. Questions that require effortful recall produce the greatest gains in memory. Feedback is crucial to learning from tests. Test-enhanced learning may be an effective tool for medical educators to use in promoting retention of clinical knowledge.


Macrophages contribute to the cellular uptake of von Willebrand factor and factor VIII in vivo.
Von Willebrand factor (VWF) and factor VIII (FVIII) circulate in a tight noncovalent complex. At present, the cells that contribute to the removal of FVIII and VWF are of unknown identity. Here, we analyzed spleen and liver tissue sections of VWF-deficient mice infused with recombinant VWF or recombinant FVIII. This analysis revealed that both proteins were targeted to cells of macrophage origin. When applied as a complex, both proteins were codirected to the same macrophages. Chemical inactivation of macrophages using gadolinium chloride resulted in doubling of endogenous FVIII levels in VWF-null mice, and of VWF levels in wild-type mice. Moreover, the survival of infused VWF was prolonged almost 2-fold in VWF-deficient mice after gadolinium chloride treatment. VWF and FVIII also bound to primary human macrophages in in vitro tests. In addition, radiolabeled VWF bound to human THP1 macrophages in a dose-dependent, specific, and saturable manner (half-maximal binding at 0.014 mg/mL). Binding to macrophages was followed by a rapid uptake and subsequent degradation of the internalized protein. This process was also visualized using a VWF-green fluorescent protein fusion protein. In conclusion, our data strongly indicate that macrophages play a prominent role in the clearance of the VWF/FVIII complex.


Intracoronary optical coherence tomography: a review of clinical applications.
Optical coherence tomography (OCT) is a light-based technology that provides very high spatial resolution images. OCT has been initially employed as a research tool to investigate plaque morphology and stent strut coverage. The introduction of frequency domain OCT allowing fast image acquisition during a prolonged contrast injection via the guiding catheter has made OCT applicable for guidance of coronary interventions. In this manuscript, the various applications of OCT are reviewed, from assessment of plaque vulnerability and severity to characteristics of unstable lesions and thrombus burden to stent optimization and evaluation of late results.


Airway management in Escobar syndrome: A formidable challenge.
Escobar syndrome is a rare autosomal recessive disorder characterized by flexion joint and digit contractures, skin webbing, cleft palate, deformity of spine and cervical spine fusion. Associated difficult airway is mainly due to micrognathia, retrognathia, webbing of neck and limitation of the mouth opening and neck extension. We report a case of a 1 year old child with Escobar syndrome posted for bilateral hamstrings to quadriceps transfer. The child had adequate mouth opening with no evidence of cervical spine fusion, yet we faced difficulty in intubation which was ultimately overcome by securing a proseal laryngeal mask airway (PLMA) and then by intubating with an endotracheal tube railroaded over a paediatric fibreoptic bronchoscope passed through the lumen of a PLMA.


Bioactivity and Cell Compatibility of β-Wollastonite Derived from Rice Husk Ash and Limestone.
The aim of this study was to prepare β-wollastonite using a green synthesis method (autoclaving technique) without organic solvents and to study its bioactivity. To prepare β-wollastonite, the precursor ratio of CaO:SiO₂ was set at 55:45. This mixture was autoclaved for 8 h and later sintered at 950 °C for 2 h. The chemical composition of the precursors was studied using X-ray fluorescence (XRF), in which rice husk ash consists of 89.5 wt % of SiO₂ in a cristobalite phase and calcined limestone contains 97.2 wt % of CaO. The X-ray diffraction (XRD) patterns after sintering showed that only β-wollastonite was detected as the single phase. To study its bioactivity and degradation properties, β-wollastonite samples were immersed in simulated body fluid (SBF) for various periods of time. Throughout the soaking period, the molar ratio of Ca/P obtained was in the range of 1.19 to 2.24, and the phase detected was amorphous calcium phosphate, which was confirmed by scanning electron microscope with energy dispersive X-ray analysis (SEM/EDX) and XRD. Fourier-transform infrared spectroscopy (FTIR) analysis indicated that the peaks of the calcium and phosphate ions increased when an amorphous calcium phosphate layer was formed on the surface of the β-wollastonite sample. A cell viability and proliferation assay test was performed on the rice husk ash, calcined limestone, and β-wollastonite samples by scanning electron microscope. For heavy metal element evaluation, a metal panel that included As, Cd, Pb, and Hg was selected, and both precursor and β-wollastonite fulfilled the requirement of an American Society for Testing and Materials (ASTM F1538-03) standard specification. Apart from that, a degradation test showed that the loss of mass increased incrementally as a function of soaking period. These results showed that the β-wollastonite materials produced from rice husk ash and limestone possessed good bioactivity, offering potential for biomedical applications.


High Blood Pressure during Pregnancy is not a Protective Factor for Preterm Infants with Very Low Birth Weight. A Case-Control Study.
Objective To evaluate whether the presence of maternal blood pressure reduces the risks of morbidity, perinatal mortality and morbidity at 24 months of age in very low birth weight infants (VLBWIs) compared with a control group. Methods A retrospective, observational, case-control study. Total 49 VLBWIs were allocated to the study group, called the maternal arterial hypertension group (AHG), and matched with 44 in the control group (CG). The infants were assessed during hospitalization and at 12 and 24 months corrected age at a specialized clinic. For the assessment of growth, the World Health Organization (WHO) Anthro software (Geneva, 2006) was used, and for the psychomotor assessment, the Denver II test was used. Results In relation to the antenatal variables, the infants of the AHG had more centralized circulation assessed by Doppler, received more corticosteroids and magnesium sulfate, and were born by cesarean section more frequently. In terms of the postnatal and in-hospital outcomes, the AHG had a higher gestational age at birth (30.7 versus 29.6 weeks) and a lower frequency of 5-minute Apgar scores of less than 7 (26.5% versus 52.3%). The CG had a higher rate of pulmonary dysplasia (30.2% versus 8.3%). There were no differences in terms of hospital mortality, complications, somatic growth and functional problems at 24 months of corrected age. Conclusion The presence of maternal hypertension, especially preeclampsia, was not a protective factor against morbidity, mortality and evolution in VLBWIs aged up to 24 months. Therefore, the clinical practice should be focused on prolonging the pregnancy for as long as possible in these conditions as well.


Single-cell transcriptome profiling of an adult human cell atlas of 15 major organs.
As core units of organ tissues, cells of various types play their harmonious rhythms to maintain the homeostasis of the human body. It is essential to identify the characteristics of cells in human organs and their regulatory networks for understanding the biological mechanisms related to health and disease. However, a systematic and comprehensive single-cell transcriptional profile across multiple organs of a normal human adult is missing. We perform single-cell transcriptomes of 84,363 cells derived from 15 tissue organs of one adult donor and generate an adult human cell atlas. The adult human cell atlas depicts 252 subtypes of cells, including major cell types such as T, B, myeloid, epithelial, and stromal cells, as well as novel COCH+ fibroblasts and FibSmo cells, each of which is distinguished by multiple marker genes and transcriptional profiles. These collectively contribute to the heterogeneity of major human organs. Moreover, T cell and B cell receptor repertoire comparisons and trajectory analyses reveal direct clonal sharing of T and B cells with various developmental states among different tissues. Furthermore, novel cell markers, transcription factors, and ligand-receptor pairs are identified with potential functional regulations in maintaining the homeostasis of human cells among tissues. The adult human cell atlas reveals the inter- and intra-organ heterogeneity of cell characteristics and provides a useful resource in uncovering key events during the development of human diseases in the context of the heterogeneity of cells and organs.


A prospective, randomized, open-label trial comparing telmisartan 80 mg with valsartan 80 mg in patients with mild to moderate hypertension using ambulatory blood pressure monitoring.
To compare the antihypertensive efficacy and tolerability of telmisartan 80 mg with valsartan 80 mg throughout a 24 h dosing interval. A prospective, randomized, open-label, blinded end point, parallel group study. Treatment efficacy was compared using ambulatory blood pressure monitoring (ABPM), cuff sphygmomanometry and calculated responder rates. Tolerability was assessed by physical examination, laboratory parameters, 12-lead electrocardiogram, blood pressure and heart rate monitoring, and evaluation of adverse events. Thirty-five centres in the United States. Four hundred and twenty-six patients with mild to moderate essential hypertension entered the study. Ninety-two per cent (n=393) completed the study. Patients underwent a four-week, single-blind, placebo run-in period before being randomly assigned to once-daily oral telmisartan 80 mg (n=214) or valsartan 80 mg (n=212) for an eight-week, open-label treatment period. Treatment with telmisartan was associated with a significantly greater mean reduction from baseline in the last 6 h ABPM mean for diastolic blood pressure compared with the valsartan-treated group (-7.5+/-0.6 mmHg versus -5.2+/-0.6 mmHg, respectively, P<0.01). Secondary analyses showed significantly greater efficacy with telmisartan 80 mg than with valsartan 80 mg, including greater mean reductions from baseline of ABPM (systolic blood pressure and diastolic blood pressure) during the daytime (06:00 to 21:59) and morning (06:00 to11:59) hours, and larger decreases in trough cuff blood pressure (P<0.01). Both treatments showed placebo-like tolerability profiles. Telmisartan 80 mg once daily was superior to valsartan 80 mg once daily in reducing diastolic blood pressure during the last 6 h of the 24 h dosing interval. These results may be due to telmisartan's longer plasma half-life or to a higher potency compared with valsartan, such that a higher dose of valsartan may produce effects similar to those of 80 mg telmisartan. These data confirm the long duration of action of telmisartan with consistent and sustained control of blood pressure over 24 h and during the last 6 h of the dosing interval. Both treatments were well tolerated; the adverse event data confirmed the excellent tolerability profiles of telmisartan and valsartan that have been reported previously.


Matrix Gla protein in tumoral pathology.
Matrix Gla protein is a vitamin K-dependent protein secreted by chondrocytes and vascular smooth muscle cells. The presence of matrix Gla protein was reported in arterial and venous walls, lungs, kidney, uterus, heart, tooth cementum and eyes. Several studies identified matrix Gla protein in tumoral pathology. Until recently, it was thought to only have an inhibitory role of physiological and ectopic calcification. New studies demonstrated that it also has a role in physiological and pathological angiogenesis, as well as in tumorigenesis. The aim of this review is to report the latest findings related to the expression and clinical implications of matrix Gla protein in different types of cancer with an emphasis on cerebral tumors.


Effects of social conditions during early development on stress response and personality traits in great tits (Parus major).
Environmental conditions during early development play a crucial role in shaping an organism's phenotype. To test how social group size affects stress response and behavioral characteristics, we used great tits (Parus major) from selection lines for exploratory behavior, a proxy for an avian personality trait, and birds from the wild in a brood size manipulation experiment. Nestlings were tested for stress response using an established stress test and after independence subjects were tested for exploratory behavior. Nestlings from small broods showed a stronger stress response than nestlings from normal-sized broods. Exploratory behavior was not affected by brood size but associated with sex ratio in the nest. Birds from female-biased broods became faster explorers than those from male-biased broods. The results demonstrate that early social conditions can affect physiological stress responses in nestlings and that behavioral personality traits measured after fledging can be affected by the social experience in the nest.


Clinician's commentary: Atypia in salivary gland fine needle aspiration.
Due to the heterogenicity and morphological overlap among the broad spectrum of benign and malignant salivary gland lesions, cytopathology result interpretations can be challenging and variable even among the most experienced head and neck pathologist. There was no standardization of cytopathology result reporting until the recently proposed "Milan system for reporting salivary gland cytopathology" (MSRSGC). MSRSGC may offer more clarity and help minimize ambiguity, but surgeons, as part of multidisciplinary teams, do not only rely on the tiered stratification and risk of malignancy assessment. With only the MSRSGC reported, there may be critical information missing from the overall diagnostic evaluation of salivary gland masses. Cytopathologist evaluation, description of findings, and expert interpretation of the fine-needle aspiration cytology along with differential diagnosis can be critical pieces of information, that is, utilized in management discussions with patients and their families. This information needs to be included in every cytopathology interpretation in addition to the MSRSGC classification. In clinical practice, decisions concerning salivary gland tumor management are not based on single examinations but incorporate information from multiple sources including patient histories, clinical symptoms and signs, physical examinations, imaging studies, and when available, cytopathology. Additional cytopathology information will likely help to improve the utility and predictive power of MSRSGC, similar to Bethesda Classification and the predictive importance of nuclear atypia in indeterminate thyroid biopsy material for thyroid neoplasms.


Patterns of nucleotide diversity and phenotypes of two domestication related genes (OsC1 and Wx) in indigenous rice varieties in Northeast India.
During the domestication of crops, individual plants with traits desirable for human needs have been selected from their wild progenitors. Consequently, genetic and nucleotide diversity of genes associated with these selected traits in crop plants are expected to be lower than their wild progenitors. In the present study, we surveyed the pattern of nucleotide diversity of two selected trait specific genes, Wx and OsC1, which regulate amylose content and apiculus coloration respectively in cultivated rice varieties. The analyzed samples were collected from a wide geographic area in Northeast (NE) India, and included contrasting phenotypes considered to be associated with selected genes, namely glutinous and nonglutinous grains and colored and colorless apiculus. No statistically significant selection signatures were detected in both Wx and OsC1gene sequences. However, low level of selection that varied across the length of each gene was evident. The glutinous type varieties showed higher levels of nucleotide diversity at the Wx locus (πtot = 0.0053) than nonglutinous type varieties (πtot = 0.0043). The OsC1 gene revealed low levels of selection among the colorless apiculus varieties with lower nucleotide diversity (πtot = 0.0010) than in the colored apiculus varieties (πtot = 0.0023). The results revealed that functional mutations at Wx and OsC1genes considered to be associated with specific phenotypes do not necessarily correspond to the phenotypes in indigenous rice varieties in NE India. This suggests that other than previously reported genomic regions may also be involved in determination of these phenotypes.


Cavity-Enhanced Raman and Helmholtz Resonator Photoacoustic Spectroscopy to Monitor the Mixed Sugar Metabolism of E. coli.
We introduce and compare two powerful new techniques for headspace gas analysis above bacterial batch cultures by spectroscopy, Raman spectroscopy enhanced in an optical cavity (CERS), and photoacoustic detection in a differential Helmholtz resonator (DHR). Both techniques are able to monitor O2 and CO2 and its isotopomers with excellent sensitivity and time resolution to characterize bacterial growth and metabolism. We discuss and show some of the shortcomings of more conventional optical density (OD) measurements if used on their own without more sophisticated complementary measurements. The spectroscopic measurements can clearly and unambiguously distinguish the main phases of bacterial growth in the two media studied, LB and M9. We demonstrate how 13C isotopic labeling of sugars combined with spectroscopic detection allows the study of bacterial mixed sugar metabolism to establish whether sugars are sequentially or simultaneously metabolized. For E. coli, we have characterized the shift from glucose to lactose metabolism without a classic diauxic lag phase. DHR and CERS are shown to be cost-effective and highly selective analytical tools in the biosciences and in biotechnology, complementing and superseding existing conventional techniques. They also provide new capabilities for mechanistic investigations and show a great deal of promise for use in stable isotope bioassays.


Rapid sensory gain with emotional distracters precedes attentional deployment from a foreground task.
The steady-state visual evoked potential (SSVEP), an electrophysiological marker of attentional resource allocation, has recently been demonstrated to serve as a neural signature of emotional content extraction from a rapid serial visual presentation (RSVP). SSVEP amplitude was reduced for streams of emotional relative to neutral scenes passively viewed at 6 Hz (~167 ms per image), but it was enhanced for emotional relative to neutral scenes when viewed as 4 Hz RSVP (250 ms per image). Here, we investigated whether these seemingly contradictory observations may be related to different dynamics in the allocation of attentional resources as a consequence of stimulation frequency. To this end, we advanced our distraction paradigm by presenting a visual foreground task consisting of randomly moving squares flickering at 15 Hz superimposed on task-irrelevant RSVP streams shown at 6 or 4 Hz, which could unpredictably switch from neutral to unpleasant content during the trial or remained neutral. Critically, our findings demonstrate that affective distractors captured attentional resources more strongly than their neutral counterparts, irrespective of whether they were presented at 6 or 4 Hz rate. Moreover, the emotion-dependent attentional deployment from the foreground task was temporally preceded by sustained sensory facilitation in response to emotional background images. Together, present findings provide evidence for rapid sustained visual facilitation but a rather slow attentional bias in favor of emotional distractors in early visual areas.


Real world data on outcomes of anti-CD38 antibody treated, including triple class refractory, patients with multiple myeloma: a multi-institutional report from the Canadian Myeloma Research Group (CMRG) Database.
Multiple myeloma (MM) remains incurable despite the availability of novel agents. This multi-center retrospective cohort study used the Canadian Myeloma Research Group Database to describe real-world outcomes of patients withanti-CD38 monoclonal antibody (mAb) refractory MM subsequently treated with standard of care (SoC) regimens. Patients with triple class refractory (TCR) disease (refractory to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 mAb) were examined as a distinct cohort. Overall, 663 patients had disease progression on anti-CD38 mAb therapy, 466 received further treatment (346 with SoC regimens were included, 120 with investigational agents on clinical trial and were excluded). The median age at initiation of subsequent SoC therapy of 67.9 (range 39.6-89.6) years with a median of 3 prior lines (range 1-9). The median PFS and OS from the start of subsequent therapy was 4.6 (95% CI 4.1-5.6) months and 13.3 (95% CI 10.6-16.6) months, respectively. The median PFS and OS of patients with TCR disease (n = 199) was 4.4 (95% CI 3.6-5.3) months and 10.5 (95% CI 8.5-13.8) months. Our results reinforce that real-world patients with relapsed MM, particularly those with TCR disease, have dismal outcomes. There remains an urgent unmet need for the development of and access to effective therapeutics for these patients.


Recovery of bluetongue virus serogroup from sera collected for a serological survey from apparently healthy cattle, from the Sudan.
Virus of the bluetongue (BT) serogroup was recovered from 11% of cattle sera collected from apparently healthy animals in Khartoum Province for the sole purpose of screening for BT antibodies. Since these sera did not contain BT antibodies, the donor cattle could have been scored as BT free in the serological survey. Virus was initially isolated in chicken embryos inoculated intravascularly, and was further adapted to Vero cell cultures. Isolates were identified as belonging to the BT serogroup using the agar gel immunodiffusion (AGID) and complement fixation (CF) tests. The results indicated that cattle in the Sudan could harbour BT virus without showing symptoms of the disease. Such an observation necessitates further work to clarify the role of cattle in the epidemiology of BT in the Sudan.


Genetic determinants of mouse hepatitis virus strain 1 pneumovirulence.
We report here investigation into the genetic basis of mouse hepatitis virus strain 1 (MHV-1) pneumovirulence. Sequencing of the 3' one-third of the MHV-1 genome demonstrated that the genetic organization of MHV-1 was similar to that of other strains of MHV. The hemagglutinin esterase (HE) protein was truncated, and reverse transcription-PCR (RT-PCR) studies confirmed previous work that suggested that the MHV-1 HE is a pseudogene. Targeted recombination was used to select chimeric viruses containing either the MHV-1 S gene or genes encoding all of the MHV-1 structural proteins, on an MHV-A59 background. Challenge studies in mice demonstrated that expression of the MHV-1 S gene within the MHV-A59 background (rA59/S(MHV-1)) increased the pneumovirulence of MHV-A59, and mice infected with this recombinant virus developed pulmonary lesions that were similar to those observed with MHV-1, although rA59/S(MHV-1) was significantly less virulent. Chimeras containing all of the MHV-1 structural genes on an MHV-A59 background were able to reproduce the severe acute respiratory syndrome (SARS)-like pathology observed with MHV-1 and reproducibly increased pneumovirulence relative to rA59/S(MHV-1), but were still much less virulent than MHV-1. These data suggest that important determinants of pneumopathogenicity are contained within the 3' one-third of the MHV-1 genome, but additional important virulence factors must be encoded in the genome upstream of the S gene. The severity of the pulmonary lesions observed correlates better with elevated levels of inflammatory cytokines than with viral replication in the lungs, suggesting that pulmonary disease has an important immunological component.


Soybean phenolic-rich extracts inhibit key-enzymes linked to type 2 diabetes (α-amylase and α-glucosidase) and hypertension (angiotensin I converting enzyme) in vitro.
This study sought to assess the inhibitory activities of phenolic-rich extracts from soybean on α-amylase, α-glucosidase and angiotensin I converting enzyme (ACE) activities in vitro. The free phenolic extract of the soybean was obtained by extraction with 80% acetone, while that of the bound phenolic extract was done by extracting the alkaline and acid hydrolyzed residue with ethyl acetate. The inhibitory action of these extracts on the enzymes activity as well as their antioxidant properties was assessed. Both phenolic-rich extracts inhibited α-amylase, α-glucosidase and ACE enzyme activities in a dose dependent pattern. However, the bound phenolic extract exhibited significantly (P < 0.05) higher α-amylase and ACE inhibition while the free phenolic extract had significantly (P < 0.05) higher α-glucosidase inhibitory activity. Nevertheless, the free phenolic extract had higher α-glucosidase inhibitory activity when compared to that of α-amylase; this property confer an advantage on soybean phenolic-rich extracts over commercial antidiabetic drugs with little or no side effect. And inhibition of ACE suggests the antihypertension potential of soybean phenolic-rich extracts. Furthermore, the enzyme inhibitory activities of the phenolic-rich extracts were not associated with their phenolic content. Therefore, phenolic-rich extracts of soybean could inhibit key-enzyme linked to type 2 diabetes (α-amylase and α-glucosidase) and hypertension (ACE) and thus could explain in part the mechanism by which soybean renders these health promoting effect.


High-dose PMA with RANKL and MCSF induces THP‑1 cell differentiation into human functional osteoclasts in vitro.
Osteoclasts are large multinuclear cells, which serve role in erosive bone disease. However, it is not possible to separate osteoclasts from cortical bone in order to culture the cells for further experiments. Therefore, a human osteoclast model is required to investigate the underlying mechanism of bone destruction. The most commonly‑used osteoclast model is the RAW264.7 cell line, a murine mononuclear macrophage cell line; however, there exists no reliable osteoclast model using a human cell line. The aim of the present study was to establish a functional osteoclast model using the THP‑1 cell line. Suspended THP‑1 cells were stimulated for 2 days with 5 or 100 ng/ml phorbol‑12 myristate‑13 acetate (PMA) in order to induce the cells to differentiate into adherent macrophages. A 10‑day stimulation with 50 ng/ml receptor activator of nuclear factor κ‑B ligand (RANKL) and macrophage colony‑stimulating factor (MCSF) was performed in order to induce macrophage differentiation into osteoclasts. Treatment with high‑dose PMA with RANKL and MCSF enabled the THP‑1 cells to form tartrate‑resistant acid phosphatase‑positive osteoclasts, which were able absorb bone in a bone resorption test. Treatment with low‑dose PMA with RANKL and MCSF failed to induce THP‑1 cell differentiation into osteoclasts. PMA alone, or a combination of RANKL and MCSF alone, is insufficient to stimulate THP‑1 cell differentiation into osteoclasts. In the present study, a reliable human osteoclast model was established using the THP‑1 cell line. This osteoclast model may provide a useful tool for further studies.


HGF/c-met/Stat3 signaling during skin tumor cell invasion: indications for a positive feedback loop.
Stat3 is a cytokine- and growth factor-inducible transcription factor that regulates cell motility, migration, and invasion under normal and pathological situations, making it a promising target for cancer therapeutics. The hepatocyte growth factor (HGF)/c-met receptor tyrosine kinase signaling pathway is responsible for stimulation of cell motility and invasion, and Stat3 is responsible for at least part of the c-met signal. We have stably transfected a human squamous cell carcinoma (SCC) cell line (SRB12-p9) to force the expression of a dominant negative form of Stat3 (S3DN), which we have previously shown to suppress Stat3 activity. The in vitro and in vivo malignant behavior of the S3DN cells was compared to parental and vector transfected controls. Suppression of Stat3 activity impaired the ability of the S3DN cells to scatter upon stimulation with HGF (c-met ligand), enhanced their adhesion, and diminished their capacity to invade in vitro and in vivo. Surprisingly, S3DN cells also showed suppressed HGF-induced activation of c-met, and had nearly undetectable basal c-met activity, as revealed by a phospho-specific c-met antibody. In addition, we showed that there is a strong membrane specific localization of phospho-Stat3 in the wild type (WT) and vector transfected control (NEO4) SRB12-p9 cells, which is lost in the S3DN cells. Finally, co-immunoprecipitation experiments revealed that S3DN interfered with Stat3/c-met interaction. These studies are the first confirm that interference with the HGF/c-met/Stat3 signaling pathway can block tumor cell invasion in an in vivo model. We also provide novel evidence for a possible positive feedback loop whereby Stat3 can activate c-met, and we correlate membrane localization of phospho-Stat3 with invasion in vivo.


JARID1-targeted histone H3 demethylase inhibitors exhibit anti-proliferative activity and overcome cisplatin resistance in canine oral melanoma cell lines.
Histone demethylases are overexpressed or display altered activity in numerous human cancers leading to alterations in cell cycle dynamics, DNA repair kinetics, and therapeutic resistance. Consequently, therapeutic targeting of histone demethylases has become an active and promising area of research in human oncology. However, the role of histone demethylases and the potential efficacy of demethylase inhibition in canine cancers remains largely unknown. In the present work, we addressed this knowledge gap by exploring the therapeutic potential of histone demethylase inhibitors (HDIs) in canine oral melanoma. Using canine melanoma cell lines, we determined that broad spectrum HDIs result in decreased cell survival and prolonged DNA damage repair kinetics. We then showed that JARID1B, a histone H3 demethylase implicated in proliferation-dormancy regulation and drug sensitivity in human cancers, is highly expressed in canine tumour tissues. HDIs targeting JARID1B, and related JARID1 family members, significantly reduced survival fractions in canine melanoma cell lines, but did not appear to modulate DNA damage repair kinetics like broad spectrum HDI treatments. Importantly, we found that the anti-proliferative effects of JARID1-targeted HDIs are preserved in cell lines resistant to platinum-based chemotherapeutics, suggesting that HDIs may serve as a viable therapeutic strategy when faced with oral melanomas that progress despite the use of conventional therapies.


AKT activation promotes PTEN hamartoma tumor syndrome-associated cataract development.
Mutations in the human phosphatase and tensin homolog (PTEN) gene cause PTEN hamartoma tumor syndrome (PHTS), which includes cataract development among its diverse clinical pathologies. Currently, it is not known whether cataract formation in PHTS patients is secondary to other systemic problems, or the result of the loss of a critical function of PTEN within the lens. We generated a mouse line with a lens-specific deletion of Pten (PTEN KO) and identified a regulatory function for PTEN in lens ion transport. Specific loss of PTEN in the lens resulted in cataract. PTEN KO lenses exhibited a progressive age-related increase in intracellular hydrostatic pressure, along with, increased intracellular sodium concentrations, and reduced Na+/K+-ATPase activity. Collectively, these defects lead to lens swelling, opacities and ultimately organ rupture. Activation of AKT was highly elevated in PTEN KO lenses compared to WT mice. Additionally, pharmacological inhibition of AKT restored normal Na+/K+-ATPase activity in primary cultured lens cells and reduced lens pressure in intact lenses from PTEN KO animals. These findings identify a direct role for PTEN in the regulation of lens ion transport through an AKT-dependent modulation of Na+/K+-ATPase activity, and provide a new animal model to investigate cataract development in PHTS patients.


Exclusionary Effects of Campsite Allocation through Reservations in U.S. National Parks: Evidence from Mobile Device Location Data.
Campsites represent highly sought after recreational amenities in the national parks of the United States. Equitable allocation of scarce recreational resources has long been a key management issue in U.S. national parks, but has become increasingly difficult in an era of increasing demand. At present, a growing number of national park campsites are allocated through an online reservation system well in advance of a camper's arrival at a park. Compounding the challenge of allocating these campsites is a long history of exclusivity within national park camping-institutionalized through campground design and predicated on a legacy of the leisure class's affinity for camping in national parks. Given national park camping's history of exclusivity, this exploratory study seeks to explore how online reservation systems may impact the demographics of national park campers. Using mobile device location data, estimated demographics were calculated for campers in five national park campgrounds in the U.S. that each contained some sites requiring reservations and some sites available on a first-come, first-served basis. We detail results from analyses of variance between campsites requiring reservations and those that are available on a first-come, first-served basis. Results suggest that for each of the five campgrounds, those campers camping in sites that require reservations came from areas with higher median household incomes, on average. In three of the five campgrounds, this difference was significant. Additionally, in an urban-proximate setting, those camping in sites requiring reservations came from areas with a higher portion of White residency than those campers in campsites not requiring reservations, on average. We conclude with discussion that includes management implications concerning the growing prominence of online reservation systems for outdoor recreation amenities, and a brief research agenda for diversity, equity, and inclusion (DEI) as they relate to campgrounds. Principally, the former group of implications includes the realization that online reservation systems present the unintended consequence of excluding low-income, and perhaps non-White, would-be campers-a conclusion drawn from the results of this exploratory study. This discussion includes an analysis of the distributive justice of online reservation systems.


Complications of laparoscopy.
The frontiers of laparoscopic surgery have extended from gynecologic procedures to general surgical techniques. As new applications for laparoscopy emerge, anesthesiologists must be familiar with the possible complications associated with the various laparoscopic procedures. Only by an appreciation of the potential complications of a procedure can their overall incidence be minimized. A systematic approach must consider all potential complications during laparoscopy. In addition to routine evaluation (i.e., depth of anesthesia and volume status), anesthesiologists must confirm that intra-abdominal pressure is less than 15 mm Hg, and that inadvertent endobronchial intubation, pneumothorax, and gas embolism have not occurred. In the case of precipitous changes in vital signs not responding to routine management, it is imperative to release the pneumoperitoneum and place the patient in the supine (or Trendelenburg) position. After cardiopulmonary stabilization, cautious slow reinsufflation then can be attempted. With persistent signs of significant cardiopulmonary impairment, however, it is sometimes necessary to convert to an open procedure.


Chronic ethanol exposure during late gestation produces behavioral anomalies in neonatal lambs.
A total of 45 pregnant ewes were assigned to one of three treatment groups: 1 g ethanol/kg maternal body weight (n = 18); pair-fed control (n = 15); and ad lib control (n = 12). Dosing started at gestational day (GD) 106, and was administered every other day until GD 134. Parturition occurred between GD 144 and 147. Analysis of the placentas indicated that ethanol exposure decreased cotyledon diameter and cotyledon weight compared to the control groups (p < 0. 05). At birth, lambs were given a Vigor Score and then behavior was assessed using a videotape monitoring system for 24 h. Offspring in the ethanol treatment group were significantly less vigorous at birth (p < 0.05). This finding reversed during the subsequent 24 h such that the ethanol-exposed lambs were significantly more active (p = 0.001) than the control lambs. Morphometric and histologic examination of the cerebral cortex and hippocampus revealed no differences amongst the three treatment groups. Collectively, the data demonstrate that moderate ethanol exposure during the third-trimester equivalent of gestation can produce placental dysmorphology and postnatal behavioral anomalies in neonatal lambs in the absence of gross neurologic injury.


Prevention of ventilator-associated pneumonia: can knowledge and clinical practice be simply assessed in a large institution?
User-friendly scores to assess knowledge of guidelines for prevention of ventilator-associated pneumonia (VAP) are scarce and have mainly evaluated nurses, but not students or physicians. Gaps between knowledge and actual clinical practice have not been sufficiently analyzed. We assessed knowledge of and adherence to guidelines for prevention of VAP among physicians, nurses, and students in adult ICUs. All adult ICU healthcare workers were invited to complete a 20-point questionnaire. The first part assessed personal knowledge of international guidelines for prevention of VAP; the second part assessed daily clinical practice. Personal knowledge and daily practice were scored from 0 to 10 points. We invited 257 ICU healthcare workers to participate in the study, and 167 (65%) accepted (32/54 physicians, 108/176 nurses, and 27/27 students). The median (IQR) personal knowledge scores for physicians, nurses, and students were 6 (5-7), 5 (4-6), and 5 (4-7), respectively. The median scores for daily clinical practice for physicians and nurses were 5 (4-6) and 4 (3-5), respectively. Healthcare workers with more than 1 year of ICU experience scored significantly better in personal knowledge than those with less experience: 6 (5-7) versus 4 (3-6), P = .004. A simple, easy-to-complete questionnaire enabled us to rapidly evaluate personal knowledge and reported clinical practice in prevention of VAP in large teaching institutions. These scores will be used as baseline figures to assess the impact of educational and intervention campaigns.


Primary Care Providers' Acceptance of Pharmacists' Recommendations to Support Optimal Medication Management for Patients with Diabetic Kidney Disease.
Patients with diabetic kidney disease (DKD) often struggle with blood pressure control. In team-based models of care, pharmacists and primary care providers (PCPs) play important roles in supporting patients' blood pressure management. To describe whether PCPs' acceptance of pharmacists' recommendations impacts systolic blood pressure (SBP) at 36 months. An observational analysis of a subset of participants randomized to the intervention arm of the Simultaneous risk factor control using Telehealth to slOw Progression of Diabetic Kidney Disease (STOP-DKD) study. STOP-DKD participants for whom (1) the pharmacist made at least one recommendation to the PCP; (2) there were available data regarding the PCP's corresponding action; and (3) there were SBP measurements at baseline and 36 months. Participants received monthly telephone calls with a pharmacist addressing health behaviors and medication management. Pharmacists made medication-related recommendations to PCPs. We fit an unadjusted generalized linear mixed model to assess the association between the number of pharmacists' recommendations for DKD and blood pressure management and PCPs' acceptance of such recommendations. We used a linear regression model to evaluate the association between PCP acceptance and SBP at 36 months, adjusted for baseline SBP. Pharmacists made 176 treatment recommendations (among 59 participants), of which 107 (61%) were accepted by PCPs. SBP significantly declined by an average of 10.5 mmHg (p < 0.01) among 47 of 59 participants who had valid measurements at baseline and 36 months. There was a significant association between the number of pharmacist recommendations and the odds of PCP acceptance (OR 1.19; 95%CI 1.00, 1.42; p < 0.05), but no association between the number of accepted recommendations and SBP. Pharmacists provided actionable medication-related recommendations. We identified a significant decline in SBP at 36 months, but this reduction was not associated with recommendation acceptance. NCT01829256.


Traditional uvulectomy; practice and belief among Sudanese children in Khartoum hospitals: A multi-center cross-sectional study.
Traditional healing practices are common in Sub-Saharan Africa. Traditional uvulectomy (TU) is the removal of the uvula with a sharp curved knife and is often practised in children under five years old. This practice is believed to have a therapeutic effect on children suffering from sore throat, vomiting or difficulty breastfeeding. This study aimed to describe the practice of traditional uvulectomy and Sudanese mothers' perception of it. A cross-sectional study was conducted in seven teaching hospitals across Khartoum State. We interviewed 385 mothers of children who presented to pediatric units using a semi-structured questionnaire. The study period spanned from July 2022-February 2023. A total of 385 mothers of children under five participated in this study. 33 % of mothers believed in the practice of traditional uvulectomy, yet only 17.9 % of children under five years had undergone TU. Reasons for performing TU included persistent cough (36.9 %), vomiting (33 %), difficulty in breastfeeding (22.6 %) and TU being a family tradition (25.7 %). Factors significantly associated with these practices were the mother's age, her level of education and the family's regional origin. Mothers reported that no major complications to the children were perceived as a result of the TU procedure. The practice of TU is prevalent among children who present to hospitals seeking medical advice. More than one-third of mothers had misconceptions regarding the uvula. Health education campaigns targeting females of childbearing age, and health practitioners at primary health centres and hospitals must raise awareness related to this practice.


Discordance in national estimates of hypertension among young adults.
In the United States, where coronary heart disease (CHD) is the leading cause of mortality, CHD risk assessment is a priority and accurate blood pressure (BP) measurement is essential. Hypertension estimates in the National Longitudinal Study of Adolescent Health (Add Health), Wave IV (2008)-a nationally representative field study of 15,701 participants aged 24-32-was referenced against NHANES (2007-2008) participants of the same age. We examined discordances in hypertension, and estimated the accuracy and reliability of blood pressure in the Add Health study. Hypertension rates (BP: ≥ 140/90 mm Hg) were higher in Add Health compared with NHANES (19% vs. 4%), but self-reported history was similar (11% vs. 9%) among adults aged 24-32. Survey weights and adjustments for differences in participant characteristics, examination time, use of antihypertensive medications, and consumption of food/caffeine/cigarettes before blood pressure measurement had little effect on between-study differences in hypertension estimates. Among Add Health participants interviewed and examined twice (full and abbreviated interviews), blood pressure was similar, as was blood pressure at the in-home and in-clinic examinations conducted by NHANES III (1988-1994). In Add Health, there was minimal digit preference in blood pressure measurements; mean bias never exceeded 2 mm Hg; and reliability (estimated as intraclass correlation coefficients) was 0.81 and 0.68 for systolic and diastolic BPs, respectively. The proportion of young adults in NHANES reporting a history of hypertension was twice that with measured hypertension, whereas the reverse was found in Add Health. Between-survey differences were not explained by digit preference, low validity, or reliability of Add Health blood pressure data, or by salient differences in participant selection, measurement context, or interview content. The prevalence of hypertension among Add Health Wave IV participants suggests an unexpectedly high risk of cardiovascular disease among US young adults and warrants further scrutiny.


Xanthogranulomatous pyelonephritis, perinephric type--a case report.
A 46 year-old woman with perinephric type of xanthogranulomatous pyelonephritis is described. She had a fever and pain with a palpable mass in her right flank. The blood analysis revealed anemia, leucocytosis, gamma-globulinemia, but no hyperlipidemia. The urine analysis showed nothing abnormal, but enterobacter was present in the urine. An intravenous pyelogram demonstrated a right non-functioning kidney. The diagnosis of a perinephric abscess was made from the x-ray and ultrasonogram, and a right nephrectomy was performed. The resected kidney had a tumor-like lump covered with Gerota's fascia at the postero-lateral side of the kidney. The cut surface of the kidney revealed an area of hemorrhage, blood clotting, abscess and a brownish yellow area in the perinephric fat tissue. The calyx and pelvis were normal. Histologically, the brownish yellow area was a granuloma with foam cell infiltration. The foam cells contained lipids. The renal parenchyma showed a non-specific chronic pyelonephritis.