Comparison of clinical signs and outcomes between dogs with presumptive ischemic myelopathy and dogs with acute noncompressive nucleus pulposus extrusion.
OBJECTIVE To compare clinical signs and outcomes between dogs with presumptive ischemic myelopathy and dogs with presumptive acute noncompressive nucleus pulposus extrusion (ANNPE). DESIGN Retrospective study. ANIMALS 51 dogs with ischemic myelopathy and 42 dogs with ANNPE examined at 1 referral hospital. PROCEDURES Medical records and MRI sequences were reviewed for dogs with a presumptive antemortem diagnosis of ischemic myelopathy or ANNPE. Information regarding signalment, clinical signs at initial examination, and short-term outcome was retrospectively retrieved from patient records. Long-term outcome information was obtained by telephone communication with referring or primary-care veterinarians and owners. RESULTS Compared with the hospital population, English Staffordshire Bull Terriers and Border Collies were overrepresented in the ischemic myelopathy and ANNPE groups, respectively. Dogs with ANNPE were significantly older at disease onset and were more likely to have a history of vocalization at onset of clinical signs, have spinal hyperesthesia during initial examination, have a lesion at C1-C5 spinal cord segments, and be ambulatory at hospital discharge, compared with dogs with ischemic myelopathy. Dogs with ischemic myelopathy were more likely to have a lesion at L4-S3 spinal cord segments and have long-term fecal incontinence, compared with dogs with ANNPE. However, long-term quality of life and outcome did not differ between dogs with ischemic myelopathy and dogs with ANNPE. CONCLUSIONS AND CLINICAL RELEVANCE Results revealed differences in clinical signs at initial examination between dogs with ischemic myelopathy and dogs with ANNPE that may aid clinicians in differentiating the 2 conditions.


Field-based measurements of personal erythemal ultraviolet exposure through a common summer garment.
The research in this paper quantifies the solar erythemal UV exposures to the skin through a common summer garment during outdoor activities. The erythemal exposures under the garment for the wet white garment exceeded a MED (minimum erythemal dose) at some anatomical sites in summer for a two-hour period. An erythemal exposure of 1.7 MED, in excess of the occupational limit for UV exposure, was measured under the white garment during swimming for a one-hour period. Clothing must form an important component of a UV protection strategy. However, it must be realised that total UV protection is not provided and significant UV exposures may be received beneath the garment, particularly for a white garment in the wet state. This re-enforces the necessity of a combination of several UV prevention strategies to minimise UV exposure.


Cost effectiveness analysis for nursing research.
With ever-increasing pressure to reduce costs and increase quality, nurses are faced with the challenge of producing evidence that their interventions and care provide value. Cost effectiveness analysis (CEA) is a tool that can be used to provide this evidence by comparative evaluation of the costs and consequences of two or more alternatives. The aim of this article is to introduce the essential components of CEA to nurses and nurse researchers with the protocol of a recently funded cluster randomized controlled trial as an example. This article provides (a) a description of the main concepts and key steps in CEA and (b) a summary of the background and objectives of a CEA designed to evaluate a nursing-led pain and symptom management intervention in rural communities compared with the current usual care. As the example highlights, incorporating CEA into nursing research studies is feasible. The burden of the additional data collection required is offset by quantitative evidence of the given intervention's cost and impact using humanistic and economic outcomes. At a time when U.S. healthcare is moving toward accountable care, the information provided by CEA will be an important additional component of the evidence produced by nursing research.


The progression of Duchenne muscular dystrophy: clinical trial of allopurinol therapy.
A 12-month clinical study of Duchenne muscular dystrophy was carried out during a double-blind trial of allopurinol therapy. The disease was monitored by assessment of muscle power and function, pulmonary function tests, and electrocardiography. Biochemical assessments were made of plasma creatine kinase, pyruvate kinase, uric acid, and urinary excretion of 3-methylhistidine and creatinine. Allopurinol did not alter the progression of the disease.


The importance of systematic genetic approach to familial schizophrenia cases and discussion of cryptic mosaic X chromosome aneuploidies in schizophrenia pathogenesis.
Abstract Objective. The aim of this study is to contribute to the understanding of schizophrenia genetics by using efficient algorithmic examination techniques including dysmorphic examination, karyotyping, and Fluoresence in situ hybridization (FISH). Methods. In this study we have investigated 20 familial schizophrenia patients from Turkey who had an affected first-degree relative. Dysmorphic examination of the schizophrenia cases and their relatives have been performed. High resolution banding (HRB), specific centromeric, subtelomeric and 22q11.2 region FISH probes were used for genotyping of patients. Results. Dysmorphic examination revealed ear, palate, nose, columella anomalies, and obesity in contributing patients, and the pale skin was noticed. The medical histories and clinical findings of two schizophrenia twins were almost identical. HRB study demonstrated the presence of 46,XX[55]/47,XXX[4]/48,XXXX[1] constitution in a paranoid schizophrenia case and 46,XX[67]/45,X[5] karyotype in her mother. FISH studies aiming subtelomeric chromosomal regions revealed no rearrangements and 22q11.2 regions were intact in all of the patients. Conclusions. The parental gonadal mosaicism lying at the origin of the mitotic aneuploidy may be the reason for mosaic X chromosome aneuploidies in our mother-daughter schizophrenia couple. Mosaic X chromosome aneuploidies may accompany schizophrenia cases and may contribute to pathogenesis of familial schizophrenia.


Guide wire-assisted cannulation for the prevention of post-ERCP pancreatitis: a systematic review and meta-analysis.
Cannulation techniques are recognized to be important in causing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, considerable controversy exists about the usefulness of the guide wire-assisted cannulation technique for the prevention of PEP. This systematic review of randomized controlled trials (RCTs) aimed to compare the guide wire-assisted cannulation technique with the contrast-assisted cannulation technique. CENTRAL, MEDLINE, EMBASE, CINAHL, and abstracts from Digestive Disease Week and the United European Gastroenterology Week were searched up to February 2012 for RCTs comparing the guide wire-assisted ERCP cannulation technique with the conventional contrast-assisted ERCP cannulation technique. The risk of bias was assessed, and outcomes were pooled by meta-analysis (random-effects model). The primary outcome measure was PEP. Secondary outcome measures included severity of PEP, primary common bile duct (CBD) cannulation success, overall CBD cannulation success, precut sphincterotomy, and other ERCP-related complications. In total, 12 RCTs (3450 patients) were included. The guide wire-assisted cannulation technique significantly reduced PEP compared with the contrast-assisted cannulation technique (risk ratio [RR] 0.51, 95 % confidence interval [CI] 0.32 - 0.82). In addition, the guide wire-assisted cannulation technique was associated with greater primary cannulation success (RR 1.07, 95 %CI 1.00 - 1.15), fewer precut sphincterotomies (RR 0.75, 95 %CI 0.60 - 0.95), and no increase in other ERCP-related complications. Subgroup analyses indicated that this significant risk reduction in PEP with the guide wire-assisted cannulation technique existed only in "non-crossover" trials (RR 0.22, 95 %CI 0.12 - 0.42). The results were robust in sensitivity analyses. Compared with the contrast-assisted cannulation technique, the guide wire-assisted cannulation technique increases the primary cannulation rate and reduces the risk of PEP, and therefore appears to be the most appropriate first-line cannulation technique.


Elevated Factor VIII Levels and Shortened APTT in Recurrent Abortions.
Thrombotic disorders have been found to be associated with recurrent abortions. Several risk factors have been identified. APTT reflects the common pathway and intrinsic pathway of coagulation cascade and hence is a good marker for thrombotic work. Elevated factor VIII: C has also been identified as risk factor for recurrent miscarriage. This study aims at identifying association of elevated factor VIII levels, shortened APTT and recurrent abortions in Indian population as little has been studied about this and the literature available is also based on studies done in European population. This study also aims to find whether shortened APTT can be an independent risk as well. Women referred to the obstetrics department with a history of early recurrent early pregnancy loss (at least three pregnancy losses before 13 weeks of gestation) were included in this study. Exclusion criteria were elevated CRP levels, positive antiphospholipid antibodies, endocrine, immunological or anatomical cause of embryo demise. A total of 68 cases of recurrent abortion were included in this study, 68 normal pregnant females (<15 weeks of gestation) were also included as controls with no history of abortion. The age group of the cases as well as control was 20-45 years. Activated partial thromboplastin time and factor VIII assay (one stage APTT based) were done on the blood samples. Increased factor VIII levels were seen in 25 cases (36.4%); 19 cases showed shortened APTT (27.3%); 12 cases showed both increased factor VIII levels as well as shortened APTT (18%). All risk factors were negative in 36 cases (52.9%). None of the controls showed elevated factor VIII levels or shortened APTT. The mean APTT values of the control subjects was 31.01 and cases were 27.01 (p=0.001). The mean factor VIII levels of case were 152.85% and control 144.953% (p=0.012). There was significant association between recurrent abortions and elevated factor VIII :c levels and shortened APTT. Shortened APTT was also identified as an independent risk factor.


Interstitial Oxide Ion Distribution and Transport Mechanism in Aluminum-Doped Neodymium Silicate Apatite Electrolytes.
Rare earth silicate apatites are one-dimensional channel structures that show potential as electrolytes for solid oxide fuel cells (SOFC) due to their high ionic conductivity at intermediate temperatures (500-700 °C). This advantageous property can be attributed to the presence of both interstitial oxygen and cation vacancies, that create diffusion paths which computational studies suggest are less tortuous and have lower activation energies for migration than in stoichiometric compounds. In this work, neutron diffraction of Nd(28+x)/3AlxSi6-xO26 (0 ≤ x ≤ 1.5) single crystals identified the locations of oxygen interstitials, and allowed the deduction of a dual-path conduction mechanism that is a natural extension of the single-path sinusoidal channel trajectory arrived at through computation. This discovery provides the most thorough understanding of the O(2-) transport mechanism along the channels to date, clarifies the mode of interchannel motion, and presents a complete picture of O(2-) percolation through apatite. Previously reported crystallographic and conductivity measurements are re-examined in the light of these new findings.


International radiation safety standards.
The system of international safety standards of the International Atomic Energy Agency (IAEA) is described with explanations as to the purpose of each level of the hierarchy. There is a system of committees that advise the IAEA and approve the safety standards and one of these committees is the Radiation Safety Standards Committee (RASSC). The Committee meets twice a year (the last meeting was 24-27 March 2003) and this note outlines the current situation with respect to published safety standards documents at the fundamentals, requirements and guides levels and the status of documents under development. Guidance on how to find more information and to keep up to date on the development of documents is provided. The forward plans of the IAEA in this area are discussed briefly.


High calcium enhances the expression of double-stranded RNA sensors and antiviral activity in epidermal keratinocytes.
Double-stranded RNA (dsRNA) sensors including TLR3, MDA5 and RIG-I are expressed in epidermal keratinocytes and play an important immunological role by enhancing various innate and adaptive immune responses. Although the role of elevated extracellular calcium concentration in keratinocyte differentiation is well understood, the effect of high calcium on dsRNA sensors is not well studied. We investigated alterations in dsRNA sensor expression and antiviral activity induced by a high extracellular concentration of calcium in epidermal keratinocytes. Normal human epidermal keratinocytes (NHEKs) were stimulated with high calcium and/or synthetic dsRNA, poly (I:C). TLR3, IFIH1 (MDA5) and DDX58 (RIG-I) expression were measured via qPCR, and IFN-β and human beta-defensin 2 (HBD2) levels were measured using ELISA. TLR3 localization was evaluated with immunocytofluorescence. Antiviral activity was quantified with virus plaque assays using herpes simplex virus type 1 (HSV-1). High calcium significantly upregulated mRNA expression of TLR3, IFIH1 and DDX58 in NHEKs. In addition, high calcium significantly enhanced poly (I:C)-induced anti-HSV-1 activity in NHEKs. The antiviral molecule HBD2 but not IFN-β induction by poly (I:C) was enhanced by high calcium. Our findings indicate that high levels of extracellular calcium enhance the expression of dsRNA sensors and augment antiviral activity in epidermal keratinocytes.


Impact of Body Mass Index on Outcomes Following Anatomic GreenLight Laser Photoselective Vaporization of the Prostate.
Introduction: Obesity can lead to increased risk of perioperative complications in surgical patients, but evidence is lacking regarding the impact of obesity on bladder outlet surgery outcomes. We sought to assess the safety and efficacy of GreenLight photoselective vaporization of the prostate (PVP) in obese patients by comparing functional outcomes and complications in men, stratified according to the body mass index (BMI). Materials and Methods: A retrospective analysis was undertaken of 424 men who underwent 180W GreenLight PVP between 2012 and 2016 at two tertiary medical centers. Patients were stratified based on the World Health Organization (WHO) classification of obesity as determined by BMI. Normal weight men had BMI <25 kg/m2, overweight men had BMI between 25 and 30 kg/m2, and obese men had BMI greater than 30 kg/m2. Primary endpoints examined were differences in intraoperative outcomes and incidence of intraoperative and postoperative complications between BMI groups. Secondary endpoints were improvements in the International Prostate Symptom Score, quality of life score, and the uroflowmetry variables, maximum urinary flow rate and postvoid residual. Results: The BMI groups did not differ regarding operative time or lasing time after matching for prostate volume, but overweight patients in the matched cohort still required higher mean energy use than normal weight men (258.6 kJ vs 233.9 kJ; p = 0.017). No significant differences between BMI groups were observed for intraoperative complications, postoperative complications, or readmission rates. All functional parameters were significantly improved at 24 months for each group, with no differences in improvement between groups. On multivariable analysis, BMI was not a significant predictor for outcomes following PVP. Conclusions: Increased BMI has a negligible effect on intraoperative parameters and does not affect postoperative complication rates or functional outcomes. GreenLight XPS 180W PVP is a safe and effective procedure in overweight and obese men.


The physician's obligation to treat AIDS patients.
Medicine's triumph over contagious disease through improved techniques of prevention and treatment in the decades before the appearance of the acquired immunodeficiency syndrome (AIDS) left physicians with little impetus to explore their feelings regarding the acceptance of personal risk in the course of patient care. The rapid expansion of the AIDS epidemic, however, has made it essential for every physician and medical student to confront this issue and determine whether he is willing to accept the minimal risks of transmission posed by the human immunodeficiency virus (HIV) to health care workers. This paper will present five arguments in support of the contention that the physician is obligated to treat all those who would benefit from his care, even when such care entails personal risk to himself. These arguments include the historical traditions of the profession, formal ethical codes, the dependent nature of the patient, the social contract, and medicine as a profession.


Complete Genome Sequence of a Klebsiella pneumoniae Strain Isolated from a Known Cotton Insect Boll Vector.
Klebsiella pneumoniae (associated with bacterial pneumonia) was previously isolated from Nezara viridula, a significant vector of cotton boll-rot pathogens. We provide the first annotated genome sequence of the cotton opportunistic strain K. pneumoniae 5-1. This data provides guidance to study the bases of cotton pathogenesis by bacteria associated with vectors.


Liquid chromatography-tandem mass spectrometry assay for simultaneous measurement of estradiol and estrone in human plasma.
Estradiol (E2) and estrone (E1) measurements form an integral part of the assessment of female reproductive function and have expanding roles in other fields. However, many E1 and E2 immunoassays have limited functional sensitivity, suffer from cross-reactivity, and display poor intermethod agreement. To overcome these problems, we developed a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the simultaneous measurement of E1 and E2. After dansyl chloride derivatization, samples were separated by fast gradient chromatography and injected into a tandem mass spectrometer after formation of positive ions with atmospheric pressure chemical ionization. The limits of detection and quantification, recovery, linearity, precision, and reference intervals were determined, and performance was compared with several immunoassays. Total run time per sample was 5 min. The multiple-reaction monitoring ion pairs were m/z 506/171 for 3-dansyl-estradiol and m/z 504/171 for 3-dansyl-estrone. The limits of detection for E1 and E2 were 12.9 pmol/L (3.5 ng/L) and 10.3 pmol/L (2.8 ng/L), respectively. Interassay imprecision (CV) was 4-20% (n = 20). The limits of quantification (functional sensitivities) for E1 and E2 were 44.1 pmol/L (11.9 ng/L) and 23.2 pmol/L (6.3 ng/L), respectively. The assay was linear to >2200 pmol/L ( approximately 600 ng/L) for each analyte. Recoveries were 93-108% for E1 and 100-110% for E2. No cross-reactivity was observed. Method comparison with several immunoassays revealed that the latter were inaccurate and prone to interferences at low E1 and E2 concentrations. LC-MS/MS allows rapid, simultaneous, sensitive, and accurate quantification of E1 and E2 in human serum.


Effectiveness of family-based eHealth interventions in cardiovascular disease risk reduction: A systematic review.
Family-based eHealth interventions to reduce cardiovascular disease risk have potential as a primary prevention strategy to improve the health of parents and their children. This systematic review evaluated the effectiveness of such interventions in modifying parent and child/adolescent risk factors such as body mass index, physical activity, dietary intakes and alcohol use. Five electronic databases were searched up to April 2020. Of 2193 articles identified, seven randomised controlled trials met inclusion criteria and were reviewed. Data were extracted regarding study setting, design, methods, eHealth technology used, intervention and control group components, retention rates, outcome measures, incentives and limitations. Risk of bias and quality assessment were carried out using Cochrane methods. A qualitative narrative data synthesis of the studies was conducted. Our review found that three studies showed an improvement in alcohol use among parents and adolescents as a result of the eHealth intervention. Among children/adolescents, two studies showed an improvement in dietary intake, one study showed an improvement in physical activity, and one study showed an improvement in body mass index as a result of the eHealth intervention. Interventions appeared more likely to be effective if they were theory-based, had longer follow-up periods, were incentivised and included regular interaction. Our findings suggest that, despite a paucity of high-quality trials, there is some evidence that family-based eHealth interventions have potential to reduce cardiovascular disease risk. However, more sufficiently powered, higher-quality trials with theory driven, clearly described interventions and unambiguous outcomes are needed.


Integrative East-West Medicine Intervention for Chronic Daily Headache: A Case Report and Care Perspective.
Chronic daily headache is a group of headache syndromes including most commonly chronic migraine and chronic tension-type headache, which often overlap, are complicated by medication overuse and are disabling, costly, and variable responsive to western pharmacotherapeutic interventions. There is growing research and awareness of integrative health approaches and therapies to address patients with chronic headache, yet limited examples of how to deliver this approach. This article reviews a commonly seen challenging case of a patient with overlapping chronic migraine and chronic tension-type headache complicated by medication overuse managed with an integrative east-west medicine intervention. This included person-centered biopsychosocial history taking, traditional Chinese medicine informed acupuncture, trigger point injections, and contributing factors modifications. A narrative review of the literature is presented to demonstrate an evidence-informed rationale for incorporating nonpharmacologic approaches to effectively help reduce the symptom burden of this patient population.


The catch mechanism of molluscan smooth muscles.
We have examined the arrangements of the thick and thin filaments of the smooth muscle of the adductor of the bivalve Cristaria plicata, Leach, in the catch state induced by acetylcholine, both in ultrathin sections and in separate filaments. The thick filaments are heavily bent and entangled and the thin filaments irregularly arranged. One thin filament may be attached to several thick filaments. When the muscle is in the relaxed state, the two kinds of filaments are seen to be in parallel. However, no difference could be observed in the periodic structure of the paramyosin core of the thick filaments in the relaxed state or in catch. Both cross-striated and checkerboard types coexist. It seems that phase transition is not directly related to catch. We propose that the disordered arrangements of the thick and thin filaments and the formation of three-dimensional anastomosed networks are the structural basis for catch, with a consequent loss of the capability of directional sliding of the filaments and requiring time to restore orderliness.


Two distinct low-voltage-activated Ca2+ currents contribute to the pacemaker mechanism in cockroach dorsal unpaired median neurons.
1. The contribution of Ca2+ currents to the endogenous firing properties of cockroach isolated adult dorsal unpaired median neurons was investigated using whole cell patch-clamp technique with 5 mM Ca2+ as the charge carrier. At least three types of Ca2+ currents, a high-voltage-activated Ca2+ current and two low-voltage-activated (LVA) Ca2+ currents, have been found in these neurons. This study focused on the LVA Ca2+ currents, which are suitable candidates in the generation of the slow predepolarization because of their low threshold of activation. 2. The global LVA Ca2+ current could be dissociated by means of nickel sensitivity, deactivation time constant and voltage dependence of time to peak, tail current amplitude and inactivation, as transient and maintained LVA Ca2+ currents. 3. The transient LVA Ca2+ current, sensitive to 100 microM Ni2+, was isolated by using a subtraction procedure. It was activated at -70 mV and half-inactivated at -59.5 mV. The inactivation was purely voltage dependent. Current-clamp experiments performed with 150 microM Ni2+ indicated that this current was involved in the initial part of the predepolarization. 4. The maintained LVA Ca2+ current, resistant to 100 microM Ni2+, was activated in a range of potential 10 mV more positive than the transient LVA Ca2+ current, and its voltage dependence of inactivation displayed a U-shaped-curve. 5. Replacing Ca2+ with Ba2+ in equimolar amount or low internal Ca2+ concentration [5 mM bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) in the pipette] induced a monotonic voltage dependence of inactivation and increased the rate of relaxation of this current. These effects were mimicked by high internal Ca2+ concentration [0.1 mM Ca2+ and no ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid in the pipette]. This demonstrated an unusual Ca2+-sensitive inactivation process that varied over a narrow range of Ca2+ concentrations. 6. Current-clamp experiments performed under 150 microM Ni2+, with 15 mM external Ca2+ concentration (which potentiated the maintained LVA current within 30 s of superfusion) or with 5 mM BAPTA in the pipette demonstrated the participation of this current in the last two-thirds of the slow predepolarizing phase. 7. Our findings demonstrated, for the first time in neurosecretory cells, the coexistence of two distinct LVA Ca2+ currents, which have specialized function in the generation of the pacemaker activity.


Sodium hyaluronate and polyvinyl alcohol artificial tear preparations. A comparison in patients with keratoconjunctivitis sicca.
An unpreserved artificial tear substitute containing 0.1% sodium hyaluronate was compared with a preparation containing 1.4% polyvinyl alcohol and 0.5% chlorobutanol in a controlled, double-masked, randomized study in patients with moderately severe keratoconjunctivitis sicca. Patients were evaluated initially, at 1, 4, and 8 weeks. The dry-eye status was evaluated by means of tear-film osmolality, tear breakup time, rose bengal staining, Schirmer's test (without anesthesia), and ocular surface-impression cytology. In general, neither preparation was found to be superior to the other. In both study groups, the mean tear-film osmolality and rose bengal staining score improved over the eight-week study, but the degree of squamous metaplasia of the bulbar conjunctival surface, as shown by impression cytology, did not change significantly.


Exclusion of candidate genes in seven Turkish families with autosomal recessive amelogenesis imperfecta.
Amelogenesis imperfectas (AI) are a group of inherited defects of dental enamel formation that show both clinical and genetic heterogeneity. Seven Turkish families segregating autosomal recessive AI (ARAI) were evaluated for evidence of a genetic etiology of AI for the seven major candidate gene loci (AMBN, AMELX, ENAM, FAM83H, KLK4, MMP20, and TUFT1). Dental and periodontal characteristics of the affected members of these families were also described. The mean scores of DMFS and dfs indices were 9.7 and 9.6, respectively. The mean PPD was 2.2 mm and the percentage of the sites with plaque and BOP were 87.8% and 72.4%, respectively. The exons and intron/exon junctions of the candidate genes were sequenced and no gene mutations were identified in any individuals. These findings support the existence of an additional gene(s) that are etiologic for ARAI in these families.


Summary and evaluation of guidelines for occupational exposure to power frequency electric and magnetic fields.
Major U.S. and international guidelines for limiting occupational exposures to EMF are evaluated. These safety guidelines are designed to prevent short-term adverse effects by maintaining bulk-tissue current densities below 10 mA m(-2) (rms). Above this level, effects of induced currents and electric fields can include stimulation of neural and cardiac tissues. The models and input data used by guideline-setting organizations to relate 50/60-Hz magnetic-field exposures to induced current densities differ significantly. In order to develop a better understanding of such differences, the current densities derived from exposure guideline models are compared to minimum thresholds for cardiac stimulation and fibrillation. The nominal minimum thresholds for cardiac stimulation and ventricular fibrillation are 100 times and 200 times greater, respectively, than the current density of 10 mA m(-2) used as a dosimetric limit. However, the assumed relationship between the 10 mA m(-2) dose limit and magnetic field exposure limits introduces additional uncertainty. The ratios between the threshold for cardiac stimulation and the calculated induced current density at the exposure limit vary between a low of 50 and a high of 526, depending upon the guideline. These ratios, as indicators of implicit safety factors, are larger than those recommended to protect against adverse effects of induced current density, including cardiac stimulation, in magnetic resonance imaging or against adverse effects of toxic chemical exposures. This review and assessment of EMF occupational exposure guidelines suggests that several scientific and compliance issues remain ambiguous or unresolved. Recommendations are made for guideline organizations to strengthen and clarify the scientific basis for the guideline process. These recommendations include the documentation of supporting data, development of operational definitions for guidelines, examination of dosimetric models, clarification of safety factors, and identification of high priority topics for future research.


Heat pain threshold and tolerance show no left-right perceptual differences at complementary sites of the human forearm.
Pain threshold and pain tolerance of heat noxious stimuli were assessed to determine whether they are equivalent when measured at three equidistant sites of both volar forearms. Heat pain threshold and tolerance were measured in 18 healthy volunteers using a standard stimulation device consisting of a thermode. Pain threshold and pain tolerance did not differ within and across forearm sites. Experimenters addressing heat pain threshold and tolerance in healthy volunteers may freely choose and change stimulation sites on both volar forearms, without the risk of confounding site effects on dependent variables. This data completes previous reports on side effects by analyzing the effect of site on the forearm for both heat pain threshold and tolerance. The absence of side and site effects may contribute to setting a more secure basis for assessments of laterality effects of painful stimulation.


Expression of respiratory mucins in fatal status asthmaticus and mild asthma.
The airways of patients with asthma are characterized by chronic inflammatory changes comprising mainly T-cells and eosinophils, and airway remodelling with goblet cell metaplasia and submucosal gland hyperplasia. Mucus hypersecretion is often a marked feature, particularly in status asthmaticus. The matrix of airway sputum consists of high molecular glycoproteins and mucins. In this study, the expression and distribution of the major gel-forming mucins MUC5AC and MUC5B were studied in fatal status asthmaticus tissues and bronchial biopsies of mild asthmatic patients. The effect of inhaled corticosteroids on the expression of these mucins was also investigated. Polyclonal antibodies specific for MUC5AC and MUC5B, and a monoclonal antibody for MUC5B were used to stain lung tissues and airway mucosal biopsies obtained from patients who died of status asthmaticus (n=5) and from mild asthmatics (n=4), respectively. Immunohistochemistry for MUC5AC revealed abundant staining of goblet cells situated in the epithelial surface lining and glandular ducts of tissues from patients with fatal asthma. MUC5B immunoreactivity was restricted to mucous cells of submucosal glands and to epithelial cells. In mild asthmatics, large amounts of MUC5B, but not MUC5AC, positive extracellular mucus was found in the airway lumen as plugs, adjacent to the epithelial lining and in the necks of glandular secretory ducts of mild asthmatics. The distribution of MUC5AC and MUC5B in bronchial biopsies of mild asthmatics was similar before and after inhaled steroid treatment. The expression of MUC5AC and MUC5B shares a similar distribution to normal airways in different states of asthma. The distribution is not affected by topical corticosteroid therapy.


A staged approach evaluation of remotely supervised myofeedback treatment (RSMT) in women with neck-shoulder pain due to computer work.
Remotely supervised myofeedback treatment (RSMT) is a relatively new intervention aimed at reducing neck-shoulder pain and disabilities. Subjects are equipped with a garment that can be worn under the clothes during daily work. Dry surface electrodes incorporated in this garment measure muscle activation (sEMG) of the trapezius muscle. The garment is connected to an ambulant device that provides feedback to the subject when muscle relaxation is insufficient. sEMG data are also sent to a secured server that is accessible by therapists for remote counseling purposes. In conformance with the evaluation stages of DeChant, RSMT was evaluated on technical feasibility, patient satisfaction, and changes in clinical outcomes. In addition, subjects were asked about their willingness to pay. The study population consisted of 10 female workers suffering from neck-shoulder pain related to computer work. Results show that in 78% of the remote counseling sessions, sufficient amounts of data were available at the server for the therapist to make an assessment of muscle tension needed for the remote counseling sessions. Subjects were highly satisfied about the usefulness and ease of use of the remote counseling. However, they were less satisfied with the technical functioning of the myofeedback system. Eighty percent of the subjects reported a reduction in pain intensity and disability directly after RSMT. Subjects were willing to contribute a maximum of 200 euro for RSMT. Based on this study, it can be concluded that RSMT is technically feasible and induces changes in clinical outcomes. However, further improvements to technical functioning and research into the clinical effectiveness are needed before this treatment can go into real deployment.


Impact of COVID-19 on incidence and treatment of intracranial aneurysms in Poland: a national study.
The COVID-19 pandemic greatly disrupted the national healthcare system in Poland, resulting in the implementation of new protocols allowing only patients with severe diagnoses to receive immediate treatment. Given that an intracranial aneurysm (IA) is regarded as one of the most severe diagnoses, we planned to assess whether the current protocol has successfully provided the standard treatment for IAs. Data on all IA cases treated from 2015 to 2020 was extracted from the JGP (a homogeneous group of patients) catalogue provided by the National Health Index of Poland (NFZ, Narodowy Fundusz Zdrowia). Poisson regression was used to determine the significance of the change in hospital admissions, and differences between proportions were analysed using the "N-1" Chi-squared test. A total of 21,801 IA patients treated during 2015-2020 were included in this study. The overall number of hospitalisations due to IAs fell in the open surgery group, but not in the endovascular cohort. Mortality rates following IA treatment increased significantly by 21% in 2020 compared to preceding years. The demographics changed as well; the patients were significantly younger during the pandemic. Our findings show that the current strategy for optimal care for patients diagnosed with IAs in Poland during the pandemic is failing to maintain high quality treatment. New methods to improve the current plan should be implemented to address future crises.


The use of intra-coronary optical coherence tomography for the assessment of sirolimus-eluting stent fracture.
Drug-eluting stents (DES) have made a tremendous impact on the practice of percutaneous coronary intervention. Recently however, long-term DES failures have become a focal point, particularly with restenosis and thrombosis. An uncommon, yet important cause of DES failure is stent fracture. Of the two established first generation DES, the sirolimus-eluting stent (SES) has been particularly linked to cases of stent fracture, likely as a result of its closed cell design compared with other DES employing an open cell system. We present 2 cases of SES fracture confirmed using high-resolution intravascular optical coherence tomography giving unique insights into the in-vivo appearance of this complication.


Isoalantolactone inhibits UM-SCC-10A cell growth via cell cycle arrest and apoptosis induction.
Isoalantolactone is a sesquiterpene lactone compound isolated from the roots of Inula helenium L. Previous studies have demonstrated that isoalantolactone possesses antifungal, anti-bacterial, anti-helminthic and anti-proliferative properties in a variety of cells, but there are no studies concerning its effects on head and neck squamous cell carcinoma (HNSCC). In the present study, an MTT assay demonstrated that isoalantolactone has anti-proliferative activity against the HNSCC cell line (UM-SCC-10A). Immunostaining identified that this compound induced UM-SCC-10A cell apoptosis but not necrosis. To explain the molecular mechanisms underlying its effects, flow cytometry and western blot analysis showed that the apoptosis was associated with cell cycle arrest during the G1 phase, up-regulation of p53 and p21, and down-regulation of cyclin D. Furthermore, our results revealed that induction of apoptosis through a mitochondrial pathway led to up-regulation of pro-apoptotic protein expression (Bax), down-regulation of anti-apoptotic protein expression (Bcl-2), mitochondrial release of cytochrome c (Cyto c), reduction of mitochondrial membrane potential (MMP) and activation of caspase-3 (Casp-3). Involvement of the caspase apoptosis pathway was confirmed using caspase inhibitor Z-VAD-FMK pretreatment. Together, our findings suggest that isoalantolactone induced caspase-dependent apoptosis via a mitochondrial pathway and was associated with cell cycle arrest in the G1 phase in UM-SCC-10A cells. Therefore, isoalantolactone may become a potential drug for treating HNSCC.


Magnesium-flush infusion into the aortic root just before reperfusion reduces the requirement for internal defibrillation and early post-perfusion arrhythmias.
Pre- and post-operative administration of magnesium has beneficial effects on post-operative ischaemia and reperfusion arrhythmias, but few studies have examined whether intra-operatively administered magnesium can prevent the effects of intra-operative arrhythmias. The aim of this randomized, double-blind study was to compare the effects of intra-operative magnesium or placebo on intra-operative arrhythmias in patients undergoing coronary bypass grafting. Patients received a flush infusion of magnesium or placebo into the aortic root before cross-clamp removal. The results showed that rate of spontaneous resumption of a cardiac rhythm was significantly higher, and number of shocks for defibrillation, energy requirement for defibrillation and rate of intra-operative ventricular tachyarrhythmias were significantly lower in the magnesium group, compared with the placebo group. The differences in need for temporary pacing, and in serum magnesium levels, were not significant. Intra-operative administration of magnesium has beneficial effects on the outcome of surgery. Larger, multicentre clinical investigations should now be undertaken.


Which perceived characteristics make product innovations appealing to the consumer? A study on the acceptance of fruit innovations using cross-cultural consumer segmentation.
In general, fruit consumption in the EU does not meet governments' recommended levels, and innovations in the fruit industry are thought to be useful for increasing fruit consumption. Despite the enormous number of product innovations, the majority of new products in the market fail within the first two years, due to a lack of consumer acceptance. Consumer segmentation may be a useful research tool to increase the success rates of new fruit products. The current study aims to identify consumer segments based on individual importance rankings of fruit choice motives. We conducted a cross-national, online panel survey on fresh fruit innovations in four European countries: the Netherlands (n=251), Greece (n=246), Poland (n=250), and Spain (n=250). Our cluster analysis revealed three homogeneous consumer segments: Average Joe, the Naturally conscious consumer, and the Health-oriented consumer. These consumer segments differed with respect to their importance ratings for fruit choice motives. Furthermore, the willingness to buy specific fruit innovations (i.e., genetically modified, functional food and convenience innovation) and the perceived product characteristics that influence this willingness differed across the segments. Our study could lead to more tailored marketing strategies aimed at increasing consumer acceptance of fruit product innovations based on consumer segmentation.


Chemistry and biological activity of secondary metabolites in Euphorbia from Iran.
The chemical constituents of some species of Euphorbia, which grow mostly in semi-desert areas in Iran and on the Alborz Mountains in the north of Tehran, have been found to include chemotaxonomically important myrsinane diterpenoids and cycloartane triterpenoids. The Euphorbia plants collected in province of Azarbaijan in the northwestern part of Iran contained mostly derivatives of skin-irritating ingenol esters. Some of the diterpenoids with myrsinane carbon skeleton inhibited enzymes such as alpha-glycosidase, urease, HIV-1 reverse transcriptase, and prolyl endopeptidase. They also showed analgesic and DNA-damaging activities. The present review describes the chemistry and biological activity of several compounds isolated from different species of Iranian Euphorbia: diterpenoids with myrsinane skeletons, flavonoids, tannins, alkanes, sterols, mono-, sesqui- and triterpenoids, skin-irritating and tumor-promoting latexes and their active ingenol diterpenoids.


Transfer learning using a multi-scale and multi-network ensemble for skin lesion classification.
Skin cancer is among the most common cancer types in the white population and consequently computer aided methods for skin lesion classification based on dermoscopic images are of great interest. A promising approach for this uses transfer learning to adapt pre-trained convolutional neural networks (CNNs) for skin lesion diagnosis. Since pre-training commonly occurs with natural images of a fixed image resolution and these training images are usually significantly smaller than dermoscopic images, downsampling or cropping of skin lesion images is required. This however may result in a loss of useful medical information, while the ideal resizing or cropping factor of dermoscopic images for the fine-tuning process remains unknown. We investigate the effect of image size for skin lesion classification based on pre-trained CNNs and transfer learning. Dermoscopic images from the International Skin Imaging Collaboration (ISIC) skin lesion classification challenge datasets are either resized to or cropped at six different sizes ranging from 224 × 224 to 450 × 450. The resulting classification performance of three well established CNNs, namely EfficientNetB0, EfficientNetB1 and SeReNeXt-50 is explored. We also propose and evaluate a multi-scale multi-CNN (MSM-CNN) fusion approach based on a three-level ensemble strategy that utilises the three network architectures trained on cropped dermoscopic images of various scales. Our results show that image cropping is a better strategy compared to image resizing delivering superior classification performance at all explored image scales. Moreover, fusing the results of all three fine-tuned networks using cropped images at all six scales in the proposed MSM-CNN approach boosts the classification performance compared to a single network or a single image scale. On the ISIC 2018 skin lesion classification challenge test set, our MSM-CNN algorithm yields a balanced multi-class accuracy of 86.2% making it the currently second ranked algorithm on the live leaderboard. We confirm that the image size has an effect on skin lesion classification performance when employing transfer learning of CNNs. We also show that image cropping results in better performance compared to image resizing. Finally, a straightforward ensembling approach that fuses the results from images cropped at six scales and three fine-tuned CNNs is shown to lead to the best classification performance.


Review: The nicotinic modulation of pain.
Pain is a physiological unpleasant sensation that associated with actual or potential tissue damage and affects the major part of human population. Numerous modulatory system control pain through a complex process. The drugs that regulate the modulators involving in this process are currently available; however, the studies to understand the process and develop new agents are still going on. In this review, it is aimed to relay information about how nicotinic receptors contribute the pain modulation. It is obvious that a wide variety of nicotinic receptors is located in both peripheral and central areas. Among these receptors α7, α4β2 and α9α10 receptor subtypes draw attention in terms of pain modulation. The fact that different receptor subtypes involve in different processes of different pain conditions leads to provide beneficial results from the agonism of α7, α4β2 and antagonism of α9α10. The major restraint of the usage of nAChR agonists is their adverse effects. However, nowadays, the side effects are reduced by the clinical developments. Additionally, positive allosteric modulators that amplify the effectiveness of nAChR ligands are in demand.


Immunohistological study of the anatomic relationship of toxoplasma antigens to the inflammatory response in the brains of mice chronically infected with Toxoplasma gondii.
The relationship of toxoplasma antigen(s) to the origin and long-term persistence of the mononuclear cell inflammatory infiltrate that is present in the brains of mice chronically infected with Toxoplasma gondii was studied by using the peroxidase-antiperoxidase immunohistochemical staining technique. C3H/Km mice were infected with the avirulent C37 strain of T. gondii and sequentially sacrificed over the ensuing 107 days. Comparable sections of each brain were prepared for routine light microscopy. Antisera to toxoplasma made in rabbits were used for immunohistological staining, and adjacent slides were also stained with conventional histological stains. The peroxidase-antiperoxidase stain demonstrated toxoplasma tissue cysts, tachyzoites, and intra- and extracellular antigen-antibody reaction products. Early infection was characterized by small tight clusters of free tachyzoites gaining access to brain substance in the absence of an inflammatory response. Once there was disruption of neural parenchyma, a mononuclear cellular infiltrate rapidly ensued. After the first days of infection, mononuclear cells were always present in all infected brains and were anatomically associated with some component of toxoplasma antigen(s). The histological picture of late infection suggested that recurrent episodes of hematogenous dissemination of tachyzoites occurred in infected mice and that such episodes were at least partially responsible for persistence of an antigenic stimulus.


Safety and Potential Effect of a Single Intracavernous Injection of Autologous Adipose-Derived Regenerative Cells in Patients with Erectile Dysfunction Following Radical Prostatectomy: An Open-Label Phase I Clinical Trial.
Prostate cancer is the most common cancer in men, and radical prostatectomy (RP) often results in erectile dysfunction (ED) and a substantially reduced quality of life. The efficacy of current interventions, principal treatment with PDE-5 inhibitors, is not satisfactory and this condition presents an unmet medical need. Preclinical studies using adipose-derived stem cells to treat ED have shown promising results. Herein, we report the results of a human phase 1 trial with autologous adipose-derived regenerative cells (ADRCs) freshly isolated after a liposuction. Seventeen men suffering from post RP ED, with no recovery using conventional therapy, were enrolled in a prospective phase 1 open-label and single-arm study. All subjects had RP performed 5-18 months before enrolment, and were followed for 6 months after intracavernosal transplantation. ADRCs were analyzed for the presence of stem cell surface markers, viability and ability to differentiate. Primary endpoint was the safety and tolerance of the cell therapy while the secondary outcome was improvement of erectile function. Any adverse events were reported and erectile function was assessed by IIEF-5 scores. The study is registered with ClinicalTrials.gov, NCT02240823. Intracavernous injection of ADRCs was well-tolerated and only minor events related to the liposuction and cell injections were reported at the one-month evaluation, but none at later time points. Overall during the study period, 8 of 17 men recovered their erectile function and were able to accomplish sexual intercourse. Post-hoc stratification according to urinary continence status was performed. Accordingly, for continent men (median IIEFinclusion = 7 (95% CI 5-12), 8 out of 11 men recovered erectile function (IIEF6months = 17 (6-23)), corresponding to a mean difference of 0.57 (0.38-0.85; p = 0.0069), versus inclusion. In contrast, incontinent men did not regain erectile function (median IIEF1/3/6 months = 5 (95% CI 5-6); mean difference 1 (95% CI 0.85-1.18), p > 0.9999). In this phase I trial a single intracavernosal injection of freshly isolated autologous ADRCs was a safe procedure. A potential efficacy is suggested by a significant improvement in IIEF-5 scores and erectile function. We suggest that ADRCs represent a promising interventional therapy of ED following prostatectomy. Danish Medical Research Council, Odense University Hospital and the Danish Cancer Society.


A Drosophila mutation that eliminates a calcium-dependent potassium current.
A mutation of Drosophila, slowpoke (slo), specifically abolishes a Ca2+-dependent K+ current, IC, from dorsal longitudinal flight muscles of adult flies. Other K+ currents remain normal, providing evidence that IC is mediated by a molecularly distinguishable set of channels. The pharmacological properties of IC are similar to those of Ca2+-dependent currents in some vertebrate cells. The muscle action potential was significantly lengthened in slo flies, indicating that IC plays the major role in its repolarization.


Predicting Patient Status in Chronic Thromboembolic Pulmonary Hypertension Using a Biophysical Model.
Chronic thromboembolic pulmonary hypertension (CTEPH) involves abnormally high blood pressure in the pulmonary vessels and is associated with small vessel vasculopathy and pre-capillary proximal occlusions. Management of CTEPH disease is challenging, therefore accurate diagnosis is crucial in ensuring effective treatment and improved patient outcomes. The treatment of choice for CTEPH is pulmonary endarterectomy, which is an invasive surgical intervention to remove thrombi. Following PEA, a number of patients experience poor outcomes or worse-than-expected improvements, which may indicate that they have significant small vessel disease. A method that can predict the extent of distal remodelling may provide useful clinical information to plan appropriate CTEPH patient treatment. Here, a novel biophysical modelling approach has been developed to estimate and quantify the extent of distal remodelling. This method includes a combination of mathematical modelling and computed tomography pulmonary angiography to first model the geometry of the pulmonary arteries and to identify the under-perfused regions in CTEPH. The geometric model is then used alongside haemodynamic measurements from right heart catheterisation to predict distal remodelling. In this study, the method is tested and validated using synthetically generated remodelling data. Then, a preliminary application of this technique to patient data is shown to demonstrate the potential of the approach for use in the clinical setting.Clinical relevance- Patient-specific modelling can help provide useful information regarding the extent of distal vasculopathy on a per-patient basis, which remains challenging. Physicians can be unsure of outcomes following pulmonary endarterectomy. Therefore, the predictive aspect of the patient's response to surgery can help with clinical decision-making.


MicroRNA-Mediated Regulation of Histone-Modifying Enzymes in Cancer: Mechanisms and Therapeutic Implications.
In the past decade, significant advances in molecular research have provided a deeper understanding of the intricate regulatory mechanisms involved in carcinogenesis. MicroRNAs, short non-coding RNA sequences, exert substantial influence on gene expression by repressing translation or inducing mRNA degradation. In the context of cancer, miRNA dysregulation is prevalent and closely associated with various stages of carcinogenesis, including initiation, progression, and metastasis. One crucial aspect of the cancer phenotype is the activity of histone-modifying enzymes that govern chromatin accessibility for transcription factors, thus impacting gene expression. Recent studies have revealed that miRNAs play a significant role in modulating these histone-modifying enzymes, leading to significant implications for genes related to proliferation, differentiation, and apoptosis in cancer cells. This article provides an overview of current research on the mechanisms by which miRNAs regulate the activity of histone-modifying enzymes in the context of cancer. Both direct and indirect mechanisms through which miRNAs influence enzyme expression are discussed. Additionally, potential therapeutic implications arising from miRNA manipulation to selectively impact histone-modifying enzyme activity are presented. The insights from this analysis hold significant therapeutic promise, suggesting the utility of miRNAs as tools for the precise regulation of chromatin-related processes and gene expression. A contemporary focus on molecular regulatory mechanisms opens therapeutic pathways that can effectively influence the control of tumor cell growth and dissemination.


Modeling of the renal kinetics of the AT1 receptor specific PET radioligand [11C]KR31173.
The radioligand [(11)C]KR31173 has been introduced for PET imaging of the angiotensin II subtype 1 receptor (AT1R). The purpose of the present project was to employ and validate a compartmental model for quantification of the kinetics of this radioligand in a porcine model of renal ischemia followed by reperfusion (IR). Ten domestic pigs were included in the study: five controls and five experimental animals with IR of the left kidney. To achieve IR, acute ischemia was created with a balloon inserted into the left renal artery and inflated for 60 minutes. Reperfusion was achieved by deflation and removal of the balloon. Blood chemistries, urine specific gravity and PH values, and circulating hormones of the renin angiotensin system were measured and PET imaging was performed one week after IR. Cortical time-activity curves obtained from a 90 min [(11)C]KR31173 dynamic PET study were processed with a compartmental model that included two tissue compartments connected in parallel. Radioligand binding quantified by radioligand retention (80 min value to maximum value ratio) was compared to the binding parameters derived from the compartmental model. A binding ratio was calculated as DVR = DV(S)/DV(NS), where DV(S) and DV(NS) represented the distribution volumes of specific binding and nonspecific binding. Receptor binding was also determined by autoradiography in vitro. Correlations between rate constants and binding parameters derived by the convolution and deconvolution curve fittings were significant (r > 0.9). Also significant was the correlation between the retention parameter derived from the tissue activity curve (Y(ret)) and the retention parameter derived from the impulse response function (f(ret)). Furthermore, significant correlations were found between these two retention parameters and DVR. Measurements with PET showed no significant changes in the radioligand binding parameters caused by IR, and these in vivo findings were confirmed by autoradiography performed in vitro. Correlations between various binding parameters support the concept of the parallel connectivity compartmental model. If an arterial input function cannot be obtained, simple radioligand retention may be adequate for estimation of in vivo radioligand binding.


Crime, inequality and public health: a survey of emerging trends in urban data science.
Urban agglomerations are constantly and rapidly evolving ecosystems, with globalization and increasing urbanization posing new challenges in sustainable urban development well summarized in the United Nations' Sustainable Development Goals (SDGs). The advent of the digital age generated by modern alternative data sources provides new tools to tackle these challenges with spatio-temporal scales that were previously unavailable with census statistics. In this review, we present how new digital data sources are employed to provide data-driven insights to study and track (i) urban crime and public safety; (ii) socioeconomic inequalities and segregation; and (iii) public health, with a particular focus on the city scale.


Environmental relative moldiness index and associations with home characteristics and infant wheeze.
Possible relationships between mold contamination, as described by the Environmental Relative Moldiness Index (ERMI), home characteristics, and the development of wheeze in the first year of life were evaluated among a cohort of urban infants (n = 103) in Syracuse, New York. Pregnant women with a history of asthma were recruited in 2001-2002 for the "Assessment of Urban Dwellings for Indoor Toxics" (AUDIT) study. When the infants were approximately 3 months of age, a home inspection was carried out and indoor environmental samples collected, including vacuumed house dust. ERMI levels in the Syracuse cohort homes were higher than the U.S. average, with an overall mean of 11.4. ERMI levels were significantly higher in homes with visible water problems (p = 0.023) and visible mold (p = 0.023). ERMI levels in apartments were significantly lower than the values measured in houses (p = 0.0003). While infants experiencing wheeze (38%) tended to live in homes with higher ERMI values than those without wheeze (ERMI values of 12.3 and 10.9, respectively), the differences did not reach statistical significance. A subset analysis limited to infants with living room samples who remained in the same home during the study (n = 25) was suggestive of an association between higher ERMI values and wheeze (p = 0.10). In summary, the ERMI is a standardized metric which allows for comparison of moldiness levels in homes across studies and regions in the United States. ERMI levels in Syracuse homes were skewed to the high end of the national scale. Higher ERMI levels were indicators of water problems, mold, and type of housing.


Current views of community and hospital pharmacists on pharmaceutical care services in the United Arab Emirates: A mixed methodological study.
Background: The profession of pharmacy has evolved significantly in recent years in terms of professional service delivery. The aim of this study was to explore the current views of pharmacists in the United Arab Emirates (UAE) on pharmaceutical care services and the nature of barriers encountered in practice using qualitative and quantitative assessment methods. Methods: A cross-sectional study was conducted among hospital and community pharmacists (n = 305) between March and May 2021, using qualitative and quantitative assessment methods. In the qualitative phase, 15 interviews were conducted to explore five main criteria: patient information, inadequate patient counseling, prescribing errors prevention and identifying drug-related problems, lack of participation in health awareness programs, and barriers to pharmaceutical care implementation. In the quantitative phase, 305 consenting pharmacists completed a questionnaire on seven criteria: demographic profile, pharmacist-physician interaction, patient counseling assessment, patient reports of adverse drug events, pharmacist participation in health awareness programs, perceptions of reducing prescribing errors and identifying drug-related problems, and barriers to appropriate pharmaceutical care implementation. Results: The results of both the qualitative and quantitative phases of the study revealed that pharmacists' influence on practice in the UAE is limited due to many factors, mainly lack of time and patients' ignorance of the pharmacist's role in the medical field. The mean responses regarding pharmacists' approach to patient counseling and patients' knowledge of pharmacists' role in managing adverse drug reactions were 77.1% and 59.7%, respectively. Active participation in health awareness programs was 64.8%. The mean positive response of participants in reducing prescribing errors and recognizing drug-related problems was 9.2%. Pharmacists' age and number of years in practice were the most important factors influencing the pharmaceutical care services implementation. Conclusion: The study has shown the need to shed light on the proper implementation of pharmaceutical care while maintaining a trusting relationship with physicians.


Characterization of susceptible chiasma configurations that increase the risk for maternal nondisjunction of chromosome 21.
Recent studies of trisomy 21 have shown that altered levels of recombination are associated with maternal non-disjunction occurring at both meiosis I (MI) and meiosis II (MII). To comprehend better the association of recombination with nondisjunction, an understanding of the pattern of meiotic exchange, i.e. the exchange of genetic material at the four-strand stage during prophase, is required. We examined this underlying exchange pattern to determine if specific meiotic configurations are associated with a higher risk of non-disjunction than others. We examined the crossover frequencies of chromosome 21 for three populations: (i) normal female meiotic events; (ii) meiotic events leading to MI non-disjunction; and (iii) those leading to MII non-disjunction. From these crossover frequencies, we estimated the array of meiotic tetrads that produced the observed crossovers. Using this approach, we found that nearly one-half of MI errors were estimated to be achiasmate. The majority of the remaining MI bivalents had exchanges that clustered at the telomere. In contrast, exchanges occurring among MII cases clustered at the pericentromeric region of the chromosome. Unlike the single exchange distributions, double exchanges from the non-disjoined populations seemed to approximate the distribution in the normal population. These data suggest that the location of certain exchanges makes a tetrad susceptible to non-disjunction. Specifically, this susceptibility is associated with the distance between the centromere and closest exchange. This result challenges the widely held concept that events occurring at MII are largely independent of events occurring at MI, and suggests that all non-disjunction events may be initiated during MI and simply resolved at either of the two meiotic stages.


Osteoporosis, genetics and hormones.
Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue. At a given age, bone mass results from the amount of bone acquired during growth, i.e. the peak bone mass (Bonjour et al., 1991, Theintz et al. 1992) minus the age-related bone loss which particularly accelerates after menopause. The rate and magnitude of bone mass gain during the pubertal years and of bone loss in later life may markedly differ from one skeletal site to another, as well as from one individual to another. Bone mass gain is mainly related to increases in bone size, that is in bone external dimensions, with minimal changes in bone microarchitecture. In contrast, postmenopausal and age-related decreases in bone mass result from thinning of both cortices and trabeculae, from perforation and eventually disappearance of the latter, leading to significant alterations of the bone microarchitecture (Fig. 1).


Impact of blood cell counts and volumes on glucose concentration in uncentrifuged serum and lithium-heparin blood tubes.
Although it is known that glucose concentration exhibits a time-dependent decay in uncentrifuged serum and lithium-heparin blood tubes, no evidence exists on how this variation may depend on blood cell counts (CBC) and volumes. Venous blood was drawn from 30 non fasting healthy volunteers into three serum and three lithium-heparin tubes. One serum and lithium-heparin tubes were centrifuged within 15 min after collection and glucose was measured with a hexokinase assay. The second and third serum and lithium-heparin tubes were maintained at room temperature for 1 and 2 h after the first tubes were centrifuged. These other tubes were then centrifuged and glucose was measured. CBC was performed in the first lithium-heparin tube, before centrifugation. The mean decrease of glucose was higher in lithium-heparin plasma than in serum (0.33 vs. 0.24 mmol/L/h; p<0.001). Glucose concentration decreased by 7% and 5% per hour in lithium-heparin plasma and serum, respectively. In univariate analysis, the absolute decrease of glucose concentration was associated with sex (higher in men than in women), red blood cell (RBC) count, hematocrit, white blood cell (WBC) count, neutrophils and monocytes in both lithium-heparin plasma and serum. In multivariate analysis, the decrease of glucose concentration remained independently associated with RBC, WBC, neutrophils and monocytes in both sample matrices. No significant association was found with platelet number and erythrocyte or platelet volume. Glucose concentration decrease in uncentrifuged lithium-heparin and serum tubes depends on the baseline number of RBC, WBC, neutrophils and monocytes within the tubes.


Heterotopic Ossification and Entrapment of the Tibial Nerve Within the Tarsal Tunnel: A Case Report.
Heterotopic ossification has been reported to occur after musculoskeletal trauma (including orthopedic procedures). This has been known to cause nerve entrapment syndromes and persistent pain, limiting joint mobility. We present a case of a 19-year old female collegiate athlete who had previously undergone ankle arthroscopy and arthrotomy to remove 2 ossicles. At approximately 1 year postoperatively, the patient developed pain when planting and pivoting her foot. Imaging revealed a radiodense lesion at the posteromedial ankle consistent with heterotopic ossification and entrapment of the tibial nerve within the tarsal tunnel. The patient underwent surgical resection and postoperative indomethacin prophylaxis. At the 1-year follow-up visit, the patient remained asymptomatic, without evidence of recurrence of the heterotopic ossification. In our review of the published data, we found no previously reported cases of heterotopic ossification causing entrapment of the tibial nerve within the tarsal tunnel. In the present case report, we describe this rare case and the postulated etiologies and pathophysiology of this disease process. In addition, we discuss the clinical signs and symptoms and recommended imaging modalities and treatment.


Facile preparation and enhanced microwave absorption properties of core-shell composite spheres composited of Ni cores and TiO2 shells.
Core-shell microspheres with Ni cores and two phases of TiO2 (anatase, rutile) shells have been successfully synthesized. The crystal structure, morphology and microwave absorption properties of the as-prepared composites were analyzed by X-ray diffraction, field-emission scanning electron microscopy, energy dispersive X-ray spectroscopy, transmission electron microscopy, and vector network analysis. The core-shell rutile TiO2-coated Ni exhibits better antioxidation ability than that of pure Ni due to the presence of the rutile TiO2 shell, which is confirmed by the thermal gravimetric analysis (TGA). In comparison with bare Ni, these two composites show better microwave absorption properties. The minimum reflection loss (RL) is -38.0 dB at 11.1 GHz with a thickness of only 1.8 mm for the Ni@TiO2 (rutile) composite. The enhanced absorption capability arises from the efficient complementarities between the magnetic loss and dielectric loss, multiple interfacial polarization, high thermal conductivity of rutile TiO2 and microwave attenuation constant. These results show that the thin high-efficiency rutile TiO2-coated Ni composite is a great potential microwave absorbing material for practical applications.


[Investigations on the regulation of secreted aspartyl proteases in a model of oral candidiasis in vivo].
By means of RT-PCR and specific primers the expression of SAP1-6 and SAP8 was investigated with respect to the time course in an in vitro candidosis model based on reconstituted human mucosal epithelium. Corresponding morphological alterations of the epithelium were documented by light microscopy. The detection of Sap was performed immunoelectron microscopically using a monoclonal antibody. In the oral candidosis model SAP1 and SAP3 transcripts were detected 42 h after inoculation corresponding to first histopathological changes. Additional SAP6 expression was observed six hours later concomitantly with germ-tube formation. Later on SAP2 and SAP8 transcripts were found after 60 h. On protein level it was possible to demonstrate Sap antigens within Candida and markedly deteriorated epithelial cells. Initial experiments with proteinase mutants and proteinase inhibitors showed reduction of histological damage. In a clinical specimen obtained from a twenty nine-year-old female patient suffering from acute oral candidosis SAP1, 3 and 6 could be demonstrated corresponding to the findings in vitro after 48 h. Investigating a clinical specimen obtained from a lesion of chronic oral candidosis in an HIV-infected patient also showed SAP2 expression. On the basis of our results a relationship between the expression on of particular SAP genes and the turn up of lesions looks as probable as a relevant contribution to the in vivo infection.


lncRNA MALAT1 Promotes EMT Process and Cisplatin Resistance of Oral Squamous Cell Carcinoma via PI3K/AKT/m-TOR Signal Pathway.
Cisplatin (DDP) is the first-line chemotherapy agent for the treatment of oral squamous cell carcinoma (OSCC). The emergence of DDP resistance leads to diminished drug efficacy and survival benefit. lncRNA MALAT1 has been considered as one of the most important factors in OSCC. It has also been reported to enhance chemo-resistance in other kinds of carcinomas. However, little is known about the role of lncRNA MALAT1 in DDP resistance of OSCC. Two kinds of human DDP-resistant cell lines (CAL-27R and SCC-9R) were developed from cisplatin-naïve cell lines (CAL-27 and SCC-9, respectively) as in vitro cell models. Cell transfection was performed to overexpress or knockdown MALAT1 in these cells. Mouse xenograft models were also established. The following measurements were performed: cell proliferation, colony formation, wound healing, transwell, and TUNEL assays, as well as Western blot and immunofluorescence staining. DDP-resistant cells showed higher expression level of MALAT1 compared to cisplatin-naïve cells. The overexpression of MALAT1 in cisplatin-naïve cells enhanced DDP resistance and suppressed apoptosis in OSCC cells. However, the knockdown of MALAT1 in DDP-resistance cells induced apoptotic cell death and restored the sensitivity to DDP. Further analyses suggested that MALAT1 might promote DDP resistance via regulating P-glycoprotein expression, epithelial-mesenchymal transition process, and the activation of PI3K/AKT/m-TOR signaling pathway. MALAT1 might be a potential therapeutic target for the treatment of DDP-resistant OSCC.


Diagnostic laparoscopy in the evaluation of right lower abdominal pain: a one-year audit.
Acute appendicitis is the commonest cause for right lower abdominal pain. Clinical features, laboratory and imaging investigations are either not very sensitive or specific, and neither is therapeutic. We aimed to define the role of diagnostic laparoscopy in patients with right lower abdominal pain. Data was collected retrospectively from January 1, 2005 to December 31, 2005. Patients admitted to the Emergency Department and subsequently transferred to the Department of Surgery, National University Hospital, Singapore, with right lower abdominal pain and who eventually underwent diagnostic laparoscopy were evaluated. 691 patients with right lower abdominal pain were admitted with suspected diagnosis of appendicitis. Diagnostic laparoscopy was undertaken in 103 patients aged 17-71 years old. Of the 83 females, 78 (94 percent) were premenopausal . Histology-proven acute appendicitis was diagnosed in 78 (75.7 percent) patients. Interestingly, within this group, 25.6 percent had other concomitant pathologies found on laparoscopy. 25 patients had a normal appendix; gynaecological causes accounted for pain in 15 of these 25 (60 percent) cases. In four (3.9 percent) patients, no pathology was found. Complication rate was 1.9 percent, which included ileus in two patients. In 32 (31.1 percent) patients, diagnostic laparoscopy altered the management plan, requiring either intervention or care by a subspecialty. Diagnostic laparoscopy is useful in evaluating patients with right lower abdominal pain, especially in those with equivocal signs of acute appendicitis. It also has the additional benefit of being therapeutic. Premenopausal women benefit the most from this procedure.


Perceptual adjustment to highly compressed speech: effects of talker and rate changes.
This study investigated the perceptual adjustments that occur when listeners recognize highly compressed speech. In Experiment 1, adjustment was examined as a function of the amount of exposure to compressed speech by use of 2 different speakers and compression rates. The results demonstrated that adjustment takes place over a number of sentences, depending on the compression rate. Lower compression rates required less experience before full adjustment occurred. In Experiment 2, the impact of an abrupt change in talker characteristics was investigated; in Experiment 3, the impact of an abrupt change in compression rate was studied. The results of these 2 experiments indicated that sudden changes in talker characteristics or compression rate had little impact on the adjustment process. The findings are discussed with respect to the level of speech processing at which such adjustment might occur.


How Does Search for Meaning Lead to Presence of Meaning for Korean Army Soldiers? The Mediating Roles of Leisure Crafting and Gratitude.
Many studies demonstrate that finding meaning in life reduces stress and promotes physical and psychological well-being. However, extant literature focuses on meaning in life among the general population (e.g., college students or office workers) in their daily lives. Thus, this study aimed to investigate the mechanisms of how individuals living in life-threatening and stressful situations obtain meaning in life, by investigating the mediating roles of leisure crafting and gratitude. A total of 465 Army soldiers from the Republic of Korea (ROK) participated in two-wave surveys with a 2-week interval. Structural equation modeling analyses indicated that the direct effects between the search for meaning, presence of meaning, leisure crafting, and gratitude were significant, except for the direct relationship between the search for meaning and the presence of meaning, and between leisure crafting and the presence of meaning. We tested indirect effects using a Monte Carlo approach and found that leisure crafting and gratitude sequentially mediated the relationship between the search for meaning and the presence of meaning. Our findings highlight the importance of the motivation behind searching for meaning, the proactive use of leisure time, and gratitude for individuals in stressful situations and controlled lifestyles. Finally, we discuss the implications and limitations of this research and future research directions.


Solvable model of gas production decline from hydrofractured networks.
We address questions that arose from studying gas and oil production from hydrofractured wells. Does past production predict the future? This depends on deducing from production as much as possible about the plausible geometries of the fracture network. We address the problem through a solvable model and use kinetic Monte Carlo and Green's function techniques to solve it. We have three main findings. First, at sufficiently long times, the production from all compact fracture networks is described by a universal function with two scaling parameters, one of which is the diffusivity of unbroken rock α and the second of which is a parameter V_{ext} with units of volume. Second, for fracture networks where the power-law distribution of fracture spacings falls below a critical value (and this appears to be the case in practice), early-time production always scales as one over the square root of time. Third, the diffusivity α that sets the scale for late-time production is inherently difficult to estimate from production data, but the methods here provide the best hope of obtaining it and thus can determine the physics that will govern the decline of unconventional gas and oil wells.


Influence of ginsenoside Rb1 on brain neurosteroid during acute immobilization stress.
This study examined whether or not acute stress is linked to increases in the neurosteroid levels, which is a well-known neurotransmitters associated with stress stimuli. The ginsenoside, Rb1, was tested in order to better understand its potential effects on altering the neurosteroid levels and ultimately attenuating stress. The optimal stressed condition was checked by measuring the 5a-dihydroprogesterone (DHP) and allopregnanolone (THP) levels in the brain after immobilization stress at various times. Based on this result, an acute stress model was set up to give 30 min of immobilization stress. The DHP and THP brain levels of the stressed mice were then investigated after administering Rb1 orally (10 mg/kg). These results were compared with the neurosteroid level in the stressed mice not given Rbl. Saline was administered orally to the nonstressed mice to check the placebo effect. Acute immobilization stress induced an increase in the THP and DHP concentration in the frontal cortex and cerebellum. When Rb1 was administered orally prior to immobilization stress, the THP level in the frontal cortex and cerebellum was significantly lower than that in the stressed animals not given Rbl. On the other hand, the DHP level was lower in the cerebellum only. This suggests that the metabolism of the brain neurosteroids is linked to psychological stress, and Rb1 attenuates the stress-induced increase in neurosteroids.


Extrathyroidal effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on thyroid hormone turnover in male Sprague-Dawley rats.
Treatment of rats with different polyhalogenated aromatic hydrocarbons strongly decreases plasma T4, with little or no decrease in plasma T3. The extrathyroidal effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on thyroid hormone turnover were studied by i.p. administration of a single dose of 10 microg TCDD/kg BW or vehicle (corn oil) to euthyroid (Eu) rats, thyroidectomized (Tx) rats, and Tx rats infused with 1 microg T4 (Tx+T4) or 0.4 microg T3 (Tx+T3)/100 g BW x day by osmotic minipumps. Tx rats showed decreased plasma T4 and T3 and increased plasma TSH levels, decreased hepatic type I deiodinase (D1) and malic enzyme activities, and increased brain type II deiodinase (D2) activities. All parameters were largely restored to Eu levels in Tx+T4 rats and, except for plasma T4 and brain D2 activity, in Tx+T3 rats, validating the thyroid hormone-replaced Tx rats as models to study the peripheral effects of TCDD. Three days after TCDD administration, plasma T4 and free T4 levels were significantly reduced in Eu and Tx+T4 rats, and plasma T3 was significantly reduced in Tx+T3, but not in Eu or Tx+T4 rats. Plasma TSH was not affected by TCDD in any group. Hepatic T4 UDP-glucuronyltransferase (UGT) activity was induced approximately 5-fold by TCDD, whereas T3 UGT activity was only increased by about 20% (P = NS) in the different groups. TCDD produced an insignificant decrease in liver D1 activity in Tx rats and an insignificant increase in brain D2 activity in Tx rats and hormone-replaced Tx rats. Hepatic malic enzyme activity was significantly increased by TCDD in all groups, except Tx rats. These results strongly suggest that the thyroid hormone-decreasing effects of TCDD are predominantly extrathyroidal and mediated by the marked induction of hepatic T4 UGT activity.


A giant dapediid from the Late Triassic of Switzerland and insights into neopterygian phylogeny.
A new Triassic neopterygian is described on the basis of a large three-dimensional neurocranium from the Rhaetian (Late Triassic) of the Kössen Formation (Schesaplana, Grisons, Switzerland). CT scanning reveals neurocranial features similar to Dapedium, suggesting that this new genus, Scopulipiscis saxciput gen. et sp. nov., was deep-bodied and potentially durophagous, although no associated dental material is known. An expanded phylogenetic analysis of actinopterygians resolves Dapediidae as a clade (inclusive of Tetragonolepis), although fails to recover any characters supporting the monophyly of the genus Dapedium. Dapediids are resolved as stem holosteans, filling a conspicuous gap in early neopterygian relationships. Pycnodonts, previously suggested as either stem teleosts or the sister group to dapediids, are resolved as a clade on the neopterygian stem. Similarities between the new taxon described here and Dapedium provide insights into morphological disparity within early members of the group-suggesting that the ecological expansion of dapediids originated prior to the End-Triassic extinction-as well as contributing to a growing understanding of endocranial anatomy in Palaeozoic and Early Mesozoic actinopterygians.


Moving toward generalizable NZ-1 labeling for 3D structure determination with optimized epitope-tag insertion.
Antibody labeling has been conducted extensively for structure determination using both X-ray crystallography and electron microscopy (EM). However, establishing target-specific antibodies is a prerequisite for applying antibody-assisted structural analysis. To expand the applicability of this strategy, an alternative method has been developed to prepare an antibody complex by inserting an exogenous epitope into the target. It has already been demonstrated that the Fab of the NZ-1 monoclonal antibody can form a stable complex with a target containing a PA12 tag as an inserted epitope. Nevertheless, it was also found that complex formation through the inserted PA12 tag inevitably caused structural changes around the insertion site on the target. Here, an attempt was made to improve the tag-insertion method, and it was consequently discovered that an alternate tag (PA14) could replace various loops on the target without inducing large structural changes. Crystallographic analysis demonstrated that the inserted PA14 tag adopts a loop-like conformation with closed ends in the antigen-binding pocket of the NZ-1 Fab. Due to proximity of the termini in the bound conformation, the more optimal PA14 tag had only a minor impact on the target structure. In fact, the PA14 tag could also be inserted into a sterically hindered loop for labeling. Molecular-dynamics simulations also showed a rigid structure for the target regardless of PA14 insertion and complex formation with the NZ-1 Fab. Using this improved labeling technique, negative-stain EM was performed on a bacterial site-2 protease, which enabled an approximation of the domain arrangement based on the docking mode of the NZ-1 Fab.


Access to specialist gastroenterology care in Canada: the Practice Audit in Gastroenterology (PAGE) Wait Times Program.
Canadian wait time data are available for the treatment of cancer and heart disease, as well as for joint replacement, cataract surgery and diagnostic imaging procedures. Wait times for gastroenterology consultation and procedures have not been studied, although digestive diseases pose a greater economic burden in Canada than cancer or heart disease. Specialist physicians completed the practice audit if they provided digestive health care, accepted new patients and recorded referral dates. For patients seen for consultation or investigation over a one-week period, preprogrammed personal digital assistants were used to collect data including the main reason for referral, initial referral and consultation dates, procedure dates (if performed), personal and family history, and patient symptoms, signs and test results. Patient triaging, appropriateness of the referral and timeliness of care were noted. Over 10 months, 199 physicians recorded details of 5559 referrals, including 1903 visits for procedures. The distribution of total wait times (from referral to procedure) nationally was highly skewed at 91/203 days (median/75th percentile), with substantial interprovincial variation: British Columbia, 66/185 days; Alberta, 134/284 days; Ontario, 110/208 days; Quebec, 71/149 days; New Brunswick, 104/234 days; and Nova Scotia, 42/84 days. The percentage of physicians by province offering average-risk screening colonoscopy varied from 29% to 100%. Access to specialist gastroenterology care in Canada is limited by long wait times, which exceed clinically reasonable waits for specialist treatment. Although exhibiting some methodological limitations, this large practice audit sampling offers broadly generalized results, as well as a means to identify barriers to health care delivery and evaluate strategies to address these barriers, with the goals of expediting appropriate care for patients with digestive health disorders and ameliorating the personal and societal burdens imposed by digestive diseases.


Structural evolution of water-in-propylene carbonate mixtures revealed by polarized Raman spectroscopy and molecular dynamics.
The liquid structure of systems wherein water is limited in concentration or through geometry is of great interest in various fields such as biology, materials science, and electrochemistry. Here, we present a combined polarized Raman and molecular dynamics investigation of the structural changes that occur as water is added incrementally to propylene carbonate (PC), a polar, aprotic solvent that is important in lithium-ion batteries. Polarized Raman spectra of PC solutions were collected for water mole fractions 0.003 ≤ χwater ≤ 0.296, which encompasses the solubility range of water in PC. The novel approach taken herein provides additional hydrogen bond and solvation characterization of this system that has not been achievable in previous studies. Analysis of the polarized carbonyl Raman band in conjunction with simulations demonstrated that the bulk structure of the solvent remained unperturbed upon the addition of water. Experimental spectra in the O-H stretching region were decomposed through Gaussian fitting into sub-bands and comparison to studies of dilute HOD in D2O. With the aid of simulations, we identified these different bands as water arrangements having different degrees of hydrogen bonding. The observed water structure within PC indicates that water tends to self-aggregate, forming a hydrogen bond network that is distinctly different from the bulk and dependent on concentration. For example, at moderate concentrations, the most likely aggregate structures are chains of water molecules, each with two hydrogen bonds.


Nutrient-rich, high-quality, protein-containing dairy foods in combination with exercise in aging persons to mitigate sarcopenia.
Sarcopenic declines in muscle mass and function contribute to the risk of falls, reduced mobility, and progression to frailty in older persons. Mitigation of sarcopenia can be achieved by consumption of higher quality protein in sufficient quantities, which current research suggests are greater than the recommended intakes of approximately 0.8 g/kg bodyweight/d. In addition, higher levels of physical activity and participation in exercise to support cardiovascular fitness and musculoskeletal function work additively with protein in attenuating sarcopenia. This narrative review provides evidence to support a recommendation for per-meal protein targets in older persons that are underpinned by knowledge of muscle protein turnover. Based on work examining acute dose-responses of muscle protein synthesis (MPS) to protein, a proposed per-meal target for protein intakes is set at approximately 0.4-0.6 g protein/kg bodyweight/meal for older persons. Habitual patterns of dietary protein intake tend to emphasize a skewed protein distribution, which would not maximize muscle anabolism. Observational studies show that more even patterns of protein intake are associated with increased muscle mass and improved muscle function. A food-based approach to achieving these protein targets would be advantageous, and the nutrient density of the protein-containing foods would be particularly important for older persons. Dairy foods provide high-quality protein and contain several nutrients of concern for older persons. This brief review provides an overview of the science underpinning why dairy foods should be a point of nutritional emphasis for older persons. Practical suggestions are provided for implementation of dairy foods into dietary patterns to meet the protein and other nutrient targets for older persons.


[Vasculitic urticaria: study of 12 cases].
Twelve cases of chronic urticaria with histopathologic features of lecocitoclastic allergic angitis are studied. The type of cutaneous lesion, personal and familiar atopic history and the presence of autoimmune disease are described. Light microscopy, direct immunofluorescence, anti DNA, antinuclear, antithyroid, Ro, La, Rnp and Sm antibodies, total complement levels, C3 and C4, rheumatoid factor, latex, ASTO, cryoglobulines and complete workup were investigated, taking into account natural progression and response to therapy. Two different groups are defined: 1) normocomplementemic (5 patients) and 2) hypocomplementemic (7 patients). They were all women except one. The cutaneous lesions were indistinguishable in the two groups. Only in the second group there was an associated disease (systemic lupus erythematosus, Sjogren syndrome disease, lupus-Sjogren overlap, autoimmune thyroid disease). Urticaria had been present from the onset of the disease in 4 patients, and occurred later during its course in 8 others. Five patients had thyroid disease (Hashimoto thyroiditis or Graves disease), two of them being mother and daughter. Another patient had a family history of Grave's disease and urticaria. Anti DNA antibodies were found in 7 cases, and anti Ro + La + in 3 cases. Response to treatment was variable with spontaneous cycles of worsening and remissions. One of the patients found a relationship with certain foods. Histopathologic results are related in both clinical normocomplementemic and hypocomplementemic groups. No significant differences were found between the two groups, but Ro+ and La+ patients exhibit more intense cariorexis and neutrophilic infiltrates.


Elevation of hippocampal MMP-3 expression and activity during trauma-induced synaptogenesis.
The matrix metalloproteinase (MMP) enzyme family contributes to the regulation of a variety of brain extracellular matrix molecules. In order to assess their role in synaptic plasticity following traumatic brain injury (TBI), we compared expression of stromelysin-1 (MMP-3) protein and mRNA in two rodent models of TBI exhibiting different levels of recovery: adaptive synaptic plasticity following central fluid percussion injury and maladaptive synaptic plasticity generated by combined TBI and bilateral entorhinal cortical lesion (TBI + BEC). We sampled the hippocampus at 7 days postinjury, targeting a selectively vulnerable brain region and a survival interval exhibiting rapid synaptogenesis. We report elevated expression of hippocampal MMP-3 mRNA and protein after TBI. MMP-3 immunohistochemical staining showed increased protein levels relative to sham-injured controls, primarily localized to cell bodies within the deafferented dendritic laminae. Injury-related differences in MMP-3 protein were also observed. TBI alone elevated MMP-3 immunobinding over the stratum lacunosum moleculare (SLM), inner molecular layer and hilus, while TBI + BEC generated more robust increases in MMP-3 reactivity within the deafferented SLM and dentate molecular layer (DML). Double labeling with GFAP confirmed the presence of MMP-3 within reactive astrocytes induced by each injury model. Semi-quantitative RT-PCR revealed that MMP-3 mRNA also increased after each injury, however, the combined insult induced a much greater elevation than fluid percussion alone: 1.9-fold vs. 79%, respectively. In the TBI + BEC model, MMP-3 up-regulation was spatio-temporally correlated with increased enzyme activity, an effect which was attenuated with the neuroprotective compound MK-801. These results show that distinct pathological conditions elicited by TBI can differentially affect MMP-3 expression during reactive synaptic plasticity. Notably, these effects are both transcriptional and translational and are correlated with functionally active enzyme.


Differential expression of CYP1A1 mRNA in gill, intestine and liver of tilapia fed with PCB Aroclor-1254 and Aroclor-1260 spiked food.
The differential expression of cytochrome P4501A1 gene expression (CYP1A1) in liver, intestine and gill of juvenile tilapia following oral exposure to polychlorinated biphenyl (PCB) Aroclor-1254 or Aroclor-1260 spiked food were investigated. The fish was fed with 0.1 g/g of body weight each day of the spiked food with a concentration of approximately 8 ppm. Fish fed with betaNF- or acetone-spiked food were used as positive and negative controls, respectively. On day 1, 3 and 7 of post-treatment, the fish were sampled and analyzed for the total accumulated levels of PCBs, as well as the induced levels of CYP1A1 mRNA. Our results indicated that the fish fed with PCBs-spiked food showed a time-dependent bioaccumulation of PCBs. The time course studies also revealed that in the first 3 days of feeding, significant increases in CYP1A1 were found in intestine (betaNF: 320% and Aroclor-1260: 290%), followed by liver (betaNF: 144%, Aroclor-1260: 123% and Aroclor-1254: 110%). The transcript levels, then declined slowly. There was no induction of gill CYP1A1 mRNA expression in all treatment groups. Among all the tested tissues, the highest intestinal CYP1A1 transcripts induction has highlighted its prompt response to dietary PCBs exposure. Our study supported the important role of intestine in response to dietary PCBs exposure. In addition, in the present study the relative potency of Aroclor-1260 over Aroclor-1254 in stimulating CYP1A1 expression was discussed, indicating that the highly chlorinated PCBs had a higher potency of bioaccumulation and CYP1A1 mRNA induction.


Folate-receptor-targeted delivery of docetaxel nanoparticles prepared by PLGA-PEG-folate conjugate.
For folate-receptor-targeted anticancer therapy, docetaxel (DTX) nanoparticles (NPs) were produced employing polylactide-co-glycolide-polyethylene glycol-folate (PLGA-PEG-FOL) conjugate. The FOL-conjugated di-block copolymer was synthesized by coupling the PLGA-PEG-NH(2) di-block copolymer with an activated folic acid. It was expected that FOL moieties were exposed on the micellar surface. The conjugates assisted in the formation of DTX NPs with an average size of 200 nm in diameter through an emulsification/solvent diffusion method. The FOL-targeted NPs showed a greater extent of intracellular uptake in FOL-receptor-positive cancer cells (SKOV3) in comparison with the non-targeted NPs, indicating that the FOL-receptor-mediated endocytosis mechanism could have a role in the cellular uptake of NPs. These results suggested that FOL-targeted DTX NPs could be a potentially useful delivery system for FOL-receptor-positive cancer cells.


Hypoglycemia Unawareness in Insulinoma Revealed with Flash Glucose Monitoring Systems.
The delayed diagnosis of insulinoma remains a clinical issue. One of the main causes of such a delay is hypoglycemia unawareness. A 53-year-old woman fell unconscious during postprandial exercises. Flash glucose monitoring (FGM) systems revealed glucose profiles with fasting hypoglycemia, which facilitated the clinical diagnosis of insulinoma even though she was unaware of her hypoglycemia. The preoperative comparison of the blood glucose values provided by FGM with those obtained from capillary blood were consistent. Thus, FGM may have potential utility in revealing the presence of insulinoma-induced hypoglycemia.