Synergistic contributions of carbonyl stress and megsin in diabetic nephropathy.
Diabetic nephropathy is the most common cause of end-stage renal failure. The primary glomerular changes in diabetic nephropathy are diffuse and nodular glomerulosclerosis, manifested by an increase in mesangial matrix. Research has demonstrated that advanced glycation end products (AGEs), oxidative stress, and carbonyl stress might play a crucial role in the pathogenesis of diabetic nephropathy via multiple mechanisms. AGEs augment extracellular matrix synthesis, contribute to the release of proinflammatory cytokines and expression of growth factors and adhesion molecules, and interact with the renin-angiotensin system. Megsin is a novel serine protease inhibitor predominantly expressed in mesanguim. Megsin is upregulated in kidney samples of patients with diabetic nephropathy. Transgenic mice overexpressing megsin spontaneously develop kidney disease characterized by mesangial injury. Megsin is likely to contribute to mesangial injury in the process of diabetic nephropathy. Lack of appropriate animal models has hampered understanding the pathogenesis of diabetic nephropathy and development of effective therapies. Megsin and AGEs are suitable targets for new drugs of diabetic nephropathy and for the development of appropriate animal models of diabetic nephropathy.


Regulation of erythropoiesis in long-term hamster marrow cultures: role of bone marrow-adherent cells.
The initial establishment of hamster long-term bone marrow (LTBM) cultures requires formation of an adherent stromal layer, but continued long-term proliferation of these cultures is best accomplished by removal of the suspension cells from the adherent layer and subsequent incubation in liquid suspension culture. Continued maintenance of bone marrow cells in the presence of the adherent layer for more than four to six weeks leads to a decline and eventual disappearance of erythroid and multipotent colony-forming cells. Addition of erythropoietin to LTBM suspension cultures produces mature, hemoglobinized erythrocytes. Incubation of the same cells plus erythropoietin in the presence of autologous parental adherent layers markedly inhibits both terminal erythroid differentiation and the number of detectable erythroid burst-forming units (BFU-Es). This erythroid inhibition occurs primarily within the first 24 hours with little or no effect on CFU-GEMMs or granulocyte-macrophage colony-forming units (GM-CFUs). However, continued incubation for seven days produces a reduction in all parameters. Removal of suspension cells from the adherent layer and restimulation with erythropoietin allows regeneration of erythropoiesis. Pretreatment of suspension cells with erythropoietin for 96 hours before exposure to the adherent culture only slightly inhibits erythropoiesis, suggesting that more mature erythroid progenitors are unaffected. Conditioned medium from the marrow adherent layer (ALCM) produces similar erythroid inhibitory effects in LTBM cultures with as little as two hours of incubation. The inhibition is actively produced by the adherent cells, since cycloheximide abolishes its production, while indomethacin has no apparent effect. Adherent marrow stromal cells may regulate hemopoiesis through negative as well as positive humoral signals, and they are particularly effective in erythroid regulation.


Progressive response to botulinum A toxin in cerebral palsy.
Botulinum A toxin (BT) has been successfully used for the management of spasticity in cerebral palsy (CP). However, the long-term results of BT have not yet been determined. We have studied the evolution of a homogeneous group of patients with CP treated with BT. All these patients had an equinus gait resulting from calf muscle spasticity without other muscle group involvement. All of these patients were treated with the same total dose (4 microg/kg) at the same time interval (three months). The mean follow-up time was 33 months. Gait evaluation was made blind on videotape recordings by two independent physicians according to five point scale. All our patients exhibited a progressive improvement in their gait pattern. None of our patients developed fixed contractures nor did any of them need surgical correction. No significant side-effects were seen. The response observed in our study could be due to a progressive symptomatic effect of BT, but it might be also explained by a change in the natural history of the spasticity related to CP, at least in this selected group of patients.


Fluorescein transport in the anterior uvea.
Rabbit ciliary body-iris preparations accumulate 14C-fluorescein against a concentration gradient when incubated in Tyrode's solution at 37 degrees C and pH 7.4 for 1 hr. Under these conditions, fluorescein metabolism is negligible. This accumulation is depressed by cyanide, dinitrophenol, iodoacetate, by incubation in glucose-free medium, and by incubation at 0 degrees C. This uptake is not inhibited significantly by incubation in sodium-free medium, and relatively high concentrations of ouabain are necessary to cause inhibition. Initial uptake studies show saturation kinetics with half-saturation concentration = 0.12 mM and maximum accumulation rate = 2.3 mmoles/hr/kg wet tissue weight. Fluorescein thus appears to accumulate by a carrier-mediated active uptake process. On the basis of series of competition experiments, it is concluded that fluorescein uptake and p-aminohippurate uptake occur by similar, although not identical, mechanisms.


NK cell genotype and phenotype at diagnosis of acute lymphoblastic leukemia correlate with postinduction residual disease.
Not all natural killer (NK) cells are equally cytotoxic against leukemia because of differences in receptor gene content and surface expression. We correlated NK cell genotype and phenotype at diagnosis of childhood acute lymphoblastic leukemia (ALL) with minimal residual disease (MRD) after induction chemotherapy. The NK cells and leukemia blasts of 244 patients were analyzed at diagnosis by killer-cell immunoglobulin-like receptor (KIR) typing and immunophenotyping. The results were correlated statistically with postinduction MRD status. The odds of being MRD positive in patients with KIR telomeric (Tel)-A/B genotype were 2.85 times the odds in those with Tel-A/A genotype (P = 0.035). MRD-positive patients were more likely to have KIR2DL5A (P = 0.006) and expressed less activating receptor NKp46 and FASL on their NK cells (P = 0.0074 and P = 0.029, respectively). The odds of being MRD positive increased by 2.01-fold for every percentage increase in NK cells expressing KIR2DL1 in the presence of HLA-C2 ligand (P = 0.034). The quantity of granzyme B inhibitor PI-9 in the leukemia blasts was greater in patients who were MRD positive (P = 0.038). Collectively, five NK cell-related factors (Tel-B-associated KIR2DL5A, NKp46, FASL, granzyme B, and PI-9) are strongly associated with MRD positivity at the end of induction with 100% sensitivity and 80% specificity. Our data support the hypothesis that NK cells with a strong effector phenotype in the setting of decreased leukemia resistance are associated with better leukemia control.


Convenient syntheses of dibenzo[c,p]chrysene and its possible proximate and ultimate carcinogens: in vitro metabolism and DNA adduction studies.
Dibenzo[c,p]chrysene (DB[c,p]C) is the only hexacyclic polycyclic aromatic hydrocarbon having two fjord regions, both in different chemical environments. Its environmental presence and relative tumorigenic potency are not known due to the lack of synthetic standards. We report here the synthesis of dibenzo[c,p]chrysene (1), its proximate carcinogens, i.e., trans-1,2-dihydroxy-1,2-dihydro-DB[c,p]C (2) and trans-11,12-dihydroxy-11,12-dihydro-DB[c,p]C (3), and possible ultimate carcinogens, i.e., anti-trans-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-DB[c,p]C (4) and anti-trans-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydro-DB[c,p]C (5). The syntheses of 1 and the appropriately methoxy-substituted DB[c,p]C (12 and 27), key intermediates for the synthesis of its proximate and ultimate metabolites, were tried first using a Suzuki cross-coupling reaction. However, the cyclization of olefins (10 and 11) gave poor yields of the desired products. An alternate method was thus developed employing a photochemical approach. The in vitro metabolism of DB[c,p]C was established with the S9 fraction of liver homogenate from phenobarbital/beta-naphthoflavone-induced Sprague-Dawley rats. The major dihydrodiol formed was identified as the fjord region 11,12-dihydroxy-11,12-dihydro-DB[c,p]C, while the major and minor phenols were identified as 11-hydroxy-DB[c,p]C and 12-hydroxy-DB[c,p]C, respectively. Further, the DNA adduction studies with the calf thymus DNA led to a mixture of dA and dG adducts for both fjord region diol epoxides (4 and 5). Interestingly, the dA to dG ratio for 1,2-dihydroxy-3,4-epoxide was much higher (3.2) compared to that of 11,12-dihydroxy-13,14-epoxide (0.5).


A controlled study of the Collaborative Care Skills Workshops versus Psycho-educational Workshops among Spanish caregivers of relatives with an eating disorder.
The aim of this study was to test the hypothesis that a negative reaction to the illness would be reduced through the "Collaborative Care Skills Workshops" programme among Spanish caregivers of relatives with an eating disorder. Caregivers were randomly allocated to either the skill-based workshops (n = 32) or psycho-educational workshops (n = 31), and assessments were carried out over time (T0 vs. T1 vs. T2 ). There were no significant differences between interventions on primary or secondary caregiver outcomes or among the patients themselves. However, caregivers in both interventions showed greater improvement at T2 on accommodating and enabling behaviours and an improvement at T1 in terms of psychological distress and appraisals towards the caregiving experience. Eating pathology, psychological distress, and some indices of psychosocial adjustment were significantly lower among the patients following both interventions (T1 ). Overall, both interventions may be able to help caregivers and patients to decrease their psychological distress. HIGHLIGHTS: Involvement of family members in the treatment could be the best resource for aiding in their relative's recovery. This is the first controlled study to test the effectiveness of the Collaborative Care Skills Workshops in Spanish caregivers. Both interventions could be implemented as both help Spanish caregivers and patients.


Oxidative DNA damage in male Wistar rats exposed to di-n-butyl phthalate.
Dialkyl phthalate esters are used in the plastic industry and widely distributed in the environment. Previously, it has been shown that di-n-butyl phthalate (DBP) produces testicular atrophy and liver enlargement in rodents, and the mechanisms behind this could involve reactive oxygen species (ROS). In this study, oxidative DNA damage was measured in terms of the premutagenic modified nucleoside 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) in nuclear DNA from liver, kidneys, and testes from rats exposed to DBP in the perinatal or preadult period. In one experiment, pregnant rats were administered 0 or 0.5 g DBP/kg/d by gavage from d 7 after conception to d 17 after delivery and organs from male offspring were analyzed. In a second experiment, 25-d-old rats were administered 0, 0.5, or 2 g DBP/kg/d by gavage for 10 d. After perinatal exposure, body and organ weights were unchanged. The 8-oxodG/10(6) dG ratio in liver DNA increased significantly in the exposed group. In contrast, the 8-oxodG/10(6) dG ratio was significantly decreased in kidney DNA, whereas it remained unchanged in the testis. After preadult exposure (postnatal d 25 to 34) the testes weight of the exposed animals were significantly decreased and severe atrophy of the seminiferous tubules was observed. The body weight of the animals in the high-dose group was significantly decreased compared to the control. The 8-oxodG levels in liver, kidney, and testis DNA remained unchanged. Although ROS has been suspected of being involved in the formation of testicular atrophy in phthalate-exposed rats, no apparent sign of oxidative DNA damage was found after phthalate exposure perinatally or during the preadult stage. With respect to phthalate-induced oxidative DNA damage in the liver, it appears that the developmental stage during exposure is important.


Sluggish Cognitive Tempo in a Child and Adolescent Clinical Outpatient Setting.
Sluggish cognitive tempo (SCT) symptoms have largely emerged from investigations of attention-deficit/hyperactivity disorder (ADHD). Recent research has demonstrated the relevance of SCT symptoms in the field of clinical child and adolescent psychiatry. The goal of this research was to study the symptoms of SCT in a clinical child and adolescent sample and to define its features and comorbid conditions. We reviewed 834 clinical records of patients referred to Child and Adolescent Mental Health Services and examined SCT symptoms and their relation with sociodemographic data, clinical diagnosis, comorbid conditions, Child Behavior Checklist dimensions, and intelligence quotient. Of the 515 patients (age range, 4 to 17 y, 62.5% male) for whom a fully completed Child Behavior Checklist for Children and Adolescents was available, 20.8% showed high levels of SCT symptoms. SCT symptoms were strongly associated with age, internalizing symptoms, learning disabilities, and ADHD inattentive subtype (ADHD-I). No significant correlations with intelligence quotient were found. We concluded that SCT symptoms are highly prevalent in a clinical sample, and that these symptoms might be related to the difficulties that some individuals have in responding to demands in their environments, such as academic or social demands, as they increase over time.


Characterization of Vestibular Perception in Patients with Persistent Postural-Perceptual Dizziness.
To assess vestibular (i.e., passive self-motion) perception in patients diagnosed with persistent postural-perceptual dizziness (PPPD). Case-controlled, cross-sectional, observational investigation. Single-center laboratory-based study. Thirteen patients with PPPD, 13 age-matched healthy control volunteers. Of those with PPPD, eight had co-occurring vestibular migraine (VM). All participants completed a vestibular threshold test battery reflecting perception with predominant inputs from ( a ) the otoliths (1-Hz interaural y -axis translation, 1-Hz superior-inferior z -axis translation), ( b ) the semicircular canals (2-Hz yaw rotation, 2-Hz tilts in the planes of the vertical canal pairs), and ( c ) and canal-otolith integration (0.5-Hz roll tilt). Direction-recognition thresholds for each vestibular threshold test condition. Across all patients with PPPD, higher thresholds for superior-inferior z -translations thresholds in comparison to age-matched healthy control participants were identified ( p < 0.001). Those patients with co-occurring VM and PPPD (PPPD/+VM) displayed significantly higher z -translation thresholds ( p = 0.006), whereas patients with PPPD without VM (PPPD/-VM) displayed significantly higher roll tilt thresholds ( p = 0.029). Patients with PPPD did not display a global worsening of passive self-motion perception as quantified by vestibular perceptual thresholds. Instead, patients with PPPD displayed elevated thresholds for only roll tilt and z -translation thresholds, with the relative change in each threshold impacted by the co-occurrence of VM. Because both z -translation and roll tilt motions are reliant on accurate gravity perception, our data suggest that patients with PPPD may exhibit impaired processing of graviceptive cues.


Helicobacter pylori-Negative MALT Lymphoma Presenting as a Massive Recurrent Gastrointestinal Hemorrhage.
Primary gastric lymphoma is rare, representing 5% of all primary gastric neoplasms. The presenting complaints of gastric mucosa-associated lymphoid tissue (MALT) lymphoma are usually nonspecific. However, life-threatening gastrointestinal bleeding from the stomach is unusual and sparsely reported. While studies reveal an indolent course, we present a case that presented with massive and recurrent hematemesis leading to hypovolemic shock secondary to endoscopically confirmed MALT lymphoma, which was treated with radiotherapy to achieve remission. She had no autoimmune diseases and tested negative for Helicobacter pylori. Our case emphasizes the importance of early diagnosis and timely intensive radiotherapy of a localized but aggressive gastric MALT lymphoma.


Ammonia synthesis by the reductive N-N bond cleavage of hydrazine using an air-stable, phosphine-free ruthenium catalyst.
The development of an effective molecular catalyst to reduce hydrazine efficiently to ammonia using a suitable reductant and proton source is demanding. Herein, an unprecedented air-stable, phosphine-free ruthenium complex is used as a potent catalyst for hydrazine hydrate reduction to generate ammonia using SmI2 and water under ambient reaction conditions. Maximizing the flow of electrons from the reductant to the hydrazine hydrate via the metal centre results in a greater yield of ammonia while minimizing the evolution of H2 gas as a competing product.


Multimodal analgesia in pain management after spine surgery.
Multimodal analgesia (MMA) is the simultaneous use of multiple analgesic medications that work in a synergistic manner to provide pain control. In recent years, spine surgery has seen the growth of multimodal perioperative protocols for managing pain. Postoperative pain following spinal procedures is a common complaint, with persistent pain even after the immediate convalescent period leading to negative impacts on health. A multidisciplinary approach is essential in reducing postoperative morbidity and complication rates. This review demonstrates the efficacy in the combined use of opioid-alternative medications such as NSAIDs, gabapentinoids, local anesthetics, acetaminophen, and other neuromodulatory pharmacologic agents. Continued research will be essential in the optimization of the MMA protocol for treating patients who undergo spine procedures.


Evolutionary Spiking Neural Networks for Solving Supervised Classification Problems.
This paper presents a grammatical evolution (GE)-based methodology to automatically design third generation artificial neural networks (ANNs), also known as spiking neural networks (SNNs), for solving supervised classification problems. The proposal performs the SNN design by exploring the search space of three-layered feedforward topologies with configured synaptic connections (weights and delays) so that no explicit training is carried out. Besides, the designed SNNs have partial connections between input and hidden layers which may contribute to avoid redundancies and reduce the dimensionality of input feature vectors. The proposal was tested on several well-known benchmark datasets from the UCI repository and statistically compared against a similar design methodology for second generation ANNs and an adapted version of that methodology for SNNs; also, the results of the two methodologies and the proposed one were improved by changing the fitness function in the design process. The proposed methodology shows competitive and consistent results, and the statistical tests support the conclusion that the designs produced by the proposal perform better than those produced by other methodologies.


Biodegradable polyurethanes: synthesis and applications in regenerative medicine.
Biostable polyurethanes (PURs) have been incorporated in biomedical devices since the 1960s. The mechanisms of degradation and compositions with improved in vivo biostability have been investigated extensively. In recent years, biodegradable PURs have been investigated for applications in regenerative medicine. In contrast to the biostable implants, these biomaterials are designed to undergo controlled degradation in vivo and promote ingrowth of new tissue. Tissue-engineered scaffolds have been fabricated from biodegradable PURs using a variety of techniques, including thermally induced phase separation, salt leaching, wet spinning, electrospinning, and carbon dioxide foaming. These materials have been reported to support the ingrowth of cells and tissue in vitro and in vivo, and undergo controlled degradation to noncytotoxic decomposition products. Due to their tunable biological, mechanical, and physicochemical properties, biodegradable PURs present compelling future opportunities as scaffolds for regeneration of tissue. This review article summarizes recent advances made in the synthesis of biodegradable PURs and the application of these materials as scaffolds for regenerative medicine.


Dodecylsulfate-induced dissociation of human alpha 2-macroglobulin. An investigation using small-angle neutron scattering and the equilibrium dialysis technique.
The dodecylsulfate-induced dissociation of the tetrameric alpha 2-macroglobulin molecule from human plasma has been investigated by the small-angle neutron scattering (SANS) method. The great advantage with the SANS method is that, by using deuterated dodecylsulfate, and contrast variation by changing the D2O/H2O ratio of the solvent, we can selectively study just the protein part, or the dodecylsulfate part, of the protein-dodecylsulfate complex. More than a thousandfold excess of dodecylsulfate (on a molar basis) is needed in order to dissociate alpha 2-macroglobulin to particles with, on average, half the original molecular mass. By combining the SANS data with results obtained by the equilibrium dialysis technique it follows that, under these circumstances, approximately one thousand dodecylsulfate molecules are associated per alpha 2-macroglobulin molecule. From the significant increase in the radius of gyration, which accompanies the dissociation process, we can conclude that the dissociation is associated with a drastic change in conformation of the protein molecule. From measurements where the dodecylsulfate part of the complex dominates the SANS signal we also get an indication that the dodecylsulfate is randomly distributed along the polypeptide chain, rather than being arranged in large clusters at certain regions of the protein molecule. By fitting the parameters of a binding model to the experimental data we obtain the result that most of the more than one thousand bound dodecylsulfate molecules, necessary for dissociation, are involved in the change in conformation, and the dissociation process is, in fact, driven by the binding of a very few extra dodecylsulfate molecules to the dissociation products. These data indicate that the dodecylsulfate-induced dissociation of alpha 2-macroglobulin is probably more complicated than just breaking, for instance, a hydrophobic interaction.


ASCO 2016 - update colorectal liver metastases.
This short review summarizes the most relevant data on colorectal liver metastases (CLM) presented at the 2016 Annual Meeting of the American Society of Clinical Oncology (ASCO). For this update, congress abstracts were grouped into three clinically relevant scenarios: CLM that are deemed upfront resectable, borderline resectable, and primarily unresectable. According to a large registry study, small, upfront resectable, solitary CLM should be resected using a parenchymal sparing technique. A prospective noninterventional study suggested that chemotherapy plus the anti-VEGF (vascular endothelial growth factor) antibody bevacizumab is effective and well tolerated in patients with borderline resectable CLM. In the setting of CLM deemed initially unresectable, a phase 2 study reported superior outcomes in terms of liver metastases resection rates as well as overall survival (OS) in patients receiving a chemotherapy triplet (FOLFIRINOX) plus a targeted agent as compared to FOLFIRI or FOLFOX4 with the same targeted therapy. Finally, a study suggested that tailoring first-line chemotherapy according to TYMS-3'UTR and ERCC1-118 polymorphism status results in higher response rates and longer progression-free survival (PFS) as well as OS.


Differential production of macrophage inflammatory protein 1gamma (MIP-1gamma), lymphotactin, and MIP-2 by CD4(+) Th subsets polarized in vitro and in vivo.
Due to differential expression of chemokine receptors, the Th1 and Th2 subsets of CD4(+) T cells differ in their migratory responses to chemokines. These differences in the migration patterns are likely to play a role in the initiation and regulation of Th1 and Th2 immune responses, inflammatory processes, and T-cell-mediated pathology. In the present study we evaluated the role of activated Th cells as producers of chemokines. Three different sources of murine Th cells were used, i.e., long-term-cultured Th1 and Th2 cell clones, Th1 and Th2 cells differentiated from naïve CD4(+) spleen and lymph node cells in vitro, and Th1 and Th2 subsets polarized in vivo using a murine experimental Leishmania major infection model. Following stimulation with anti-CD3, macrophage inflammatory protein 1gamma (MIP-1gamma) and lymphotactin were produced selectively by Th1 cells but not by Th2 cells. In contrast, only Th2 cells produced MIP-2. The possible biological relevance of these data was substantiated by the finding that in vivo-polarized Th1 cells, but not Th2 cells, produced MIP-1gamma and lymphotactin while in vivo-polarized Th2 cells secreted MIP-2. The above data demonstrate that Th1 and Th2 cells differ in their ability to produce chemokines, suggesting that Th1 and Th2 subsets differentially contribute to recruitment of cells into inflammatory foci.


Effectiveness of immersive virtual reality training to improve sitting balance control among individuals with acute and sub-acute paraplegia: A randomized clinical trial.
Spinal cord injury (SCI) is a disabling condition with physical, psychological, and financial consequences. The study's goal is to compare the effectiveness of immersive virtual reality (VR) training in balance among individuals with incomplete paraplegia to that of functional electrical stimulation (FES). Two groups, randomized clinical trial. Neurological Physiotherapy Out Patient Department, Tertiary Care Hospital. Eighteen people aged 18-60 years with incomplete SCI. VR training along with conventional physical therapy (CPT) and FES for Rectus Abdominis and Erector Spinae with CPT five times a week for 4 weeks. The outcome measures were Modified Functional Reach Test (mFRT) and Function in Sitting Test (FIST) to assess sitting balance and Spinal Cord Independence Measure III (SCIM III) for the level of independence. Assessments were taken before initiating treatment and at the end of the 2 and 4 weeks after treatment. Within-group analyses for the mFRT values were performed using Repeated Measures ANOVA test, and between-group analyses were performed using the independent t-test test. Friedman and Mann-Whitney U-tests were used for analyzing FIST and SCIM III. All variables (mFRT and FIST) improved significantly in both groups (P < 0.05), with the VR + CPT group showing a more significant result than the FES + CPT group (P value < 0.05), except for SCIM III. VR as an adjunct to CPT demonstrated proved to be an effective treatment to improve balance among individuals with incomplete paraplegia.Trial registration: Clinical Trials Registry India identifier: CTRI/2020/03/024080.


[Amyotrophic lateral sclerosis that begins with voice and deglution alterations].
Amyotrophic lateral sclerosis is a progressive degenerative neuromuscular disease of insidious onset. It involves upper and lower motor neurons and causes both spastic and atrophic muscular symptoms. More than one fourth of patients have complaints relating to the head and neck (bulbar palsy); thus, the otolaryngologist may be the first physician to see them. In bulbar forms of Amyotrophic Lateral Sclerosis, voice and/or swallowing difficulties are often the initial signs of disturbance. Predominant symptoms are slurred speech, hoarseness, dysphagia, and dyspnea. Muscular weakness, atrophy, and fasciculation are noted on examination. We show a case and revise bibliography.


[Laparoscopic inguinal hernia repair "IPOM" with Dual-Mesh].
The authors report their experience on laparoscopic hernioplasty using the Intraperitoneal Onlay Mesh Repair (IPOM) in 56 patients. 34 patients had a bilateral hernia, 6 of which were recurrent and 22 had a monolateral hernia, of which 9 had recurrent hernia. Overall, a total of 90 hernias were treated. The hernia repair was performed utilizing "GORE-TEX DualMesh Plus biomaterial with holes" in the first 32 cases and the latest "...Corduroy" type in the remaining 24 cases. The prostheses were fixed with titanium spiral tacks (Protack, AutoSuture, Tyco Healthcare). No intraoperative complications occurred and no conversion was necessary. Five minor post-operative complications (5.5%), 2 seromas and 3 transient paresthesias, were observed. Four patients (7.1%) needed analgesics after the first 24 hours. Mean hospital stay was 36 hours, with a minimum of 24 and a maximum of 48. Mean resumption of normal activity was 8 days with return to work within two weeks. At an average 18 months follow-up, 3 recurrences were recorded (3.3%). The results of this study as well as the meta-analysis of the series presented in the Literature, indicate that the IPOM may be a feasible, safe and effective procedure in the treatment of recurrent and bilateral hernias or when a hernia repair is performed during other laparoscopic procedures. The IPOM has infact been shown to be faster and easier than the other more commonly performed laparoscopic hernioplasties (TAPP and TEP). These data may also suggest to utilize this technique in particular cases of primitive hernia such as very active young males or heavy duty workers. However the limited series and the short follow-up ask for randomized prospective long term studies to definitely ascertain the true incidence of recurrence and therefore the effectiveness of this attractive procedure.


POLLAR: Impact of air POLLution on Asthma and Rhinitis; a European Institute of Innovation and Technology Health (EIT Health) project.
Allergic rhinitis (AR) is impacted by allergens and air pollution but interactions between air pollution, sleep and allergic diseases are insufficiently understood. POLLAR (Impact of air POLLution on sleep, Asthma and Rhinitis) is a project of the European Institute of Innovation and Technology (EIT Health). It will use a freely-existing application for AR monitoring that has been tested in 23 countries (the Allergy Diary, iOS and Android, 17,000 users, TLR8). The Allergy Diary will be combined with a new tool allowing queries on allergen, pollen (TLR2), sleep quality and disorders (TRL2) as well as existing longitudinal and geolocalized pollution data. Machine learning will be used to assess the relationship between air pollution, sleep and AR comparing polluted and non-polluted areas in 6 EU countries. Data generated in 2018 will be confirmed in 2019 and extended by the individual prospective assessment of pollution (portable sensor, TLR7) in AR. Sleep apnea patients will be used as a demonstrator of sleep disorder that can be modulated in terms of symptoms and severity by air pollution and AR. The geographic information system GIS will map the results. Consequences on quality of life (EQ-5D), asthma, school, work and sleep will be monitored and disseminated towards the population. The impacts of POLLAR will be (1) to propose novel care pathways integrating pollution, sleep and patients' literacy, (2) to study sleep consequences of pollution and its impact on frequent chronic diseases, (3) to improve work productivity, (4) to propose the basis for a sentinel network at the EU level for pollution and allergy, (5) to assess the societal implications of the interaction. MASK paper N°32.


First Integrative Morphological and Genetic Characterization of Tremoctopus violaceussensu stricto in the Mediterranean Sea.
An integrative approach based on morphological and genetic analyses was undertaken for the first time to confirm the species identification of Mediterranean samples belonging to the genus Tremoctopus. Sequences of two mtDNA genes (cytochrome c oxidase subunit (COI) and 16S) were generated for the first time from Mediterranean samples. Both the similarity-based identifications and tree-based methods indicated that three females can be identified as Tremoctopus violaceus sensu stricto in agreement with their morphological classifications. All Mediterranean sequences clustered with the sequences of Tremoctopus violaceus from the Gulf of Mexico and were clearly differentiated from the sequences attributed to T. gracilis and T. robsoni. The chromatic pattern of the web and some features of gill filaments, arms formula, stylets, radulae, beaks, and stomach contents were given for all the samples; 105,758, 20,140, and 11,237 oocytes were estimated in the mature, immature, and developing samples, respectively. The presence of four spermatangia inside the cavity of the maturing female suggested the ability of this species to mate before reaching full maturity with more partners. Age investigation using beaks, performed for the first time in T. violaceus and within the genus gave results consistent with the different sizes and maturity conditions of the samples.


Surgery and target agents for renal cell carcinoma treatment: the path between proper interaction.
Renal cell carcinoma accounts for 3% of all solid tumors and currently causes about 3,500 deaths/year in the UK. Once an orphan disease, it has undergone an impressive change in its natural history with an improvement in overall survival, thanks to the development of new target agents. In its management, renal cell carcinoma has been treated with both surgical and medical approaches. Nowadays, many more drugs are available, especially in the metastatic setting, so that we should reconsider the peculiar role of surgery and its interaction with target agents. Cytoreductive nephrectomy still plays a major role in the management of the disease, though no really solid data have been still obtained. Adjuvant and neoadjuvant settings, instead, are still under evaluation, especially new adjuvant therapies involving the numerous target agents we have. Finally, metastasectomy has a controversial role, with some evidence of more efficacy than the medical treatment, though it shows too many biases to be considered certain. The picture that comes out suggests a complex frame, in which we have great power to act, but in which we need to better comprehend the interactions that could be created between surgery and medical therapies, to achieve an optimal multimodal treatment for renal cell carcinoma.


CAR Peer Learning Guide.
Peer learning is a quality initiative used to identify potential areas of practice improvement, both on a patient level and on a systemic level. Opportunities for peer learning include review of prior imaging studies, evaluation of cases from multidisciplinary case conferences, and review of radiology trainees' call cases. Peer learning is non-punitive and focuses on promoting life-long learning. It seeks to identify and disseminate learning opportunities and areas for systems improvement compared to traditional peer review. Learning opportunities arise from peer learning through both individual communication of cases reviewed for routine work, as well as through anonymous presentation of aggregate cases in an educational format. In conjunction with other tools such as root cause analysis, peer learning can be used to guide future practice improvement opportunities. This guide provides definitions of terms and a synthetic evidence review regarding peer review and peer learning, as well as medicolegal and jurisdictional considerations. Important aspects of what makes an effective peer learning program and best practices for implementing such a program are presented. The guide is intended to be a living document that will be updated regularly as new data emerges and peer learning continues to evolve in radiology practices.


The nocebo effect across health outcomes: A systematic review and meta-analysis.
The nocebo effect represents a growing concern in clinical settings. Nocebo effects occur when the treatment context generates negative expectancies that trigger the experience or worsening of negative symptoms beyond any effects attributable to the treatment itself. Despite being identified in a range of outcomes and conditions, from pain to Parkinson's disease, there has not been an attempt to systematically quantify the nocebo effects across health outcomes. The purpose of the present review was thus to systematically review and meta-analyze the nocebo literature to quantify the size of the nocebo effect across outcomes and examine which factors moderate the size of the nocebo effect, including process of induction, treatment type, or health outcome. Systematic searches of PubMed, PychInfo, Medline, and Web of Science identified 130 (n = 8,219) independent eligible studies. To be included, studies had to include both a nocebo and control group/condition, which were compared to isolate the nocebo effect size. Overall, the magnitude of the nocebo effect was medium (g = 0.522) and highly heterogeneous. Two key moderators emerged: health outcome and process of induction. Here, the nocebo effect was medium for most somatic outcomes and affect, with no significant effect on worsening cognitive performance. Further, inducing nocebo effects through instruction in combination with conditioning produced larger nocebo effects. The present review suggests nocebo effects can be reliably induced across somatic health outcomes, and interventions that target the effect of instructions will be of critical importance to reducing the occurrence of nocebo effects. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


When to Refer a Hearing-impaired Patient for a Cochlear Implant Evaluation.
To explore the predictive value of utilizing routine audiometry to best determine cochlear implant (CI) candidacy using AzBio sentences. A retrospective chart review was performed between 2011 and 2018 for 206 adult patients who underwent CI evaluation assessed with AzBio sentences. Better hearing ear word recognition score (WRS) using Northwestern University-6 word lists presented at decibel hearing level from a standard audiogram was used to determine when best to refer a patient for CI evaluation. Predicted AzBio scores from multivariate regression models were calculated and compared with the actual CI candidacy to assess accuracy of the regression models. Race, marital status, hearing aid type, better hearing ear WRS, and HL were all independently and significantly associated with AzBio testing in quiet on univariate analyses. Better hearing ear WRS and better hearing ear decibel hearing level predicted AzBio Quiet on multivariate regression analysis. For AzBio +10 dB signal-to-noise ratio (SNR), sex, and better hearing ear WRS each significantly predicted speech perception testing. Predicted CI candidacy was based on AzBio sentence testing of ≤60% for the ease of statistical analysis. Regression models for AzBio sentence testing in quiet and +10 dB SNR agreed with the actual testing most of the time (85.0 and 87.9%, respectively). A generalized linear model was built for both AzBio testing in quiet and +10 dB SNR. A WRS of <60% in the better hearing ear derived from a routine audiogram will identify 83.1% of CI candidates while appropriately excluding 63.8% of patients.


Characterization of Water Structure and Phase Behavior within Metal-Organic Nanotubes.
Water behavior under nanoconfinement varies significantly from that in the bulk but also depends on the nature of the pore walls. Hybrid compound offers the ideal system to explore water behavior in complex materials, so a model metal-organic nanotube (UMONT) material was utilized to explore the behavior of water between 100 and 293 K. Single-crystal X-ray and neutron diffraction revealed the formation of a filled Ice-I arrangement that was previously predicted to only occur under high pressures. 17O NMR spectra suggest that the onset of melting for the water in the UMONT channels occurs at 98 K and the presence of ice-like water up to 293 K, indicating that the complete ice-water transition does not occur before dehydration of the material. Overall, the water behavior differs significantly from hydrophobic single-walled carbon nanotubes indicating precise control over water can be achieved through rational design of hybrid materials.


[Effects of ranitidine on regenerating parietal cells. A stereologic study].
In this work, we have carried out a stereological and morphological study in order to verify the effects of Ranitidine on regenerating parietal cells. We have used a control group and operated or non-operated groups treated with 2, 10 and 50 mg/kg/day Ranitidine. In operated groups an ulcer was provoked by cauterization with a metallic plate in the gastric fundus. Groups treated with high doses of Ranitidine showed an increase in the connective tissue of the gastric mucosa. The stereological study in treated groups shows a decrease in the parietal volume density, and an increase in the cellular profile. Changes detected in the parietal volume density would originate a decrease in the production of CIH.


Microangiopathy and pregnancy.
Diabetic microangiopathy is a frequent complication of longstanding diabetes mellitus. Micro vascular lesions may have severe implications for both maternal and foetal health. Patients with advanced underlying lesions are at increased risk of progression during pregnancy. Severe retinal lesions can progress during pregnancy and one year after delivery. Poor glycaemic control prior to conception and rapid improvement during pregnancy are other risk factors of progression. Treatment of lesions with high risk of progression and progressive blood glucose lowering in the preconception period can improve the prognosis. Diabetic nephropathy predisposes to preeclampsia, premature delivery, intrauterine growth retardation and perinatal mortality. Patients with elevated creatinine levels are at increased risk of permanent impairment of kidney function. These patients should be closely monitored and their blood pressure tightly controlled. Gastroparesis may be aggravated by pregnancy hyper emesis. Autonomic neuropathy may result in erratic maternal glucose control, foetus growth retardation and foetal loss.


Exceptional Response to Erdafitinib in FGFR2-Mutated Metastatic Pancreatic Ductal Adenocarcinoma.
Despite advances in cancer therapeutics, pancreatic ductal adenocarcinoma (PDAC) remains among the deadliest malignancies, with a poor prognosis at time of diagnosis. Research in PDAC has suggested that adaptive signaling in the tumor microenvironment may promote tumor proliferation and survival. Several FGFR fusion genes-specifically FGFR2-are involved with the creation and progression of cancer. These mutations are found in a variety of cancer types. This report presents a unique case of a young patient with stage IV PDAC with a known FGFR2 fusion. This molecular alteration afforded a remarkable response to FGFR inhibitor therapy, erdafitinib, after the patient experienced disease progression on multiple chemotherapy regimens.


[Ischemic contractures of the forearm and hand].
This article gives an overview of anatomy, pathophysiology, aetiology, and diagnosis of the compartment syndrome and the resulting ischaemic necrosis of the upper extremity. The relation between compartment syndrome and infection is pointed out. Whereas the therapy of a manifest compartment syndrome is rather uniform consisting in decompression of the involved fascial compartment, the treatment of the ischaemic muscle necrosis is manifold. It depends upon severity and location of the disease. Only the mildest involvement can be treated by nonoperative measures. Surgically, neurolysis, excision of necrotic musculature and scar, muscular slide, elongating tenotomy, tendon transposition and free vascularized muscle transplantation have to be considered. Only the availability of all treatment options gives the surgeon the choice of treatment that fits the demands of the individual patient best.


[Serum vitamin K concentration and nutrition].
Vitamin K (VK) is well known for its role in the synthesis of a number of blood coagulation factors. VK is also an important factor for bone metabolism via gamma-carboxylation of VK-dependent proteins such as osteocalcin, matrix Gla protein, and protein S. Recently, it is rare that severe VK deficiency is observed. However, low dietary VK intake or low VK status has been shown to be associated with low bone mineral density and increased hip fracture risk. These studies suggest that there is potential VK insufficiency in bone, even in sufficient VK status for blood coagulation. In the present review, the studies concerning relationship between serum VK concentration and bone health, including pharmacokinetics of VK analogues (such as phylloquinone and menaquinone) and factors which affect on blood circulation of VK, are reviewed.


Mobile Technologies for Managing Heart Failure: A Systematic Review and Meta-analysis.
Randomized clinical trials (RCTs) conducted among heart failure (HF) patients have reported that mobile technologies can improve HF-related outcomes. Our aim was to conduct a meta-analysis to evaluate m-Health's impact on healthcare services utilization, mortality, and cost. We searched MEDLINE, Cochrane, CINAHL, and EMBASE for studies published between 1966 and May-2017. We included studies that compared the use of m-Health in HF patients to usual care. m-Health is defined as the use of mobile computing and communication technologies to record and transmit data. The outcomes were HF-related and all-cause hospital days, cost, admissions, and mortality. Our search strategy resulted in 1,494 articles. We included 10 RCTs and 1 quasi-experimental study, which represented 3,109 patients in North America and Europe. Patient average age range was 53-80 years, New York Heart Association (NYHA) class III, and Left Ventricular Ejection Fraction <50%. Patients were mostly monitored daily and followed for an average of 6 months. A reduction was seen in HF-related hospital days. Nonsignificant reductions were seen in HF-related cost, admissions, and mortality and total mortality. We found no significant differences for all-cause hospital days and admissions, and an increase in total cost. m-Health reduced HF-related hospital days, showed reduction trends in total mortality and HF-related admissions, mortality and cost, and increased total costs related to more clinic visits and implementation of new technologies. More studies reporting consistent quality outcomes are warranted to give conclusive information about the effectiveness and cost-effectiveness of m-Health interventions for HF.


Growth of colorectal polyps: redetection and evaluation of unresected polyps for a period of three years.
BACKGROUND, AIMS, AND PATIENTS: In a prospective follow up and intervention study of colorectal polyps, leaving all polyps less than 10 mm in situ for three years, analysis of redetection rate, growth, and new polyp formation was carried out in 116 patients undergoing annual colonoscopy. The findings in relation to growth and new polyp formation were applied to 58 subjects who received placebo. Redetection rate varied from 75-90% for each year, and was highest in the rectum and sigmoid colon. There was no net change in size of all polyps in the placebo group, however, polyps less than 5 mm showed a tendency to net growth, and polyps 5-9 mm a tendency to net regression in size, both for adenomas and hyperplastic polyps. This pattern was verified by computerised image analysis. Patients between 50 and 60 years showed evidence of adenoma size increase compared with the older patients, and the same was true for those with multiple adenomas (four to five) compared with those with a single adenoma. The new adenomas were significantly smaller and 71% were located in the right side of the colon. Patients with multiple adenomas had more new polyps at all the follow up examinations than patients with a single adenoma. One patient developed an invasive colorectal carcinoma, which may be evolved from a previously overlooked polyp. Two polyps, showing intramucosal carcinoma after follow up for three years, were completely removed, as judged by endoscopy and histological examination. The results show that follow up of unresected colorectal polyps up to 9 mm is safe. The consistency of growth retardation of medium sized polyps suggests extended intervals between the endoscopic follow up examinations, but the increased number of new polyps in the proximal colon indicates total colonoscopy as the examination of choice. The growth retardation of the medium sized polyps may partly explain the discrepancy between the prevalence of polyps and the incidence of colorectal cancer.


Structure and transcriptional regulation of the ovine placental lactogen gene.
Ovine placental lactogen (oPL), a member of the growth hormone/prolactin gene family, is produced by chorionic binucleate cells at the maternal-fetal interface, and is thought to modulate metabolic processes and enhance fetal growth. We have determined that the oPL gene contains five exons and four introns, and the transcriptional start site was mapped 91 bp 5' of the initiation codon (AUG). An additional 4.5 kb of 5'-flanking sequence was sequenced and used for transient transfection analysis in human (BeWo) and rat (Rcho-1) choriocarcinoma cell lines to examine trophoblast cell-specific activity. Trophoblast cell-specific transactivation of the reporter gene was conferred by the proximal 1. 1 kb of oPL gene 5'-flanking sequence. Transfection of deletion constructs derived from the 1.1 kb of 5'-flanking sequence resulted in varying profiles of transactivation between the two choriocarcinoma cell lines, but maximal activation in both cell lines resided within the proximal 383 bp of oPL gene 5'-flanking sequence. DNase I protection analysis using ovine chorionic binucleate cell nuclear protein, identified 19 footprints within the 1.1-kb sequence, six of which are located within the 383-bp region. Electrophoretic mobility-shift assays and mutational analysis identified two functional GATA (-67, -102) sequences as transactivators of the oPL gene. However, a previously undefined element (GAGGAG) residing at -338 and -283 is required for full transactivation, and mutation of either significantly reduces reporter activity. In addition, an AP-2 site (-58) and an E-box (-163) were identified and may coordinate oPL transactivation. Transcriptional regulation of human and rodent PL genes has been previously characterized, and our results indicate that tissue-specific regulation of oPL expression may result from cis-acting elements in common with human and rat genes expressed within the placenta. However, our data indicate that regulation of oPL also results from novel cis-acting elements.


Apo E-containing lipoproteins in low or high density lipoprotein deficiency.
Apolipoprotein (apo) E-containing subfractions of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and high density lipoprotein (HDL) have been described in normolipidemic and hyperlipidemic subjects. These lipoproteins exist, however, in the presence of large amounts of apo A-I- and apo B-containing lipoproteins so that it has been difficult to assess the independence of these apo E-containing subclasses from the major lipoprotein classes. The present study has approached this question by taking advantage of three hypolipidemic states in which one or more of the major apolipoproteins is deficient or absent. After separating lipoproteins from whole plasma by molecular sieve chromatography followed by radioimmunoassay of column fractions, we found that two subjects with abetalipoproteinemia had no apo E-containing lipoproteins the size of VLDL or IDL and all the plasma apo E was in a fraction of large HDL. Two subjects with Tangier disease and two with familial apo A-I/C-III deficiency had extremely low levels of HDL cholesterol and of apo A-I-containing lipoproteins. In spite of the absence of classical HDL, a major fraction of apo E-containing lipoproteins was reproducibly observed at the elution volume characteristic of large HDL and was identical to that found in normal subjects. These data thus suggest the existence of apo E-containing lipoproteins that are the size of HDL and are not dependent upon the presence of either apo B or apo A-I. While studies in normal subjects indicate that apo E is associated with other apolipoproteins in HDL, further investigations will be needed to determine the full composition of these apo E-containing lipoproteins in the lipoprotein-deficient patients described in this report.


OXA-48 and CTX-M-15 extended-spectrum beta-lactamases in raw milk in Lebanon: epidemic spread of dominant Klebsiella pneumoniae clones.
Raw milk has recently been reported as a source of extended-spectrum beta-lactamase (ESBL) and carbapenemase genes. We thus investigated the prevalence of ESBL- and carbapenemase-producing Enterobacteriaceae in raw milk in Lebanon in order to assess the risk of transfer of these bacteria to humans. A high prevalence (30.2 %) of CTX-M-15-producing K. pneumoniae was detected in raw bovine milk. Three main K. pneumoniae clones were identified by PFGE and MLST typing. Southern blot experiments revealed that one of these clones carried the blaCTX-M-15 gene chromosomally. Moreover, one OXA-48-producing K. pneumoniae ST530 and seven CTX-M-15-producing Escherichia coli sharing the same ST were also detected. These findings highlight the spread of dominant CTX-M-15-producing K. pneumoniae clones and OXA-48-producing isolates in the food chain. Milk, which is mostly consumed raw in Lebanon, may be a source of human exposure to ESBLs and carbapenemases.


[Depression and cardiovascular disease: pathogenetic factors of the stress concept].
To date cardiovascular disorders still represent the most frequent cause of death in our western hemisphere. A number of prospective studies have now been able to show that patients with no prior history of heart disease run a higher risk of developing cardiovascular problems, if they either suffered a number of depressive symptoms or showed a depressive syndrome. Similarly, in patients who have suffered a myocardial infarction the presence of a depressive syndrome is frequently associated with poor clinical prognosis and outcome. Within this context the knowledge of the pathophysiological relationship between affective and cardiovascular disorders constitutes an essential element for instituting effective preventive measures for protecting depressed patients against the risk of suffering cardiovascular problems. The activation of stress-responsive systems during depressive episodes may contribute to metabolic risk factors and dysbalance of the autonomic heart regulation. The present overview provides a summary of current knowledge and findings within this area of research.


Early Postnatal Exposure to Cigarette Smoke Leads to Later Airway Inflammation in Asthmatic Mice.
Asthma is one of the most common airway inflammatory diseases. In most cases, asthma development is related to ubiquitous harmful environmental exposure factors in early-life. Previous studies have indicated that smoking can promote asthma development and increase the difficulty of asthma control. The aim of this study was to determine the effects of early-life CS exposure on ovalbumin (OVA)-sensitized asthmatic mice. Pathological and immunological functions were analyzed in an adult asthma mice model in which mice were sensitized with OVA combined with early-life CS exposure. Mice exposed to CS for only 5 weeks demonstrated significantly reduced pulmonary compliance, increased airway inflammation, and augmented cellular and humoral immune responses. In addition, CS inhalation was sufficient to facilitate OVA sensitization and challenge asthmatic development. Meanwhile, CS exposure amplified regulatory T cell-mediated immunity inhibition, but still did not offset the increased effector T cell-mediated inflammatory response. Early-life CS exposure is significantly associated with later pulmonary injury and aggravation of T-cell immunologic derangement in asthmatic mice.


The clinicopathological features, treatment outcomes and follow-up results of 47 ectopic thyroid gland cases: a single-center retrospective study.
Ectopic thyroid gland (ETG) is an uncommon clinical condition, presenting various challenges and limitations in its regulate diagnosis and treatment currently. This study aims to enhance our understanding of ETG and improve the strategies for its diagnosis and treatment. The retrospective single-center study was conducted, encompassing clinical data from ETG patients screened at our institution between 2013 and 2022. Patients were categorized based on the location of the disease, and follow-ups were performed on each. This study included a total of 47 patients who were confirmed to hav confirmed to have ETG. Among them, we found 29 cases of accessory thyroid and 18 cases of aberrant thyroid. Furthermore, 42 cases exhibited the single ETG, while 5 cases displayed the double ETG. The distribution of the ETG was as follows: 20 were lingual, 10 were submandibular, 10 were lateral cervical, 4 were thoracic mediastinal, 1 was esophageal, and 7 were ovarian. Of these cases, 22 patients underwent surgery, 18 received thyroid hormone replacement therapy, and 7 were placed under observation. All patients were followed up for 59.4 (12-117) months. No significant abnormalities were detected at the conclusion of the follow-up period. ETG is frequently observed in the head and neck, particularly in lingual. Accessory thyroid glands are commonly reported, with most cases being single ETG. Notably, these glands usually do not manifest specific clinical symptoms. Therefore, the appropriate and comprehensive examinations during the initial diagnosis are crucial to avoid misdiagnosis. Treatment should be individualized, and long-term follow-up is essential for managing ETG effectively.


Chronic administration of a new potent agonist of growth hormone- releasing hormone induces compensatory linear growth in growth hormone-deficient rats: mechanism of action.
To assess the efficacy of a potent agonist analog of GH-releasing hormone (GH-RH), [Dat1,Gln8,Orn12,21,Abu15,Nle27,Asp28,A gm29]hGH-RH(1-29) (JI-38), we investigated the effects of its chronic administration on growth responses in monosodium glutamate (MSG)-lesioned and normal young rats. Body weight (BW), body length (BL), tibia length (TIL), and tail length (TAL) were monitored. Basal serum GH concentrations, GH responses to bolus injections of GH-RH, pituitary GH and serum IGF-I concentrations were measured by RIA. Pituitary GH-RH receptor concentration and binding affinity was also evaluated after the treatment. Neonatal treatment with MSG resulted, as expected, in blunted growth and a decrease in serum and pituitary GH concentration and serum IGF-I levels. A reduction in GH-RH receptor concentration, associated with increased binding affinity of the GH-RH receptor was also found. Chronic administration of GH-RH agonist JI-38 in doses of 2 micrograms at 12-hour intervals for 2 weeks markedly increased the GH responsiveness to GH-RH and stimulated growth, with MSG-treated animals achieving the growth rate of normal controls. Acceleration of growth was associated with stimulated GH synthesis and IGF-I secretion, although basal serum GH levels did not change. Pituitary GH-RH receptor concentration and binding affinity were not significantly modified by the treatment. Treatment of normal young growing rats with agonist JI-38 did not further increase the normal growth acceleration in these rats, but stimulated the GH synthesis and augmented the GH secretory responsiveness. The treatment of MSG-lesioned rats with GH-RH agonist was generally more effective in female than in male animals, and in some cases masked the sex differences in growth rate. Our findings provide the first evidence that the blunted growth rate of the MSG-lesioned rats is associated with a decreased pituitary GH-RH receptor concentration. Our work demonstrates that administration of GH-RH agonist JI-38 is able to restore the normal growth rate of the GH-deficient rats by stimulating GH synthesis and IGF-I secretion.


Recent Advances on Microbiota Involvement in the Pathogenesis of Autoimmunity.
Autoimmune disorders derive from genetic, stochastic, and environmental factors that all together interact in genetically predisposed individuals. The impact of an imbalanced gut microbiome in the pathogenesis of autoimmunity has been suggested by an increasing amount of experimental evidence, both in animal models and humans. Several physiological mechanisms, including the establishment of immune homeostasis, are influenced by commensal microbiota in the gut. An altered microbiota composition produces effects in the gut immune system, including defective tolerance to food antigens, intestinal inflammation, and enhanced gut permeability. In particular, early findings reported differences in the intestinal microbiome of subjects affected by several autoimmune conditions, including prediabetes or overt disease compared to healthy individuals. The present review focuses on microbiota-host homeostasis, its alterations, factors that influence its composition, and putative involvement in the development of autoimmune disorders. In the light of the existing literature, future studies are necessary to clarify the role played by microbiota modifications in the processes that cause enhanced gut permeability and molecular mechanisms responsible for autoimmunity onset.


Stimulation of L-type calcium channels increases tyrosine hydroxylase and dopamine in ventral midbrain cells induced from somatic cells.
Making high-quality dopamine (DA)-producing cells for basic biological or small molecule screening studies is critical for the development of novel therapeutics for disorders of the ventral midbrain. Currently, many ventral midbrain assays have low signal-to-noise ratio due to low levels of cellular DA and the rate-limiting enzyme of DA synthesis, tyrosine hydroxylase (TH), hampering discovery efforts. Using intensively characterized ventral midbrain cells derived from human skin, which demonstrate calcium pacemaking activity and classical electrophysiological properties, we show that an L-type calcium agonist can significantly increase TH protein levels and DA content and release. Live calcium imaging suggests that it is the immediate influx of calcium occurring simultaneously in all cells that drives this effect. Genome-wide expression profiling suggests that L-type calcium channel stimulation has a significant effect on specific genes related to DA synthesis and affects expression of L-type calcium receptor subunits from the CACNA1 and CACNA2D families. Together, our findings provide an advance in the ability to increase DA and TH levels to improve the accuracy of disease modeling and small molecule screening for disorders of the ventral midbrain, including Parkinson's disease.


Personality status of wrestlers of varying abilities as measured by a sport specific version of a personality inventory.
The purpose of the study was to examine the relationship between personality and ability in wrestling. A wrestling-specific version of the Jackson Personality Inventory (JPI-W) was constructed and compared to the parent JPI. Wrestlers were categorized as qualifiers (N = 46) or nonqualifiers (N = 52) on the basis of an ability classification scheme which involved the previous year's performance at specified tournaments. These two groups were then examined for differences on eight JPI scales (anxiety, energy level, interpersonal affect, organization, risk taking, self esteem, social participation, and tolerance), eight corresponding JPI-W scales, wrestling age category (senior, junior, and juvenile), and wrestling experience. The results indicated that in comparison to nonqualifiers, qualifiers had significantly greater wrestling experience and higher self esteem as measured by the JPI-W.


Qualitative and semiquantitative polymerase chain reaction testing for cytomegalovirus DNA in serum allows prediction of CMV related disease in liver transplant recipients.
To identify cytomegalovirus (CMV) infection in liver transplant recipients by polymerase chain reaction (PCR) techniques and to separate the cases in which CMV related disease will occur, for whom treatment is indicated, from those in whom infection will remain innocuous. The combination of qualitative and semiquantitative PCR of serum and urine was assessed to determine whether these assays can identify those at risk of CMV related disease and compared their performance with conventional approaches to diagnosis. Qualitative PCR of serum had superior specificity, sensitivity, and positive and negative predictive values compared with urine DEAFF (detection of early antigen fluorescent foci) and PCR of urine. All episodes of CMV related disease were associated with the presence of CMV DNA by PCR in serum or urine; CMV was detected before clinical onset in 70% and 60% of cases, respectively. The period over which CMV DNA could be detected was not correlated with CMV related disease. Both peak viral load and cumulative viral load estimated using a semiquantitative PCR method on serum samples positive by the qualitative method could be used to distinguish asymptomatic infection from CMV related disease with 100% specificity and sensitivity. In contrast semiquantitative PCR of urine was of little value. An approach based on PCR testing with a combination of qualitative and subsequently semiquantitative serum samples would improve the diagnosis of CMV infection and aid identification of those patients at risk of CMV related disease, allowing treatment to be targeted specifically.


Assessing long-term health and cost outcomes of patient-centered medical homes serving adults with poor diabetes control.
The patient-centered medical home (PCMH) is an integrated primary care delivery model particularly suited for patients with poor diabetes control. Although PCMH models targeting adults with diabetes have shown some early success, little is known about the long-term benefits of medical homes in terms of health and cost outcomes. The performance of a PCMH model in adults with poor diabetes control was assessed using simulated controlled trial data obtained from the Archimedes model of disease progression and health care utilization. Using the Cardio-Metabolic Risk data set, we compared health and cost outcomes over a 20-year period between adults with poor diabetes control (HbA1c >9%) receiving standard care and these same adults receiving care under a PCMH model with a 49% HbA1c intervention improvement rate at a per-beneficiary per-month care management cost of $20 per month. The results suggest that the PCMH model has the potential to not only reduce the proportion of the population with bilateral blindness, foot amputations, and myocardial infarctions-and the mortality rate-but it can also do so in a cost-effective manner ($7898 per quality-adjusted life year). The PCMH model is cost saving for the population 50 to 64 years old and it is particularly cost-effective for men ($883 per quality-adjusted life year). Moreover, these effects are relatively large for adults 30 to 49 years old (lower bilateral blindness and death rates), women (lower foot amputation and death rates), and men (lower bilateral blindness and myocardial infarction rates). The PCMH model has potential long-term benefits to both patients with poor diabetes control as well as health care systems and providers willing to invest in this health care delivery approach.


[Critical evaluation of preoperative instrumental staging of rectal tumors. Research on the adequate use of US, CT and MR].
Both traditional exams (rectal exploration, rectoscopy, barium enema, CEA) and advanced imaging (31 US, 40 CT and 11 MR) were performed for preoperative evaluation of rectal carcinoma in order to assess the accuracy of radiological imaging in the T and N staging. The results obtained have not been considered satisfactory and it is felt that US, CT and MR should not be employed routinely for rectal staging. Indeed accuracy of US, CT and MR is respectively 64%, 75% and 81% in the T evaluation and 64%, 70% and 64% in the N staging. In order to evaluate the effective usefulness of these three latter imaging techniques a double therapeutical choice was proposed. The first treatment option was suggested on the basis of traditional staging while a second choice was given considering US, TC and MR data also. Operatory findings subsequently allowed a definitive judgement on the influence of the different techniques on treatment selection. US has furnished useful data that could have allowed us to modify treatment in one case while in 5 other cases diagnostic error would have influenced treatment negatively. CT was useful in 5 cases while in 7 cases it would have influenced treatment choice negatively. MR would have been useful in one case and harmful in another. It is concluded that only patients with large neoplasms (stages T3 and T4) benefit from CT and MR staging with the exception of those cases that have tumors above the peritoneal fold or in strict relation with the sphincter structures. US was useful only in evaluating relations of neoplasms of the anterior rectal wall with nearby pelvic structures.


Pesticide occurrence in selected South Florida canals and Biscayne Bay during high agricultural activity.
Climate and soil conditions in South Florida along with an extensive canal system facilitate movement of agricultural pesticides into surface waters. In a two-year study (2002-2004) of the currently used pesticides in South Florida, atrazine, endosulfan, metolachlor, chlorpyrifos, and chlorothalonil were the most frequently detected in the canals and in Biscayne Bay, with average concentrations of 16, 11, 9.0, 2.6, and 6.0 ng/L, respectively. Concentrations of atrazine and chlorpyrifos were highest near corn production. Chlorothalonil and endosulfan concentrations were highest near vegetable production, with no clear trend for metolachlor, which is used on multiple crops. Concentration data were used to calculate an aquatic life hazard potential for the planting period (November) versus the harvest period (March). This analysis indicated that a higher hazard potential occurs during harvest, primarily from the use of endosulfan. These data will also serve to document canal conditions prior to implementation of the Comprehensive Everglades Restoration Plan (CERP).


Gene deletion explains both in vivo and in vitro generated chromosome 2 aberrations associated with murine myeloid leukemia.
Ninety-five percent of radiation-induced murine myeloid leukemias contain chromosome 2 aberrations. A dominant molecular defect has not yet been identified: both deletions and breakpoint-specific events have been postulated. We have generated a model in which chromosome 2 lesions have been generated in vitro in a clonal tumor cell line. In this study cytogenetic and molecular comparisons are made between two of these in vitro generated lesions and eight derived in vivo: seven by the conventional radiation protocol, and one by infection with Moloney leukemia virus. All 10 lines consistently exhibited hemizygous loss of an 18 cM region between Hoxd-4 and II-1 alpha, with variable breakpoints at both ends. These results are consistent with deletion of a gene in common rather than breakpoint-specific events, for lesions resulting from all three protocols. This will allow a novel approach to the identification of a putative tumor suppressor gene, ie to describe the biological effect of the in vitro generated deletion, and to clone the gene by complementation. In preparation for this approach, we have further narrowed the region to approximately 6.5 cM by microsatellite mapping of 22 radiation-induced F1 tumors. In addition, we have eliminated the possibility that imprinting ablates expression from the remaining undeleted chromosome.


Effect of an additional health-professional-led exercise programme on clinical health outcomes after hip fracture.
To examine the effect of an additional 2-week health professional-led functional exercise programme compared to usual care for patients after hip fracture during a short-term nursing home stay directly after hospital discharge. One hundred and forty participants, 65 years or older with hip fracture, admitted to a short-term nursing home stay were randomised to an intervention group or control group. Participants in the intervention group (n = 78) received the experimental programme consisted of functional exercises, performed by health care professionals up to four times a day, 7 days a week, in addition to usual care during a 2-week short-term nursing home stay. Participants in the control group (n = 62) received usual care alone. Primary outcome was Short Physical Performance Battery (SPPB). Secondary outcomes were Timed Up & Go, New Mobility Score, The University of California, Los Angeles Activity Scale, Fall Efficacy Scale International, The EuroQol five dimension five-level questionnaire, and Numeric Rating Scale for pain. Outcome measures were assessed after 2 weeks in a short-term nursing home stay and 3 months after hip fracture surgery. The activity monitor ActivPal registered activity during the 2-week short-term nursing home stay. No statistically significant differences between groups was found in any outcomes after 2 weeks or 3 months (p > 0.05). There were statistically significant within-group improvements in primary outcome SPPB and in most secondary outcomes at all time points in both groups (p > 0.05). A 2-week health professional-led functional exercise programme in addition to usual care demonstrated no difference in clinical outcomes compared to usual care alone up to 3 months after hip fracture. The patients with hip fracture are fragile and vulnerable in this early phase, and usual physiotherapy may be sufficient to improve their physical function. ClinicalTrials.gov NCT02780076.


[Biological action of plutonium-239 on Salmonella typhimurium].
Salmonella typhimurium cells were exposed in a 239Pu citrate solution. Cell death and induction of gene mutations were an exponential function of gamma radiation dose. LD37 was 34.8 Gy; mutation doubling dose, 19 Gy.


Effects of grass silage and soybean meal supplementation on milk production and milk fatty acid profiles of grazing dairy cows.
The effects of supplementation with grass silage and replacement of some corn in the concentrate with soybean meal (SBM) on milk production, and milk fatty acid (FA) profiles were evaluated in a replicated 4 x 4 Latin square study using 16 dairy cows grazing pasture composed of ryegrass, Kentucky bluegrass, and white clover. Each experimental period lasted for 3 wk. The 4 dietary treatments were PC, 20 h of access to grazing pasture, supplemented with 6 kg/d of corn-based concentrate mixture (96% corn; C); PCSB, 20 h of access to grazing pasture, supplemented with 6 kg/d of corn- and SBM-based concentrate mixture (78% corn and 18% SBM; CSB); SC, 7 h of access to grazing pasture during the day and 13 h of ad libitum access to grass silage at night, supplemented with 6 kg/d of C concentrate; and SCSB, 7 h of access to grazing pasture during the day and 13 h of ad libitum access to grass silage at night, supplemented with 6 kg/d of CSB concentrate. The concentrate mixtures were offered twice each day in the milking parlor and were consumed completely. Grass silage supplementation reduced dietary crude protein and concentration of total sugars, and dietary SBM inclusion increased dietary crude protein concentration and decreased dietary starch concentration. Milk yield and energy-corrected milk were increased by SBM supplementation of cows with access to grass silage. Milk protein concentration was lower in cows offered grass silage, regardless of whether SBM was fed. Dietary SBM inclusion tended to increase milk fat concentration. Plasma urea N was reduced by silage feeding and increased by SBM supplementation. Supplementation with grass silage overnight could represent a useful strategy for periods of lower pasture availability. Dietary inclusion of SBM in solely grazing cows had no effects on milk production and composition, exacerbated the inefficient capture of dietary N, and increased diet cost. Grass silage supplementation affected milk FA profiles, increasing both the FA derived from de novo synthesis and those derived from rumen microbial biomass, and decreasing the sum of C18 FA (mostly derived from diet or from mobilization of adipose tissue reserves). Milk fat concentrations of conjugated linoleic acid cis-9, trans-11, vaccenic acid (18:1 trans-11), and linolenic acid (18:3n-3) were unaffected by grass silage supplementation, suggesting that partial replacement of pasture by unwilted grass silage does not compromise the dietary quality of milk fat for humans.


New Insights into the Hypotensins from Tityus serrulatus Venom: Pro-Inflammatory and Vasopeptidases Modulation Activities.
The Tityus serrulatus scorpion is considered the most dangerous of the Brazilian fauna due to the severe clinical manifestations in injured victims. Despite being abundant components of the venom, few linear peptides have been characterized so far, such as hypotensins. In vivo studies have demonstrated that hypotensin I (TsHpt-I) exerts hypotensive activity, with an angiotensin-converting enzyme (ACE)-independent mechanism of action. Since experiments have not yet been carried out to analyze the direct interaction of hypotensins with ACE, and to deepen the knowledge about these peptides, hypotensins I and II (TsHpt-II) were studied regarding their modulatory action over the activities of ACE and neprilysin (NEP), which are the peptidases involved in blood pressure control. Aiming to search for indications of possible pro-inflammatory action, hypotensins were also analyzed for their role in murine macrophage viability, the release of interleukins and phagocytic activity. TsHpt-I and -II were used in kinetic studies with the metallopeptidases ACE and NEP, and both hypotensins were able to increase the activity of ACE. TsHpt-I presented itself as an inhibitor of NEP, whereas TsHpt-II showed weak inhibition of the enzyme. The mechanism of inhibition of TsHpt-I in relation to NEP was defined as non-competitive, with an inhibition constant (Ki) of 4.35 μM. Concerning the analysis of cell viability and modulation of interleukin levels and phagocytic activity, BALB/c mice's naïve macrophages were used, and an increase in TNF production in the presence of TsHpt-I and -II was observed, as well as an increase in IL-6 production in the presence of TsHpt-II only. Both hypotensins were able to increase the phagocytic activity of murine macrophages in vitro. The difference between TsHpt-I and -II is the residue at position 15, with a glutamine in TsHpt-I and a glutamic acid in TsHpt-II. Despite this, kinetic analyzes and cell assays indicated different actions of TsHpt-I and -II. Taken together, these results suggest a new mechanism for the hypotensive effects of TsHpt-I and -II. Furthermore, the release of some interleukins also suggests a role for these peptides in the venom inflammatory response. Even though these molecules have been well studied, the present results suggest a new mechanism for the hypotensive effects of TsHpt-I.


Comorbidity of PTSD, Major Depression, and Substance Use Disorder Among Adolescent Victims of the Spring 2011 Tornadoes in Alabama and Joplin, Missouri.
The purpose of this study was twofold: (1) to estimate the prevalence of comorbid posttraumatic stress disorder (PTSD), major depressive episode (MDE), and substance use disorder (SUD); and (2) to identify risk factors for patterns of comorbidity among adolescents affected by disasters. A population-based sample of 2,000 adolescents (51% female; 71% Caucasian, 26% African American) aged 12 to 17 years (M = 14.5, SD = 1.7) and their parents was recruited from communities affected by the spring 2011 tornadoes in Alabama and Joplin, Missouri. Participants completed structured telephone interviews assessing demographic characteristics, impact of disaster, prior trauma history, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), symptoms of posttraumatic stress disorder (PTSD) and major depressive episode (MDE), and substance use disorder (SUD) symptoms. Prevalence estimates were calculated for PTSD + MDE, PTSD + SUD, MDE + SUD, and PTSD + MDE + SUD. Hierarchical logistic regression was used to identify risk factors for each comorbidity profile. Overall prevalence since the tornado was 3.7% for PTSD + MDE, 1.1% for PTSD + SUD, 1.0% for MDE + SUD, and 0.7% for PTSD + MDE + SUD. Girls were significantly more likely than boys to meet criteria for PTSD + MDE and MDE + SUD (ps < .05). Female gender, exposure to prior traumatic events, and persistent loss of services were significant risk factors for patterns of comorbidity. Parental injury was associated with elevated risk for PTSD + MDE. Adolescents should be evaluated for comorbid problems, including SUD, following disasters so that appropriate referrals to evidence-based treatments can be made. Results suggest that screening procedures to identify adolescents at risk for comorbid disorders should assess demographic characteristics (gender), impact of the disaster on the family, and adolescents' prior history of stressful events.


Estimating GFR in adult patients with hematopoietic cell transplant: comparison of estimating equations with an iohexol reference standard.
Formal evaluation of kidney function before and after hematopoietic cell transplant is important to determine conditioning regimens, type of transplant, and medication dosing. Serum creatinine and estimating equations may not accurately assess kidney function. Existing estimating equations for GFR were compared with an iohexol measure of GFR in a prospective cohort study of 50 patients undergoing hematopoietic cell transplant and subsequent care at the Fred Hutchinson Cancer Research Institute from 2009 to 2013. Patients underwent iohexol GFR, serum creatinine, and cystatin C determination at baseline and day 100 posthematopoietic cell transplant. Iohexol GFR measurements were compared with the CKD Epidemiology Collaboration, Inker CKD Epidemiology Collaboration cystatin C with and without serum creatinine, Modification of Diet in Renal Disease, and Cockcroft-Gault estimating equations using Bland-Altman analysis and McNemar's test. The iohexol measurements were also compared with blood samples collected simultaneously on filter paper. Mean differences between iohexol GFR and eGFR on the basis of Bland-Altman analyses ranged from -20.6 to +15.4 ml/min per 1.73 m(2) at baseline and -12.7 to +12.9 ml/min per 1.73 m(2) at day 100. The CKD Epidemiology Collaboration and Modification of Diet in Renal Disease estimating equations classified 64% of patients with a GFR<90 at baseline compared with 38% by iohexol GFR (P=0.003 and P<0.01, respectively). No statistically significant differences were seen at day 100. The filter paper GFR had a mean difference of 0 at baseline and 5.9 at day 100. Additionally, 21%-37% and 57%-89% of eGFRs were within 10% and 30%, respectively, of the iohexol GFR at baseline, and 16%-34% and 72%-84% were within 10% and 30%, respectively, of the iohexol GFR at day 100; 98% of the filter paper estimates at baseline were within 30%, and 46% were within 10% of iohexol GFR. The estimating equations are neither accurate nor precise in the hematopoietic cell transplant population, and clinical decision may require measurement of GFR.


Mechanism of Cs Immobilization within a Sodalite Framework: The Role of Alkaline Cations and the Si/Al Ratio.
Conditioning of radioactive waste generated from the operation of medical institutions, nuclear cycle facilities, and nuclear facilities is important for the safety of the environment. One of the most hazardous radionuclides is radioactive cesium. There is a need for more effective solutions to contain radionuclides, especially cesium (Cs+). Geopolymers are promising inorganic materials that can provide a large active surface area with adjustable porosity and binding capacity. The existence of nanosized zeolite-like structures in aluminosilicate gels was shown earlier. These structures are candidates for immobilizing radioactive cesium (Cs+). However, the mechanisms of their interactions with the aluminosilicate framework related to radionuclide immobilization have not been well studied. In this work, the influence of alkaline cations (Na+ or K+) and the aluminosilicate framework structure on the binding capacity and mechanism of interaction of geopolymers with Cs+ is explored in the example of a sodalite framework. The local structure of the water molecules and alkaline ions in the equilibrium state and its behavior when the Si/Al ratio was changed were studied by DFT.


The sulfamate functional group as a new anchor for solid-phase organic synthesis
[reaction: see text] Sulfamate derivatives were loaded on trityl chloride resin, and two variants of cleavage were developed for this sulfamate anchor: an acid treatment to easily restore the free sulfamate and a nucleophilic treatment to generate the corresponding phenol. In addition to loading/cleavage assays and stability experiments, a model sequence of reactions was performed with the new sulfamate anchor to show its applicability in further combinatorial solid-phase synthesis of libraries of biologically relevant sulfamate derivatives.


Late mesh migration after Nissen funduplication mimicking a gastric neoplasm.
A 63-year-old female with a Nissen funduplication that was diagnosed nine years previously presented with abdominal pain, weight loss and occasional dysphagia of a few months duration. A computed tomography (CT) scan identified an extensive gastric tumor with a subtle curvature and cardia with distal esophagus circumferential enlargement. Gastroscopy identified gastric linitis plastica with many attached residues. The biopsy was compatible with inflammatory changes. A linear echoendoscopy identified an area at the cardia level that was compatible with a foreign body with a lineal hyperechoic irregular focus.


Macrophage plasticity in skeletal muscle repair.
Macrophages are one of the first barriers of host defence against pathogens. Beyond their role in innate immunity, macrophages play increasingly defined roles in orchestrating the healing of various injured tissues. Perturbations of macrophage function and/or activation may result in impaired regeneration and fibrosis deposition as described in several chronic pathological diseases. Heterogeneity and plasticity have been demonstrated to be hallmarks of macrophages. In response to environmental cues they display a proinflammatory (M1) or an alternative anti-inflammatory (M2) phenotype. A lot of evidence demonstrated that after acute injury M1 macrophages infiltrate early to promote the clearance of necrotic debris, whereas M2 macrophages appear later to sustain tissue healing. Whether the sequential presence of two different macrophage populations results from a dynamic shift in macrophage polarization or from the recruitment of new circulating monocytes is a subject of ongoing debate. In this paper, we discuss the current available information about the role that different phenotypes of macrophages plays after injury and during the remodelling phase in different tissue types, with particular attention to the skeletal muscle.


Clinicians' Selection Criteria for Video Visits in Outpatient Care: Qualitative Study.
Video visits with patients were introduced into outpatient care at a hospital in Sweden. New behaviors and tasks emerged due to changes in roles, work processes, and responsibilities. This study investigates the effects of the digital transformation-in this case, how video visits in outpatient care change work processes and introduce new tasks-to further improve the concept of video visits. The overarching goal was to increase the value of these visits, with a focus on the value of conducting the treatment for the patient. Through the real-time, social interactional features of preparing for and conducting video visits with patients with obesity, this study examines which patients the clinicians considered suitable for video visits and why. The aim was to identify the criteria used by clinicians when selecting patients for video visits to understand what criteria the clinicians used as the grounds for their selection. Qualitative methods were used, including 13 observations of video visits at 2 different clinics and 14 follow-up interviews with clinicians. Transcripts of interviews and field notes were thematically analyzed, discussed, and synthesized into themes. From the interviews, 20 different arguments for selecting a specific patient for video visits were identified. Analyzing interviews and field notes also revealed unexpressed arguments that played a part in the selection process. The unexpressed arguments, as well as the implicit reasons, for why a patient was given the option of video visits can be understood as the selection criteria for helping clinicians in their decision about whether to offer video visits or not. The criteria identified in the collected data were divided into 3 themes: practicalities, patient ability, and meeting content. Not all patients with obesity undergoing treatment programs should be offered video visits. Patients' new responsibilities could influence the content of the meeting and the progress of the treatment program. The selection criteria developed and used by the clinicians could be a tool for finding a balance between what the patient wants and what the clinician thinks the patient can manage and achieving good results in the treatment program. The criteria could also reduce the number and severity of disturbances and limitations during the meeting and could be used to communicate the requirements they represent to the patient. Some of the criteria are based on facts, whereas others are subjective. A method for how and when to involve the patient in the selection process is recommended as it may strengthen the patient's sense of responsibility and the relationship with the clinician.


Healthcare information technology's relativity problems: a typology of how patients' physical reality, clinicians' mental models, and healthcare information technology differ.
To model inconsistencies or distortions among three realities: patients' physical reality; clinicians' mental models of patients' conditions, laboratories, etc; representation of that reality in electronic health records (EHR). To serve as a potential tool for quality improvement of EHRs. Using observations, literature, information technology (IT) logs, vendor and US Food and Drug Administration reports, we constructed scenarios/models of how patients' realities, clinicians' mental models, and EHRs can misalign to produce distortions in comprehension and treatment. We then categorized them according to an emergent typology derived from the cases themselves and refined the categories based on insights gained from the literature of interactive sociotechnical systems analysis, decision support science, and human computer interaction. Typical of grounded theory methods, the categories underwent repeated modifications. We constructed 45 scenarios of misalignment between patients' physical realities, clinicians' mental models, and EHRs. We then identified five general types of misrepresentation in these cases: IT data too narrowly focused; IT data too broadly focused; EHRs miss critical reality; data multiplicities-perhaps contradictory or confusing; distortions from data reflected back and forth across users, sensors, and others. The 45 scenarios are presented, organized by the five types. With humans, there is a physical reality and actors' mental models of that reality. In healthcare, there is another player: the EHR/healthcare IT, which implicitly and explicitly reflects many mental models, facets of reality, and measures thereof that vary in reliability and consistency. EHRs are both microcosms and shapers of medical care. Our typology and scenarios are intended to be useful to healthcare IT designers and implementers in improving EHR systems and reducing the unintended negative consequences of their use.


Pediatric echocardiograms performed at primary centers: Diagnostic errors and missing links!
The present study was undertaken to assess the accuracy of pediatric echocardiograms done at non-tertiary centers and to evaluate the relationship of inaccurate interpretations with age, echocardiogram performer and complexity of congenital heart disease (CHD). The echocardiogram reports of 182 consecutive children with CHD (5 days-16 years) who were evaluated at a non-tertiary center and subsequently referred to our center were reviewed. Age of the child at echocardiogram, echocardiogram performer and complexity of CHD were noted. These reports were compared with echocardiogram done at our center. Discrepancies were noted and categorized. To assess our own error rate, we compared our echocardiogram reports with the findings obtained during surgery (n = 172), CT scan (n = 9) or cardiac catheterization reports (n = 1). Most of the children at the non-tertiary center (92%) underwent echocardiogram by personnel other than a pediatric cardiologist. Overall, diagnostic errors were found in 69/182 (38%) children. Moderate and major discrepancies affecting the final management were found in 42/182 (23%) children. Discrepancies were higher when the echocardiogram was done by personnel other than pediatric cardiologist (P < 0.01) and with moderate and high complexity lesions (P = 0.0001). There was no significant difference in proportion of these discrepancies in children ≤ 1 year vs. >1 year of age. A significant number of pediatric echocardiograms done at non-tertiary centers had discrepancies that affected the management of these children. More discrepancies were seen when the echocardiogram performer was not a pediatric cardiologist and with complex CHD.


Sudden cardiac death during nighttime hours.
In the absence of apparent triggers, sudden cardiac death (SCD) during nighttime hours is a perplexing and devastating phenomenon. There are few published reports in the general population, with insufficient numbers to perform sex-specific analyses. Smaller studies of rare nocturnal SCD syndromes suggest a male predominance and implicate sleep-disordered breathing. The purpose of this study was to identify mechanisms of nighttime SCD in the general population. From the population-based Oregon Sudden Unexpected Death Study, we evaluated SCD cases that occurred in the community between 10 PM and 6 AM (nighttime) and compared them with daytime cases. Univariate comparisons were evaluated using Pearson χ2 tests and independent samples t tests. Logistic regression was used to further assess independent SCD risk. A total of 4126 SCD cases (66.2% male, 33.8% female) met criteria for analysis and 22.3% (n = 918) occurred during nighttime hours. Women were more likely to present with nighttime SCD than men (25.4% vs 20.6%; P < .001). In a multivariate regression model, female sex (odds ratio [OR] 1.3 [confidence interval (CI) 1.1-1.5]; P = .001), medications associated with somnolence/respiratory depression (OR 1.2 [CI 1.1-1.4]; P = .008) and chronic obstructive pulmonary disease/asthma (OR 1.4 [CI 1.1-1.6]; P < .001) were independently associated with nighttime SCD. Women were taking more central nervous system-affecting medications than men (1.9 ± 1.7 vs 1.4 ± 1.4; P = .001). In the general population, women were more likely than men to suffer SCD during nighttime hours and female sex was an independent predictor of nighttime events. Respiratory suppression is a concern, and caution is advisable when prescribing central nervous system-affecting medications to patients at an increased risk of SCD, especially women.


The copper influx transporter human copper transport protein 1 regulates the uptake of cisplatin in human ovarian carcinoma cells.
Cells selected for resistance to cisplatin are often cross-resistant to copper and vice versa, and the major copper influx transporter copper transport protein 1 (CTR1) has been shown to regulate the uptake of cisplatin, carboplatin, and oxaliplatin in yeast. To further define the role of hCTR1 in human tumor cells, the ovarian carcinoma cell line A2780 was molecularly engineered to increase expression of hCTR1 by a factor of 20-fold. Enhanced expression of hCTR1 in the A2780/hCTR1 cells was associated with a 6.5-fold increase in basal steady-state copper content and a 13.7-fold increase in initial copper influx, demonstrating that the exogenously expressed hCTR1 was functional in altering copper homeostasis. The A2780/hCTR1 cells accumulated 46% more platinum after a 1-h exposure to 2 microM cisplatin, and 55% more after a 24 h exposure, than the control A2780/empty vector cells. The initial uptake of cisplatin was 81% higher in the A2780/hCTR1 cells when measured at 5 min. Thus, increased expression of hCTR1 had a substantially larger effect on the cellular pharmacology of copper than cisplatin. Interestingly, the increased uptake of copper and cisplatin was accompanied by only a marginal increase in sensitivity to the cytotoxic effect of copper and cisplatin, and there was no increase in the extent of cisplatin-DNA adduct formation. Thus, although increased expression of hCTR1 mediates greater cellular accumulation of copper and cisplatin, hCTR1 delivers these compounds into intracellular compartments from which they do not have ready access to their key cytotoxic targets.