Infundibular neurons of the human hypothalamus simultaneously reactive with antisera against endorphins, ACTH, MSH and beta-LPH.
In man, discrete neurons of the infundibular (arcuate) nucleus contain compounds that can be stained with anti-endorphin (alpha and beta), anti-ACTH, anti-MSH (alpha and beta) and anti-beta-LPH immune sera (I.S.). In the fetus, certain neurons stain with anti-beta-endorphin or anti((17--39)ACTH starting from the 11th week of fetal life. At the ultrastructural level, these neurons contain elementary granules that are immunoreactive with anti-beta-endorphin. In the adult, neurons immunoreactive with anti-beta-endorphin are found in the infundibular nucleus. Their axonal fibers terminate around blood vessels in the neurovascular zone and in the pituitary stalk, or establish contacts with non-immunoreactive perikarya of the infundibular nucleus. These neurons can be stained with anti(17--39)ACTH and anti-beta-endorphin I.S. The most reactive are also stained moderately with anti-alpha-MSH, anti-beta-MSH, anti-beta-LPH, anti-alpha-endorphin, or anti(1--24)ACTH I.S. These results indicate that, in man, compound(s) identical with or immunologically related to endorphins, beta-LPH, ACTH and MSH are secreted by certain hypothalamic neurons. These agents probably originate from a common precursor molecula similar to the so-called pro-opiocortin.


[Extracorporeal shock wave lithotripsy of sialoliths as a new noninvasive outpatient treatment concept].
The rapid progression of Extracorporeal Shock Wave Lithotripsy (ESWL) opens new possibilities in painless non-invasive treatment of salivary gland stones under local therapy. Procedure and first very promising success in the clinical appliance to sialolithiasis is shown as follows.


Retroperitoneoscopic adrenalectomy for adrenal tumors via a single large port.
Laparoscopic adrenalectomy is generally performed with carbon dioxide insufflation of the cavity and requires multiple trocars. This study reports the outcomes of retroperitoneoscopic adrenalectomy (RA) for adrenal tumors via a single port using a large cylinder without carbon dioxide insufflation. Fifty-four patients with adrenal tumors were treated using RA via a single large port. The average tumor size was 2.6 cm. For surgery, patients were placed in the lateral decubitus position with slight flexion, and a 4.5-cm skin incision was performed below the 12th rib in the midaxillary line. The retroperitoneal space was dissected using index fingers and a balloon dilator. A rectoscope tube with a 4-cm diameter was inserted, and the adrenal glands were removed endoscopically via the single large port without carbon dioxide insufflation. This procedure was completed in 53 patients (98.1%). The average duration of surgery was 203 minutes, and the mean estimated blood loss was 252 mL. Four patients (7.4%) required blood transfusion. Postoperative major complications, including fulminant hepatitis and pulmonary thrombosis, were observed in two patients (3.7%), and the patient with hepatic disease died on the 14th postoperative day. The mortality rate after surgery thus was 1.9%. However, no local tumor recurrence or hormonal relapse has occurred at a median follow-up of 34 months. This procedure appears to be effective and relatively minimally invasive. However, it is limited by the narrow working space and restriction of the manipulation of instruments.


Pharmacokinetics and pharmacodynamics of long-term continuous-infusion doxorubicin.
Steady-state plasma levels of doxorubicin and doxorubicinol were analyzed in 32 patients with advanced cancer, each of whom was given doxorubicin by long-term continuous infusion at progressively increasing infusion rates. Patients received doxorubicin for 2 to 50 weeks at rates of 0.2 to 6.1 mg/m2/day. Dose-limiting stomatitis and leukopenia were observed. The mean maximum steady-state doxorubicin concentration was 6.04 ng/ml at a mean maximum infusion rate of 3.92 mg/m2/day. Clearance mechanisms did not appear to be saturated at the durations or infusion rates used in this study. The maximum steady-state doxorubicin level and the ln (initial WBC) were significant correlates of the ln (nadir WBC) (p = 0.002 and 0.02, respectively). A model was constructed according to these two parameters that significantly describes ln (nadir WBC) (p = 0.001). Neither age, infusion rate, nor doxorubicinol level correlated with nadir WBC. Stomatitis did not correlate with any of these parameters. The demonstration of this pharmacodynamic relationship highlights the potential importance of pharmacologic data collection in ongoing attempts to predict the clinical effects of anticancer drugs.


Brain metastases of melanoma--mechanisms of attack on their defence system by engineered stem cells in the microenvironment.
This report gives a better emphasis on the role of targeted effectors (e.g. a combination of 5-FC with CD-NSPCs as compared to the application of NSPCs alone) and how such delivery of pro-drug activating enzymes and other tumor-killing substances may overcome melanocytic defence system, interact with and promote the host defence and immune response modulations not only in melanoma but, potentially, in other highly-metastatic cancers.


The independent and joint associations of physical activity and body mass index with myocardial infarction: The Tromsø Study.
Physical activity and overweight are associated with myocardial infarction (MI). However, their joint association with MI remains unclear. Our objective was to examine the independent and joint association between leisure-time physical activity (LTPA), body mass index (BMI) and MI. This prospective cohort study included 16,572 men and women (47.5% women) aged 20-54 years who took part in the second Tromsø Study. At baseline in 1979-80 LTPA was assessed by questionnaire. Data on MI was collected and adjudicated through hospital and causes of death registries between 1979 and 2013. Cox proportional hazards models were used to examine the independent and joint associations between LTPA, BMI and MI. The final sample included 16,104 individuals. During a median follow up of 34 years, 1613 incident cases of MI were recorded. Physical inactivity and elevated BMI were both independently associated with MI (p for trend 0.02 and <0.001). In joint analyses, normal weight, inactive individuals had a 20% higher risk of MI compared to their active counterparts (hazard ratio (HR) 1.20 (1.02-1.41)). The highest risk of MI was seen in obese, inactive individuals when compared to normal weight, active individuals (HR 3.20 (2.30-4.44)). The risk of MI increased with increasing BMI regardless of the activity level. HRs were lower for active compared to inactive individuals within the same BMI category. The findings suggest that LTPA and BMI are independently associated with risk of MI. LTPA seems to attenuate but not eliminate the risk of MI associated with excess bodyweight.


Is it really a STEMI or Takotsubo cardiomyopathy?
The goal of this column is to provide a case that is pertinent to the medical transport industry and provides teaching points for crewmembers who are actively involved in out-of-hospital transport, whether by air or by other means. In this issue, we have the opportunity to examine two similar cases from a single crew (nurse/paramedic) that occurred within several months of each other and to describe a moderately rare condition that mimics a common diagnosis encountered by critical care personnel.


Polymeric micelles loaded with (1,2-diaminocyclohexane)platinum(II) against colorectal cancer.
We investigated the potential of nanomedicine in loading the oxaliplatin parent complex (1,2-diaminocyclohexane)platinum(II)-loaded polymeric micelles (DACHPt/m) against multiple liver metastases from colon cancer in a mouse model. The efficacy of DACHPt/m or oxaliplatin (on days 14 and 21 after inoculation of tumor cells) was evaluated in a mouse model of liver metastasis for murine colon adenocarcinoma C26 cells. In vivo antitumor effects were evaluated by recording the number of liver metastases and weights of metastatic livers after treatment (day 28). The accumulation of drugs in tumors and liver parenchyma was analyzed using ion coupled plasma-mass spectrometry 24 h after administration of DACHPt/m or oxaliplatin (n = 5). We assessed renal and hepatic toxicities through changes in creatinine, aspartate transaminase, and alanine transaminase on the last day of the antitumor activity experiment. Mice receiving DACHPt/m had significantly fewer metastatic nodules (P = 0.038) and lower liver weights (P = 0.038) than those receiving oxaliplatin. The accumulation of DACHPt/m in the metastatic liver was significantly higher than that of oxaliplatin, whereas the distribution of micelles in healthy liver tissues was limited. Mice treated with DACHPt/m also showed significantly lower serum creatinine levels than those treated with oxaliplatin (P = 0.007), whereas serum aspartate transaminase and alanine transaminase levels for both drugs were not different. High levels of DACHPt/m accumulate in metastatic livers, producing a strong antitumor effect without severe adverse effects. DACHPt/m is a safe approach for managing liver metastasis from colorectal cancer.


Inductive interactions in early embryonic development.
This is an update of a previous review (Current Opinion in Cell Biology 2:969-974) in which we discussed recent work attempting to understand the sequence of inductive interactions responsible for establishing the body plan of the early embryo. As before, we concentrate on inductive interactions in amphibian embryos, where significant progress has been made in the past two years. In this update, however, we also consider recent embryological data obtained with amniote embryos such as the chick, together with complementary data provided by genetic analyses of mouse and Drosophila development.


Identifying the white matter structural network of motor reserve in early Parkinson's disease.
Motor reserve refers to the individual capacity to cope with nigrostriatal dopamine depletion in Parkinson's disease (PD). This study aimed to explore the white matter structural network associated with motor reserve in patients with newly diagnosed PD. A total of 238 patients with early-stage drug-naïve PD who underwent 18F-FP-CIT PET and brain MRI scans at initial assessment were enrolled. We estimated individual motor reserve based on the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) scores and dopamine transporter availability in the posterior putamen using a residual model. Then, we performed threshold-free network-based statistics (TFNBS) analysis to identify the structural brain network associated with the estimated motor reserve. We also assessed the effect of the network connectivity strength on the longitudinal increase in levodopa-equivalent dose (LED). The mean age at PD symptom onset was 69.10 ± 9.03 years and the mean UPDRS-III score at the time of PD diagnosis was 22.44 ± 9.72. TFNBS analysis identified a motor reserve-associated structural network whose nodes were mainly in the frontal region and cerebellum. Higher network strength (i.e., greater motor reserve) was associated with a slower longitudinal increase in LED during a 3-year follow-up period. The structural brain network is associated with motor reserve in patients with PD. Connectivity strength within the identified network indicates the individual's capacity to tolerate PD-related pathologies, which is maintained with disease progression and affects the long-term motor prognosis of PD.


Enantioselective synthesis of 3-hydroxy oxindoles by ytterbium-catalysed decarboxylative addition of β-ketoacids to isatins.
A ytterbium(III)-indapybox catalysed enantioselective decarboxylative addition reaction of β-ketoacids to isatins is described. The biologically important 3-hydroxy oxindoles were obtained in high yields and excellent enantioselectivities.


Metabolic activation of the brachium conjunctivum during induced hypothermia.
During hypothermia induced in ground squirrels by the halothane-heliox method, 2-deoxyglucose uptake of a white matter structure, the brachium conjunctivum, increased relative to the surrounding gray matter structures. The possibility of 2-deoxyglucose uptake by glial as well as neuronal elements in the brachium conjunctivum and the implications of this observation for the use of optical density ratios is discussed.


Angiotensin Antagonist Inhibits Preferential Negative Memory Encoding via Decreasing Hippocampus Activation and Its Coupling With the Amygdala.
Exaggerated arousal and dysregulated emotion-memory interactions are key pathological dysregulations that accompany the development of posttraumatic stress disorder (PTSD). Current treatments for PTSD are of moderate efficacy, and preventing the dysregulations during exposure to threatening events may attenuate the development of PTSD symptomatology. In a preregistered double-blind, between-subject, placebo-controlled pharmaco-functional magnetic resonance imaging design, this proof-of-concept study examined the potential of a single dose of the angiotensin II type 1 receptor antagonist losartan (LT) to attenuate the mnemonic advantage of threatening stimuli and the underlying neural mechanism via combining an emotional subsequent memory paradigm with LT (n = 29) or placebo (n = 30) and a surprise memory test after a 24-hour washout. LT generally improved memory performance and abolished emotional memory enhancement for negative but not positive material, while emotional experience during encoding remained intact. LT further suppressed hippocampus activity during encoding of subsequently remembered negative stimuli. At the network level, LT reduced coupling between the hippocampus and the basolateral amygdala during successful memory formation of negative stimuli. Our findings suggest that LT may have the potential to attenuate memory formation for negative but not positive information by decreasing hippocampus activity and its functional coupling strength with the amygdala. These findings suggest a promising potential of LT to prevent preferential encoding and remembering of negative events, a mechanism that could prevent the emotion-memory dysregulations underlying the development of PTSD symptomatology.


Sexual dimorphism in the pituitary-adrenal response to tumor necrosis factor-alpha, but not to interleukin-6, in the rat.
It is known that the pituitary-adrenal responses to lipopolysaccharide and interleukin (IL)-1 are sexually dimorphic in rodents, with females having an enhanced secretion of adrenocorticotropin (ACTH) and corticosterone. This study investigated whether the ACTH and corticosterone responses to tumor necrosis factor (TNF)-alpha and IL-6, two principal proinflammatory cytokines, are also modulated by the sex steroid milieu in the rat. Mature male and female rats received an intravenous administration of TNF-alpha(10 microg/kg) and IL-6 (10 microg/kg), and changes in plasma ACTH and corticosterone levels were determined over time. The effect of gonadectomy on the hormonal responses was also examined in both sexes. TNF-alpha induced significantly higher responses of ACTH and corticosterone in females than in males, and this sexual difference was abolished by gonadectomy in both sexes. By contrast, the hormonal responses to IL-6 were not significantly affected by either gender or gonadectomy. These results suggest a sex steroid-dependent modulation of the TNF-alpha-induced, but not the IL-6-induced, ACTH and corticosterone secretion in the rat. Further evidence for the sexually dimorphic neuroimmunoendocrine activity is reported herein.


The Differential Risk of Mortality Among Users of Overactive Bladder Anticholinergic Medications and β3 Agonists.
Anticholinergic overactive bladder (OAB) medications have been studied in large observational studies to determine if they are associated with a greater risk of mortality (potentially because of their effects on the heart or the brain). Studies in different populations of old adults have shown that oxybutynin is associated with a significantly higher risk of mortality of 26-58% in comparison to other OAB anticholinergic medications or β3 agonists. In general, anticholinergic OAB medications may increase the risk of mortality, and a single multicountry study showed that β3 agonist users had a 20% lower risk of mortality compared to OAB anticholinergic users. PATIENT SUMMARY: Older adults who started using a traditional type of medication for overactive bladder (oxybutynin) had a higher risk of dying compared to people who used newer types of anticholinergic medications and to people who used overactive bladder medications that work in a different way.


Osteochondral lesions of the talus: size, age, and predictors of outcomes.
In this article, our research on osteochondral lesions of the talus (OLTs) is summarized, the orthopedic literature is reviewed, and the direction of future research and treatment trends are discussed. Our research has explored the role of lesion size, significance of marrow edema, relationship of patient age, importance of lesion containment, and role of a stable cartilage lesion cap in the prognosis and outcomes of these lesions. We have identified smaller sized lesions, younger patients and contained lesions as independent predictors of success for the operative treatment of OLTs. Our data should facilitate the development of a more comprehensive treatment algorithm to more accurately predict success in operative management of these lesions.


Competition for dispersal agents among tropical trees: influences of neighbors.
We distinguish factors influencing seed dispersal that are potentially under the control of parent plants from those that are not in a Panamanian population of the neotropical nutmeg, Virola surinamensis (Myristicaceae).In the first category, we find that individual variation in crop size and nutritional components of the aril failed to explain any variation in the proportion of fruits taken from fruiting trees. The ratio of edible aril to indigestible seed explained a significant but small (13%) portion of variation in the fraction of fruits taken by tropical birds. These results suggest that the potential for ongoing natural selection on fruit and crop characteristics by dispersal agents exists, but is periodic or weak. On the other hand, the number of fruits available to birds within 50 m of any given Virola tree profoundly influenced the extent to which it secured dispersal. More than three times as much variation (42%) in relative dispersal could be explained by the number of "competing" Virola fruits during the peak of an individual tree's fruiting season. When isolated plants are eliminated from the analysis, the depressive effect of competition with neighbors explains 72% of the variation in individual dispersal. These results suggest that birds seek out clumps of fruiting trees, but that intraspecific competition for a limited disperser assemblage occurs within the clumps.Our results are a first step towards separating attributes of the plant that are potentially under the influence of natural selection by dispersal agents from emergent population effects that can override individual advantage in crop or fruit characteristics.


Importance of novel sequence alterations in the FHIT gene on formation of breast cancer.
The character, role and impact of FHIT gene alterations, for which recent studies have shown that the gene has a role in the early stage of carcinogenesis in breast cancer, are still unclear. Thus, the current study evaluated FHIT gene mutations from breast tissue of women with malignant and benign breast disease and to elucidate the frequency and type of mutations in this gene. Mutations in exons 5-9 of the FHIT gene were screened using the intronic primer pairs in 83 breast (67 malignant and 16 benign) tissue samples by single-strand conformational polymorphism and sequencing analysis. FHIT mutations were detected in 13 of the 67 malignant cases (19.4%) and 2 of the 16 benign cases (12.5%). Four different sequence variants were determined: two novel frame shift mutations (codon 90 insA, codon 146 delT), one intronic novel mutation (IVS8 -17 insA), and one previously identified silent transition type alteration (codon 88 C to T). In addition, determination of this silent alteration caused formation of new exonic splicing enhancer (ESE) motifs on mutated sequences by using the ESEfinder program. Our data contribute significantly to that currently known about the presence of FHIT gene mutations on the formation of breast cancer.


Predicting liquid chromatography-electrospray ionization/mass spectrometry signal from the structure of model compounds and experimental factors; case study of aripiprazole and its impurities.
A priori estimation of analyte response is crucial for the efficient development of liquid chromatography-electrospray ionization/mass spectrometry (LC-ESI/MS) methods, but remains a demanding task given the lack of knowledge about the factors affecting the experimental outcome. In this research, we address the challenge of discovering the interactive relationship between signal response and structural properties, method parameters and solvent-related descriptors throughout an approach featuring quantitative structure-property relationship (QSPR) and design of experiments (DoE). To systematically investigate the experimental domain within which QSPR prediction should be undertaken, we varied LC and instrumental factors according to the Box-Behnken DoE scheme. Seven compounds, including aripiprazole and its impurities, were subjected to 57 different experimental conditions, resulting in 399 LC-ESI/MS data endpoints. To obtain a more standard distribution of the measured response, the peak areas were log-transformed before modeling. QSPR predictions were made using features selected by Genetic Algorithm (GA) and providing Gradient Boosted Trees (GBT) with training data. Proposed model showed satisfactory performance on test data with a RMSEP of 1.57 % and a of 96.48 %. This is the first QSPR study in LC-ESI/MS that provided a holistic overview of the analyte's response behavior across the experimental and chemical space. Since intramolecular electronic effects and molecular size were given great importance, the GA-GBT model improved the understanding of signal response generation of model compounds. It also highlighted the need to fine-tune the parameters affecting desolvation and droplet charging efficiency.


Localization and phototoxic effect of zinc sulfophthalocyanine photosensitizer in human colon (DLD-1) and lung (A549) carcinoma cells (in vitro).
Photodynamic therapy (PDT) is a therapeutic modality used for treating cancerous cells. It has been previously shown that mixed sulfonated metallophthalocyanine complex, zinc sulfophthalocyanine (ZnPcS(mix)) is effective in destroying lung cancer cells. This study aimed to determine subcellular localization of ZnPcS(mix) and its effect on two cancer cell lines. ZnPcS(mix) was activated at a wavelength of 680 nm with 5 J/cm². Colon (DLD-1) and lung (A549) cancer cell lines were used. Subcellular localization of ZnPcS(mix) was determined by fluorescence microscopy. Toxicity of PS alone and combination of light and PS (PDT) was determined by cell morphology, viability, proliferation and cytotoxicity. Cells which received no irradiation (0 J/cm²), irradiation alone (5 J/cm²) or treated with PS alone (no irradiation) served as controls. ZnPcS(mix) localized in both lysozomes and mitochondria in both A549 and DLD-1 cells. A549 cells treated with PDT showed a significant decrease in viability and proliferation in all PS concentrations used, while in DLD-1 cells a significant decrease was seen with concentrations of 10, 20 and 40 μM. In absence of light, ZnPcS(mix) did not result in cellular toxicity in A549 cells whereas in DLD-1 cells it resulted in a reduction in cell proliferation only at a concentration of 40 μM. ZnPcS(mix) was effective in inducing cell death in both cell lines when localized in vital organelles such mitochondria and lysozomes which are essential for cell functioning. Photoactivated ZnPcS(mix) affected the cells at different concentration and yielded good therapeutic results in vitro.


The effects of training in time-limited dynamic psychotherapy: changes in therapeutic outcome.
The present study explored the effects on therapeutic outcomes of training therapists in brief manualized therapy. As part of the Vanderbilt II project, each of 16 therapists (8 psychiatrists and 8 clinical psychologists) treated 2 moderately disturbed adult patients using his or her customary short-term treatment methods; they then received a year of training in a manualized form of brief dynamic therapy, Time-Limited Dynamic Psychotherapy (TLDP); finally, they administered TLDP to 2 additional patients. It was hypothesized that training would result in improved outcomes generally and that differentially greater improvement would be seen in patients commonly considered less suitable for brief dynamic therapy. Outcome data obtained at termination failed to support either hypothesis. Measurements of interpersonal dependency obtained at a one-year follow-up were consistent with the first hypothesis, but the follow-up data were inconsistent with the second. A systematic review of the 32 posttraining cases suggested that the majority of the therapists had not achieved basic competence at TLDP. Die hier beschriebene Studie untersucht die Wirkungen eines Trainings in manualisierter Kurzzeitherapie auf das Therapierergebnis. Als Teil des Vanderbilt II Projektes behandelten jeweils 16 Therapeuten (8 Psychiater und 8 klinische Psychologen) zwei mittelgradig beeinrächtigte erwachsene Patienten mit den ihnen vertrauten Kurzzeitbehandlungsmethoden. Danach wurden sie über ein Jahr in einer manualisierten Form psychodynamischer Kurzzeittherapie ausgebildet und wandten diese Therapie auf zwei weitere Patienten an. Es wurde angenommen, dass die Ausbildung in besseren Ergebnisdaten, die bei Ende der Therapie erhoben wurden, konnten diese Hypothese nicht bestätigen. Maße für die interpersonale Abhängigkeit zu einem Einjahreskatamnesezeitpunkt waren mit der ersten Hypothese konform, aber inkonsistent mit der zweiten. Eine systematische Untersuchung der 32 nach der Ausbildung behandelten Fälle legt nahe, dass die Mehrzahl der Therapeuten keine grundlegende Kompetenz in zeitlich limitierter dynamischer Psychotherapie erworben hatte. Cette éude explore les effets sur les résultats thérapeutiques de la formation des thérapeutes dans une thérapie brève, manualissée. Dans le cadre du projet Vanderbilt II, chacun des 16 thérapeutes (8 psychiatrs et 8 psychologues cliniciens) a traité deux patients adultes modérément perturbés, chacun par sa méthode habituelle de thérapie brève; ensuite ils ont reçu une formation d'une année dans une méthode manualisée de thérapie brève, la Psychothérapie Dynamique Limitée dans le Temps (TLDP); pour finir, ils ont appliqué la TLDP à de meilleurs résultats en général, et qu'une amélioration comparativement plus importante sera observée chez des patients habituellement considérés comme moins adaptés à une thérapie dynamique brè. Les résultats obtenus à la terminaison n'ont pu confirmer aucune de ces hypothèses. Des mesures de la dépendance interpersonnelle une année après étaient consistantes avec la première hypothèse, mais les données catamnestiques étaient inconsistantes avec la deuxième. Une revue systématique des 32 cas après formation a suggéré que la majorité des thérapeutes n'avait pas acquis une compétence de base en TLDP. Este estudio exploró la efectividad del entrenamiento de terapeutas en una terapia breve manualizada. Como parte del proyecto Vanderbilt II, dieciséis terapeutas (ocho psiquiatras y ocho psicólogos clínicos) trataron dos pacientes adultos mooderadamente perturbados con sus métodos habituales de tratamiento a corto plazo. Estos terapeutas recibieron luego un año de entrenamiento en terapia dinámica breve manualizada que se Ilamó Psicoterapia Dinámica de Tiempo limitado (TLDP). Finalmente, administraron esta TLDP a dos pacientes más. La hipótesis fue que el entrenamiento ilevaría, en general, a resultados mejores y que habría mayor mejoramiento en pacientes menos aptos para una terapia dinámica breve. Los resultados a la terminación no apoyaron ninguna de las dos hipótesis. Las mediciones de dependencia interpersonal al año de seguimiento resultaron consistentes con la primera hipótesis, mientras que los resultados de seguimiento fueron inconsistentes con la segunda. Una revisión sistemática de los treinta y dos casos luego del entrenamiento sugiere que la mayoría de los terapeutas no había l.


Infographics Improve Comprehension and Recall at the Orthopaedic Journal Club.
Information graphics, abbreviated to infographics, convey information using visualisations and images. This format of presenting research has been shown to be preferred by 80% of clinicians when compared to text articles. The weekly Journal Club was audited within our institution over a period of 10 weeks. Five weeks of article presentations using plain text abstract displays preceded 5 weeks of infographic display. A multiple-choice questionnaire was constructed weekly so as to test the attendees' recall and comprehension. A total of 1036 multiple-choice questions were answered across the 10 weeks, which included 553 questions (53.4%) based on the standard Journal Club format, and 483 questions (46.6%) on infographic displays. The use of infographics saw significantly improved test results from 42% to 65.8% (p < 0.001). Questions were answered correctly 1.5 times more often following infographic introduction. Infographics were preferred over plain text abstracts by 78% of team members. Infographics enhanced the audience's comprehension and recall of orthopaedic research when used as a presentation tool at the Journal Club. The majority of clinicians preferred infographic displays to plain text abstracts. Research was perceived as being more engaging, and thus more suitable for dissemination, such that key messages could be shared with surgeons, researchers and patients worldwide.


Investigation of non-National Immunization Program vaccination intentions in rural areas of China.
China's current immunization program was revised in 2007. Some common childhood vaccines such as those for influenza, pediatric pneumonia, Haemophilus influenzae, varicella, and rotavirus have not been included in the National Immunization Program (NIP) and need to be purchased by children's guardians at their own expense. Rural areas, constrained by economic development and vaccine awareness, have a low non-NIP vaccination rate and more family medical expenses and social burden. This study aims to examine the awareness and attitude of rural parents about non-NIP vaccines and relevant factors influencing their vaccination intention to provide strategic suggestions for expanding and improving the Chinese government's NIP policy. A qualitative method of in-depth interviews were conducted for this study. We interviewed 30 rural parents in a central Chinese village to investigate their awareness of non-NIP vaccines and their vaccination intention and behavior. All the interview data were analyzed through the Colaizzi seven-step data analysis method. This study summarized the individual and social level factors influencing the non-NIP vaccination intention of rural parents. The individual level factors include four themes: perceived severity with physical harm, treatment consumption (cost of the treatment of the subject diseases), psychological burden, and social consequences being subthemes; perceived vulnerability with age vulnerability, medical history, immune quality (children's underlying immune status), and environmental vulnerability (sanitary condition of the rural environment) as subthemes; perceived efficacy with effect perception, psychological comfort, protective strength, and functional compensation (functions of non-NIP vaccines unreplaceable by NIP vaccines) being subthemes; and perceived cost consisting of two subthemes cost burden and adverse reaction. The social level influencing factors include the vaccination opinions in rural social networks, the accessibility of health services and vaccine products, and the guidance and promotion of vaccination policies. These factors act outside of individuals' subjective awareness and influence decisions regarding non-NIP vaccination in rural areas. Based on these influencing factors, this study constructs a structural model for non-NIP vaccination decision-making process in rural areas of China. The results play a guiding role in directing attention to children's health, promoting non-NIP vaccination, facilitating the dissemination of vaccine knowledge in rural areas, and improving NIP policies and practices in China.


Co-culture system of human skin equivalents with mouse neural spheroids.
This study describes a co-culture system of human skin equivalents (HSEs) and dorsal root ganglion (DRG) neurons. We prepared spheroids of mouse DRG neurons with or without Schwann cells (SCs). Spheroids comprising DRG neurons and SCs showed longer neurite extensions than those comprising DRG neurons alone. Neurite extension of more than 1 mm was observed from spheroids cultured inside HSEs, whereas neurite extension was primarily observed on the surface of HSEs from spheroids cultured on HSEs. We propose that our model may be a useful tool for studying neurite extension in the human skin.


Prevalence and clinical profile of heart failure patients with atrial fibrillation in a tertiary hospital in Kano, Nigeria.
Atrial fibrillation (AF) is one of the most prevalent sustained arrhythmias that is seen in clinical practice. AF commonly coexists with heart failure (HF) and there is growing evidence that it confers an adverse prognostic impact on the natural course of the disease. We set out to describe the prevalence and clinical profile of HF patients with AF in Aminu Kano Teaching Hospital (AKTH), Kano, Nigeria. We conducted a cross-sectional study of all adults aged 18 years and above, who presented at the AKTH, Kano, and were hospitalised for HF. Those who consented were consecutively recruited into the study. Sociodemographic and clinical characteristics of patients at presentation were documented. Thromboembolic risk was assessed using CHA2DS2-VASc scoring system. A 12-lead electrocardiogram recording was obtained from each of the recruited patients to confirm the presence of AF. The prevalence of AF was determined amongst the admitted HF patients. Those with AF were compared with those without AF in terms of sociodemographic and clinical characteristics. A total of 240 Nigerians were recruited. Sixty per cent were female and the whole group had a mean age of 50.85 ± 18.90 years. The prevalence of AF was found to be 12.5% amongst the recruited HF patients. The HF patients with AF had a significantly higher mean age (58 ± 16.7 years vs. 49.8 ± 19.0 years) (P = 0.021), and they also had a higher prevalence of palpitation and body swelling. The mean CHA2DS2-VASc score of the AF patients was 3.4 ± 1.0. AF is prevalent amongst HF patients in our environment with high thrombotic risk. More studies are needed to fully study the prevalence of AF and its clinical profile amongst HF patients in our country.


Principles of statistical analysis in nursing and healthcare research.
In the first of three papers on statistical analysis, Nicola Crichton gives an overview of using statistical analysis in nursing and health care research.


The impact of stereotactic large-core needle biopsy in the treatment of patients with nonpalpable breast lesions: a study of diagnostic accuracy in 510 consecutive cases.
The objective of this study was to assess the usefulness of stereotactic large-core needle biopsy (LCNB) in the management of nonpalpable breast lesions (NBL) and compare it with stereotactic fine-needle aspiration biopsy (SFNA) performed simultaneously in a significant number of cases. From November 1993 through June 1997, 510 consecutive patients with NBL underwent 14-gauge LCNB with 354 women undergoing simultaneous 21-gauge SFNA in the same lesson. Mammographic findings lesion size, number of core biopsy specimens, complications and diagnoses of both techniques were analysed. Surgical biopsy, tumorectomy or mastectomy was indicated for malignancy or poor correlation between SFNA or LCNB results and clinical or radiological findings. Values of diagnostic accuracy of both LCNB and SFNA were determined. The ratio benign surgical biopsies/malignant surgical biopsies (BB/CB) of the series was calculated. A total of 171 patients underwent surgical treatment: in 31 (18.1%) a benign process or atypical ductal hyperplasia was the final diagnosis. The ratio BB/CB was 0.22. Sensitivity and specificity were 93.2 and 100%, respectively, for LCNB, and 77.2 and 92.3%, respectively, for SFNA with cytological analysis. Large-core needle biopsy provides more accurate diagnosis than SFNA in the management of nonpalpable breast lesions and obviates a surgical diagnostic procedure in a significant number of cases.


Author Correction: High-protein diets increase cardiovascular risk by activating macrophage mTOR to suppress mitophagy.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Outwardly rectifying chloride channels and CF: a divorce and remarriage.
Outwardly rectifying Cl- channels were originally thought to be the central element in cystic fibrosis. The role of these channels in CF was questioned to such an extent that doubts were raised about the validity of the original experiments. Recent data reestablishes a role for outwardly rectifying Cl- channels (ORCC) in CF and suggests that the protein encoded by the CF gene, the cystic fibrosis transmembrane regulator (CFTR), can effect the regulation of more than one channel in the airway. This minireview deals with the rise, fall, and resurrection of the role of outwardly rectifying Cl- channels in CF.


Spatial distribution and temporal variation of metals in the vicinity of a municipal solid waste incinerator after a modernization of the flue gas cleaning systems of the facility.
In June 1994 and 1997, the concentrations of a number of elements were determined in soil and herbage samples collected in the vicinity of a municipal solid waste incinerator (MSWI) (Tarragona, Catalonia, Spain). In August 1997, an adaptation to the EU legislation on pollutant emissions from the stack was carried out to the incinerator. In June 1999, soil and herbage samples were collected again at the same sampling points and the levels of arsenic (As), cadmium (Cd), chromium (Cr), lead (Pb), manganese (Mn), mercury (Hg), nickel (Ni) and vanadium (V) were measured by ICP-MS or AAS with graphite furnace. The results are compared with those obtained in the 1994 and 1997 surveys. In the period 1997-1999, the only significant changes in soil levels corresponded to Cd and Pb, with decreases of 21.0% and 53.5%, respectively. In vegetation, only Mn levels showed a significant reduction, which contrasts with the notable increases found in the concentrations of As, Hg and Ni. According to the results of this survey, it seems evident that other metal emission sources in the same area of study are masking the environmental improvements carried out in the MSWI.


3-Amino thioacridone, a selective cyclin-dependent kinase 4 inhibitor, attenuates kainic acid-induced apoptosis in neurons.
The mechanisms underlying selective neuronal cell death in kainic acid-mediated neurodegeneration are not fully understood. We have recently demonstrated that in cerebellar granule neurons, kainic acid induces the expression of proteins associated with cell-cycle progression. In the present study we show that 3-amino thioacridone (3-ATA), a selective cyclin-dependent kinase 4 inhibitor, attenuates kainic acid-induced apoptosis in cerebellar granule neurons. When neurons were pre-treated with 3-ATA 10 microM for 24 h, they were less susceptible to damage induced by kainic acid 500 microM, since the number of dead cells decreased significantly. In flow cytometry studies using propidium iodide staining, 3-ATA also reduced the ratio of apoptotic cells induced by kainic acid. Moreover, 3-ATA decreased the proportion of cells with a condensed nucleus from 55% to 22%. Our data suggest that the cell cycle pathway is involved in the mechanism of apoptosis mediated by kainic acid and that cyclin-dependent kinase 4 plays a prominent role in this process. 3-ATA may to prevent the apoptosis associated with neurodegenerative disorders without the over-activation of excitatory amino acid receptors.


Mechanistic Understanding of Efficient Polyethylene Hydrocracking over Two-Dimensional Platinum-Anchored Tungsten Trioxide.
Chemical upcycling of polyethylene (PE) can convert plastic waste into valuable resources. However, engineering a catalyst that allows PE decomposition at low temperatures with high activity remains a significant challenge. Herein, we anchored 0.2 wt.% platinum (Pt) on defective two-dimensional tungsten trioxide (2D WO3 ) nanosheets and achieved hydrocracking of high-density polyethylene (HDPE) waste at 200-250 °C with a liquid fuel (C5-18 ) formation rate up to 1456 gproducts ⋅ gmetal species -1 ⋅ h-1 . The reaction pathway over the bifunctional 2D Pt/WO3 is elucidated by quasi-operando transmission infrared spectroscopy, where (I) well-dispersed Pt immobilized on 2D WO3 nanosheets trigger the dissociation of hydrogen; (II) adsorption of PE and activation of C-C cleavage on WO3 are through the formation of C=O/C=C intermediates; (III) intermediates are converted to alkane products by the dissociated H. Our study directly illustrates the synergistic role of bifunctional Pt/WO3 catalyst in the hydrocracking of HDPE, paving the way for the development of high-performance catalysts with optimized chemical and morphological properties.


Hydrogen bonding to the bound dioxygen in oxy cobaltous myoglobin reduces the superhyperfine coupling to the proximal histidine.
Electron spin echo envelope modulation (ESEEM) spectroscopy was used to study the electron-nuclear coupling in two oxygenated cobalt-substituted hemoproteins, myoglobin (oxyCoMb) and a monomeric hemoglobin from Glycera dibranchiata (oxyCoHbgly). The modulation frequency components in ESEEM spectra of both proteins arose from the coupling to the N epsilon of the proximal histidyl imidazole. The hyperfine and quadrupole coupling parameters for these two nitrogens, calculated by computer spectral simulation, are Aiso = 2.46 MHz, e2qQ = 2.15 MHz, and eta = 0.4 for oxyCoMb and Aiso = 3.70 MHz, e2qQ = 2.70 MHz, and eta = 0.5 for oxyCoHbgly. A hyperfine coupling of 0.6 MHz, found for oxyCoMb in D2O but not for oxyCoHbgly in D2O, was assigned to the coupling to a deuteron that is hydrogen-bonded to the O2 ligand in oxyCoMb. This hydrogen bonding is believed to be responsible for the reduction in hyperfine and nuclear quadrupole coupling to the proximal histidyl imidazole N epsilon in oxyCoMb. A molecular orbital model for O2 adducts of cobaltous compounds [Tovrog et al. (1976) J. Am. Chem. Soc. 98, 5144] was used to understand the hydrogen bond-induced reduction in 14N superhyperfine coupling in oxyCoMb.


Cyclic GMP modulators and excitotoxic injury in cerebral cortical cultures.
N-Methyl-D-aspartate (NMDA) receptor activation generates nitric oxide (NO) and cyclic GMP (cGMP) and produces 'excitotoxic' neuronal injury. To examine the possible role of cGMP in excitotoxicity, we evaluated the effects of agents that stimulate or inhibit cGMP activity on the release of lactate dehydrogenase from neuron-enriched cortical cultures. cGMP analogs exhibited no toxicity, and inhibitors of guanylate cyclase or of cGMP-dependent enzymes failed to protect cultures from the toxic effects of NMDA or the NO donor sodium nitroprusside. These findings argue against a role for cGMP in the pathogenesis of excitotoxic neuronal injury.


A Randomized 2x2 Factorial Clinical Trial of Renal Transplantation: Steroid-Free Maintenance Immunosuppression with Calcineurin Inhibitor Withdrawal after Six Months Associates with Improved Renal Function and Reduced Chronic Histopathology.
The two most significant impediments to renal allograft survival are rejection and the direct nephrotoxicity of the immunosuppressant drugs required to prevent it. Calcineurin inhibitors (CNI), a mainstay of most immunosuppression regimens, are particularly nephrotoxic. Until less toxic antirejection agents become available, the only option is to optimize our use of those at hand. To determine whether intensive rabbit anti-thymocyte globulin (rATG) induction followed by CNI withdrawal would individually or combined improve graft function and reduce graft chronic histopathology-surrogates for graft and, therefore, patient survival. As previously reported, a single large rATG dose over 24 hours was well-tolerated and associated with better renal function, fewer infections, and improved patient survival. Here we report testing whether complete CNI discontinuation would improve renal function and decrease graft pathology. Between April 20, 2004 and 4-14-2009 we conducted a prospective, randomized, non-blinded renal transplantation trial of two rATG dosing protocols (single dose, 6 mg/kg vs. divided doses, 1.5 mg/kg every other day x 4; target enrollment = 180). Subsequent maintenance immunosuppression consisted of tacrolimus, a CNI, and sirolimus, a mammalian target of rapamycin inhibitor. We report here the outcome of converting patients after six months either to minimized tacrolimus/sirolimus or mycophenolate mofetil/sirolimus. Primary endpoints were graft function and chronic histopathology from protocol kidney biopsies at 12 and 24 months. CNI withdrawal (on-treatment analysis) associated with better graft function (p <0.001) and lower chronic histopathology composite scores in protocol biopsies at 12 (p = 0.003) and 24 (p = 0.013) months, without affecting patient (p = 0.81) or graft (p = 0.93) survival, or rejection rate (p = 0.17). CNI (tacrolimus) withdrawal at six months may provide a strategy for decreased nephrotoxicity and improved long-term function in steroid-free low immunological risk renal transplant patients. ClinicalTrials.gov NCT00556933.


Changes in amphipod (Crustacea) assemblages associated with shallow-water algal habitats invaded by Caulerpa racemosa var. cylindracea in the western Mediterranean Sea.
The effects of the invasive species Caulerpa racemosa var. cylindracea (hereafter C. racemosa) on amphipod assemblages associated with shallow-water rocky habitats were studied. Two habitats located along the SE Iberian Peninsula were compared; invaded and non-invaded. The results showed that growth of C. racemosa affects habitat structure, influencing the species composition and biomass of macroalgae, and detritus accumulation. In turn, such changes in habitat features affected the associated amphipod assemblages with different ecological requirements. However, the species richness of amphipods was relatively high in both habitats, while the species composition of amphipods changed completely. For example, some species such as Ampithoe ramondi and Hyale schmidti did not colonize invaded habitats, while others such as Apocorophium acutum were favoured by the spread of C. racemosa. Habitat invasion by C. racemosa can have an important influence on biotic assemblages, modifying both habitat structure and the associated fauna, with unknown effects on the overall ecosystem.


Dating the age of a nuclear event by gamma spectrometry.
The age of a nuclear event can be determined by measuring the activity of two fission products. The event studied was a short irradiation, of a small sample of uranium, in a nuclear reactor. Two types of a clock were investigated: non-isobaric and isobaric parent-daughter fission products. Measurements of the source by gamma spectrometry yielded very good agreement between true and measured ages. The accuracy of each clock and the upper and lower age limits of applicability were studied.


Influential Serum Kinases (Non-sFlt-1) and Phosphatases in Preeclampsia-Systemic Review and Metanalysis.
The early identification of women with an increased risk of preeclampsia (PE) is desirable, but apart from soluble fms-like tyrosine kinase-1 (sFlt-1), few biomarkers have previously been identified as relevant for predicting preeclampsia. Since kinases and phosphatases regulate critical biological processes and previous evidence suggests a potential role of these molecules in preeclampsia, we performed this systematic review and metanalysis. The objective was to determine if there are kinases and phosphatases whose serum levels are different between women with and without PE, being relevant biomarkers of PE. We followed the recommendations of Cochrane and the Preferred Reported Items for Systematic Reviews and Metanalysis (PRISMA) to perform this study. The MESH terms preeclampsia, kinases, phosphatases, angiopoietins, soluble tyrosine protein kinase receptor (sTIE2), and cellular-mesenchymal-epithelial transition factor (c-MET) were combined to find relevant articles in the PubMed, PROSPERO, and Cochrane databases. Then, a qualitative and quantitative analysis was performed in R Studio software. From 580 abstracts identified, 37 were included in the final analysis, which comprised 24,211 pregnant women (2879 with PE and 21,332 women without PE [HP]. The pooled analysis showed that serum creatine kinase (CK) (SMD: 2.43, CI 95% 0.25-4.62) was significantly higher in PE, whereas sTIE2 and anti-angiogenic factor soluble c-Met (sMet)were significantly lower in PE than in HP (SMD: -0.23, CI95% -0.37 to -0.09; and SMD:0.24, CI95% 0.01-0.47, respectively). Adenosine monophosphate-activated protein kinase (AMPK), angiopoietin-1 (ANG-1), angiopoietin-2 (ANG-2), the ratio angiopoietin-1/angiopoietin-2, acid phosphatase, and alkaline phosphatase were not different between women with PE and HP. In summary CK, sTIE2, and c-MET are relevant biomarkers of PE. It is desirable to incorporate them into current models for PE prediction to evaluate their utility as biomarkers.


Validity and reliability of the Berlin questionnaire for the detection of moderate or severe obstructive sleep apnea in patients aged 40 years or older detected from primary care.
The obstructive sleep apnea syndrome (OSA) is a highly prevalent condition. In Spain and other countries, only 5%-9% of patients with OSA have been diagnosed and treated. The lack of accessibility to diagnosis is considered the main cause of this situation through easy-to-use screening instruments, it is necessary to check their validity and reliability in the context where they are to be used. To validate the Spanish translation of the Berlin questionnaire for screening for moderate or severe OSA in patients aged 40 years or more detected in primary care. A descriptive observational study, with a first qualitative phase of transcultural adaptation to Spanish using the translation-back-translation method. Setting: primary care level of the Spanish National Health System. A total of 255 patients recruited from 7 healthcare centers completed the study. The Berlin questionnaire was administered to the recruited patients, and subsequently, a respiratory polygraphy was performed to confirm the diagnosis of OSA. The concurrent criterion validity of the questionnaire and its reliability in terms of internal consistency and reproducibility (intra-observer agreement) were analyzed. The patients' mean age was 54.76 years (SD: 6.57; 95% CI: 53.53-54.99), and 54.12% were men (95% CI: 47.96-60.27). We found that 61.57% (95% CI: 55.57-67.57) presented OSA (apnea-hypopnea index-AHI >5), and 45.5% (95% CI: 17.05-57.92) presented moderate or severe (AHI >15) OSA. The Berlin questionnaire, with a cut-off point of 4.5, showed a sensitivity of 76.77% (95% CI: 67.94-85.59), a specificity of 74.49% (95% CI: 65.35-83.63), a positive predictive value of 75.25% (95% CI: 66.34-84.16), a negative predictive value of 76.04% (95% CI: 66.98-85.10), and an area under the curve of 0.786 (95% CI: 0.721-0.851). Cronbach's alpha coefficient was 0.730 (95% CI: 0.668-0.784), and the Kappa index was 0.739 (95% CI, 0.384-1.000). The Spanish adaptation of the Berlin questionnaire has good validity and reliability as a test for the diagnostic screening of moderate or severe OSA in patients aged 40 years or older. The findings of our study confirm that primary care physicians should use such screening tools to predict OSA.


An unexpected paradox: wall shear stress in the aorta is less in patients with severe atherosclerosis regardless of obesity.
Obesity is a widespread condition that is more prevalent in Western countries compared to others. Aortic atherosclerosis (AA) is a condition that frequently has been associated with obesity. An obesity paradox, where morbidly obese decedents had either no or minimal AA compared to nonobese decedents, recently has been described by some of us. The explanation for this almost counterintuitive paradox has yet to be determined, but a number of hypotheses were advanced, including hemodynamic factors producing aortic wall shear stress (WSS). The purpose of the present study was to determine if there was a relationship between AA and WSS, as determined by postmortem measurement of aortic wall diameters. Circumferences of the aorta at the levels of the ascending, thoracic and abdominal aorta were measured in 274 consecutive autopsies over 2-year period of time. AA was assessed using a previously described grading scale as either mild or severe. Circumferences were mathematically converted to diameters and WSS was calculated using the Hagen-Poiseuille formula. Two different methods to estimate cardiac output were used, both based on literature methods, one of which was body mass index (BMI) dependent, and the other BMI independent. Univariate and multivariable analyses of the relationship between WSS, age, BMI, gender, race and severity of AA were performed. Of the 274 decedents, 140 had mild and 134 had moderate to severe AA. BMI <35 was associated with moderate to severe AA. WSS was inversely correlated with AA in all these segments of the aorta in each BMI subgroup with the exception of the ascending aorta for decedents with BMI ≤35 kg/m2. Contrary to what we had hypothesized, WSS was not a determinant of the obesity paradox. However, among all the variables analyzed, a history of hypertension, diabetes mellitus and age were significant factors for developing AA (relative risk [RR] 0.35, P = .039; RR 1.51, P = .0006, RR 1.19, P = .0001, respectively). Our data demonstrate that WSS was unexpectedly lower in decedents with moderate and severe AA as compared to those with mild AA. This observation, which requires further investigations, was seen in all BMI ranges and was confirmed by 2 methods to calculate WSS.


Visualization of patent ductus arteriosus using real-time three-dimensional echocardiogram: Comparative study with 2D echocardiogram and angiography.
To determine the feasibility and accuracy of real time 3D echocardiography (RT3DE) in determining the dimensions and anatomical type of the patent ductus arteriosus (PDA). The study included 42 pediatric patients with a mean age of 3.6 years (ranging from 2 months to 14 years) who were referred for elective percutaneous PDA closure. All patients underwent full 2D echocardiogram as well as RT3DE with off line analysis using Q lab software within 6 h from their angiograms. The PDA was studied as regard the anatomical type, length of the duct as well as the ampulla and the pulmonary end of the PDA. Data obtained by RT3DE was compared against 2D echocardiogram and the gold standard angiography. Offline analysis of the PDA was feasible in 97.6% of the cases while determination of the anatomical type using gated color flow 3D acquisitions was achieved in 78.5% of the cases. The pulmonary end of the duct was rather elliptical using 3D echocardiogram. There was significant difference between the pulmonary end measured by 3D echocardiogram and angiography (P < 0.001). There was no significant difference between either the length or the ampulla of the PDA measured by 3D echocardiogram and that measured by angiography (P value = 0.325 and 0.611, respectively). There was a good agreement between both 2D or 3D echocardiogram and angiography in determining the anatomical type of the PDA (K = 0.744 and 0.773, respectively). However 3D echocardiogram could more accurately determine type A and type E ductus compared to 2D echocardiogram. 3D echocardiogram was more accurate than 2D echocardiogram in determining the length and the ampulla of the PDA. The morphologic assessment of the PDA using gated 3D color flow was achieved in 78.5% of the patients. Nevertheless the use of 3D echocardiogram in assessment of small vascular structures like PDA in children with rapid heart rates is still of limited clinical value.


Assessment of left ventricular diastolic function using color kinesis: differentiation between normal and pseudonormalized patterns.
Doppler examination of transmitral flow has been widely used to noninvasively assess left ventricular (LV) diastolic function. However, it has been demonstrated that transmitral flow velocity is dependent on LV relaxation and left atrial pressure. Increases in left atrial pressure compensate for the effects of impaired LV relaxation, frequently resulting in a "pseudonormalization" of the transmitral flow pattern. The purpose of this study was to assess whether analysis of diastolic color kinesis (CK) can be applied to differentiation between normal and pseudonormalized (PN) patterns of LV inflow. We studied 60 subjects with a ratio of early to late transmitral peak velocities (E/A) greater than 1.0 according to conventional Doppler echocardiography. All subjects simultaneously underwent measurement of the early diastolic mitral annular velocity (e'), which was measured by tissue Doppler imaging, and LV ejection fraction (EF), which was calculated by the modified Simpson method. Study subjects were classified into the following three groups according to the value of e' and EF: (1) the normal group (e' > 10 cm/s, EF > 60%), including 20 subjects (mean age 35 ± 10 years); (2) the PN1 group (e' < 7 cm/s, EF > 50%), consisting of 20 patients [mean age 63 ± 11 years, 15 patients with hypertensive heart disease (HHD), 5 patients with aortic valve stenosis]; and (3) the PN2 group (e' < 7 cm/s, EF < 50%), consisting of 20 patients (mean age 61 ± 17 years, 18 patients with dilated cardiomyopathy, 2 patients with HHD). Diastolic CK images were obtained for each subject from the LV midpapillary short-axis view. Analysis of CK diastolic images was performed using ICK software. The CK-diastolic index (CK-DI) was defined as the calculated LV segmental filling fraction during the first 30% of diastole, expressed as a percentage. The mean CK-DI was determined from the average CK-DI of six LV segments. The mean CK-DI was 70.9% ± 6.5% in the normal group, 46.3% ± 10.4% in the PN1 group, and 36.3% ± 5.1% in the PN2 group. The mean CK-DI was significantly reduced in the PN1 and PN2 groups compared with the normal group (P < 0.0001). Although there was no difference in e' (PN1 group: 4.6 ± 1.8 cm/s, PN2 group: 4.4 ± 1.7 cm/s) between the two pseudonormalized patient groups, the mean CK-DI was significantly reduced in the PN2 group compared with the PN1 group (P < 0.005). The reduction in mean CK-DI was seen not only in pseudonormalized patients with LV systolic dysfunction but also in those with preserved LV systolic function. The analysis of diastolic CK with ICK software is a useful method for detecting delayed early diastolic relaxation. We concluded that diastolic CK images may be applied to differentiating between normal and pseudonormalized patterns of LV inflow.


Hyperalgesia produced by intrathecal substance P and related peptides: desensitization and cross desensitization.
The hyperalgesic effect of intrathecally administered substance P (SP), physalaemin, eledoisin and eledoisin-related peptide (ERP) was investigated in the rat tail flick test. Hyperalgesia produced by SP (2.5-15 micrograms, 1.9-11 nmol) was maximal 10-20 min after injection, lasted 30 min and was dose-related. The effect was mimicked by all of the peptides examined. The rank order of potency was physalaemin greater than SP greater than eledoisin greater than ERP. Desensitization to the hyperalgesic effect of SP was produced by three repeated intrathecal injections. Rats desensitized to SP no longer responded to physalaemin or ERP, indicating cross-desensitization. Phentolamine continued to produce hyperalgesia following such desensitization. The demonstration of a hyperalgesic effect for SP provides further support for a role for SP in nociceptive transmission. The receptor mediating this effect appears to be a SP-P subtype. Cross-desensitization between peptides suggests an action on the same receptor.


Neuropathy with susceptibility to compression aggravated by herniated disk. Early pathological and electrodiagnostic studies.
We describe a patient with a foot drop attributable to both herniated disk and peripheral neuropathy susceptible to external compression. Early electrodiagnostic studies and sural nerve biopsy indicated a role for myelin dysfunction in this disorder.


Multi-frame Attention Network for Left Ventricle Segmentation in 3D Echocardiography.
Echocardiography is one of the main imaging modalities used to assess the cardiovascular health of patients. Among the many analyses performed on echocardiography, segmentation of left ventricle is crucial to quantify the clinical measurements like ejection fraction. However, segmentation of left ventricle in 3D echocardiography remains a challenging and tedious task. In this paper, we propose a multi-frame attention network to improve the performance of segmentation of left ventricle in 3D echocardiography. The multi-frame attention mechanism allows highly correlated spatiotemporal features in a sequence of images that come after a target image to be used to augment the performance of segmentation. Experimental results shown on 51 in vivo porcine 3D+time echocardiography images show that utilizing correlated spatiotemporal features significantly improves the performance of left ventricle segmentation when compared to other standard deep learning-based medical image segmentation models.


A novel point mutation (G-1 to T) in a 5' splice donor site of intron 13 of the dystrophin gene results in exon skipping and is responsible for Becker muscular dystrophy.
The mutations in one-third of Duchenne and Becker muscular dystrophy patients remain unknown, as they do not involve gross rearrangements of the dystrophin gene. We now report a defect in the splicing of precursor mRNA (pre-mRNA), resulting from a maternally inherited mutation of the dystrophin gene in a patient with Becker muscular dystrophy. This defect results from a G-to-T transversion at the terminal nucleotide of exon 13, within the 5' splice site of intron 13, and causes complete skipping of exon 13 during processing of dystrophin pre-mRNA. The predicted polypeptide encoded by the aberrant mRNA is a truncated dystrophin lacking 40 amino acids from the amino-proximal end of the rod domain. This is the first report of an intraexon point mutation that completely inactivates a 5' splice donor site in dystrophin pre-mRNA. Analysis of the genomic context of the G-1-to-T mutation at the 5' splice site supports the exon-definition model of pre-mRNA splicing and contributes to the understanding of splice-site selection.


[New nondispersive infrared spectrometry in 13C-urea breath tests].
13C-urea breath tests have become clinical routine in the diagnosis of Helicobacter pylori infection. For the analysis of the 13CO2/12CO2 enrichment in breath, less expensive alternatives to the expensive mass spectrometry (IRMS) have been developed, based on isotope-selective infrared spectroscopy (NDIRS). In this prospective study we tested under clinical conditions a simplified and thus less expensive NDIR-spectrometer by comparing it with mass spectroscopy. 100 patients (53 men, 47 women, mean age 59+/-14 years) with dyspeptic symptoms were tested for Helicobacter pylori infection using the 13C-urea breath test. The isotope ratio analysis of the breath samples was performed in duplicate, both using IRMS and NDIRS. The results of the baseline-corrected 13CO2 -exhalation values between IRMS and NDIRS were in excellent agreement. The mean difference between both methods was 0.05+/-1.16 . Evaluating the qualitative urea breath test results in reference to IRMS as the reference, the NDIRS had a sensitivity of 95 % and a specificity of 99 %. This newly developed isotope-selective nondispersive infrared spectroscopy is going to become a reliable, and low-cost alternative to expensive isotope ratio mass spectrometry in the analysis of 13C-breath tests. All these characteristics make NDIRS particularly suitable for laboratories where the daily number of assays is small or for use in the doctor's office


Immunometabolism modulation, a new trick of edible and medicinal plants in cancer treatment.
The edible and medicinal plants (EMPs) are becoming an abundant source for cancer prevention and treatment since the natural and healthy trend for modern human beings. Currently, there are more than one hundred species of EMPs widely used and listed by the national health commission of China, and most of them indicate immune or metabolic regulation potential in cancer treatment with numerous studies over the past two decades. In the present review, we focused on the metabolic influence in immunocytes and tumor microenvironment, including immune response, immunosuppressive factors and cancer cells, discussing the immunometabolic potential of EMPs in cancer treatment. There are more than five hundred references collected and analyzed through retrieving pharmacological studies deposited in PubMed by medical subject headings and the corresponding names derived from pharmacopoeia of China as a sole criterion. Finally, the immunometabolism modulation of EMPs was sketch out implying an immunometabolic control in cancer treatment.


Contrast sensitivity in pigeons: a comparison of behavioral and pattern ERG methods.
Contrast sensitivity (CS) is often used to assess spatial and temporal vision in animals. Conventional behavioral psychophysical techniques are both time and labor intensive, whereas measurement of CS functions by means of the pattern electroretinogram (PERG) is considerably more rapid and efficient. Are the two methods comparable, however? To answer this question, contrast-sensitivity functions were obtained using both the PERG and behavioral psychophysics in the same subjects, which were White Carneaux pigeons. The stimuli, in both methods, were phase-reversing, contrast-modulated sweeps of sinusoidal gratings. The PERG-CS functions were recorded via corneal electrodes and the behavioral data were collected using a modified staircase method that used moderate food deprivation and food reward. The results indicated that the PERG-CS functions had comparable bandwidth and peak spatial frequency to the behavioral CS functions. The PERG-CS functions, however, were lower on average than the behavioral curves by about 54%. The visual acuity of the two methods, as estimated from the high-frequency cutoff of the CS functions, differed by 37%. Both of these values are roughly consistent with the square root of 2 advantage of binocular viewing (behavioral method) over monocular viewing (PERG method). In addition, the peak spatial frequency showed a decrease of 0.125 c/deg with the PERG method and bandwidth was reduced by approximately 0.5 octave. These findings suggest that the PERG is an acceptable alternative to behavioral measurement of CS functions, especially in animal psychophysics, if one takes into account the underestimation of CS by the PERG method and the small changes in peak spatial frequency and bandwidth.


In for a Penny, in for a Pound: Obesity weighs heavily on both cost and outcome in trauma.
The current literature offers mixed conclusions regarding the effect of increased body mass index (BMI) on outcomes after trauma laparotomy. This study evaluated the impact of obesity on outcomes and cost for patients undergoing trauma laparotomy at a level 1 trauma center. Data on patients requiring trauma laparotomy in 2016 were prospectively collected and patients were stratified by BMI. Statistical analyses were used to determine variables significantly associated with patient morbidity and length of stay. 313 patients underwent trauma laparotomy: 225 non-obese, 69 obese, and 19 morbidly obese. Obese and morbidly obese patients had longer ICU and hospital lengths of stay (LOS), more ventilator days, larger hospital costs, and higher morbidity compared to non-obese patients. Obesity was an independent predictor for patient morbidity, ICU, and hospital LOS. Morbidity and length of stay increased with worsening obesity after trauma laparotomy, contributing to rising hospital costs.


Williams Syndrome Associated With Autism Spectrum Disorder: A Case Report and Review of the Literature.
We present a case report of patient H., a four-year-old male who was brought to the neurogenetics clinic of a university hospital. He was diagnosed with Williams syndrome (WS), which was confirmed by microarray; the patient was also diagnosed with autism spectrum disorder (ASD) by the pediatric neurology department. It is known that due to WS's phenotypical pattern, a co-diagnosis of both ASD and WS is apparently unlikely and often ignored. This case report discusses how this matter is addressed in the literature to understand the overlap of these two diseases, treating this case as a study model.


The effects of vitamin A nutritional status on microsomal lipid peroxidation and alpha-tocopherol level in rat liver.
In vitamin A-deficient rats, liver glutathione peroxidase activity was decreased, alpha-tocopherol content was strongly enhanced, but microsomal liquid peroxidation remained unchanged.


Reciprocal inhibitory effects of intravenous d-methamphetamine self-administration and wheel activity in rats.
Some epidemiological and cessation studies suggest physical exercise attenuates or prevents recreational drug use in humans. Preclinical studies indicate that wheel activity reduces cocaine self-administration in rats; this may, however, require the establishment of compulsive wheel activity. Effects of concurrent wheel activity on intravenous d-methamphetamine (METH) self-administration were examined in male Wistar and Sprague Dawley rats with negligible prior wheel experience. Wistar rats self-administered METH (0.05 mg/kg/inf) under a fixed-ratio 1 (FR1) schedule with concurrent access to an activity wheel during sessions 1-14, 8-21 or 15-21. Control rats which did not self-administer METH had access to an activity wheel during sessions 1-14, 8-21 or 15-28. Sprague Dawley rats self-administered METH (0.1 mg/kg/inf) under FR1 for 14 sessions with either concurrent access to a locked or an unlocked activity wheel. METH self-administration was lower when the wheel was available concurrently from the start of self-administration training in both strains, even though Sprague Dawley rats self-administered twice as many METH infusions and ran one-sixth as much on the wheel compared to Wistar rats. Wheel access initiated after 7 or 14 days had no effect on METH self-administration in Wistar rats. Wheel activity was significantly reduced in these groups compared with the group with concurrent wheel and METH access for the first 14 sessions. These data show that METH self-administration is reduced by exercise if initiated from the start of self-administration and that prior METH self-administration experience interferes with the value of exercise as a reinforcer.


Dissociation of visual and auditory language comprehension capacity in aphasia.
Visual language comprehension capacity was compared with auditory language comprehension capacity in 26 aphasic subjects. The Token Test was used for both modalities. By the means of the difference in scores on the two tests three groups were separated, that is (1) a group with no essential difference between the two capacities, (2) a group with superior reading capacity and (3) a group with superior auditory capacity. Particular attention was directed to the second group. Seven subjects showed this type of dissociated comprehension. The group was found to be heterogeneous in their linguistic characteristics. The clinical type of aphasia included not only Wernicke's aphasia but also Broca's aphasia. A possible psychological explanation underlying this phenomenon was attempted. Anatomical correlation was also attempted. The hypothesis of sparing the left inferior parietal lobe is proposed as an explanation of why visual comprehension was better preserved than auditory comprehension.


The centripetal endoscopic sinus surgery in patients with cystic fibrosis: A preliminary study.
The main aim of this study is to analyze the possible differences between clinical, demographic or genetic characteristics, in Cystic Fibrosis (CF) patients with chronic rhinosinusitis (CRS) with different phenotype. The secondary objective is to describe the possible benefit of surgery with Centripetal Endoscopic Sinus Surgery (CESS). The study includes 56 who performed CT scan of the paranasal sinuses. They were divided in 3 group according to phenotype: CRS without Nasal Polyps (NP); CRS with NP; CRS complicated with Mucocele. The clinical symptoms, age, gender, genotype, microbial colonization and pulmonary disease stage were collected and analyzed to assess possible statistically significant differences. Regarding the 7 patients who performed CESS surgery, the number of hospitalizations, intravenous (iv) antibiotic courses, respiratory exacerbations, the FEV1, the Lund-Mackay Score (LMS) and the SNOT 22 were evaluated before and 1 year after surgery. No statistically significant differences regarding clinical symptoms between the 3 groups were identified (p > 0.05). Furthermore, there were no differences in age, gender, genotype, microbial colonization and pulmonary disease stage (p > 0.05). Regarding the patients who performed CESS, no significative difference in FEV1 progression was found. A reduction in hospitalization, pulmonary exacerbation and in the number of iv antibiotic courses resulted statistically significant different (p = 0.004; <0.001 and <0.001 respectively). A significant improvement in SNOT-22 and LMS (p < 0.001) was obtained. Radiological monitoring of the rhinosinus disease is necessary regardless of the clinical expression of the disease. The presence of CRS with NP complicated by mucocele is frequent and independent of the patient's age and clinical manifestations. An extensive surgical approach could represent the gold standard for patients with CF in consideration of the potential important advantages to perform a total toilet of all the sinuses and nasal cavities and at the same time eliminating a potential microbiological reservoir.


Preamyloid lesions and cerebrovascular deposits in the mechanism of dementia: lessons from non-beta-amyloid cerebral amyloidosis.
The importance of amyloid plaques in the pathogenesis of dementia is usually centered on beta-amyloid (Abeta) and its role in Alzheimer's disease (AD). However, since fibrillar plaques correlate poorly with neurodegeneration, challenging their importance in the mechanism(s) of dementia, investigators turned their focus to the importance of soluble oligomers and the role of preamyloid and cerebrovascular deposits. Two non-Abeta cerebral amyloidoses, familial British and Danish dementias (FBD and FDD), share many aspects of AD, including cognitive impairment and the presence of neurofibrillary tangles in limbic areas. The lack of compact plaques in FDD and in many areas in FBD further questions the importance of these lesions in the mechanism of dementia. The main components of the deposits--ABri and ADan--are structurally unrelated to Abeta and yet they all have a high tendency to oligomerize and assemble into amyloid fibrils in vitro and form ion-like channels in lipid membranes. Thus, different amyloid species have the capability to induce similar neuropathological changes, which are neither exclusive for Abeta nor dependent on the presence of compact plaques. These findings reaffirm the notion that non-Abeta amyloidoses constitute alternative models to study the role of preassembled amyloid subunits in neuronal death.


Intrauterine desensitization enables long term survival of human oligodendrocyte progenitor cells without immunosuppression.
Immune rejection can be reduced using immunosuppressants which are not viable for premature infants. However, desensitization can induce immune tolerance for premature infants because of underdeveloped immune system. The fetuses of Wistar rats at 15-17 days gestation were injected via hOPCs-1 into brain, muscles, and abdomen ex utero and then returned while the fetuses of control without injection. After 6 weeks of desensitization, the brain and muscles were transplanted with hOPCs-1, hNSCs-1, and hOPCs-2. After 10 and 34 weeks of desensitization, hOPCs-1 and hNSCs-1 in desensitized groups was higher than that in the control group while hOPCs-2 were rejected. Treg, CD4CD28, CD8CD28, and CD45RC between the desensitization and the control group differed significantly. Inflammatory cells in group with hOPCs-1 and hNSCs-1 was lower than that in the control group. hOPCs-1 can differentiate into myelin in desensitized groups. Wistar rats with desensitization developed immune tolerance to desensitized and transplanted cells.


Mosaics of ancient mitochondrial DNA: positive indicators of nonauthenticity.
Research into ancient mitochondrial DNA is plagued by contamination, post mortem damage, and other artefacts. The stringent set of controls suggested by Cooper and Poinar a few years ago are, however, rarely followed in practice, and even when applied carefully, these criteria need not be sufficient to guarantee authenticity. The fairly relaxed prerequisites now common for ancient population studies have opened the door for all kinds of contamination and sequencing errors to enter ancient mtDNA data. To reject or question authenticity of particular sequencing results a posteriori, one can follow similar strategies of focused database comparisons that have proven to be effective and successful in the case of flawed modern mtDNA data.


Sulforaphane Does Not Protect Right Ventricular Systolic and Diastolic Functions in Nrf2 Knockout Pulmonary Artery Hypertension Mice.
Nrf2 is a nuclear transcription factor and plays an important role in the regulation of oxidative stress and inflammation. We recently demonstrated that sulforaphane (SFN) protected mice from developing pulmonary arterial hypertension (PAH) and right ventricular (RV) dysfunction by elevating cardiac Nrf2 expression and function. Here we further investigate Nrf2 dependence for SFN-mediated prevention of PAH and RV dysfunction in an Nrf2 knockout mouse model. We used male global Nrf2-knockout mice and male C57/6 J wild type mice in the following groups: Control group received room air and vehicle control; SuHx group received SU5416 and 10% hypoxia for 4 weeks to induce PAH; SuHx+SFN group received both SuHx and sulforaphane, a Nrf2 activator, for 4 weeks. Transthoracic echocardiography was performed to quantify RV function and estimate pulmonary vascular resistance over 4 weeks. PAH was confirmed using invasive RV systolic pressure measurement at 4 weeks. All Nrf2 knockout mice survived the 4-week SuHx induction of PAH. SuHx caused progressive RV diastolic/systolic dysfunction and increased RV systolic pressure. The development of RV diastolic dysfunction occurred earlier in the Nrf2 knockout PAH mice when compared with the wide type PAH mice. SFN partially or completely reversed SuHx-induced RV diastolic/systolic dysfunction and increased RV systolic pressure in wild-type mice, but not in Nrf2 knockout mice. Our findings demonstrated the essential role of Nrf2 in SFN-mediated prevention of RV dysfunction and PAH, and increasing Nrf2 activity in patients with PAH may have therapeutic potential.


Transgenic double-stranded RNA rice, a potential strategy for controlling striped stem borer (Chilo suppressalis).
Although the striped stem borer (SSB, Chilo suppressalis Walker) is a devastating pest of rice that causes significant economic losses, management options are currently limited. Plant-mediated RNA interference (RNAi) is an emerging crop protection technique in which transgenic plants are modified to express insect-specific double-stranded RNAs (dsRNAs) that trigger RNAi silencing in target pests. In this study, an RNAi-based screen of 35 candidate SSB genes identified a small heat shock protein gene (CssHsp) as a potential plant-based RNAi target. To assess its utility in planta, a total of 39 transgenic rice plants were generated, with 11 independent transformants found to contain a single copy of the dsCssHsp expression cassette. In life-time feeding bioassays, three transgenic lines (DS10, DS35, DS36) were found to have significant negative impacts on SSB populations. After feeding for 8 days, mortality in the three transgenic lines exceeded 60%. By pupation, mortality further increased to 90% and few SSB survived to eclosion. Gene expression analyses confirmed that CssHsp transcript levels were significantly reduced after feeding on the transgenic dsCssHsp rice. These results demonstrate the potential for developing a plant-mediated RNAi strategy targeting CssHsp as a more biorational field-based approach for SSB control. © 2021 Society of Chemical Industry.


Synergistic regulation of uterine radial artery adaptation to pregnancy by paracrine and hemodynamic factors.
Fetal growth throughout pregnancy relies on delivery of an increasing volume of maternal blood to the placenta. To facilitate this, the uterine vascular network adapts structurally and functionally, resulting in wider blood vessels with decreased flow-mediated reactivity. Impaired remodeling of the rate-limiting uterine radial arteries has been associated with fetal growth restriction. However, the mechanisms underlying normal or pathological radial artery remodeling are poorly understood. Here, we used pressure myography to determine the roles of hemodynamic (resistance, flow rate, shear stress) and paracrine [β-estradiol, progesterone, placental growth factor (PlGF), vascular endothelial growth factor] factors on rat radial artery reactivity. We show that β-estradiol, progesterone, and PlGF attenuate flow-mediated constriction of radial arteries from nonpregnant rats, allowing them to withstand higher flow rates in a similar manner to pregnant vessels. This effect was partly mediated by nitric oxide (NO) production. To better understand how the combination of paracrine factors and shear stress may impact human radial artery remodeling in the first half of gestation, computational models of uterine hemodynamics, incorporating physiological parameters for trophoblast plugging and spiral artery remodeling, were used to predict shear stress in the upstream radial arteries across the first half of pregnancy. Human microvascular endothelial cells subjected to these predicted shear stresses demonstrated higher NO production when paracrine factors were added. This suggests that synergistic effects of paracrine and hemodynamic factors induce uterine vascular remodeling and that alterations in this balance could impair radial artery adaptation, limiting blood flow to the placenta and negatively impacting fetal growth.NEW & NOTEWORTHY Placenta-specific paracrine factors β-estradiol, progesterone, and placental growth factor attenuate flow-mediated constriction of the rate-limiting uterine radial arteries, enabling higher flow rates in pregnancy. These paracrine factors induce their actions in part via nitric oxide mediated mechanisms. A synergistic combination of paracrine factors and shear stress is likely necessary to produce sufficient levels of nitric oxide during early human pregnancy to trigger adequate uterine vascular adaptation.


Radioiodination of S-type lipopolysaccharide. Possibilities and limitations of labelling of the carbohydrate chain by periodate oxidation.
S-type Lipopolysaccharide (LPS) from E. coli O 139:K 82 (B) was radiolabelled by coupling 125I-tyramine to the carbohydrate chain of LPS after oxidation of sugar residues carrying vicinal hydroxy groups, with sodium metaperiodate. The specific activity amounted to 1.3 kBq/microgram LPS. As LPS is a mixture of molecules with different carbohydrate chain lengths that are associated to large micelles of high kinetic stability, the preparation and the properties of the tracer exhibit some peculiarities. Most important, partial cleavage of the carbohydrate chains of LPS is caused on radioiodination by the procedure described. As a consequence, the tracer differs markedly from the starting LPS with respect to carbohydrate chain length distribution. Another feature of special interest is the variation of the specific activity (radioactivity/unit mass) for LPS molecules of different carbohydrate chain lengths. Because of the kinetic stability of LPS micelles, the equilibration of radioiodinated and non-radioactive LPS aggregates requires their solubilization by a detergent and its subsequent removal by dialysis. It could be demonstrated that short-chain LPS molecules predominantly associate to larger micelles than long-chain molecules. Regardless of these restrictions, the 125I-LPS proved to be useful for certain analytical purposes.


Development and characterization of a mouse model of duodenogastric reflux.
Rat models of duodenogastric reflux have been used to study gastric stump cancer (GSC), but the underlying molecular mechanisms are poorly understood. Unlike rats, mice can be genetically modified, providing a superior model for studying the molecular mechanisms underlying GSC development, which is associated with duodenogastric reflux. This study aimed at developing a mouse model of duodenogastric reflux. C57BL/6 mice were randomly assigned to the control (n = 6), sham operation (n = 9), or gastrojejunostomy group (n = 12). Mice were sacrificed at 1, 3, and 6 months after surgery. Stomach tissue was stained with hematoxylin and eosin. Lesions were classified as chronic inflammation, intestinal metaplasia, or atypical hyperplasia. Nine mice underwent gastrojejunostomy without mortality. The animals in the gastrojejunostomy group exhibited chronic inflammation at 1, 3, and 6 months after surgery, showing intestinal metaplasia (n = 2) and atypical hyperplasia (n = 1) at 3 months and intestinal metaplasia (n = 2) and atypical hyperplasia (n = 2) at 6 months. The mice in the control group did not exhibit chronic inflammation or intestinal metaplasia, whereas those in the sham operation group exhibited chronic inflammation at 1, 3, and 6 months after surgery, without intestinal metaplasia or atypical hyperplasia. Intestinal metaplasia or atypical hyperplasia were more common in the gastrojejunostomy group than in the sham operation group (p = 0.012). A duodenogastric reflux mouse model can be created using gastrojejunostomy without gastrectomy.


Impact of prolonged sitting on lower and upper limb micro- and macrovascular dilator function.
What is the central question of this study? The prevalence of sedentary behaviour in the workplace and increased daily sitting time have been associated with the development of cardiovascular disease; however, studies investigating the impact of sitting on vascular function remain limited. What is the main finding and its importance? We demonstrate that there is a marked vulnerability of the vasculature in the lower and upper limbs to prolonged sitting and highlight the importance of physical activity in restoring vascular function in a limb-specific manner. Sedentary behaviour in the workplace and increased daily sitting time are on the rise; however, studies investigating the impact of sitting on vascular function remain limited. Herein, we hypothesized that 6 h of uninterrupted sitting would impair limb micro- and macrovascular dilator function and that this impairment could be improved with a bout of walking. Resting blood flow, reactive hyperaemia to 5 min cuff occlusion (microvascular reactivity) and associated flow-mediated dilatation (FMD; macrovascular reactivity) were assessed in popliteal and brachial arteries of young men at baseline (Pre Sit) and after 6 h of uninterrupted sitting (Post Sit). Measures were then repeated after a 10 min walk (~1000 steps). Sitting resulted in a marked reduction of resting popliteal artery mean blood flow and mean shear rate (6 h mean shear rate, -52 ± 8 s(-1) versus Pre Sit, P < 0.05). Interestingly, reductions were also found in the brachial artery (6 h mean shear rate, -169 ± 41 s(-1) versus Pre Sit, P < 0.05). Likewise, after 6 h of sitting, cuff-induced reactive hyperaemia was reduced in both the lower leg (-43 ± 7% versus Pre Sit, P < 0.05) and forearm (-31 ± 11% versus Pre Sit, P < 0.05). In contrast, popliteal but not brachial artery FMD was blunted with sitting. Notably, lower leg reactive hyperaemia and FMD were restored after walking. Collectively, these data suggest that prolonged sitting markedly reduces lower leg micro- and macrovascular dilator function, but these impairments can be fully normalized with a short bout of walking. In contrast, upper arm microvascular reactivity is selectively impaired with prolonged sitting, and walking does not influence this effect.


[The economic importance of individual health services (IGeL) in ophthalmology over time: survey results from 2010 and 2020].
Individual health services (IGeL) enable patients to receive medical services not covered by social health care; however, there is no central data collection on IGeL in Germany. This study illustrates the spectrum of IGeL provided in the field of ophthalmology as an example of the importance of IGeL in Germany based on survey results. Nationwide, 10% of ophthalmologists in private practice were randomly selected in this anonymous survey in 2010 and 2020 while in 2020 in addition to the randomized 10% of ophthalmologists the same ophthalmologists from 2010 were contacted. By means of a written questionnaire, ophthalmologists were asked about their practice structure, total revenue from IGeL as well as the frequency and price of specific IGeL. Income from IGeL was estimated at an average of 21% of the regular service volume in 2010 and 23% in 2020. Glaucoma IGeL and medical report IGeL were offered by almost all ophthalmologists and glaucoma screening being performed most frequently with an average frequency of over 150 examinations/month. IGeL, such as HRT IGeL were offered by significantly fewer ophthalmologists in 2020 than in 2010, while IGeL based on other technological procedures such as glaucoma OCT were offered more frequently in 2020. The volume of IGeL provided in established ophthalmological practices was stable between 2010 and 2020. The range of services offered in 2020 compared to 2010 reflects a dynamic change associated with the entry of new technologies into routine care.


Homecare referrals and 12-week outcomes following surgery for cancer.
To determine characteristics of patients undergoing cancer surgery who do and do not receive homecare referral after hospitalization, relative to poor discharge outcomes. Secondary analysis of a randomized clinical trial. Urban, academic cancer center in the northeastern United States. 375 patients 60 years and older and admitted for solid tumor cancer surgery. Stepwise, multiple logistic regression using patient characteristics related to homecare referrals or those related to poor discharge outcomes. Homecare referral and poor discharge outcome. Patients 70 years or older, single, hospitalized for a week or more for a late-stage cancer, with greater than four comorbid conditions, and discharged with more than four daily activity impairments, depressive symptoms, and a need for skilled nursing care were more likely to require home care. Patients not referred to home care who received adjuvant cancer therapies were about three times more likely to have poor discharge outcomes. Patients who were referred for home care had characteristics similar to medical or surgical patients documented in the literature. However, younger patients with lengthy hospital stays and recipients of adjuvant cancer therapy did poorly after discharge and may benefit from home care. Certain characteristics, such as age, single marital status, depression, and cognition, should trigger further assessment of patients' needs after discharge, including anticipating needs of patients who will receive adjuvant therapies.


Transition-Metal-Free Borylation of Allylic and Propargylic Alcohols.
The base-catalyzed allylic borylation of tertiary allylic alcohols allows the synthesis of 1,1-disubstituted allyl boronates, in moderate to high yield. The unexpected tandem performance of the Lewis acid-base adduct, [Hbase](+) [MeO-B2 pin2 ](-) favored the formation of 1,2,3-triborylated species from the tertiary allylic alcohols and 1-propargylic cyclohexanol at 90 °C.


Innervation mapping of the hind paw of the rat using Evans Blue extravasation, Optical Surface Mapping and CASAM.
Although numerous studies investigate sensory regeneration and reinnervation of the hind paw of the rat after nerve damage, no comprehensive overview of its normal innervation is present in literature. The Evans Blue extravasation technique is a well-known technique to study patterns of skin innervation. This technique has been performed differently by various groups but was never used to study the entire skin innervation in rats' hind paw including all three branches of the sciatic nerve and the saphenous nerve in detail. In this paper, we have used the Evans Blue extravasation technique to chart the skin areas innervated by the sural, peroneal, tibial and/or saphenous nerves, which together innervate the entire hind paw of the rat, and use a new technique to analyze the distribution, overlap and variability of the results. The technique is based on analysis of whole hind paws using Optical Surface Mapping (OSM) in combination with the Computer Assisted Surgical Anatomy Mapping (CASAM) technology. While the plantar hind paw is mainly innervated by the tibial nerve, the dorsal hind paw is supplied by the sural, peroneal and the saphenous nerve. Although our results basically concur with the general nerve-specific innervation of the rat hind paw, they show considerable detail in their areas of overlap as well as in the amount of variability between animals. These results will be invaluable to study and evaluate patterns of innervation and reinnervation of intact and damaged nerve fibers.


Contemporary Surgical Management and Outcomes for Anal Melanoma: A National Cancer Database Analysis.
Anal melanoma is a rare disease with a poor prognosis. Limited data are available regarding oncologic outcomes during the last decade and surgical practice patterns. This study aimed to investigate survival and operative oncologic outcomes for patients with anal melanoma. The National Cancer Database (2004-2013) was used to identify patients with nonmetastatic anal melanoma who underwent surgical treatment. The primary outcome was overall survival. The study enrolled 439 patients in the local excision group and 214 patients in the abdominoperineal resection (APR) group. The patients in the APR group were older (70 vs 65 years; p < 0.001) and had larger tumors (40 vs 25 mm; p < 0.001). After resection, the APR patients were more likely to have positive lymph nodes (65.7% vs 12.5%; p < 0.001) and less likely to have positive margins (10% vs 29.8%; p < 0.001). Overall survival did not differ significantly between the APR and local excision patients (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.67-1.01; p = 0.06). The patients undergoing local excision showed was a significant survival advantage for those with negative margins (HR, 0.70, 95% CI, 0.53-0.93; p = 0.009). Among the patients undergoing APR, a significant survival advantage was observed for those with negative nodes (HR, 0.50; 95% CI, 0.35-0.69; p = 0.002) and negative margins (HR, 0.34; 95% CI, 0.15-0.77; p < 0.001). The overall survival of anal melanoma patients is similar after local excision and APR. Patients with positive margins, positive lymph nodes, or both have a significantly decreased overall survival.


Clinical efficacy of probiotics in prevention of infectious diseases among hospitalized patients in ICU and non-ICU wards in clinical randomized trials: A systematic review.
The present study aimed to review probiotics' clinical efficacy in preventing infectious diseases among hospitalized patients in ICU and non-ICU wards. A search of Medline, EMBASE, The Cochrane Library, Science Direct, Open Grey, and Google Scholar was conducted for eligible publications from 2002 to 2020 following the requirements outlined in the PRISMA guideline. The search strategy was based on the combination of the following terms: "probiotics," "prebiotics," "synbiotics," and "cross-infection." The logical operators "AND" (or the equivalent operator for the databases) and "OR" (e.g., probiotics OR prebiotics OR synbiotics) were used. The results indicated that the probiotic consumption caused a significant reduction in antibiotic-associated diarrhea (AAD) and Clostridioides difficile infection (CDI) in 2/8 randomized clinical trials (RCTs) investigating AAD/CDI. Also, 5/12 clinical trials highlighted the considerable effects of probiotics on the reduction or prevention of ventilator associated pneumoniae (VAP), so the mean prevalence of VAP was lower in the probiotic group than in the placebo group. The total rate of nosocomial infections among preterm infants was nonsignificantly higher in the probiotic group compared to the control group. This systematic review shows that the administration of probiotics has moderate preventive or mitigating effects on the occurrence of VAP in ICU patients, CDI, AAD, and nosocomial infections among children. Consequently, applying antibiotics along with the proper probiotic species can be advantageous.