[Descending aorta perfusion through median sternotomy in primary repair of aortic interruption complex].
Circulatory arrest is frequently used in aortic arch reconstruction in pediatric cardiac surgery. However, risks of postoperative acute renal failure and neurological deficit can not be ignored. We performed primary repair of aortic interruption in one-month old girl. After commencing extracorporeal circulation with bicaval venous cannulae and with arterial cannulae into the pulmonary trunk and the innominate artery, the descending aorta was cannulated just superior to the diaphragm. The cannula in the pulmonary trunk was then removed. Arch reconstruction and closure of the ventricular septal defect were performed with continuous perfusion to the brain and the lower body. The extracorporeal circulation time and the aortic cross-clamp time were 117 min and 21 min, respectively. Postoperative renal function was excellent, and there was no finding of neurological deficit. Cannulation of the descending aorta is a simple and useful technique with safety, in arch reconstruction in infants.


Screening and scenarios of traffic emissions at Trier, Germany.
In the course of the European Council Directive on permissible air pollutant limit values, valid starting from 2005 there is an urgent call for action, particularly for fine dust (PM10). Current investigations (Junk & Helbig 2003, Reuter & Baumüller 2003) show that the limit values in certain places in congested areas are exceeded. Only if it is possible to locate these Hot Spots purposeful measures to reduce the ambient air pollution can be conducted. For an efficient identification of these Hot Spots numerical computer models or establishing special measurements networks are too expensive. Using the statistical model STREET 5.0 (KTT 2003) a cost-effective screening of the air pollution situation caused by the traffic can be done. STREET is based on the 3-dimensional micro-scale non-hydrostatic flow- and dispersion model MISCAM (Eichhorn 1989). The results of over 100.000 different calculations with MISCAM are stored in a Database and used to calculate the emissions with STREET. In collaboration with the city council of Trier more than 150 streets were investigated, mapped, and calculated. A special urban climate measuring network supplies the necessary meteorological input data about the wind field and precipitation events in the valley of the Moselle. Information about road width and road orientation as well as building density was derived from aerial photographs. Traffic censuses and mobile air pollutants measurements supplied the remaining input data. We calculated the mean annual air pollutant concentrations for NO2, CO, SO2, O3, benzene as well as PM10. A comparison of the model results with the values obtained from the stations of the central emission measuring network of Rhineland-Palatinate (ZIMEN, annual report 2002) shows very good agreements. The model was not only used to calculate the annual air pollutant but also for urban planning and management. The absolute level of the air pollutant is mainly dependent on the amount of traffic in the street canyons. Therefore four different case-scenarios with varying quantity of traffic were calculated and interpreted for each street. The results of the calculation show that on the basis of the mean values for both NO2 and benzene, it is not to be expected that the limits Furthermore the model can be used to find the maximum tolerable numbers of cars for a street without exceeding the air pollutant thresholds.


Transcutaneous Po2 monitoring in neonatal intensive care.
The transcutaneous Po2 monitoring technique was applied in 20 newborns. The method proved reliable during hypoxemia, normoxemia and hyperoxemia, with a high correlation between Ptco2 and Pao2 in simultaneously obtained arterial samples. Although Ptco2 reliably reflects changes in Pao2, occasional arterial samples are still required for establishing the relationship between Ptco2 and Pao2, especially in patients with impaired circulation. When this relationship has been determined, the therapist may rely on the recorded Ptco2 level for hours, given that the energy supply required to maintain the electrode at a preset temperature level remains constant. A considerable difference between Ptco2 and Pao2 or a change in the energy supply level to the electrode may alert the therapist to check the patient's circulatory status. The Ptco2 technique is now fully developed and can be recommended for use in neonatal intensive care.


Structure and Function of Parkin, PINK1, and DJ-1, the Three Musketeers of Neuroprotection.
Autosomal recessive forms of Parkinson's disease are caused by mutations in three genes: Parkin, PINK1, and DJ-1. These genes encode for proteins with distinct enzymatic activities that may work together to confer neuroprotection. Parkin is an E3 ubiquitin ligase that has been shown to ubiquitinate substrates and to trigger proteasome-dependent degradation or autophagy, two crucial homeostatic processes in neurons. PINK1 is a mitochondrial protein kinase whose activity is required for Parkin-dependent mitophagy, a process that has been linked to neurodegeneration. Finally, DJ-1 is a protein homologous to a broad class of bacterial enzymes that may function as a sensor and modulator of reactive oxygen species, which have been implicated in neurodegenerative diseases. Here, we review the literature on the structure and biochemical functions of these three proteins.


The role of microbiology in models of dental caries.
Models of dental caries (laboratory, animal, and human in situ models) vary markedly in their microbiological complexity. Laboratory models range from mono-cultures of cariogenic species providing an acidic challenge to enamel, to the development of diverse mixed cultures growing on a habitat-simulating medium in an artificial mouth or chemostat. The latter systems are of value in determining either mechanisms of action or cause-and-effect relationships--e.g., between dietary components or antimicrobial agents and the microflora. Laboratory models have also shown that the sensitivity of oral bacteria to inhibitors is markedly reduced when growing in biofilms such as dental plaque. Animal models have proved unequivocally that caries is an infectious and transmissible disease. Their use has enabled comparisons to be made of (a) the cariogenic potential of different bacterial species, (b) the role of the diet, and (c) the effects of potential anti-caries agents. It has been claimed that no caries-protective agent currently in use has failed a rodent test. In situ human models have been designed to permit the development of "natural" plaque on standardized enamel surfaces freely exposed to the human oral environment. The microflora that develops on unadulterated surfaces is similar in composition to that found at comparable sites on vital teeth. Demineralization can be accelerated by the inoculation of additional cariogenic bacteria coupled with either intra- or extra-oral sucrose rinses. The increased realism associated with the transition from laboratory to human in situ models is countered by a reduced ability to control or manipulate the system for experimental purposes. Thus a hierarchy of tests is needed for the study of anti-caries agents, each requiring a varying degree of microbiological complexity.


[The registered nurse and the battle against tuberculosis in Brazil: 1961-1966].
The objective of this study was to describe the circumstances that promoted the implementation of the new Program for Action Against Tuberculosis in Brazil (Programa de Ação na Luta contra a Tuberculose no Brasil) and discuss the strategies used by registered nurses from the Santa Maria State Hospital, Guanabara State, to adjust nursing care to the new program against tuberculosis. This was performed through document research, interviews, and statements from nurses working at the time of the reorganization. Documents were analyzed based on the concepts of habitus, field, and symbolic power by Pierre Bourdieu, and included written and oral documents as well as secondary sources. The reorganization of the nursing service was performed under the leadership of a nurse whose symbolic capital assigned power and prestige to implement the necessary changes. It is concluded that the work of that nurse made it possible to implement the new program and contributed to establishing the position and importance of the registered nurse in providing care to individuals with tuberculosis, for prevention and cure.


Visual impairments in the first year after traumatic brain injury.
This article reviews literature regarding individuals with traumatic brain injury who have vision related impairments up to one year, post-injury. Such impairments may impact rehabilitation of activities of daily living and mobility since vision is integral in much of what one does on a daily basis. Search of Medline, Ovid, and PubMed was performed using terms including: traumatic brain injury, visual deficits after brain injury, vision and traumatic brain injury, and ADLs after brain injury. Eighteen studies were analyzed and reviewed. A range of visual and visual-motor impairments are seen across the severity of traumatic brain injury. Visual impairment negatively impacts independence in mobility and activities of daily living. Common sensorimotor visual symptoms reported by those with traumatic brain injury include blurred vision, reading problems, double vision or eyestrain, dizziness or disequilibrium in visually-crowded environments, visual field defects, light sensitivity, and color blindness. This review should alert the reader to common visual complaints and defects seen after traumatic brain injury. It is important to screen persons who have suffered traumatic brain injury for sensorimotor vision deficits early on in recovery so that these issues may be addressed and recovery of function and independence in the community are not delayed.


Prospective assessment of stereotactic ablative surgery for intractable major depression.
Despite therapeutic advances for major depression, a subset of patients with this disorder does not respond to conventional treatment. Stereotactic ablative procedures such as anterior cingulotomy have been performed in severely affected, treatment-resistant patients, but the long-term results of such procedures are not fully understood. Findings are reported for 33 patients with severe treatment-resistant major depression who underwent ablative stereotactic procedures (dorsal anterior cingulotomy followed if necessary by subcaudate tractotomy). Preoperative and long-term postoperative Beck Depression Inventory scores were obtained along with postoperative Clinical Global Improvement values. Both were analyzed to evaluate patients' responses to the surgical procedure(s). At mean follow-up of 30 months after one or more stereotactic ablative procedures, 11 patients (33.3%) were classified as responders, 14 (42.4%) were partial responders, and 8 (24.2%) did not respond to the surgical procedure(s). Among those (17) who underwent only one procedure, seven (41.2%) responded, whereas six (35.3%) and four (23.5%) showed partial or no response, respectively. Among patients who required multiple surgical procedures, four patients (25%) responded, whereas eight (50%) and four (25%) patients demonstrated partial or no responses, respectively, at long-term follow-up evaluations. Approximately 75% of depression patients previously resistant to antidepressant therapies received partial or substantial benefit from stereotactic ablative procedures. Those requiring only a single anterior cingulotomy tended to demonstrate more pronounced responses than patients who underwent multiple surgical procedures.


Thymic Epithelial Cell Support of Thymopoiesis Does Not Require Klotho.
Age-related thymic involution is characterized by a decrease in thymic epithelial cell (TEC) number and function parallel to a disruption in their spatial organization, resulting in defective thymocyte development and proliferation as well as peripheral T cell dysfunction. Deficiency of Klotho, an antiaging gene and modifier of fibroblast growth factor signaling, causes premature aging. To investigate the role of Klotho in accelerated age-dependent thymic involution, we conducted a comprehensive analysis of thymopoiesis and peripheral T cell homeostasis using Klotho-deficient (Kl/Kl) mice. At 8 wk of age, Kl/Kl mice displayed a severe reduction in the number of thymocytes (10-100-fold reduction), especially CD4 and CD8 double-positive cells, and a reduction of both cortical and medullary TECs. To address a cell-autonomous role for Klotho in TEC biology, we implanted neonatal thymi from Klotho-deficient and -sufficient mice into athymic hosts. Kl/Kl thymus grafts supported thymopoiesis equivalently to Klotho-sufficient thymus transplants, indicating that Klotho is not intrinsically essential for TEC support of thymopoiesis. Moreover, lethally irradiated hosts given Kl/Kl or wild-type bone marrow had normal thymocyte development and comparably reconstituted T cells, indicating that Klotho is not inherently essential for peripheral T cell reconstitution. Because Kl/Kl mice have higher levels of serum phosphorus, calcium, and vitamin D, we evaluated thymus function in Kl/Kl mice fed with a vitamin D-deprived diet. We observed that a vitamin D-deprived diet abrogated thymic involution and T cell lymphopenia in 8-wk-old Kl/Kl mice. Taken together, our data suggest that Klotho deficiency causes thymic involution via systemic effects that include high active vitamin D levels.


Purification and initiation of structural characterization of human peripheral myelin protein 22, an integral membrane protein linked to peripheral neuropathies.
Gene duplications, deletions, and point mutations in peripheral myelin protein 22 (PMP22) are linked to several inherited peripheral neuropathies. However, the structural and biochemical properties of this very hydrophobic putative tetraspan integral membrane protein have received little attention, in part because of difficulties in obtaining milligram quantities of wild type and disease-linked mutant forms of the protein. In this study a fusion protein was constructed consisting of a fragment of lambda repressor, a decahistidine tag, an intervening TEV protease cleavage site, a Strep tag, and the human PMP22 sequence. This fusion protein was expressed in Escherichia coli at a level of 10-20 mg/L of protein. Following TEV cleavage of the fusion partner, PMP22 was purified and its structural properties were examined in several different types of detergent micelles using cross-linking, near and far-UV circular dichroism, and nuclear magnetic resonance (NMR) spectroscopy. PMP22 is highly helical and, in certain detergents, shows evidence of stable tertiary structure. The protein exhibits a strong tendency to dimerize. The 1H-15N TROSY NMR spectrum is well dispersed and contains signals from all regions of the protein. It appears that detergent-solubilized PMP22 is amenable to detailed structural characterization via crystallography or NMR. This work sets the stage for more detailed studies of the structure, folding, and misfolding of wild type and disease-linked mutants in order to unravel the molecular defects underlying peripheral neuropathies.


Is incidental prophylactic oophorectomy an acceptable means to reduce the incidence of ovarian cancer?
According to previous reports, the lifetime risk of developing ovarian carcinoma is 1.4%. This figure varies with age from 6.6 per 100,000 among women aged 35 to 39 years up to 55.1 per 100,000 among women aged 75 to 79 years. Prophylactic oophorectomy remains a modality to decrease the incidence of ovarian cancer. What proportion of women diagnosed with an ovarian malignancy had a preceding laparotomy at which time a prophylactic oophorectomy could have been performed? We reviewed the new ovarian cancer diagnoses seen in patients between August 1988 and August 1993 at the Ottawa Regional Cancer Foundation. Four hundred and four patients were identified. These patients were analyzed for preceding abdominal surgery, age, time to disease progression, time to death, time to death from other causes, and average follow-up. The previous abdominal surgeries were divided into: (1) major gynecological surgery; and (2) general surgery procedures, which were further divided into laparotomy and pelvic surgery (group A surgeries) and general surgery that included other abdominal surgeries (ie, appendectomy, cholecystectomy) where access to the pelvis could be more difficult (group B surgeries). A total of 270 abdominal surgeries was performed, prior to the diagnosis of ovarian cancer. The group was stratified according to the timing of the surgery (< or =40 years, 41 to 45 years, 46 to 50 years, >50 years). Based on these data, and on the grouping of general gynecologic surgeries plus the general surgical procedures of group A, 10.9% of ovarian cancers would have been prevented if prophylactic oophorectomy had been performed in patients who had surgery over 40 years of age; over 45 years this was 6.7%, over 50 years it was 4%. If one adds all major surgeries, including general surgery groups A and B, the results were 26.9% over 40 years of age, 20% over 45, and 16.6% over 50. We found that, depending on the age of the patient, prophylactic oophorectomy results in a 4% to 10.9% reduction in the incidence of ovarian carcinoma. This increases to 16.6% to 26.9% if one considers general surgery procedures in which access could be more difficult. Although we are not advocating the frequent use of this procedure, we recommend that surgeons routinely discuss this option before surgery with their postmenopausal female patients over 49 years of age. Given that the decision for prophylactic oophorectomy is multifaceted, we feel that a risk scoring for ovarian cancer and a discussion of the risk and benefit ratio should be undertaken. The ultimate goal is to heighten patient awareness of the risk factors to ensure that an informed decision is made concerning this consistently lethal disease.


The Design, Development, and Evaluation of a Qualitative Data Collection Application for Pregnant Women.
This article explores the development and evaluation of a smartphone mobile software application (app) to collect qualitative data. The app was specifically designed to capture real-time qualitative data from women planning a vaginal birth after caesarean delivery. This article outlines the design and development of the app to include funding, ethics, and the recruitment of an app developer, as well as the evaluation of using the app by seven participants. Data collection methods used in qualitative research include interviews and focus groups (either online, face-to-face, or by phone), participant diaries, or observations of interactions. This article identifies an alternative data collection methodology using a smartphone app to collect real-time data. The app provides real-time data and instant access to data alongside the ability to access participants from a variety of locations. This allows the researcher to gain insight into the experiences of participants through audio or video recordings in longitudinal studies without the need for constant interactions or interviews with participants. Using smartphone applications can allow researchers to access participants who are traditionally hard to reach and access their data in real time. Evaluating these apps before use in research is invaluable.


High pregnancy rates in humpback whales (Megaptera novaeangliae) around the Western Antarctic Peninsula, evidence of a rapidly growing population.
Antarctic humpback whales are recovering from near extirpation from commercial whaling. To understand the dynamics of this recovery and establish a baseline to monitor impacts of a rapidly changing environment, we investigated sex ratios and pregnancy rates of females within the Western Antarctic Peninsula (WAP) feeding population. DNA profiling of 577 tissue samples (2010-2016) identified 239 males and 268 females. Blubber progesterone levels indicated 63.5% of the females biopsied were pregnant. This proportion varied significantly across years, from 36% in 2010 to 86% in 2014. A comparison of samples collected in summer versus fall showed significant increases in the proportion of females present (50% to 59%) and pregnant (59% to 72%), consistent with demographic variation in migratory timing. We also found evidence of annual reproduction among females; 54.5% of females accompanied by a calf were pregnant. These high pregnancy rates are consistent with a population recovering from past exploitation, but appear inconsistent with recent estimates of WAP humpback population growth. Thus, our results will help to better understand population growth potential and set a current baseline from which to determine the impact of climate change and variability on fecundity and reproductive rates.


Ultra-sensitive and plasmon-tunable graphene photodetectors for micro-spectrometry.
We demonstrate an ultra-sensitive photodetector based on a graphene/monolayer MoS2 vertical heterostructure working at room temperature. Highly confined plasmon waves are efficiently excited through a periodic array of monolayer graphene ribbons in which plasmon resonance has remarkably large oscillator strength, resulting in a sharp optical absorption peak in the normal-incidence transmission spectrum. A significant amount of electron-hole pairs are produced in graphene ribbons by optical absorption, separated by the built-in electric field across the graphene/MoS2 heterojunction. The responsivity reaches up to 1 × 107 A W-1 at room temperature due to very strong resonance in the heterostructure, yielding a highly sensitive graphene-based photodetector. Additionally, the absorption can be tuned over a wide spectral range (6-16 μm) by varying gate biasing. The ultra-sensitive, spectrally tunable photodetector could be potentially used as a promising candidate for mid-infrared micro-spectrometers.


Comparative study on the phytochemical profiles and cellular antioxidant activity of phenolics extracted from barley malts processed under different roasting temperatures.
Consumption of cereal foods has been related to health improvement, which is partly because of their phytochemicals. To explore the functionality and effective application of barley malt, a widely consumed nutritional food, the entire phytochemical profiles and bioactivities of three common barley malt products obtained under different roasting temperatures were analyzed. Results showed that they are abundant in phenolics including flavonoids with high antioxidative activities, as displayed by cellular antioxidant activity (CAA), oxygen radical absorbance capacity, peroxyl radical scavenging capacity, and DPPH and ABTS radical scavenging assays. Among the three barley malts, the raw barley malt bound extract and the dark barley malt free extract exhibited higher CAA values, while the raw barley malt contained a negligible amount of bound phenolics. An efficacious antiproliferation capacity of the dark barley malt free extract was detected in Caco-2 cells. Results also provide an insight into the positive attributes of thermal processing for the biofunctionality of barley malts, especially through the tuning of the accessibility and variability of beneficial phytochemicals.


Polar bear mother-offspring interactions in maternity dens in captivity.
Two female polar bears at Dierenrijk Zoo in the Netherlands were monitored at their maternity den one day before the birth of their cubs and three days postpartum. Each bear was monitored for 96 hr to document behaviour and vocalisations. The goal was to obtain insight into the differences between the mother that lost her litter and the other that successfully reared her cubs. Six groups of cub vocalisations were identified: Comfort, Discomfort, Distress, Nursing Attempts, Nursing, and No Vocalisation. Maternal vocalisations were split into three groups: Calm, Grooming, and Stress. Maternal behaviours were also split into three groups: Active, Rest, and Stress. The unsuccessful mother produced more stress vocalisations before and during the birth of her cub, whereas the successful mother appeared less stressed. Vocalisations indicate that the cub that died tried to nurse but was unsuccessful. The unsuccessful mother showed less stress as her cub got weaker and vocalised less. From this I suggest that maternal stress was a factor in cub mortality.


Fructose precipitates calcium phosphate in the kidneys of female rats fed magnesium-deficient diets.
We have previously shown the synergistic interaction between fructose and magnesium (Mg) deficiency on renal calcification of female rats. The purpose of the present study was to determine whether the calcification formed in the kidneys of female rats fed an Mg-deficient fructose diet is due to phosphate or oxalate precipitates of calcium. The rats were divided into two dietary groups: fructose without Mg and starch with Mg. Rats were fed their respective diets for 9 weeks, and 24 h urine was collected for measuring urinary output, pH, Mg and calcium (Ca). The rats were then fasted overnight and after decapitation, blood was immediately collected for measuring plasma Ca and Mg, and the kidneys were removed. Left kidneys were used to determine their Mg and Ca contents, and right kidneys were dissected and fixed in neutral buffered formalin. Formalin-fixed specimens for microscopy were processed in paraffin using conventional procedures. Histochemical analysis was conducted by staining serial paraffin sections with haematoxylin, eosin, PAS-Schiff, alcian blue and trichrome. The sections were stained by the von Kossa method for calcium phosphate and by the silver hydroperoxide method for calcium oxalate. Only calcium phosphate was detected in the corticomedullary junction of the kidneys of female rats fed Mg-deficient fructose. The hypercalcaemia, hypercalciuria, and hypomagnesuria observed in the fructose group may cause calcium phosphate crystallization. A possible mechanism for the interaction between magnesium deficiency, fructose and oestrogen may be through parathyroid hormone which increases tubular fluid Ca and phosphorus (TF[Ca]x[P]). Further studies are required to prove the mechanism proposed here.


Idiopathic polypoidal choroidal vasculopathy of the macula.
The authors evaluated the clinical, fluorescein, and indocyanine green (ICG) angiographic characteristics of the macular variant of idiopathic polypoidal choroidal vasculopathy (IPCV). Observational case series. The records, photographs, and fluorescein and ICG angiograms of eight eyes of seven patients with IPCV lesions confined to the macula were reviewed. The visual acuity, fundus examination, fluorescein and ICG angiographic characteristics, and clinical course were compared. All patients demonstrated polypoidal lesions arising from macular choroidal vessels on ICG angiography. One patient had bilateral lesions. These lesions appeared hyperfluorescent in the early phases of both fluorescein and ICG angiography. Late-phase leakage was seen in cases associated with subretinal fluid or exudate. None of these patients demonstrated polypoidal lesions arising from the peripapillary choroidal circulation or peripapillary choroidal neovascularization. Three eyes with polypoidal lesions that were associated with subretinal fluid and exudates were treated with photocoagulation. Five eyes were not treated. Final visual acuity ranged from 20/20 to hand motions. Severe visual loss was associated with vitreous and subretinal hemorrhage, but this resolved without permanent severe visual loss in several cases. In the macular variant of IPCV, ICG and fluorescein angiography demonstrate characteristic macular polypoidal lesions without evidence of peripapillary lesions. The vascular origin of these polypoidal lesions appears to be the macular choroidal circulation. This is distinguished from classic IPCV, in which lesions appear to arise from the peripapillary choroidal circulation. Visual prognosis appears to be good, with most patients retaining visual acuity of 20/80 or better. If subretinal fluid or exudates reduce visual acuity, photocoagulation should be considered.


A computerised microscope focusing technique.
An automatic focusing technique for a computer-controlled optical microscope is described, which is based on an algorithm originally proposed by Mendelsohn and Mayall. The procedure is capable of attaining a focusing accuracy of less than 1/20 micron in the slide-objective distance. The dependence of focusing accuracy and time to focus on the scanner signal-to-noise ratio, and the change in the focus position with time, are discussed.


Femoral Endovenectomy with Iliac Stenting for Chronic Iliofemoral Venous Occlusion.
A 62-year-old man with progressive swelling on his left thigh and leg was referred to the Division of Vascular Surgery. Anticoagulation therapy did not prevent or improve the symptoms of chronic deep vein thrombosis (DVT) from his left external iliac vein to posterior tibial vein. He had no trauma history nor any accidents. He underwent femoral endovenectomy, thrombectomy and stent insertion in left iliac vein. The patient had additional balloon angioplasty for stenosis in left common femoral vein. He had an uneventful postoperative recovery without complication. Leg swelling has been improving and follow-up continues under anticoagulation. We report a case of femoral endovenectomy with iliac stenting, which may be an efficacious treatment for chronic DVT.


The automaticity of Mahaim fibre and its response to effective ablation.
Typical accessory pathways (APs) of Wolf-Parkinson-White syndrome have been widely discussed in recent decades. However, the characteristics of the special AP, Mahaim fibre, are not so clear. It is known that these fibres have antegrade conduction only, long conduction time, decremental node-like conduction and automaticity properties. This study was to elucidate the automaticity of Mahaim fibre and its response to effective ablation. Thirteen patients with Mahaim fibre (ten atrioventricular and three atriofascicular accessory pathways) were subjected to electrophysiological study and radiofrequency ablation via catheter. The incidence and characteristics of anautomatic rhythm originating from Mahaim fibre were observed during the whole procedure, especially during radiofrequency current delivery. Repetitive and short-run automatic rhythm (rate: 65-72 beats per minute), with a QRS morphology similar to that of clinical pre-excited atrioventricular re-entrant tachycardia (AVRT), occurred in two patients during sinus rhythm. Conduction via Mahaim fibre was successfully eliminated by radiofrequency current. Fourteen applications of RF were associated with irregularly accelerated automatic tachycardia of Mahaim fibre (with a sensitivity of 78%), lasting for 1.2-14 seconds. However, such automatic tachycardia of Mahaim fibre did not occur during 54 failed applications of radiofrequency current. Mahaim fibre has the function of automaticity. The accelerated automatic tachycardia of Mahaim fibre occur red during radiofrequency catheter ablation can be used as a predictor for successful procedure.


Immunologic recovery following autologous stem-cell transplantation with pre- and posttransplantation rituximab for low-grade or mantle cell lymphoma.
Rituximab may improve transplant outcomes but may delay immunologic recovery. Seventy-seven patients with low-grade or mantle cell lymphoma received autologous stem-cell transplantation (ASCT) on a phase II study. Rituximab 375 mg/m(2) was administered 3 days before mobilization-dose cyclophosphamide, then weekly for four doses after count recovery from ASCT. Immune reconstitution was assessed. Sixty percent of transplants occurred in first remission. Actuarial event-free survival (EFS) and overall survival (OS) were 60% and 73%, respectively, at 5 years, with 7.2-year median follow-up for OS in surviving patients. Median EFS was 8.3 years. Older age and transformed lymphomas were independently associated with inferior EFS, whereas day 60 lymphocyte counts did not predict EFS or late infections. Early and late transplant-related mortality was 1% and 8%, with secondary leukemia in two patients. B-cell counts recovered by 1-2 years; however, the median IgG level remained low at 2 years. Late-onset idiopathic neutropenia, generally inconsequential, was noted in 43%. ASCT with rituximab can produce durable remissions on follow-up out to 10 years. Major infections do not appear to be significantly increased or to be predicted by immune monitoring.


Safety, formulation, and in vitro antiviral activity of the antimicrobial peptide subtilosin against herpes simplex virus type 1.
In the present study the antiviral properties of the bacteriocin subtilosin against Herpes simplex virus type 1 (HSV-1) and the safety and efficacy of a subtilosin-based nanofiber formulation were determined. High concentrations of subtilosin, the cyclical antimicrobial peptide produced by Bacillus amyloliquefaciens, were virucidal against HSV-1. Interestingly, at non-virucidal concentrations, subtilosin inhibited wild type HSV-1 and aciclovir-resistant mutants in a dose-dependent manner. Although the exact antiviral mechanism is not fully understood, time of addition experiments and western blot analysis suggest that subtilosin does not affect viral multiplication steps prior to protein synthesis. Poly(vinyl alcohol) (PVOH)-based subtilosin nanofibers with a width of 278 nm were produced by the electrospinning process. The retained antimicrobial activity of the subtilosin-based fibers was determined via an agar well diffusion assay. The loading capacity of the fibers was 2.4 mg subtilosin/g fiber, and loading efficiency was 31.6%. Furthermore, the nanofibers with and without incorporated subtilosin were shown to be nontoxic to human epidermal tissues using an in vitro human tissue model. Taking together these results subtilosin-based nanofibers should be further studied as a novel alternative method for treatment and/or control of HSV-1 infection.


Statistical Evaluation of Transformation Methods Accuracy on Derived Pathological Vectorcardiographic Leads.
Objective: Vectorcardiography (VCG) as an alternative form of ECG provides important spatial information about the electrical activity of the heart. It achieves higher sensitivity in the detection of some pathologies such as myocardial infarction, ischemia and hypertrophy. However, vectorcardiography is not commonly measured in clinical practice, and for this reason mathematical transformations have been developed to obtain derived VCG leads, which in application in current systems and subsequent analysis can contribute to early diagnosis and obtaining other useful information about the electrical activity of the heart. Methods and procedures: The most frequently used transformation methods are compared, namely the Kors regression method, the Inverse Dower transformation, QLSV and the Quasi-orthogonal transformation. These transformation methods were used on 30 randomly selected records with a diagnosis of myocardial infarction from the Physikalisch-Technische Bundesanstalt (PTB) database and their accuracy was evaluated based on the calculation of the mean square error (MSE). MSE was subjected to statistical evaluation at a significance level of 0.05. Results: Based on statistical testing using the nonparametric multiselective Kruskall-Wallis test and subsequent post-hoc analysis using the Dunn method, the Kors regression as a whole method achieved the most accurate transformation. Conclusion: The results of statistical analysis provide an evaluation of the accuracy of several transformation methods for deriving orthogonal leads, for possible application in measuring and evaluation systems, which may contribute to the correct choice of method for subsequent analysis of electrical activity of the heart at orthogonal leads to predict various diseases.


Doctor, Will You Pray for Me? Responding to Patients' Religious and Spiritual Concerns.
Religion and spirituality in the United States have been shifting, and physicians are treating patients with increasingly diverse beliefs. Physicians' unfamiliarity with these beliefs poses critical challenges for medical education and practice. Despite efforts to improve medical education in religion/spirituality, most doctors feel their training in these areas is inadequate. This article draws on the author's conversations with providers and patients over several years in various clinical and research contexts in which religious/spiritual issues have arisen. These conversations provided insights into how patients and their families commonly, and often unexpectedly, make religious/spiritual comments to their providers or question their providers about these topics, directly or indirectly. Comments are of at least 9 types that fall within 4 broad domains: (1) perceiving God's role in disease and treatment (in causing disease, affecting treatment outcomes, and knowing disease outcomes), (2) making medical decisions (seeking God's help in making these decisions and determining types/extents of treatment), (3) interacting with providers (ascertaining providers' beliefs, having preferences regarding providers, and requesting prayer with or by providers), and (4) pondering an afterlife. Because of their beliefs or lack of knowledge, doctors face challenges in responding and often do so in 1 of 4 broad ways: (1) not commenting, (2) asking strictly medical questions, (3) referring the patient to a chaplain, or (4) commenting on the patient's remark. Medical education should thus encourage providers to recognize the potential significance of patients' remarks regarding these topics and to be prepared to respond, even if briefly, by developing appropriate responses to each statement type. Becoming aware of potential differences between key aspects of non-Western faiths (e.g., through case vignettes) could be helpful. Further research should examine in greater depth how patients broach these realms, how physicians respond, and how often medical school curricula mention non-Western traditions.


Behavioral regulation of hypothalamic temperature.
Animals will work to produce changes in hypothalamic temperature. The two main inputs, skin and hypothalamic temperatures, combine to control this behavior. Specifically, the rate at which rats work for changes in hypothalamic temperature is proportional to the sum of the weighted displacements of skin and hypothalamic temperatures from their respective neutral values.


[Effect of electroacupuncture at "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) on collagen-induced arthritis and secretory function of knee-joint synoviocytes in rats].
To observe the effect of electroacupuncture (EA) of "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) on collagen-induced arthritis (CIA) and its underlying mechanism in regulating the secretory function of knee-joint synovial cells in CIA rats. Thirty-six Wistar rats were equally randomized into control, model and EA groups. CIA model (rheumatoid arthritis) was duplicated by intradermal injection of Bovine type II collagen into the back of the anesthetized rats. EA (2 Hz, 2 mA) was applied to "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) for 30 min, once a day for 30 days. The paw volume was measured by using a Plethysmometer and hot water tail-flick tests (50 degrees C) were conducted for detecting the rats' pain threshold (PT) before and after the treatment. The contents of PGE2, IL-1beta and TNF-alpha in supernatant of the cultured joint synoviocytes were detected by enzyme linked immunosorbent assay (ELISA). In comparison with control group, the swelled paw volume, the declined PT, PGE2, TNF-alpha and IL-1beta contents in knee-joint synoviocyte supernatant were significantly higher in model group (P < 0.05). Compared with model group, PT increased obviously (P < 0.05); paw volume, supernatant PGE2, TNF-alpha and IL-1beta contents decreased obviously (P < 0.05) in EA group. EA of ST 36 and SP 6 has a pronounced therapeutic effect in relieving knee joint pain and inflammation in CIA rats, which may be related to its effect in regulating the secretory function of the knee-joint synoviocytes.


Measles cluster at a university in the United Kingdom.
Measles remains an infection of public health importance. We describe a cluster of measles in a university setting between April and May 2007. The outbreak took place over a period of six weeks and involved nine students, eight of whom lived in halls of residence. Due to the potential for significant spread in an institutional setting, a public health investigation was initiated to identify the source of the outbreak. Follow up of cases was undertaken proactively with the university and local general practitioners. Salivary fluid test kits and questionnaires were sent to suspected cases. Seven salivary test kits were returned, but only one questionnaire was returned. Four cases were confirmed as measles. Although seven students had been previously immunised, immunity was only demonstrated in three. Public health investigations were hampered by the poor return rate of questionnaire and oral fluid sampling kits despite proactive follow up by public health staff, as well as the break for summer vacation. Nevertheless, our report highlights the public health effort in investigating such outbreaks and the importance of reinforcing immunisation to college and university students.


Rhizobium leguminosarum genes involved in early stages of nodulation.
Nodulation genes from Rhizobium leguminosarum have been subcloned and transferred to a strain of R. phaseoli with its symbiotic plasmid deleted (and therefore its nodulation and nitrogen fixation genes). Normal infection and nodule development occurred when these strains were added to the roots of Pisum sativum (peas) and Vicia hirsuta. The pea nodules were examined by electron microscopy; bacteroid forms were seen surrounded by peribacteroid membranes and using immuno-gold labelling it was shown that the nodule cells contained leghaemoglobin within the cytoplasm. By subcloning and analysing the nodulation region it was found that a small (3.2 X 10(3) bases) fragment of DNA contained three genes involved in root hair curling, the first observed step in the interaction between R. leguminosarum and the root hair cells of these legumes.


Spatial analysis of stunting determinants in 514 Indonesian districts/cities: Implications for intervention and setting of priority.
While the national prevalence of stunting in Indonesia has decreased, the level remains high in many districts/cities and there is significant variation. This ecological study employed aggregated data from the Basic Health Research Report and the District/City Poverty Data from 2018. We investigated the determinants of stunting prevalence at the district/city level, including autocorrelation applying the spatial autoregressive (SAR) model. The analyses revealed stunting prevalence above the national average in 282 districts/cities (54.9%), i.e. ≥30% in 297 districts/cities (57.8%) and ≥40% in 91 districts/cities (17.7%). Autocorrelation was found between Sumatra, Java, Sulawesi as well as Bali, East Nusa Tenggara and West Nusa Tenggara (Bali NTT NTB). The SAR modelling revealed the following variables with significant impact on the stunting prevalence in various parts of the country: closet defecation, hand washing, at least four antenatal care visits during pregnancy, poverty, immunisation and supplementary food for children under 5 years.


Octopamine enhances dark-adaptation in Limulus ventral photoreceptors.
Limulus ventral photoreceptors receive synaptic input from fibers that emerge from the brain and that appear to use octopamine as a transmitter. Exogenous application of octopamine has been shown to increase levels of intracellular cAMP in ventral photoreceptors, but the resulting physiological effects have been unclear. In this report, we show that octopamine increases the rate of dark-adaptation following a bright light. Since a similar increase in the rate of dark-adaptation is produced by IBMX (1 mM) and forskolin (100 microM), drugs shown previously to raise the concentration of cAMP, the octopamine effect may be mediated by cAMP. Our results suggest that dark-adaptation, a fundamental process of photoreceptors, is under efferent neural control.


The role of spatial frequencies for facial pain categorization.
Studies on low-level visual information underlying pain categorization have led to inconsistent findings. Some show an advantage for low spatial frequency information (SFs) and others a preponderance of mid SFs. This study aims to clarify this gap in knowledge since these results have different theoretical and practical implications, such as how far away an observer can be in order to categorize pain. This study addresses this question by using two complementary methods: a data-driven method without a priori expectations about the most useful SFs for pain recognition and a more ecological method that simulates the distance of stimuli presentation. We reveal a broad range of important SFs for pain recognition starting from low to relatively high SFs and showed that performance is optimal in a short to medium distance (1.2-4.8 m) but declines significantly when mid SFs are no longer available. This study reconciles previous results that show an advantage of LSFs over HSFs when using arbitrary cutoffs, but above all reveal the prominent role of mid-SFs for pain recognition across two complementary experimental tasks.


Human amniotic fluid stem cell injection therapy for urethral sphincter regeneration in an animal model.
Stem cell injection therapies have been proposed to overcome the limited efficacy and adverse reactions of bulking agents. However, most have significant limitations, including painful procurement, requirement for anesthesia, donor site infection and a frequently low cell yield. Recently, human amniotic fluid stem cells (hAFSCs) have been proposed as an ideal cell therapy source. In this study, we investigated whether periurethral injection of hAFSCs can restore urethral sphincter competency in a mouse model. Amniotic fluids were collected and harvested cells were analyzed for stem cell characteristics and in vitro myogenic differentiation potency. Mice underwent bilateral pudendal nerve transection to generate a stress urinary incontinence (SUI) model and received either periurethral injection of hAFSCs, periurethral injection of Plasma-Lyte (control group), or underwent a sham (normal control group).For in vivo cell tracking, cells were labeled with silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate (MNPs@SiO2 (RITC)) and were injected into the urethral sphincter region (n = 9). Signals were detected by optical imaging. Leak point pressure and closing pressure were recorded serially after injection.Tumorigenicity of hAFSCs was evaluated by implanting hAFSCs into the subcapsular space of the kidney, followed two weeks later by retrieval and histologic analysis. Flow activated cell sorting showed that hAFSCs expressed mesenchymal stem cell (MSC) markers, but no hematopoietic stem cell markers. Induction of myogenic differentiation in the hAFSCs resulted in expression of PAX7 and MYOD at Day 3, and DYSTROPHIN at Day 7. The nanoparticle-labeled hAFSCs could be tracked in vivo with optical imaging for up to 10 days after injection. Four weeks after injection, the mean LPP and CP were significantly increased in the hAFSC-injected group compared with the control group. Nerve regeneration and neuromuscular junction formation of injected hAFSCs in vivo was confirmed with expression of neuronal markers and acetylcholine receptor. Injection of hAFSCs caused no in vivo host CD8 lymphocyte aggregation or tumor formation. hAFSCs displayed MSC characteristics and could differentiate into cells of myogenic lineage. Periurethral injection of hAFSCs into an SUI animal model restored the urethral sphincter to apparently normal histology and function, in absence of immunogenicity and tumorigenicity.


A stromal cell-derived factor-1 releasing matrix enhances the progenitor cell response and blood vessel growth in ischaemic skeletal muscle.
Although many regenerative cell therapies are being developed to replace or regenerate ischaemic muscle, the lack of vasculature and poor persistence of the therapeutic cells represent major limiting factors to successful tissue restoration. In response to ischaemia, stromal cell-derived factor-1 (SDF-1) is up-regulated by the affected tissue to stimulate stem cell-mediated regenerative responses. Therefore, we encapsulated SDF-1 into alginate microspheres and further incorporated these into an injectable collagen-based matrix in order to improve local delivery. Microsphere-matrix impregnation reduced the time for matrix thermogelation, and also increased the viscosity reached. This double-incorporation prolonged the release of SDF-1, which maintained adhesive and migratory bioactivity, attributed to chemotaxis in response to SDF-1. In vivo, treatment of ischaemic hindlimb muscle with microsphere-matrix led to increased mobilisation of bone marrow-derived progenitor cells, and also improved recruitment of angiogenic cells expressing the SDF-1 receptor (CXCR4) from bone marrow and local tissues. Both matrix and SDF-1-releasing matrix were successful at restoring perfusion, but SDF-1 treatment appeared to play an earlier role, as evidenced by arterioles that are phenotypically older and by increased angiogenic cytokine production, stimulating the generation of a qualitative microenvironment for a rapid and therefore more efficient regeneration. These results support the release of implanted SDF-1 as a promising method for enhancing progenitor cell responses and restoring perfusion to ischaemic tissues via neovascularisation.


What is the optimal management option for occupational asthma?
The optimal management of occupational asthma remains uncertain in clinical practice. The aim of this review was to analyse the published information pertaining to the management of occupational asthma in order to produce evidence-based statements and recommendations. A systematic literature search was conducted up to March 2010 to identify original studies addressing the following different treatment options: 1) persistence of exposure; 2) pharmacological treatment; 3) complete avoidance of exposure; 4) reduction of exposure; and 5) the use of personal protective equipment. After full text evaluation of 83 potentially relevant articles, 52 studies were retained for analysis. The conclusions from this systematic review are limited by the methodological weaknesses of most published studies. Critical analysis of available evidence indicates that: 1) persistent exposure to the causal agent is more likely to result in asthma worsening than complete avoidance; 2) there is insufficient evidence to determine whether pharmacological treatment can alter the course of asthma in subjects who remain exposed; 3) avoidance of exposure leads to recovery of asthma in less than one-third of affected workers; 4) reduction of exposure seems to be less beneficial than complete avoidance of exposure; and 5) personal respiratory equipment does not provide complete protection.


Expression and localization of protein inhibitor of neuronal nitric oxide synthase in Duchenne muscular dystrophy.
In skeletal muscle fibers, nitric oxide is synthesized by neuronal nitric oxide synthase (nNOS), which normally associates with the dystrophin complex in close proximity to the sarcolemma. Many reports have documented that very low levels of nNOS protein exist in muscle fibers of Duchenne muscular dystrophy (DMD) patients. In this study we investigated the functional significance of PIN (protein inhibitor of nNOS) in targeting of nNOS to the sarcolemma and the association between nNOS and the dystrophin complex in normal and dystrophic muscle fibers. Northern blotting for PIN mRNA in normal mouse muscles and muscles of mdx mice (an animal model of DMD) revealed a significant rise in PIN mRNA in dystrophic muscles compared with normal muscles. Immunohistochemical analysis showed that, in normal mouse muscle fibers, PIN expression was localized at the sarcolemma, peripheral nuclei, and the sarcoplasm. By comparison, PIN protein in muscles from mdx mice was more concentrated around the sarcolemma and central nuclei. The presence of PIN protein expression in muscles from mdx mice was evident despite the significant reduction in nNOS and dystrophin protein expressions in these fibers. In muscle sections of DMD patients, the absence of nNOS protein expression was accompanied by maintained PIN expression. Prominent PIN expression was also detectable in macrophages infiltrating dystrophic muscle fibers both in mdx mice and DMD patients. These results suggest that PIN expression in muscles from mdx mice and DMD patients is controlled by factors different from those involved in the regulation of nNOS and dystrophin. Moreover, our results indicate that PIN is not an integral component of the dystrophin complex inside skeletal muscle fibers.


Glomerular structural-functional relationship models of diabetic nephropathy are robust in type 1 diabetic patients.
Studies of structural-functional relationships have improved understanding of the natural history of diabetic nephropathy (DN). However, in order to consider structural end points for clinical trials, the robustness of the resultant models needs to be verified. This study examined whether structural-functional relationship models derived from a large cohort of type 1 diabetic (T1D) patients with a wide range of renal function are robust. The predictability of models derived from multiple regression analysis and piecewise linear regression analysis was also compared. T1D patients (n = 161) with research renal biopsies were divided into two equal groups matched for albumin excretion rate (AER). Models to explain AER and glomerular filtration rate (GFR) by classical DN lesions in one group (T1D-model, or T1D-M) were applied to the other group (T1D-test, or T1D-T) and regression analyses were performed. T1D-M-derived models explained 70 and 63% of AER variance and 32 and 21% of GFR variance in T1D-M and T1D-T, respectively, supporting the substantial robustness of the models. Piecewise linear regression analyses substantially improved predictability of the models with 83% of AER variance and 66% of GFR variance explained by classical DN glomerular lesions alone. These studies demonstrate that DN structural-functional relationship models are robust, and if appropriate models are used, glomerular lesions alone explain a major proportion of AER and GFR variance in T1D patients.


Consensus-based perspectives of pediatric inpatient eating disorder services.
There are few evidence-based guidelines for inpatient pediatric eating disorders. The aim was to gain perspectives from those providing and receiving inpatient pediatric eating disorder care on the essential components treatment. A modified Delphi technique was used to develop consensus-based opinions. Participants (N = 74) were recruited for three panels: clinicians (n = 24), carers (n = 31), and patients (n = 19), who endorsed three rounds of statements online. A total of 167 statements were rated, 79 were accepted and reached a consensus level of at least 75% across all panels, and 87 were rejected. All agreed that families should be involved in treatment, and thatpsychological therapy be offered in specialist inpatient units. Areas of disagreement included that patients expressed a desire for autonomy in sessions being available without carers, and that weight gain should be gradual and admissions longer, in contrast to carers and clinicians. Carers endorsed that legal frameworks should be used to retain patients if required, and that inpatients are supervised at all times, in contrast to patients and clinicians. Clinicians endorsed that food access should be restricted outside meal times, in contrast to patients and carers. The findings indicate areas of consensus in admission criteria, and that families should be involved in treatment, family involvement in treatment, while there was disagreement across groups on topics including weight goals and nutrition management. Perspectives from patients, carers, and clinicians may be useful to consider during future revisions of best practice guidelines.


Impact of patient, system, and environmental factors on utilization of air medical transport after trauma.
Air medical transport (AMT) improves outcomes for severely injured patients. The decision to fly patients is complex and must consider multiple factors. Our objective was to evaluate the interaction between geography, patient and environmental factors, and emergency medical services (EMS) system resources on AMT after trauma. We hypothesize significant geographic variation in AMT utilization will be associated with varying levels of patient, environmental, and EMS resources. Patients transported by EMS in the Pennsylvania state trauma registry 2000-2017 were included. We used our previously developed Air Medical Prehospital Triage (AMPT, ≥2 points triage to AMT) score and Geographic EMS Index (GEMSI, higher indicates more system resources) as measures for patient factors and EMS resources respectively. A mixed-effects logistic regression model determined the association of AMT utilization with patient, system, and environmental variables. There were 195,354 patients included. Fifty-five percent of variation in AMT utilization was attributed to geographic differences. Triage to AMT by the AMPT score was associated with nearly twice the odds of AMT utilization [aOR: 1.894; 95%CI: 1.765-2.032; p < 0.001]. Each one-point increase in GEMSI was associated with a 6.1% reduction in odds of AMT [0.939; 0.922-0.957; p < 0.001]. Younger age, rural location, and more severe injuries were also associated with increased odds of AMT (p < 0.05). When categorized by GEMSI level, the AMPT score and patient factors were more important for predicting AMT utilization in the middle tercile (moderate EMS resources) compared to the lower (low EMS resources) and higher tercile (high EMS resources). Weather, season, time-of-day, and traffic were all associated with AMT utilization (p < 0.05). Patient, system, and environmental factors are associated with AMT utilization which varies geographically and by EMS/trauma system resource availability. A more comprehensive approach to AMT triage could reduce variation and allow more tailored efforts towards optimizing resource allocation and outcomes. III, epidemiological.


Case management: a heritage more than a century old.
The roots of case management are more than a century deep. This innovative approach to managing, coordinating, expediting, and facilitating patient care is neither new nor exclusively limited to nursing practice. A review of the historic literature reveals that the evolution of case management is a byproduct of creative healthcare efforts associated with different disciplines, including nursing, medicine, mental health, public health, and social work. This article presents a historical review of significant milestones in the evolution of the field of case management and its related tools (i.e., clinical pathways).


Direct observation of abortive initiation and promoter escape within single immobilized transcription complexes.
Using total-internal-reflection fluorescence microscopy equipped with alternating-laser excitation, we were able to detect abortive initiation and promoter escape within single immobilized transcription complexes. Our approach uses fluorescence resonance energy transfer to monitor distances between a fluorescent probe incorporated in RNA polymerase (RNAP) and a fluorescent probe incorporated in DNA. We observe small, but reproducible and abortive-product-length-dependent, decreases in distance between the RNAP leading edge and DNA downstream of RNAP upon abortive initiation, and we observe large decreases in distance upon promoter escape. Inspection of population distributions and single-molecule time traces for abortive initiation indicates that, at a consensus promoter, at saturating ribonucleoside triphosphate concentrations, abortive-product release is rate-limiting (i.e., abortive-product synthesis and RNAP-active-center forward translocation are fast, whereas abortive-product dissociation and RNAP-active-center reverse translocation are slow). The results obtained using this new methodology confirm and extend those obtained from diffusing single molecules, and pave the way for real-time, single-molecule observations of the transitions between various states of the transcription complex throughout transcription.


Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase II.
A common landmark of activated genes is the presence of trimethylation on lysine 4 of histone H3 (H3K4) at promoter regions. Set1/COMPASS was the founding member and is the only H3K4 methylase in Saccharomyces cerevisiae; however, in mammals, at least six H3K4 methylases, Set1A and Set1B and MLL1 to MLL4, are found in COMPASS-like complexes capable of methylating H3K4. To gain further insight into the different roles and functional targets for the H3K4 methylases, we have undertaken a genome-wide analysis of H3K4 methylation patterns in wild-type Mll1(+/+) and Mll1(-)(/)(-) mouse embryonic fibroblasts (MEFs). We found that Mll1 is required for the H3K4 trimethylation of less than 5% of promoters carrying this modification. Many of these genes, which include developmental regulators such as Hox genes, show decreased levels of RNA polymerase II recruitment and expression concomitant with the loss of H3K4 methylation. Although Mll1 is only required for the methylation of a subset of Hox genes, menin, a component of the Mll1 and Mll2 complexes, is required for the overwhelming majority of H3K4 methylation at Hox loci. However, the loss of MLL3/MLL4 and/or the Set1 complexes has little to no effect on the H3K4 methylation of Hox loci or their expression levels in these MEFs. Together these data provide insight into the redundancy and specialization of COMPASS-like complexes in mammals and provide evidence for a possible role for Mll1-mediated H3K4 methylation in the regulation of transcriptional initiation.


Assessment of areca nut use, practice and dependency among people in Guwahati, Assam: a cross-sectional study.
Areca nut is the fourth most commonly used psychoactive substance worldwide after tobacco, alcohol and caffeine. In India, it is perceived in various ways, ranging from a 'fruit of divine origin' in Hindu religious ceremonies to a mouth freshener. Areca nut use both on its own and with tobacco additives is addictive. The aim of this study was to understand the pattern of areca nut consumption, to determine the Knowledge, Attitude and Practices (KAP) among areca nut users and the dependency associated with areca nut use. A cross sectional study was conducted in Guwahati, Assam using a self-administered questionnaire eliciting the pattern of areca nut consumption, KAP among users and understanding their dependency using Betel Quid Dependence Scale. The chewers of areca nut alone with or without betel quid, gutkha and tobacco participated in the study. Areca nut users were selected using purposive sampling method from the vendor shops of all the four assembly areas of the city. Their participation was voluntary and free not to answer or quit the survey. The data was analysed using SPSS software. A total of 500 participants were approached in all four areas, 479 completed the survey (response rate 95%). The people who participated in the study were mostly male with an average age of 40 years, educated to secondary level or higher, married and self-employed. Betel quid with tamul was the most prevalent form of areca nut chewing in both men and women. About 441 (92%) participants experienced pleasure when chewing areca nut and 327 (68%) chewed it to relieve stress. Only 86 (18%) of subjects had ever tried to quit chewing areca nut and 387 (81%) thought that it was highly addictive. The results revealed relatively high levels of endorsement for 'physical and psychological urgent need' (mean = 43%) and 'increasing dose' (mean = 50%), whereas endorsement level for 'maladaptive use' was low (mean = 16%). Areca nut use (tamul) is of major concern in India and many Southeast Asian countries and its use has been increasing across the globe. The evidence suggests a dependence similar to tobacco use and policy makers need to refine its strategy for control of its use by engaging with multiple stakeholders and adapting it to local context with surveillance and cessation guidelines in order to address this issue.


Immunochemical characterization of a polyclonal human antibody to factor IX.
Inhibitors of clotting factors occuring in humans are often antibody molecules synthesized in response to exogeneous proteins used in replacement therapy. Extensive studies of inhibitors to factor VIII indicate such antibodies may be monoclonal or polyclonal in nature. To date, only one factor IX inhibitor has been subjected to detailed immunochemical analysis and it appears to be a monoclonal IgGA lambda antibody. We have discovered a second inhibitor of factor IX in a patient with severe hemophilia B and have subjected it to immunochemical analysis. Studies on this second inhibitor have been carried out before and after an anamnestic response. Column chromatography, preparative zone electrophoresis, and specific inhibitor neutralization assays using monospecific heterologous antisera to human immunoglobulin classes, subclasses, and light-chain types indicate that the antibody is of the IgG class and contains both kappa and lambda light chains and probably all four IgG subclasses. Thus, the inhibitor appears to be polyclonal by immunochemical and structural criteria. In addition, preparative isoelectric focusing of pre- and postanamnestic inhibitor samples indicates that recruitment of new clones of IgG antibody occurs as a result of anamnesis. It is conceivable that an antibody initially restricted in immunoglobulin subclass became polyclonal following an anamnestic response.


[Effect of light deprivation on enzymic activity of synaptosomes and mitochondria of rabbit cortex visual region].
The specific activity of markers-enzymes in the subcellular fractions of the rabbit visual analyzer cortical end, the synaptosomes and mitochondria of nerve cells, changed under the effect of early long deprivation. For cytochromoxidase and Na+, K+-ATPase it lowers considerably in all subfractions, for monoaminoxidase and Mg2+-ATPase it rises mainly in synaptosomes; the activity of acetyl cholinesterase lowers per 1 g of tissue. In the light two weeks later a tendency is observed to normalization of the studied indexes. The specific activity of cytochrome oxidase (except for free mitochondria) and Na+, K+-ATPase reaches the control, that of monoaminoxidase also partially normalizes, but not competely; Mg2+ATPase in all the subfractions is more inhibited than in the control. This evidences for the effect of light deprivation on the activity of the enzymes associated with different cycles of metabolic processes, first of all, of oxidation and ion transport. These changes are reversible when visual impulsation is recovered. Disturbances in chemism at the subcellular level are specific for different enzymic systems and are not the same in certain subfractions of great hemispheres.


Are carcinogens responsible for the superimposed neoplastic changes occurring in mouse tumor cells? The effect of methylcholanthrene and urethane on pulmonary adenomas and of methylcholanthrene on mammary carcinomas.
Three spontaneous pulmonary adenomas of C mice, morphologically resembling those induced by methylcholanthrene or urethane, were propagated in host after host under conditions such that the neoplastic cells were directly exposed, while proliferating, to one or the other of these agents. The successive periods of test lasted for more than a year in some instances, the total exposure to the carcinogens far exceeding that required to change normal pulmonary cells into adenoma cells. One of the adenomas remained unaltered, and the others underwent cancerous changes; but these took place with equal frequency in the control growths, and their occurrence was neither hastened nor delayed by the carcinogens. Two polymorphous mammary carcinomas of "milk-factor" type, with the characteristic tendency to form acini and tubules, were exposed to methylcholanthrene in the same way as the pulmonary adenomas and for periods quite as long. Their cells continued to differentiate, and in other respects underwent no significant change. Urethane had no influence on the rate of growth of the adenomas exposed to it; methylcholanthrene, on the other hand, markedly retarded the enlargement both of them and of the mammary tumors. Its inhibitory influence was not passed on from cell to cell however; when freed of the carcinogen by further transplantation, the retarded tumors grew as fast as the controls. Furthermore the retardation caused no evident delay in the occurrence of cancerous changes in the adenomas. One of the adenomas was maintained in twelve parallel lines while under test and new tumors arose in nine of them, the earliest appearing more than fifteen months after initial transfer of the growth. Always it was an adenoma solidum, this appearing almost concurrently in eight of the nine lines. In six of them it was soon followed by carcinomas, the sequence of events and the morphological findings both indicating that they had derived from it. Individually the cancers were widely various, but they were similar on the whole from line to line. Carcinomas of a wholly different aspect arose from the other adenoma undergoing cancerous change, and they were not preceded by adenoma solidum. In both instances the character of the superimposed neoplastic alterations seemed to have been determined by some inherent trait of the adenoma concerned.


Long-Term Outcomes in Survivors of Childhood Cancer: A 30-Year Experience From India.
Despite an increasing number of survivors of childhood cancer (CCS) in low- and middle-income countries, survivorship care is in its nascent stages. We describe the spectrum of late effects seen, challenges faced, and lessons learnt over three decades of a late effects program in India. We describe the demographics and profile of late effects of all CCS survivors enrolled in our After Completion of Treatment Clinic from February 5, 1991 (inception) to February 4, 2021. We analyzed the trends by the decade of diagnosis. There were 3,067 CCS survivors, the median age was 18 years (range, 3-57 years), and the median follow-up was 11 years (range, 2-46 years). Two thirds (62.4%) had either no or mild late effects, 480 (15.6%), 497 (16.2%), and 162 (5.3%) had grades 2, 3, and 4 late effects, with 67 deaths reported. Notable late effects were chronic viral hepatitis (7.8%), thyroid dysfunction (7.5%), other endocrine issues (13.6%), psychosocial issues (57%), neurocognitive impairment (4.1%), and metabolic syndrome (4%). The cumulative incidence and severity of late effects showed a consistent decline by the decade of diagnosis. Twenty-two percent of survivors are lost to follow-up. Survivors of childhood cancer treated on contemporary treatment protocols have a significantly lower side-effect profile. Attrition to long-term follow-up and psychosocial issues are significant concerns. Understanding the unique spectrum of late effects and establishing a holistic support system go a long way in ensuring the long-term physical and mental health and psychosocial concerns of childhood cancer survivors in low- and middle-income countries.


Low-Gradient Severe Mitral Stenosis: Hemodynamic Profiles, Clinical Characteristics, and Outcomes.
Background Optimal management of patients with severe mitral stenosis ( MS ) and low transmitral gradient is incompletely understood. Methods and Results We examined 101 consecutive patients with severe rheumatic MS (mitral valve area ≤1.5 cm2) who underwent balloon valvuloplasty. Low gradient was defined as mean transmitral gradient <10 mm Hg and low flow as stroke volume index ≤35 mL/m2 by echocardiography. Symptoms and mortality data were collected. Systolic, diastolic, and arterial function were characterized by measuring left ventricular (LV) end-systolic elastance, LV stiffness constant (β), diastolic capacitance (predicted LV end-diastolic volume at a common LV filling pressure of 30 mm Hg), and effective arterial elastance. Low gradient (<10 mm Hg) was present in 55 patients, including low flow/low gradient in 11 and normal flow/low gradient in 44 patients, and high gradient was present in 46 patients. Participants with low-flow/low-gradient (LG) MS were older with higher rates of atrial fibrillation (64%) and subvalvular thickening, higher afterload, and decreased LV compliance with lower ejection fraction (57±10% versus 65±4% versus 63±6%, P=0.002) but similar end-systolic elastance compared with patients with normal-flow/ LG and high-gradient MS . The normal-flow/ LG group had larger mitral valve area and lower left atrial pressure by catheterization, as well as favorable long-term outcomes compared with the low-flow/ LG and high-gradient MS group. A total of 40% of patients with LG MS had no symptomatic benefit from valvuloplasty compared with 18% of patients with high-gradient MS ( P=0.02). Conclusions Presence of low gradient in patients with severe MS was associated with lesser symptomatic benefit from valvuloplasty. In the subset with low stroke volume index, this may be related to independent ventricular-vascular uncoupling, decreased LV compliance, and high prevalence of atrial fibrillation in addition to intrinsic MS .


Microperimetry in age-related macular degeneration: association with macular morphology assessed by optical coherence tomography.
Microperimetry is a technique that is increasingly used to assess visual function in age-related macular degeneration (AMD). In this study, we aimed to evaluate the relationship between retinal sensitivity measured with macular integrity assessment (MAIA) microperimetry and optical coherence tomography (OCT)-based macular morphology in AMD. Prospective, cross-sectional study. All participants were imaged with colour fundus photographs used for AMD staging (Age-Related Eye Disease Study scale), spectral-domain OCT (Spectralis, Heidelberg, Germany) and swept-source OCT (Topcon, Japan). Threshold retinal sensitivity of the central 10° diameter circle was assessed with the full-threshold, 37-point protocol of the MAIA microperimetry device (Centervue, Italy). Univariable and multivariable multilevel mixed-effect linear regression models were used for analysis. We included 102 eyes with AMD and 46 control eyes. Multivariable analysis revealed that older age (p<0.0001), advanced AMD stage (p<0.0001) and reduced retinal thickness (p<0.0001) were associated with decreased mean retinal sensitivity. No associations were found between choroidal thickness and retinal sensitivity within the macula. Within the 10° diameter circle of the macula, the presence of ellipsoid disruption, subretinal fluid, atrophy and fibrosis, and outer retinal tubulation on OCT images was also associated with decreased retinal sensitivity (all p<0.05). There is an association between TRS as determined by MAIA microperimetry and several OCT structural parameters across various stages of AMD. This study highlights the relevance of microperimetry as a functional outcome measure for AMD.


End-to-End Fovea Localisation in Colour Fundus Images With a Hierarchical Deep Regression Network.
Accurately locating the fovea is a prerequisite for developing computer aided diagnosis (CAD) of retinal diseases. In colour fundus images of the retina, the fovea is a fuzzy region lacking prominent visual features and this makes it difficult to directly locate the fovea. While traditional methods rely on explicitly extracting image features from the surrounding structures such as the optic disc and various vessels to infer the position of the fovea, deep learning based regression technique can implicitly model the relation between the fovea and other nearby anatomical structures to determine the location of the fovea in an end-to-end fashion. Although promising, using deep learning for fovea localisation also has many unsolved challenges. In this paper, we present a new end-to-end fovea localisation method based on a hierarchical coarse-to-fine deep regression neural network. The innovative features of the new method include a multi-scale feature fusion technique and a self-attention technique to exploit location, semantic, and contextual information in an integrated framework, a multi-field-of-view (multi-FOV) feature fusion technique for context-aware feature learning and a Gaussian-shift-cropping method for augmenting effective training data. We present extensive experimental results on two public databases and show that our new method achieved state-of-the-art performances. We also present a comprehensive ablation study and analysis to demonstrate the technical soundness and effectiveness of the overall framework and its various constituent components.


Regional antibiotic prophylaxis in elbow surgery.
In this study we describe a technique for the delivery of regional antibiotic prophylaxis in patients undergoing elbow surgery and compare tissue antibiotic concentrations achieved by this technique with those achieved by standard systemic intravenous prophylaxis. We collected bone and fat samples from patients undergoing elective elbow surgery who had received regional antibiotic prophylaxis and measured the tissue antibiotic concentration. For comparison, we measured the antibiotic concentration in bone and fat samples taken from patients undergoing elective shoulder surgery who had received systemic prophylaxis. Mean tissue antibiotic concentrations were significantly higher in the regional antibiotic group (bone, 1484 microg/g vs 35.8 microg/g; fat, 1422.7 microg/g vs 10.7 microg/g; P <.05). No adverse effects were encountered with regional antibiotic delivery. The delivery of regional antibiotic prophylaxis in elbow surgery achieves higher tissue antibiotic concentrations than those achieved with standard systemic delivery. This technique may help reduce the risk of perioperative infection in elbow surgery.


Clinical performance of the (1,3)-β-D-glucan assay in early diagnosis of nosocomial Candida bloodstream infections.
Microbiological diagnosis of nosocomial candidemia is negatively affected by suboptimal culture yield. Alternative methods are not fully reliable as an aid in candidemia diagnosis. Recently, the detection of (1,3)-β-D-glucan (BG) has been shown to be very promising in this setting. We carried out a prospective study on the clinical usefulness of BG detection in early diagnosis of candidemia. BG detection was performed in patients with fever unresponsive to antibacterial agents and risk factors for candidemia. BG detection was done with the Fungitell test. A total of 152 patients were included in the study; 53 were proven to have candidemia, while in 52 patients candidemia was excluded on microbiological and clinical bases. The remaining 47 patients were considered to have possible candidemia. In summary, 41 of 53 candidemia patients (77.3%), 9 of 52 patients without candidemia (17.3%), and 38 of 47 patients with possible candidemia (80.8%) were positive in the BG assay. With these results, the sensitivity and the specificity of the assay were 77% and 83%, respectively. BG levels of >160 pg/ml were highly predictive of candidemia. In 36 of 41 patients with candidemia and positive BG testing, the BG assay was performed within 48 h from when the first Candida-positive blood sample for culture was drawn, thus allowing a possible earlier start of antifungal therapy. Based on these results, the BG assay may be used as an aid in the diagnosis of nosocomial candidemia. The timing of assay performance is critical for collecting clinically useful information. However, the test results should be associated with clinical data.


Variables controlling the secretion of a somatomedin-like peptide by cultured porcine smooth muscle cells.
Somatomedin-C, a peptide growth factor that is also termed insulin-like growth factor I, stimulates smooth muscle cell replication; however, these cells proliferate in somatomedin-C-deficient medium. We postulated, therefore, that these cells might release a somatomedin-like molecule into the surrounding culture medium. Porcine aortic smooth muscle cells that were exposed to serum-free Dulbecco's modified minimum essential medium for 24 hours were found to release a somatomedin-like molecule that could be detected by a specific radioimmunoassay for somatomedin-C. Several variables in the design of tissue culture conditions were found to regulate the secretion of the somatomedin-like peptide. There was an inverse relationship between somatomedin-like peptide secretion and culture density. Cultures grown to a density of 110,000 cells/well secreted 0.18 +/- 0.02 U/ml per 10(5) cells, whereas cultures grown to 38,000 cells/well secreted 0.59 +/- 0.06 U/ml per 10(5) cells (P less than 0.001). Serum deprivation and days of preincubation before initiation of an experiment were found to influence somatomedin-like peptide secretion significantly. Platelet-derived growth factor, which stimulates smooth muscle cell replication, was a potent stimulant of somatomedin-like peptide secretion. Exposure to a concentration of 500 ng/ml platelet-derived growth factor induced a 2.8-fold increase in somatomedin-like peptide secretion over basal levels, (i.e., 0.37 +/- 0.05 to 0.98 +/- 0.7 U/ml, P less than 0.001). The effect of platelet-derived growth factor was enhanced (41% increase) by concomitant incubation with 1% somatomedin-C-deficient platelet poor plasma.(ABSTRACT TRUNCATED AT 250 WORDS)


Reducing Unnecessary Acid Suppression Use in Hospitalized Patients: A Description of Targeted Strategies Implemented Across a Large Health System.
Ensuring the appropriate use of proton pump inhibitors (PPIs) and histamine type 2-receptor antagonists (H2RAs) is an important hospital patient safety and quality initiative because therapy may be inappropriately continued during transitions of care. In this article, we aim to describe the impact of targeted quality improvement strategies to reduce unnecessary acid suppression use in hospitalized patients across a large health system. Beginning January 1, 2018, focused quality improvement strategies to prevent unnecessary initiation and continuation of proton pump inhibitors (PPIs) and histamine type 2-receptor antagonists (H2RAs) were implemented throughout a large health system. Targeted strategies were initially tested as part of the PPI deprescribing Institute for Healthcare Improvement (IHI) International Innovators Network initiative and were expanded to include H2RAs for hospitalized patients. Strategies to decrease PPIs and H2RAs during hospitalization included standardization of stress ulcer prophylaxis care pathways, evidence-based order set modifications, technology-driven support, and clinical pharmacy metric performance to goal. PPI/H2RA days of therapy (DOT) per 1000 patient days were measured from the first quarter (1Q) of 2017 to the fourth quarter (4Q) of 2021 to determine if implemented strategies resulted in improvement. After quality improvement strategies were implemented, the number of PPI/H2RA DOT was reduced by 7.9 days per 1000 patient days each quarter over 4 years. The average PPI/H2RA DOT per 1000 patient days decreased from 592 (1Q 2017) to 439 (4Q 2021). In the fourth quarter of 2018, 45 hospitals (28%) achieved a 10% reduction in combined PPI/H2RA DOT per 1000 patient days, and 121 hospitals (97%) attained the goal of greater than 25% of eligible patients deprescribed PPI/H2RA for ICU patients in the fourth quarter of 2019. In the fourth quarter of 2020, 97 hospitals (87%) met the metric of 40% or more of eligible patients deprescribed from PPI/H2RA in or after an ICU stay, and 85 hospitals (87%) reached 50% or more of eligible patients deprescribed PPI/H2RA in or after an ICU stay in 4Q2021. Targeted quality improvement strategies decreased unnecessary PPI and H2RA use for a large health system over 4 years. Continually evaluating measured results along with establishing a new clinical pharmacy metric goal each year to encourage further improvement contributed to deprescribing success.


Estimates of absorbed energy in trabecular bone due to beta-particles or electrons.
A computer code, DAB-BE, has been written which can be used to calculate the absorbed energies of beta particles or electrons deposited inside human trabecular bone. The radiation source geometry can be either uniformly distributed in the whole bone or located at a fixed point inside the bone. Bremsstrahlung effects are not considered in these calculations. Results are presented and discussed for six monoenergetic sources of electrons distributed uniformly in a mathematical representation of the arm. In addition, a fixed point source configuration of 1.0 MeV monoenergetic electrons was studied.


Epidemiology of secondary fluid bolus therapy for infection-associated hypotension.
Fluid bolus therapy (FBT) is a common therapy for hypotensive sepsis, but no studies have compared primary FBT (in the first 6 hours after presentation to the emergency department [ED]) with secondary FBT (6-24 hours after presentation to the ED). We aimed to describe the patterns of use, physiological sequelae and outcomes of patients with hypotensive sepsis who were treated with primary FBT or combined primary and secondary FBT (secondary FBT). A retrospective observational study of patients with hypotensive sepsis presenting to the ED of a tertiary hospital from 1 January to 31 December 2010. We studied 100 consecutive eligible patients (primary FBT, n = 52; secondary FBT, n = 48). Secondary FBT occurred in the ward (n = 31) or in the intensive care unit (n = 17). More patients receiving secondary FBT had sepsis with undefined focus or septic shock (P = 0.005, P = 0.0001, respectively), and fewer patients receiving secondary FBT had pneumonia (P = 0.0004). At 24 hours, the use of secondary FBT was similar for patients admitted to the ward and the ICU, and represented about 40% of all secondary fluids given. The volume of any bolus was greater during primary resuscitation, and the size of physiological changes associated with FBT diminished with time. The mortality rate at 28 days was 27%, and was similar for ward and ICU admissions. Secondary FBT is given to about half of patients presenting with hypotensive sepsis, takes place in wards more often than in the ICU and delivers a significant proportion of overall fluids, but is associated with limited changes in measured physiological variables.


Interaction between melatonin and estradiol on morphological and morphometric features of MCF-7 human breast cancer cells.
Melatonin has been shown to have a direct inhibitory effect on the proliferation of estrogen-responsive MCF-7 human breast cancer cells, involving an interaction with estradiol. The anti-proliferative effect of melatonin is reversed by the addition of estradiol to the culture. In the present study, we examined whether inhibition by melatonin and subsequent estrogen rescue of MCF-7 cells are correlated with morphological and morphometric changes in these cells. After 4 days of exposure to melatonin, MCF-7 cells showed significantly smaller cell and nuclear sizes than other groups. These morphometric results were closely related to the ultrastructural features observed in these cells. While control and estradiol-treated cells showed increased tumor characteristics, melatonin-treated cells presented greater differentiation, in keeping with their epithelial origin (presence of cytokeratin filament bundles, conspicuous rough endoplasmic reticulum, and Golgi cisternae together with the presence of prominent nucleoli at the nuclear level). Additionally, some melatonin-treated cells displayed degenerative features (mitochondrial swelling with disruption of cristae, cytoplasmic vacuolation, nuclear chromatin disgregation and cell lysis). The addition of estradiol to cells previously incubated with melatonin reversed the changes induced by the latter and these cells showed the same ultrastructural features as the control cells. Our results support the notion that melatonin exerts its antitumor effect through a cell-cycle-specific mechanism by delaying the entry of MCF-7 cells into mitosis. This allows the tumor cells to achieve greater differentiation. The fact that the morphometric and morphological effects induced by melatonin are counteracted by estrogens suggests a cell-cycle acceleration induced by estradiol.


[Mechanical stresses as factors in the autoregulation of morphogenesis].
Since morphogenetic processes are nonlinear, feedback must be essential for their regulation. Two concepts of feedback in morphogenesis are developed: 1) inhibition by diffusing morphogenetic substances and 2) action of mechanical strain resulting from morphogenetic movements. The data on the role of mechanical strain in formation of integral structure of embryonic tissues, primary demarcation of embryonic epithelia and mesenchymal rudiments and bending of epithelial layers are presented. Evolutionary aspects of morphogenetic role of mechanical strain and its possible use in applied biotechnology are discussed.


Beyond the early stages: insights from the ASSURE registry on bioresorbable vascular scaffolds.
Bioresorbable vascular scaffolds (BVS) have been available on the European market since November 2011. The ASSURE registry aims to investigate the safety and efficacy of the Absorb everolimus-eluting bioresorbable vascular scaffold in a real-world setting. Patients with de novo coronary artery disease were consecutively enrolled at six German centres in this prospective registry. Outcomes were procedural success, cardiovascular death, myocardial infarction, and ischaemia-driven target lesion revascularisation (TLR). Angiographic parameters were assessed quantitatively and visual estimates of lesion dimensions were studied. One hundred and eighty-three patients were treated. In 128 (64.7%) lesions a complex ACC/AHA morphology was present. Procedural success was achieved in all patients. Acute gain was 1.54±0.51 mm, resulting in a final minimal lumen diameter (MLD), which met the baseline reference vessel diameter (RVD), although visual estimates overrated the RVD by 0.5±0.5 mm. Up to 12 months, one patient (0.5%) had died from gastrointestinal bleeding, three (1.7%) non-target vessel myocardial infarctions occurred, and five (2.8%) TLR had become necessary because of restenosis. One-year results suggest that bioresorbable vascular scaffolds for de novo coronary artery disease are associated with favourable clinical and functional outcomes in routine clinical practice despite a visually overestimated RVD.


Identification of a muropeptide precursor transporter from gut microbiota and its role in preventing intestinal inflammation.
The gut microbiota is a considerable source of biologically active compounds that can promote intestinal homeostasis and improve immune responses. Here, we used large expression libraries of cloned metagenomic DNA to identify compounds able to sustain an anti-inflammatory reaction on host cells. Starting with a screen for NF-κB activation, we have identified overlapping clones harbouring a heterodimeric ATP-binding cassette (ABC)-transporter from a Firmicutes. Extensive purification of the clone's supernatant demonstrates that the ABC-transporter allows for the efficient extracellular accumulation of three muropeptide precursor, with anti-inflammatory properties. They induce IL-10 secretion from human monocyte-derived dendritic cells and proved effective in reducing AIEC LF82 epithelial damage and IL-8 secretion in human intestinal resections. In addition, treatment with supernatants containing the muropeptide precursor reduces body weight loss and improves histological parameters in Dextran Sulfate Sodium (DSS)-treated mice. Until now, the source of peptidoglycan fragments was shown to come from the natural turnover of the peptidoglycan layer by endogenous peptidoglycan hydrolases. This is a report showing an ABC-transporter as a natural source of secreted muropeptide precursor and as an indirect player in epithelial barrier strengthening. The mechanism described here might represent an important component of the host immune homeostasis.


Olfactory Stimulation Successfully Improves Swallowing Function of Aged Rats Through Activating Central Neuronal Networks and Downstream DHPR-RyR-mediated Neuromuscular Activities.
Presbyphagia is age-related changes in swallowing function, which imposes a high risk of aspiration in older adults. Considering olfactory stimulation (OS) can influence behavioral activities by modulating neuronal excitability, the present study aims to determine whether OS could improve the swallowing function of aged rats through activating the central neuronal networks and downstream muscular activities participated in the control of swallowing. Aged male Wistar rats received OS by inhaling a mixture of plant-based volatile molecules twice a day for 12 days were subjected to functional magnetic resonance imaging (fMRI) and c-fos, choline acetyltransferase (ChAT) immunostaining to detect the neuronal activities of the orbitofrontal cortex (OFC) and medullary nuclei engaged in swallowing control, respectively. The functional effects of OS on downstream pharyngeal muscle activity were examined by evaluating the dihydropyridine receptor-ryanodine receptor (DHPR-RyR)-mediated intramuscular Ca2+ expression, and analyzing the amplitude/frequency of muscle contraction, respectively. In untreated rats, only moderate signal of fMRI and mild c-fos/ChAT expression was detected in the OFC and medullary nuclei, respectively. However, following OS, intense signals of fMRI and immunostaining were clearly expressed in the orbitofronto-medullary networks. Functional data corresponded well with above findings in which OS significantly enhanced DHPR-RyR-mediated intramuscular Ca2+ expression, effectively facilitated a larger amplitude of pharyngeal muscle contraction, and exhibited better performance in consuming larger amounts of daily dietary. As OS successfully activates the neuromuscular activities participated in the control of swallowing, applying OS may serve as an effective, easy, and safe strategy to greatly improve the swallow function of aging populations.


Plasma vitamin B12 level as a potential cofactor in studies of human immunodeficiency virus type 1-related cognitive changes.
Studies of cognitive function in subjects with human immunodeficiency virus type 1 (HIV-1) infection who remain relatively asymptomatic (ie, Centers for Disease Control stages II and III) have provided widely variable estimates of cognitive impairment. In view of the finding that approximately 25% of asymptomatic HIV-1-infected subjects demonstrate either marginal or overt vitamin B12 deficiency, we have investigated plasma vitamin B12 status as a potential cofactor in studies of HIV-1-related cognitive impairment. When cognition was assessed in asymptomatic (Centers for Disease Control stages II and III) HIV-1-infected participants taking into consideration vitamin B12 status, those subjects with low plasma vitamin B12 levels (less than 180 pmol/L) performed more poorly than did those with normal (greater than or equal to 180 pmol/L) vitamin B12 status on specific measures of information processing speed and visuospatial problem-solving skills. These findings suggest that concurrent vitamin B12 deficiency may be a cofactor in subtle cognitive changes observed in the asymptomatic stages of HIV-1 infection. These differences in prevalence of low plasma vitamin B12 levels may help to explain differences among studies in the proportion of HIV-1-infected subjects showing cognitive impairment.


The role of music in the lives of older adults with dementia ageing in place: A scoping review.
The number of people around the world living with dementia is predicted to rise from 44 million to 135 million by 2050. Traditional treatments for dementia have been largely unsuccessful and prompted the emergence of alternative strategies. Music is emerging as an effective therapeutic strategy for older adults with dementia however, most of the work to date has focused on institutions. The purpose of this scoping review was to summarize what is known about the role and impact that music plays in the lives of community-dwelling older adults with dementia. Using a five-stage framework for conducting a scoping review, analysis revealed three ways in which music influences the lives of community-dwelling older adults with dementia: (a) reduced agitation, (b) improved cognition, and (c) enhanced social well-being. The concept of personhood provided a lens with which to conceptualize the findings and highlights the need for continued research.