Effect of nonsurgical periodontal therapy. II. Severely advanced periodontitis.
Healing events following nonsurgical periodontal therapy in patients with periodontal pockets up to 12 mm deep were investigated. Incisors, cuspids and premolars in 16 patients were treated by plaque control and supra- and subgingival debridement using hand or ultrasonic instruments in a split mouth approach. The results were evaluated by recording of plaque scores, bleeding on probing, probing pocket depths and probing attachment levels. Minimal change in gingival conditions occurred during the initial 3 months of experimentation, which were utilized for plaque control measures alone. Subsequent to instrumentation and during the following 9-month period, a gradual and marked improvement of periodontal conditions took place. During the remaining 12 months of the 24-month experimental period no further changes of the recorded parameters were noted. No differences in results could be observed when comparing hand versus ultrasonic instrumentation, or when comparing the results of 2 different operators. Initially, a total of 305 sites demonstrated probing pocket depths greater than or equal to 7 mm. At the 24-month examination 43 such sites remained. The results indicate that there is no certain magnitude of initial probing pocket depth where nonsurgical periodontal therapy is no longer effective.


Demonstration of Actinomyces and Arachnia species in cervicovaginal smears by direct staining with species-specific fluorescent-antibody conjugate.
For direct observation of microaerophilic actinomycetes by fluorescent antibody, a procedure was developed in which pepsin treatment and rhodamine conjugate of normal serum were used to reduce nonspecific staining in cervicovaginal smears. Actinomyces israelii, Actinomyces naeslundii, and Arachnia propionica were observed in cervicovaginal smears from women who did use and who did not use an intrauterine contraceptive device. A. israelii was found more commonly in women with an intrauterine contraceptive device, but no evidence was obtained that the use of an intrauterine contraceptive device influenced the presence of either A. propionica or A. naeslundii.


Immune dysregulation in amyotrophic lateral sclerosis: mechanisms and emerging therapies.
Neuroinflammation is a common pathological feature of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), and is characterised by activated CNS microglia and astroglia, proinflammatory peripheral lymphocytes, and macrophages. Data from clinical studies show that multiple genetic mutations linked to ALS (eg, mutations in SOD1, TARDBP, and C9orf72) enhance this neuroinflammation, which provides compelling evidence for immune dysregulation in the pathogenesis of ALS. Transgenic rodent models expressing these mutations induce an ALS-like disease with accompanying inflammatory responses, confirming the immune system's involvement in disease progression. Even in the absence of known genetic alterations, immune dysregulation has been shown to lead to dysfunctional regulatory T lymphocytes and increased proinflammatory macrophages in clinical studies. Therefore, an improved understanding of the biological processes that induce this immune dysregulation will help to identify therapeutic strategies that circumvent or ameliorate the pathogenesis of ALS. Emerging cell-based therapies hold the promise of accomplishing this goal and, therefore, improving quality of life and extending survival in patients with ALS.


Asymmetric second-stage concentrators.
Given a linear (2-D) primary optical concentrator and a convex close surface of any shape and location (within known limits) underneath, an ideal second-stage reflective element that redirects the primary radiation onto a section of that surface may be designed. A useful application is to asymmetric two-stage concentrators for solar energy, the primary of which is not shaded from the illuminating source by the secondary.


The terrible twos: How children cope with frustration and tantrums and the effect of maternal and paternal behaviors.
Experimental Frustration Procedures with 158 children (15-39 months) of two-parent families were conducted, with each parent separately involved. We examined diverse characteristics of children's frustration and focused on specific behaviors of how children coped and parents supported them. In addition, external observers measured child attachment security (via Attachment Q Sort) toward the mother and the father during two home visits. Children with high attachment security became frustrated later and for a shorter time, and fathers, as compared to mothers, relieved these frustration patterns and reduced them. Although 22.2% children exhibited intense frustration responses up to tantrums, levels remained unaffected by child gender, but decreased with child age. Time-lag analyses revealed that children's self-comforting behaviors reduced frustration responses only by around 20%, but self-distracting (in younger children) and pretend-playing (in older children) by around 50% and 70%. Of the parent behaviors, demonstrating reduced children's frustration by up to 40% whereas distracting and reframing by around 60% (mothers) and 80% (fathers). In general, mothers tended to protect the child from distress, whereas fathers assisted the child in coping with frustration. However, if mothers soothed and fathers encouraged, children's frustration intensified.


Identification of Drugs in Parenteral Pharmaceutical Preparations from a Quality Assurance and a Diversion Program by Direct Analysis in Real-Time AccuTOFTM-Mass Spectrometry (DART-MS).
In healthcare settings drug diversion and impairment of physicians are major concerns requiring a rapid and efficient method for surveillance and detection. A Direct Analysis in Real Time ion source coupled to a JEOL AccuTOFTM time-of-flight mass spectrometer (DART-MS) method was developed to screen parenteral pharmaceutical formulations for potential drug diversion. Parenteral pharmaceutical formulations are also known as injectable formulations and are used with intravenous, subcutaneous, intramuscular and intra-articular administration. A library was created using the mass spectra data collected by a DART-MS operated in switching mode at 20, 60 and 90 V settings. This library contained 17 commonly encountered drugs in parenteral pharmaceutical formulations that included the surgical analgesic: fentanyl, hydromorphone and morphine; anesthetic: baclofen, bupivacaine, ketamine, midazolam, ropivacaine and succinylcholine; and a mixture of other drug classes: caffeine, clonidine, dexamethasone, ephedrine, heparin, methadone, oxytocin and phenylephrine. Randomly selected 200 de-identified parenteral pharmaceutical formulations containing one or more drugs were submitted for analysis to the FIRM Toxicology Laboratory at Virginia Commonwealth University Health and were screened using the DART-MS. The drug contents of the de-identified formulations were previously confirmed by a published high performance liquid chromatography (HPLC) method. The drugs in the formulations were rapidly and successfully identified using the generated library. The DART-MS and HPLC results were in complete agreement for all 200 parenteral pharmaceutical formulations.


[Transposition of the great arteries: results of treatment in the years 1967--1980 (author's transl)].
To demonstrate how the prognosis for a newborn with transposition of the great arteries (TGA) has improved, the clinical data of 121 children diagnosed between January 1967 and December 1979 were reviewed. 104 patients had an initial balloon atrial septostomy; 34 infants needed palliative operations (resection of ductus or coarctation, banding of the pulmonary artery and aortic-pulmonary anastomosis). Corrective surgery was according to Mustard (43), Senning (7), Rastelli (5) or an anatomic correction (2). 80% of the infants survived the first month of life. 25% died between the first month and corrective surgery. The mortality of the intraatrial switch operations decreased from 28% before 1976 to 12% in the following years. After Mustard's operation cardiac rhythm disturbances occurred in 39.4%, hemodynamic complications in 24,2% of the cases. Neurological complications developed more frequently in children with simple TGA (27.3%) than in children with combined TGA (18.2%). Owing to improvement of conservative and operative treatment the 2-years survival rate increased from 48.5% between 1967--1970 to 62.5% between 1977--1979.


Aeromonas salmonicida Bacteremia Associated with Chronic Well Water Consumption in a Patient with Diabetes.
Aeromonas salmonicida is associated with superficial skin infections in fish. Its virulence factors allow colonization of water including surface water such as salt water, beaches, and fresh water wells. Moreover, it is possible for immunocompromised patients to develop invasive disease after chronic exposure to Aeromonas spp. through contaminated water. While there are reports of Aeromonas spp. bacteremia following water ingestion, there have been no reports of A. salmonicida bacteremia from water consumption. We report the first case of A. salmonicida bacteremia in a patient with diabetes due to chronic consumption of well water.


Rising Events and Improved Outcomes of Gastrointestinal Bleed With Shock in USA: A 12-year National Analysis.
Limited information is available based on single-center studies on trends of incidence and outcomes in gastrointestinal (GI) bleed with shock. We analyzed data from 2002 to 2013 National Inpatient Sample. Using ICD-9 codes we identified 6.4 million hospital discharges of GI bleed from National Inpatient Sample database. Events were analyzed based on type of GI bleed, in-hospital mortality, hemodynamic status, and use of blood products. GI bleed with shock results in higher hospital mortality (20.77% with shock vs. 2.6% without shock). Between 2002 and 2013, there has been an increase in the percentage of upper and lower GI bleed with shock (1.35% to 4.92% and 1.49% to 3.06%) along with a reduction in mortality in both upper GI bleed with shock (26.9% to 13.8%) and lower GI bleed with shock (54.7% to 19.7%). Consistent with the rise in GI bleed with shock was an increase in blood product utilization. Packed red blood cell (pRBC) transfusion was associated with reduction in mortality in both nonvariceal upper GI bleed with shock (18.3% without pRBC vs. 13.9% receiving pRBC) and lower GI bleed with shock (36.05% without pRBC vs. 22.13% receiving pRBC), but did not affect mortality in variceal upper GI bleed with shock (31.79% vs. 32.22%). GI bleed with shock carries a higher mortality and have been steadily increasing from 2002 to 2013. pRBC transfusion was associated in improved mortality in GI bleed with shock except variceal bleed.


Comparison of three solid phase supports for promoting three-dimensional growth and function of human liver cell lines.
An extracorporeal liver support system will require that liver cells maintain their normal differentiated function. This is more likely to be achieved utilizing a three-dimensional culture configuration rather than a simple monolayer culture. We present data on a human liver cell line attached and maintained on different three-dimensional supports, porous glass (Siran), silicon (Immobasil), and calcium-alginate beads. Albumin, fibrinogen, prothrombin, alpha1-acid glycoprotein and alpha1-antitrypsin secretions were measured. Proliferation was slower on each of the three-dimensional supports than on the monolayer culture. The protein secretion of all 5 proteins was highest in cells encapsulated in alginate; silicon beads supported greater protein secretion than glass. Cells on silicon or within alginate were rounded; those on glass grew in 2 configurations as flattened monolayers and as rounded colonies. Cells in alginate secreted as much protein as the whole liver (e.g., albumin, 14.88 g/10(12) cells/day compared to the whole liver, approximately 12 g/day). Three-dimensional culture of a human liver cell line leads to both proliferation and a high synthetic capacity, an important feature of cells suitable for an extracorporeal liver support system.


[Primary hyperthyroidism 1996].
55 prospectively documented patients aged 20-84 (median 67) years (47 women, 8 males) underwent surgery for primary hyperparathyroidism (pHPT). The most frequent symptoms and associated conditions were nephrolithiasis (42%) and neuropsychiatric symptoms (39%). Only one case of asymptomatic and one case of "normocalcemic" pHPT were found in this series. 47 patients (89%) were cured following initial neck exploration, and 3 further patients (6%) were cured by a second operation. Reoperation also led to cure in 2 patients operated on elsewhere in the first instance. 6 patients (11%) had double adenoma (bilaterally) and 36% of the adenomas had an ectopic location, with an intrathyroidal adenoma in 2 cases. In 2 patients sternotomy was carried out. Persistent pHPT was observed in 3 patients (following initial exploration in 2 cases and reoperation in one). These patients had a supernumerary adenomatous gland with ectopic location in 2 cases and a double adenoma with ectopic position of one adenoma in a further case. One 80-year-old patient died post-operatively from intestinal ischemia. 2 patients had permanent postoperative hypoparathyroidism; in no case was a permanent recurrent laryngeal nerve palsy observed. Bilateral parathyroid exploration with thyroid mobilization by capsular dissection is the procedure of choice for pHPT. In 2 patients with the MEN 2A-syndrome and with medullary thyroid carcinoma thyroidectomy, lymphadenectomy and autotransplantation of normal parathyroids to the arm was performed, with normal parathyroid function in both cases.


Effects of cement-curing mode and light-curing unit on the bond durability of ceramic cemented to dentin.
The aim of this study was to evaluate the effects of different light-curing units and resin cement curing types on the bond durability of a feldspathic ceramic bonded to dentin. The crowns of 40 human molars were sectioned, exposing the dentin. Forty ceramic blocks of VITA VM7 were produced according to the manufacturer's recommendations. The ceramic surface was etched with 10% hydrofluoric acid / 60s and silanized. The dentin was treated with 37% phosphoric acid / 15s, and the adhesive was applied. The ceramic blocks were divided and cemented to dentin according to resin cement / RC curing type (dual- and photo-cured), light-curing unit (halogen light / QTH and LED), and storage conditions (dry and storage / 150 days + 12,000 cycles / thermocycling). All blocks were stored in distilled water (37°C / 24h) and sectioned (n = 10): G1 - QTH + RC Photo, G2 - QTH + RC Dual, G3 - LED + RC Photo, G4 - LED + RC Dual. Groups G5, G6, G7, and G8 were obtained exactly as G1 through G4, respectively, and then stored and thermocycled. Microtensile bond strength tests were performed (EMIC), and data were statistically analyzed by ANOVA and Tukey's test (5%). The bond strength values (MPa) were: G1 - 12.95 (6.40)ab; G2 - 12.02 (4.59)ab; G3 - 13.09 (5.62)ab; G4 - 15.96 (6.32)a; G5 - 6.22 (5.90)c; G6 - 9.48 (5.99)bc; G7 - 12.78 (11.30)ab; and G8 - 8.34 (5.98)bc. The same superscript letters indicate no significant differences. Different light-curing units affected the bond strength between ceramic cemented to dentin when the photo-cured cement was used, and only after aging (LED > QTH). There was no difference between the effects of dual- and photo-cured resin-luting agents on the microtensile bond strength of the cement used in this study.


Characterization of a new candidate isotopic reference material for natural Pb using primary measurement method.
A lead isotopic standard solution with natural abundance has been developed by applying a mixture of a solution of enriched 208Pb and a solution of enriched 204Pb (208Pb-204Pb double spike solution) as bracketing method. The amount-of-substance ratio of 208Pb:204Pb in this solution is accurately measured by applying EDTA titrimetry, which is one of the primary measurement methods, to each enriched Pb isotope solution. Also metal impurities affecting EDTA titration and minor lead isotopes contained in each enriched Pb isotope solution are quantified by ICP-SF-MS. The amount-of-substance ratio of 208Pb:204Pb in the 208Pb-204Pb double spike solution is 0.961959 ± 0.000056 (combined standard uncertainty; k = 1). Both the measurement of lead isotope ratios in a candidate isotopic standard solution and the correction of mass discrimination in MC-ICP-MS are carried out by coupling of a bracketing method with the 208Pb-204Pb double spike solution and a thallium internal addition method, where thallium solution is added to the standard and the sample. The measured lead isotope ratios and their expanded uncertainties (k = 2) in the candidate isotopic standard solution are 18.0900 ± 0.0046 for 206Pb:204Pb, 15.6278 ± 0.0036 for 207Pb:204Pb, 38.0626 ± 0.0089 for 208Pb:204Pb, 2.104406 ± 0.00013 for 208Pb:206Pb, and 0.863888 ± 0.000036 for 207Pb:206Pb. The expanded uncertainties are about one half of the stated uncertainty for NIST SRM 981, for 208Pb:204Pb, 207Pb:204Pb and 206Pb:204Pb, or one eighth, for 208Pb:206Pb and 207Pb:206Pb, The combined uncertainty consists of the uncertainties due to lead isotope ratio measurements and the remaining time-drift effect of mass discrimination in MC-ICP-MS, which is not removed by the coupled correction method. In the measurement of 208Pb:204Pb, 207Pb:204Pb and 206Pb:204Pb, the latter contribution is two or three times larger than the former. When the coupling of a bracketing method with the 208Pb-204Pb double spike solution and a thallium internal addition method is applied to the analysis of NIST SRM 981, the measured lead isotope ratios are in good agreement with its certified values. This proves that the developed method is not only consistent with the conventional one by NIST SRM 981 but also enables measurement of the lead isotope ratios with higher precision.


Antifungal In Vitro Activity of Pilosulin- and Ponericin-Like Peptides from the Giant Ant Dinoponera quadriceps and Synergistic Effects with Antimycotic Drugs.
Venoms from ants comprise a rich source of bioactive peptides, including antimicrobial peptides. From the proteome and peptidome of the giant ant Dinoponera quadriceps venom, members of five known classes of antimicrobial peptides were disclosed (e.g., dermaseptin-, defensin-, ICK-, pilosulin- and ponericin-like types). Based on comparative analysis, these family members have structural determinants that indicate they could display antimicrobial activities. In previous works, pilosulin- and ponericin-like peptides were demonstrated to be active against bacteria, fungi, and parasites. Herein, the antifungal activity of ponericin- and pilosulin-like peptides were assessed, aiming at the expansion of the knowledge about AMPs in predatory ants and the development of new microbicide strategies to deal with difficult-to-treat fungal infections. Synthetic pilosulin- (Dq-2562, Dq-1503, and Dq-1319) and ponericin-like (Dq-3162) peptides were evaluated for their fungicide and fungistatic activities against different species of Candida, including a drug-resistant clinical strain. The MICs and MLCs were determined for all peptides individually and in combination with general antifungal drugs by the microdilution method. The time-kill kinetic curves were set up by means of a luminescent reagent, of which the light signal is proportional to the number of viable cells. The candicidal synergism observed by the combination of subinhibitory concentrations of peptides and general antimycotic drugs were quantified by the checkerboard test and fluorescent dye permeation assay. The influence of ergosterol on the antifungal activity was verified by supplementation of culture medium. The pilosulin- (Dq-2562 and Dq-1503) and ponericin-like (Dq-3162) were the most active peptides, displaying a broad spectrum of antifungal activity in vitro, with MICs in the range of 0.625 to 10 µM. The combination of peptides and conventional antimycotic drugs displayed a synergistic reduction in the MIC values of individual peptides and drugs, while soluble ergosterol in the culture medium increased the MICs. The fungicide and fungistatic activity of the individual peptides and peptides in combination with antimycotics were time-dependent with a rapid onset of action and long-lasting effect, which involved membrane disruption as an underlying mechanism of their action. Altogether, pilosulin- and ponericin-like peptides from the giant ant D. quadriceps venom display a broad-spectrum of candicidal activity, what allows their inclusion in the row of the antifungal peptides and gives support for further studies on the development of strategies to fight candidiasis.


The role of positive information provision in open-label placebo effects.
Open label placebos (OLPs) appear generally efficacious among clinical samples, but the empirical evidence regarding their use in non-clinical and sub-clinical samples, as well as when administered independent of a convincing rationale, is mixed. Healthy participants (N = 102) were randomised to either a 6-day course of OLP pills with information provision (OLP-plus: N = 35), without information provision (OLP-only: N = 35), or no-treatment control group (N = 32). OLP pills were described as enhancing physical (symptoms and sleep) and psychological (positive and negative emotional) well-being. Well-being was assessed at baseline and on Day 6. Expectancies and adherence were measured. OLP administration interacted with baseline well-being. The OLP-plus group demonstrated increased well-being on all outcomes other than positive emotions, but only when they reported decreased baseline well-being. OLP-only and control groups did not differ. The OLP-plus group demonstrated elevated expectancies, that mediated the OLP effect on physical symptoms relative to control, but only when well-being was lower than average at baseline (i.e. moderated-mediation). Results demonstrate the importance of information provided with OLPs. The moderating effect of baseline outcomes may reconcile inconsistent results regarding clinical and non-clinical samples. Accounting for baseline symptoms in non-clinical and sub-clinical samples is likely to enhance our understanding of when OLPs are effective.


Arterial injuries from femoral artery cannulation with port access cardiac surgery.
Although minimally invasive (MI) cardiac surgery reduces blood loss, hospital stay, and recovery time, some MI approaches require femoral arterial cannulation, which introduces a heretofore unknown risk of femoral arterial injury. This study was performed to examine the risk of femoral arterial injury after Port Access MI cardiac surgery (PA-MICS) with femoral cannulation. Data were prospectively obtained on 739 consecutive patients who had PA-MICS with femoral cannulation between June 1996 and April 2000, identifying any patient with new (<30 days postoperative) arterial insufficiency from the cannulation site. Patient characteristics (gender, age, height, weight, body surface area, smoking, peripheral vascular disease, diabetes) and operative variables (cannula size, cross-clamp time) were examined with univariate and multivariate analysis to identify risk factors for arterial injury. Injuries were defined and classified by radiologic and intraoperative assessment, and follow-up was obtained by patient examination and from the medical records. Femoral arterial occlusion (FAC) occurred in 0.68% (5/739) of patients (4 women, 1 man; age range 26-74 years). The risk of femoral injury was higher in women: 1.31% vs 0.23% (p = 0.07). One patient had intraoperative limb ischemia from iliofemoral dissection and was treated by axillopopliteal bypass. Four patients presented postoperatively with claudication. Three of these had iliofemoral arterial occlusion or localized iliofemoral dissection and were treated with iliofemoral bypass, and 1 patient had localized femoral artery stenosis treated by angioplasty. With a mean follow-up of 17.8 months (range 13-26 months) limb salvage was achieved in all patients. Secondary or tertiary interventions were required in 40% (2/5), both in patients with iliofemoral occlusion, and 1 patient (20% of femoral injuries, 0.135% of overall series) has chronic graft occlusion and long-term claudication. The risk of arterial injury after femoral arterial cannulation and perfusion for Port Access surgery was low (0.68%). This risk is increased in women and is unpredictable. Initial vascular repair has a significant failure rate, and secondary interventions are often necessary. Although the femoral cannulation and perfusion technique is safe overall, the risk must be clearly recognized.


Cranial Nerve Palsies in the Setting of Arachnoid Cysts: A Case Series and Literature Review.
Arachnoid cysts (ACs) are benign lesions typically believed to not cause neurologic defects in the adult population and are most often found incidentally on imaging. We describe 2 patients with ACs potentially leading to isolated cranial nerve (CN) dysfunction. We describe 2 patients, 1 with a fourth nerve palsy and the other with a sixth nerve palsy found to have ACs on MRI brain imaging in locations that potentially caused a compressive CN palsy. We review previous literature of ACs presenting with CN III, IV, or VI palsy. Patient 1 was a 62-year-old man who presented with a 22-year history of diplopia with strabismus examination consistent with a congenital CN IV palsy. Despite multiple surgeries, his CN IV palsy insidiously worsened. An AC in the posterior fossa with mass effect on the quadrigeminal plate and asymmetric atrophy of the right superior oblique was identified on imaging. Patient 2 was an 80-year-old man who presented with an 18-year history of diplopia and was found to have a left esotropia and abduction deficit consistent with complete CN VI palsy. An AC in the left cavernous sinus was identified on imaging. He underwent strabismus surgery with satisfactory resolution of diplopia. We identified a total of 18 previously published cases: 8 reports of CN III palsy, 4 reports of CN IV palsy, and 6 reports of CN VI palsy. Patient ages ranged from 1 to 67 with a median of 34.5. In 16/18 (89%) cases, the diagnosis of ACs was made within 1 year of symptom onset. Surgical removal of the AC was successful in resolving diplopia in 7/12 (58%) cases. In no case was strabismus surgery performed as primary treatment. Although ACs are typically congenital asymptomatic lesions, we present a case series of 2 patients with ACs in anatomic locations that potentially caused chronic, progressive, isolated CN palsies leading to strabismus. Our literature review revealed that most published cases detailing this clinical scenario resulted in neurosurgical fenestration of ACs with mixed results. Our cases represent 2 patients with AC-associated CN palsy treated with strabismus surgery.


Health risks from occupational exposures to mechanical vibration.
Health effects of occupational exposure to hand-transmitted vibration (HTV) and whole-body vibration (WBV) are reviewed. Excessive exposure to HTV from powered processes or tools is associated with an increased occurrence of symptoms and signs of disorders in the vascular, neurological and musculoskeletal systems of the upper limbs. This complex set of disorders is called hand-arm vibration syndrome. Long-term occupational exposure to intense WBV is associated with an increased risk for disorders of the lumbar spine and the connected nervous system. With a lower probability, the neck-shoulder, the gastrointestinal system, the female reproductive organs, the peripheral veins, and the cochleo-vestibular system are also assumed to be affected by WBV. However, there is weak epidemiological support for WBV-induced disorders of organ systems other than the lower back. In addition to the health effects of human vibration, this review provides information on methods for the protection and health surveillance of vibration-exposed workers according to the European Directive 2002/44/EC on mechanical vibration.


[Puvatherapy and systemic lupus erythematosus].
An unusual case characterized by autoimmune hemolytic anemia, fever, polyarthralgias, was developed after PUVAtherapy. Investigation revealed ESR accelerated, complement consumption, diminished levels of C4 and C3, high levels of ANA were detected. In recent years, lupus erythematosus like syndrome was related with photosensitivity provoked by PUVA-therapy. Long-wave ultraviolet light was consider a precipitating factor in the development of autoimmune phenomena. On the contrary, in other researches suggests that PUVA induced alterations are not antigenic this discrepancy remains to be clarified. However this iatrogenic risk must be avoided with a clinical and serological controls.


Postprandial platelet activation is related to postprandial plasma insulin rather than glucose in patients with type 2 diabetes.
Postprandial hyperglycemia is associated with platelet activation. We thus investigated if meal-induced platelet activation could be attenuated by meal insulin. A randomized, double-blind, cross-over study was performed to compare postprandial platelet activation after premeal injections of placebo or insulin aspart (0.1 and 0.2 units/kg) in 18 patients with type 2 diabetes mellitus (T2DM). Platelet activation was assessed by flow cytometry, without and with stimulation by the thromboxane analog U46619 or ADP. Measurements were before and after premeal blood glucose standardization (to 6-7 mmol/L by insulin infusion, if needed) and at 90 min after the meal. Premeal insulin reduced postprandial hyperglycemia by 2-3 mmol/L compared with placebo. Postmeal insulin levels were doubled with placebo and further elevated with insulin injections. The standardized meal enhanced U46619-induced platelet P-selectin expression by 23% after placebo; this response was more than doubled after premeal insulin. U46619-induced fibrinogen binding was unchanged after meal intake with placebo but was markedly enhanced (by ~50-60%) after premeal insulin. Postprandial platelet activation correlated positively to postprandial insulin levels and inversely to glucose levels. Premeal insulin infusion was also associated with platelet activation. Our results suggest that postprandial insulin rather than glucose accounts for postprandial platelet activation in T2DM patients.


Triazolopyrimidines as a New Herbicidal Lead for Combating Weed Resistance Associated with Acetohydroxyacid Synthase Mutation.
Acetohydroxyacid synthase (AHAS; also known as acetolactate synthase; EC 18.104.22.168, formerly EC 126.96.36.199) is the first common enzyme in the biosynthetic pathway leading to the branched-chain amino acids in plants and a wide range of microorganisms. Weed resistance to AHAS-inhibiting herbicides, increasing at an exponential rate, is becoming a global problem and leading to an urgent demand of developing novel compounds against both resistant and wild AHAS. In the present work, a series of novel 2-aroxyl-1,2,4-triazolopyrimidine derivatives (a total of 55) were designed and synthesized with the aim to discover an antiresistant lead compound. Fortunately, the screening results indicated that many of the newly synthesized compounds showed a better, even excellent, inhibition effect against both the wild-type Arabidopsis thaliana AHAS and P197L mutants. Among them, compounds 5-3 to 5-17, compounds 5-19 to 5-26, compounds 5-28 to 5-45, and compound 5-48 have the lower values of resistance factor (RF) and display a potential power to overcome resistance associated with the P197L mutation in the enzyme levels. Further greenhouse in vivo assay showed that compounds 5-15 and 5-20 displayed "moderate" to "good" herbicidal activity against both the wild type-and the resistant (P197L mutation) Descurainia sophia, even at a rate as low as 0.9375 (g of ai/ha). The above results indicated that these two compounds could be used as new leads for the future development of antiresistance herbicides.


Exploring men's perceived educational experiences in a baccalaureate program.
Nursing school is the first place that men are likely to experience nursing in the professional sense. This study explored and documented men's perceptions of their experiences in baccalaureate nursing education. Face-to-face audiotaped interviews were conducted with 13 male nursing students who were in their last semester at three baccalaureate nursing programs. Qualitative methods were used to analyze their responses. The findings showed a lack of enjoyment of nursing school, the importance of career opportunities, frustrating communication differences, and the desire for more male nurse educators. Recommendations for future research include obtaining female students' perspectives on these questions, researching male students from different types of programs, and studying male graduate students to discover why so few become educators.


[Functional states in students under examination stress].
Functional states were studied in students in the intersession period and just before exams. It was found that there was an increase in markers of sympathetic activity and a reduction in markers of parasympathetic tone of the autonomic nervous system. A considerable individual variability in the pattern of a reaction was revealed in relation to the body mass index in students.


Regulation of high-density lipoprotein metabolism.
There is compelling evidence from human population studies that plasma levels of high-density lipoprotein (HDL) cholesterol correlate inversely with cardiovascular risk. Identification of this relationship has stimulated research designed to understand how HDL metabolism is regulated. The ultimate goal of these studies has been to develop HDL-raising therapies that have the potential to decrease the morbidity and mortality associated with atherosclerotic cardiovascular disease. However, the situation has turned out to be much more complex than originally envisaged. This is partly because the HDL fraction consists of multiple subpopulations of particles that vary in terms of shape, size, composition, and surface charge, as well as in their potential cardioprotective properties. This heterogeneity is a consequence of the continual remodeling and interconversion of HDL subpopulations by multiple plasma factors. Evidence that the remodeling of HDLs may impact on their cardioprotective properties is beginning to emerge. This serves to highlight the importance of understanding not only how the remodeling and interconversion of HDL subpopulations is regulated but also how these processes are affected by agents that increase HDL levels. This review provides an overview of what is currently understood about HDL metabolism and how the subpopulation distribution of these lipoproteins is regulated.


Competitive interactions of ionic surfactants with salbutamol and bovine serum albumin: a molecular spectroscopy study with implications for salbutamol in food analysis.
The effect of ionic surfactants, sodium dodecyl sulfate (SDS) and N-cetyl-N,N,N-trimethylammonium bromide (CTAB), on the interaction between β-agonist salbutamol (SAL) and bovine serum albumin (BSA) was investigated with the use of fluorescence spectroscopy (FLS) and chemometrics methods [multivariate curve resolution-alternating least-squares (MCR-ALS) and parallel factor analysis algorithm (PARAFAC)]. It was found that the binding constant of SAL to BSA in the presence of CTAB was much larger than that without this ligand. The ligand/BSA stoichiometry was 4:1, that is, (CTAB)4-BSA, and was 2:1 with the ligand, that is, (SAL)2-BSA. These results were obtained from the concentration profiles extracted by MCR-ALS for all three reactants. Quantitative information on the complex CTAB-BSA-SAL species was obtained with the resolution of the excitation-emission fluorescence three-way data matrices by PARAFAC. This research has implications for the analysis of SAL in food and might be performed in laboratories associated with organizations such as the U.S. Food and Drug Administration (FDA) and the International Olympic Committee (IOC).


[Usefulness of continuous duodenal catheterization and drainage in the postoperative period after papillosphincteroplastic operations].
The Authors claim the continuous emptying of the duodenum after papillosphincteroplastic useful in preventing APP. In order to prove it they present 27 running cases of sphicteroplastic so treated in which the postoperative amylasemy did not exceed the normal values.


Genomic and transcriptome analyses reveal that MAPK- and phosphatidylinositol-signaling pathways mediate tolerance to 5-hydroxymethyl-2-furaldehyde for industrial yeast Saccharomyces cerevisiae.
The industrial yeast Saccharomyces cerevisiae is a traditional ethanologenic agent and a promising biocatalyst for advanced biofuels production using lignocellulose materials. Here we present the genomic background of type strain NRRL Y-12632 and its transcriptomic response to 5-hydroxymethyl-2-furaldehyde (HMF), a commonly encountered toxic compound liberated from lignocellulosic-biomass pretreatment, in dissecting the genomic mechanisms of yeast tolerance. Compared with the genome of laboratory model strain S288C, we identified more than 32,000 SNPs in Y-12632 with 23,000 missense and nonsense SNPs. Enriched sequence mutations occurred for genes involved in MAPK- and phosphatidylinositol (PI)- signaling pathways in strain Y-12632, with 41 and 13 genes containing non-synonymous SNPs, respectively. Many of these mutated genes displayed consistent up-regulated signature expressions in response to challenges of 30 mM HMF. Analogous single-gene deletion mutations of these genes showed significantly sensitive growth response on a synthetic medium containing 20 mM HMF. Our results suggest at least three MAPK-signaling pathways, especially for the cell-wall integrity pathway, and PI-signaling pathways to be involved in mediation of yeast tolerance against HMF in industrial yeast Saccharomyces cerevisiae. Higher levels of sequence variations were also observed for genes involved in purine and pyrimidine metabolism pathways.


Generation of functional blocking monoclonal antibodies against mouse interleukin-12 p40 homodimer and monomer.
The role of interleukin (IL)-12 (p40:p35) and IL-23 (p40:p19) is becoming clear in immune response and inflammation. However, biological functions of IL-12 p40 homodimer (p40(2)) and monomer (p40) remain poorly understood due to the lack of specific monoclonal antibodies (MAb). Earlier we have demonstrated that both p40(2) and p40 activate microglia and macrophages to induce the expression of iNOS and TNF-alpha. To facilitate the studies on p40(2) and p40 further, we here describe the production of neutralizing MAb against mouse p40(2) and p40 for the first time after immunization of Armenian hamsters with recombinant p40(2). Antibodies produced from clones a3-1d and d7-12c specifically recognized p40(2) but not p40, IL-12, and IL-23. These MAbs also inhibited p40(2)- but not p40-, IL-12-, and IL-23-induced production of inflammatory molecules and activation of NF-kappaB. On the other hand, antibodies produced from clones a3-3a and a3-7g specifically recognized p40 and inhibited p40- but not p40(2)-, IL-12-, and IL-23-induced production of inflammatory molecules and activation of NF-kappaB. While MAbs a3-1d and d7-12c were used to establish p40(2)-specific ELISA, we utilized MAbs a3-3a and a3-7g to develop p40-specific ELISA. Interestingly, the production of p40(2) and p40 but not IL-12 in mouse peritoneal macrophages and primary microglia was an immediate early response to bacterial lipopolysaccharides. Furthermore, double-stranded RNA, the active component of a viral infection, induced the production of p40(2) and p40 but not IL-12 in macrophages and microglia. These results indicate the presence of different regulatory mechanisms for the production of IL-12p40(2)/p40 and IL-12p70.


Disseminated coccidioidomycosis with lung, skin and lymph node involvement: report of a case.
Coccidioidomycosis is a deep mycotic infection endemic to the southwestern United States. Although it has also been reported to occur in nonendemic areas, it has rarely been reported in Taiwan. We report a case of disseminated coccidioidomycosis which is the first such case reported on this island. The 28-year-old male patient developed a nonproductive cough and fever while travelling in Arizona. Chest roentgenogram revealed infiltration of the right lower lung field and enlargement of the right paratracheal lymph nodes. The titer for the complement fixation test for coccidioidin was 1:32. The patient was treated with ketoconazole for 3 months with good clinical response. However, submandibular lymphadenopathy and a macular skin lesion were noted one month after discontinuation of treatment. During hospitalization, both pathologic findings from a submandibular lymph node and a scratching smear of the skin lesion contained Coccidioides immites. The patient was put on ketoconazole again for another 6 months. Lesions on chest film were resolved and the coccidioidin complement fixation titer was gradually reduced. The patient received regular follow-up and no evidence of relapse has been seen. In this report, clinical manifestations, diagnostic methods and recent advances in the treatment of coccidioidomycosis are discussed. Because of increasing intercontinental travel and the increasing usage of immunosuppressive agents, we expect that more cases will be found in Taiwan. Keeping this disease in mind when making a differential diagnosis is the best way to make an accurate diagnosis.


Mucopolysaccharidosis IVA: correlation between genotype, phenotype and keratan sulfate levels.
Mucopolysaccharidosis IVA (MPS IVA) is caused by deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), leading to systemic skeletal dysplasia because of excessive storage of keratan sulfate (KS) in chondrocytes. In an effort to determine a precise prognosis and personalized treatment, we aim to characterize clinical, biochemical, and molecular findings in MPS IVA patients, and to seek correlations between genotype, phenotype, and blood and urine KS levels. Mutation screening of GALNS gene was performed in 55 MPS IVA patients (severe: 36, attenuated: 13, undefined: 6) by genomic PCR followed by direct sequence analysis. Plasma and urine KS levels were measured by ELISA method. Genotype/phenotype/KS correlations were assessed when data were available. Fifty-three different mutations including 19 novel ones (41 missense, 2 nonsense, 4 small deletions, 1 insertion, and 5 splice-site) were identified in 55 patients and accounted for 93.6% of the analyzed mutant alleles. Thirty-nine mutations were associated with a severe phenotype and ten mutations with an attenuated one. Blood and urine KS concentrations in MPS IVA patients were age-dependent and markedly higher than those in age-matched normal controls. Plasma and urine KS levels in MPS IVA patients with the severe phenotype were higher than in those with an attenuated form. This study provides evidence for extensive allelic heterogeneity of MPS IVA. Accumulation of mutations as well as clinical descriptions and KS levels allows us to predict clinical severity more precisely and should be used for evaluation of responses to potential treatment options.


Identification and validation of a hypoxia-immune signature for overall survival prediction in lung adenocarcinoma.
Objective: The interaction between immunity and hypoxia in tumor microenvironment (TME) has clinical significance, and this study aims to explore immune-hypoxia related biomarkers in LUAD to guide accurate prognosis of patients. Methods: The LUAD gene expression dataset was downloaded from GEO and TCGA databases. The immune-related genes and hypoxia-related genes were acquired from ImmPort and MSigDB databases, respectively. Genes related to immune and hypoxia in LUAD were obtained by intersection. The significantly prognostic genes in LUAD were obtained by LASSO and Cox regression analyses and a prognostic model was constructed. Kaplan-Meier and receiver operating characteristic curves were generated to evaluate and validate model reliability. Single-sample gene set enrichment analysis (ssGSEA) and gene set variation analysis (GSVA) were employed to analyze immune cell infiltration and pathway differences between high- and low-risk groups. Nomogram and calibration curves for survival curve and clinical features were drawn to measure prognostic value of the model. Results: The prognosis model of LUAD was constructed based on seven immune-hypoxia related genes: S100P, S100A16, PGK1, TNFSF11, ARRB1, NCR3, and TSLP. Survival analysis revealed a poor prognosis in high-risk group. ssGSEA result suggested that activities of immune cells in high-risk group was remarkably lower than in low-risk group, and GSVA result showed that immune-related pathway was notably activated in low-risk group. Conclusion: Immune-hypoxia related genes were found to be prognostic biomarkers for LUAD patients, based on which a 7-immune-hypoxia related gene-signature was constructed. This model can assess immune status of LUAD patients, and provide clinical reference for individualized prognosis, treatment and follow-up of LUAD patients.


Laparoscopic adjustable gastric banding: a 10 year follow-up study.
A comprehensive obesity management can only be accomplished by a multidisciplinary team. Despite the numerous efforts made, a winning solution has not been reached yet. When patients do not respond to conventional treatment, LAGB (Laparoscopic Adjustable Gastric Banding) is a generally effective approach with minimal involvement in anatomical modification. The aim of this study is to highlight how LAGB can guarantee long-term weight loss and a reduced incidence of complications and reoperations, when it is integrated in a multidisciplinary context and in a long period of close follow-up. 50 patients underwent LAGB between 2007 and 2008. From the sixth month after surgery, the LAGB was calibrated every 8-12 weeks, depending on the patient's response to the dietetic program and on his/her clinical and psychological situation. The follow up was planned every two weeks during the first six months after surgery, subsequently once a month during the first year; then every three months up to three years after surgery and every six months thereafter. After 6 months we found a significant weight loss that was progressive up to the second year. From the second year after surgery, the patients maintained their weight up to the tenth year of follow-up, without weight regain. In addition, an improvement of all metabolic parameters was found. LAGB guarantees good results in terms of weight loss and metabolic control; the careful choice of patients and a close and accurate follow-up are essential for the success of this surgical procedure.


[Gene transfer to treat rheumatoid arthritis].
Intraarticular transfer of exogenous genes could be useful for treatment of rheumatoid arthritis. The joints are not easy for drug accession while gene therapy can deliver therapeutic genes directly into the joints. Also, long-term expression of the transferred genes is expected. Anti-inflammatory genes, including interleukin-1 receptor antagonist gene, have been used in experimental arthritis models and in a clinical trial for treatment of rheumatoid arthritis. However, during gene therapy of other diseases, tragic accidents associated with viral vectors occurred. Since then, they have hampered clinical application of the gene therapy. Genes for treatment should be selected carefully and gene delivery methods should be optimized to resume clinical trials.


Seizures regulate the cation-Cl- cotransporter NKCC1 in a hamster model of epilepsy: implications for GABA neurotransmission.
The balance between the activity of the Na+/K+/Cl- cotransporter (NKCC1) that introduces Cl- into the cell and the K+/Cl- cotransporter (KCC2) that transports Cl- outside the cell is critical in determining the inhibitory or excitatory outcome of GABA release. Mounting evidence suggests that the impairment of GABAergic inhibitory neurotransmission plays a crucial role in the pathophysiology of epilepsy, both in patients and animal models. Previous studies indicate that decreased KCC2 expression is linked to audiogenic seizures in GASH/Sal hamsters, highlighting that Cl- imbalance can cause neuronal hyperexcitability. In this study, we aimed to investigate whether the Na+/K+/Cl- cotransporter NKCC1 is also affected by audiogenic seizures and could, therefore, play a role in neuronal hyperexcitability within the GASH/Sal epilepsy model. NKCC1 protein expression in both the GASH/Sal strain and wild type hamsters was analyzed by immunohistochemistry and Western blotting techniques. Brain regions examined included cortex, hippocampus, hypothalamus, inferior colliculus and pons-medulla oblongata, which were evaluated both at rest and after sound-inducing seizures in GASH/Sal hamsters. A complementary analysis of NKCC1 gene slc12a2 expression was conducted by real-time PCR. Finally, protein and mRNA levels of glutamate decarboxylase GAD67 were measured as an indicator of GABA release. The induction of seizures caused significant changes in NKCC1 expression in epileptic GASH/Sal hamsters, despite the similar brain expression pattern of NKCC1 in GASH/Sal and wild type hamsters in the absence of seizures. Interestingly, the regulation of brain NKCC1 by seizures demonstrated regional specificity, as protein levels exclusively increased in the hippocampus and hypothalamus. Complementary real-time PCR analysis revealed that NKCC1 regulation was post-transcriptional only in the hypothalamus. In addition, seizures also modulated GAD67 mRNA levels in a brain region-specific manner. The increased GAD67 expression in the hippocampus and hypothalamus of the epileptic hamster brain suggests that NKCC1 upregulation overlaps with GABA release in these regions during seizures. Our results indicate that seizure induction causes dysregulation of NKCC1 expression in GASH/Sal animals, which overlaps with changes in GABA release. These observations provide evidence for the critical role of NKCC1 in how seizures affect neuronal excitability, and support NKCC1 contribution to the development of secondary foci of epileptogenic activity.


Comparison of different methods of erythrocyte dysmorphism analysis to determine the origin of hematuria.
There is disagreement regarding the performance of conventional optical microscopy to assess the origin of hematuria. The aim of this study was to determine the optimal cutoff point for dysmorphic cells in order to detect glomerular hematuria by optical and phase-contrast microscopy. In total, 131 urine samples (66 from patients with glomerulopathies and 65 from nephrolithiasis patients) were evaluated in a blinded fashion. The percentages of doughnut cells and acanthocytes were verified by optical and phase-contrast microscopy. A total of 131 patients were randomly allocated to the derivation (n = 73) and validation (n = 58) groups. Receiver-operating characteristic (ROC) curves were plotted to check the discriminatory power of each group and the best cutoff points were determined by the Youden index in the derivation group and subsequently tested in the validation group. All areas under the ROC curve (AUCs) were statistically significant using both methods (conventional optical and phase-contrast microscopy) and both groups (derivation and validation). AUCs did not differ between different glomerulopathies. The best cutoff point to determine the glomerular origin of hematuria by total dysmorphic cells was 22% using an optical conventional microscope and 40% by phase-contrast microscopy. We determined the best cutoff points to interpret erythrocyte dysmorphism and demonstrated that it is possible to discriminate the origin of hematuria by evaluating erythrocyte dysmorphism in urinalysis using either an optical or a phase-contrast microscope.


Comparative biochemical and immunological studies of bacterial glutamine synthetases.
Antisera prepared against adenylylated and unadenylylated Escherichia coli glutamine synthetase cross-reacted with the glutamine synthetases from a number of gram-negative bacteria and one gram-variable species as demonstrated by immunodiffusion and inhibition of enzyme activity. In contrast, the antisera did not cross-react with the glutamine synthetases from gram-positive bacteria (with one exception) nor with the synthetases of higher organisms. Modification of the various glutamine synthetases by covalent attachment of adenosine 5'-monophosphate (or other nucleotides) was tested for by determining whether or not snake venom phosphodiesterase altered catalytic activity in a manner similar to its effect on adenylylated E. coli glutamine synthetase. Only the activity of the glutamine synthetases from gram-negative bacteria grown with specific levels of nitrogen sources could be altered by snake venom phosphodiesterase. In addition, a relative order of antigenic homology between cross-reacting enzymes was suggested based on the patterns of spur formation in the immunodiffusion assay.


Substitution effects of diborane on the interaction with borazine (inorganic benzene).
The gas phase interaction between borazine (IBz) and diborane (DB) has been investigated using MP2/6-311++G** and M05-2X/6-311++G** methods. The calculations have also been carried out at the same levels on the intermolecular complex formed between benzene (Bz) and DB to compare the modes of interaction. The complexation pattern found in IBz...DB is similar to that of Bz...DB due to their structural similarity. The calculated stabilization energies (SEs) at the MP2/6-311++G** level of theory for IBz...DB and Bz...DB complexes are 1.67 and 3.06 kcal/mol, respectively. The corresponding values obtained from the M05-2X/6-311++G** level of calculation are 2.55 and 3.43 kcal/mol. The variation in the SEs between IBz...DB and Bz...DB is due to the differences in the pi-electron distributions of IBz and Bz rings. Since, DB contains a three center-two electron (3c-2e) electron deficient bond, the substitution of nonbridge hydrogen atoms (H) by different functional groups may influence the nature of interaction between the DB and IBz. Thus, the nonbridge H atom in DB has been substituted by electron withdrawing (CN and Cl) and electron donating (CH(3)) groups. The interaction between substituted DBs and IBz has also been investigated using CCSD(T), MP2, and M05-2X methods. Results reveal that the substitution of the nonbridge H atom of DB by a cyano group significantly influences the calculated stabilization energies (SEs) and geometrical parameters whereas substitution by Cl and CH(3) groups marginally affects the stabilities and geometrical parameters of the substituted complexes. The calculated SEs of various substituted DB and IBz complexes range from 1.87 to 7.91 kcal/mol. Furthermore, evidence shows that SEs vary linearly with the number of substituents present in the complexes. The energy decomposition analysis using the density functional theory-symmetry adopted perturbation theory (DFT-SAPT) method confirms the predominant role played by the dispersion interaction in the stabilization of the various complexes when compared to the electrostatic interaction.


DNA binding and adduct formation of 7,12-dimethylbenz[a]-anthracene by rat mammary epithelial cell aggregates in vitro.
Freshly isolated mammary epithelial cell aggregates from female Sprague-Dawley rats metabolized 7,12-dimethylbenz-[a]anthracene (DMBA) to bay-region anti- and syn-dihydrodiolepoxides that bound to deoxyguanosine and deoxyadenosine residues in cellular DNA. After 24 h of incubation 68% of the DMBA (0.4 micrograms/ml) was metabolized and 58% of the extracellular metabolites were water-soluble. DMBA-DNA binding increased rapidly during the initial 24 h of incubation. Formation of the bay-region syn-dihydrodiolepoxide:deoxyadenosine adduct increased linearly throughout the 24 h, whereas formation of deoxyadenosine and deoxyguanosine adducts with the bay-region anti-dihydrodiolepoxide increased rapidly following a delay of 12 h.


Profiles of Racial Socialization Messages from Mothers and Fathers and The Colorblind and Anti-Black Attitudes of Asian American Adolescents.
Racial equality requires coalitions and solidarity across racial groups, but there continues to be racially colorblind and anti-Black attitudes within the Asian American community, a diverse community consisting of individuals with ancestral origins in East, Southeast, and South Asia. However, there is limited research on the factors that contribute to the development of these attitudes among Asian Americans. Parents could potentially play an important role in perpetuating or challenging the colorblind and anti-Black messages that pervade U.S. society. Thus, the current study investigates how 309 Asian American adolescents' (M age = 16.8; SD = 1.15; 50.5% female) perceptions of parents' racial socialization messages about race and racism relate to the youth's racial attitudes. Latent profiles of youth's perceptions of mothers' and fathers' racial socialization messages and their associations with colorblind racial attitudes and anti-Black attitudes were examined. For mothers, three socialization profiles were identified: Race Avoidant, Race Hesitant, and Race Embracing; for fathers, two socialization profiles were identified: Race Avoidant and Race Embracing. Adolescents with Race Embracing mothers reported less anti-Black attitudes compared to those who had Race Hesitant mothers. For fathers, there were no differences among the profiles and anti-Black attitudes. However, surprisingly, adolescents with Race Embracing fathers were more likely to have colorblind racial attitudes compared to those with Race Avoidant fathers. The findings highlight the importance of racial socialization in the development of Asian American adolescents' racial attitudes to continue fighting for interracial solidarity.


Monkeypox Virus Infection Resulting from an Occupational Needlestick - Florida, 2022.
In August 2022, the Florida Department of Health notified CDC of a nurse who acquired monkeypox through an occupational exposure while providing care to a patient with monkeypox. To date, occupationally acquired Monkeypox virus (MPXV) infections in health care personnel (HCP) have been rarely reported during the 2022 multinational outbreak (1,2). This report describes the first reported U.S. case and recommends approaches for preventing occupationally acquired MPXV infections in HCP.


De novo grown bone on exposed implant surfaces using photodynamic therapy and recombinant human bone morphogenetic protein-2: case report.
The reconstruction of bone on exposed implant surfaces requires an almost complete elimination of attached bacteria. Only then is new bone growth possible. This case report describes a new way to kill biofilms with photodynamic therapy and to augment bone by using recombinant human bone morphogenetic protein-2. Though the new technique of bone tissue engineering causes some problems, new bone growth on uncovered implant surfaces is successful to a large extent.


Modeling gene regulation from paired expression and chromatin accessibility data.
The rapid increase of genome-wide datasets on gene expression, chromatin states, and transcription factor (TF) binding locations offers an exciting opportunity to interpret the information encoded in genomes and epigenomes. This task can be challenging as it requires joint modeling of context-specific activation of cis-regulatory elements (REs) and the effects on transcription of associated regulatory factors. To meet this challenge, we propose a statistical approach based on paired expression and chromatin accessibility (PECA) data across diverse cellular contexts. In our approach, we model (i) the localization to REs of chromatin regulators (CRs) based on their interaction with sequence-specific TFs, (ii) the activation of REs due to CRs that are localized to them, and (iii) the effect of TFs bound to activated REs on the transcription of target genes (TGs). The transcriptional regulatory network inferred by PECA provides a detailed view of how trans- and cis-regulatory elements work together to affect gene expression in a context-specific manner. We illustrate the feasibility of this approach by analyzing paired expression and accessibility data from the mouse Encyclopedia of DNA Elements (ENCODE) and explore various applications of the resulting model.


Disaggregation is a Mechanism for Emission Turn-On of ortho-Aminomethylphenylboronic Acid-Based Saccharide Sensors.
ortho-Aminomethylphenylboronic acid-based receptors with appended fluorophores are commonly used as molecular sensors for saccharides in aqueous media. The mechanism for fluorescence modulation in these sensors has been attributed to some form of photoinduced electron transfer (PET) quenching, which is diminished in the presence of saccharides. Using a well-known boronic acid-based saccharide sensor (3), this work reveals a new mechanism for fluorescence turn-on in these types of sensors. Compound 3 exhibits an excimer, and the associated ground-state aggregation is responsible for fluorescence modulation under certain conditions. When fructose was titrated into a solution of 3 in 2:1 water/methanol with NaCl, the fluorescence intensity increased. Yet, when the same titration was repeated in pure methanol, a solvent in which the sensor does not aggregate, no fluorescence response to fructose was observed. This reveals that the fluorescence increase is not fully associated with fructose binding, but instead disaggregation of the sensor in the presence of fructose. Further, an analogue of the sensor that does not contain a boronic acid (4) responded nearly identically to 3 in the presence of fructose, despite having no functional group with which to bind the saccharide. This further supports the claim that fluorescence modulation is not primarily a result of binding, but of disaggregation. Using an indicator displacement assay and isothermal titration calorimetry, it was confirmed that fructose does indeed bind to the sensor. Thus, our evidence reveals that while binding occurs with fructose in the aqueous solvent system used, it is not related to the majority of the fluorescence modulation. Instead, disaggregation dominates the signal turn-on, and is thus a mechanism that should be investigated in other ortho-aminomethylphenylboronic acid-based sensors.


Drug resistance-associated changes in sphingolipids and ABC transporters occur in different regions of membrane domains.
We have recently shown that two ATP binding cassette (ABC) transporters are enriched in Lubrol-resistant noncaveolar membrane domains in multidrug-resistant human cancer cells [Hinrichs, J. W. J., K. Klappe, I. Hummel, and J. W. Kok. 2004. ATP-binding cassette transporters are enriched in non-caveolar detergent-insoluble glycosphingolipid-enriched membrane domains (DIGs) in human multidrug-resistant cancer cells. J. Biol. Chem. 279: 5734-5738]. Here, we show that aminophospholipids are relatively enriched in Lubrol-resistant membrane domains compared with Triton X-100-resistant membrane domains, whereas sphingolipids are relatively enriched in the latter. Moreover, Lubrol-resistant membrane domains contain more protein and lipid mass. Based on these results, we postulate a model for detergent-insoluble glycosphingolipid-enriched membrane domains consisting of a Lubrol-insoluble/Triton X-100-insoluble region and a Lubrol-insoluble/Triton X-100-soluble region. The latter region contains most of the ABC transporters as well as lipids known to be necessary for their efflux activity. Compared with drug-sensitive cells, the detergent-insoluble glycosphingolipid-enriched membrane domains (DIGs) in drug-resistant cells differ specifically in sphingolipid content and not in protein, phospholipid, or cholesterol content. In drug-resistant cells, sphingolipids with specific fatty acids (especially C24:1) are enriched in these membrane domains. Together, these data show that multidrug resistance-associated changes in both sphingolipids and ABC transporters occur in DIGs, but in different regions of these domains.


Duodenal ulcers are a major cause of gastrointestinal bleeding after cardiac surgery.
To determine the incidence of gastrointestinal (GI) bleeding in patients after cardiac surgery, assess the perioperative risk factors, and determine the type of GI tract pathology associated with bleeding events. At a tertiary referral hospital, all cardiac surgery patients having a postoperative GI bleed from April 2002 to March 2012 were identified. To determine bleeding etiology, only patients requiring endoscopy were included in the analysis. By retrospective review of 3 prospectively maintained databases, the incidence and independent predictors of GI bleeding, as well as endoscopic findings, were determined. Ninety-one GI bleeding events that required endoscopy were identified in 9017 patients. Those that bled were aged 71 ± 12 years, and 76% were men. Sixty-three percent of these patients had valve surgery and 37% had an isolated coronary artery bypass grafting. The overall incidence of GI bleeding was 1.01%, with an upper GI source accounting for 78%. Endoscopy data found a duodenal ulcer as the bleeding source in 71%, whereas stress gastritis accounted for 8%. Preoperative risk factors for bleeding included age ≥70 years, ejection fraction <35%, congestive heart failure, cerebrovascular disease, chronic kidney disease, and gastrointestinal disease. A preoperative history of atrial fibrillation and anticoagulation with Coumadin also was associated with bleeding. Patients that bled had a 30-day mortality rate of 8.8%, which was significantly greater than patients who did not bleed (4.3%; P = .03). Clinical variables can be used to identify patients at high risk for GI bleeding after cardiac surgery. When GI bleeding occurs, the most common cause is duodenal ulceration, which has an association with Helicobacter pylori infection. These findings may provide an opportunity to initiate preoperative preventative strategies.


Synthesis, spectral characterization, and pharmacological importance of new 4H-1,4-benzothiazines, their sulfone analogues, and ribofuranosides.
The present article describes the synthesis of new 4H-1,4-benzothiazines via condensation and oxidative cyclization of substituted 2-aminobenzenethiols with compounds containing active methylene groups. It is believed that the reaction proceeds via intermediary of the enaminoketone system. The sulfone derivatives were synthesized by oxidation of 4H-1,4-benzothiazines using 30% hydrogen peroxide in glacial acetic acid. Benzothiazines were used as bases to prepare ribofuranosides by treatment with a sugar derivative (β-D-ribofuranosyl-1-acetate-2,3,5-tribenzoate). The pharmacological importance of the synthesized compounds was evaluated by their, antimicrobial properties against various bacterial strains and fungal species. The structures of the compounds have been confirmed by spectral and chemical analysis.


Hookah Smoking: Assessing College Students' Behaviors, Attitudes, and Knowledge.
Purpose: The objective of this study was to assess college students' behaviors, attitudes, and knowledge regarding hookah smoking.Methods: A convenience sample of 200 students from various majors, including allied health and nursing students, was used to conduct this study at a university located in the Midwestern United States. Respondents were asked about any past, current, and future hookah smoking behaviors. Likert-scale questions were used to assess attitudes regarding hookah smoking. Respondents were also asked ten questions regarding the history of and health effects of hookah smoking. A knowledge score was calculated based on the number of questions answered correctly. Survey data were analyzed using independent sample t-tests and a one-way ANOVA test at a significance level of p<0.05.Results: A total of 200 out of 204 surveys were returned, yielding an overall response rate of 98%. Sixty-eight percent of respondents reported having participated in hookah smoking, with time of first-time use ranging from 14 to 21 years of age. About one third of the respondents (32%) reported participating in hookah smoking in the previous 30 days. The majority (68%)of respondents estimated that they would not participate in hookah smoking in five years time. Over half of the respondents reported that it is socially acceptable to participate in hookah smoking and 43% reported that hookah smoking has relaxation benefits. The overall mean knowledge score regarding the health effects of hookah usage was 4.4 questions correct out of 10. There was a significant difference (p=.038) in the mean knowledge scores between hookah users (4.70) and non-users (3.81). When comparing the knowledge of allied health and nursing majors to all other majors, the allied health and nursing group scored significantly higher (p=.017) than the non-allied health and nursing majors, with mean scores of 4.80 and 3.81, respectively. Thirty-nine percent of the respondents were unaware that hookah tobacco and related smoke can cause oral cancer.Conclusion: Based on the high rates of college student use and the low knowledge scores, this study supports need for more education about hookah smoking and its health consequences.


Optimization of the anti-cancer activity of phosphatidylinositol-3 kinase pathway inhibitor PITENIN-1: switching a thiourea with 1,2,3-triazole.
We previously reported encouraging in vitro and in vivoanti-cancer activity of N-((3-chloro-2-hydroxy-5-nitrophenyl)carbamothioyl)benzamide (termed PITENIN-1). In the current work, we describe the structure-activity relationship study of PIT-1 series, based on the replacement of central thiourea unit with a 1,2,3-triazole, which leads to increased liver microsomal stability, drug likeness and toxicity towards cancer cells.


Tricuspid valve chordal rupture due to airbag injury and review of pathophysiological mechanisms.
Blunt trauma to the chest is associated with significant morbidity and mortality. The latter is usually due to an aortic transection, whereas the former is related to myocardial contusion, cardiac valve injury, coronary artery disruption and intracardiac shunts due to the formation of septal defects. The main mechanisms causing these injuries are due to the sudden deceleration force and compression within the chest cavity. Moreover, there is also the sudden increase in intravascular pressure due to a mechanical compression effect and a hormonal adrenergic surge during the event. We report a case of a tricuspid valve injury caused by the deployment of the airbag during a high-speed impact car accident and the subsequent damage to the tricuspid valve chordal mechanism. The patient's management and the pathophysiological mechanisms involved in the injury are reviewed.


The chemical synthesis of O-alpha-L-fucopyranosyl-(1 goes to 2)-O-beta-D-galactopyranosyl-(1 goes to 3)-O-[alpha-L-fucopyranosyl-(1 goes to 4)]-2-acetamido-2-deoxy-D-glucopyranose, the Lewis b blood-group antigenic determinant.
An approach has been developed for the rapid synthesis of benzyl 2-acetamido-2-deoxy-3-O-beta-D-galactopyranosyl-beta-D-glucopyranoside (5). Disaccharide 5 was per(trimethylsilyl)ated, to provide the fully protected trimethylsilyl (Me3Si) derivative which, on treatment with pyridine-acetic anhydride-acetic acid for 2 days, gave the disaccharide derivative having O-acetyl groups selectively at the primary positions and Me3Si groups at the secondary positions. The latter groups were readily cleaved by treatment with aqueous acetic acid in methanol, to afford benzyl 2-acetamido-6-O-acetyl-3-O-(6-O-acetyl-beta-D-galactopyranosyl)-2-deoxy-beta-D- glucopyranoside, which, is isopropylidenation, gave the desired, key intermediate 9, having two hydroxyl groups free. Condensation of 9 with 2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl bromide, under catalysis by halide ion, afforded the tetrasaccharide derivative, from which the title tetrasaccharide was obtained by systematic removal of the protecting groups. The structure of the final product, and of various other intermediates, was established by 1H- and 13C-n.m.r. spectroscopy.


"Worse than being married": the exodus of British doctors from the National Health Service to Canada, c. 1955-75.
Despite a sizeable literature on the evolution of health insurance in Britain and Canada, there is virtually no research on the transnational migration of physicians between these countries in the immediate postwar period. This article hopes to address this neglected subject. Three inter-related topics will be examined. First, the paper will summarize the debate over physician emigration from the National Health Service (NHS) in postwar Britain. It will demonstrate how British social scientists and politicians began to come to grips with a major demographic exodus of British-trained doctors in the late 1950s and early 1960s. Second, it will analyze the changing health human resource situation in 1960s Canada, which focused, for practical and cultural reasons, on General Medical Council of Britain licensed practitioners. Third, through oral interviews of British-trained physicians who settled in Canada during the 1960s, it will examine the professional and personal reasons why physicians left Britain for Canada. It reveals that, among a myriad of personal issues that motivated a physician to leave the NHS, the inflexibility and hierarchical nature of British medicine loomed very large. The paper will conclude by reflecting on the contemporary significance of this fascinating historical phenomenon.


Assessment of MK-467, a peripheral alpha 2-adrenergic receptor antagonist, with intravenous clonidine.
The activity of MK-467, a new peripherally acting alpha 2-antagonist, was assessed in volunteers by a randomized, double-blind, crossover design. One hour after administration of either 15 mg or 30 mg MK-467 or placebo, 200 micrograms clonidine was given intravenously and observations were made for a further 8 hours. Clonidine reduced plasma norepinephrine levels to 79% +/- 7% of that of control 1 hour after infusion, an effect that was antagonized by low-dose MK-467 (p less than 0.05). Mean systolic blood pressure increased by 4 mm Hg in the first hour after the 30 mg dose of MK-467 (p less than 0.01), although there was no significant difference between the 3 study days in the maximal clonidine-induced decrease in systolic pressure, diastolic pressure, or heart rate. Clonidine induced a peak increase in mean blood glucose of 13%, which was antagonized by both doses of MK-467 (p less than 0.05). Plasma insulin was suppressed by clonidine from 72 +/- 14 to 47 +/- 7 IU.L-1, an effect antagonised by both doses of MK-467 (p less than 0.05 in each case). MK-467 had no effect on clonidine-induced increased drowsiness, xerostomia, or increase in growth hormone secretion, which is consistent with it being a peripherally acting specific alpha 2-antagonist. The small effect of MK-467 on clonidine-induced changes in plasma glucose and insulin suggests that peripheral alpha 2-adrenergic receptors play only a minor role in normal glucose homeostasis.


2D-fluoroscopic based navigation for Gamma 3 nail insertion versus conventional procedure- a feasibility study.
Intramedullary nailing is a standard surgical procedure for fixation of proximal femoral fractures, but is associated with considerable radiation exposure for controlling the implant placement, due to the percutaneous insertion technique.The aim of this study was the evaluation of potential benefits of 2D-fluoroscopic based navigation focused on the reduction of radiation exposure, a decrease of procedure time, as well as an increase of accuracy for Gamma3 nail insertions. Twenty randomized Gamma3 nail insertions were performed in non-fractured synthetic femora according to the manufactures operation guidelines (group I) or with use of a 2D-fluoroscopic based navigation system (group II). Time of different steps of the procedure and the radiation exposure were measured, as well as the accuracy evaluated in postoperative CT scans. All Gamma3 nails were placed without any technical problems. Independent of the used procedure, the overall operating time (group I: 584 ± 99.2 sec; group II: 662 ± 64.9 sec; p=0.06) and accuracy of the final nail-positions were equivalent, but the radiation exposure was significantly reduced (92% reduction in fluoroscopic images and 91% reduction in fluoroscopic time, p< 0.01), using the 2D fluoroscopic based navigation procedure. 2D-fluoroscopic based navigation for Gamma3 nail insertion facilitates a relevant reduction of radiation exposure with equivalent accuracy of the final implant position and no prolonged operating time. This promising procedure modification is independent of different cephalomedullary implant manufacturers and specific implant designs, but needs to be evaluated in further clinical settings.


Modern biologics for rabies prophylaxis and the elimination of human cases mediated by dogs.
Introduction: Rabies is a major viral zoonosis and neglected tropical disease, with a global distribution. Humans, domestic animals, and wild mammals are susceptible to infection. Etiological agents reside in the Order Mononegavirales, Family Rhabdoviridae, Genus Lyssavirus. This acute, progressive encephalitis causes the highest case fatality of any conventional infectious disease. Tens of millions of humans become exposed annually to the bites of infected mammals, predominantly in Asia and Africa. Despite the existence of effective vaccines and immune globulins, tens of thousands of people, typically children in the developing world, succumb. Areas covered: Concentrating upon both historical and major published references from the peer-reviewed literature over the past 5 years, we describe current biologics for rabies prevention, newly recommended principles for prophylaxis, and relevant future products in the developmental pipeline. Expert opinion: Modern human rabies biologics are pure, potent, safe, and efficacious, when used in a timely and appropriate manner. Few individuals survive after clinical signs. Anti-viral compounds are not licensed. Experimental therapy, while obviously desirable, is highly controversial. Education on bite prevention and integrated risk management are critical. Access to affordable care, dose-sparing, and shortened regimens of human rabies biologics remain key.


Residual limb pain is not a diagnosis: a proposed algorithm to classify postamputation pain.
Although postamputation pain (PAP) syndromes have been described since the 16th century, taxonomy of these conditions remains ill-defined. The term "Residual Limb Pain" fails to distinguish between distinct diagnostic entities such as neuroma, complex regional pain syndrome, and somatic pathology. Even phantom limb pain (PLP), although easily distinguished from residual limb pain (RLP), has not been consistently delineated from other PAP syndromes. A systematic review of the literature was conducted to identify the degree of delineation of various post amputation pain states and what diagnostic criteria were utilized if any. Furthermore, papers that involved treatment modalities were reviewed to determine efficacy of treatment. Of the 151 papers reviewed, none further categorized RLP into more specific diagnostic criteria. Furthermore, the literature contains numerous case reports, case series, letters to the editors, and grossly underpowered studies demonstrating significant positive results, yet few high-quality randomized controlled trials. Describing and defining the distinct clinical entities, intuitively, is a prerequisite to developing optimal treatments. The reported variation in the incidence of PAP phenomena may well represent inconsistency in assessment tools and diagnostic categories rather than variation in prevalence of these conditions. In this paper, we review the historical evolution of the current understanding of these syndromes and propose an algorithm for uniform classification.


Antidiarrheal activity of hexane extract of Citrus limon peel in an experimental animal model.
Acute diarrhea is one of the major illnesses that cause death in children, despite clinical interventions and the use of oral rehydration therapy. Thus, there is need to discover other effective, affordable and accessible treatments for this disease. Therefore, this study was carried out to investigate the effects of hexane extract of Citrus limon peel (HECLP) on castor oil-induced diarrhea in rats. Diarrhea was induced in male albino Wistar rats weighing 100-150 g. The antidiarrheal activity of HECLP at different oral dosages (5, 10 and 20 mg/kg) was investigated by counting the number of wet fecal pellets. Animals were further treated with propranolol, prazosin, nifedipine and atropine to assess the effects of receptor blockers on the activities of the extract. The effects of HECLP on castor oil-induced enteropooling and the intestinal transit time of activated charcoal were also evaluated. Each of the 3 doses of C. limon significantly reduced (P < 0.05) the number of wet fecal pellets produced by animals, with 20 mg/kg HECLP producing the highest percentage inhibition (34.2%). Wet fecal pellet inhibition by the standard drug loperamide (3 mg/kg p.o.) was 68.4% relative to the negative control. Blockage of β adrenergic receptors by propanolol abolished the antidiarrheal effects of HECLP. Intestinal fluid accumulation was inhibited by 68.7% and 78.5% by 20 mg/kg HECLP and loperamide respectively. Furthermore, 20 mg/kg HECLP significantly (P < 0.05) reduced the percentage intestinal transit time (21.4% ± 1.42%), relative to the control (34.2% ± 4.29%); atropine (5 mg/kg, intraperitoneal injection) significantly (P < 0.001) reduced the percentage intestinal transit time to 11.2% ± 0.85%. These results suggest that C. limon peel possesses antidiarrheal effects through antisecretory and antimotility mechanisms that act through the β adrenergic system.


Earlier than expected introductions of the Bemisia tabaci B mitotype in Brazil reveal an unprecedented, rapid invasion history.
During 1991, in Brazil, the presence of the exotic Bemisia tabaci B mitotype was reported in São Paulo state. However, the duration from the time of initial introduction to population upsurges is not known. To investigate whether the 1991 B mitotype outbreaks in Brazil originated in São Paulo or from migrating populations from neighboring introduction sites, country-wide field samples of B. tabaci archived from 1989-2005 collections were subjected to analysis of mitochondrial cytochrome oxidase I (mtCOI) and nuclear RNA-binding protein 15 (RP-15) sequences. The results of mtCOI sequence analysis identified all B. tabaci as the NAFME 8 haplotype of the B mitotype. Phylogenetic analyses of RP-15 sequences revealed that the B mitotype was likely a hybrid between a B type parent related to a haplotype Ethiopian endemism (NAFME 1-3), and an unidentified parent from the North Africa-Middle East (NAF-ME) region. Results provide the first evidence that this widely invasive B mitotype has evolved from a previously undocumented hybridization event. Samples from Rio de Janeiro (1989) and Ceará state (1990), respectively, are the earliest known B mitotype records in Brazil. A simulated migration for the 1989 introduction predicted a dispersal rate of 200-500 km/year, indicating that the population was unlikely to have reached Ceará by 1990. Results implicated two independent introductions of the B mitotype in Brazil in 1989 and 1990, that together were predicted to have contributed to the complete invasion of Brazil in only 30 generations.


Salt Sensitive Tet-Off-Like Systems to Knockdown Primordial Germ Cell Genes for Repressible Transgenic Sterilization in Channel Catfish, Ictalurus punctatus.
Repressible knockdown approaches were investigated for transgenic sterilization in channel catfish, Ictalurus punctatus. Two primordial germ cell (PGC) marker genes, nanos and dead end, were targeted for knockdown, and an off-target gene, vasa, was monitored. Two potentially salt sensitive repressible promoters, zebrafish adenylosuccinate synthase 2 (ADSS) and zebrafish racemase (Rm), were each coupled with four knockdown strategies: ds-sh RNA targeting the 5' end (N1) or 3' end (N2) of channel catfish nanos, full-length cDNA sequence of channel catfish nanos for overexpression (cDNA) and ds-sh RNA targeting channel catfish dead end (DND). Each construct had an untreated group and treated group with sodium chloride as the repressor compound. Spawning rates of full-sibling P₁ fish exposed or not exposed to the constructs as treated and untreated embryos were 93% and 59%, respectively, indicating potential sterilization of fish and repression of the constructs. Although the mRNA expression data of PGC marker genes were inconsistent in P₁ fish, most F₁ individuals were able to downregulate the target genes in untreated groups and repress the knockdown process in treated groups. The results indicate that repressible transgenic sterilization is feasible for reproductive control of fish, but more data from F₂ or F₃ are needed for evaluation.


Crystal structure of the IIB subunit of a fructose permease (IIBLev) from Bacillus subtilis.
The bacterial phosphoenolpyruvate-dependent phosphotransferase system (PTS) mediates both the uptake of carbohydrates across the cytoplasmic membrane and their phosphorylation. During this process, a phosphoryl group is transferred from phosphoenolpyruvate via the general PTS proteins enzyme I, HPr and the sugar-specific components IIA, IIB to the transported sugar. The crystal structure of the IIB subunit of a fructose transporter from Bacillus subtilis (IIBLev) was solved by MIRAS to a resolution of 2.9 A. IIBLev comprises 163 amino acid residues that are folded into an open, mainly parallel beta-sheet with helices packed on either face. The phosphorylation site (His15) is located on the first loop (1/A) at one of the topological switch-points of the fold. Despite different global folds, IIBLev and HPr have very similar active-site loop conformations with the active-site histidine residues located close to the N terminus of the first helix. This resemblance may be of functional importance, since both proteins exchange a phosphoryl group with the same IIA subunit. The structural basis of phosphoryl transfer from HPr to IIAMan to IIBMan was investigated by modeling of the respective transition state complexes using the known HPr and IIAMan structures and a homology model of IIBMan that was derived from the IIBLev structure. All three proteins contain a helix that appears to be suitable for stabilization of the phospho-histidine by dipole and H-bonding interactions. Smooth phosphoryl transfer from one N-cap position to the other appears feasible with a minimized transition state energy due to simultaneous interactions with the donor and the acceptor helix.


[Introduction of labor epidural analgesia in Wakayama].
Labor epidural analgesia is unfamiliar to parturients in Wakayama Prefecture partly because of insufficient information and medical services for expectant mothers given by anesthesiologists and other medical staffs. We offered introductory approaches for providing epidural analgesia for labor and delivery in our obstetric care unit. The preliminary survey among midwives, who are crucial for gravitas, revealed their negative attitude to painless labor assisted by epidural technique, while they opted for natural childbirth. Obstetricians also responded negatively toward epidural analgesia during labor because of their concern about forceps and prolonged delivery. We spent considerable time to achieve better communication with midwives and obstetricians in order to improve our professional qualities for caring labor pain. After practical approach of labor epidural analgesia, midwives came to accept epidural analgesia as an option during childbirth.


Allele-specific expression reveals interactions between genetic variation and environment.
Identifying interactions between genetics and the environment (GxE) remains challenging. We have developed EAGLE, a hierarchical Bayesian model for identifying GxE interactions based on associations between environmental variables and allele-specific expression. Combining whole-blood RNA-seq with extensive environmental annotations collected from 922 human individuals, we identified 35 GxE interactions, compared with only four using standard GxE interaction testing. EAGLE provides new opportunities for researchers to identify GxE interactions using functional genomic data.


Real time in situ chemical characterization of submicrometer organic particles using direct analysis in real time-mass spectrometry.
Direct analysis in real time mass spectrometry (DART-MS) is used to analyze the surface chemical composition of nanometer-sized organic aerosol particles in real time at atmospheric pressure. By introducing a stream of particles in between the DART ionization source and the atmospheric pressure inlet of the mass spectrometer, the aerosol is exposed to a thermal flow of helium or nitrogen gas containing some fraction of metastable helium atoms or nitrogen molecules. In this configuration, the molecular constituents of organic particles are desorbed, ionized, and detected with reduced molecular ion fragmentation, allowing for compositional identification. Aerosol particles detected include alkanes, alkenes, acids, esters, alcohols, aldehydes, and amino acids. The ion signal produced by DART-MS scales with the aerosol surface area rather than volume, suggesting that DART-MS is a viable technique to measure the chemical composition of the particle interface. For oleic acid, particle size measurements of the aerosol stream exiting the ionization region suggest that the probing depth depends upon the desorption temperature, and the probing depth is estimated to be on the order of 5 nm for a 185 nm diameter particle at a DART heater temperature of 500 °C with nitrogen as the DART gas. The reaction of ozone with submicrometer oleic acid particles is measured to demonstrate the ability of this technique to identify products and quantify reaction rates in a heterogeneous reaction.


Epidemiology of rheumatic heart disease among primary school children in western Kenya.
A community survey was conducted to determine the prevalence of rheumatic heart disease in Kenyan children in all primary schools in 2 sublocations in Western Kenya. In total, 3631 children (97% school attendance) aged from 5 to 15 years were examined by one experienced physician and 2 cardiologists between September and December 1985. Six children were found to have evidence of rheumatic heart disease, giving a prevalence rate of 1.7/1000. As all cases occurred in the age group between 10 and 15 years, the rate was calculated for this group as 2.4/1000. None of these patients had previously been diagnosed as having rheumatic fever. There were 3 males and 3 females. Four patients had mitral regurgitation, one had aortic regurgitation and one had mitral stenosis. Three had electrocardiographic evidence of left atrial abnormality and one showed findings of left ventricular hypertrophy but two patients had normal tracings. Half were symptomatic with dyspnoea on exertion and two gave a history of fleeting polyarthritis. The socio-economic status (peasant), family size (mean = 6 siblings) and the number of children sleeping per room were the same in both the cases with rheumatic heart disease and their controls. The health workers achieved low scores (mean 26%) with regard to the clinical diagnosis, treatment and prevention of rheumatic fever at the level of primary health care. Rheumatic heart disease, nonetheless, was relatively insignificant in the overall picture of health care of school children in Western Kenya.


Potential and distribution of transplanted hematopoietic stem cells in a nonablated mouse model.
Increasingly, allogeneic and even more often autologous bone marrow transplants are being done to correct a wide variety of diseases. In addition, autologous marrow transplants potentially provide an opportune means of delivering genes in transfected, engrafting stem cells. However, despite its widespread clinical use and promising gene therapy applications, relatively little is known about the mechanisms of engraftment in marrow transplant recipients. This is especially so in the nonablated recipient setting. Our data show that purified lineage negative rhodamine 123/Hoechst 33342 dull transplanted hematopoietic stem cells engraft into the marrow of nonablated syngeneic recipients. These cells have multilineage potential, and maintain a distinct subpopulation with "stem cell" characteristics. The data also suggests a spatial localization of stem cell "niches" to the endosteal surface, with all donor cells having a high spatial affinity to this area. However, the level of stem cell engraftment observed following a transplant of "stem cells" was significantly lower than that expected following a transplant of the same number of unseparated marrow cells from which the purified cells were derived, suggesting the existence of a "nonstem cell facilitator population," which is required in a nonablated syngeneic transplant setting.


Antenatal screening for aneuploidy.
There are several methods of antenatal screening for aneuploidy. Most are aimed at the identification of women at increased risk of Down syndrome, the most common abnormal karyotype conferring a significant risk of serious long-term morbidity. Traditional maternal-age-based screening has largely been replaced by programmes based on biochemical markers in maternal serum in the second trimester of pregnancy. However, in recent years there has been a considerable drive towards earlier screening such that there are now a range of potential programmes based on various combinations of maternal age, serum markers and ultrasound findings. There is currently much debate as to which are the most effective methods of screening for aneuploidy.


Characteristics associated with low food and fluid intake in long-term care residents with dementia.
This article describes the prevalence, assessment, and treatment of, as well as characteristics associated with, the food and fluid intake of 407 residents with dementia in 45 assisted living facilities and nursing homes. Overall, 54% of observed residents had low food intake, and 51% had low fluid intake. Staff monitoring of residents, having meals in a public dining area, and the presence of noninstitutional features were each associated with higher food and fluid intake.


Treatment options for cyclic vomiting syndrome.
Since its initial description nearly two centuries ago, treatment of idiopathic cyclic vomiting syndrome (CVS) remains largely empiric because of its obscure pathogenesis and the paucity of controlled therapeutic trials. Despite these challenges, this report reviews open-label trials, retrospective case series, and upcoming consensus guidelines to update the treatment. The treatment approach to a patient with CVS should include consideration of lifestyle changes including avoidance of potential triggers, prophylactic drug therapy to prevent subsequent episodes, abortive and/or supportive care treatment during acute episodes, and support of the family. The mainstays of drug therapy include antimigraine, anti-emetic, and anticonvulsive medications used for prophylactic, abortive, and supportive therapy, with reported efficacies of between 40% and 90%. Prophylactic antimigraine and anticonvulsive agents are used to prevent episodes. Antimigraine triptans are used to abort episodes. Antiemetic agents can reduce the severity of episodes and are best used in conjunction with sedatives.


Graphene-Based Three-Dimensional Capacitive Touch Sensor for Wearable Electronics.
The development of input device technology in a conformal and stretchable format is important for the advancement of various wearable electronics. Herein, we report a capacitive touch sensor with good sensing capabilities in both contact and noncontact modes, enabled by the use of graphene and a thin device geometry. This device can be integrated with highly deformable areas of the human body, such as the forearms and palms. This touch sensor detects multiple touch signals in acute recordings and recognizes the distance and shape of the approaching objects before direct contact is made. This technology offers a convenient and immersive human-machine interface and additional potential utility as a multifunctional sensor for emerging wearable electronics and robotics.


Beating Heart of Cytochrome c Oxidase: The Shared Proton of Heme a3 Propionates.
Cytochrome c oxidase (CcO) pumps protons from the N-side to the P-side and consumes electrons from the P-side of the mitochondrial membrane driven by energy gained from reduction of dioxygen to water. ATP synthesis uses the resulting proton gradient and electrostatic potential difference. Since the distance a proton travels through CcO is too large for a one-step transfer process, proton-loading sites (PLS) that can carry protons transiently are necessary. One specific pump-active PLS couples to the redox reaction, thus energizing the proton to move across the membrane against electric potential and proton gradient. The PLS should also prevent proton backflow. Therefore, the propionates of the two redox-active hemes in CcO were suggested as PLS candidates although, according to CcO crystal structures, none of the four propionates can be protonated on account of strong H-bonds. Here, we show that modeling the local structure around heme a3 propionates enhances significantly their capability of carrying a proton jointly. This was not possible for the propionates of heme a. The modeled structures are stable in molecular dynamics simulations (MDS) and are energetically similar to the crystal structure. Precise electrostatic energy computations of MDS data are used to estimate the pKA values of all titratable residues in CcO. For the modeled structures, the heme a3 propionates have pKA values high enough to host a proton transiently but not too high to fix the proton permanently. The change in pKA throughout the redox reaction is sufficient to push the proton to the P-side of the membrane and to provide the protons with the necessary amount of energy for ATP synthesis.