Fetal ventricular strain in uncomplicated and selective growth-restricted monochorionic diamniotic twin pregnancies and cardiovascular response in pre-twin-twin transfusion syndrome.
Our primary aim was to confirm whether intertwin discordance in ventricular strain and ductus venosus (DV) time intervals predicts twin-twin transfusion syndrome (TTTS). Secondary aims were to create gestational-age ranges for ventricular strain in uncomplicated monochorionic diamniotic (MCDA) twin pregnancies without selective intrauterine growth restriction (sIUGR) and to characterize the relationship of ventricular strain with gestational age in MCDA twin pregnancies with sIUGR that did not develop TTTS. In the period 2015-2018, we enrolled 150 MCDA twin pregnancies consecutively into this prospective, blinded study of global longitudinal left and right ventricular strain. With the observer blinded to twin pairing and pregnancy outcome, videoclips of the four-chamber view, which had been recorded during ultrasound surveillance in the usual window for development of TTTS (16-26 completed gestational weeks), underwent offline measurement of strain. Uncomplicated MCDA twin pregnancies, without sIUGR, were used to test the association between strain, gestational age and estimated fetal weight using mixed-effects multilevel regression. Inter-rater reliability was tested in 208 strain measurements in 31 fetuses from pregnancies which did not develop TTTS and within-fetus variation was assessed in 16 such fetuses, in which multiple four-chamber views were taken on the same day. The effect of sIUGR on strain in otherwise uncomplicated MCDA twin pregnancy was analyzed. MCDA twin pregnancies were defined as 'pre-TTTS' when, having been referred for TTTS evaluation, they did not satisfy Quintero staging criteria, but subsequently developed TTTS requiring laser treatment. MCDA pregnancies which did not develop TTTS comprised the 'non-TTTS' group. Cardiovascular parameters measured in these cases included tissue Doppler parameters and DV early filling time as a percentage of the cardiac cycle (DVeT%). Intertwin strain and DVeT% discordance was compared between non-TTTS and pre-TTTS cases, matched for gestational age. Paired strain data were available for intertwin comparison in 127/150 MCDA twin pregnancies, comprising 14 pre-TTTS and 113 non-TTTS pregnancies, after exclusions. Scans were collected at a median frame rate of 97 (range, 28-220) Hz. Laser therapy was performed at a median gestational age of 20.6 (range, 17.2-26.6) weeks. There were no group differences in right (RV) or left (LV) ventricular strain discordance between 68/113 non-TTTS and 13/14 pre-TTTS MCDA twin pregnancies < 20 completed gestational weeks (RV, P = 0.338; LV, P = 0.932). DVeT% discordance > 3.6% was found in eight of 13 pre-TTTS pregnancies. In non-TTTS pregnancies, the estimated variability in ventricular strain within each twin during the day was high (RV, 19.7; LV, 12.9). However, within each pair (intertwin variation), variability was low (RV, 5.5; LV, 2.9). Interclass correlation reflecting the proportion of total variability represented by the variability between twin pairs was low (RV, 0.22; LV, 0.18). Both RV (P < 0.001) and LV (P = 0.025) strain showed a negative association with gestational age. Among non-TTTS MCDA twin pregnancies, LV strain was, on average, higher by 1.83 in sIUGR compared with normally grown fetuses (P = 0.023), with no statistically significant difference in RV strain (P = 0.271). Although ventricular strain has been reported previously as a possible predictor of developing TTTS, in this blinded, prospective study, we found no significant intergroup differences in ventricular strain in pre-TTTS compared with age-matched non-TTTS MCDA twin pregnancies. We recommend using DVeT% discordance as a more practical screening tool in MCDA twin pregnancies. This study also provides new information on the changes with gestational age, and the biological and technical variation, of global longitudinal ventricular strain in uncomplicated MCDA twin pregnancies and those with isolated sIUGR. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Expression of epidermal growth factor receptor in normal colorectal mucosa, adenoma, and carcinoma.
Using the monoclonal antibody EGF-R1, the expression of epidermal growth factor receptor (EGFR) was investigated immunohistochemically in normal colonic mucosa distant from and adjacent to colonic neoplasms, in 25 adenomas and in 144 unselected colorectal carcinomas. EGFR expression was an inconsistent phenomenon in each of these conditions. It was not expressed in 23/44 non-neoplastic mucosa specimens distant from and in 26/44 mucosae adjacent to colon tumours; 15/25 adenomas and 71 (49.3%) of the carcinomas failed to contain detectable amounts of EGFR. In contrast, large amounts of EGFR were found in 4 non-neoplastic mucosae at both locations, in 3 adenomas and in 11 (7.6%) carcinomas. The remaining cases showed complex patterns of EGFR-expression. In comparing mucosae close to and distant from a colonic tumour, only minor differences in EGFR content were observed. The intra-individual comparison of the mode of EGFR expression in non-neoplastic and neoplastic epithelium revealed an overexpression of EGFR in carcinomas in about one third of the 44 cases examined. One third showed no obvious differences, and one third showed lower levels of EGFR expression within the tumour. We conclude that the mode of EGFR expression in normal and neoplastic colon epithelium is variable and reflective of inter-individual constitutive differences rather than of abnormalities in gene regulation. Statistical analysis failed to reveal correlations between the mode of EGFR expression and tumour grade, type or Dukes stage.


The reimagination of sustainable integrated care in Ontario, Canada.
To encourage clinical and financial efficiency, the Canadian province of Ontario initiated an integrated care program - Integrated Funding Models (IFMs) that required collaboration and coordination across acute and post-acute care sectors. This research shows how program implementers went beyond policy-makers' original designs, to make integrated care sustainable for chronic diseases. Forty-five interviews were conducted with program participants at three chronic disease programs, as well as with policymakers. Interviews were conducted over two phases; during early implementation in 2016, and as programs matured in 2018. Data were analyzed through a cultural constructivist lens to understand how participants shaped programs. Participants desired greater accountability and control. Participants in the first program wanted localized control over decision-making. In the second, participants initiated greater control over financial uncertainty. In the third program, hospital participants sought greater control over community care. Participants across programs simultaneously wanted integrated care to be expanded holistically, spatially, and temporally for patients, extending the length of care, and expanding the spaces in which care was provided. Findings also suggest a gap between program implementers' and policymakers' conceptualizations of integrated care. This work shows how IFMs were reimagined in ways that transcended their original conceptualization as spatially and temporally delimited initiatives aimed at improving coordination and efficiency. It has practical implications for those facing sustainability challenges in other contexts.


Randomized trial comparing pulmonary alterations after conventional with venovenous bypass versus piggyback liver transplantation.
During the anhepatic phase of conventional liver transplantation (LT), the inferior vena cava (IVC) is cross-clamped and venovenous bypass (VVB) is usually indicated for diversion of IVC and portal blood flow. VVB can theoretically lead to pulmonary complications due to the contact of the blood with the surfaces of the circuit. In the piggyback method, preservation of the IVC avoids VVB. The aim of this study is to compare pulmonary alterations after conventional with VVB versus piggyback LT. Sixty-seven patients were randomized for conventional VVB (n = 34) or piggyback (n = 33) LT. Pulmonary static compliance (C(st)) and Pa(O2)/F(IO2) ratio were measured pre- and post-LT. Chest X-rays were obtained daily from the 1st to the 5th postoperative day. Pre- and post-LT C(st) were 73.4 +/- 36.0 mL/cm H(2)O and 59.7 +/- 22.0 mL/cm H(2)O in the conventional group and 69.1 +/- 20.0 mL/cm H(2)O and 58.7 +/- 27.1 mL/cmH(2)O in the piggyback group. The difference between the two groups was not significant (P =.702). C(st) significantly decreased after LT (P =.008). The pre- and post-LT Pa(O2)/F(IO2) were 455.6 +/- 126.6 mm Hg and 463.1 +/- 105.9 mm Hg in the conventional group and 468.9 +/- 114.1 mm Hg and 483.3 +/- 119.8 mm Hg in the piggyback group. The difference among the two groups was not significant (P = 0.331). There was no significant difference after LT (P =.382). Upon the radiological evaluation, piggyback group presented a higher frequency of pulmonary infiltrates (80.6% vs. 50.0%; P =.025). In conclusion, piggyback LT recipients have a higher rate of pulmonary infiltrates when compared to those operated upon using the conventional VVB method.


Overexpression of N-acetylglucosaminyltransferases III and V in human melanoma cells. Implications for MCAM N-glycosylation.
An important role in cancer pathogenesis is attributed to N-glycans with "bisecting" N-acetylglucosamine and beta1-6 branches but the exact mechanisms still remain to be elucidated. Two structures are formed by Golgi beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase (EC = 220.127.116.11, GnT-III) and alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A (EC = 126.96.36.199, GnT-V) respectively. The enzymes are encoded by MGAT3 and MGAT5 genes. The aim of this study was to establish two human melanoma cell lines with induced overexpression of GnT-III or GnT-V and to perform a preliminary functional characterization. WM-266-4 cells were stably transfected with human MGAT3 or MGAT5 cDNAs. GnT-III and GnT-V activities were assayed with a novel HPLC method based on labeling of N-glycan acceptor with 2-aminobenzamide (adapted from Taniguchi et al., 1989). Higher expression and activities of glycosyltransferases were detected. Increased amounts of "bisected" and beta1-6 branched N-glycans were present on melanoma cell adhesion molecule (known as MCAM/MUC18). However, cells did not display significant differences in viability and capabilities to migrate through an endothelial layer. To the best of our knowledge, the result of our study is the first to demonstrate that "bisected" N-glycans can be carried by MCAM. Moreover, increased modification of this protein by the two glycosyltransferases in WM-266-4-GnT-III cells was the consequence of the overexpression of only one enzyme. The obtained model can be useful for studying mechanisms of N-glycans branching and better understanding of their role in cancer progression. The proposed modification of the glycosyltransferase activity assay has shown to be a good alternative for 2-aminopyridine based HPLC systems.


Whole abdominal irradiation for tumors of the uterine corpus.
Between November 1981 and December 1985, 16 patients with high-risk tumors of the uterine corpus were treated with a postoperative course of whole abdominal-pelvic irradiation. Thirteen patients had carcinomas and three had sarcomas. All patients had complete pelvic surgery including extrafascial (or modified radical) hysterectomy and bilateral salpingo-oophorectomy, pelvic node sampling, evaluation of peritoneal cytology, and resection of extrauterine metastases when indicated. All patients were free of gross visible tumor after surgery. Target doses of radiation were 3000 cGy to the upper abdomen and 4500 cGy to the pelvis. Median follow-up was 24 months for survivors (range, 17 to 63 months). The disease-free survival and overall survival at 17 months was 50%. Six of the 16 (38%) patients suffered intraabdominal relapse. One patient had a significant complication (bowel perforation). The data from this pilot study suggest that whole abdominal-pelvic irradiation may be useful only in the management of some patients with few high risk features of endometrial carcinoma. Patients with extensive extra-uterine involvement and with sarcoma histology do not appear to benefit from this experimental therapy.


Effect of nanobubbles on friction forces between hydrophobic surfaces in water.
The interaction between hydrophobic surfaces in aqueous solutions is particularly important because it is encountered in many industrial processes. Even though advances in surface science have been tremendous, the nature of the hydrophobic interaction remains one of the greatest challenges to the field. In this work an atomic force microscope (AFM) was used to measure the normal and lateral interactions between a silica bead and a smooth silica substrate hydrophobized by esterification with 1-octanol. The experiments were performed in water and in water after alcohol-water exchange, a method that has been shown to increase the occurrence and size of nanobubbles at the hydrophobic surface and in turn result in a longer range hydrophobic force due to capillary bridge formation. It was found that the alcohol-water exchange had a significant impact on the friction force due to the increased size of the capillary, which increased adhesion.


Effect of segmental versus marginal mandibular resection on local and lymph node recurrences in oral squamous cell carcinoma: is tumorous bone infiltration or location and resulting soft tissue recurrences a long-term problem?
Oral squamous cell carcinomas (OSCCs) adjacent to the mandible or with clinically suspected bone infiltration are surgically treated either with marginal or segmental resections. This retrospective study compared both resections regarding local recurrence and lymph node recurrence or secondary lymph node metastases. All consecutive primary OSCC cases between January 2007 and December 2015 that underwent mandibular marginal or segmental resection were included. Rates of local and lymph node recurrences or secondary metastases and possible risk factors such as tumor localization according to Urken's classification were recorded. In total, 180 patients with 85 marginal (group I) and 95 segmental (group II) mandibular resections were analyzed. The local recurrence rates were comparable between the groups (28.2% vs. 27.4%; p = 0.897). Lymph node recurrences or secondary metastases were higher in group I (9.4% (n = 8) vs. 6.2% (n = 6); p = 0.001). Tumor localization appears to affect the outcomes. Significantly fewer local and lymph node recurrences/metastases were found for Urken's classification SB and S calculated by two-proportion z-test (p = 0.014 and 0.056, respectively). Local recurrences mostly emerged from soft tissues, which should be resected more radically than the bones. While bone infiltration appears technically well controllable from an oncologic point of view, local recurrences and lymph node recurrences/metastases remain an issue. Regular clinical aftercare with imaging is crucial to detect recurrences.


Near-infrared calibration models for estimating volatile fatty acids and methane production from in vitro rumen fermentation of different total mixed rations.
Volatile fatty acids (VFA) and methane (CH4) are the major products of rumen fermentation. The VFA are considered an energy source for the animal and rumen microbiota, and CH4 (which is released by eructation) is considered an energy loss. Quantification of these fermentation products is fundamental for the evaluation of feeds and diets, and provides important information regarding the use of nutrients by ruminants. Near-infrared (NIR) spectroscopy is increasingly used for the evaluation of animal feeds because it is rapid, nondestructive, noninvasive, and inexpensive; does not require reagents; and the results are reproducible. The aim of this study was to develop NIR calibration models for estimating the production of VFA (acetic, propionic, butyric, valeric, isovaleric, and isobutyric acids), total gas, and CH4 using in vitro gas production tests with buffered rumen inoculum throughout fermentation. Fifty-four total mixed rations (TMRs) were examined, and rumen fluid was manually collected from 2 dry Holstein dairy cows that had ruminal fistulas and were fed at maintenance energy levels. Then, 30 mL of buffered rumen fluid was incubated in bottles with ~220 mg of TMR. The total gas, VFA, and CH4 were measured after 2, 5, 9, 24, 30, 48, and 72 h of rumen incubation for each TMR. The VFA were measured on 32 randomly selected TMR. In particular, 7 bottles were used for each TMR, one for each incubation time. Methane was measured in the headspace and VFA were measured in the buffered rumen fluid. The bottles were considered experimental units for calibration purposes. The production of CH4 was quantified from the bottle headspaces by gas chromatography, and total gas production was measured using a pressure transducer at each incubation time. Two aliquots of the fermented liquids were sampled by opening the bottles at each incubation time, and (1) the concentrations of VFA were determined by gas chromatography or (2) spectra were obtained from Fourier-transform NIR spectroscopy. The data were randomly divided into calibration and validation data sets. The average concentrations of acetic acid (45.30 ± 11.92 and 43.86 ± 11.93 mmol/L), propionic acid (14.97 ± 6.08 and 14.38 ± 6.56 mmol/L), butyric acid (8.47 ± 3.47 and 8.65 ± 3.79 mmol/L), total gas (111.34 ± 81.90 and 116.46 ± 82.44 mL/g of organic matter), and CH4 (9.65 ± 9.45 and 10.35 ± 9.33 mmol/L) were similar in the 2 data sets. The best calibration models were retained based on the coefficient of determination (R2) and the ratio of prediction to deviation (RPD). The R2 values for prediction of VFA ranged from 0.69 (RPD = 3.28) for valeric acid to 0.94 (RPD = 4.20) for acetic acid. The models also provided good predictions of CH4 (R2 = 0.89, RPD = 3.05) and cumulative gas production (R2 = 0.91, RPD = 3.30). The models described here precisely and accurately estimated the production of CH4 and VFA during in vitro rumen fermentation tests. Validations at additional laboratories may provide more robust calibrations.


Impairment of the thymus-dependent humoral immune response by syngeneic or allogeneic pregnancy.
Pregnancy results in a diminished capacity of the gravid mouse to respond to thymus-dependent antigens. The IgM response to thymus dependent and independent antigens is relatively unaltered whereas the IgG response to thymus-dependent antigens is markedly suppressed in both syngeneic and allogeneic pregnancy. The impairment of the humoral immune response is not due to loss of antibody-forming precursor lymphocytes (AFPL) from the spleen since their number remains unaltered. During pregnancy the spleen becomes enlarged and the precursor frequency is diluted somewhat but the AFPLs retain their normal activity in vitro. This implies an alteration in their amplification by accessory cells (T cells or macrophages) is responsible for the impaired IgG responses.


Dual isotope F-18 FDG and Tc-99m RBC imaging for lung cancer.
To produce fluorodeoxyglucose (FDG) images with markers for normal organs and large blood vessels in patients with suspected lung cancer. Dual isotope SPECT images were made using F-18 FDG- and Tc-99m-labeled autologous red cells. FDG-positive lesions are localized in relation to major structures when they are viewed in a fused rotating three-dimensional display or in cross sections. Tc-99m red cell and FDG fusion imaging provides relative location information for lung tumors.


Timing of Insulin with Meals in the Hospital: a Systems Improvement Approach.
Coordination of glucose monitoring, mealtimes, and insulin delivery in the hospital is complex, involving interactions between multiple key agents and overlapping workflows. The purpose of this review is to evaluate the scope of the problem as well as to assess evidence for interventions. In recent years, there has been an emphasis on systems-based approaches which address multiple contributing components of the problem at once in an effort to more seamlessly integrate workflows. Technological advances, such as decision support systems and advances in automated insulin delivery, and strategies that minimize the need for complex insulin regimens hold promise for future study. Evaluation of the coordination of insulin delivery is limited by a lack of standardized metrics and systematically collected mealtimes. Nevertheless, successful efforts include system-wide multicomponent interventions, though advances in therapeutic approaches may be of value.


Treatment of Neurological Manifestations of Gluten Sensitivity and Coeliac Disease.
The aim of this paper was to overview the current literature in order to establish the available treatment options for the neurological manifestations of gluten-related disorders (serologically confirmed gluten sensitivity and coeliac disease). A range of debilitating neurological manifestations is increasingly being recognized in patients with gluten sensitivity with and without enteropathy even in the absence of gastrointestinal symptoms. Ataxia is the commonest neurological manifestation, followed by peripheral neuropathy. Epilepsy, headache, encephalopathy, various movement disorders, cognitive impairment, and muscle disorders have also been linked to gluten sensitivity and coeliac disease and are discussed in this review. Strict gluten-free diet is an effective first-line treatment of the neurological manifestations of gluten-related disorders. Very few patients will require additional immunosuppressive treatment usually in the form of mycophenolate.


Trisomy 12 in Burkitt-like lymphoma associated with acquired immunodeficiency syndrome.
Cytogenetic abnormalities have been reported in lymphoproliferative disorders, the most common of which is the t(8;14) translocation in Burkitt and Burkitt-like lymphomas. We report a 30-year-old homosexual male with Burkitt-like lymphoma and trisomy 12. This patient presented with persistent generalized lymphadenopathy and subsequently developed advanced lymphoma. Cell surface markers revealed a monoclonal pattern containing mu heavy chain and kappa light chain immunoglobulins. Cytogenetic analysis of bone marrow involved with lymphoma revealed an additional chromosome #12. Mitogen-stimulated cultures of peripheral blood showed a normal 46,XY karyotype. Trisomy 12 has been found in chronic lymphocytic leukemia and in other low-grade B-cell lymphoproliferative disorders, but not in Burkitt-like lymphoma.


Double crush syndrome of the median nerve revealing a primary non-Hodgkin's lymphoma of the flexor digitorum superficialis muscle.
Extranodal manifestations of lymphoma are well described in the literature and occur in 20 to 30% of patients. Skeletal muscle involvement is rare. We describe the case of a patient with non-Hodgkin's lymphoma in a forearm muscle. At the age of 86, the featured patient started experiencing continuous, progressive and high intensity pain that was more frequent at night and localized in the right dominant hand. It was associated with paresthesia and hypoesthesia, primarily in the thumb, index finger and middle finger. Clinical examination and electrodiagnosis led to the diagnosis of carpal tunnel syndrome. The patient underwent carpal tunnel release at a private hand center. The progression was unfavorable. Additional clinical examination and electrodiagnosis showed compression of the anterior interosseous nerve (double crush syndrome). The patient was referred to our university hand center for further management. Magnetic resonance imaging showed a large mass of about 20cm occupying the entire anterior compartment of the forearm and enclosing the median nerve. Biopsies were performed and revealed a diffuse large B-cell primary non-Hodgkin's lymphoma. The patient underwent chemotherapy and radiotherapy. Six months later, the patient was in complete remission. Muscular involvement during lymphoma is rare. Biopsy is mandatory; needless radical surgery can be avoided because lymphoma is primarily a non-surgical disease. The key points of the treatment process are reviewed.


Accumulation of wet-deposited radiocaesium and radiostrontium by spring oilseed rape (Brássica napus L.) and spring wheat (Tríticum aestívum L.).
The accumulation of (134)Cs and (85)Sr within different parts of spring oilseed rape and spring wheat plants was investigated, with a particular focus on transfer to seeds after artificial wet deposition at different growth stages during a two-year field trial. In general, the accumulation of radionuclides in plant parts increased when deposition was closer to harvest. The seed of spring oilseed rape had lower concentrations of (85)Sr than spring wheat grain. The plants accumulated more (134)Cs than (85)Sr. We conclude that radionuclides can be transferred into human food chain at all growing stages, especially at the later stages. The variation in transfer factors during the investigation, and in comparison to previous results, implies the estimation of the risk for possible transfer of radionuclides to seeds in the event of future fallout during a growing season is still subject to considerable uncertainty.


Acetyl-CoA carboxylase 1 is a suppressor of the adipocyte thermogenic program.
Disruption of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) in mice induces browning in inguinal white adipose tissue (iWAT). However, adipocyte FASN knockout (KO) increases acetyl-coenzyme A (CoA) and malonyl-CoA in addition to depletion of palmitate. We explore which of these metabolite changes triggers adipose browning by generating eight adipose-selective KO mouse models with loss of ATP-citrate lyase (ACLY), acetyl-CoA carboxylase 1 (ACC1), ACC2, malonyl-CoA decarboxylase (MCD) or FASN, or dual KOs ACLY/FASN, ACC1/FASN, and ACC2/FASN. Preventing elevation of acetyl-CoA and malonyl-CoA by depletion of adipocyte ACLY or ACC1 in combination with FASN KO does not block the browning of iWAT. Conversely, elevating malonyl-CoA levels in MCD KO mice does not induce browning. Strikingly, adipose ACC1 KO induces a strong iWAT thermogenic response similar to FASN KO while also blocking malonyl-CoA and palmitate synthesis. Thus, ACC1 and FASN are strong suppressors of adipocyte thermogenesis through promoting lipid synthesis rather than modulating the DNL intermediates acetyl-CoA or malonyl-CoA.


p38 MAP kinase plays a role in G2 checkpoint activation and inhibits apoptosis of human B cell lymphoma cells treated with etoposide.
p38 MAPK is mainly activated by stress stimuli and mediates signals that regulate various cellular responses, including cell-cycle progression and apoptosis, depending on cell types and stimuli. Here we examine the role of p38 in regulation of apoptosis and cell cycle checkpoint in Daudi B-cell lymphoma cells treated with the topoisomerase II inhibitor etoposide. Etoposide activated p38, inhibited the G2/M transition with the persistent inhibitory phosphorylation of Cdc2 on Tyr15, and caused apoptosis of Daudi cells. Inducible expression of a dominant negative p38alpha mutant in Daudi cells reduced the inhibition of Cdc2 as well as G2/M arrest and augmented apoptosis induced by etoposide. SB203580, a specific inhibitor of p38alpha and p38beta, similarly reduced the inhibitory phosphorylation of Cdc2 as well as G2/M arrest and augmented apoptosis of Daudi cells treated with etoposide. These results suggest that p38 plays a role in G2/M checkpoint activation through induction of the persistent inhibitory phosphorylation of Cdc2 and, thereby, inhibits apoptosis of Daudi cells treated with etoposide. The present study, thus, raises the possibility that p38 may represent a new target for sensitization of lymphoma cells to DNA-damaging chemotherapeutic agents.


Endemic pyoderma in Ghana: a survey in rural villages.
The prevalence and characteristics of pyoderma in a randomly sampled rural population in Ghana has been studied. Findings are compared with studies reported in recent literature which describe pyoderma in other countries. In the present study, conducted in 1975 as part of the Danfa Project's Village Health Survey, pyoderma was diagnosed in 19.4% of villagers examined. Peak rates occurred in the five to nine-year-old age group, and pyoderma was more prevalent among males and unskilled labourers and farmers than among those engaged in more sedentary occupations. Non-bullous impetigo was most common (72% of lesions) and, in contrast to other studies, non-group A-streptococci predominated in these lesions (82% of streptococcal lesions were Group G, 18% Group C). Current knowledge of transmission and control of pyoderma is discussed.


Intravenous access in infants and children.
At times, nothing is more difficult, time consuming or frustrating than obtaining vascular access in the pediatric patient. Today, technologic improvements in catheter design and imaging techniques have significantly facilitated line placement and increased the available options for vascular access. All clinicians involved in the care of pediatric patients should have knowledge of the various methods available for venous access, as well as their relative indications, advantages and disadvantages. This article discusses various sites used for venous access in the pediatric patient, as well as techniques that may be used by the pediatrician and those that require surgical consultation.


Intertrochanteric partial osteotomy for posterior hip approach.
The posterior dislocation remains one unresolved complication of the posterior approach to the hip joint. In this study, a variation of the posterior hip approach - a partial osteotomy of the greater trochanter - was performed in order to investigate whether it provides better stability to the operated hip joint and reduces the risk of dislocation. We carried out a partial intertrochanteric osteotomy, initially in a cadaveric model and then in 68 patients (30 acute neck of femur fractures and 38 patients with hip osteoarthritis) requiring a total hip replacement. The osteotomised fragment was reattached with wires. All arthroplasties were cemented with Müller acetabular component and Charnley-type stem with a 28-mm interchangeable neck. Intraoperatively, all hips were tested for stability. After the osteosynthesis of the osteotomised fragment, hip dislocation points were increased more than 15% in the flexion and 10% in the internal rotation plane of movement. At one year follow up, no dislocation was observed in the clinical component of the study. This technique was found reliable in providing a stable hip joint.


Sildenafil citrate: lessons learned from 3 years of clinical experience.
In the 3 y since its initial approval, sildenafil has become the most widely used treatment for erectile dysfunction (ED) and has been prescribed to more than 13 million patients worldwide. Significant improvements in erectile function have been demonstrated in double-blind, placebo-controlled studies in diverse patient populations. A significant treatment effect has been shown with sildenafil in men with ED and a history of diabetes, cardiovascular disease, minor depression, spinal cord injury and multiple sclerosis. In addition, promising results have been shown in patients with treated prostate cancer, end-stage renal disease, Parkinson's disease and spina bifida and in multiple-organ transplant recipients. Postmarketing data of the use of sildenafil in clinical practice confirm the efficacy and safety found in clinical trials and high satisfaction with treatment. Public awareness of the common occurrence of ED and the high likelihood of a potentially favorable response to an oral treatment increased dramatically with the introduction of sildenafil. Physicians, however, are still not comfortable with ED management, which negatively affects pharmacotherapy response rates and patients' compliance to treatment. Continuing medical education seems mandatory to overcome existing problems in ED management.


The biology of mucus: Composition, synthesis and organization.
In this review we discuss mucus, the viscoelastic secretion from goblet or mucous producing cells that lines the epithelial surfaces of all organs exposed to the external world. Mucus is a complex aqueous fluid that owes its viscoelastic, lubricating and hydration properties to the glycoprotein mucin combined with electrolytes, lipids and other smaller proteins. Electron microscopy of mucosal surfaces reveals a highly convoluted surface with a network of fibers and pores of varying sizes. The major structural and functional component, mucin is a complex glycoprotein coded by about 20 mucin genes which produce a protein backbone having multiple tandem repeats of Serine, Threonine (ST repeats) where oligosaccharides are covalently O-linked. The N- and C-terminals of this apoprotein contain other domains with little or no glycosylation but rich in cysteines leading to dimerization and further multimerization via SS bonds. The synthesis of this complex protein starts in the endoplasmic reticulum with the formation of the apoprotein and is further modified via glycosylation in the cis and medial Golgi and packaged into mucin granules via Ca2+ bridging of the negative charges on the oligosaccharide brush in the trans Golgi. The mucin granules fuse with the plasma membrane of the secretory cells and following activation by signaling molecules release Ca2+ and undergo a dramatic change in volume due to hydration of the highly negatively charged polymer brush leading to exocytosis from the cells and forming the mucus layer. The rheological properties of mucus and its active component mucin and its mucoadhesivity are briefly discussed in light of their importance to mucosal drug delivery.


[Mathematical foundation for biophysical methods in fetal monitoring. III. Magnetocardiography, phonocardiography, polycardiography, and Doppler blood flow analysis].
Magnetocardiography, phonocardiography, polycardiography and blood flow analysis based on Doppler phenomenon are described discussing the importance of these methods in fetal monitoring in pregnancy and labour.


Schizophrenia and the serotonin transporter gene.
A case control study was conducted among cases with schizophrenia (DSM IV criteria) and screened adult controls from three cohorts. Bi-allelic polymorphisms in the promoter region of the serotonin transporter gene (5-HTT) were examined in conjunction with those of the serotonin 5-HT2a receptor (HTR2). No significant association with 5-HTT was detected among US Caucasians (n = 207), African-Americans (n = 84) or Caucasians from Sweden (n = 221). However, survival analysis suggested an association with the age at onset among the Swedish cases. The association should be considered tentative as it was not evident in the smaller US samples. The following exploratory analyses among the US samples were also not significant: associations with subgroups of patients based on familiality or response to medications, or altered risk due to the joint effects of 5-HTT and HTR2 genotypes.


Regulatory aspects of mitochondrial phospholipase A2: correlation of hydrolysis rates with substrate configuration as evidenced by 31P-NMR.
The influence of variation of the phospholipid composition in model membranes composed of phosphatidylcholine and phosphatidylethanolamine on the hydrolysis of these phospholipids by rat liver mitochondrial phospholipase A2 was investigated. With the pure phospholipids, phosphatidylethanolamine was hydrolyzed over 30-times faster than phosphatidylcholine. Upon increasing the mole percentage of phosphatidylethanolamine in mixtures, a gradual, though non-linear, increase in the initial rate of hydrolysis of this phospholipid was observed. By contrast, phosphatidylcholine hydrolysis remained constant up to about 50 mol% phosphatidylethanolamine, whereafter a sudden fall-off of activity was observed. This drop in the hydrolysis rate coincided with a transition of the phospholipid structure from bilayer to an as yet unidentified organization characterized by an isotropic signal in the 31P-NMR spectra recorded in the presence of Ca2+. The occurrence of this phase was clearly dependent on Ca2+, since mixtures with identical composition in the absence of Ca2+ remained largely in bilayer configuration. That the structure adopted by phospholipids is of importance for their susceptibility to attack by this intracellular phospholipase A2 became evident also in studies with the single phospholipids in the absence or presence of Triton X-100 above the critical micellar concentration. While phosphatidylcholine hydrolysis was inhibited in mixed micelles as compared to its bilayer organization, the hydrolysis of phosphatidylethanolamine in mixed micelles was 3-fold that in the hexagonal HII phase.


Incidence and patterns of surgical glove perforations: experience from Addis Ababa, Ethiopia.
Surgical glove perforation is a common event. The operating staff is not aware of the perforation until the procedure is complete, sometimes in as high as 70% of the incidences. Data from Ethiopia indicates that the surgical workforce suffers from a very surgery related accidents, however there is paucity of data regarding surgical glove perforation. The main objective is to describe the incidence and patterns of surgical glove perforation during surgical procedures and to compare the rates between emergency and elective surgeries at one of the main hospitals in Addis Ababa Ethiopia. This is a prospective study, performed at the Minilik II referral hospital, Addis Ababa. All surgical gloves worn during all major surgical procedures (Emergency and Elective) from June 1-July 20, 2016 were collected and used for the study. Standardised visual and hydro insufflation techniques were used to test the gloves for perforations. Parameters recorded included type of procedure performed, number of perforations, localisation of perforation and the roles of the surgical team. A total of 2634 gloves were tested, 1588 from elective and 1026 from emergency procedures. The total rate of perforation in emergency procedures was 41.4%, while perforation in elective surgeries was 30.0%. A statistically significant difference (P < 0.05) was found in between emergency and elective surgeries. There were a very high rate of perforations of gloves among first surgeons 40.6% and scrub nurses 38.8% during elective procedures and among first surgeons (60.14%), and second assistants (53.0%) during emergency surgeries. Only 0.4% of inner gloves were perforated. The left hand, the left index finger and thumb were the most commonly perforated parts of the glove. Glove perforation rate was low among consultant surgeons than residents. Our reported perforation rate is higher than most publications, and this shows that the surgical workforce in Ethiopia is under a clear and present threat. Measures such as double gloving seems to have effectively prevented cutaneous blood exposure and thus should become a routine for all surgical procedures. Manufacturing related defects and faults in glove quality may also be contributing factors.


From dermatological conditions to COVID-19: Reasoning for anticoagulation, suppression of inflammation, and hyperbaric oxygen therapy.
COVID-19 generates a complex systemic inflammatory response that can lead to death due to wide macrophage activation, endothelial damage, and coagulation in critically ill patients. SARS-CoV-2-induced lung injury due to inflammatory mediated thrombosis could be similar to the livedoid vasculopathy in the skin, supporting a translational comparison of these clinical settings. In this article, we discuss anticoagulation, suppression of inflammatory response, and hyperbaric oxygen therapy in the context of severe COVID-19 and livedoid vasculopathy.


Iron Deficiency in Patients with Inflammatory Bowel Diseases: A Prospective Multicenter Cross-Sectional Study.
Iron deficiency (ID) is a frequent condition in patients with inflammatory bowel disease (IBD). Our aim was to investigate the prevalence of ID in patients with IBD. This was a prospective multicenter cross-sectional study conducted in 21 gastroenterology departments in France between January and March 2020. All adult patients with confirmed IBD who were admitted to the hospital were eligible for inclusion. ID was defined as ferritinemia ≤ 100 μg/L in patients with signs of inflammation (C-reactive protein (CRP) ≥ 5 mg/L) or ferritinemia < 30 μg/L in the absence of inflammation. In total, 1036 IBD (685 Crohn's disease and 351 ulcerative colitis) patients (52.1% women) with a mean age of 41.8 ± 15.5 years were recruited. Approximately half of the patients (504, 51.1%) were in disease remission at the time of enrollment. Systematic monitoring of iron status was performed in 12/21 (57%) participating centers, including measurements of ferritin (12/12, 100%), hemoglobin (11/12, 92%), transferrin saturation (TSAT) (6/12, 50.0%), and serum iron (5/12, 42%). About one-fifth of the patients had been treated with intravenous iron (218, 21.0%), whereas only a small percentage received oral iron (36, 3.5%). ID occurred in 97 patients (23.7% CI 95% 19.8-28.1). Patients with moderate/severe IBD activity (OR: 3.66; CI 95% 24.4-61.2; p = 0.007) or concomitant anemia (OR: 3.66; CI 95% 1.97-6.78; p < 0.001) had an increased likelihood of having ID. Patients with moderate/severe IBD activity or concomitant anemia are at increased risk of ID. Early detection and management of ID in patients with IBD is recommended.


Rift Valley fever MP-12 vaccine elicits an early protective immune response in mice.
Rift Valley fever virus (RVFV) is an important mosquito-borne pathogen that causes outbreaks of severe disease in people and livestock throughout Africa and the Arabian Peninsula. The development of an effective veterinary and human vaccine to protect against Rift Valley fever (RVF) disease remains a high priority. The live attenuated RVFV MP-12 is a promising vaccine candidate for the prevention of RVF in both human and domestic ruminants. The aim of this study was to determine the onset of protective immunity elicted in mice by a single dose of this vaccine. Groups of CD-1 mice were vaccinated intraperitoneally with RVFV MP-12 vaccine and challenged on days 2, 5, 6 and 7 post-vaccination (PV) with a lethal dose of virulent RVFV. The mice were observed once daily for terminal morbidity and blood samples were obtained from the retro-orbital sinus complex on days 23 and 28 PV of surviving mice to determine RVFV neutralizing antibody titers. In one test, 2 of 3 mice challenged on day 2 PV survived and all 3 mice challenged at days 5 and 7 PV also survived. A second test of 10 mice per group was performed, and half (5) of those challenged at day 2 PV survived while all (10) survived challenge at day 4 and 6 PV. All surviving animals develop antibody that ranged from 1:80 to 1:1,280 PV. In a separate experiment, RVFV MP-12 vaccinated CD-1 mice, but not challenged developed a low viremia for the first 3 days PV and neutralzing antibody was detected on days 5 through day 28 PV. These findings demonstrated that the RVFV MP-12 vaccine elicited a rapid protective immune response in mice as early as 2 days PV, thus further supporting the effectiveness of this vaccine candidate for preventing RVF among humans and domestic ruminants.


Laypersons' esthetic perception of various computer-generated diastemas: a pilot study.
Managing excess anterior spacing is a common problem in dental practice. During orthodontic or restorative treatment planning, clinicians must decide how to distribute this space. However, few reports are available in the dental literature about the attractiveness and esthetic impact of anterior spaces other than midline diastemas. The purpose of this study was to compare the esthetic perception of 4 different anterior diastemas, including simian diastemas (symmetrical diastemas between lateral incisor and canine), diastemas suggested by Frush and Fisher (asymmetrical diastemas between lateral incisor and canine and between central and lateral incisor), and by Lombardi (slight midline diastema and 2 larger diastemas between central and lateral incisors), and a midline diastema. A picture of a young woman's smiling face was modified by using photoediting software to create the 4 previously mentioned diastemas. The resulting pictures were presented to laypersons questioned in French public places. The participants were asked to rank the pictures from most to least attractive, then to rate them with a mark from 1 to 10. One hundred and five participants completed the questionnaire. The median ranks and scores attributed to the pictures from most to least attractive were as follows: simian diastemas, 1 and 8; Frush and Fisher diastemas, 2 and 7; Lombardi diastemas, 3 and 5; and midline diastemas, 4 and 4, respectively. The hierarchy (simian diastemas>Frush and Fisher diastemas>Lombardi diastemas>midline diastemas) could be established statistically for the scores (P=.03, P<.001, and P<.001, respectively) but not for the ranks when adjusting on subjects' sex and age (P=.11, P=.03, and P=.06, respectively). The results showed an esthetic hierarchy of anterior diastemas. The negative perception of anterior diastemas seems to mainly be related to the presence and width of a midline diastema. These results can guide clinical decisions for patients with excess anterior spacing.


Enterotoxigenic potential of coagulase-negative staphylococci.
Staphylococci are a worldwide cause of human and animal infections including life-threatening cases of bacteraemia, wound infections, pyogenic lesions, and mastitis. Enterotoxins produced by some staphylococcal species were recognized as causative agents of staphylococcal food poisoning (SFP), being also able to interrupt human and animal immune responses. Only enterotoxins produced by Staphylococcus aureus were as yet well characterized. Much less is known about enterotoxigenic potential of coagulase-negative species of genus Staphylococcus (CNS). The pathogenic role of CNS and their enterotoxigenicity in developing SFP has not been well established. Although it has been reported that enterotoxigenic CNS strains have been associated with human and animal infections and food poisoning, most of research lacked a deeper insight into structure of elements encoding CNS enterotoxins. Recent studies provided us with strong evidence for the presence and localization of enterotoxin-coding elements in CNS genomes and production of enterotoxins. Thus, the importance of pathogenic potential of CNS as a source of staphylococcal enterotoxins has been highlighted in human and animal infections as well as in food poisoning.


Towards the molecular origin of glutamate CEST (GluCEST) imaging in rat brain.
Chemical exchange saturation transfer (CEST) signals at 3 ppm acquired with high irradiation powers, termed GluCEST, have been suggested as an indicator of glutamate in neural systems. However, amines in proteins may also contribute to the GluCEST signal, but they have been ignored in previous studies. This study aims to investigate the molecular origins and specificity of GluCEST signal in rat brain. Dialysis was used to selectively remove small molecules, such as glutamate and other metabolites, from tissue homogenates prepared from rat brain. This approach allowed the specific influence of proteins on GluCEST to be measured. Clean CEST effects were also quantified by a 2-step analysis, which first used a fitting approach to quantify the asymmetric magnetization transfer effect and an inverse subtraction to remove it, and then combined an apparent exchange-dependent relaxation method with asymmetric analysis to remove the direct water saturation and T1 weighting. The removal of glutamate and other small metabolites by dialysis decreases the GluCEST signal by approximately 24%, indicating that a major contributor to GluCEST in the brain is amines in proteins under our experimental conditions. Data from in vivo GluCEST measurements should be interpreted with caution, especially in disorders in which changes in the content or conformation of proteins are expected.


Three-dimensional chromatin organization in cardiac development and disease.
Recent technological advancements in the field of chromatin biology have rewritten the textbook on nuclear organization. We now appreciate that the folding of chromatin in the three-dimensional space (i.e. its 3D "architecture") is non-random, hierarchical, and highly complex. While 3D chromatin structure is partially encoded in the primary sequence and thereby broadly conserved across cell types and states, a substantial portion of the genome seems to be dynamic during development or in disease. Moreover, there is growing evidence that at least some of the 3D structure of chromatin is functionally linked to gene regulation, both being modulated by and impacting on multiple nuclear processes (including DNA replication, transcription, and RNA splicing). In recent years, these new concepts have nourished several investigations about the functional role of 3D chromatin topology dynamics in the heart during development and disease. This review aims to provide a comprehensive overview of our current understanding in this field, and to discuss how this knowledge can inform further research as well as clinical practice.


Increased cardiovascular risk in rats with primary renal dysfunction; mediating role for vascular endothelial function.
Primary chronic kidney disease is associated with high cardiovascular risk. However, the exact mechanisms behind this cardiorenal interaction remain unclear. We investigated the interaction between heart and kidneys in novel animal model for cardiorenal interaction. Normal Wistar rats and Munich Wistar Fromter rats, spontaneously developing renal dysfunction, were subjected to experimental myocardial infarction to induce cardiac dysfunction (CD) and combined cardiorenal dysfunction (CRD), respectively (N = 5-10). Twelve weeks later, cardiac- and renal parameters were evaluated. Cardiac, but not renal dysfunction was exaggerated in CRD. Accelerated cardiac dysfunction in CRD was indicated by decreased cardiac output (CD 109 ± 10 vs. CRD 79 ± 8 ml/min), diastolic dysfunction (E/e') (CD 26 ± 2 vs. CRD 50 ± 5) and left ventricular overload (LVEDP CD 10.8 ± 2.8 vs. CRD 21.6 ± 1.7 mmHg). Congestion in CRD was confirmed by increased lung and atrial weights, as well as exaggerated right ventricular hypertrophy. Absence of accelerated renal dysfunction, measured by increased proteinuria, was supported by absence of additional focal glomerulosclerosis or further decline of renal blood flow in CRD. Only advanced peripheral endothelial dysfunction, as found in CRD, appeared to correlate with both renal and cardiac dysfunction parameters. Thus, proteinuric rats with myocardial infarction showed accelerated cardiac but not renal dysfunction. As parameters mimic the cardiorenal syndrome, these rats may provide a clinically relevant model to study increased cardiovascular risk due to renal dysfunction. Peripheral endothelial dysfunction was the only parameter that correlated with both renal and cardiac dysfunction, which may indicate a mediating role in cardiorenal interaction.


The effect of lactic acid sprays on the keeping qualities of meat during storage.
Spraying the meat surface of skinned cow heads with 1% v/v lactic acid resulted in significant reduction in total viable counts of bacteria at storage temperatures of 4, 15 and 20 degrees C. The number of coliform bacteria was also reduced at all three temperatures but the reductions were not statistically significant on most occasions. However, after five and two days at 15 degrees C and 20 degrees C, respectively, when the initial effect of acid appeared to be lost, the number of coliforms on sprayed heads exceeded those on unsprayed heads. The shelf lives of all sprayed heads were observed to have been extended for about three days at 4 degrees C and one day for both 15 degrees C and 20 degrees C.


Factors associated with quality of care in inflammatory bowel diseases: a view from patient's side using the IQCARO quality of care decalogue.
Quality of care (QoC) is a highly important topic in inflammatory bowel disease (IBD). We recently elaborated a decalogue of QoC indicators (IQCARO-QoC) developed by IBD patients. The aim of the present study was to assess the factors associated with patients' evaluation of QoC in Spain using the IQCARO-QoC Decalogue recently developed by IBD patients. A survey including patients' socio-demographic and clinical characteristics, and the IQCARO-QoC Decalogue, was completed by IBD patients. We described patients' assessment of QoC across Spanish patients. A univariable and multivariable analysis was performed to explore the associations between patients' characteristics and QoC. Questionnaires from 788 participant patients were analysed. Participants' mean age was 43.4 years, 63% were females and 58% had Crohn's disease. The mean QoC score was 8.1 (± 2.4 SD) points out of a maximum of 10. Items with the lowest score were related to the provision of information and the implication of the medical team throughout the entire patient care. Factors associated with better QoC scores included: being employed better disease control, fewer numbers of unscheduled visits, and being followed by a gastroenterologist specialized in IBD. Spanish patients' reported QoC seems to be globally good although there is room for improvement, especially in providing adequate information to patients. Care provided by specialized IBD gastroenterologists seems to be related with higher QoC scores.


Pharmacokinetics of intravenous cyclophosphamide in man, estimated by gas-liquid chromatography.
A simple gas chromatographic assay utilising alkali flame ionisation detection is described for the estimation of cyclophosphamide as its trifluoroacetate derivative from plasma. Examination of five patients following intravenous cyclophosphamide gave values of 8.9 h (SD 2.7) for the half-life and 0.061 liters/h/kg (SD 0.011) for whole-body clearance of the drug.


25-Hydroxyvitamin D3 metabolism in mitochondria from primary renal cultures.
Previous in vitro studies concerning the renal metabolism of 25-hydroxyvitamin D3 (25(OH)D3) to form 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25R-dihydroxyvitamin D3 (24,25(OH)2D3) have utilized intact cell systems. In reflecting upon the possible mechanisms by which hormonally induced changes in the production of 1,25(OH)2D3 and 24,25(OH)2D3 may be brought about, we asked whether altered mitochondrial hydroxylase activities can quantitatively account for changes in the total cellular output of these steroids. Our objective was to delineate between extramitochondrial processes (e.g. altered substrate delivery), and those events restricted to the renal mitochondria (altered hydroxylase activities). We have examined the effect of pretreating primary cultures of chick kidney cells with either 1,25(OH)2D3 or parathyroid hormone (PTH) on 25(OH)D3-hydroxylase activities present in subsequently isolated mitochondria. Pretreatment with 10(-7) M 1,25(OH)2D3 reduced 1 alpha-hydroxylase activity in both cells and mitochondria to approximately 60% of control values by 1 h, and to 25-30% by 2 h. The effect of PTH (10 ng/ml) in both mitochondrial and whole cell preparations was an approximate 40% increase in measured 1 alpha-hydroxylase activity. 10 microM forskolin (FSK) elicited an approximate 2-fold increase in 1,25(OH)2D3 production. Reciprocal effects were observed with respect to 24-hydroxylase activity in both whole cell and mitochondrial preparations in response to exogenous 1,25(OH)2D3, PTH, and FSK. The findings demonstrate that these hormones initiate intracellular events which lead directly to altered 25(OH)D3 1 alpha- and 24-hydroxylase activities within the renal mitochondria.


A Distinctive Pattern of Beauveria bassiana-biotransformed Ginsenoside Products Triggers Mitochondria/FasL-mediated Apoptosis in Colon Cancer Cells.
Ginseng is one of the most commonly used adaptogens. Transformation into the minor ginsenosides produces compounds with more effective action. Beauveria bassiana, a teleomorph of Cordyceps bassiana, is a highly efficient producer of mammalian steroids and produces large amounts of sugar-utilizing enzymes. However, the fermentation of steroid glycosides in ginseng with B. bassiana has never been studied. Thus, we evaluated the bioconversion of the major ginsenosides in white ginseng by B. bassiana. Interestingly, B. bassiana increased the total amount of protopanaxadiols and hydrolyzed Rb1 into minor ginsenosides, exhibiting high levels of Rd and Rg3, as well as moderate levels of Rb2 and Rc analyzed by high-performance liquid chromatography coupled with evaporative light-scattering detection. The β-glucosidase activity was highly increased, which led to the selective elimination of sugar moiety at the 20-C position of Rb1 to Rd, followed by Rg3. Rb2 and Rc accumulated because of the minimal activities of α-L-arabinopyranosidase and α-L-arabinofuranosidase, respectively. The fermentation product exerted dose-dependent cytotoxicity in HCT-15 cells, which are resistant to ginseng. The product, but not white ginseng, exhibited apoptotic effects via the Fas ligand and caspase 8/9. This study demonstrates for the first time that the B. bassiana-fermented metabolites have potent apoptotic activity in colon cancer cells, linking to a therapeutic use.


Effect rates of different modalities for treatment of prolactin adenomas.
Results of treatment of 963 patients with prolactin adenomas described in the literature were reviewed. The patient population was stratified into four subgroups: women and men with serum prolactin levels above and below 100 ng/ml for each of the treatment modalities: transsphenoidal surgery, bromocriptine, heavy ion radiation, conventional radiation, and transsphenoidal surgery plus conventional radiation. The five largest series within each subgroup were included. Success rates and recurrence rates were calculated for: (1) reduction of tumor size, (2) normalization of serum prolactin levels, and (3) normalization of other pituitary functions. Complication rates were calculated for procedural impairment of other pituitary functions. Transsphenoidal surgery was found to be the most effective treatment for lasting control, and bromocriptine for temporary control, of prolactin adenomas. Recurrent adenomas were most effectively treated by transsphenoidal surgery if serum prolactin levels were below 100 ng/ml. If serum prolactin levels were above 100 ng/ml, bromocriptine was the most effective treatment. Heavy ion radiation, with success rates comparable to those of transsphenoidal surgery and bromocriptine, but with lower recurrence rates, may eventually prove the most effective treatment of all.


MHC-restricted cytotoxic T-lymphocyte assay: an improved method based on normal and SV40-immortalized rabbit epidermal target cells.
Although several techniques are available to evaluate cell-mediated immunity, numerous difficulties have prevented their use in rabbits. Cytotoxic T-lymphocyte (CTL) assays have been used to determine the ex vivo cytolytic activity of CD8+ T-lymphocytes in immunization protocols. However, this assay cannot be performed with rabbit peripheral blood mononuclear cell (PBMC) targets because of their high spontaneous (51)Cr release. To overcome this intrinsic difficulty shown by rabbit cells, syngeneic normal and SV40-immortalized cells were prepared from skin biopsies. The results show that: (i) skin-derived rabbit fibroblasts can be used as target cells after infection with a fowlpox virus recombinant; (ii) SV40-immortalized skin fibroblasts appear to be more appropriate for repeated assays; (iii) antigen-expanded T-cells and fresh PBMCs can be used as effectors with a similar efficiency; and (iv) dissociation of adherent skin fibroblast target cells with EDTA is to be preferred over TrypLE enzymatic treatment.


Nonosseous lesions of the anterior cruciate ligaments in childhood and adolescence.
Damage of the knee joint has increased during the last few years owing to overindulgence in sports. The anterior cruciate ligaments play a major role in knee joint stability. Treatment of injured knee joint structures in childhood and adolescence is more complicated than in adults. From 1972 to 1987 we have seen 330 patients with knee injuries, 28 of whom had nonosseous lesions of the anterior curciate ligaments. Of these, 20 were followed-up; 17 children were operated on primarily, 3 were conservatively immobilized. On follow-up, 15 patients showed signs of residual instability. Primary treatment depends on the presence and the extent of associated injuries of the knee joint.


N-adamantyl-4-methylthiazol-2-amine suppresses lipopolysaccharide-induced brain inflammation by regulating NF-κB signaling in mice.
We report that N-adamantyl-4-methylthiazol-2-amine (KHG26693), a novel thiazole derivative, can prevent lipopolysaccharide (LPS)-induced brain inflammation in mice. In this LPS-induced model of brain inflammation, administration of KHG26693 effectively prevented increases in the levels of IL-1β, TNF-α, prostaglandin E2, malondialdehyde, and nitric oxide, and mitigated reductions in the levels of superoxide dismutase in the hippocampus. KHG26693 also prevented reductions in the levels of hippocampal brain-derived neurotrophic factors. Furthermore, pretreatment with KHG26693 prior to LPS treatment dramatically attenuated the elevation of inducible nitric oxide synthase and cyclooxygenase-2 protein levels. Moreover, pretreatment with KHG26693 significantly suppressed LPS-induced phosphorylation of NF-κB and IκBα through the inactivation of IKKβ. Additionally, KHG26693 caused the downregulation of LPS-induced cystathionine-b-synthase gene expression in the brain. Although the clinical relevance of our findings remains to be determined, our data suggest that KHG26693 might prevent neuronal cell injury via the reduction of inflammation and oxidative stress in the brain.


Comparison of electron and chemical ionization modes for the quantification of thiols and oxidative compounds in white wines by gas chromatography-tandem mass spectrometry.
A rapid, sensitive method for assaying volatile impact compounds in white wine was developed using gas chromatography-tandem mass spectrometry (GC-MS/MS) technology, with a triple quadrupole analyzer operating in chemical ionization and electron impact mode. This GC-MS/MS method made it possible to assay volatile thiols (3SH: 3-sulfanylhexanol, formerly 3MH; 3SHA: 3-sulfanylhexyl acetate, formerly 3MHA; 4MSP: 4-methyl-4-sulfanylpentan-2-one, formerly 4MMP; BM: benzenemethanethiol; E2SA: ethyl 2-sulfanylacetate; and 2FM: 2-furanmethanethiol) and odoriferous oxidation markers (Sotolon: 4,5-dimethyl-3-hydroxy-2(5)H-furanone, methional, and phenylacetaldehyde) simultaneously in dry white wines, comparing electron impact (EI) and chemical ionization (CI) modes. More molecular ions were produced by CI than protonated molecules, despite the greater fragmentation caused by EI. So, even using the best reactant gas giving the highest signal for thiols, EI was the best ionization mode, with the lowest detection limits. For all compounds of interest, the limits of quantification (LOQ) obtained were well below their detection thresholds (ranging from 0.5 to 8.5ng/L for volatile thiols and 65-260ng/L for oxidation markers). Recovery rates ranged from 86% to 111%, reproducibility (in terms of relative standard deviation; RSD) was below 18% in all cases, with correlation coefficients above 0.991 for all analytes. The method was successfully applied to the analysis of compounds of interest in Sauvignon Blanc wines from a single estate and ten different vintages.


Ouabain-induced stimulation of sodium-hydrogen exchange in rat optic nerve astrocytes.
Sodium-dependent transporters are inhibited indirectly by the Na-K-ATPase inhibitor ouabain. Here we report stimulation of sodium-hydrogen exchange (NHE) in ouabain-treated cells. BCECF was used to measure cytoplasmic pH in cultured rat optic nerve astrocytes. Ammonium chloride was applied to acid load the cells. On removal of ammonium chloride, cytoplasmic pH fell abruptly, then gradually recovered toward baseline. Ouabain (1 microM) did not change cell sodium content, but the rate of pH recovery increased by 68%. Ouabain speeded pH recovery both in the presence and absence of bicarbonate. In bicarbonate-free medium, dimethylamiloride, an NHE inhibitor, eliminated the effect of 1 microM ouabain on pH recovery. Western blot analysis showed an NHE1 immunoreactive band but not NHE2, NHE3, or NHE4. Immunoprecipitation studies showed phosphorylation of NHE1 in cells treated with 1 microM ouabain. Ouabain evoked an increase of cAMP, and the effect of 1 microM ouabain on pH recovery was abolished by H-89, a protein kinase A inhibitor. 8-Bromoadenosine-cAMP increased the pH recovery rate, and this recovery was not further increased by ouabain. Although 1 microM ouabain did not alter cytoplasmic calcium concentration, it stimulated calcium entry after store depletion, a response abolished by 2-APB. Ouabain-induced stimulation of pH recovery was suppressed by inhibitors of capacitative calcium entry, SKF-96365, and 2-APB, as well as the cytoplasmic calcium chelator BAPTA. The cAMP increase in ouabain-treated cells was abolished by BAPTA and 2-APB. Taken together, the results are consistent with increased capacitative calcium entry and subsequent cAMP-PKA-dependent stimulation of NHE1 in ouabain-treated cells.


The forgotten cohort-lessons learned from prehospital trauma death: a retrospective cohort study.
Trauma related deaths remain a relevant public health problem, in particular in the younger male population. A significant number of these deaths occur prehospitally without transfer to a hospital. These patients, sometimes termed "the forgotten cohort", are usually not included in clinical registries, resulting in a lack of information about prehospitally trauma deaths. The aim of the present study was to compare patients who died prehospital with those who sustained life-threatening injuries in order to analyze and potentially improve prehospital strategies. This cohort study included all primary operations carried out by Switzerland's largest helicopter emergency medical service (HEMS) between January 1, 2011, and December 31, 2021. We included all adult trauma patients with life-threatening or fatal conditions. The outcome of this study is the vital status of the patient at the end of mission, i.e. fatal or life-threatening. Injury, rescue characteristics, and interventions of the forgotten trauma cohort, defined as patients with a fatal injury (NACA score of VII), were compared with life-threatening injuries (NACA score V and VI). Of 110,331 HEMS missions, 5534 primary operations were finally analyzed, including 5191 (93.8%) life-threatening and 343 (6.2%) fatal injuries. More than two-thirds of patients (n = 3772, 68.2%) had a traumatic brain injury without a significant difference between the two groups (p > 0.05). Thoracic trauma (44.6% vs. 28.7%, p < 0.001) and abdominal trauma (22.2% vs. 16.1%, p = 0.004) were more frequent in fatal missions whereas pelvic trauma was similar between the two groups (13.4% vs. 12.9%, p = 0.788). Pneumothorax decompression rate (17.2% vs. 3.7%, p < 0.001) was higher in the forgotten cohort group and measures for bleeding control (15.2% vs. 42.7%, p < 0.001) and pelvic belt application (2.9% vs. 13.1% p < 0.001) were more common in the life-threating injury group. Chest decompression rates and measures for early hemorrhage control are areas for potential improvement in prehospital care.


Ease of use and preference of a new versus widely available prefilled insulin pen assessed by people with diabetes, physicians and nurses.
FlexTouch® (FT; Novo Nordisk A/S, Bagsvaerd, Denmark) is a new prefilled insulin pen that has no push-button extension and low injection force. This multi-centre, crossover usability study evaluated the perceptions of, and preference for, FT versus another widely used prefilled pen, SoloStar® (SS; Sanofi, Paris, France), by people with diabetes and healthcare professionals. Following instruction, participants performed injections into a foam cushion, randomly alternating between doses of 20, 40 and 80 international units (IU). Participants then answered questions on usability and preference. In all, 59 people with diabetes and 61 healthcare professionals (30 physicians and 31 nurses) took part. Overall, significantly more respondents preferred to use FT than SS (83 vs 10%, respectively), found FT easier to use (83 vs 9%) and would recommend FT to others (83 vs 8%; p < 0.001 for all). More respondents found it 'very/fairly easy' to reach the push-button and to inject 20, 40 and 80 IU with FT (93, 90 and 88% to inject, respectively) than with SS (73, 43 and 15% to inject, respectively; p < 0.001 for all). Most respondents chose FT as giving them the most confidence in correct and complete insulin delivery (76 vs 6%; p < 0.001) and considerably more were 'very/rather confident' in managing their daily insulin injections with FT than with SS (88 vs 58%). Most participants rated FT as easier to use and to inject with, were more confident in its accuracy of insulin delivery and preferred it to SS.


Lacidipine self-nanoemulsifying drug delivery system for the enhancement of oral bioavailability.
Low bioavailability of Lacidipine (LD), an calcium channel blocker pose many challenges in the treatment of hypertension. The objective of this study was to formulate and characterize LD self-nanoemulsifying drug delivery systems (SNEDDS) to improve oral bioavailability of the drug. Formulations were evaluated for globule size, surface morphology, emulsification time, cloud point, drug content, in vitro dissolution, ex vivo permeation, stability and oral bioavailability studies. Captex 810D, TPGS, Tween-60, Transcutol P and PEG 400 was selected based on the solubility study results. The optimized SNEDDS readily gets nanoemulsified at 37 °C with droplet size of 41 nm when mixed with 200 times of its water. Transmission electron microscope photographs confirmed the spherical shape of the globules. In vitro dissolution of SNEDDS showed more than 80% of drug release within 15 min. The ex vivo permeation of LD from SNEDDS is 4.8- and 9-fold higher compared to pure drug in the absence and presence of verapamil respectively. The stability study of the SNEDDS confirmed no environmental effect on the physical nature and drug content. Oral bioavailability of SNEDDS is 2.5 times higher than marketed tablet. The results suggest that, the SNEDDS formulation can be used as a possible alternative for the traditional oral formulations of LD to improve its oral bioavailability.


Social Support, Caregivers, and Chronic Kidney Disease.
The morbidity and mortality associated with chronic kidney disease remains unacceptably high. Psychosocial issues in CKD patients are frequently overlooked yet are often modifiable risk factors for mortality. Addressing patient perception of social support can potentially improve patient outcomes.


Troubleshooting of the determination of bisphenol A at ultra-trace levels by liquid chromatography and tandem mass spectrometry.
Determination of trace amounts of bisphenol A (BPA) may cause problems mainly related to the presence of BPA in solvents (even in LC-MS grade), laboratory vessels, and plastic equipment used for sample preparation. Variable and sometimes significant amounts of BPA present in the background cause problems in obtaining good repeatability of measurements at the ultra-trace levels. Such observations (i.e., poor repeatability of results) were made during development of the LC-MS/MS method for determination of BPA in human serum samples. The method included gradient separation of the sample's constituents. The BPA peak was present in the chromatograms not only when procedural blanks were injected but also when void injections were made. One of the possible ways to eliminate background contamination is to change the source of solvents, use a different water purification system, and introduce rigorous equipment cleaning procedures. However, despite the use of these recommended guidelines, the peak of BPA was still present in the system blank. It was observed that the intensity of the BPA peak was proportional to the time of column conditioning. It was concluded that BPA, present in the components of the mobile phase, is being enriched in the front of the separation column during its conditioning (i.e., when mobile phase elution strength was low). This paper describes effects of gradient and isocratic elution conditions on LC-MS/MS system blank. The problem of spurious BPA peak, originating from the mobile phase, was solved by replacing gradient with isocratic elution mode. The use of isocratic elution conditions with the mobile phase of relatively high elution strength (50% of acetonitrile) allowed elimination of the peak of BPA coming from the mobile phase and significantly improved the precision of determination of BPA at low concentration levels.


High doses of methylprednisolone with or without alizapride in the prevention of cisplatin-induced emesis. A randomized, double-blind, crossover study.
Fifty-two patients undergoing cisplatin-based chemotherapy were randomized to receive either methylprednisolone (1 g i.v. total dose) or methylprednisolone plus alizapride (800 mg i.v. total dose). Major control of emesis (less than or equal to 2 episodes of vomiting) was obtained in around 30% of patients, without difference between the two arms. The combined antiemetic treatment was significantly superior to the single drug in reducing overall number of vomiting episodes (median: 4 vs. 9), duration of emesis (2 vs. 4.5 h), and number of patients with more than 5 vomiting episodes (47.5 vs. 62.5%). Both antiemetic regimens had negligible toxicity and were easily given to outpatients. Though some superiority has been shown for the combined treatment over the single methylprednisolone, the low rate of major control of emesis does not warrant for further investigations of this regimen in cisplatin-treatment patients.


Interventional management of recurrent paroxysmal atrial fibrillation despite isolated pulmonary veins: impact of an ablation strategy targeting inducible atrial tachyarrhythmias.
Pulmonary vein isolation (PVI) is an effective treatment option for paroxysmal atrial fibrillation (PAF). Reconnection of pulmonary veins (PVs) is the predominant cause for recurrence of PAF. However, treatment of patients with recurrence of PAF despite isolated PV in the absence of extra-PV foci remains challenging. Of 265 patients undergoing repeat catheter ablation (CA) for recurrence of PAF 21 (8%) patients (14 men, age 58 ± 14 years) showed no reconnection of PV. Therefore, inducibility of sustained atrial arrhythmias was tested. If sustained atrial fibrillation (AF) or sustained atrial tachycardia (AT) was induced, patients underwent CA. During follow-up (FU), Holter- and Tele-electrocardiogram were performed. In 19 (91%) of 21 patients, sustained atrial arrhythmias [16 (84%) AF; 3 (15%) patients AT] were induced. One patient showed PAF. Eighteen patients underwent CA aiming for termination of induced arrhythmia. In 14 (77%) patients, termination into sinus rhythm was achieved. Despite extensive CA, three (16%) patients were externally cardioverted. No periprocedural complications occurred. During 21.2 ± 6.8-month FU, 10 (53%) patients were free of any arrhythmia. Paroxysmal atrial fibrillation recurred in 4 (21%) and AT in 5 (26%) patients. One patient showed persistent AF. Repeat CA was scheduled and successfully performed for these patients. In patients with recurrence of PAF despite isolated PV, termination of induced atrial arrhythmias can be achieved in most patients by defragmentation and AT ablation. Moreover, this ablation strategy results in favourable mid-term outcome results.


Band Edges Engineering of 2D/2D Heterostructures: The C3 N4 /Phosphorene Interface.
We investigate the interface between carbon nitride (C3 N4 ) and phosphorene nanosheets (P-ene) by means of Density Functional Theory (DFT) calculations. C3 N4 /P-ene composites have been recently obtained experimentally showing excellent photoactivity. Our results indicate that the formation of the interface is a favorable process driven by Van der Waals forces. The thickness of P-ene nanosheets determines the band edges offsets and the charge carriers' separation. The system is predicted to pass from a nearly type-II to a type-I junction when the thickness of P-ene increases, and the conduction band offset is particularly sensitive. Last, we apply the Transfer Matrix Method to estimate the efficiency for charge carriers' migration as a function of the P-ene thickness.


Hydrogen sulfide-producing Citrobacter diversus. A re-emphasis of the potential ability of all Enterobacteriaceae to manifest this quality.
Among 68 strains of Citrobacter diversus isolated in a community hospital in a year and a half, six were characterized by late H2S production in iron-agar slants, while otherwise typical. Although not recorded in standard tabulations, the potential for Enterobacteriaciae to develop this quality by plasmid transfer appears to be virtually unlimited, and dictates caution in the use of failure to produce H2S as a criterion for exclusion. In the present group, the use of the adonitol reaction as a means of distinguishing these organisms from more typical H2S producers is emphasized.


Reactivity recovery of guar gum coupled mZVI by means of enzymatic breakdown and rinsing.
Microscale zerovalent iron (mZVI) reduces chlorinated aliphatic hydrocarbons (CAHs) to harmless compounds, but the sedimentation of the mZVI particles in the injection fluid limits the injectability of the particles during field applications. In this study, mZVI particles in suspension were stabilized by green polymer guar gum, which had a positive impact on mZVI stability, but decreased the reactivity of the particles towards CAHs by 1 to 8 times. Guar gum (GG) was found to adsorb onto the mZVI surface, inhibiting contact between the chlorinated compounds and the reactive iron surface. Indications were found for intermolecular hydrogen bonding between mZVI and the guar gum. Subsequent addition of commercially available enzymes resulted in the cleavage of the polysaccharide guar gum into lower molecular fragments, but not in improved reactivity. The reactivity recovery of guar gum coupled mZVI was recovered after intensive rinsing of the iron particles, removing the guar gum fragments from the particles. Overall, this study shows that CAHs can be treated efficiently by guar gum stabilized mZVI after reactivation by means of enzymatic breakdown and rinsing.


Inter-relationships between pituitary-adrenal hormones and catecholamines during a 6-day Nordic ski race.
The aim of the study was to investigate the inter-relationships between pituitary-adrenal hormones and catecholamines during a prolonged competition over 6 days. Plasma adrenocorticotropic hormone (ACTH), cortisol (C), beta-endorphin (beta EP), free and sulphated adrenaline (A) and noradrenaline (NA) were measured in 11 volunteer male subjects during a national Nordic-ski race (323 km). Blood samples were obtained before the competition in the evening as control (D0), and before and after each day's racing (D1-D6). The mean daily heart rate (fc) was calculated from fc values recorded every minute during the race. The results showed the following: changes in mean fc [from 147 (SEM 3) to 156 (SEM 3) beats.min-1 according to the day] were not significant during the race. Diurnal variations in ACTH, beta EP and C were no longer apparent after the race: evening levels were higher than their respective D0 values during the race, except on D3 when there was a lack of response to exercise in the three hormones. Unlike ACTH and beta EP, pre- and postexercise C values on D1 and D2 were higher than those on the subsequent days (P less than 0.001). In contrast, there was a progressive accumulation of A and NA in pre- and postrace concentrations which reached a plateau in about 4 days. Positive correlations between exercise responses in ACTH, C and beta EP were found especially on D3 and D6 (P less than 0.001) but there were no significant correlations between catecholamines and the other three hormones. Thus, prolonged competition over 6 days evoked different control mechanisms for hormones of the pituitary-adrenal axis and catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of sulfate and phosphate on the deposition of plasmid DNA on silica and alumina-coated surfaces.
The influence of sulfate and phosphate on the deposition kinetics of plasmid DNA on solid surfaces was examined at a constant 300mM ionic strength in both NaCl-Na2SO4 and NaCl-NaH2PO4-Na2HPO4 mixing solutions with varied sulfate and phosphate concentrations at pH 6.0 by utilizing a quartz crystal microbalance with dissipation (QCM-D). Two representative solid surfaces, both silica and alumina-coated surfaces, were concerned in this study. To better understand the effects of sulfate and phosphate on plasmid DNA deposition, QCM-D data were complemented by diffusion coefficients and zeta potentials of DNA as a function of examined solution conditions. The presence of sulfate and phosphate in solutions decreased the deposition efficiencies of plasmid DNA on both silica and alumina-coated surfaces. Moreover, the deposition efficiencies decreased with increasing concentrations of sulfate/phosphate. With sulfate/phosphate ions present in solutions, the deposition kinetics of plasmid DNA on both silica and alumina-coated surfaces were mainly controlled by classic Derjaguin-Landau-Verwey-Overbeek (DLVO) interactions.


Reversibility of renal cortical lesions induced in rats by high doses of nitrilotriacetate in chronic feeding studies.
The effects in the renal cortex of the male rat of continuous administration of a high dose of nitrilotriacetate (NTA) for 24 months were compared with those of the administration of a similar dose for 18 months followed by a 6-month recovery period on the control diet. The results suggest that discontinuation of treatment interrupts the sequence of events leading to tumour formation. This study indicates that all stages in the proposed pathogenesis of renal tubular tumour formation by NTA, up to the occurrence of adenomatous hyperplasia and neoplasia, are reversible. Apparently, tumour development is dependent on the continuous administration of high doses of NTA in the presence of toxic injury to the majority of nephrons.


Diversity and Seasonal Dynamics of Ticks on Ring-Tailed Coatis Nasua nasua (Carnivora: Procyonidae) in Two Urban Areas from Midwestern Brazil.
Understanding the diversity and ecology of ectoparasites in wild animals is essential for surveillance of vector-borne diseases. Coatis (Nasua nasua) easily adapt to anthropized areas, favoring close contact with domestic animals and humans, with the possibility of exchange of ectoparasites and pathogens. The present study aimed to identify the diversity of ticks parasitizing coatis from forest urban areas of midwestern Brazil, to evaluate the seasonal dynamics of ticks during the seasons of the year, and to assess the correlation between tick species and gender and age of the sampled coatis. For this purpose, 103 coatis were captured in two Conservation areas, both located in Campo Grande city, Mato Grosso do Sul state, Midwestern Brazil. The animals' entire body was inspected for the presence of ectoparasites, and ticks were removed for taxonomic identification. In total, 168 captures were performed in both areas during the observational study considering the first capture and recaptures. In total, 2242 ticks were collected: 838 Amblyomma larvae, 1241 A. sculptum nymphs, and 150 A. dubitatum nymphs. Thirteen adult ticks were identified as three males and five females of A. sculptum and two males and three females of A. ovale. While a quantity of Amblyomma larvae was observed in the first months of the year (January, April and May), Amblyomma nymphs showed a higher quantity during the months of July, August, October and November. No statistical difference was observed when comparing mean intensity and prevalence of Amblyomma larvae, nymphs of A. sculptum and A. dubitatum between the two sampled areas, males vs. females and immature vs. mature animals. In conclusion, three tick species were identified parasitizing coatis from forested urban fragments in midwestern Brazil, namely A. dubitatum nymphs, A. sculptum adults and nymphs, and A. ovale adults. Coatis from anthropized areas seem to present tick species diversity lower than those from natural areas. The lack of statistical difference regarding mean intensity and prevalence of Amblyomma larvae and nymphs between males vs. females and immature vs. mature animals might have reflected the gregarious behavior of coatis, since adult males live together with females and offspring outside and inside the mating season, forming large groups of individuals.


Coexistence and the comparative light relations of the submersed macrophytes Myriophyllum spicatum L. and Vallisneria americana Michx.
The Eurasian watermilfoil (Myriophyllum spicatum L.) has partially replaced wild celery (Vallisneria americana Michx.) as a community dominant in the littoral zones of lakes of Madison, Wisconsin. The two species have very different growth forms, with that of M. spicatum corresponding more closely to the optimal growth form simulated by the macrophyte production model WEED. The objective of this research was to investigate the mechanisms by which Vallisneria could compensate for its nonoptimal growth form and coexist with Myriophyllum.A quantification of midsummer growth form for the two species at a rooting depth of 80-90 cm showed that M. spicatum had 68% of its shoot biomass within 30 cm of the surface, whereas V. americana had 62% of its leaf biomass within 30 cm of the bottom. Vallisneria had a light extinction coefficient ranging from 0.013 to 0.019 m2·g-1, much higher than the value (ca. 0.006 m2·g-1) for M. spicatum. This indicates less effective penetration of light to lower leaves of V. americana. Half-saturation constants describing the light-dependence of carbon uptake in "shade" and "sun" tissues ranged from 60-197 microeinsteins·m-2·s-1 for V. americana, and 164-365 μeinsteins·m-2·s-1 for M. spicatum. The optimum temperature for photosynthesis was 33.6°C for M. spicatum and 32.6°C for V. americana, but Myriophyllum was nearly twice as effective at carbon uptake at 10°C. Integration of all of the above features with WEED showed that, for midsummer conditions, V. americana more than compensated for apparently disadvantageous morphological features by its greater physiological adaptability to low light regimes. Coupled with the temperature-dependence of photosynthesis, it appears that V. americana is favored by midsummer conditions, whereas M. spicatum is at an advantage at other times.


Surgery for thyroid Hürthle cell tumours--a single institution experience.
The objective of the study was to report a series of patients with Hürthle cell tumours. We reviewed medical records of single institution from January 1982 to December 2002, including follow-up information. We identified 199 patients with Hürthle cell tumours (HCT), 88 patients with Hürthle cell carcinoma (HCC) and 111 patients with Hürthle cell adenoma (HCA). The HCC group had significantly longer duration of the disease and larger tumours (4.8 vs 3.8 cm) compared with HCA group. Gender appeared to play significant role in patients with HCT (women outnumbered man by 7:1; p < 0.01). Surgical management for 80% of patients with HCA consisted of hemithyroidectomy and total thyroidectomy in 87% patients in the HCC group. Temporary laryngeal nerve palsy and temporary hypoparathyroidismus were not seen in HCA group, in HCC group were confirmed in 2.27 and 3.41%, respectively. Four patients with HCC relapsed and two died of HCC. HCC has outlook for favorable outcome when treated radically with total thyroidectomy.


Enantiospecific, selective cyclooxygenase-2 inhibitors.
Cyclooxygenase inhibition studies with novel indomethacin alkanolamides demonstrate the potential for dramatic differences in inhibitor properties conferred by subtle structural modifications. The transformation of non-selective alpha-(S)-substituted indomethacin ethanolamides to potent, COX-2 selective inhibitors by simple stereocenter inversion highlights this property.


[Morphology of human skeletal muscle and its adaptability to different training conditions].
Endurance exercise training improves the oxidative capacity of the muscles directly involved in training. Structurally we find an increase in capillary supply and an enlargement of the mitochondrial compartment of muscle fibers. In contrast, strength training increases the muscle fiber's content of contractile proteins at the expense of the oxidative structures. Both types of training enhance substrate content of muscle fibers. In strength training we find more glycogen, in endurance training more lipids and more glycogen in trained muscle fibers.


[The surgical treatment of cerebral ischaemia due to vertebral artery and subclavian artery insufficiency (author's transl)].
Results of reconstructive vascular surgery in 86 patients with vertebral artery and subclavian artery insufficiency are reported. 1. The neurologic symptomatology can be improved effectly and persistend by an astonishing small risk of operation. 2. The basic disease remains untreated and reduces life-expectancy. 3. The The valuation of reconstructive vascular surgery for the human rehabilitation is missing biometric facts. The advantage can't be described according to the statistics, it helps patients to a worth living life.


Ozonation of piperidine, piperazine and morpholine: Kinetics, stoichiometry, product formation and mechanistic considerations.
Piperidine, piperazine and morpholine as archetypes for secondary heterocyclic amines, a structural unit that is often present in pharmaceuticals (e.g., ritalin, cetirizine, timolol, ciprofloxacin) were investigated in their reaction with ozone. In principle the investigated compounds can be degraded with ozone in a reasonable time, based on their high reaction rate constants with respect to ozone (1.9 × 10(4)-2.4 × 10(5) M(-1) s(-1)). However, transformation is insufficient (13-16%), most likely due to a chain reaction, which decomposes ozone. This conclusion is based on OH scavenging experiments, leading to increased compound transformation (18-27%). The investigated target compounds are similar in their kinetic and stoichiometric characteristics. However, the mechanistic considerations based on product formation indicate various reaction pathways. Piperidine reacts with ozone via a nonradical addition reaction to N-hydroxypiperidine (yield: 92% with and 94% without scavenging, with respect to compound transformation). However, piperazine degradation with ozone does not lead to N-hydroxypiperazine. In the morpholine/ozone reaction, N-hydroxymorpholine was identified. Additional oxidation pathways in all cases involved the formation of OH with high yields. One important pathway of piperazine and morpholine by ozonation could be the formation of C-centered radicals after ozone or OH radical attack. Subsequently, O2 addition forms unstable peroxyl radicals, which in one pathway loose superoxide radicals by generating a carbon-centered cation. Subsequent hydrolysis of the carbon-centered cation leads to formaldehyde, whereby ozonation of the N-hydroxy products can proceed in the same way and in addition give rise to hydroxylamine. A second pathway of the short-lived peroxyl radicals could be a dimerization to form short-lived tetraoxides, which cleave by forming hydrogen peroxide. All three products have been found.


Regulation of phosphatidylinositol 4-phosphate 5-kinase from Schizosaccharomyces pombe by casein kinase I.
Phosphatidylinositol ()P 5-kinase (PtdIns(4)P 5-kinase) catalyzes the last step in the synthesis of phosphatidylinositol 4, 5-bisphosphate (PtdIns(4,5)P2). PtdIns(4,5)P2 is a precursor of diacylglycerol and inositol 1,4,5-trisphosphate and is also involved in regulation of actin cytoskeleton remodeling and membrane traffic. To satisfy such varied demands in several aspects of cell physiology, synthesis of PtdIns(4,5)P2 must be stringently regulated. In this paper we describe extraction, purification, and characterization of PtdIns(4)P 5-kinase from the plasma membranes of Schizosaccharomyces pombe. We also provide evidence that PtdIns(4)P 5-kinase is phosphorylated and inactivated by Cki1, the S. pombe homolog of casein kinase I. Phosphorylation by Cki1 in vitro decreases the activity of PtdIns(4)P 5-kinase. In addition, and most importantly, overexpression of Cki1 in S. pombe results in a reduced synthesis of PtdIns(4,5)P2 and in a lower activity of PtdIns(4)P 5-kinase associated with the plasma membrane. These results suggest that PtdIns(4)P 5-kinase is a target of Cki1 in S. pombe and that Cki1 is involved in regulation of PtdIns(4, 5)P2 synthesis by phosphorylating and inactivating PtdIns(4)P 5-kinase.


Childhood antecedents of adult degenerative disease.
The pathogenetic links between diet and diseases such as hypertension and atherosclerosis remain the subject of much controversy. This article reviews the evidence about the relationship between diet and these two widespread adult conditions, proposes an approach for their early recognition, examines the rationale and safety of dietary changes, and formulates specific recommendations.


CoMFA analysis of dual/multiple PPAR activators.
Dual or multiple activators are agents which act at more than one biological target and produce synergistic therapeutic effect. Computational methods can be successfully employed in designing dual activators. 'Additivity of molecular fields' concept was recently introduced to help design new dual activators. This concept is employed in this work to explore the scope and limitations of the concept, with the help of reported PPARalpha/gamma/delta multiple activators. Three individual CoMFA models were first generated, followed by dual and multiple models. Dual PPARalpha/gamma CoMFA model could be developed successfully. However, dual PPARgamma/delta, dual PPARalpha/delta and multiple PPARalpha/gamma/delta CoMFA models could not be very well developed. This follows from the poor correlation observed in the PPARdelta CoMFA model.


Interleukin-1 induces changes in norepinephrine metabolism in the rat brain.
Interleukin-1 (IL-1) is a hormone that, apart from playing a key role in immune and inflammatory processes, can also affect mechanisms under brain control. To gain a better understanding of the action of this cytokine on the CNS, its effects on the contents of norepinephrine (NE), dopamine (DA) and serotonin (5-HT), and their main metabolites and precursors, were evaluated in different regions of the forebrain, brain stem, and spinal cord. Following administration of human recombinant IL-1 (beta form) to rats, a modest decrease in the content of NE was observed in the hypothalamus as well as in the dorsal posterior brain stem. However, the most relevant finding was that 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), the main NE metabolite, and the relation MHPG/NE were increased in all the regions studied, revealing a stimulatory effect of IL-1 on NE metabolism in the CNS. This effect seems to be specific for NE since no comparable changes in the brain content of DA, 5-HT, or its metabolite, 5-hydroxyindole acetic acid, were detected after administration of the cytokine. However, tryptophan was significantly increased in all brain regions and in the cervical spinal cord. The capacity of IL-1 to affect the metabolism of NE, a neurotransmitter involved in the control of a variety of brain functions, provides further proof for the relevance of this cytokine in brain-immune interactions.


Placental multiple chorionic cysts in maternal scleroderma.
We present a case of a pregnant woman with scleroderma (Ssc) whose placenta showed multiple chorionic cysts and severe fibrotic changes and large infarcted areas at the maternal side. Fetal growth was appropriate for gestational age and amniotic fluid volume was normal, but fetal tachycardia, loss of variability, and late deceleration were detected by non-stress test at 29 weeks of gestation. She was diagnosed as having non-reassuring fetal status and delivered a female baby who weighed 1092 g (Apgar score 6/9) by Caesarean section. Placental surface cysts are rare findings and their effect on pregnancy is poorly understood, but an association with intrauterine growth restriction (IUGR) has been reported. This is the first report of a pregnant woman with scleroderma showing multiple placental cysts.