Functional and morphological evaluation of different polypropylene-mesh modifications for abdominal wall repair.
Modern surgical hernia repair depends increasingly on synthetic meshes for the reconstruction of the abdominal wall. Despite the undisputed advantages of the polypropylene (PP) meshes currently available (Marlex, Prolene), reports of complications after implantation are increasing. Although, serious complications such as perforation and fistula formation are rare, minor and local complaints such as seromas, misfeelings and a decreased abdominal wall mobility are observed in about one-half of the patients. In regard to the exaggerated strength of the currently available mesh modifications a reduction of the material should improve the integration of the meshes into the artificial abdominal wall. In the present study, the commercially available basic mesh Prolene has been compared to two newly constructed PP-mesh modifications with reduced amounts of PP. The modifications have gradually been adopted to the physiological requirements of abdominal wall stability and mobility by reducing the amount of PP to 64% (E-BLUE) and 24% (variant A) of the Prolene mesh (developed by ETHICON, Norderstedt, Germany). All PP-mesh variants have been implanted in a rat model and studied by 3D-photogrammetry, tensiometry, light- and electron microscopy, as well as morphometry over implantation intervals of 3, 7, 14, 21 and 90 days. The data show that current constructions of PP-meshes are oversized and definitely restrict abdominal wall mobility in the present model. Sufficient stability of the artificial abdominal wall is even guaranteed by PP-mesh modifications with a reduction of PP-quantity to about 25% of the Prolene mesh. The degree of fibrosis directly correlated with abdominal wall restriction, whereas the formation of connective tissue in the interface PP-fibre/host-issue depends on the amount and activity of the inflammatory reaction. The quantity and quality of inflammation, again, directly relies to the amount of PP and to the surface area in contact with the recipient tissues. Altogether, the present study suggests that a modification of the PP-meshes could be helpful to prevent major and minor complications of surgical PP-meshes.


Use of ultrasound to guide radiation boost planning following lumpectomy for carcinoma of the breast.
To determine if sonographic localization of the breast lumpectomy site is feasible and useful in boost planning. The operative beds following lumpectomy were localized by ultrasound in 22 patients (15-infiltrating ductal, 7-ductal carcinoma in situ; size: .4-2.0 cm). Twelve patients had two ultrasound examinations on different days for a total of 34 examinations. Twenty-one patients had their course of boost electron therapy planned using ultrasound to guide field placement. While the patient was in the treatment position, the surgical scar was placed at the machine's isocenter. With the electron cone in place, the ultrasound transducer was placed within the cone on top of the surgical scar. The biopsy site was localized and the light field maneuvered so that it's central axis would follow the axis of the transducer, transecting both the scar and biopsy site. The operative bed was highly visible in 26 ultrasound examinations, visible in 7, and subtly visible in 1. Every biopsy site showed some hypoechoic area but most appeared as the mixed hypoechoic pattern. Ultrasound appearances were mixed or mostly hypoechoic (28), anechoic with irregular walls (4), and echoic (hypoechoic compared to parenchyma) (2). In two cases the surgeon placed surgical clips in the operative bed, and in both cases several of these clips could be identified at the margins of the operative bed as hyperechoic foci with shadowing. The mean depth of the operative bed was 21 mm (range 17-36 mm). In 12 patients, two ultrasound examinations were performed on different days, and the mean depth difference between these scans was 2 mm with a range of 0-5 mm. Among patients with two scans we found that both the location and appearance of the operative bed was highly reproducible. Ultrasound can successfully be used to localize the biopsy site and facilitate boost field placement in patients treated with lumpectomy and radiation.


Spatially resolved ultrasonic attenuation in resistance spot welds: implications for nondestructive testing.
Spatial variation of ultrasonic attenuation and velocity has been measured in plane parallel specimens extracted from resistance spot welds. In a strong weld, attenuation is larger in the nugget than in the parent material, and the region of increased attenuation is surrounded by a ring of decreased attenuation. In the center of a stick weld, attenuation is even larger than in a strong weld, and the low-attenuation ring is absent. These spatial variations are interpreted in terms of differences in grain size and martensite formation. Measured frequency dependences indicate the presence of an additional attenuation mechanism besides grain scattering. The observed attenuations do not vary as commonly presumed with weld quality, suggesting that the common practice of using ultrasonic attenuation to indicate weld quality is not a reliable methodology.


What about using sniffin' sticks 12 items test to screen post-COVID-19 olfactory disorders?
Post-COVID-19 Olfactory impairment has a negative impact on quality of life. The Sniffin Sticks test 12 items (SST-12) can be used in quick olfactory disorders screening. Its evaluation in a post-covid-19 situation was the main objective of this work. All patient impaired with a post-COVID olfactory loss were included while consulting to the ENT department. The clinical examination included an olfaction recovery self-assessment (VAS), a nasofibroscopy, a quality of life (QoL) assessment, the complete Sniffin' Sticks Test (SST), and the SST-12. Among the 54 patients included, 92% (n = 50) were correctly screened as olfactory impaired by SST-12. We report excellent correlations between SST-12 and SST (rho (52) = 0.98, p < 0.001), QoL(rho(52) = 0.33 p = 0.016), or VAS (rho(52) = 0.49, p < 0.001) assessments. SST-12 is a quick and reliable tool to screen large-scale population of post-COVID-19 olfactory impaired patients and could be used in a general daily clinical practice.


Arthroscopy Should be Used With Caution for Gunshot Wounds to the Hip.
To evaluate the safety and efficacy of hip arthroscopy immediately following gunshot wound (GSW) to the hip. Patients who received hip arthroscopy for GSWs from 2006 to 2020 by 2 surgeons at a level I trauma center were identified by Current Procedural Terminology codes. Inclusion criteria were those patients who suffered a GSW to the hip, received hip arthroscopy for treatment, and had a minimum follow-up of 2 months. The exclusion criteria were any patients younger than 18 years of age. Medical records were reviewed for patient demographics, surgical details, clinical outcomes, and complications. A total of 50 hip arthroscopy cases were identified by Current Procedural Terminology codes. Of the 50 cases identified, 8 patients met the inclusion criteria. All 8 patients were male, African-American, and the mean age was 31 years (range, 19-54 years) with mean follow-up of 14 months. Five of 8 cases were noted to have poor visualization with arthroscopy. Common reasons for poor visualization were difficult access to the bullet fragments, morbid obesity, hematoma formation, and pre-existing arthritis. Of these 5 cases, 2 were converted to open procedures to retrieve the remaining bullet fragments. One patient developed abdominal compartment syndrome, most likely due to increased pulse pressure over a prolonged operative period and involvement of the acetabular fovea. Emergent exploratory laparotomy and abdominal compartment fluid release were performed, and the patient had an otherwise unremarkable hospital course. There are risks with the use of arthroscopic methods to remove GSW fragments, which may be greater than elective hip arthroscopy. Certain factors, such as the surgeon's arthroscopic experience, locations of bullets fragments, visual quality, length of procedure, and concomitant acetabular fractures, must be considered before proceeding with arthroscopy. Therapeutic case series.


Outcomes of a telehealth intervention for homebound older adults with heart or chronic respiratory failure: a randomized controlled trial.
Telehealth care is emerging as a viable intervention model to treat complex chronic conditions, such as heart failure (HF) and chronic obstructive pulmonary disease (COPD), and to engage older adults in self-care disease management. We report on a randomized controlled trial examining the impact of a multifaceted telehealth intervention on health, mental health, and service utilization outcomes among homebound medically ill older adults diagnosed with HF or COPD. Random effects regression modeling was used, and we hypothesized that older adults in the telehealth intervention (n = 51) would receive significantly better quality of care resulting in improved scores in health-related quality of life, mental health, and satisfaction with care at 3 months follow-up as compared with controls (n = 51) and service utilization outcomes at 12 months follow-up. At follow-up, the telehealth intervention group reported greater increases in general health and social functioning, and improved in depression symptom scores as compared with usual care plus education group. The control group had significantly more visits to the emergency department than the telehealth group. There was an observed trend toward fewer hospital days for telehealth participants, but it did not reach significance at 12 months. Telehealth may be an efficient and effective method of systematically delivering integrated care in the home health sector. The use of telehealth technology may benefit homebound older adults who have difficulty accessing care due to disability, transportation, or isolation.


SV40 T/t-common polypeptide enhances the sensitivity of HER2-overexpressing human cancer cells to anticancer drugs cisplatin and doxorubicin.
HER2-overexpressing cancer cells are resistant to cisplatin (CDDP) and doxorubicin (DXR). Here we report that SV40 T/t-common polypeptide could specifically sensitize HER2-overexpressing cancer cells to CDDP and DXR and specifically enhance CDDP- or DXR-induced apoptosis in these cells. This activity of T/t-common may be attributed to its ability to inhibit Bcl-2 and Bcl-XL and to suppress ERK activity in CDDP- or DXR-treated HER2-overexpressing cancer cells. T/t-common could enhance the antitumor activity of DXR on HER2-overexpressing ovarian tumor in NOD/SCID mice, suggesting that combination therapy using T/t-common and chemotherapeutic agents may provide a new approach for treating HER2-overexpressing cancers.


3D printing a biocompatible elastomer for modeling muscle regeneration after volumetric muscle loss.
Volumetric muscle loss (VML) injuries due to trauma, tumor ablation, or other degenerative muscle diseases are debilitating and currently have limited options for self-repair. Advancements in 3D printing allow for the rapid fabrication of biocompatible scaffolds with designer patterns. However, the materials chosen are often stiff or brittle, which is not optimal for muscle tissue engineering. This study utilized a photopolymerizable biocompatible elastomer - poly (glycerol sebacate) acrylate (PGSA) - to develop an in vitro model of muscle regeneration and proliferation into an acellular scaffold after VML injury. Mechanical properties of the scaffold were tuned by controlling light intensity during the 3D printing process to match the specific tension of skeletal muscle. The effect of both geometric (channel sizes between 300 and 600 μm) and biologic (decellularized muscle extracellular matrix (dECM)) cues on muscle progenitor cell infiltration, proliferation, organization, and maturation was evaluated in vitro using a near-infrared fluorescent protein (iRFP) transfected cell line to assess cells in the 3D scaffold. Larger channel sizes and dECM coating were found to enhance cell proliferation and maturation, while no discernable effect on cell alignment was observed. In addition, a pilot experiment was carried out to evaluate the regenerative capacity of this scaffold in vivo after a VML injury. Overall, this platform demonstrates a simple model to study muscle progenitor recruitment and differentiation into acellular scaffolds after VML repair.


Crystal structure of (2,2'-bi-pyridine-κ2N,N')bis-(3,5-di-tert-butyl-o-benzo-quinonato-κ2O,O')ruthenium(II).
In the title mononuclear complex, [Ru(C14H20O2)2(C10H8N2)], the RuII ion has a distorted octa-hedral coordination environment defined by two N atoms of the chelating 2,2'-bi-pyridine ligand and four O atoms from two 3,5-di-tert-butyl-o-benzo-quinone ligands. In the crystal, the complex mol-ecules are linked by inter-molecular C-H⋯O hydrogen bonds and π-π stacking inter-actions between the 2,2'-bi-pyridine ligands [centroid-centroid distance = 3.538 (3) Å], resulting in a layer structure extending parallel to the ab plane.


Causal Inference and Explaining Away in a Spiking Network.
While the brain uses spiking neurons for communication, theoretical research on brain computations has mostly focused on non-spiking networks. The nature of spike-based algorithms that achieve complex computations, such as object probabilistic inference, is largely unknown. Here we demonstrate that a family of high-dimensional quadratic optimization problems with non-negativity constraints can be solved exactly and efficiently by a network of spiking neurons. The network naturally imposes the non-negativity of causal contributions that is fundamental to causal inference, and uses simple operations, such as linear synapses with realistic time constants, and neural spike generation and reset non-linearities. The network infers the set of most likely causes from an observation using explaining away, which is dynamically implemented by spike-based, tuned inhibition. The algorithm performs remarkably well even when the network intrinsically generates variable spike trains, the timing of spikes is scrambled by external sources of noise, or the network is mistuned. This type of network might underlie tasks such as odor identification and classification.


Comparing hospital costs and length of stay for cancer patients in New York State Comprehensive Cancer Centers versus nondesignated academic centers and community hospitals.
To explore differences in costs and lengths of stay for cancer patients admitted to National Cancer Institute-designated Comprehensive Cancer Centers, nondesignated academic medical centers, and community hospitals in New York State. We use patient-level data from the New York State Statewide Planning and Research Cooperative System Hospital Inpatient Discharges dataset for the years 2017-2019. We employ ordinary least squares and Poisson regressions to compare hospital costs and length of stay for cancer patients, controlling for hospital type, patient demographics, and patient health. Our key outcomes are differences in costs and lengths of stay. We use data on patient demographics, total treatment costs, and lengths of stay for patients discharged from New York hospitals with cancer-related diagnoses between 2017 and 2019. We determine that inpatient costs were 27% higher (95% CI 0.252, 0.285), but length of stay was 12% shorter (95% CI -0.131, -0.100), in Comprehensive Cancer Centers relative to community hospitals. The results imply that, in New York State, Comprehensive Cancer Centers are a magnet for more complex oncology cases and administer more expensive treatments. That expertise, however, seems to be responsible for more efficient care delivery and thorough discharge planning, allowing for shorter average lengths of stay.


Dual-time 18F-FDG PET/CT for the detection of liver metastases in breast cancer.
The aim was to investigate the diagnostic potential of dual-time-point F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) in patients with breast cancer with known or suspected liver metastases and to assess its clinical value on clinical management. A total of 151 consecutive patients with breast cancer who underwent F-FDG PET/CT scan for staging or restaging, in whom an additional delayed scan of the liver was performed, were retrospectively evaluated. Overall, F-FDG PET/CT showed the presence of 146 liver metastases in 57 patients. Overall, 54 of these lesions were clearly identified at standard whole-body acquisition, 49 were suspected and 43 were missed in early acquisition. Only 59.6% of patients with liver involvement were clearly identified at the first scan. A high percentage of patients (48.3%) showed at least one liver lesion suspected on standard acquisition which was not more confirmed in late scan. Maximum tumour standardized uptake value of liver metastases was significantly higher in delayed as compared with standard acquisition (6.5±2.4 vs. 5.3±1.6; P<0.0001). The higher detection rate in late acquisition altered patient management in a relative low number of cases in the whole series (15.8%) and in a higher proportion (28.6%) in the group of patients with exclusive liver involvement. The results of the study revealed the potential usefulness of late liver acquisition in patients with breast cancer with suspected or known liver metastases. Its use should be advocated in case of inconclusive results on standard acquisition to improve the study interpretation confidence or to increase the accuracy in specific clinical settings.


[Frequency of stable chromosomal aberrations determined by FISH in 49 Chernobyl nuclear accident liquidators exposed to various doses of radiation].
FISH technique was tested on the 49 liquidators of the Chernobyl Accident. Groups were formed according to average group exposure doses and/or individual ones determined by the method of EPR. The essential variability of spontaneous and irradiation-induced frequencies of reciprocal translocations was observed. In groups with the lowest EPR-doses (below 25 cGy) the average cytogenetic dose was considerably higher then doses determined by EPR-method. The best coincidences between average in-group EPR- and FISH-doses were in the group with 25-50 cGy doses for "acute irradiation" model and in the group with 50-100 cGy and higher for "chronic irradiation" model.


Serum albumin and muscle strength: a longitudinal study in older men and women.
To examine whether low serum albumin is associated with low muscle strength and future decline in muscle strength in community-dwelling older men and women. Population-based cohort study. The Longitudinal Aging Study Amsterdam. Six hundred seventy-six women and 644 men aged 65 to 88. Serum albumin was determined at baseline. Muscle strength was assessed using grip strength at baseline, after 3 (n=1,009), and 6 (n=741) years. The outcomes were continuous baseline muscle strength, 3- and 6-year change in muscle strength, and a dichotomous indicator for substantial decline (a decrease if > or =1 standard deviations for women=11 kg, for men=12 kg) in muscle strength. Mean serum albumin concentration+/-standard deviation was 45.0+/-3.3 g/L for women and 45.2+/-3.2 g/L for men. At baseline, adjusting for age, lifestyle factors, and chronic conditions, lower serum albumin was cross-sectionally associated with weaker muscle strength (P<.001) in women and men. After 3 years of follow-up, mean decline in muscle strength was -5.6+/-10.9 kg in women and -9.6+/-11.9 kg in men. After adjustment for potential confounders, lower serum albumin was associated with muscle strength decline over 3 years (P<.01) in women and men (beta=0.57, standard error (SE)=0.18; beta=0.37, SE=0.16, respectively). Lower serum albumin was also associated with substantial decline in muscle strength in women (per unit albumin (g/L) adjusted odds ratio (OR)=1.14, one-sided 95% confidence limit (CL)=1.07) and men (per unit albumin (g/L) adjusted OR=1.14, 95% CL=1.08). Similar but slightly weaker associations were found between serum albumin and 6-year change in muscle strength (P<.05). These results suggest that low serum albumin, even within the normal range, is independently associated with weaker muscle strength and future decline in muscle strength in older women and men.


Gas phase activity of anti-FITC antibodies immobilized on a surface acoustic wave resonator device.
In this paper we present the results of a series of experiments on the activity of antibodies in a vapor phase sensor. For these experiments the sensor component was a ST-Quartz resonator with a center frequency of approximately 250 MHz. Anti-FITC antibodies were attached to the electrodes on the device surface via a protein-A crosslinker. Surface acoustic wave (SAW) resonator devices with various coatings were mounted in TO-8 packages, inserted into our sensor head module and subjected to various fluorescent analyte gases. Numerous controls were performed including the use of coated and uncoated devices along with devices coated with antibodies which were not specific for the target analyte. The SAW immunosensor response was monitored and a baseline frequency shift was observed when the analyte being presented was the antigen for the immobilized antibody. To provide an independent measure of antibody/antigen binding, the devices were removed from the sensor head, washed with a buffer solution to remove any unbound analyte, and then inspected using a confocal laser scanning microscope (CLSM). Since all the analytes being used in these experiments were fluorescent this afforded us the opportunity to visualize the attachment of the analyte to the antibody film. Given the high resolution of the CLSM, we were able to identify the location of the attachment of the fluorescent analytes relative to the 1.5 microm wide electrodes of the SAW device. We believe that these experiments demonstrate that we have achieved real time molecular recognition of these small molecules in the vapor phase.


Synthesis of 11C-labeled DNA polymerase-β inhibitor 5-methoxyflavone and PET/CT imaging thereof.
"Cell-cycle hypothesis" is emerging in recent years to suggest that aberrant cell cycle re-entry of differentiated neurons leads to a remarkable genetic disequilibrium which is likely to be the primary cause of neuronal apoptosis. DNA polymerase-β is involved in neuronal DNA replication during cell cycle re-entry, thus constituting a promising target for Alzheimer's disease treatment. Recently, 5-methoxyflavone was identified as a candidate molecule endowed with good biological activity and selectivity on the DNA pol-β in multiple in vitro AD models. In vivo assays, especially the brain uptake of 5-methoxyflavone, is need to be evaluated for further development for AD treatment. We report herein the synthesis of 11C-labeled 5-methoxyflavone, and the evaluation of in vivo properties of 5-[11C]methoxyflavone in rodents. The strategy for synthesis of 5-[11C]methoxyflavone was developed by treating precursor 5-hydroxyflavone with [11C]CH3I and KOH in anhydrous DMF. 5-[11C]Methoxyflavone was purified, then evaluated in mice by using PET/CT imaging. The 5-[11C]methoxyflavone was synthesized conveniently in an average decay corrected yield of 22% (n = 3) with a radiochemical purity >99%. The average molar radioactivity of 5-[11C]methoxyflavone was 383 GBq/μmol. The average concentration was 0.107 μg/mL. PET/CT imaging in mice showed 5-[11C]methoxyflavone rapidly passed through the blood-brain barrier with 8.36 ± 0.61%ID/g at 2 min post injection, and the radioactivity accumulation in brain was still noticeable with 2.48 ± 0.59%ID/g at 28 min post injection. The clearance rate was 3.37 (brain2 min/brain28 min ratio). The blood and muscle uptakes were low. The lung displayed high initial uptake and subsequent rapid clearance, while the liver and kidney displayed a relatively slow clearance. Real-time imaging showed that 5-[11C]methoxyflavone accumulated immediately in the heart, then transferred to the liver and intestine, and was not observed in lower digestive tract. 5-[11C]Methoxyflavone was synthesized conveniently in one step. The results of PET/CT imaging in C57BL/6 mice suggested 5-[11C]methoxyflavone possesses appropriate pharmacokinetic properties and favorable brain uptake, thus being proved to be suitable for further development for AD treatment.


Photocycle of point defects in highly- and weakly-germanium doped silica revealed by transient absorption measurements with femtosecond tunable pump.
We report pump-probe transient absorption measurements addressing the photocycle of the Germanium lone pair center (GLPC) point defect with an unprecedented time resolution. The GLPC is a model point defect with a simple and well-understood electronic structure, highly relevant for several applications. Therefore, a full explanation of its photocycle is fundamental to understand the relaxation mechanisms of such molecular-like systems in solid state. The experiment, carried out exciting the sample resonantly with the ultraviolet (UV) GLPC absorption band peaked at 5.1 eV, gave us the possibility to follow the defect excitation-relaxation dynamics from the femto-picosecond to the nanosecond timescale in the UV-visible range. Moreover, the transient absorption signal was studied as a function of the excitation photon energy and comparative experiments were conducted on highly- and weakly-germanium doped silica glasses. The results offer a comprehensive picture of the relaxation dynamics of GLPC and allow observing the interplay between electronic transitions localized on the defect and those related to bandgap transitions, providing a clear evidence that the role of dopant high concentration is not negligible in the earliest dynamics.


Cytarabine with high-dose mitoxantrone induces rapid complete remissions in adult acute lymphoblastic leukemia without the use of vincristine or prednisone.
To evaluate the efficacy and safety of a new induction regimen for adult acute lymphoblastic leukemia (ALL) that does not contain vincristine or corticosteroids. Thirty-seven adult patients with newly diagnosed ALL and lymphoblastic lymphoma were treated with a dose-intense induction regimen. This regimen was designed to increase the fraction of patients achieving an early complete remission (CR) in an attempt to increase long-term disease-free survival. The induction regimen was cytarabine (Ara-C) 3 g/m2/d for 5 days and mitoxantrone 80 mg/m2 as a single dose on day 3. Granulocyte colony-stimulating factor (G-CSF) 200 micrograms/ m2/d beginning on day 7 was used to promote early myeloid recovery. There were 31 CRs (84%). Median time to CR was 34 days, median hospital stay was 28 days, and the median number of days with a neutrophil count less than 500/microL was 18. There were three patients with resistant disease who experienced treatment failure and three early deaths from sepsis. Four patients with Philadelphia chromosome-positive (Ph+) ALL achieved hematologic and cytogenetic CRs. This dose-intense induction regimen produced a high incidence of CRs with acceptable toxicity without the use of vincristine or corticosteroids. Comparisons with our prior vincristine/prednisone-based induction regimen (the L-20 protocol) suggest that patients treated on the current study were more likely to achieve a CR and that they achieved this remission earlier than patients treated with a traditional four-drug (vincristine, prednisone, doxorubicin, and cyclophosphamide) induction regimen.


Duramycin effects on the structure and function of heart mitochondria. I. Structural alterations and changes in membrane permeability.
The polypeptide antibiotic duramycin has been reported to interact specifically with two lipids: phosphatidylethanolamine (PE) and monogalactosyldiacylglycerol (Navarro et al. (1985) Biochemistry 24, 4645-4650). PE is a major component of mitochondrial membranes. Duramycin was used to examine the role of PE in maintenance of mitochondrial structure and membrane permeability properties with the following results: (1) Duramycin addition to isolated rat heart mitochondria produced abrupt organelle contraction which was followed, depending on composition of the suspending medium, by pronounced swelling. The most notable morphological effect of the antibiotic was ruffling or crenelation of the outer membrane, which resulted ultimately in its separation from the inner membrane. (2) Low concentrations (less than 5 microM) of the antibiotic selectively increased the permeability of the mitochondrial inner membrane to cations and small solutes. This effect was blocked by atractyloside, a highly specific inhibitor of the adenine nucleotide translocator, by palmitoyl coenzyme A, by N-ethylmaleimide, and by AMP, ADP and ATP but not GDP or GTP, implicating the adenine nucleotide translocator in the selective permeability increase. (3) Higher concentrations of duramycin induced a more generalized permeability increase which was not subject to inhibition by compounds capable of interacting with the adenine nucleotide translocator.


Anomalous left coronary artery arising from the pulmonary artery discovered beyond infancy.
Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a congenital heart defect rarely diagnosed beyond infancy. We present a 9-year-old girl who had once been diagnosed as congenital coronary artery fistula. Echogenic mitral chordae tendineae, multiple coronary collaterals within the ventricular septum and free ventricular wall, and a shunting flow from the left coronary artery into the pulmonary artery were prominent echocardiographic features of ALCAPA. Reimplantation of the left coronary artery directly onto the aorta achieved a favorable outcome with regression of left ventricular size and alleviation of mitral regurgitation.


The association of 1-year weight loss from bariatric surgery and self-reported sleep: a prospective cohort.
This study examined the association of weight loss following bariatric surgery with self-reported sleep quality after accounting for other sleep-related factors. Participants were from the Bariatric Experience Long Term (BELONG) study. Participants completed a survey up to 6 months before surgery and approximately 1 year after surgery. The Pittsburgh Sleep Quality Index (PSQI) was used to measure sleep quality. One-year percentage total weight loss (%TWL) was determined from electronic medical records. Covariates included demographics, Charlson Comorbidity Index, geocoded variables to assess neighborhood quality, and physical activity. The authors assessed the association between %TWL at 1 year and PSQI component scores with separate cumulative logit models. There were 997 participants in the analytic cohort. Participants were 86.2% women, 37.0% Hispanic, and 13.7% Black adults. Mean one-year %TWL was 26.3 (SD 8.7). Each 1% increase in %TWL was associated with a 3% better daytime dysfunction score (odds ratio = 1.03; 95% CI: 1.02-1.05) and a 2% better sleep quality score (odds ratio = 1.02; 95% CI: 1.00-1.03). No significant differences were found for the other PSQI components. Weight loss from bariatric surgery was associated with better self-reported sleep at 1 year. For people undergoing bariatric surgery, there may be an added benefit of better sleep.


Oxidative DNA damage, lipid peroxidation and nephrotoxicity induced in the rat kidney after ferric nitrilotriacetate administration.
8-Hydroxydeoxyguanosine (8-OH-dG) was examined in the kidneys of rats after single i.p. administration of ferric nitrilotriacetate (Fe-NTA) for variable periods of time at various doses along with the measurement of lipid peroxidation and serum biochemical parameters and histopathological examination. Though lipid peroxide level increased rapidly and decreased sharply after reaching a much higher peak 1 h after treatment, significant higher levels of 8-OH-dG were observed at 1, 6 and 24 h after injection. On the other hand, the increase of 8-OH-dG formation was observed in a similar dose-dependent manner to the appearance of nephrotoxic responses in terms of serum biochemical and histopathological changes.


Iophendylate or spillage from epidermoid--a diagnostic dilemma on cranial MR imaging.
MR characteristics of iophendylate in spinal subarachnoid space are well known. Still, it is difficult to differentiate it from spilled contents of epidermoid on cranial MR imaging.


The stoichiometry and energetics of oxygenic phototrophic growth.
The values of gross metabolic flows in cells are essentially interconnected due to conservation laws of chemical elements and interrelations of biochemical coupling. Therefore, the overall stoichiometry of cellular metabolism, such as the biomass quantum yield, the ratio between linear and circular flows via the electron transport chain, etc., can be calculated using balances of metabolic flows in the network branching points and coupling ratios related to ATP formation and expenditures. This work has studied the energetic stoichiometry of photosynthetic cells by considering the transfer of reductivity in the course of biochemical reactions. This approach yielded rigorous mathematical expressions for biomass quantum yield and other integral bioenergetic indices of cellular growth as functions of ATP balance parameters. The effect of cellular substance turnover has been taken into account. The obtained theoretical estimation of biomass quantum yield is rather close to experimental data which confirms the predictive capacity of this approach.


The role of herpes simplex virus ribonucleotide reductase small subunit carboxyl terminus in subunit interaction and formation of iron-tyrosyl center structure.
Herpes simplex virus ribonucleotide reductase consists of two nonidentical subunits, proteins R1 and R2, which are required together for activity. Active R2 protein contains a tyrosyl free radical and a binuclear iron center. A truncated form of the R2 subunit, lacking 7 amino acid residues in the carboxyl terminus, was constructed, overexpressed in Escherichia coli and purified to homogeneity. In the presence of ferrous iron and oxygen, the truncated protein readily generated similar amounts of tyrosyl free radical as the intact protein. However, the radical showed differences in EPR characteristics in the truncated protein compared with the normal one, indicating an altered structural arrangement of the radical relative to the iron center. The truncated R2* protein was completely devoid of binding affinity to the R1 protein, demonstrating that the subunit interaction is totally dependent on the 7 outermost carboxyl-terminal amino acids of protein R2.


Hydralazine prevents endothelial dysfunction, but not the increase in superoxide production in nitric oxide-deficient hypertension.
Dilator responses, superoxide anion-production, endothelial nitric oxide (NO) synthase and soluble guanylyl cyclase expression were determined in aortic rings from Wistar rats treated for 5 weeks either with the NO synthase inhibitor NG-nitro-L-arginine-methylester (L-NAME), L-NAME plus hydralazine or placebo. In the L-NAME-treated group, acetylcholine-induced relaxation was significantly attenuated whereas it was nearly normal in the L-NAME/hydralazine group. This difference was even more pronounced following inhibition of the endogenous superoxide dismutase using diethyldithiocarbamate. Aortic superoxide production was significantly elevated in both L-NAME-treated groups and hydralazine had no acute effect on superoxide formation. Expression of endothelial NO synthase was similar in all three groups whereas the attenuated soluble guanylyl cyclase expression in rats treated with L-NAME was nearly normalised by concomitant hydralazine treatment. These results demonstrate that in NO-deficient hypertension hydralazine treatment improves vasodilator responses but not the increased superoxide production.


Evaluation of the Quality of Life of Patients Using Circular External Fixator in a Trauma Hospital.
Objective To evaluate the quality of life of patients using an Ilizarov type external fixator for the treatment of complicated fractures and their sequelae. Method This is an observational and cross-sectional study, in which the 36-item short form survey (SF-36) questionnaire (translated into Portuguese) was applied during outpatient consultations in 2 periods, in the months of July 2018 and January 2019. The patients who participated in the study underwent their surgical procedures between January and June 2018. Results We evaluated 36 patients using an external Ilizarov fixator. We observed a predominance of male patients, with a mean age of 37.9 years. Fractures of leg bones and their complications represented half of the sample. Improvement in functional capacity and emotional aspects of the patients was observed throughout the treatment. Conclusion The use of the circular external fixator is an important and effective method for the surgical treatment of complex fractures and their sequelae. This study allowed us to conclude that, after treatment, patients achieved functional return to daily activities with adequate quality of life.


Combined phaco-vitrectomy provides lower costs and greater area under the curve vision gains than sequential vitrectomy and phacoemulsification.
A majority of phakic patients undergoing pars plana vitrectomy for epiretinal membrane or macular hole require subsequent cataract surgery within 1-2 years. Combined phaco-vitrectomy eliminates the need for a second surgery and may enable patients to attain their best vision sooner. This study aims to compare the visual outcomes, complication rates, and costs of combined phaco-vitrectomy versus sequential vitrectomy followed by cataract surgery. Records were searched by CPT® codes to identify patients with both cataract and vitrectomy surgery at our institution over a 5-year period (2013-2018). Chart review included medical history, demographics, exam findings, operating room records, visual acuity (VA), and clinical outcomes. Statistical analyses were performed with SPSS v19 (IBM). Area under the curve for visual acuity was calculated as the trapezoidal mean of the change in Early Treatment of Diabetic Retinopathy Study letters. After exclusion, 81 eyes of 78 patients underwent both cataract and vitrectomy surgeries at our institution. Thirty-four eyes underwent separate, sequential vitrectomy then phacoemulsification surgery, and 47 eyes had combined phaco-vitrectomy surgery. Total operating room times (120.81 ± 3.41 vs 161.03 ± 5.45 min; p < 0.0001) and associated costs were significantly lower in the combined surgery compared with those in the sequential surgery group. Baseline and final visual acuity were similar between the two groups. Baseline VA was 35.53 letters (~ 20/200) and 32.81 letters (~ 20/220) and increased to final VA of 63.74 (~ 20/53) and 60.91 letters (~ 20/61), in the sequential and combined groups respectively. Area under the curve for vision was greater in the combined surgery group, with subjects gaining an average of + 9.11 ± 3.32 letters from sequential surgery, and + 19.53 ± 3.53 letters in the combined surgery group (p = 0.04). Additionally, patients in the combined group attained their best visual acuity 449 days (15 months) sooner than those receiving sequential surgery. Combined phaco-vitrectomy surgery resulted in greater area under the curve visual acuity benefit and attainment of best visual acuity 15 months sooner compared with conventional sequential surgeries. There were no significant differences in complication rates or clinical outcomes between the groups, but operative times and costs were lower for combined surgery, supporting a favorable cost-benefit ratio. Graphical abstract.


Effect of corticosteroid dosing on outcomes in high-grade immune checkpoint inhibitor hepatitis.
Consensus guidelines recommend high-dose corticosteroids (1-2 mg/kg/day methylprednisolone equivalents) for treating grade ≥3 immune checkpoint inhibitor (ICI) hepatitis. We examined the effect of corticosteroid dosing on time to alanine aminotransferase (ALT) normalization, need for additional immunosuppression, and steroid-related complications. We conducted a retrospective cohort study of 215 ICI-treated patients from 2010 to 2020 who developed grade ≥3 (ALT > 200 U/L) ICI hepatitis. Patients were grouped by initial corticosteroid dose (≥1.5 mg/kg or <1.5 mg/kg methylprednisolone equivalents). Propensity scores were calculated predicting the risk of receiving the higher steroid dose and used in inverse probability of treatment weighted (IPTW) logistic or Cox regression. The 87 patients in the ≥1.5 mg/kg group received higher initial (2.0 vs. 0.8 mg/kg/day, p < 0.001) and maximum (2.0 vs. 1.0 mg/kg/day, p < 0.001) steroid doses than the 128 patients in the <1.5 mg/kg group. There was no difference between the higher versus lower-dose groups in development of steroid-refractory hepatitis (OR 1.22, 95% CI 0.79-1.89, p = 0.365) on IPTW-logistic regression. In patients with steroid-responsive disease, there was no difference between the two groups in time to ALT normalization using either standard Cox regression (HR 1.02, 95% CI 0.72-1.45, p = 0.903) or IPTW-Cox regression (HR 1.09, 95% CI 0.78-1.51, p = 0.610). The ≥1.5 mg/kg group had longer exposure to corticosteroids (median 60 vs. 44 days, p = 0.005) and higher incidences of infection (18.4% vs. 7.0%, relative risk [RR] 2.6, 95% CI 1.2-5.6, p = 0.011) and hyperglycemia requiring treatment (23.3% vs. 7.8%, RR 3.0, 95% CI 1.5-6.0, p = 0.001). In patients with high-grade ICI hepatitis, initial treatment with 1 mg/kg/day methylprednisolone equivalents provides similar hepatitis outcomes with reduced risk of steroid-related complications when compared with higher-dose regimens.


Adherence to clinical guidelines in the prevention of coronary heart disease in type II diabetes mellitus.
The study aimed to assess adherence of prescribed medication in primary care to nationally recognised guideline criteria using case note review applying a previously developed medication assessment tool for coronary heart disease (MAT-CHD). Setting Primary care medical centre serving 17,991 patients. A sample of 208 from 463 patients with type 2 diabetes aged 20-75 years with or without a history of ischaemic heart disease (IHD). Patients' records were accessed via medical and pharmacy databases. The criteria of the 23-item audit tool were applied to medical records from case notes in order to quantify adherence to individual guideline criteria. Frequency of adherence to agreed definitions of medication use quality criteria. A total of 1,433 guideline criteria were applied and 1,107 (77.2%, CI: 75.0, 79.4) criteria standards were met with 326 (22.7%, CI: 20.6, 25.0) non-adherences. The overall adherence to guideline criteria was significantly lower for secondary prevention than for primary prevention (74.4 vs. 80.1%, P<0.05; Chi square). Justification recorded in the case notes was identified for 54 (17%, CI: 13, 21) of those non-adherences. The MAT-CHD highlighted areas for review and possible improvement. The tool can be used in primary care from case record examination and offers a means of co-operation between community pharmacists and general practitioners in clinical guideline implementation.


Impact of working memory capacity on predominance of parietal over frontal P300 amplitude.
Working memory-related neural activity varies with task load, and these neural variations can be constrained by working memory capacity (WMC). For instance, some studies suggest that parietal and frontal P300 amplitudes, reflecting working memory functioning, vary differentially with task load and WMC. The present study explored whether the predominance of parietal over frontal P300 amplitude is related to WMC, and whether this relationship varies according to task load. Thirty-one adults aged 20-40 years performed a Sternberg task with two set sizes (2 vs. 6 items), during which event-related potentials were recorded. This allowed us to explore the P300 and estimate the magnitude of its parietal over frontal predominance, calculated as a parietal over frontal predominance index (PFPI). Participants also performed the Digit Span and alpha span tests, which were used to compute an independent index of WMC. Results revealed the classic parietal over frontal P300 predominance. They also indicated that the PFPI decreased as task load increased, owing mainly to an increase in frontal P300 amplitude. Interestingly, WMC was positively correlated with the PFPI, suggesting that individuals with greater WMC exhibited greater parietal over frontal predominance. These correlations did not vary across set sizes. Parietal over frontal predominance was reduced in individuals with lower WMC, who relied more on frontal neural resources. This frontal upregulation may have reflected the recruitment of supplementary attentional executive operations to compensate for less efficient working memory maintenance operations.


Antidepressants as add-on treatment to antipsychotics for people with schizophrenia and pronounced negative symptoms: a systematic review of randomized trials.
The aim of our meta-analysis was to review the evidence base for the efficacy and safety of antipsychotic and antidepressant combinations in the treatment of the negative symptoms of schizophrenia and schizophrenia-like psychoses. Randomized controlled trials comparing the combination of antidepressants and antipsychotics with antipsychotics alone for patients with pronounced negative symptoms in schizophrenia were searched for by accessing the register of randomized controlled trials of the Cochrane Schizophrenia group. The studies identified were independently inspected and their quality assessed by two reviewers. The principal outcome of interest was the reduction of negative symptoms. Dichotomous data were analyzed using the relative risk and continuous data were analyzed using standardized mean differences, both specified with 95% confidence intervals. It was possible to include seven trials (n = 202) examining antidepressants as add-on to antipsychotics in this review. Except for one study, all included studies used first generation antipsychotics. While there was often merely a trend in favour of augmentation of antipsychotics with antidepressants in the small single studies, the meta-analytic combination resulted in a statistically significant superiority in the outcome reduction of negative symptoms as a whole. Statistically significant differences between groups in terms of specific subscores of the SANS were found, but the results were inconsistent. The combination of antipsychotics and antidepressants may be more effective in treating negative symptoms of schizophrenia than antipsychotics alone, but this finding needs to be corroborated by further large trials.


Sensory impairment and beta-amyloid deposition in the Baltimore longitudinal study of aging.
Beta-amyloid (Aβ) plaque deposition is a biomarker of preclinical Alzheimer's disease (AD). Impairments in sensory function are associated with cognitive decline. We sought to investigate the relationship between PET-indicated Aβ deposition and sensory impairment. Using data from 174 participants ≥55 years in the Baltimore Longitudinal Study of Aging, we analyzed associations between sensory impairments and Aβ deposition measured by PET and Pittsburgh Compound B (PiB) mean cortical distribution volume ratio (cDVR). The combinations of hearing and proprioceptive impairment and hearing, vision, and proprioceptive impairment, were positively correlated with cDVR (β = 0.087 and p = 0.036, β = 0.110 and p = 0.018, respectively). In stratified analyses of PiB+ participants, combinations of two, three, and four sensory impairments (all involving proprioception) were associated with higher cDVR. Our findings suggest a relationship between multi-sensory impairment (notably proprioceptive impairment) and Aβ deposition, which could reflect sensory impairment as an indicator or potentially a risk factor for Aβ deposition.


A comparative study of dye removal using fly ash treated by different methods.
The effect of different methods for fly ash treatment using conventional chemical, sonochemical and microwave method on dye adsorption in aqueous solution was investigated. Three basic dyes, methylene blue, crystal violet and rhodamine B, are employed for adsorption testing. It is found that fly ash shows different adsorption capacity depending on type of dyes. Chemical treatment using HCl will increase the adsorption capacity. The adsorption capacity of HCl treated fly ash varies with the preparation conditions. Microwave treatment is a fast and efficient method while producing the sample with the highest adsorption capacity. Solution pH and inorganic salts in dye solution can significantly influence the adsorption. The adsorption data have been analysed using Langmuir, Freundlich and Redlich-Peterson isotherms. The results indicate that the Freundlich and Redlich-Peterson models provide the better correlations with the experimental data.


Protective effect of alpha-melanocyte-stimulating hormone (α-MSH) on the recovery of ischemia/reperfusion (I/R)-induced retinal damage in a rat model.
The present study demonstrates capacity of α-MSH to augment recovery from ischemia/reperfusion (I/R)-induced retinal damage in vivo and correlation of its protective effects with expression of heme oxygenase-1 (HO-1). Used techniques include ocular ischemia and reperfusion, electroretinography, histology, electron microscopy, and molecular-biological techniques. The results demonstrate the α-MSH-mediated inhibition of I/R-induced functional deterioration of the retina. Outcomes suggest that the protective effects of α-MSH occur mainly through HO-1-dependent pathways but HO-1-independent mechanisms may also contribute to protection. The observation that post-ischemic treatment with α-MSH exhibits therapeutic efficacy in the same range as pre-ischemic treatment, is a novel result. This outcome suggests a highly conserved protective role for α-MSH as a major stress response mechanism--and offers the possibility for development of novel therapeutic strategies utilizing this hormone, in particular in treatment of conditions resulting from I/R injury, such as deterioration of retinal microcirculation. The merit of the study lies in the fact that I/R injury contribute significantly to the severity of retinopathies. However, currently there are no evidence-based treatments for retinal I/R injury available for clinical use. Our finding suggests that α-MSH may have a very wide range of uses in the prevention of I/R-mediated pathologies.


[Effects of power frequency magnetic field on Ca2+ transport of skeletal muscle sarcoplasmic reticulum vesicles].
To investigate the effects of power frequency magnetic field on the Ca2+ transport dynamics of isolated sarcoplasmic reticulum vesicles. The assays of Ca2+ uptake time course and the Ca2+-ATPase activity of sarcoplasmic reticulum vesicles were investigated by using dynamic mode of spectrometry with a Ca2+ dye; Ca2+ release channel activation was examined by 3H-ryanodine binding and Ca2+ release assays; membrane fluidity of sarcoplasmic reticulum vesicles was examined by fluorescence polarization, without or with exposure to the vesicles at a 0.4 mT, 50 Hz sinusoidal magnetic field. 0.4 mT, 50 Hz sinusoidal magnetic field exposure caused about a 16% decline of the initial Ca2+ uptake rate from a (29.18 +/- 3.90) pmol.mg(-1).s(-1) to a (24.60 +/- 3.81) pmol.mg(-1).s(-1) and a 26% decline of the Ca2+-ATPase activity from (0.93 +/- 0.05) micromol.mg(-1).min(-1) to (0.69 +/- 0.07) micromol.mg(-1).min(-1) of sarcoplasmic reticulum vesicles, whereas caused a 15% increase of the initial Ca2+ release rate from (4.83 +/- 0.82) pmol.mg(-1).s(-1) to (5.65 +/- 0.43) pmol.mg(-1).s(-1) and a 5% increase in 3H-ryanodine binding to the receptor from (1.10 +/- 0.12) pmol/mg to (1.16 +/- 0.13) pmol/mg, respectively. The decline of Ca2+-ATPase activity and the increase of Ca2+ release channel activity should result in a down-regulation of Ca2+ dynamic uptake and an up-regulation of Ca2+ release induced by exposing the sarcoplasmic reticulum to a 0.4 mT, 50 Hz power frequency magnetic field.


High-Fat Diet Causes Constipation in Mice via Decreasing Colonic Mucus.
Constipation is one of the most common gastrointestinal complaints. Although the causes of constipation are varied, dietary habits have a significant influence. Excessive fat intake is suggested as one of the main causes of constipation; however, the exact mechanism is unknown. To investigate whether a high-fat diet (HFD) causes constipation in mice and to clarify the underlying mechanism, focusing on the amount of colonic mucus. Six-week-old male C57BL/6 mice were randomly divided into two groups: mice fed with HFD and those with normal chow diet (NCD). Fecal weight, water content, total gastrointestinal transit time, and colon transit time were measured to determine whether the mice were constipated. The colonic mucus was evaluated by immunostaining and quantified by spectrometry. Malondialdehyde (MDA) was measured using the thiobarbituric acid (TBA) test as a marker for oxidative stress. Compared to the NCD group, the weight of feces was less in the HFD group. In the functional experiment, the total gastrointestinal transit time and colon transit time were longer in the HFD group. Furthermore, HFD significantly reduced the amount of colonic mucus. In addition, the reduction in colonic mucus caused by surfactant resulted in constipation in the NCD group. HFD causes constipation with delayed colon transit time possibly via the reduction in colonic mucus in mice.


Statistical equivalence and test-retest reliability of delay and probability discounting using real and hypothetical rewards.
Delay discounting (DD) and probability discounting (PD) refer to the reduction in the subjective value of outcomes as a function of delay and uncertainty, respectively. Elevated measures of discounting are associated with a variety of maladaptive behaviors, and confidence in the validity of these measures is imperative. The present research examined (1) the statistical equivalence of discounting measures when rewards were hypothetical or real, and (2) their 1-week reliability. While previous research has partially explored these issues using the low threshold of nonsignificant difference, the present study fully addressed this issue using the more-compelling threshold of statistical equivalence. DD and PD measures were collected from 28 healthy adults using real and hypothetical $50 rewards during each of two experimental sessions, one week apart. Analyses using area-under-the-curve measures revealed a general pattern of statistical equivalence, indicating equivalence of real/hypothetical conditions as well as 1-week reliability. Exceptions are identified and discussed.


Quantitative analysis of the risk of type 2 diabetes and fatty liver in non-obese individuals by computed tomography.
To explore the risk of fatty liver and type 2 diabetes with quantitative parameters of abdominal computed tomography (CT) in a non-obese population. A retrospective analysis of abdominal CT and hospitalization records of inpatients admitted from May 2019 to May 2021 were divided into a non-obese control group (n = 143 cases) and a non-obese diabetes group (n = 105 cases). The measured abdominal CT parameters included body width, liver and spleen CT values, and the ratio of the liver CT value to the spleen CT value (L/S ratio). Logistic regression was used to analyze the risk factors for diabetes in non-obese individuals. Three variables including body width (P < 0.001), liver CT value (P = 0.013), and L/S ratio (P = 0.002) were significantly correlated with the presence of diabetes in non-obese individuals. Body width, liver CT value, and L/S ratio can be used to indicate the risk of type 2 diabetes in non-obese individuals.


Inhibition of DCLK1 sensitizes resistant lung adenocarcinomas to EGFR-TKI through suppression of Wnt/β-Catenin activity and cancer stemness.
Lung adenocarcinoma is the most common form of lung cancer, accounting for 60% of non-small cell lung cancer (NSCLC) cases in Asian patients. Importantly, nearly half of these patients have epithelial growth factor receptor (EGFR) mutations. Though EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are recommended as the first-line therapy for NSCLC patients, the development of resistance reduces their efficiency and limits their application. As the complicated and heterogeneous mechanism of acquired resistance among individuals, the efficiency of anti-angiogenesis therapy, immune checkpoint inhibitors, or chemo-radiotherapies is rather less promising. In this research, we investigated the role of the tumor stem cell marker DCLK1 in EGFR-TKI resistance of lung adenocarcinoma. We discovered that DCLK1 was critical in maintaining the stemness of tumor cells through the Wnt/β-Catenin pathway, which was conducive to the development of EGFR-TKI resistance. Inhibiting DCLK1 activity restored the sensitivity of TKI-resistant tumor cells and organoids. Moreover, our study showed that DCLK1 inhibitor had a synergistic effect in controlling tumor growth when combined with EGFR-TKIs. Overall, our study provides new insights into EGFR-TKI resistant lung adenocarcinoma through inhibition of DCLK1 expression.


Hepatocyte growth factor and c-Met inhibition by hepatic cell hypoxia: a potential mechanism for liver regeneration failure in experimental cirrhosis.
Hepatic resection in cirrhotic patients is associated with impaired liver regeneration and poor clinical outcome. Because experimental cirrhosis is associated with hepatic cell hypoxia, we herein investigated whether hypoxia might alter the mechanisms of liver regeneration in the cirrhotic liver. Cirrhosis was induced by diethylnitrosamine in rats. Immunohistochemistry was performed to assess hepatocellular hypoxia and proliferation 24 hours after a two-thirds partial hepatectomy (PH) in cirrhotic and control rats. Cultured hepatocytes and myofibroblastic hepatic stellate cells were submitted to hypoxia using anaerobic jars. Hepatocyte growth factor (HGF) and c-Met expressions were determined by reverse transcriptase-polymerase chain reaction, Northern blot, and Western blot. In control rats, hypoxia was restricted to perivenular hepatocytes, and PH induced a marked increase in hepatocyte proliferation and in liver HGF expression, whereas c-Met expression remained unchanged. In cirrhotic rats, hypoxia was detected virtually in all of the hepatocytes, and PH induced no significant change in hepatocyte proliferation and in liver HGF expression, whereas c-Met expression was decreased as compared to normal livers. In vitro, the expression of HGF in myofibroblastic hepatic stellate cells and of c-Met in hepatocytes underwent a dramatic decrease under hypoxia. Our results suggest that hepatocellular hypoxia causes inhibition of HGF (and of c-Met)-mediated proliferation and thereby might contribute to liver regeneration failure in cirrhotic liver.


Late-life depression is associated with arterial stiffness: a population-based study.
To determine whether arterial stiffness is associated with depression in the elderly. Population-based cross-sectional study. In Ommoord, a suburb of Rotterdam, the Netherlands. Three thousand seven hundred four subjects of the Rotterdam Study aged 60 and older. Arterial stiffness was assessed using the distensibility of the carotid artery and the carotid-femoral pulse wave velocity. All participants were screened for depressive symptoms with the Center for Epidemiologic Studies-Depression scale. Those with depressive symptoms had a psychiatric evaluation to establish a diagnosis of depressive disorders according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Participants with increased arterial stiffness were more likely to have depressive symptoms. Odds ratios (ORs) for depressive symptoms were 1.24 (95% confidence interval (CI) = 1.01-1.52) per standard deviation decrease in carotid distensibility and 1.17 (95% CI = 1.00-1.38) per standard deviation increase in aortic pulse wave velocity. The association was stronger for depressive disorders meeting DSM-IV criteria (OR = 1.44, 95% CI = 1.03-2.03; OR = 1.48, 95% CI = 1.16-1.90, respectively). Control for atherosclerosis, as measured by the ankle-to-brachial index or presence of plaques in the carotid artery, did not change the associations. This study shows an association between arterial stiffness and depression in the elderly. The findings are compatible with the vascular depression hypothesis. These data suggest that arterial stiffness may partly cause the proposed relationship between vascular factors and depression.


Potentiation of T-lymphocyte function by bleomycin.
Bleomycin, an anti-cancer drug, hitherto thought to have no effect on the immune response, was found to increase contact sensitivity in the guinea pig to 2,4-dinitrofluorobenzene. The drug was given in a single dose (125 mg/kg) on the day of or up to 3 days after sensitization, to achieve this effect. The drug was ineffective if given 3 days before or 4 days after sensitization. In addition, if given 2 or 3 days after sensitization, it caused increased T-cell proliferation in lymph nodes draining the skin sensitization site. It is suggested that the potentiating effect of bleomycin is not on suppressor cell function, as with cyclophosphamide, but might have an effect on local interleukin 2 production, particularly if given when T-cell proliferation is on the increase.


Effects of a low power laser beam guided by optic fiber on rat brain striatal monoamines and amino acids.
In vivo, helium-neon and nitrogen laser beams guided by optic fiber to rat caudate nucleus decreased concentrations of dopamine and serotonin, while distant laser radiation to frontal cortex did not affect striatal dopamine. In vitro, laser radiation to pure monoamines and amino acids decreased concentrations only of aspartic acid and norepinephrine. The effects in vivo are attributed to a combination of photolysis and altered brain metabolism.


One-step real time RT-PCR for detection of microRNAs.
Rapid and simple methods for microRNA (miRNA) detection are essential for biological research of miRNAs and clinical diagnosis. Here we describe a sensitive and specific real time RT-PCR (also RT-qPCR) method for miRNA quantification. The whole detection process including reverse transcription and PCR is performed in one PCR tube by a one-step operation on a real-time PCR system. The results display a wide linear range from 0.1 amol to 10 fmol with a detection limit of 12.6 zmol for miRNA let-7a detection. Let-7a in small RNA samples extracted from tumor cells has been successfully detected by this method. This method is cost-effective, simple and rapid, and has the advantages in the high-throughput routing assay of given miRNAs, as well as in non-model research that has less specific kits and reagents.


Relationship between video head impulse test, ocular and cervical vestibular evoked myogenic potentials, and compartmental magnetic resonance imaging classification in menière's disease.
Currently, it is possible to assess in vivo the morphology of each compartment of the endolymphatic spaces 4 hours after an intravenous administration of gadolinium on magnetic resonance imaging (MRI). The aim of this study was to assess the correlation between otolithic and ampullar functions (cervical vestibular evoked myogenic potential [cVEMP], ocular vestibular evoked myogenic potential [oVEMP], video head impulse test [VHIT]) and delayed inner ear MRI based on a compartmental, anatomically based classification that included the cochlea, the saccule, the utricle, and the ampullas. Retrospective case-control study. In this retrospective study, we performed three-dimensional fluid-attenuated inversion recovery sequences with delayed acquisition in 26 healthy subjects and 31 definite Menière's disease (MD) patients. Each subject was then graded on MRI on the basis on cochlear, saccular, utricular, and ampullar hydrops in MD patients. All patients underwent pure-tone audiometry, VHIT, cVEMP, and oVEMP testing. Cochlear, saccular, utricular, and ampullar hydrops were found on MRI in 88%, 91%, 50%, and 8.5% respectively. We found no significant correlation between the presence of saccular hydrops versus cVEMP, utricular hydrops versus oVEMP, and ampullar hydrops versus VHIT. However, the severity of endolymphatic hydrops on MRI was correlated to the degree of hearing loss. We proposed a compartmental, anatomically based classification for endolymphatic hydrops on MRI, which included the whole vestibular compartment. Using this classification, we observed increasing morphological changes as the disease evolved, affecting first the saccule, then the utricle, and finally the ampullas. The severity of vestibular endolymphatic hydrops is only correlated to hearing loss severity. 3 Laryngoscope, 130:E444-E452, 2020.


Transcutaneous amorphous preparation co-delivering curcumin and modified aptamer as a synergistic approach for the amelioration of psoriasis-like skin inflammation.
The aim is to achieve the targeting function of Aptamer 21-2 (Apt) by modifying glycyrrhizic acid (GA) to obtain Apt-GA and by delivering it through mesoporous silica in μm-size (μmS). Moreover, it is planned to induce synergistic effects of the novel amorphous preparation of Apt-GA with curcumin (Cur) in the treatment of psoriasis. UV/vis spectrophotometric analysis and Fourier transform infrared spectroscopy were performed to demonstrate the linkage of Apt and GA. The replacement of GA with Apt-GA in GA-Cur-μmS did not make a difference in the amorphous state, but showed superior fluorescence of Cur in the inflamed dermis similar to psoriatic induced by imiquimod. Consequently, compared to GA-Cur-μmS and Apt, Apt-GA-Cur-μmS exhibited less pronounced psoriatic characteristics in vivo, including Psoriasis Area and Severity Index, histological image, immunohistochemistry and immuno-fluorescence labeling neutrophils. The enzyme-linked immunosorbent assay showed a similar phenomenon that less IL-17A was observed after treatment with Apt-GA-Cur-μmS than with GA-Cur-μmS or Apt. Our finding suggests that this novel Apt delivery system achieved the Apt targeting function in the dermis by taking advantage of GA and μmS, and exhibited synergistic anti-psoriatic effect by co-delivering curcumin.


Very rapid nucleotide sequence analysis of improved, double-stranded minipreps.
Recently, the combination of double-stranded sequencing and Sequenase has been used to accomplish rapid, high-performance sequencing. This combination is relatively resistant to the usual compression effects of palindromes seen with sequencing enzymes such as Klenow fragment of DNA polymerase I or reverse transcriptase. However, for optimal results the method has still relied on plasmids purified by centrifugation through CsCl gradients. The preparation of large-scale cultures, CsCl gradients, and subsequent dialysis are time-consuming processes. The present report describes an improved, miniprep procedure which eliminates the need for CsCl gradients or single-stranded vectors. The effectiveness of the procedure is due to increased ampicillin concentration which amplifies the plasmids, destruction of contaminating enzymes by diethylpyrocarbonate treatment, and vortexing to facilitate rapid sample handling. Sequences of the resulting minipreps are equal in resolution and quality to sequences of CsCl-gradient-purified plasmids.


A new quinolone and acetylcholinesterase inhibitors from a sponge-associated fungus Penicillium sp. SCSIO41033.
The chemical investigation of the EtOAc extract from the solid rice medium cultured with a sponge-associated fungus Penicillium sp. SCSIO41033 led to the isolation of two quinolones including a new one, penicinolone (1), three xanthone derivatives (3-5), and four anthraquinones (6-9). Their structures were determined by comprehensive analysis of 1H and 13C NMR, COSY, HSQC, and HMBC spectroscopic, and HRESIMS mass spectrometric data. The bioactive assays revealed that compounds 1 and 2 showed no antimicrobial activities against five bacteria and eight fungi, and compounds 5, 8 and 9 exhibited inhibition against AChE with IC50 values of 45.9, 42.5 and 40.5 μg/mL. Molecular docking analysis was performed to explore the interactions between active molecules and AChE protein, which indicated that xanthone and anthraquinone derivatives had the potential for developing AChE inhibitors.


Perturbation theory for kinks and its application for multisoliton interactions in hydrodynamics.
Using an integrable Gardner equation as an example, a perturbation theory is developed for systems in which limiting-amplitude solitons exist in the form of a pair of distanced kinks. Approximate equations describing multisoliton interactions are derived and further used for modeling the evolution of an arbitrary set of solitons. The results are compared with an exact solution and numerical results. The theory is applied to data from observation of a train of strongly nonlinear internal waves in the ocean.


Are risk factors necessary for pretest probability assessment of coronary artery disease? A patient similarity network analysis of the PROMISE trial.
Pretest probability (PTP) calculators utilize epidemiological-level findings to provide patient-level risk assessment of obstructive coronary artery disease (CAD). However, their limited accuracies question whether dissimilarities in risk factors necessarily result in differences in CAD. Using patient similarity network (PSN) analyses, we wished to assess the accuracy of risk factors and imaging markers to identify ≥50% luminal narrowing on coronary CT angiography (CCTA) in stable chest-pain patients. We created four PSNs representing: patient characteristics, risk factors, non-coronary imaging markers and calcium score. We used spectral clustering to group individuals with similar risk profiles. We compared PSNs to a contemporary PTP score incorporating calcium score and risk factors to identify ≥50% luminal narrowing on CCTA in the CT-arm of the PROMISE trial. We also conducted subanalyses in different age and sex groups. In 3556 individuals, the calcium score PSN significantly outperformed patient characteristic, risk factor, and non-coronary imaging marker PSNs (AUC: 0.81 vs. 0.57, 0.55, 0.54; respectively, p < 0.001 for all). The calcium score PSN significantly outperformed the contemporary PTP score (AUC: 0.81 vs. 0.78, p < 0.001), and using 0, 1-100 and > 100 cut-offs provided comparable results (AUC: 0.81 vs. 0.81, p = 0.06). Similar results were found in all subanalyses. Calcium score on its own provides better individualized obstructive CAD prediction than contemporary PTP scores incorporating calcium score and risk factors. Risk factors may not be able to improve the diagnostic accuracy of calcium score to predict ≥50% luminal narrowing on CCTA.


Effect of magnification and field of view on reading speed using a CCTV.
Reading speeds were measured in 18 subjects with normal vision and 10 with low vision for each of 20 experimental conditions with different magnifications and field sizes on the Closed Circuit Television System (CCTV). There was a significant difference between the results for the two groups of subjects. These results suggested that in low-vision patients with faster reading speeds, minimum magnification for maximum field size on the CCTV would be valid advice. For low-vision patients who read more slowly, reading speed may improve at higher magnifications despite reduced field size.


Chile Confronts its Environmental Health Future After 25 Years of Accelerated Growth.
Chile has recently been reclassified by the World Bank from an upper-middle-income country to a high-income country. There has been great progress in the last 20 to 30 years in relation to air and water pollution in Chile. Yet after 25 years of unrestrained growth, there remain clear challenges posed by air and water pollution, as well as climate change. The aim of this study was to review environmental health in Chile. In late 2013, a 3-day workshop on environmental health was held in Santiago, Chile, bringing together researchers and government policymakers. As a follow-up to that workshop, here we review the progress made in environmental health in the past 20 to 30 years and discuss the challenges of the future. We focus on air and water pollution and climate change, which we believe are among the most important areas of environmental health in Chile. Air pollution in some cities remains among the highest in the continent. Potable water is generally available, but weak state supervision has led to serious outbreaks of infectious disease and ongoing issues with arsenic exposure in some regions. Climate change modeling in Chile is quite sophisticated, and a number of the impacts of climate change can be reasonably predicted in terms of which areas of the country are most likely to be affected by increased temperature and decreased availability of water, as well as expansion of vector territory. Some health effects, including changes in vector-borne diseases and excess heat mortality, can be predicted. However, there has yet to be an integration of such research with government planning. Although great progress has been made, currently there are a number of problems. We suspect that the Chilean experience in environmental health may be of some use for other Latin American countries with rapid economic development.


Management of low back pain. Current assessment and formulation of a blueprint for the health care delivery system of the future.
This article outlines the authors' recommendations for future health care delivery to patients with low back pain and presents one potential blueprint for a modified delivery system. A group of multidisciplinary physicians and support staff that functions as a unified team with common goals is best positioned to overcome the challenges of providing quality care in a managed care environment. The burden on those who manage patients with spine disorders is to define and prove that high quality medical care results in genuine cost savings and better value for the health care customer.


Goal-directed therapy based on rScO2 monitoring in elderly patients with one-lung ventilation: a randomized trial on perioperative inflammation and postoperative delirium.
The incidence of postoperative delirium (POD) is high in elderly patients with one-lung ventilation, which is mostly related to the impairment of cerebral oxygen supply/demand balance during operation. (Surgical) stress can cause changes to normal physiological function and increase oxygen supply to the brain. When cerebral oxygen supply/demand is unbalanced, other organs may have already suffered from hypoperfusion or even hypoxic damages leading to increased release of inflammatory factors. Regional saturation of cerebral oxygenation (rScO2) monitoring can noninvasively monitor the variation of regional cerebral oxygen supply/demand balance in real time, and it has a good correlation with the occurrence of POD. S-100β is one of the markers commonly used to predict and diagnose POD, and lactate is one of the important indicators for the quality of tissue perfusion. The study explores whether the goal-directed therapy based on rScO2 monitoring can reduce perioperative inflammatory factor levels and POD incidence in elderly patients with one-lung ventilation and improve tissue perfusion. The study is registered on Chinese Clinical Trial Registry (ChiCTR2100054888). A total of 159 patients scheduled for thoracoscopic lobectomy under general anesthesia were divided into the control group (n = 81) and the goal-directed therapy group (GDT group, n = 78). On the basis of the conventional management in the control group, the GDT group applied goal-directed rScO2 monitoring to maintain rScO2 at ±20% baseline level during one-lung ventilation. The levels of interleukin-1β, interleukin-6, tumor necrosis factor-α, and lactate; the intensity of postoperative pain; and the incidence of POD before anesthesia (T1), at the end of operation (T2), on day 1 after operation (T3), on day 3 after operation (T4), and on day 7 after operation or before discharge (T5) were compared respectively between the two groups. The incidence of POD at T3 and the awakening time in the GDT group were lower than those in the control group (P < 0.05). During T2 to T4, the levels of inflammatory factors and lactate concentration in the control group were higher than those in the GDT group (P < 0.05). During T3 to T4, the levels of C-reactive protein and lactate in the control group were higher than those in the GDT group (P < 0.05). During T2 to T3, the levels of S-100β in the control group were higher than those in the GDT group (P < 0.05). The levels of inflammatory factors and lactate concentration in both groups during T2 to T4 were higher than those at T1 and T5 (P < 0.05), and there was no statistical difference at T1 versus T5 (P > 0.05). There was no significant difference in postoperative pain intensity, the incidence of agitation during awakening, and postoperative hospital stays between the two groups. Goal-directed therapy based on rScO2 monitoring can reduce perioperative inflammatory factor levels, postoperative delirium incidence, and postoperative awakening time and improve tissue perfusion in elderly patients with one-lung ventilation. The Chinese Clinical Trial Registry ChiCTR2100054888 . Registered on 28 December 2021.


[Effects of growth hormone treatment on anthropometrics, metabolic risk, and body composition variables in small for gestational age patients].
Small for gestational age (SGA) children without catch-up growth can benefit from treatment with growth hormone (rhGH). However, they should be monitored very closely because they are at increased risk of metabolic syndrome. A group of 28 SGA children with a mean age of 8.79 years and undergoing treatment with rhGH were selected for evaluation. Over the course of 4 years, an annual evaluation was performed on the anthropometric variables (weight, height, body mass index [BMI], growth rate, blood pressure and waist perimeter), metabolic risk variables (glycaemia, glycosylated haemoglobin, cholesterol ratio, insulinaemia, insulin-like growth factor 1[IGF1], IGF binding protein-3 [IGFBP-3], IGF1/IGFBP3 ratio, and HOMA index), and body composition variables. Treatment with rhGH was associated with a significant increase in height (-2.76±.11 SD to -1.53±.17 SD, P=.000), weight (-1.50±.09 SD to -1.21±.13 SD; P=.016), and growth rate (-1.43±.35 SD to .41±.41 SD; P=.009), without a corresponding change in the BMI. Insulinaemia (9.33±1.93mU/ml to 16.55±1.72mU/ml; P=.044) and the HOMA index (3.63±.76 to 6.43±.67; P=.042) increased, approaching insulin resistance levels. No changes were observed in the lipid profile. Body composition changes were observed, with a significant increase in lean mass (73.19±1.26 to 78.74±1.31; P=.037), and a reduction of fat mass (26.81±1.26 to 21.26±1.31; P=.021). Treatment with rhGH is effective for improving anthropometric variables in SGA patients who have not experienced a catch-up growth. It also produces changes in body composition, which may lead to a reduction in risk of metabolic syndrome. However, some insulin resistance was observed. It is important to follow up this patient group in order to find out whether these changes persist into adulthood.


Effect of soil organic amendments on the behavior of bentazone and tricyclazole.
The effect of soil amendment with different organic residues from olive oil production on the sorption and leaching of two pesticides used in rice crops (bentazone and tricyclazole) was compared in order to understand their behavior and to improve soil properties by recycling an abundant agricultural residue in Andalucía (S. Spain). A residue from olive oil production (AJ), the organic compost derived from this organic waste (CA) and a biochar (BA) made from CA were used. A soil devoted to rice cultivation, IFAPA (I), was amended at 2% (w/w) of each amendment individually (I+AJ, I+CA and I+BA). In order to evaluate the effect of dissolved organic matter (DOM) from these amendments on bentazone and tricyclazole behavior, the DOM from the amendments was extracted, quantified and characterized by fluorescence spectroscopy and FT-IR. The affinity of DOM for soil surfaces was evaluated with (I) soil and two other soils of different physicochemical properties, ARCO (A) and GUAD (G). These studies revealed differences in DOM quantity, quality and affinity for the used soils among amendments which can explain the different sorption behavior observed for tricyclazole in the amended soils. Leaching assays under saturated/unsaturated conditions revealed a slight delay of bentazone in I+CA and I+BA soils when compared to I+AJ, that can be related to the higher DOM content and much lower specific surface area of AJ. In contrast, tricyclazole was not detected in any of the leachates during the leaching assay. Extraction of tricyclazole residues from soil columns showed that the fungicide did not move below 5cm in the higher sorptive systems (I+CA, I+BA). The sorption of DOM from amendments on soil during the transport process can decrease the mobility of the fungicide by changing the physicochemical properties of the soil surface whose behavior may be dominated by the adsorbed DOM.


Novel hydrolytic resistant antibacterial monomers for dental resin adhesive.
To evaluate the properties of novel hydrolytic resistant antibacterial monomers and to determine the properties of resin adhesives containing these monomers. Methacrylamide-based QAC (Quaternary Ammonium Compound) monomers, 1-(11-Methacryla-midoundecyl)pyridine-1-ium bromide (MAUPB) and 1-(12-Methacryl-amidododecyl)pyridine-1-ium bromide (MADPB), and their methacrylate-derivatives, N-(1-Methacryloylundecanyl)pyridinium bromide (MUPB) and N-(1-Methacryloyldodecanyl)pyridinium bromide (MDPB), were synthesized and characterized. The minimum inhibitory (MIC) and bactericidal (MBC) concentrations were determined against S.mutans and E.faecalis. Cytotoxicity of unpolymerized monomers were evaluated using L-929 and MDPC-23. Each monomer was incorporated into experimental resins (BisGMA/TEGDMA/CQ/EDMAB or BisGMA/HEMA/CQ/EDMAB) at 10wt%. FTIR Spectra were collected for degree of conversion (DC%) measurement. Bacterial attachment on resin disks were determined by fluorescent microscope. Mechanical properties of experimental resins were evaluated by flexural strength & modulus and shear bond strength testing. The antibacterial activity of MDPB≥MUPB>MADPB>MAUPB. The TC50 of MAUPB> MADPB>MUPB >MDPB. Incorporation of MAUPB in BisGMA/TEGDMA-based resin, had no significant effect on DC%, while significantly increase DC% in BisGMA/HEMA-based Resin. MUPB and MAUPB containing resins showed less viable bacterial attachment than pure resins. After 3-month storage, resins containing MAUPB illustrated higher flexural strength than their corresponding resins containing MUPB. BisGMA/HEMA-based resin containing MAUPB illustrated significantly higher resin-dentin shear bond strength than that of MUPB and pure resin. Methacrylamide monomer containing QAC, MAUPB, possessed antibacterial properties and superior physical and mechanical properties when incorporated in resin adhesives as compared to their corresponding methacrylate monomer, MUPB. Methacrylamide-based QAC monomers are potentially used to formulate antibacterial hydrolytic resistant resin adhesives and enhance resin-dentin bond strength.


Application of a coproantigen ELISA as an indicator of efficacy against multiple life stages of Fasciola hepatica infections in sheep.
At present diagnosis of true resistance and determination of drug efficacy in Fasciola hepatica infection rely solely on terminal experiments. The coproantigen ELISA (cELISA) has been reported previously as a sensitive and specific tool appropriate to detect treatment failure, and potentially drug resistance. Two studies were conducted to determine whether the cELISA was appropriate for on-farm efficacy and resistance testing in Australian Merino sheep. In Study 1 sheep were infected orally with 50 F. hepatica metacercariae on three occasions, twelve, six and two weeks prior to a single flukicide treatment with triclabendazole, closantel or albendazole. Sheep were sampled weekly for a further seven weeks prior to necropsy. Following effective treatment, no faecal antigen was detected from 1 week. When immature stages (≤6 weeks) survived treatment, coproantigen reappeared from 6 weeks post-treatment. Therefore, cELISA conducted 1-4 weeks after treatment will demonstrate obvious treatment failure against adult F. hepatica, but is not sufficiently sensitive to detect survival of immature fluke until these reach maturity. In study 2, fluke burdens of sheep necropsied 13 weeks post single infection were compared to fecal worm egg counts (FWEC) and cELISA at necropsy. Regression analysis demonstrated that cELISA correlated strongly with fluke burden, whilst FWEC correlated weakly with cELISA. The correlation between FWEC and fluke burden was also weak, although stronger than that of FWEC with cELISA. The cELISA is an appropriate tool for monitoring effectiveness of treatments against Fasciola hepatica if an adult infection is present, however when immature stages of the parasite are present it is not as reliable. Where immature parasites are present it is recommended that initial cELISA be followed with a secondary cELISA at least 6 weeks after treatment to ensure resistance to immature stages is detected. Further testing is justified for monitoring the effectiveness of control programs by detecting adult populations that have survived a treatment regime.


Chronotropic responsiveness of developing sinoatrial and ventricular rat myocytes to autonomic agonists following adrenergic and cholinergic innervation in vitro.
The chronotropic responses of isolated sinoatrial node and ventricular muscle cells to neurotransmitters were compared in vitro with and without selective adrenergic and cholinergic innervation. Explants of either thoracolumbar sympathetic ganglion or sacrococcygeal spinal cord were added to cultures of newborn rat sinus node regions or ventricular apexes harvested before the onset of autonomic innervation in vivo. Catecholamine synthesis was detected by glyoxylic acid histofluorescence. Acetylcholine synthesis was indicated by monoclonal antibody labeling of choline acetyltransferase. After electrical or pharmacological stimulation of neurons, the chronotropic response of individual myocardial cells confirmed the presence of neuroeffector transmission; the nature of the myocyte response identified the stimulated neuron as either adrenergic or cholinergic. Chronotropic responses of all myocardial cells to norepinephrine or acetylcholine were transcribed on a recorder coupled to a video photoconductive cell monitor. Isolated sinoatrial node cells were supersensitive to norepinephrine and acetylcholine; thresholds were 3 x 10(-16) M and 6 x 10(-15) M, respectively. These sinoatrial node cells remained sensitive to both norepinephrine and acetylcholine after the development of innervation in vitro. Ventricular cells also were sensitive with thresholds of 3 x 10(-11) M and 6 x 10(-14) M to norepinephrine and acetylcholine, respectively. However, following in vitro innervation, ventricular cells were significantly less sensitive to norepinephrine and acetylcholine (thresholds 3 x 10(-9) M and 6 x 10(-11) M). These data are the first to demonstrate that neurotrophic modulation is not homogeneous throughout the myocardium and that it may be dependent on the specific myocardial cell innervated.


The impact of Medicare coverage policies on health care utilization.
To determine whether Medicare coverage policies affect utilization of services in Medicare. We constructed an analysis data set for eight different procedures using secondary data obtained from Medicare claims (1999-2002) and Medicare coverage policies posted on Center for Medicare and Medicaid Services website. We analyzed the impact of coverage policies using difference-in-difference approach in a regression framework. We found that in only one case (transesophageal echocardiography) out of eight did utilization change (reduced by 13.6 percent) after the effective date of the local policies. There is no systematic pattern that policies affect utilization, and the type of coverage policy does not seem to play an important role in its impact. Coverage policies have the potential but do not consistently impact utilization as policy makers intend and expect them to do. These findings raise significant policy questions about the effectiveness of Medicare coverage policies, which deserve further study.


Effect of time of day of insemination and the position of the egg in the oviduct on the fertility of turkeys.
Turkeys were inseminated at six different times of the day (1:00 p.m., 3:00 p.m., 5:00 p.m., 6:00 p.m., 9:00 p.m., and 12:00 a.m.) to determine the effect of time of day of insemination and the stage of egg formation on fertility. Significantly (P less than .01) lower fertility resulted from insemination at 1:00 p.m. than from inseminations thereafter. Significantly higher fertility resulted from 9:00 p.m. and 12:00 a.m. insemination than from preceding times. Highest fertility resulted when inseminations were performed 8 to 18 hours prior to oviposition whereas lowest fertility resulted from hens inseminated both in the last seven hours of shell deposition and during the approximate time of ovulation.


Circadian Disruption Associated with Alzheimer's Disease.
Alzheimer's disease (AD) is increasing in prevalence and has a significant impact on caregivers and the healthcare system. One of the many physiologic process affected by AD is the circadian system, with disruption reflected in abnormalities of the sleep-wake cycle. This interaction is bidirectional, with circadian and sleep disruption influencing disease progression. Understanding the bidirectional relationship between AD and circadian disruption may allow for earlier recognition of the potential to develop dementia as well as improved targeted approaches for therapy. Therapies including melatonin and bright light therapy may be advantageous in improving sleep and circadian rhythms and preventing the progression of disease. However, unfortunately, these modalities are not curative, and additional research is needed to improve treatment options for these individuals.


Altered expression of membrane inhibitors of complement in human gastric epithelium during Helicobacter-associated gastritis.
Membrane inhibitors of complement are thought to protect bystander cells from complement mediated damage. Expression of these proteins is enhanced in the colonic mucosa of patients with ulcerative colitis. Our aim was to investigate the regulation of complement activity in Helicobacter-associated chronic gastritis. We immunohistochemically assayed expression of three membrane inhibitors of complement, decay accelerating factor (DAF; CD55), 20 kDa homologous restriction factor (HRF20; CD59) and membrane cofactor protein (MCP; CD46), in 55 biopsy specimens of the human gastric mucosa. DAF, expressed in 33 (60%) of biopsy specimens, and HRF20, expressed in 45 (82%) of the samples, were located mainly on the apical surface of the epithelial cells, whereas MCP, expressed in 48 (87%) of the biopsies, was found on the basolateral surface. We found strong correlation between expression of DAF on gastric mucosal epithelium and the severity of mucosal infiltration of neutrophils (rs = 0.875, P < 0.0001) and mononuclear cells (rs = 0.773, P < 0.0001). No significant correlation was observed between HRF20 expression and neutrophil or mononuclear cell infiltration, while there was a weak negative correlation between MCP expression and these cellular infiltrations. When we assayed immunostaining of Helicobacter pylori (H. pylori) in these biopsy specimens, strong correlation with the degree of neutrophil (P < 0.0001) and mononuclear cell (P < 0.0001) infiltration were observed. The expression of DAF and H. pylori infection in these biopsies were also significantly (P < 0.0001) correlated. No correlation between HRF20 expression and H. pylori infection was observed, but we did find a significant negative correlation (P < 0.005) between the expression of MCP and H. pylori infection. Our results, demonstrating altered expression of membrane inhibitors of complement in gastric mucosa during inflammation and/or H. pylori infection, suggest that complement may significantly participate in the pathology of gastric inflammation. Moreover, DAF and MCP may play an important role in the regulation of complement activation in the alimentary tract.


Application of chemical and biological tests for estimation of current state of a tailing dump and surrounding soil from the region of Tarniţa, Suceava, Romania.
This paper presents the results from a study on the current state of tailing dump, surrounding soil and water in the region of Tarniţa-Suceava, Romania. A number of chemical analyses and germination tests were applied in an attempt to estimate the ability of soil to maintain the plants growing, the bioavailability, and heavy metals uptake. Total heavy metals, exchangeable metals, acidity, and carbon and nitrogen content were determined. A modified sequential extraction method was used to determine geochemical phase distribution of heavy metals. The most abundant heavy metals in the studied samples were Cu, Zn, and Pb. Elevated concentrations of As were also found. The results from sequential extraction revealed that up to 51% of copper was retained by amorphous and crystalline iron oxides in soil. Higher content of lead was noticed in amorphous iron oxide fraction. The heavy metal concentration in river water during dry season varied from 0.13 mg/L (Fe) to 4.2 mg/L (Zn) and was below the maximum contamination level for drinking water. The soil toxicity and heavy metal bioavailability of tailing dump material and surrounding soils were studied by germination tests. The germinated plantlets on the studied soils were found to accumulate elevated concentrations of heavy metals thus indicating the bioavailability of soil contaminants. Soil decontamination by distilled water or magnesium nitrate solution was found to be efficient enough to improve the capability of the studied soils to support the germination process.


2,6-Di-amino-4-chloro-pyrimidine-succinic acid (2/1).
In the title 2:1 co-crystal, 2C4H5ClN4·C4H6O4 the complete succinic acid mol-ecule is generated by a crystallographic centre of symmetry. In the crystal, pairwise O-H⋯N and N-H⋯O hydrogen bonds link the pyrimidine and succinic acid mol-ecules, generating R 2 2(8) loops. The pyrimidine mol-ecules are linked by pairwise N-H⋯N hydrogen bonds, again generating R 2 2(8) loops. Collectively, the hydrogen bonds link the components into corrugated (100) sheets. The Hirshfeld surface is presented.


Dataset on the psychosocial impact in families with children with developmental and epileptic encephalopathies.
Caring for children with developmental and epileptic encephalopathies (DEE) can be challenging for primary caregivers due to the complexity of the condition and the need to provide ongoing care. This has a psychosocial impact on their quality of life, including increased stress, anxiety, and depression, as well as an impact on their support network, work, and relationship with the affected child. It is important that caregivers receive help to manage the psychosocial impact of caring for a child with DEE and promote their long-term well-being. Besides, it is critical that policymakers receive quantitative data about this impact to adequately respond to the needs of these families. To this end, a database was developed using the Childhood Rare Epilepsy Social Impact Assessment (CRESIA) psychosocial impact measurement instrument to quantitatively assess the quality of life of caregivers.


Functionalization of divinylbenzene/N-vinylpyrrolidone copolymer particles: ion exchangers for solid phase extraction.
A series of four-mixed mode ion exchangers for SPE, consisting of either weak or strong cation or anion exchangers, have been synthesized by functionalization of spherical, porous particles made from a copolymer of N-vinylpyrrolidone and divinylbenzene. These materials are able to selectively retain and release acidic and basic solutes through the judicious choice of wash solvent pH, as shown through the use of SPE recovery tests.


Clinical characteristics of 12 cases of appendiceal diverticulitis: a comparison with 378 cases of acute appendicitis.
Previous authors have suggested that a diverticulum of the vermiform appendix has a higher risk of perforation than acute appendicitis. Therefore, this study compared appendiceal diverticulitis with acute appendicitis to explain the characteristics of appendiceal diverticulitis. Data for this study came from a retrospective analysis at the Department of Surgery at Fukuoka Tokushukai Hospital from January 2005 to June 2008. Twelve cases of appendiceal diverticulitis and 378 cases of acute appendicitis were analyzed. The patients with appendiceal diverticulitis were older than those with acute appendicitis (42.7 ± 15.4 vs. 29.1 ± 17.7; p = 0.009). The white blood cell (WBC) level was lower (11332 ± 4658 vs. 14236 ± 3861; p = 0.011) and the CRP level was higher (8.65 ± 8.94 vs. 4.34 ± 6.34, p = 0.022) in those with appendiceal diverticulitis than in those with acute appendicitis. A preoperative diagnosis for appendiceal diverticulitis was made in 4 out of 12 (33.3%) by ultrasonography (US). The perforation rate was higher in appendiceal diverticulitis than that in acute appendicitis (33.3 vs. 9.8%; p = 0.009). Appendiceal diverticulitis is more likely to perforate over the progression of the clinical course, which would mandate appendectomy when appendiceal diverticulitis is detected by US, even if the patient has no severe abdominal pain.