Substance P induces a rise in intracellular calcium concentration in human T lymphocytes in vitro: evidence of a receptor-independent mechanism.
The neuropeptide substance P (SP) has been shown to play an important role as a mediator of neurogenic inflammation. Moreover, in vitro SP is capable of modulating the activity of lymphocytes, monocytes and polymorphonuclear cells. We have examined one of the early events that occur after addition of SP to human peripheral blood mononuclear cells (PBMC). Addition of 10(-6)-10(-4) M SP to human peripheral blood mononuclear cells results in a dose-dependent rise in intracellular calcium concentration as determined by FACS analysis. We show that the effect of SP cannot be attenuated by the SP receptor antagonist [D-Pro4,D-Trp7,9]-SP(4-11), indicating that the response is not mediated via a SP receptor. Amphiphilic peptides like SP appear to have the capacity to insert themselves into the cell membrane and interact directly with intracellular proteins. This hypothesis is supported by the fact that the amphiphilic analogue of SP, [D-Pro2,D-Phe7,D-Trp9]-SP, is capable of inducing a calcium response in our system, although it is known as an SP receptor antagonist. Functionally, we show that SP increases the proliferative response of T cells induced by suboptimal concentrations of the mitogen PHA. These data provide evidence of a potential role of SP in the regulation of lymphocyte activation.


BMI and Body Fat Mass Is Inversely Associated with Vitamin D Levels in Older Individuals.
To assess the association between obesity (measured by Body Mass Index (BMI) and fat percentage) and serum 25(OH)D levels in older persons. Cross-sectional analysis of data from 'the B-PROOF study' (B-vitamins for the Prevention Of Osteoporotic Fractures). 2842 participants aged 65 years and older. BMI and fat percentage, measured by Dual Energy X-ray, and serum 25(OH)D levels. Mean age was 74 years (6.5 SD), with 50% women. Mean serum 25(OH)D levels were 55.8 nmol/L (25 SD). BMI and total body fat percentage were significant inversely associated with serum 25(OH)D levels after adjustment for confouders (β-0.93; 95% CI [-1.15; -0.71], p<0.001 and β-0.84; 95% CI [-1.04; -0.64], p<0.001). This association was most prominent in individuals with a BMI in the 'overweight' and 'obesity' range (β -1.25 and -0.96 respectively) and fat percentage in the last two upper quartiles (β-1.86 and -1.37 respectively). In this study, higher BMI and higher body fat percentage were significantly associated with lower serum 25(OH)D levels in older persons. This association was particularly present in individuals with overweight, and higher fat percentages, suggesting that these persons are at increased risk of vitamin D insufficiency.


Pain modulation in the adrenergically stimulated area postrema in the alert guinea pig.
The effect of chemical stimulation of the area postrema (AP) with noradrenalin (NOR) and its blocking agents was studied in alert guinea pigs submitted to noxious peripheral stimuli (electric shock). The animal's motor defense and vocalizing responses during and after nociceptive stimulation were studied. Topical administration of NOR in the AP at a concentration of 150 microgram/microliter decreased the vocalizing and movement responses with both threshold and overthreshold stimulation. Phentolamine (5 microgram/microliter) elicited the opposite response, i.e. increase in vocalization and movements. Propranolol elicited a brief reduction of the threshold response. These results suggest an involvement of the AP in the mechanism of nociceptive stimulation through alpha-adrenergic mediation. The inhibition of the response to the noxious stimulus may be the consequence of a vagal activation triggered by the AP.


The influence of social factors on common mental disorders. Destabilisation and restitution.
This study distinguishes between processes that cause individuals to experience symptoms--destabilisation--and those that are associated with loss of symptoms over time--restitution. It is shown that different clinical, social, and personality variables are associated with each of these processes. Where destabilisation is concerned, it is shown that different variables were associated with the development of symptoms of anxiety and those of depression. Different variables were associated with restitution, and they did not show the same relationship with the symptom dimensions of anxiety and depression as those which were associated with destabilisation.


Metagenome-Assembled Genomes from Photo-Oxidized and Nonoxidized Oil-Degrading Marine Microcosms.
We performed deep metagenomic sequencing on hydrocarbon-degrading marine microcosms designed to experimentally determine the effect of photo-oxidation on oil biodegradation dynamics. Assembly, binning, and dereplication yielded 73 unique metagenome-assembled genomes (MAGs) from 6 phyla, of which 61 are predicted to be over 90% complete.


The minimum land area requiring conservation attention to safeguard biodiversity.
Ambitious conservation efforts are needed to stop the global biodiversity crisis. In this study, we estimate the minimum land area to secure important biodiversity areas, ecologically intact areas, and optimal locations for representation of species ranges and ecoregions. We discover that at least 64 million square kilometers (44% of terrestrial area) would require conservation attention (ranging from protected areas to land-use policies) to meet this goal. More than 1.8 billion people live on these lands, so responses that promote autonomy, self-determination, equity, and sustainable management for safeguarding biodiversity are essential. Spatially explicit land-use scenarios suggest that 1.3 million square kilometers of this land is at risk of being converted for intensive human land uses by 2030, which requires immediate attention. However, a sevenfold difference exists between the amount of habitat converted in optimistic and pessimistic land-use scenarios, highlighting an opportunity to avert this crisis. Appropriate targets in the Post-2020 Global Biodiversity Framework to encourage conservation of the identified land would contribute substantially to safeguarding biodiversity.


Correction: Development of G: a test in an amphibious fish.
Figure 3 legend has been corrected to state: "Difference matrices for pairwise-trait phenotypic correlations (rP, below diagonal) and pairwise-trait genetic correlations (rG, above diagonal) from 1, 15, and 100 DPH. Differences are color coded by strength and direction. Differences shown in gray are positive and differences shown in black are negative. When ages are similar, the colored square is small; when ages are very different, the colored square fills the cell. EPL Epural length, EPA epural angle, PHPL parahypural length, PHPA parahypural angle, HYPL hypural length, HYPW hypural width, and SL standard length."


Synergistic efficacy of PI3Kδ inhibitor with anti-PD-1 mAbs in immune-humanized PDX model of endocrine resistance hormone receptor-positive advanced breast cancer.
Endocrine resistance hormone receptor-positive (HR+) advanced breast cancer (ABC) is generally insensitive to immunecheckpoint inhibitors (ICIs). This study sought to determine whether PI3Kδ inhibitor could enhance the sensitivity of endocrine resistance HR + advanced BC to ICIs by reducing immune evasion. Patient-derived HR + ABC xenografts were implanted into immune-humanized NSG mice and subsequently treated with YY20394 (PI3Kδ inhibitor) and camrelizumab. The mice were monitored for tumor progression, biochemical blood indicators, and peripheral blood T-cell subsets. The xenografted tumors were collected at the end of the treatment cycle and subjected to HE staining, immunohistochemistry and protein phosphorylation analysis. Besides, the xenografted tumors were also used to isolate primary breast cancer cells (BCCs) and regulatory T-cells (Tregs), which were subsequently used to evaluate drug sensitivity in vitro. The humanized PDX model showed a favorable initial treatment response to camrelizumab combined with YY20394 and manageable toxicity. YY20394 plus camrelizumab showed a strong inhibitory effect on HR + BC in vivo mediated by suppression of Treg activity and an increased proportion of CD8+ T cells. Mice bearing tumors treated with YY20394 and camrelizumab had less invasion, mitotic figures, and ki67 expression, while having higher IL-12 expression compared with other groups. Mechanistically, YY20394 only effectively inhibited the PI3K pathway and proliferation activity in Tregs but not in BCCs. Our study suggests PI3Kδ inhibitor could the enhance the efficacy of ICIs in HR + BC PDX models by combating immune suppression and provides a feasible approach that may overcome the resistance of ICIs in HR + BC patients.


Association of structural glycoproteins with lipids or lipoproteins.
Gradient density ultracentrifugation was used to assess the lipid binding of 125I-labelled structural glycoproteins and standard proteins. The results show that solubilized structural glycoproteins from cartilage or aorta will associate spontaneously with lipids or lipoproteins. In addition, structural glycoprotein preparations from tissues which have not been delipidated contain a fraction which is already associated with lipid. Standard proteins do not behave in the same way. It is proposed that structural glycoprotein-lipid binding may be one of the mechanisms involved in the intercellular deposition of plasma lipoproteins in atherosclerotic arteries.


Adult congenital pulmonary valve insertion using a new bioprosthetic aortic valve: Inspiris.
We describe successful placement of the Inspiris Resilia aortic valve in the pulmonary position. This valve has advantages for immediate benefit and future percutaneous interventions, making it a promising prosthesis for adult congenital patients.


Assessment of cardiac baroreflex function during fixed atrioventricular pacing using baroreceptor-stroke volume reflex sensitivity.
Baroreflex sensitivity in paced patients. The baroreceptor-heart rate (HR) reflex has prognostic value in cardiovascular medicine. However, it cannot be used in chronotropically incompetent or paced patients. In healthy subjects, the baroreceptor-stroke volume (SV) reflex, with power spectral analysis of SV and blood pressure (BP) variations in the low-frequency band, serves as an alternate measure of the baroreceptor-cardiac reflex. This study examined the baroreceptor-stroke volume (SV) reflex sensitivity in the supine and 60 degrees upright positions in paced patients. We studied 16 recipients of dual-chamber pacemakers paced at a fixed rate. The hemodynamics and baroreceptor-SV reflex sensitivity were measured during atrioventricular (AV) sequential pacing every 5 minute in the supine and 60 degrees upright positions. Mean SV decreased from 42.0+/-20.1 mL in the supine to 36.6+/-16.1 mL in the upright position (P<0.05), whereas BP and total peripheral resistance did not change. A significant fall in baroreceptor-SV reflex sensitivity from 29.2+/-18.0%/mmHg to 19.5+/-15.5%/mmHg was observed during upright tilt (P<0.005). Fixed-rate AV sequential pacing did not blunt the decrease in baroreceptor-SV reflex sensitivity consistent with the arterial baroreflex gain response to upright posture. The decreased baroreceptor-SV reflex sensitivity occurring with the upright posture may reflect a baroreflex-induced inotropic effect secondary to vagal withdrawal and sympathetic activation.


Preoperative and intraoperative risk factors for acute kidney injury after hip fracture surgery: a cohort retrospective study.
Hip fractures have several adverse effects on patients' morbidity and mortality. Postoperative Acute kidney injury (AKI) is one of the complications that have a significant impact on the patient's overall prognosis. We aimed to identify AKI risk after hip fracture surgery and the preoperative and intraoperative risk factors. We conducted a retrospective cohort study in a tertiary care hospital on adult patients who underwent surgery for hip fractures between January 2015 and August 2021. All clinical data were reviewed. A total of 611 patients were included (age = 76.44 ± 9.69 years). 126 (20.6%) of them developed AKI postoperatively. In multilinear logistic regression analysis, factors associated with postoperative AKI included eGFR [odds ratio (OR): 0.98; 95% confidence interval (CI): 0.97-0.99 with a p value .01], spinal anesthesia [OR: 1.78; 95% CI: 1.1-2.9 with a p value .01], and partial hip replacement (PHR) type of surgery [OR: 0.56; 95% CI: 0.32-0.96 with a p value .036]. The development of postoperative AKI was the strongest factor that increase mortality of the patients as the (HR = 2.42, CI 95% [1.57-3.74]; p value <.001). In this study, we highlight that lower eGFR, and spinal anesthesia were associated with a higher risk of AKI, and PHR surgery has lower odds to develop AKI. Postoperative AKI is associated with a higher mortality rate after hip fracture surgery.


EMT transcription factors: implication in osteosarcoma.
The primary malignant bone tumor, osteosarcoma, is a deadly disorder. Its etiology is complex, and treatment is mostly obscure. The transcription factors (TFs) involved in epithelial to mesenchymal transition (EMT) have significant role in osteosarcoma. A number of evidence suggests that overexpression of EMT-TFs, such as Twist, Snails and Zebs, is involved in complex pathogenesis of osteosarcoma. Recent research studies have showed some extent of promise in osteosarcoma treatment by targeting these EMT-TFs. However, success in research on osteosarcoma-EMT-TFs axis is just in primary stage, and a long way to go. Targeting Twist, Snail or Zeb by specific molecules or chemotherapeutic agents may provide a new dimension in osteosarcoma treatment by controlling metastasis.


Thyroid lymphoma. The case for combined modality therapy.
Radiation therapy with or without surgery is generally considered standard treatment for lymphoma of the thyroid. Because of the small number of cases, the role of chemotherapy or combined modality treatment is difficult to determine. The published literature was analyzed, supplemented by a series from Yale, for the incidence of local and distant relapse after radiation therapy, chemotherapy, or combined modality treatment for Stage I-II thyroid lymphoma. Patients with advanced disease or in whom radiation was probably inadequate were excluded. Only patients receiving an anthracyline-based regimen were considered in the group with chemotherapy. Patients receiving single agents or non-anthracycline-based regimens were excluded from analysis or, if they also received radiation, were included in the group that received radiation only. Including a series from Yale, a total of 211 patients with Stage IE and IIE thyroid lymphoma were identified. Distant and overall relapse rate were significantly lower in the group that received combined modality treatment. Local relapse was also less, but the difference was not statistically significant. In a small number of patients with disease confined to the neck, the results with radiation were similar to combined modality treatment if the mediastinum was included in the treatment port. Although mucosa-associated lymphoma tissue lymphomas are thought to have a low distant recurrence rate and are therefore often treated with local therapy alone, a review of the published literature suggests that 30% of thyroid lymphomas with clinically localized disease will have a distant relapse. The addition of chemotherapy to radiation significantly lowered distant and overall recurrence.


Peripheral and brainstem auditory function in paroxysmal (px) White Leghorn chicks.
The paroxysmal (px) chick is a mutant White Leghorn (Gallus domesticus) which appears normal at hatching and during the subsequent week. By ca. 8 days posthatching, various symptoms develop, of which the most obvious are depressed food intake (anorexia) and audiogenic seizures. Histological evidence suggests that central auditory and vestibular nuclei and fiber tracts begin to degenerate prior to seizure onset. This degeneration, which affects central and peripheral components of both systems, becomes increasingly severe over time although auditory stimulation continues to elicit seizures. Characterization and analysis of peripheral and brainstem auditory response to auditory stimuli indicated that major response differences between px and normal chicks exist in peaks reflecting brainstem activity (P3A, P3B, P4A, P5A). In 5 of 8 px chicks, these later response peaks were either grossly abnormal in terms of amplitude and latency (including amplitude input/output functions) or often entirely absent. Early peaks (P1A and P2A), however, in px waveforms were normal in morphology and amplitude, indicating normal function of peripheral auditory structures. Although lower body temperature of px chicks may account for some of the longer latencies observed, other abnormalities (e.g. absence of peaks) could not be produced in normal birds by induced hypothermia.


Effect of vegetation types on soil arbuscular mycorrhizal fungi and nitrogen-fixing bacterial communities in a karst region.
Arbuscular mycorrhizal (AM) fungi and nitrogen-fixing bacteria play important roles in plant growth and recovery in degraded ecosystems. The desertification in karst regions has become more severe in recent decades. Evaluation of the fungal and bacterial diversity of such regions during vegetation restoration is required for effective protection and restoration in these regions. Therefore, we analyzed relationships among AM fungi and nitrogen-fixing bacteria abundances, plant species diversity, and soil properties in four typical ecosystems of vegetation restoration (tussock (TK), shrub (SB), secondary forest (SF), and primary forest (PF)) in a karst region of southwest China. Abundance of AM fungi and nitrogen-fixing bacteria, plant species diversity, and soil nutrient levels increased from the tussock to the primary forest. The AM fungus, nitrogen-fixing bacterium, and plant community composition differed significantly between vegetation types (p < 0.05). Plant richness and pH were linked to the community composition of fungi and nitrogen-fixing bacteria, respectively. Available phosphorus, total nitrogen, and soil organic carbon levels and plant richness were positively correlated with the abundance of AM fungi and nitrogen-fixing bacteria (p < 0.05). The results suggested that abundance of AM fungi and nitrogen-fixing bacteria increased from the tussock to the primary forest and highlight the essentiality of these communities for vegetation restoration.


alpha-1-Antitrypsin metabolism in the protein-deficient weanling rat.
Protein-deficient weanling rats fed on a 30 g casein/kg diet for 3 weeks lost albumin but maintained the level of serum alpha-1-antitrypsin, the most abundant protease inhibitor in blood. alpha-1-Antitrypsins from malnourished rats and control rats (given 250 g casein/kg diet) differed; the protease inhibitor from protein-deficient animals: (1) was more acidic, (2) appeared slightly larger (57 400 v. 56 000 daltons) on sodium dodecyl sulphate (SDS)-polyacrylamide gels, (3) had a more acidic Pi type and increased anodal mobility at pH 8.9, (4) bound more concanavalin-A and contained more carbohydrate, specifically two to three extra sialic acid residues. The amino sugar and neutral sugar contents of both preparations of alpha-1-antitrypsin were the same. Analysis of the products of cyanogen-bromide cleavage revealed that alpha-1-antitrypsin preparations from protein-deficient rats contain an extra glycopeptide that was not present in alpha-1-antitrypsin from control animals. In vivo studies showed that the increased sialic acid content of alpha-1-antitrypsin of protein-deficient rats did not alter the half-life of the molecule in the blood of control rats. However, the fractional catabolic rate of alpha-1-antitrypsin from either well-nourished or protein-deficient rats was significantly (P less than 0.01) lower in protein-deficient rats than in control rats (0.0247/h v. 0.0406/h). The decreased fractional catabolic rate could not be explained by changes in hepatic mannosyl-, galactosyl- or N-acetylhexosaminyl receptors since liver perfusion studies showed that bovine serum albumin, when covalently modified separately with each of these ligands, was extracted from the perfusion medium as rapidly or more rapidly by livers from malnourished animals. Perfused livers from protein-deficient rats secrete three times more alpha-1-antitrypsin than do livers from well-nourished animals. The decreased fractional catabolic rate and increased rate of biosynthesis and secretion of the glycoprotein by livers from protein-deficient animals may account for the maintenance of alpha-1-antitrypsin levels during protein malnutrition.


Prognostic significance of systemic immune-inflammation index in patients with ovarian cancer: a meta-analysis.
The prognosis of several malignancies has been influenced by the systemic immune-inflammation index (SII); however, its association with the prognostic outcome of ovarian cancer (OC) remains controversial. The present meta-analysis focused on the systemic and comprehensive identification of the role of SII in predicting OC prognosis. We searched the Web of Science, PubMed, Cochrane Library, Embase, and China National Knowledge Infrastructure (CNKI) from inception until March 6, 2023. To predict the prognostic value of SII for overall survival (OS) and progression-free survival (PFS) in patients with OC, we calculated pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The meta-analysis included six studies involving 1546 patients. The combined results showed that a high SII was significantly associated with poor OS (HR=2.70, 95% CI=1.98-3.67, p<0.001) and poor PFS (HR=2.71, 95% CI=1.78-4.12, p<0.001) in OC patients. These results were confirmed using subgroup and sensitivity analyses. Our results concluded that a high SII significantly predicted poor OS and PFS in patients with OC. Therefore, it can be speculated that the SII may have an independent effect on the prognosis of OC.


Safety and Efficacy of Multilevel Thoracolumbar Vertebroplasty in the Simultaneous Treatment of Six or More Pathologic Compression Fractures.
To assess the safety and efficacy of multilevel thoracolumbar vertebroplasty in the simultaneous treatment of ≥ 6 painful pathologic compression fractures. Retrospective review was conducted of 50 consecutive patients treated with vertebroplasty for ≥ 6 pathologic compression fractures in a single session for pain palliation at a tertiary single cancer center from 2015 to 2019. Outcomes measured included procedural safety according to Common Terminology Criteria for Adverse Events (CTCAE), change in 4-week postprocedure back pain by numeric rating scale (NRS), comparison of daily opioid medication consumption, and development of skeletal-related events. A total of 397 pathologic compression fractures were treated during 50 sessions (mean, 7.9 per patient ± 1.5). Mean procedure duration was 162 minutes ± 35, mean postoperative hospitalization duration was 1.6 days ± 0.9, and mean follow-up duration was 401 days ± 297. Seven complications were recorded, including 1 case of symptomatic polymethyl methacrylate pulmonary embolism. No major complications (CTCAE grade 4/5) were reported. NRS pain score was significantly decreased (5.0 ± 1.8 vs 1.7 ± 1.4; P < .0001), with a mean score decrease of 3.3 points (66%). Opioid agent use decreased significantly (76 mg/24 h ± 42 vs 45 mg/24 h ± 37; P = .0003), with a mean decrease of 30 mg/24 h (39%). Skeletal-related events occurred in 7 patients (14%). Multilevel vertebroplasty for ≥ 6 pathologic compression fractures is safe and provides significant palliative benefit when performed simultaneously.


Autoradiographic study of tritium-labeled misonidazole in the mouse.
The localization of tritiated misonidazole metabolites in a number of normal tissues in the mouse is reported from autoradiography. The labeled misonidazole was injected at 750 or 75 mg/kg body weight (Rel. Sp. Act. 74 and 740 MBq/mg respectively). The grain count ratio, parenchyma:stroma, for selected tissues was: liver (centrilobular zone) 13; meibomian gland (acini) 68, (duct) 116; esophagus (keratinized layer) 61; enamel organ 17. It is concluded that there are a number of tissues which will accumulate MISO metabolites although they may not all be hypoxic.


Topological mechanisms involved in the formation of clathrin-coated vesicles.
By examining the basic characteristics of clathrin lattices, we discover that simple topological rules impose strict constraints on clathrin lattice transformations. These constraints require that internal bond rearrangements take place in conjunction with the addition or removal of pairs of clathrin triskelions within the interior of existing clathrin lattice patches. Similar constraints also are relevant to coated-vesicle shape changes and their budding-off from pit lattices. Via specific illustrations, successive vesicles with hexagonal-barrel and other coats are shown to grow out from the interior of a initially flat clathrin-coated pit so long as free triskelions are available from cytoplasm. Concomitantly, we present mathematical derivations of several simple and useful topological equations. These equations govern the numbers of nonhexagonal clathrin lattice facets and their variations during internal shape transformations and justify the proposed mechanisms of triskelion pair insertion and removal.


Initial presentation of hemolytic uremic syndrome in a boy with systemic lupus erythematosus.
Associating systemic lupus erythematosus (SLE) with an initial presentation of hemolytic uremic syndrome (HUS) is rare. We report on a 13-year-old boy admitted to our hospital with an initial complaint of bilateral knee pain and multiple petechiae on both lower extremities. Diagnosis of atypical HUS was established according to the clinical triad of HUS without a veriotoxin-producing organism in his stool and the pathological finding compatible to thrombotic microangiopathy. In addition, his symptoms fulfilled the 1982 revised criteria for the classification of SLE. After methylprednisolone and cyclophosphamide pulse therapies, his laboratory findings and general condition improved. No plasmapheresis or any plasma infusion was required.


Intraperitoneal heparin reduces peritoneal permeability and increases ultrafiltration in peritoneal dialysis patients.
Patients on long-term treatment with peritoneal dialysis (PD) suffer from increasing peritoneal permeability and loss of ultrafiltration as a result of persistent inflammation, which may be triggered by bioincompatible dialysis fluids. Heparins have anti-inflammatory and anticoagulant properties. We have examined the effect of intraperitoneal (IP) low-molecular weight heparin (tinzaparin) on peritoneal permeability and ultrafiltration in PD patients. By means of a double-blinded cross-over design, 21 PD patients were randomized to receive either placebo or tinzaparin intraperitoneally once a day for two treatment periods of 3 months, separated by a wash-out period. The effect of heparin on peritoneal permeability and ultrafiltration was assessed using the 4 h standard peritoneal equilibration test. IP tinzaparin reduced significantly the dialysate-to-plasma ratios (D/P) of creatinine (P < 0.01), urea (P < 0.01) and albumin (P<0.05). In addition, the ratio of glucose concentration in dialysate at 4 h dwell to that of 0 h dwell (D(4)/D(0)) was increased (P<0.05) along with an increase in ultrafiltration volume (P<0.05). IP tinzaparin reduces peritoneal permeability to small solutes and increases ultrafiltration in PD patients.


Sterol synthesis in cultured human renal cell cancer.
Studies on sterol synthesis in cultured human renal cell carcinoma were conducted in an attempt to elucidate the mechanism by which clear cell tumors accumulate cholesterol in the cytoplasm. Cultured renal cell carcinoma requires serum lipoproteins for optimal growth. In some renal cell carcinomas cellular cholesterol content was significantly higher than that present in cultured kidney cells under similar conditions. Renal cell carcinoma synthesizes sterols from labeled acetate. The rate of sterol synthesis is inversely proportional to the levels of exogenous cholesterol in the growth medium, suggesting the presence of a negative feedback mechanism. In addition, the conversion of 27-carbon-atom sterol precursors to cholesterol appears to be slow and inefficient under the presnt conditions. We conclude that an aberrant regulation of cholesterol synthesis cannot be invoked necessarily to explain cholesterol accumulation in renal cell carcinoma.


BmKK4, a novel toxin from the venom of Asian scorpion Buthus martensi Karsch, inhibits potassium currents in rat hippocampal neurons in vitro.
A novel short-chain peptide BmKK4 was isolated from the venom of Asian scorpion Buthus martensi Karsch. It is composed of 30 amino acids including six cysteine residues, and shares less than 25% sequence identity with the known alpha-KTx toxins. The action of BmKK4 on voltage-dependent potassium currents was examined in acutely dissociated hippocampal neurons of rat. BmKK4 (10-100 microM) inhibited both the delayed rectifier and fast transient potassium current in concentration-dependent manners. The inhibition was reversible and voltage-independent. BmKK4 caused a depolarizing shift (about 10 mV) of the steady-state activation curve of the currents, without changing their steady-state inactivation behavior. The unique amino acid sequence and electrophysiological effects suggest that BmKK4 represent a new subfamily of potassium channel toxins.


Toward unbiased assessment of treatment and prevention: modeling household transmission of pandemic influenza.
Providing valid and reliable estimates of the transmissibility and severity of pandemic influenza in real time is key to guide public health policymaking. In particular, early estimates of the transmissibility are indispensable for determining the type and intensity of interventions. A recent study by House and colleagues in BMC Medicine devised a stochastic transmission model to estimate the unbiased risk of transmission within households, applying the method to datasets of the 2009 A/H1N1 influenza pandemic. Here, we discuss future challenges in household transmission studies and underscore the need to systematically collect epidemiological data to decipher the household transmission dynamics. We emphasize the need to consider three critical issues for future improvements: (i) capturing age-dependent heterogeneity within households calls for intensive modeling efforts, (ii) the timeline of observation during the course of an epidemic and the length of follow-up should be aligned with study objectives, and (iii) the use of laboratory methods, especially molecular techniques, is encouraged to distinguish household transmissions from those arising in the community.See related article: http://www.biomedcentral.com/1741-7015/10/117.


Laterite as a low-cost adsorbent in a sustainable decentralized filtration system to remove arsenic from groundwater in Vietnam.
In the Red River Delta, Vietnam, arsenic (As) contamination of groundwater is a serious problem where more than seventeen million people are affected. Millions of people in this area are unable to access clean water from the existing centralized water treatment systems. They also cannot afford to buy expensive household water filters. Similar dangerous situations exist in many other countries and for this reason there is an urgent need to develop a cost-effective decentralized filtration system using new low-cost adsorbents for removing arsenic. In this study, seven locally available low-cost materials were tested for arsenic removal by conducting batch adsorption experiments. Of these materials, a natural laterite (48.7% Fe2O3 and 18.2% Al2O3) from Thach That (NLTT) was deemed the most suitable adsorbent based on arsenic removal performance, local availability, stability/low risk and cost (US$ 0.10/kg). Results demonstrated that the adsorption process was less dependent on the solution pH from 2.0 to 10. The coexisting anions competed with As(III) and As(V) in the order, phosphate > silicate > bicarbonate > sulphate > chloride. The adsorption process reached a fast equilibrium at approximately 120-360 min, depending on the initial arsenic concentrations. The Langmuir maximum adsorption capacities of NLTT at 30 °C were 512 μg/g for As(III) and 580 μg/g for As(V), respectively. Thermodynamic study conducted at 10 °C, 30 °C, and 50 °C suggested that the adsorption process of As(III) and As(V) was spontaneous and endothermic in nature. A water filtration system packed with NLTT was tested in a childcare centre in the most disadvantaged community in Ha Nam province, Vietnam, to determine arsenic removal performance in an operation lasting six months. Findings showed that the system reduced total arsenic concentration in groundwater from 122 to 237 μg/L to below the Vietnam drinking water standard of 10 μg/L.


Mechanisms controlling normal defecation and the potential effects of spinal cord injury.
Spinal cord injury frequently leads to bowel dysfunction with the result that emptying the bowel can occupy a significant part of the day and reduce the quality of life. This chapter contains an overview of the function and morphology of the normal distal gut in the human, and of gut behaviour in normal defecation. In humans, this can be monitored and is described, but knowledge of the mechanisms controlling it is limited. Work on animals has shown that the intrinsic activity of the smooth muscles and their interactions with the enteric nervous system can program the activity that is necessary to expel waste material, but the external anal sphincter is controlled through somatic nerves. The gut however also receives input from the central nervous system through autonomic nerves, and a spinal reflex centre exists. Voluntary effort to induce defecation can influence all the control mechanisms, but the precise importance of each is not understood. The behaviour and properties of the individual muscles in the normal human rectum and anal canal are described, including their responses to intrinsic nerve stimulation and adrenergic and cholinergic agonists. The effects of established spinal cord injury are then considered. For convenience, supraconal and conal/cauda equina lesions are considered as two categories. Prolongation of transit times and disordered defecation are common problems. Supraconal lesions result in reduced resting anal pressures and increased risk of fecal incontinence. The acute effects of spinal cord injury are described, with injury causing ileus (prolonged total gastrointestinal transit times), constipation (prolonged colonic transit times) and fecal incontinence (passive leakage).


Severe hypervitaminosis A in siblings: evidence of variable tolerance to retinol intake.
A 2-year-old boy had signs and symptoms of chronic hypervitaminosis A. A course of increasing severity led to eventual death. A younger brother later had similar clinical features. Chicken liver spread containing up to 420 IU/g vitamin A was the likely source of intoxication. Markedly elevated circulating retinyl ester levels have persisted in the surviving sibling for 3 subsequent years despite severe restriction of vitamin A intake. A therapeutic trial of the carbohydrate-derived complexing agent 2-hydroxypropyl-beta-cyclodextrin was initiated. Circulating retinyl esters transiently increased during the infusion (from 407 to 4791 micrograms/dL), and urinary total vitamin A excretion, undetectable before infusion, increased to 23 micrograms/dL after infusion. The frequency of hypervitaminotic episodes has decreased somewhat in the 2 years since the infusion, probably related to dietary vitamin A restriction. The occurrence of this syndrome in two brothers, while a sister ingesting the same diet remains completely healthy, suggests an inherited variance in tolerance to vitamin A intake.


Associations Between High Levels of High-Density Lipoprotein Cholesterol and the Presence and Severity of Coronary Artery Disease in Patients Who Have Undergone Coronary Computed Tomography Angiography.
Although a recent study in a Japanese cohort indicated that extremely high-density lipoprotein cholesterol (HDL-C, ≥ 90 mg/dL) had an adverse effect on atherosclerotic cardiovascular disease mortality, we could not conclude that high levels of HDL-C were associated with the presence or severity of coronary artery disease (CAD). We enrolled 1,016 patients who were clinically suspected to have CAD and who underwent coronary computed tomography angiography (CCTA). The number of significantly stenosed coronary vessels (vessel disease (VD), ≥ 50% coronary stenosis is diagnosed as CAD) and the Gensini score were quantified using CCTA, and the lipid profile was measured. The patients were divided into four groups according to the HDL-C level: < 40 mg/dL (n = 115, low), 40 - 59 mg/dL (n = 530, normal), 60 - 89 mg/dL (n = 335, high) and ≥ 90 mg/dL (n = 36, very-high). The percentage (%) of CAD in the low, normal, high and very-high groups was 69%, 55%, 42% and 25%, respectively (P for trend < 0.01). The Gensini score in the low, normal, high and very-high groups was 20 ± 25, 12 ± 16, 8 ± 12 and 4 ± 6, respectively (P for trend < 0.01). The very-high group showed the lowest triglyceride (TG) levels among the four groups. There were no significant differences in the level of low-density lipoprotein cholesterol or % use of statin among the four groups. Finally, the presence of CAD was independently associated with a low level of HDL-C, in addition to age, male, high systolic blood pressure and hemoglobin A1c, but not TG, by a multivariate logistic regression analysis. High levels of HDL-C at the time of CCTA for screening were associated with a reduced presence and severity of CAD.


Fatal digoxin poisoning: an unsuccessful resuscitation with use of digoxin-immune Fab.
A 1-month-old infant suffered cardiac arrest shortly after presentation to the emergency department. The child had a history of heart disease treated with digoxin. The infant died despite intensive resuscitative efforts, including the use of digoxin-specific Fab antibodies. A brief discussion of this case and the use of digoxin-specific antibodies is presented.


Triple-source saddle-curve cone-beam photon counting CT image reconstruction: A simulation study.
The most common detector material in the PC CT system, cannot achieve the best performance at a relatively higher photon flux rate. In the reconstruction view, the most commonly used filtered back projection, is not able to provide sufficient reconstructed image quality in spectral computed tomography (CT). Developing a triple-source saddle-curve cone-beam photon counting CT image reconstruction method can improve the temporal resolution. Triple-source saddle-curve cone-beam trajectory was rearranged into four trajectory sets for simulation and reconstruction. Projection images in different energy bins were simulated by forward projection and photon counting CT respond model simulation. After simulation, the object was reconstructed using Katsevich's theory after photon counts correction using the pseudo inverse of photon counting CT response matrix. The material decomposition can be performed based on images in different energy bins. Root mean square error (RMSE) and structural similarity index (SSIM) are calculated to quantify the image quality of reconstruction images. Compared with FDK images, the RMSE for the triple-source image was improved by 27%, 21%, 14%, 8%, and 6% for the reconstrued image of 20-33, 33-47, 47-58, 58-69, 69-80 keV energy bin. The SSIM was improved by 1.031%, 0.665%, 0.396%, 0.235%, 0.174% for corresponding energy bin. The decomposition image based on corrected images shows improved RMSE and SSIM, each by 33.861% and 0.345%. SSIM of corrected decomposition image of iodine reaches 99.415% of the original image. A new Triple-source saddle-curve cone-beam PC CT image reconstruction method was developed in this work. The exact reconstruction of the triple-source saddle-curve improved both the image quality and temporal resolution.


Genetic stability of the antagonistic character of Enterococcus faecalis ssp. liquefaciens and the detection of a new inhibitory bacteriocin-like substance.
The inhibitory capacity of strain S-48 of Enterococcus faecalis ssp. liquefaciens was studied. The strain produces a broad-spectrum peptide antibiotic (AS-48) that has been characterized elsewhere. The isolation of mutants from S-48 after mutagenic treatment revealed another inhibitory substance which remained masked in the wild strain. The protein nature and restricted spectrum of this substance points to its being a bacteriocin.


Results of keratoprosthesis.
The technique of keratoprosthesis was used in 21 cases of severe and intractable forms of keratopathy during the past 3 1/2 years. The results in terms of visual acuity were satisfactory in more than half the cases. Significant problems that occurred after this procedure included the diagnosis and management of glaucoma, vitreitis, and retroprosthetic membrane. There were no instances of extrusion of the keratoprosthesis nor were there any cases of endophthalmitis. However, one case developed necrosis of the tissue around the optical cylinder on the eyelid after surgery. Although its use is limited to only some forms of keratopathy, keratoprosthesis seems to offer a solution in cases where no other treatment is available.


EU Regulatory Pathways for ATMPs: Standard, Accelerated and Adaptive Pathways to Marketing Authorisation.
Advanced therapy medicinal products (ATMPs) require evaluation by the European Medicines Agency's Committee for Advanced Therapies prior to being placed on the European market, subject to a Marketing Authorisation granted by the European Commission. In common with other medicinal products, various regulatory pathways are available for taking ATMPs through clinical trials to market authorisation, and the regulatory pathway taken will depend on a product's characteristics and the target patient population. With the industry poised to deliver more late-stage clinical and commercial ATMPs for serious diseases with high unmet medical need (e.g., T cell immunotherapies for cancer), bringing medicines to patients through optimized regulatory strategies and expedited pathways is assuming greater importance. The European Medicines Agency's priority medicines (PRIME) scheme was introduced in 2016 specifically to enable this, and eligibility has been granted to 19 ATMPs as of the fourth quarter (Q4) 2018. Furthermore, two chimeric antigen receptor (CAR) T cell therapies, Yescarta and Kymriah, have recently completed their journeys through the scheme to Marketing Authorisation. This review discusses how the regulatory pathway for any particular ATMP, with or without PRIME designation, is determined and navigated.


Establishment and application of a novel T cell clonality analysis using single-strand conformation polymorphism of T cell receptor messenger signals.
To identify the existence of antigen specific T cell responses and to follow the changes of these reactions, it is considered useful to evaluate whether certain T cells clonally accumulate in the lymphocyte population. For this purpose, we have established a novel method to analyze T cell clonality using a combination of reverse transcriptase-polymerase chain reaction of T cell receptor beta chain transcripts and single-strand conformation polymorphism (SSCP). Using this method, we obtained a smear-like pattern of electrophoresed DNA from the heterogeneous T cell population. On the other hand, a single T cell clone exhibits a band in the appropriate VP amplification and an accumulated T cell clone in a heterogeneous lymphocyte population is identified as a band in the background smear pattern. If a lymphocyte population was stimulated by an antigen either in vitro or in vivo, several distinct bands were found to be generated in the background smear. Thus, the dynamic changes of T cell clonal responses could be monitored with this method. Analyses of several immunological disorders, including autoimmune diseases, malignant disorders, and transplantations, revealed the involvement of antigen-specific T cell immune responses in these disorders. Furthermore, taking advantage of the reproducible mobility of a band of SSCP gel, we are now able to compare identities of the accumulated T cell clones in different samples without the need for nucleotide sequencing of each clone. Such information can thus elucidate the occurrence of uniform or stable immunological reactions in the host and also suggests that these reactions play an important role in vivo. Therefore, taken together, the above described novel T cell clonality analysis is considered to be useful in studying the T cell immune responses in various fields of immunology.


Annual booster vaccination and the risk of equine influenza to Thoroughbred racehorses.
Equine influenza (EI) outbreaks occurred among horses on four racing yards (two National Hunt, one Flat, one mixed National Hunt racing/breeding yard) in Ireland within a 4-week period. To carry out a detailed analysis of racing yards affected in order to identify the source of infection and monitor virus spread among a vaccinated population. Observational field study. Epidemiological and vaccination data along with repeat clinical samples were collected from 118 horses on four premises. Failure to implement appropriate biosecurity measures following the introduction of new arrivals and the return of horses from equestrian events contributed to disease spread as did the movement of horses within premises. Mixing of racing and non-racing populations with inadequate vaccination histories also facilitated virus transmission. The index case(s) on all premises was vaccinated in accordance with the Turf Club rules. Vaccine breakdown was observed across all products in 27/80 horses (33.8%) with an up-to-date vaccination record. Eighteen of the 27 (66.7%) horses had not received a booster vaccination within the previous 6 months and 10 (37%) horses were due annual booster vaccination at the time of developing clinical signs. The interpretation of laboratory results followed a delay in veterinary intervention. Annual booster vaccination should not be relied on as the sole preventative measure against EI. The findings of this study suggest that increasing the frequency of booster vaccinations may be beneficial particularly in young horses and that synchronised scheduling of vaccination regimes across racing yards may contribute to high-risk periods for EI virus (EIV) transmission.


Factors associated with social anxiety in South Korean adults with epilepsy.
The aim of this study was to examine social anxiety in South Korean adults with epilepsy and to identify associated factors. This was a cross-sectional, multicenter study in South Korea. Social anxiety was assessed using short forms of the Social Phobia Scale (SPS-6) and Social Interaction Anxiety Scale (SIAS-6). The SPS-6 scores ≥9 and SIAS-6 scores ≥12 were considered indicative of social phobia and social interaction anxiety, respectively. The Patient Health Questionnaire-9 (PHQ-9); Stigma Scale-Revised (SS-R); Disclosure Management Scale; Family Adaptation, Partnership, Growth, Affection, Resolve (F-APGAR) scale; and a questionnaire assessing knowledge about epilepsy were also used. Of a total of 219 patients with epilepsy, 21% and 11% had SPS-6 scores ≥9 and SIAS-6 scores ≥12, respectively. In logistic regression analysis, SPS-6 scores ≥9 were independently associated with SS-R scores of 4-9 (odds ratio [OR]: 8.626, 95% confidence interval [CI]: 2.515-29.587, p = .001), SS-R scores 1-3 (OR: 5.496, 95% CI: 1.757-17.197, p = .003), and PHQ-9 scores ≥10 (OR: 4.092, 95% CI: 1.823-9.185, p = .001). In contrast, SIAS-6 scores ≥12 were related only to PHQ-9 scores ≥10 (OR: 8.740, 95% CI: 3.237-23.599, p < .001). Belonging to a dysfunctional family and lack of knowledge about epilepsy tended to be associated with social phobia (p = .071) and social interaction anxiety (p = .090), respectively. Epilepsy-related variables were not related to social anxiety. Social anxiety is not rare in patients with epilepsy. In this study, social phobia was associated with perceived stigma and depressive symptoms, whereas social interaction anxiety was related only to depressive symptoms in patients with epilepsy.


Modelling how antimicrobial resistance spreads between wards.
Moving patients between wards and prescribing high levels of antibiotics increases the spread of bacterial infections that are resistant to treatment in hospitals.


High-Throughput PCR for DNA Part Generation.
This protocol describes a high-throughput approach to PCR for the generation of over a thousand amplicons in parallel. Modern liquid handling robotics are used to accelerate reaction setup, miniaturize reaction volumes, and dramatically reduce reagent and consumable cost. Although the focus is on generating DNA parts for use in DNA assembly techniques, this methodology can be applied to any workflow where the parallel production of hundreds or thousands of PCR amplicons is required.


Fungal transformation of norandrostenedione with Cunninghamella blakesleeana and anti-bacterial activity of the transformed products.
Although the discovery of antibiotics has decreased the spread and severity of infectious diseases, their uncontrolled use has lead to the emergence of bacterial resistance to existing chemotherapeutic agents. Bacterial disease thus remains a challenge for health authorities in worldwide and especially in sub-Saharan Africa. Despite their efficacy, the miss-use of medicinal plants for the treatment of infectious diseases couple to the farming and hunting activities has contribute enormously to the destruction of many medicinal plant species. In search of an alternative for new and effective agents against bacterial infection, norandrostenedion (19-nor-4-androsten-3,17-dione) (1), was biotransformed by Cunninghamella blakesleeana ATCC 8688A and yielded a new metabolite, 6α,10 β -dihydroxy-19-nor-4-androsten-3-one (2), together with three known compounds, 10 β -hydroxy-19-nor-4-androsten-3,17-dione (3), 6 β,10 β,17 β -trihydroxy-19-nor-4-androsten-3-one (4) and 10 β,17 β -dihydroxy-19-nor-4-androsten-3-one (5). Their structures were elucidated on the basis ofspectroscopic techniques: NMR analysis (1D and 2D) and HRIE-MS and by comparison with previously reported data. In addition, the agar diffusion method was used to evaluate the diameter of the inhibition zone and INT colorimetric assay for MIC values. All metabolites obtained showed a potent and varied activity against tested bacteria. These results support the uses of biotransformation to develop new antimicrobial compounds for clinical application.


MicroRNA840 (MIR840) accelerates leaf senescence by targeting the overlapping 3'UTRs of PPR and WHIRLY3 in Arabidopsis thaliana.
MicroRNAs negatively regulate gene expression by promoting target mRNA cleavage and/or impairing its translation, thereby playing a crucial role in plant development and environmental stress responses. In Arabidopsis, the MIR840 gene is located within the overlapping 3'UTR of the PPR and WHIRLY3 (WHY3) genes, both being predicted targets of miR840* and miR840, the short maturation products of MIR840. Gain- and loss-of-function of MIR840 in Arabidopsis resulted in opposite senescence phenotypes. The highest expression levels of the MIR840 precursor transcript pre-miR840 were observed at senescence initiation, and pre-miR840 expression is significantly correlated with a reduction in PPR, but not WHY3, transcript levels. Although a reduction of transcript level of PPR, but not WHY3 transcript levels were not significantly affected by MIR840 overexpression, its protein levels were strongly reduced. Mutating the cleavage sites or replacing the target sequences abolishes the miR840*/miR840-mediated degradation of PPR transcripts and accumulation of WHY3 protein. In support for this, concurrent knockdown of both PPR and WHY3 in wild-type plants resulted in a senescence phenotype resembling that of the MIR840-overexpressing plant. This indicates that both PRR and WHY3 are targets in the MIR840-mediated senescence pathway. Moreover, single knockout mutants of PPR and WHY3 show a convergent upregulated subset of senescence-associated genes, which are also found among those induced by MIR840 overexpression. Our data provide evidence for a regulatory role of MIR840 in plant senescence.


Subjective assessment of nutritional status-validity and reliability of a modified Detsky index in a Swedish setting.
In the search for a clinically useful nutritional index for use in a European context, we have translated an American nutritional assessment index - Subjective Global Assessment (SGA), and tested the modified translated version for validity and reliability in a Swedish setting. Judgements by an expert panel resulted in a mean agreement of 71% for clarity, 80% for content validity and 65% for internal consistency. Construct validity was demonstrated by the use of contrasting patient-groups (n = 20) and by 90% agreement with a medical expert as 'gold standard' for unknown patients (n = 20). Inter-rater reliability showed 75% agreement by 3 Registered Nurses (RNs) (n = 20). The individual Kappas for the raters varied from 0.68 to 0.89. The study showed difficulties experienced by raters in relating certain aspects in the SGA-index to normality. However, we concluded that a modified SGA-index translated from one language to another, with all the problems of cultural and idiomatic differences, can be of value for assessing and documenting pre-operative nutritional status of patients undergoing gastrointestinal surgery in a Swedish setting.


Expression of the human foamy virus bel-1 transactivator in insect cells.
The human foamy virus (HFV) bel-1 transactivator protein was expressed in insect cells by a recombinant baculovirus. For the generation of the recombinant baculovirus, Acbel-1, the bel-1 gene of an HFV mutant was used, that bears truncations in the bel-1 overlapping bel-2 open reading frame. Acbel-1 infected Sf9 cells produced high amounts of recombinant protein of the same electrophoretic mobility (36 kD) as bel-1 expressed in mammalian cells. The baculovirus expressed bel-1 protein was readily identified by a polyclonal rabbit serum directed against bel-1 in immunoblot assay. As in mammalian cells, bel-1 was predominantly localized to the nucleus of Acbel-1 infected insect cells. The baculovirus expressed bel-1 protein will be of use to determine the action of this novel viral transactivator more precisely.


Search for HRV-parameters that detect a sympathetic shift in heart failure patients on β-blocker treatment.
A sympathetic shift in heart rate variability (HRV) from high to lower frequencies may be an early signal of deterioration in a monitored patient. Most chronic heart failure (CHF) patients receive β-blockers. This tends to obscure HRV observation by increasing the fast variations. We tested which HRV parameters would still detect the change into a sympathetic state. β-blocker (Carvedilol®) treated CHF patients underwent a protocol of 10 min supine rest, followed by 10 min active standing. CHF patients (NYHA Class II-IV) n = 15, 10m/5f, mean age 58.4 years (47-72); healthy controls n = 29, 18m/11f, mean age 62.9 years (49-78). Interbeat intervals (IBI) were extracted from the finger blood pressure wave (Nexfin®). Both linear and non-linear HRV analyses were applied that (1) might be able to differentiate patients from healthy controls under resting conditions and (2) detect the change into a sympathetic state in the present short recordings. Linear: mean-IBI, SD-IBI, root mean square of successive differences (rMSSD), pIBI-50 (the proportion of intervals that differs by more than 50 ms from the previous), LF, HF, and LF/HF ratio. Non-linear: Sample entropy (SampEn), Multiscale entropy (MSE), and derived: Multiscale variance (MSV) and Multiscale rMSSD (MSD). In the supine resting situation patients differed from controls by having higher HF and, consequently, lower LF/HF. In addition their longer range (τ = 6-10) MSE was lower as well. The sympathetic shift was, in controls, detected by mean-IBI, rMSSD, pIBI-50, and LF/HF, all going down; in CHF by mean-IBI, rMSSD, pIBI-50, and MSD (τ = 6-10) going down. MSD6-10 introduced here works as a band-pass filter favoring frequencies from 0.02 to 0.1 Hz. In β-blocker treated CHF patients, traditional time domain analysis (mean-IBI, rMSSD, pIBI-50) and MSD6-10 provide the most useful information to detect a condition change.


Influence of Probiotics Feed Supplementation on Hypopharyngeal Glands Morphometric Measurements of Honeybee Workers Apis mellifera L.
More scientific study and methods that are compatible with the honeybee-specific probiotic bacteria are needed in modern beekeeping to increase the productivity and well-being of honeybees. The goal of the current study set out to investigate the possible effects of probiotics previously isolated from the honeybee intestinal tract and soybean patties on nurse worker bee hypopharyngeal gland (HPG) development. The experimentation was carried out in four different treatment groups in which probiotics and soybean patties were provided in different proportions, with control colonies. Results showed that there was a significant increase in HPG morphometric parameters of bees in all experimental groups. Control nurse worker fed with sugar syrup for only 2 weeks had the smallest HPG morphometric parameters. The highest HPG diameter 14.89 ± 0.097 µm and surface area 0.065 ± 0.001µm2 were observed in the bees group fed with both probiotic and soya patty. Additionally, the same trend was observed in all morphometric parameters with the bees group fed with probiotic bacteria and soya patty. More royal jelly can be produced by larger HPGs than by smaller ones. Thus, the use of probiotics as a natural alternative tool boosted the development of Apis mellifera nurse workers' HPG that will positively affect the beekeepers' economy by providing a higher yield of royal jelly production. Overall, the study's findings show that probiotics are a useful feed supplement for honeybees.


Optimization of the moving-bed biofilm sequencing batch reactor (MBSBR) to control aeration time by kinetic computational modeling: Simulated sugar-industry wastewater treatment.
A novel approach was applied for optimization of a moving-bed biofilm sequencing batch reactor (MBSBR) to treat sugar-industry wastewater (BOD5=500-2500 and COD=750-3750 mg/L) at 2-4 h of cycle time (CT). Although the experimental data showed that MBSBR reached high BOD5 and COD removal performances, it failed to achieve the standard limits at the mentioned CTs. Thus, optimization of the reactor was rendered by kinetic computational modeling and using statistical error indicator normalized root mean square error (NRMSE). The results of NRMSE revealed that Stover-Kincannon (error=6.40%) and Grau (error=6.15%) models provide better fits to the experimental data and may be used for CT optimization in the reactor. The models predicted required CTs of 4.5, 6.5, 7 and 7.5 h for effluent standardization of 500, 1000, 1500 and 2500 mg/L influent BOD5 concentrations, respectively. Similar pattern of the experimental data also confirmed these findings.


Thermal strain resulting from protective clothing of an armored vehicle crew in warm conditions.
The purpose of the study is to define a method of evaluation of physiological strain resulting from protective garments worn in warm conditions by the armored vehicle crew. A technique is developed evaluating evaporative transfer through clothing by continuous weighing of the active man (accuracy +/- 3/g). An index is defined (Iw) as the ratio of steady-state evaporating rate in clothed conditions to steady-state evaporation of nude subject in the same conditions of work and heat stress. The Iw index is significantly related to physiological strain determined by increased body heat content and reduced tolerance time. The results are compared to other previous findings concerning evaporative transfer through clothing and physiological strain indexes. The technique shows that evaporation through heavy clothing is not negligible. It is suggested that usual static measurements using physical models underestimate the evaporative heat transfer through clothing layers.


Identification and characterization of a new HNH restriction endonuclease with unusual properties.
Restriction-modification (R-M) systems form a large superfamily constituting bacterial innate immunity mechanism. The restriction endonucleases (REases) are very diverse in subunit structure, DNA recognition, co-factor requirement, and mechanism of action. Among the different catalytic motifs, HNH active sites containing REases are the second largest group distinguished by the presence of the ββα-metal finger fold. KpnI is the first member of the HNH-family REases whose homologs are present in many bacteria of Enterobacteriaceae having varied degrees of sequence similarity between them. Considering that the homologs with a high similarity may have retained KpnI-like properties, while those with a low similarity could be different, we have characterized a distant KpnI homolog present in a pathogenic Klebsiella pneumoniae NTUH K2044. A comparison of the properties of KpnI and KpnK revealed that despite their similarity and the HNH motif, these two enzymes have different properties viz oligomerization, cleavage pattern, metal ion requirement, recognition sequence, and sequence specificity. Unlike KpnI, KpnK is a monomer in solution, nicks double-stranded DNA, recognizes degenerate sequence, and catalyses the degradation of DNA into smaller products after the initial cleavage at preferred sites. Due to several distinctive properties, it can be classified as a variant of the Type IIS enzyme having nicking endonuclease activity. KEY POINTS: • KpnK is a distant homolog of KpnI and belongs to the ββα-metal finger superfamily. • Both KpnI and KpnK have widespread occurrence in K. pneumoniae strains. • KpnK is a Type IIS restriction endonuclease with a single-strand nicking property.


[A 17-year-old girl with bilateral swollen upper eyelids].
Case of a 17-year-old female with rhinitis, intermittent fever, painful enlarged lymph nodes and painless bilateral upper eyelid swelling. Complicated sinusitis and vascular pathology were ruled out, but Epstein-Barr serology was positive. Bilateral upper eyelid edema can be an early presentation of mononucleosis infectiosa and is called the Hoagland sign.


Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation and Cancer.
The prevention of stroke in patients with atrial fibrillation (AF) and cancer is challenging because patients are at increased bleeding and thrombotic risk. The authors sought to assess left atrial appendage occlusion (LAAO) as a safe and effective strategy for reducing stroke at no increased bleeding risk in cancer patients with AF. We reviewed patients with nonvalvular AF who underwent LAAO at Mayo Clinic sites from 2017 to 2020 and identified those who had undergone prior or current treatment for cancer. We compared the incidence of stroke, bleeding, device complications, and death with a control group who underwent LAAO without malignancy. Fifty-five patients were included; 44 (80.0%) were male, and the mean age was 79.0 ± 6.1 years. The median CHA2Ds2-VASc score was 5 (Q1-Q3: 4-6), with 47 (85.5%) having a prior bleeding event. Over the first year, ischemic stroke occurred in 1 (1.4%) patient, bleeding complications in 5 (10.7%) patients, and death in 3 (6.5%) patients. Compared with controls who underwent LAAO without cancer, there was no significant difference in ischemic stroke (HR: 0.44; 95% CI: 0.10-1.97; P = 0.28), bleeding complication (HR: 0.71; 95% CI: 0.28-1.86; P = 0.19), or death (HR: 1.39; 95% CI: 0.73-2.64; P = 0.32). Within our cohort, LAAO in cancer patients was achieved with good procedural success and offered a reduction in stroke at no increased bleeding risk similar to noncancer patients.


Upregulation of both PDGF-BB and PDGF-BB receptor in human bladder fibroblasts in response to physiologic hydrostatic pressure.
Bladder outlet obstruction can lead to the deposition of extracellular matrix and a resultant decrease in bladder wall compliance. Platelet-derived growth factor (PDGF) is a potent mitogen for fibroblasts and can increase the deposition of extracellular matrix. We attempt to determine if the expression of PDGF-BB and its receptor are altered in human bladder fibroblasts and bladder smooth muscle cells when exposed to hydrostatic pressures in the physiologic range. Cultured human bladder fibroblasts and smooth muscle cells were evaluated in vitro by using a novel device that controls for hydrostatic pressure. Cells were exposed to pressures of 20 and 40 cmH(2)O for up to 72 h. Western blot analyses and RT-PCR were performed to evaluate expression of both PDGF-BB and PDGF-BB receptor. PDGF-BB and its receptor increased up to 22-fold and 8-fold, respectively, when human bladder fibroblasts were exposed to 40 cmH(2)O sustained hydrostatic pressure, while at 20 cmH(2)O the effect was minimal until 72 h. mRNA for the PDGF-BB receptor in human bladder fibroblasts increased in comparison to control. Western blot analyses demonstrated that exposure of human bladder smooth muscle cells to a sustained hydrostatic pressure of 20 and 40 cmH(2)O for up to 72 h did not alter expression of either PDGF-BB or its receptor. Both PDGF-BB and its receptor in human bladder fibroblasts were upregulated in a time- and pressure-dependent manner after as little as 24 h exposure to pressures of < or =40 cmH(2)O. Our results provide support for a potential role of both PDGF-BB and its receptor in bladder fibrosis secondary to increased intravesical pressure. Newer selective PDGF receptor antagonists may prove beneficial in preventing bladder wall fibrosis in patients with either anatomic or functional bladder outlet obstruction.


Taurine promotes estrogen synthesis by regulating microRNA-7a2 in mice ovarian granulosa cells.
Taurine, acting as a free amino acid, is widely distributed and plays multiple functions, including its regulating effect on estrogen synthesis in ovary. However, the mechanisms of taurine regulating estrogen synthesis in granulosa cells are not well understood. In this study, we identify whether microRNA-7a2 (miR-7a2) is involved in the signaling of taurine regulating estrogen synthesis in mouse granulosa cells for the first time. The results demonstrated that taurine transporter (TauT) co-localized with miR-7a in mouse ovarian granulose cells. Further, taurine treatment markedly enhanced the expression of miR-7a and Cyp19a1 in mouse ovaries and increased serum 17β-estradiol (E2) concentration. Meanwhile, miR-7a2 knockout reversed the effect of taurine on E2. In addition, Golgi apparatus protein 1 (Glg1), a downstream target gene of miR-7a2, was significantly down-regulated by taurine, while Glg1 knockdown markedly increased the Cyp19a1 expression and E2 synthesis. Moreover, taurine affected miR-7a expression via activating p38 signaling. These results suggest that taurine promotes E2 synthesis through p38/miR-7a/Glg1/Cyp19a1 signaling pathway, which is crucial to understand the function and mechanism of taurine on estrogen synthesis.


Cardiopulmonary resuscitation for in-hospital events in the emergency department: A comparison of adult and pediatric outcomes and care processes.
To compare outcomes from in-hospital cardiopulmonary resuscitation (CPR) in the emergency department (ED) for pediatric and adult patients and to identify factors associated with differences in outcomes between children and adults. Retrospective analysis of the Get With The Guidelines--Resuscitation database from January 1, 2000 to September 30, 2010. All patients with CPR initiated in the ED requiring chest compressions for ≥ 2 min were eligible; trauma patients were excluded. Patients were divided into children (<18 yo) and adults (≥ 18 yo). Patient, event, treatment, and hospital factors were analyzed for association with outcomes. Univariate analysis was performed comparing children and adults. Multivariate analysis was used to determine factors associated with outcomes. 16,834 events occurred in 608 centers (16,245 adult, 537 pediatric). Adults had more frequent return of spontaneous circulation (53% vs 47%, p = 0.02), 24h survival (35% vs 30%, p = 0.02), and survival to discharge (23% vs 20%, p = NS) than children. Children were less frequently monitored (62% vs 82%) or witnessed (79% vs 88%), had longer duration (24 m vs 17 m), more epinephrine doses (3 vs 2), and more frequent intubation attempts (64% vs 55%) than adults. There were no differences in time to compressions, vasopressor administration, or defibrillation between children and adults. On multivariate analysis, age had no association with outcomes. Survival following CPR in the ED is similar for adults and children. While univariate differences exist between children and adults, neither age nor specific processes of care are independently associated with outcomes.


Incorporating carbon sequestration into lake management: A potential perspective on climate change.
Exploring the carbon sequestration capacity of water ecosystems would contribute to coping with climate change. This study conducted an integrated method framework to achieve an improved understanding of the relationship between carbon sequestration and lake ecosystem components, as well as provide a new perspective on climate change for policymakers. The vertically generalized production model revealed the carbon sequestration capacity of lakes. The hierarchical linear model identified the cross-scale factors affecting phytoplankton. Then a developed multi-agents-based model with scenario analysis provided adaptive management strategies for carbon sequestration. Furthermore, we applied the integrated framework in the 63 polluted lakes of Wuhan. The results showed that the average carbon sequestration per unit area was at 0.87 kgC·m-2·a-1, which was greater than that of the ocean and forest ecosystems, indicating that the lakes had a potential capacity for carbon sequestration. Total phosphorus had the strongest effect on the Chl-a (chlorophyll a) concentration (fixed effect (γ) =6.82, P < 0.1), followed by total nitrogen (γ = 6.38, P < 0.05), Rotifer biomass (γ = 1.95, P < 0.01) and water temperature (γ = 1.27, P < 0.05). These results indicated that the bottom-up effect of chemical factors on phytoplankton was greater than the top-down effect of zooplankton. The proportion of grassland at the whole-lakes level would have a negative synergistic impact on the Chl-a with changing the micro water temperature at the part-lakes level (γ = -46.64, P < 0.05). There was no significant interaction effect between land cover change and total nitrogen (phosphorus) on the Chl-a. Therefore, we could indirectly confirm that point source pollution emissions would synergistically affect the Chl-a and carbon sequestration along with the effects of physical-chemical conditions. The coordinated proportional control of nitrogen and phosphorus and the artificial controlling biomass of zooplankton-feeding fish were proposed to improve carbon sequestration and water quality for lake management.


Liquid nitrogen storage of Anaplasma marginale complement-fixation antigen by a multiple small aliquot technique.
Anaplasma marginale complement fixation test antigens were frozen as drops in liquid nitrogen using an easily constructed apparatus. Economy in the use of antigen was achieved as the frozen drops were retrieved from storage in any required volume. The potency of the antigen was unaffected by the freezing and thawing technique. The technique is useful for storing other biological reagents.


[Effect of imidapril on the effective refractory period and sodium current of ventricular noninfarction zone in healed myocardial infarction].
To investigate the effects of imidapril (IMI) on effective refractory period (ERP) and sodium current (I(Na)) of myocytes in ventricular noninfarction zone of healed myocardial infarction (HMI) in rabbit models. Rabbits with left coronary artery ligation were prepared and IMI (0.625 mg x kg(-1) x d(-1), 8 weeks) was orally administered. The ERP and sodium current were recorded. The ERP in HMI heart was prolonged. The ERP in IMI group was lower significantly than that of HMI group. The I(Na) density of myocyte in HMI ventricle decreased obviously. V 1/2 of steady state inactivation of I(Na) shifted to hyperpolarization, and time constant (tau) of recovery from inactivation in HMI ventricular myocyte was longer than that of sham ventricular myocyte. I(Na) density in IMI group increased markedly as compared with that of HMI group. IMI was shown to reverse the abnormal prolongation of ERP in rabbit heart with the HMI and increase I(Na) density. It may be the mechanism of IMI preventing against antiarrhythmia in healed myocardical infarction.


Mechanisms of benthic algal recovery following spates: comparison of simulated and natural events.
We conducted a manipulative field experiment to examine individual and interactive effects of scour and short-term nutrient enrichment (4 h exposure) on postspate recovery of benthic algae in a desert stream. We then compared recovery from these simulated-spate conditions to algal recovery patterns following a natural spate that increased water-column nutrient levels for 2 weeks. That event differentially scoured communities on artificial substrata in place for a long-term experiment, significantly reducing biomass in 49-day-old communities but causing no significant reduction of biomass in older, 133-day-old communities. Thus, we were able to examine recovery of scoured and non-scoured benthic algal communities under natural post-spate conditions. Both natural and simulated spates reduced actual and relative abundances of diatoms within communities. In the manipulative experiment, scoured communities accrued biomass more rapidly than those not subjected to scour, but short-term enrichment had not effect. Accrual of diatoms and green algae was stimulated by the scour manipulations, while cyanobacteria maintained equal rates of growth in all treatments. Following the natural spate, diatom and green-algal densities increased in scoured communities, but recovery of algal biomass was slow on both scoured and non-scoured substrata, primarily because cyanobacteria, the dominant algal group on all tiles, did not increase under exposure to highly nitrate-enriched waters. Rates of algal cell accrual were inversely correlated with the amount of algal biomass present at the start of a recovery sequence. Algal immigration rates measured immediately after the natural spate and during an interflood period in the same season did not differ, indicating that the algal drift pool was not augmented by disturbance. Benthic algal recovery following spates is strongly influenced by the degree of scour generated by the event, but recovery patterns are also affected by the length of post-spate enrichment and the taxonomic composition of the affected community.


Repair of surviving hair cells in the damaged mouse utricle.
Sensory hair cells (HCs) in the utricle are mechanoreceptors required to detect linear acceleration. After damage, the mammalian utricle partially restores the HC population and organ function, although regenerated HCs are primarily type II and immature. Whether native, surviving HCs can repair and contribute to this recovery is unclear. Here, we generated the Pou4f3DTR/+; Atoh1CreERTM/+; Rosa26RtdTomato/+ mouse to fate map HCs prior to ablation. After HC ablation, vestibular evoked potentials were abolished in all animals, with ∼57% later recovering responses. Relative to nonrecovery mice, recovery animals harbored more Atoh1-tdTomato+ surviving HCs. In both groups, surviving HCs displayed markers of both type I and type II subtypes and afferent synapses, despite distorted lamination and morphology. Surviving type II HCs remained innervated in both groups, whereas surviving type I HCs first lacked and later regained calyces in the recovery, but not the nonrecovery, group. Finally, surviving HCs initially displayed immature and subsequently mature-appearing bundles in the recovery group. These results demonstrate that surviving HCs are capable of self-repair and may contribute to the recovery of vestibular function.


Novel Iminocoumarin Derivatives: Synthesis, Spectroscopic and Computational Studies.
Three novel iminocoumarin derivatives with high quantum yield are synthesized from 3-benzimidazole substituted coumarin and different aromatic aldehydes. The photophysical behavior of the synthesized compounds was studied using UV-visible and fluorescence spectroscopy in polar and non-polar solvents. The compounds show absorption maxima at around 450 nm and emission maxima at around 500 nm. The quantum yields of compounds in dichloromethane and chloroform are more than 0.90. The absorption, emission and quantum yield of compounds are dependent on the polarity of solvents. Along with an intense absorption, these compounds show shoulder absorption peak in the studied solvents. The solvent polarity plots revealed the charge transfer process in the synthesized molecules from donor to acceptor. Density Functional Theory and Time Dependent Density Functional Theory computations have been used to have more understanding of the structural, molecular, electronic and photophysical parameters of the dyes. The dyes were characterized by FT-IR, (1)H NMR, (13)C NMR and mass spectral analysis.


Cobalt-immunocytochemical identification of peptidergic neurons in Calliphora innervating central and peripheral targets.
Certain neurons of the blowfly, Calliphora erythrocephala, show immunoreactivity to anti-gastrin/cholecystokinin (CCK) COOH terminal specific antisera. However, as is common to immunocytochemical staining, much of the structure of the immunoreactive neurons escapes detection. We describe here whole-neuron identification by backfilling with Co2+ and subsequent silver reduction, combined with immunocytochemistry of the filled cells. Cobalt-silver filled neurons can be examined directly by fluorescence microscopy for the presence of a secondary, rhodamine-conjugated antibody linked to the primary one. Two peptide-containing pathways have been resolved, one leading out of the brain to the corpus cardiacum, the other innervating certain higher brain centres, such as the central body. Both arise from neurosecretory cells of the mid-brain. Immunoreactive peptidergic neurons leading, respectively, to the corpus cardiacum and to the central body have been matched to single nerve cells visualized by Golgi impregnation, cobalt backfilling or focal injection of cobalt into the brain.


The short-term regulation of fatty acid synthesis in the rat epididymal adipocytes.
Lipogenesis and fatty acid synthetase (FAS) activity of isolated rat adipocytes that were treated with insulin or epinephrine were studied. Insulin stimulated incorporation of radioactivity from D-[U-14C]glucose into CO2, saponifiable and non-saponifiable fractions, whereas epinephrine promoted lipolysis and oxidation of glucose into CO2. Whereas insulin stimulated fatty acid synthesis, epinephrine had no effect. Changes in FAS specific activity of insulin- or epinephrine-treated adipocytes were insignificant and could not account for insulin-stimulated lipogenesis. Rat adipocyte FAS, unlike hepatic FAS, was not subject to short-term regulation by insulin, although fatty acid synthesis showed such a response.


Neural and muscular alterations of the plantar flexors in middle-aged women.
Considering the large population of middle-aged adults, it is important to understand the age-related change in lower limb muscles and the possible mechanisms before old age (> 65 years old). The purpose of this study was to investigate age-related neural and muscular alterations of the plantar flexors in young and middle-aged women. Twenty two middle-aged (54.0 ± 5.8 yrs) and 17 young (21.8 ± 1.4 yrs) recreationally active women performed rapid maximal voluntary isometric contractions (MVIC) of the plantar flexors. Absolute and normalized rate of torque development (RTD) and electromyography (EMG) were examined. Electrical stimulation was used to examine voluntary activation and contractile properties of the muscle. Ultrasonography was used to examine medial and lateral gastrocnemius muscle thickness and pennation angle. A 6-minute walk and sit to stand task were also performed by all participants. The middle-aged women had significantly lower MVIC torque (141 ± 49 vs. 109 ± 30 Nm, P = 0.031), absolute RTD (753.0 ± 313.6 vs. 423.0 ± 156.1 Nm/s, P = 0.001), and normalized peak RTD (554.0 ± 191.0 vs. 388.0 ± 91.9% MVIC/s, P = 0.001). Normalized early RTD0-50 and late RTD100-200, voluntary activation, and EMG were similar between groups. Resting twitch data showed that time to peak (124.0 ± 20.4 vs. 143.0 ± 16.7 ms, P = 0.002) and half relaxation time (73.1 ± 15.2 vs. 107.0 ± 28.2 ms, P < 0.001) was significantly faster for the young women. Thickness was greater in the lateral gastrocnemius (1.6 ± 0.2 vs. 1.4 ± 0.2 cm, P = 0.006) for the young women. Pennation angle of both muscles were greater for the young women (15.8 ± 3.9 vs. 13.1 ± 2.7 degrees, P < 0.05). Performance of the 6-minute walk was similar between groups, however, the young women performed more repetitions during the sit to stand task (25.6 ± 6.7 vs. 18.3 ± 4.7 reps, P < 0.001). Compared to young women, middle-age women were shown to have lower MVIC torque, peak RTD, and functional performance. Muscle architecture and contractile properties are affected by aging.


Addressing Obesity in Preconception, Pregnancy, and Postpartum: A Review of the Literature.
Reproductive-aged women (aged 19 to 50 years) are a key population warranting focused research for the prevention of overweight and obesity. This review highlights the importance of addressing weight before, during and after pregnancy. Obesity decreases fertility during the preconception period; increases the risk of adverse pregnancy outcomes including gestational diabetes, pre-eclampsia and caesarean section and postpartum weight retention; and increases the long-term health risks for both the mother and offspring. Despite overwhelming efficacy evidence on solutions, there are significant implementation gaps in translating this evidence into pragmatic models of care and real-world solutions. Interventions during preconception, pregnancy and postpartum are likely to be cost-effective or cost-saving, with future investigation needed in the preconception and postpartum period. International clinical guidelines and public health policies are needed for a concerted effort to prevent unhealthy weight gain in these life stages and to reverse the significant adverse health outcomes for women and the next generation.


Pharmacological characteristics of tremor, rigidity and hypokinesia induced by reserpine in rat.
The experiments characterized the dose- and time-dependence of parkinsonian motor signs induced by reserpine in rats and a standardized system of manipulation of animals, evaluation of symptoms and analysis of data was devised. The assay procedure yielded no more than 0.5, 4.5 and 0.0% false positives with the evaluation of tremor, rigidity and hypokinesia, respectively. A dose-dependent and often complete blockade of all three signs was obtained with L-DOPA plus carbidopa (10:1) as well as with other classes of pharmacological agents that are used in the treatment of Parkinson's disease, i.e. direct or indirect dopamine (DA) agonists (amantadine, pergolide, lisuride) and inhibitors of monoamine oxidase (MAO) (clorgyline, pargyline, deprenyl, tranylcypromine). The inhibitor of the uptake of DA, nomifensine, and anticholinergics, 5-hydroxytryptamine (5-HT) antagonists, histamine antagonists and tricyclic antidepressants exerted little or no effect. The effects of putative agonists and antagonists at alpha 1- and alpha 2-adrenoceptors were also examined. Yohimbine blocked tremor and rigidity, but not hypokinesia, at 0.66 and 0.28 mg/kg, respectively. It is suggested that alpha-adrenergic mechanisms and, in particular, alpha 2-adrenoceptors, may be involved in reserpine-induced tremor and rigidity. Noradrenergic and dopaminergic systems can conceivably interact to progressively generate these different motor signs.


Robust R-peak detection in an electrocardiogram with stationary wavelet transformation and separable convolution.
R-peak detection is an essential step in analyzing electrocardiograms (ECGs). Previous deep learning models reported their performance primarily in a single database, and some models did not perform at the highest levels when applied to a database different from the testing database. To achieve high performances in cross-database validations, we developed a novel deep learning model for R-peak detection using stationary wavelet transform (SWT) and separable convolution. Three databases (i.e., the MIT-BIH Arrhythmia [MIT-BIH], the Institute of Cardiological Technics [INCART], and the QT) were used in both the training and testing models, and the MIT-BIH ST Change (MIT-BIH-ST), European ST-T, TELE and MIT-BIH Noise Stress Test (MIT-BIH-NST) databases were further used for testing. The detail coefficient of level 4 decomposition by SWT and the first derivative from filtered ECGs were used for model inputs, and the interval of 150 ms centered at marked peaks was used for labels. Separable convolution with atrous spatial pyramidal pooling was selected as the model's architecture, and noise-augmented waveforms of 5.69 s duration (2048 size in 360 Hz) were used in training. The model performance was evaluated using cross-database validation. The F1 scores of the peak detection model were 0.9994, 0.9985, and 0.9999 in the MIT-BIH, INCART, and QT databases, respectively. When the above three databases were pooled, the F1 scores were 0.9993 for fivefold cross-validation and 0.9991 for cross-database validation. The model performance remained high for MIT-BIH-ST, European ST-T, and TELE, with F1 scores of 0.9995, 0.9988, and 0.9790, respectively. The model performance when trained by severe noise augmentation increased for the MIT-BIH-NST database (F1 scores from 0.9504 to 0.9759) and decreased for the MIT-BIH database (F1 scores from 0.9994 to 0.9991). The present SWT and separable convolution-based model for R-peak detection yields a high performance even for cross-database validations.


Interferon affects intracellular calmodulin levels.
Interferon lowers calmodulin levels in two cell lines sensitive to its antiproliferative effect. Further, in synchronized cells, interferon strongly inhibits the increase in calmodulin observed when control cells enter the S phase, and concomitantly inhibits DNA synthesis. Calmodulin has been implicated in the control of cell proliferation and an increase in this protein seems to be necessary for the progression of cells into the S phase of the cell cycle. Therefore, the effect of interferon on calmodulin content might constitute part of the molecular mechanism by which interferon inhibits DNA synthesis.


Repeated peribulbar injections of triamcinolone acetonide: a successful and safe treatment for moderate to severe Graves' ophthalmopathy.
In this study, we aimed to evaluate the efficacy of peribulbar triamcinolone injections to treat inflammatory signs of Graves' ophthalmopathy (GO) in patients with moderate to severe GO and associated optic neuropathy (ON). Twenty-one patients with active GO [clinical activity score (CAS) > or = 4] and systemic thyroid disease under control were enrolled in this prospective pilot study. Peribulbar triamcinolone acetonide was injected in each orbit (42 eyes), in four doses of 20 mg at 2-week intervals. Ophthalmological examination including CAS evaluation, visual field, computerized tomography (CT) scan and digital photography were performed before and after treatment. Twenty-one patients (11 with moderate disease, 10 with ON) were enrolled in this study and followed for at least 14 months. Initial mean CAS was 6.38 +/- 1.49, which dropped to 1.8 +/- 1.12 after 6 months of treatment (P = 0.01; mean difference of 4.57 +/- 1.56; range 1-8 score points). ON was diagnosed in 10 patients. Of these, 66% improved with peribulbar triamcinolone exclusively. A transitory increase in intraocular pressure in two patients was controlled with topic medication. Peribulbar triamcinolone injections reduce the inflammatory signs of moderate GO, as measured by the CAS, and could also be used as an alternative treatment for ON. Randomized clinical trials are needed to compare the results of triamcinolone peribulbar injections to those of other treatment modalities.


Preferences of adult patients with allergic rhinitis for the sensory attributes of fluticasone furoate versus fluticasone propionate nasal sprays: a randomized, multicenter, double-blind, single-dose, crossover study.
Product attributes influence patient preference for intranasal corticosteroid therapy in allergic rhinitis (AR). The aim of the study was to compare the product sensory attributes and patient preferences of fluticasone furoate (FF) and fluticasone propionate (FP) nasal sprays in patients with symptomatic perennial and/or seasonal AR. This randomized, multicenter, double-blind, single-dose, crossover study enrolled 127 patients with a diagnosis of AR as determined by respiratory symptoms and a positive skin test to perennial and/or seasonal allergens within 12 months prior to the study. Patients could not use FF or FP within 4 weeks prior to the start of the study. Patients were randomized 1:1 to receive FF (110 microg) followed by FP (200 microg) or FP followed by FF. A 10-minute washout period occurred before crossover dosing. Following each treatment, patient-rated sensory attributes were assessed immediately and 2 minutes after treatment on 2 questionnaires using a 7-point Likert scale (scored from 0-6) rating odor, taste, aftertaste, drip down the throat, urge to sneeze, soothing feeling, irritation, and nose runoff. At the end of the crossover dosing and after completion of the attributes questionnaires, preference for individual attributes of FF or FP nasal spray and overall patient preference were evaluated in a third questionnaire that asked "Based on these attributes, which product did you prefer overall?" Additionally, a follow-up phone call was conducted 24 hours after the study to assess any adverse events following study treatment. Patients (mean age, 39.7 years; 80% white; 65% women) preferred FF nasal spray over FP nasal spray overall (60% vs 33%; P = 0.003) and based on the individual attributes of odor (64% vs 29%; P < 0.001), taste (47% vs 21%; P < 0.001), aftertaste (44% vs 22%; P = 0.002), drip down the throat (43% vs 27%; P = 0.037), and nose runoff (49% vs 19%; P < 0.001). Patient ratings favored FF versus FP (median differences, P < 0.001) with respect to odor, taste, dripping down the throat, and nose runoff, both immediately and 2 minutes after dosing, but there were no significant differences with respect to whether the medication felt soothing, caused nasal irritation, or made patients sneeze. Fifty-two percent (63/121) of patients replied that they were very likely to comply with FF treatment versus FP treatment (38% [45/120]; P = 0.02) if the medications were prescribed. Three patients (2%) reported adverse events (dizziness, headache, nasal congestion) during treatment with FF. In this study of adult AR patients, the sensory attributes of FF were preferred over those of FP following single-dose administration.


Leucocyte aggregation in burned patients.
Leucocyte aggregation describes one type of biophysical behaviour of white cells. To test whether this parameter is changed in burned patients, 15 burn victims were investigated immediately after admission into hospital. Cell counts and aggregation were measured and related to the prognosis of the injury. Compared with normal controls, burning injury is associated with higher white cell counts and enhanced leucocyte aggregation. Fatal injuries showed a (non-significant) tendency for higher aggregation values than survivors. There are significant positive correlations between white cell counts, maximal aggregation values and the burned body surface area. The results suggest that leucocyte aggregation is pathologically enhanced in response to burns. Possibly this alteration is of prognostic importance.


The effect of bandwidth on the quality of transmitted pediatric echocardiograms.
Remote access to pediatric cardiology diagnostic services is enabled by real-time transmission of echocardiographic images. Several transmission bandwidths have been used but there has been little analysis of image quality provided by different bandwidths. We designed a study of the quality of transmitted images at various bandwidths. Two echocardiographers viewed randomly a series of 13 recorded pediatric echocardiographic images either directly or after transmission using 1 of 4 bandwidths: 256; 384; 512; or 768 kbps. An image clarity scoring scale was used to assess image quality of cardiac structures. Measurable differences were found in image quality with different transmission bandwidths; 512 kbps was the minimum for consistently clear imaging of all cardiac structures examined. Bandwidth greater than 512 kbps confers sharper images subjectively although this could not be quantified by our methods.


Differences in the fecal microbiota of dairy calves reared with differing sources of milk and levels of maternal contact.
The practice of rearing cows and calves together is gaining popularity on dairy farms, with different systems currently under assessment in mainland Europe, the United Kingdom, and Oceania. Research into the effects of cow-calf rearing has primarily focused on direct health and welfare implications, and little work has examined the role of different rearing paradigms on calf microbiota. We trialed a cow-calf rearing system on a Canadian dairy farm and compared fecal microbiota of these calves with the microbiota of calves reared according to the conventional practice of the same farm (separated from the dam and fed waste milk). At 4 wk, the conventionally reared calves had reduced relative abundance of Lactobacillus and higher relative abundance of other taxa, including Sutterella, Prevotella, and Bacteroides. We also detected predicted functional differences, such as reduced l-tryptophan biosynthesis in conventionally reared calves. These results suggest that maternal contact may influence the calf microbiota, but the observed differences are also likely related to other aspects of the rearing environment independent of maternal contact (e.g., potential exposure to antibiotic residues in waste milk). These findings provide preliminary evidence of the effects of early rearing environments on the establishment of the dairy calf fecal microbiota. This research is needed, given the critical role of the bovine gut microbiome in behavioral, metabolic, and immune development.


2020 healthcare management in Canada: a new model home next door.
The Commission on the Future of Health Care in Canada asked whether Medicare is sustainable in its present form. Well, Medicare is not sustainable for at least six reasons. Given a long list of factors, such as Canada's changing dependency ratio, the phenomenon of diminishing returns from increased taxation, competing provincial expenditure needs, low labour and technological productivity in government-funded healthcare, the expectations held by baby boomers, and the evolving value sets of Canadians--Medicare will impoverish Canada within the next couple of decades if not seriously recast. As distasteful as parallel private-pay, private-choice healthcare may be to some policy makers and providers who grew up in the 1960s, the reality of the 2020s will dictate its necessity as a pragmatic solution to a systemic problem.


Characterization of atrial arrhythmias in body surface potential mapping: A computational study.
Atrial tachycardia (AT), flutter (AFL) and fibrillation (AF) are very common cardiac arrhythmias and are driven by localized sources that can be ablation targets. Non-invasive body surface potential mapping (BSPM) can be useful for early diagnosis and ablation planning. We aimed to characterize and differentiate the arrhythmic mechanisms behind AT, AFL and AF from the BSPM perspective using basic features reflecting their electrophysiology. 19 simulations of 567-lead BSPMs were used to obtain dominant frequency (DF) maps and estimate the atrial driving frequencies using the highest DF (HDF). Regions with |DF-HDF|≤1Hz were segmented and characterized (size, area); the spatial distribution of the differences |DF-atrialHDFestimate| was qualitatively analyzed. Phase singularity points (SPs) were detected on maps generated with Hilbert transform after band-pass filtering around the HDF (±1Hz). Connected SPs along time (filaments) and their histogram (heatmaps) were used for rotational activity characterization (duration, spatiotemporal stability). Results were reproduced in clinical layouts (252 to 12 leads) and with different rotations and translations of the atria within the torso, and compared with the original 567-lead outcomes using structural similarity index (SSIM) between maps, sensitivity and precision in SP detection and direct feature comparison. Random forest and least-square based algorithms were used to classify the arrhythmias and their mechanisms' location, respectively, based on the obtained features. Frequency and phase analyses revealed distinct behavior between arrhythmias. AT and AFL presented uniform DF maps with low variance, while AF maps were more heterogeneous. Lower differences from the atrial HDF regions correlated with the driver location. Rotational activity was most stable in AFL, followed by AT and AF. Features were robust to lower spatial resolution layouts and modifications in the atrial geometry; DF and heatmaps presented decreasing SSIM along the layouts. The classification of the arrhythmias and their mechanisms' location achieved balanced accuracy of 72.0% and 73.9%, respectively. Non-invasive characterization of AT, AFL and AF based on realistic models highlights intrinsic differences between the arrhythmias, enhancing the BSPM utility as an auxiliary clinical tool.