Unravelling intricate interactions among atmospheric bromeliads with highly overlapping niches in seasonal systems.
Biotic and abiotic interactions are important factors that explain community assembly. For example, epiphytic communities are shaped by tree traits that can act as environmental filters, but also by positive and/or negative interactions among coexisting epiphytes on a tree. Here, we studied interactions among three widespread atmospheric bromeliads with overlapping niches (Tillandsia recurvata, T. tricholepis and T. pohliana), using experimental data about facilitation through seed capture, interspecific interaction during seed germination and competition among adult individuals. We aim to understand how species interactions are reflected in the natural coexisting patterns of epiphytes in communities at high and low tree densities. Tillandsia pohliana showed higher facilitation by capturing almost all wind-dispersing seeds, and had the largest reduction in seed germination in the presence of any adult individual, also presenting a relatively high rate of adult mortality in the presence of other individuals. Our results indicate higher colonisation ability for T. pohliana and distinct strategies of rapid exploitation of T. recurvata and T. tricholepis individuals. In natural communities, the coexistence among atmospheric bromeliads may be hampered by dispersal limitations in wind-dispersed epiphytes at high tree density conditions, but a negative effect of T. recurvata on T. pohliana is still reflected in their reduced coexistence. However, competitive patterns observed in the experimental data may be overshadowed by a possible mass effect driving large communities under such conditions. Our results show the joint effect of positive interactions and high dispersal levels on the community patterns of atmospheric bromeliads.


[Intraoral protrusion devices in obstructive sleep apnea. Dental findings and possible treatments].
Oral protrusive devices are regarded as an alternative treatment option for snoring and mild to moderate obstructive breathing disorders. In addition to the polysomnographic indication based on the respiratory and somnographic findings, healthy stomatognatic conditions with sufficient dental retention for the device are essential for a successful treatment. The sleep laboratory of the University Hospital of Freiburg i. Br. referred 112 patients with obstructive sleep apnea to the Department of Orthodontics for treatment with an oral protrusive device. All patients were examined clinically and with a panoramic radiograph with regard to continuous treatment. To maximize treatment success and minimize dental side effects, close collaboration with dental colleagues is necessary in treatment with an oral protrusive device. Acute periodontitis, periodontal lesions, insufficient dental anchorage, and temporomandibular symptoms can result in unwanted dental side effects and therefore limit the indication of this therapeutic approach.


Effects of monoamine reuptake inhibitors on cocaine self-administration in rats.
The objective of this study was to investigate the effects of acute administration of monoamine reuptake inhibitors on cocaine self-administration in rats. Pretreatment with GBR 12909 (1-5.6 mg/kg, IV), a dopamine-selective reuptake inhibitor, produced a dose-dependent and large reduction in the self-administration of cocaine (1 mg/kg/infusion). The 3- and 5.6-mg/kg doses of GBR 12909 produced downward shifts in the dose-response curves for cocaine (0.3-3 mg/kg/infusion) self-administration. Unlike GBR 12909, the norepinephrine-selective reuptake inhibitors, desipramine and nisoxetine, at a 10-mg/kg dose produced small, but significant, reductions in the self-administration of cocaine (1 mg/kg/infusion). The 10-mg/kg dose of fluoxetine, a serotonin-selective reuptake inhibitor, produced a small, but not significant, reduction in the self-administration of cocaine. The 10-mg/kg dose of desipramine, nisoxetine, or fluoxetine produced brief respiratory distress and motor abnormalities immediately following IV injections, thereby suggesting that this dose is close to the toxic range for all three drugs. Desipramine, nisoxetine, or fluoxetine at nontoxic doses of 1 and 3 mg/kg had no significant effects on cocaine self-administration. These data indicate that the acute enhancement of endogenous dopaminergic activity by pretreatment with dopamine reuptake inhibitor reduces the total intake of cocaine, thus supporting the hypothesis that the dopamine is critically involved in the reinforcing properties of cocaine. The data also suggest that the acute enhancements in the endogenous norepinephrine or serotonin systems by nontoxic doses of norepinephrine- or serotonin-selective reuptake inhibitors do not appear to alter the reinforcing properties of cocaine.


Erratum: Optic nerve sheath diameter-guided extubation plan in obese patients undergoing robotic pelvic surgery in steep Trendelenburg position: A report of three cases.
[This corrects the article on p. 896 in vol. 62, PMID: 30532328.].


Radiological aspects of diffuse alveolar haemorrhage.
This paper describes chest X-ray (CXR) and computed tomography (CT) findings of diffuse alveolar haemorrhage (DAH). We retrospectively reviewed 23 episodes of DAH in 20 patients, 17 of known aetiology and three of unknown aetiology. All cases were studied by CXR and 15 also by CT. Parenchymal consolidations and ground-glass opacities were evaluated after dividing each lung into three regions (upper, middle, lower) for a total of six zones. Consolidations or ground-glass opacities were identified on CXR in 16/20 patients, mainly in the middle fields (73%). In 4/20 patients, all with Wegener's granulomatosis, CXR was negative or demonstrated only nodular opacities; in two of these cases, CT revealed ground-glass opacities. A complete follow-up was available for ten patients: initially, they showed consolidation opacities in 36/60 zones, which persisted in 16/60 after 7 days and in 11/60 after 15 days. Conversely, ground-glass opacities increased after 7 days owing to the partial regression of consolidation opacities, and they markedly diminished after 15 days. DAH is radiologically characterised by a nonspecific alveolar-filling pattern. Diagnosis or suspicion of DAH needs to be supported by the evidence of haemoptysis and/or rapid-onset anaemia. CT is superior in detecting ground-glass opacities and is required in cases of suspected DAH with normal CXR findings.


Injuries in elite-level women's football-a two-year prospective study in the Irish Women's National League.
We investigated the pattern of injuries in elite-level women's football in Ireland, during a two-season prospective injury surveillance study in the Women's National League (WNL). Seven out of the eight clubs (271 players) in the WNL were followed prospectively during the 2018 and 2019 seasons. The injury incidence rate in matches (19.2/1000 h) was 7.5 times higher than in training (2.5/1000 h). Players, on average, sustained 0.69 injuries per season (266 injuries/383 player seasons), which equates to 15 time-loss injuries per season for a squad of 22 players. The majority of the injuries sustained by players were lower extremity injuries (85%), of which, 46% had a non-contact injury mechanism. Muscle, ligament, and contusion injuries were the most common injury types, while the ankle, knee, and thigh were the most commonly injured body sites. The most common injuries sustained over the two seasons were lateral ankle sprains (13.9%), hamstring strains (12.4%), knee meniscus/cartilage injuries (7.5%), adductor strains (6%), quadriceps strains (4.5%), and ankle contusions (4.5%). The injuries with the highest injury burden were ACL injuries (59 days lost/1000 h), knee meniscus/cartilage injuries (23/1000 h), lateral ankle sprains (21/1000 h), hamstring strains (12/1000 h), MCL sprains (11/1000 h), and quadriceps strains (11/1000 h). There were 8 ACL tears documented over the 2 seasons, which accounted for 28% of all time lost to injury with a mean days lost per injury of 247. We recommend that clubs in the WNL in Ireland should implement injury risk mitigation strategies, with a particular focus on injuries with a high injury burden.


Nuclear Receptor Subfamily 4 Group A Member 1 Overexpression Prolongs Free Flap Allotransplant Graft Survival by Inducing T-Cell Anergy in the Rat.
New strategies to inhibit acute rejection are needed for further applications of composite tissue allotransplantation. The nuclear receptor subfamily 4 group A member 1 (NR4A1) is considered a key controller of maintaining tolerance homeostasis. However, the effect of NR4A1 in suppressing rejection responses after allotransplantation remains unknown. Brown Norway rat groin flaps were transplanted into Lewis rat recipients. The recipients were administrated cytosporone B, an NR4A1 activator. NR4A1 expression and graft survival time were assessed. T helper type 1 and regulatory T cell populations in the second lymphoid organ were detected by flow cytometry. Furthermore, a retrovirus containing NR4A1 was constructed and transfected to T cells in vitro. After stimulation, interleukin 2 and interferon gamma secretions were detected in the T cells. Administration of cytosporone B activated NR4A1 expression in allotransplant recipients and was associated with prolonged survival time of the vascularized free flap allograft. T helper type 1 cells in the recipient secondary lymphoid organs were decreased, whereas the population of regulatory T cells did not change. Interleukin 2 and interferon gamma were suppressed in vitro in the T cells overexpressing NR4A1. We demonstrated that the overexpressed NR4A1 is associated with suppressed graft rejection response. The suppression effect may attribute to induction of T-cell anergy and blockade of key immunologic cytokines.


"Our Patients Are Different": Predictors of Seclusion and Restraint in 31 Psychiatric Hospitals.
Research in recent years has demonstrated that the use of coercive measures such as seclusion and restraint differs very much between hospitals within a country. In 2015, a central register for all coercive measures in the German federal state of Baden-Wuerttemberg has been established for 32 hospitals treating involuntary patients. The objective of the present study was to identify factors that determine the differences between these hospitals. Data on coercive measures and diagnoses from the central register in 2015-2017 were linked with structural data of the 32 hospitals and their supply areas. On average, coercive measures were applied in 6.7% of cases (SD = 2.8%; Min-Max = 0.35-12.0%). The proportion of affected cases was significantly correlated with the proportion of involuntary patients (r = 0.56), the proportion of cases with affective or neurotic, stress-related and somatoform disorders (r = -0.42), number of hospital beds (r = 0.44), a sheltered home associated with the hospital (r = 0.43) and number of addiction counseling centers per 100,000 inhabitants in the service area (r = -0.39). The final regression model only included the proportion of involuntary cases as a significant predictor (standardized beta = 0.55, adjusted R 2 = 0.27). The predominating part of the considerable variance observed between hospitals could not be explained by structural variables. The proportion of involuntary patients had a significant impact, but a considerable amount of unexplained variance due to different practices within psychiatric hospitals remains.


A cost evaluation method for transferring municipalities to solid waste source-separated system.
Most of Israel's waste is disposed in landfills, threatening scarce land resources and posing environmental and health risks. The aim of this study is to estimate the expected costs of transferring municipalities to solid waste source separation in Israel, aimed at reducing the amount of waste directed to landfills and increasing the efficiency and amount of recycled waste. Information on the expected costs of operating a solid waste source separation system was gathered from 47 municipalities and compiled onto a database, taking into consideration various factors such as costs of equipment, construction adjustments and waste collection and disposal. This database may serve as a model for estimating the costs of entering the waste source separation system for any municipality in Israel, while taking into consideration its specific characteristics, such as size and region. The model was used in Israel for determining municipalities' eligibility to receive a governmental grant for entering an accelerated process of solid waste source separation. This study displays a user-friendly and simple operational tool for assessing municipalities' costs of entering a process of waste source separation, providing policy makers a powerful tool for diverting funds effectively in promoting solid waste source separation.


Molecular detection of Rickettsia, Anaplasma, Coxiella and Francisella bacteria in ticks collected from Artiodactyla in Thailand.
A total of 79 ticks collected from Sambar deer (Cervus unicolor), Barking deer (Muntiacus muntjak) and Wild boar (Sus scrofa) were examined by PCR for the presence of Rickettsia, Anaplasma, Coxiella, and Francisella bacteria. Of the 79 ticks, 13% tested positive for Rickettsia, 15% tested positive for Anaplasma, 4% tested positive for Coxiella, and 3% tested positive for Francisella. Interestingly, triple infection with Anaplasma, Rickettsia and Francisella was determined in a Dermacentor auratus tick. Moreover, another triple infection with Rickettsia, Anaplasma, and Coxiella was found in a Haemaphysalis lagrangei tick. Double infection of Rickettsia with Coxiella was also detected in another H. lagrangei tick. From the phylogenetic analyses, we found a Rickettsia sp. with a close evolutionary relationship to Rickettsia bellii in the H. lagrangei tick. We also found the first evidence of a Rickettsia sp. that is closely related to Rickettsia tamurae in Rhipicephalus (Boophilus) microplus ticks from Thailand. H. lagrangei and Haemaphysalis obesa ticks collected from Sambar deer tested positive for Anaplasma species form the same clade with Anaplasma bovis. In contrast, other H. lagrangei ticks collected from Sambar deer and D. auratus ticks collected from Wild boar were also reported for the first time to be infected with an Anaplasma species that is closely related to Anaplasma platys. The phylogenetic analysis of the 16S rRNA gene of Coxiella bacteria revealed that Coxiella symbionts from H. lagrangei formed a distinctly different lineage from Coxiella burnetii (a human pathogen). Additionally, Francisella bacteria identified in D. auratus ticks were found to be distantly related to a group of pathogenic Francisella species. The identification of these bacteria in several feeding ticks suggests the risk of various emerging tick-borne diseases and endosymbionts in humans, wildlife, and domestic animals in Thailand.


Micro-percutaneous nephrolithotomy in the treatment of pediatric nephrolithiasis: A single-center experience.
We aimed to clarify the applicability and safety of micro-PNL (microperc) in the treatment of pediatric kidney stones. A single center prospective trial was initiated, and microperc was performed in 40 children using the same two methods: the classical all-seeing needle and microsheath method. Stone fragmentation was performed using a 200-μm holmium:YAG laser fiber. The mean age of the patients was 6.3±4.4years (range: 7months-16years). Fourteen were less than 3years old. The average calculous size was 16.5mm (range: 10-36mm). In 20 patients, access was achieved through the all-seeing needle method. In the other patients, access was achieved by the microsheath method. Conversion to mini-PNL was required in 2 patients due to intraoperative bleeding in one and a high stone burden in the other. The mean hospital stay was 3.8±1.2days (range: 1-10days), and the mean hemoglobin decrease was 0.7±0.3mg/dl (range: 0-1.7mg/dl).The duration of surgery and fluoroscopic screening was 75min and 3.7min, respectively. A DJ stent was placed in 11 patients due to a high stone burden. A ureteral stent was left for 1day in the rest of the cases. Complete clearance was achieved in the other 32 children. None of the patients required transfusion caused by renal hemorrhage. In 1 patient, extravasation of the irrigation fluid caused abdominal distention. As assessed by KUB and/or an ultrasound, the overall stone-free rate at 6weeks was 80%. There were residual fragments in 6 patients (15%). Our results show that microperc is a safe and effective procedure for the treatment of pediatric kidney stones. Children with small renal calculi and with nonobstructed collecting systems are suitable for microperc.


Determination of cytokine protein levels in oral secretions in patients undergoing radiotherapy for head and neck malignancies.
Cytokines may be elevated in tumor and normal tissues following irradiation. Cytokine expression in these tissues may predict for toxicity or tumor control. The purpose of this pilot study was to determine the feasibility of measuring local salivary cytokine levels using buccal sponges in patients receiving chemo-radiation for head and neck malignancies. 11 patients with epithelial malignancies of the head and neck were recruiting to this study. All patients received radiotherapy to the head and neck region with doses ranging between 60 - 67.5 Gy. Chemotherapy was delivered concurrently with radiation in all patients. Salivary samples were obtained from high dose and low dose regions prior to treatment and at three intervals during treatment for assessment of cytokine levels (IL-4, IL-6, IL-8, IL-10, EGF, MCP-1, TNF-α, and VEGF). Cytokine levels were detectable in the salivary samples. Salivary cytokine levels of IL-4, IL-6, IL-8, EGF, MCP-1, TNF- α , and VEGF were higher in the high dose region compared to the low dose region at all time points (p < 0.05). A trend toward an increase in cytokine levels as radiation dose increased was observed for IL-6, IL-8, MCP-1, and TNF-α. Assessment of salivary cytokine levels may provide a novel method to follow local cytokine levels during radiotherapy and may provide a mechanism to study cytokine levels in a regional manner.


Helicobacter pylori biofilms are disrupted by nanostructured lipid carriers: A path to eradication?
Bacterial biofilms account for 80% of all chronic infections, with cells being up to 1000 times more resistant to antibiotics than their planktonic counterparts. The recently discovered ability of Helicobacter pylori to form biofilms once again highlights why this bacterium is one of the most successful human pathogens. The current treatments failure rate reaches 40% of cases, emphasizing that new therapeutic options are a pressing need. Nanostructured lipid carriers (NLC), with and without docosahexaenoic acid (DHA), were very effective against H. pylori planktonic cells but their effect on H. pylori biofilms was unknown. Here, DHA-loaded NLC (DHA-NLC) and NLC without any drug (blank NLC) were tested on an optimized H. pylori in vitro floating mature biofilm model. DHA-NLC and blank NLC reduced the total biofilm biomass and had a bactericidal effect against both biofilm and planktonic bacteria in all the concentrations tested (0.125-2 mg/mL). DHA-NLC achieved biofilm biomass reduction in a concentration ~ 8 times lower than blank NLC (0.125 vs 1 mg/mL, respectively). Both NLC were bactericidal at the lowest concentration tested (0.125 mg/mL) although with different efficiency, i.e. a decrease of ∼6 log10 for DHA-NLC and ∼5 log10 for blank NLC. In addition, the equivalent amount of free DHA (3.1 μM) only reduced bacterial viability in ∼2 log10, demonstrating the synergistic effect of DHA and NLC in the treatment of H. pylori biofilms. Nevertheless, although viable bacteria were not detected by colony forming unit (CFU) counting after treatment with both NLC, confocal microscopy imaging highlighted that some H. pylori cells remained alive. In addition, scanning electron microscopy (SEM) analysis confirmed an increase in bacteria with a coccoid morphology after treatment, suggesting a transition to a viable but non-culturable (VBNC) state. Altogether, it is herein established that NLC, even without any drug, are promising for the management of H. pylori bacteria organized in biofilms, opening new perspectives for the eradication of this gastric pathogen.


Interactions of airborne graphene oxides with the sexual reproduction of a model plant: When production impurities matter.
The increasing use of graphene-related materials (GRMs) in everyday-life products raises concerns for their possible release into the environment and consequent impact on organisms. GRMs have widely varying effects on plants and, according to recent evidences, graphene oxide (GO) has the potential to interfere with the sexual reproduction owing to its acidic properties and production residues. Here, stigmas of the model plant Cucurbita pepo (summer squash) were subjected to simulated dry depositions of GO and GO purified from production residues (PGO). Stigmas were then hand-pollinated and GRM deposition was checked by ESEM and confocal microscopy. Analysis of stigma integrity, pH homeostasis and pollen-stigma interactions did not reveal negative effects. Fruit and seed production were not affected, but GO depositions of 22.1 ± 7.2 ng mm-2 affected the normal development of seeds, decreasing seed dimensions, seed germination and germination speed. The elemental analysis revealed that GO has significant quantities of production residues, such as strong acids and oxidants, while PGO has only traces, which justifies the differences observed in the effects caused by the two materials. Our results show that GO depositions of up to 11.1 ± 3.6 ng mm-2, which fall within the variation range of total dry particulate matter depositions reported in the literature, are safe for reproduction of C. pepo. This is the first "safety" limit ever recorded for depositions of "out-of-the-box" GO concerning the reproduction of a seed plant. If confirmed for wind-pollinated species, it might be considered for policymaking of GRMs emissions in the air.


Expression profile and bioinformatics analysis of circRNA and its associated ceRNA networks in longissimus dorsi from Lufeng cattle and Leiqiong cattle.
This paper aims to explore the role of circRNA expression profiles and circRNA-associated ceRNA networks in the regulation of myogenesis in the longissimus dorsi of cattle breeds surviving under subtropical conditions in southern China by RNA sequencing and bioinformatics analysis. It also aims to provide comprehensive understanding of the differences in muscle fibers in subtropical cattle breeds and to expand the knowledge of the molecular networks that regulate myogenesis. With regard to meat quality indicators, results showed that the longissimus dorsi of LQC had lower pH (P < 0.0001), lower redness (P < 0.01), lower shear force (P < 0.05), and higher brightness (P < 0.05) than the longissimus dorsi of LFC. With regard to muscle fiber characteristics, the longissimus dorsi of LQC had a smaller diameter (P < 0.0001) and higher density of muscle fibers (P < 0.05). The analysis results show that the function of many circRNA-targeted mRNAs was related to myogenesis and metabolic regulation. Furthermore, in the analysis of the function of circRNA source genes, we hypothesized that btacirc_00497 and btacirc_034497 may regulate the function and type of myofibrils by affecting the expression of MYH6, MYH7, and NEB through competitive linear splicing.


Exosomal miR-155-5p derived from glioma stem-like cells promotes mesenchymal transition via targeting ACOT12.
Tumor-associated exosomes play essential roles in intercellular communication and the foundation of cancer microenvironment in glioma. Many mRNAs, microRNAs (miRNAs) and proteins contained in tumor-associated exosomes can be transferred to recipient cells and contribute to the progression of tumor. Nevertheless, the cellular communication between malignant cells with different heterogeneities or characteristics and resultant tumor progression are still unclear in glioma. Here, we show that exosomes released from glioma stem-like cells (GSCs) contain a significant increasing level of miR-155-5p and could be horizontally transferred to surrounding glioma cells. High expression of miR-155-5p in plasma exosomes from patients was associated with glioma diagnosis and grading. Mechanically, we found that miR-155-5p markedly reduced the expression of acetyl-CoA thioesterase 12 (ACOT12), which played as a tumor suppressor in glioma. Furthermore, mesenchymal transition was significantly promoted in glioma cells treated with GSCs-derived exosomes. In conclusion, GSCs-derived exosomal miR-155-5p play a critical role in glioma progression and facilitating tumor aggressive growth by targeting ACOT12 and promoting mesenchymal transition. Exosomal miR-155-5p is also a potential predictive biomarker for glioma, which may provoke the development of novel diagnostic and therapeutic strategies against glioma.


Activation of the Hippocampal DRD2 Alleviates Neuroinflammation, Synaptic Plasticity Damage and Cognitive Impairment After Sleep Deprivation.
Sleep loss is commonplace nowadays and profoundly impacts cognition. Dopamine receptor D2 (DRD2) makes a specific contribution to cognition, although the precise mechanism underlying how DRD2 affects the cognitive process after sleep deprivation remains unclear. Herein, we observed cognitive impairment and impaired synaptic plasticity, including downregulation of synaptophysin and PSD95, decreased postsynaptic density thickness, neuron complexity, and spine density in chronic sleep restriction (CSR) mice. We also observed downregulated hippocampal DRD2 and Cryab expression in the CSR mice. Meanwhile, NF-κB translocation from the cytoplasm to the nucleus occurred, indicating that neuroinflammation ensued. However, hippocampal delivery of the DRD2 agonist quinpirole effectively rescued these changes. In vitro, quinpirole treatment significantly decreased the release of proinflammatory cytokines in microglial supernatant, indicating a potential anti-neuroinflammatory effect of Drd2/Cryab/NF-κB in CSR mice. Our study provided the evidence that activation of the Drd2 may relieve neuroinflammation and improve sleep deprivation-induced cognitive deficits.


Transoral Laser Microsurgery in Recurrent Laryngeal Cancer: A Systematic Review and Meta-analysis.
To determine the oncological outcomes of salvage transoral laser microsurgery (TLM) in the treatment of patients suffering from recurrent laryngeal cancer. PubMed/MEDLINE, Cochrane Library, and Scopus databases were searched. English language, original studies investigating oncological outcomes of TLM in adult patients with recurrent laryngeal cancer were included. Data were pooled using a distribution-free approach for estimating summary local control (LC), disease-specific survival (DSS), and overall survival (OS) curves with random effects. Two hundred and thirty-five patients underwent salvage TLM after primary (chemo)radiotherapy. The mean follow-up time was 60.8 months (95% CI: 32.7-88.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 74.2% (61.7-89.4), 53.9% (38.5-75.3), and 39.1% (25.2-60.8). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 88.4% (82.0-95.3), 67.8% (50.9-90.3), and 58.9% (42.7-81.1). Two hundred and seventy-one patients underwent TLM after primary laser treatment. The mean follow-up time was 70.9 months (95% CI: 36.9-104.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 72.2% (64.7-80.6), 53.2% (42.2-66.9), and 40.4% (29.6-55.2). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 92.1% (85.5-99.1), 77.0% (64.4-92.0), and 67.1% (51.6-87.3). TLM is a valuable treatment option for the management of locally recurrent laryngeal carcinoma if performed by experienced surgeons and following rigorous patients' selection criteria. Further studies should be conducted to define stage-based clinical guidelines. NA Laryngoscope, 133:1425-1433, 2023.


Bone Morphology and Strength in the Mid-Diaphysis of the Humerus and Metacarpus in Dairy Calves Prior to Weaning.
Calf growth rate in relation to future milk production has been thoroughly studied; however, the observation of growth arrest lines in bones from heifers with humeral fractures has highlighted the need to understand bone growth in relation to calf growth. The aim of this study was to describe the relationship of peripheral quantitative computed tomography (pQCT)-derived measures of bone strength and morphology with gross measurements of size and growth in pre-weaning dairy calves. Liveweight, height, body length, girth and leg length were measured at one, six and twelve weeks of age. At these intervals, the mid-diaphysis of the metacarpus was also scanned in the live animal using pQCT. At six and twelve weeks old, a subset of calves were euthanised and the humerus was collected and scanned at the mid-diaphysis using pQCT. Differences in growth patterns were observed between the metacarpus and humerus over time. Weight was the best predictor for measures of periosteal circumference and stress strain index (R2 = 0.49-0.58) in the metacarpus, and also the best predictor for measures of stress strain index at all ages in the humerus (R2 = 0.94). The strong relationship with weight and bone measures emphasises the need for adequate preweaning nutrition for future bone growth.


Therapeutic abortion. The 1975 report from Ullevål Hospital.
The results from a prospective study of 1228 therapeutic abortions (the 1975 material) are reported. First trimester pregnancies (1028 cases) were terminated by suction and curettage and second trimester pregnancies by prostaglandins (200 cases). The overall follow-up (4-6 weeks after termination) was 94.3%. The incidence of perforation was 0.5% of the surgical terminations, none of which, however, resulted in any other complications. The mean incidence of re-admission was 3.9%, the main causes being retained products or pelvic infection. The mean incidence of pelvic infection (salpingitis/parametritis) was 1.6%. The highest incidence of pelvic infection was found in early pregnancies (less than 8 weeks) or nulliparous women (2.7%) and the lowest (1.5%) in the induction group.


Ammoglanis natgeorum, a new miniature pencil catfish (Siluriformes: Trichomycteridae) from the lower Atabapo River, Amazonas, Venezuela.
A new species of the sand-dwelling catfish genus Ammoglanis is described from a marginal habitat of the lower Atabapo River, a left-bank blackwater tributary of the upper Orinoco River in Amazonas, Venezuela, adjacent to the border with Colombia. Ammoglanis natgeorum is distinguished from all congeners by trunk pigmentation pattern consisting of scattered ventral chromatophores concentrated around the anal-fin base and numerous additional meristic and anatomical characteristics. A. natgeorum is the second species of Ammoglanis described from the Orinoco River basin after Ammoglanis pulex, and several shared character states (e.g., eight total dorsal-fin rays, overall coloration pattern and presence of two finger-like papillae posterior to chin) suggest that it is more closely related to Ammoglanis obliquus (from the central Amazon basin) and A. pulex than to other congeners.


Cranial MRI of neurologically impaired children suffering from neonatal hypoglycaemia.
Metabolic disturbances such as anoxia and hypoglycaemia are important in causing maldevelopment of the neonatal brain. While there have been some pathology studies of the effects of neonatal hypoglycaemia on brain development, reports of MRI findings in such infants have been rare. To describe the MRI findings in neurologically handicapped children who had suffered from neonatal hypoglycaemia and to evaluate the relationship between the neurological impairment and neonatal hypoglycaemia. We retrospectively evaluated the MRI findings in eight full-term infants with neonatal symptomatic hypoglycaemia who later exhibited neurological handicap. The age at which the MRI scans were obtained ranged from 9 months to 8 years 10 months (mean 4 years 1 month, median 4 years). The most striking findings were prolonged T1 weighting and T2 weighting in the parieto-occipital periventricular deep white matter in six patients, suggesting abnormal or delayed myelination. Dilatation of the lateral ventricles, especially of the trigones, was observed in five patients in whom the distance between the posterior horns of the lateral ventricles and the adjacent sulci was reduced. The volume of white matter relative to grey matter was reduced in two patients. In addition, four patients exhibited cerebral cortical atrophy, mainly in the occipital lobe. These findings suggest that neonatal hypoglycaemia may cause delayed or abnormal myelination, especially in the parieto-occipital, periventricular, deep white matter, and may cause cerebral cortical atrophy, especially in the occipital lobe.


Effect of low-level laser therapy (904 nm) and static stretching in patients with knee osteoarthritis: a protocol of randomised controlled trial.
Osteoarthritis (OA) is a highly prevalent and disabling disease. It is estimated that by 2030 the prevalence of symptomatic OA could reach 30 % of the population above 60 years. This randomised controlled trial will investigate the effect of low-level laser therapy (LLLT) and static stretching exercises, as monotherapy and in combination, on pain, quality of life, function, mobility, knee range of motion (KROM) and hamstring shortening in participants with knee OA. This study will involve 145 people aged 50-75 years with symptomatic-radiographic knee OA. It will consist of two types of treatments: Low-level laser therapy (LLLT) and stretching exercises. The patients will be randomly allocated to five groups LLLTACTIVE+Stretch, LLLTPLACEBO+Stretch, Stretch, LLLT and Control (n = 29 each). Treatment frequency will be three sessions/week for all active groups. LLLT will involve the use of a Gallium-Arsenide laser (904 nm, 40 milliwatts, 3 J/point, 27 J/knee) over 24 sessions for the monotherapy group and 9 sessions for the LLLT+Stretch groups. Stretching will consist of seven exercises completed over 24 sessions. The control group will receive a booklet. Participants will be treated for 2 months (Stretch, LLLT and Control groups) or 3 months (LLLT + Stretch groups). Participants and the outcome assessor will be blind to treatment allocation throughout the study. The primary outcome is pain measured by Visual Analogue Scale. Secondary outcomes include quality of life assessed by Western Ontario and McMaster Universities Arthritis Index, function by Lequesne Algofunctional Index, mobility by Timed Up and Go Test, KROM by goniometry of knee flexion and hamstring shortening by popliteal angle. The statistical method will follow the principles of per-protocol analysis. Although exercise therapy is considered an effective treatment in patients with knee osteoarthritis, the knowledge of which exercise modalities would be the most appropriate for this population is lacking. LLLT has been used as resource to increase the effects of physical therapy. However, the specific dose and treatment frequency need to be better defined. The findings from this randomised controlled trial will provide evidence of the efficacy or otherwise, of LLLT and stretching exercises in the management of knee OA symptoms. NCT01738737 at ClinicalTrials.gov.


Pollination ecology of Yucca elata : An experimental study of a mutualistic association.
The pollination biology of a population of 250 Yucca elata (Liliaceae) plants was studied in southern New Mexico. Yucca elata and the prodoxid yucca moth Tegeticula yuccasella have a mutualistic association that is essential for the successful sexual reproduction of both species. However, a wide range of other invertebrate species visit flowers during the day and at night. Our aim was to quantify the role of yucca moths and other invertebrate visitors in pollination and fruit set, using manipulative field experiments. Inflorescences were bagged during the day or night (N=12 inflorescences) to restrict flower visitors to either nocturnal or diurnal groups. Yucca moths were active exclusively nocturnally during the flowering period and thus did not visit inflorescences that were unbagged during the day. None of the 4022 flowers exposed only to diurnal visitors set fruit, whereas 4.6% of the 4974 flowers exposed only to nocturnal visitors (including yucca moths) produced mature fruit. The proportion of flowers producing fruit in the latter treatment was not significantly different from unbagged control inflorescences. In a series of experimental manipulations we also determined that: (1) flowers opened at dusk and were open for two days on average, but were only receptive to pollen on the first night of opening; (2) pollen must be pushed down the stigmatic tube to affect pollination; and (3) most plants require out-cross pollination to produce fruit. The combination of these results strongly suggests that yucca moths are the only species affecting pollination in Y. elata, and that if another species was to affect pollination, it would be a rare event.


PpAtg30 tags peroxisomes for turnover by selective autophagy.
Autophagy, an intrinsically nonselective process, can also target selective cargo for degradation. The mechanism of selective peroxisome turnover by autophagy-related processes (pexophagy), termed micropexophagy and macropexophagy, is unknown. We show how a Pichia pastoris protein, PpAtg30, mediates peroxisome selection during pexophagy. It is necessary for pexophagy, but not for other selective and nonselective autophagy-related processes. It localizes at the peroxisome membrane via interaction with peroxins, and during pexophagy it colocalizes transiently at the preautophagosomal structure (PAS) and interacts with the autophagy machinery. PpAtg30 is required for formation of pexophagy intermediates, such as the micropexophagy apparatus (MIPA) and the pexophagosome (Ppg). During pexophagy, PpAtg30 undergoes multiple phosphorylations, at least one of which is required for pexophagy. PpAtg30 overexpression stimulates pexophagy even under peroxisome-induction conditions, impairing peroxisome biogenesis. Therefore, PpAtg30 is a key player in the selection of peroxisomes as cargo and in their delivery to the autophagy machinery for pexophagy.


Resilient organizations: matrix model and service line management.
Resilient organizations modify structures to meet the demands of the marketplace. The author describes a structure that enables multihospital organizations to innovate and rapidly adapt to changes. Service line management within a matrix model is an evolving organizational structure for complex systems in which nurses are pivotal members.


An NMR thermometer for cryogenic magic-angle spinning NMR: the spin-lattice relaxation of (127)I in cesium iodide.
The accurate temperature measurement of solid samples under magic-angle spinning (MAS) is difficult in the cryogenic regime. It has been demonstrated by Thurber et al. (J. Magn. Reson., 196 (2009) 84-87) [10] that the temperature dependent spin-lattice relaxation time constant of (79)Br in KBr powder can be useful for measuring sample temperature under MAS over a wide temperature range (20-296 K). However the value of T(1) exceeds 3 min at temperatures below 20K, which is inconveniently long. In this communication, we show that the spin-lattice relaxation time constant of (127)I in CsI powder can be used to accurately measure sample temperature under MAS within a reasonable experimental time down to 10 K.


Circulating immunoreactive growth hormone releasing hormone concentrations and growth hormone response to growth hormone releasing hormone in short children.
To study the role of peripheral immunoreactive growth hormone releasing hormone (ir-GHRH) concentrations and the GHRH test in the evaluation of growth hormone (GH) secretion in short stature, 46 children with a mean age of 9.4 years (range 1.6-16.3 years) and a mean relative height score of -3.2 SD (range -5.0-2.1 SD) were investigated. The children were divided into prepubertal (n = 35) and pubertal (n = 11) and the prepubertal children further into three groups based on their maximal GH responses to insulin-induced hypoglycaemia (IIH) and clonidine: (1) GH deficient subjects (maximal GH < 10 micrograms/l in both tests); (2) discordant responders (maximal GH < 10 micrograms/l in one test and > or = 10 micrograms/l in the other); and (3) normal responders (maximal GH > or = 10 micrograms/l in both tests). Peripheral ir-GHRH concentrations were measured during the IIH test by radioimmunoassay after purification of plasma samples on Sep-pak cartridges. Among the prepubertal children 10 fell into group 1, 16 into group 2 and 9 into group 3. Children in group 1 were older than those in group 3. There were no significant differences in relative heights and weights or absolute and relative growth velocities between the groups. Subjects in groups 1 and 2 had lower maximal GH responses to GHRH than those in group 3. There were no significant differences in the basal plasma ir-GHRH concentrations between the groups. Nine children (19.6%) had somatotrophs with a poor response to a single dose of exogenous GHRH (maximal GH < 10 micrograms/l).(ABSTRACT TRUNCATED AT 250 WORDS)


Two Cases of Lingual Arteriovenous Malformations with Comorbidities Treated by Glue Embolization: A Report with Review of Literature.
Arteriovenous malformations (AVMs) involving the tongue are uncommon lesions in the head and neck region. They present with bleeding that can be massive and life-threatening apart from debilitating symptoms of pain, ulcers, difficulty in phonation or swallowing. Various therapeutic approaches have been used in their management-surgery, endovascular embolization, radiation and ablation procedures like laser ablation. We report two patients-a 34 year-old man and 56 year-old female who presented with massive bleeding due to lingual AVM and had comorbidities as liver cirrhosis and chronic medical renal disease respectively, and treated with glue embolization, with a review of the literature.


Surgical versus nonsurgical treatment of unilateral dislocated low subcondylar fractures: a clinical study of 52 cases.
To compare open versus closed reduction of unilaterally dislocated low subcondylar fractures in adults, 101 consecutive dentulous patients were treated either by closed reduction with a median of 4 weeks of maxillomandibular fixation, or with a median of 6 weeks of maxillomandibular fixation after surgical repositioning and transosseous wiring of the dislocated condylar fragment. No selection of patients was done for either treatment. Fifty-two patients were seen at a median of 2 years postoperatively. Complications such as malocclusion, mandibular asymmetry, impaired masticatory function, and pain located to the affected joint or masticatory muscles were seen significantly more frequent in patients treated with closed reduction compared with those treated surgically (P = .005). Neither the degree of dislocation of the proximal fragment, concomitant mandibular fractures, nor the absence of posterior occlusal support seemed to influence the results.


The effect of peripheral nerve cross-union on connections of single Ia fibers to motoneurons.
The distribution of Ia terminals to alpha-motoneurons has been investigated under conditions where a) the Ia fiber innervates a foreign muscle and b) the motor axon innervates a foreign muscle. This distribution has been assessed by examining which motoneurons develop an EPSP in response to stimulation of a single Ia afferent fiber. Cross-union of the medial gastrocnemius and lateral gastrocnemius-soleus nerves has been performed in 5--8 day old kittens and the effect of this procedure on Ia connections to alpha-motoneurons has been investigated in the adult about one year later. No rearrangement of synaptic connections has been observed under these conditions. The connections from self-unioned Ia afferents and to self-unioned motoneurons are also normal. The individual EPSP's in these motoneurons with regenerated axons have normal rise times. The findings of normal Ia connections as well as normal EPSP rise times in alpha-motoneurons with regenerated motor axons indicates reversibility of the changes seen in axotomized motoneurons.


Research progress in modern structure of platinum complexes.
Since the antitumor activity of cisplatin was discovered in 1967 by Rosenberg, platinum-based anticancer drugs have played an important role in chemotherapy in clinic. Nevertheless, platinum anticancer drugs also have caused severe side effects and cross drug resistance which limited their applications. Therefore, a significant amount of efforts have been devoted to developing new platinum-based anticancer agents with equal or higher antitumor activity but lower toxicity. Until now, a large number of platinum-based complexes have been prepared and extensively investigated in vitro and in vivo. Among them, some platinum-based complexes revealing excellent anticancer activity showed the potential to be developed as novel type of anticancer agents. In this account, we present such platinum-based anticancer complexes which owning various types of ligands, such as, amine carrier ligands, leaving groups, reactive molecule, steric hindrance groups, non-covalently binding platinum (II) complexes, Platinum(IV) complexes and polynuclear platinum complexes. Overall, platinum-based anticancer complexes reported recently years upon modern structure are emphasized.


N-Methyl-D-aspartate receptor antagonist MK-801 attenuates morphine tolerance and associated glial fibrillary acid protein up-regulation: a proteomic approach.
It is well known that long-term morphine administration results in tolerance, which limits the clinical use of this drug in pain management. Male Wistar rats were randomly assigned to receive one of four different infusions: morphine [15 microg/h, intrathecal (i.t.)], saline, MK-801 (5 microg/h, i.t.) plus morphine (15 microg/h, i.t.), or MK-801 (5 microg/h, i.t.) alone. Morphine infusion induced a maximal antinociceptive effect on day 1 and tolerance on day 3, and the maximal anti-receptive tolerance was observed on day 5. Co-infusing MK-801 with morphine attenuated morphine's anti-receptive tolerance. Two-dimensional gel electrophoretic analysis of spinal proteins revealed that eight protein spots were up-regulated in morphine-tolerant rats, and that they were significantly inhibited by MK-801 co-infusion. Among the up-regulated proteins, glial fibrillary acid protein (GFAP), a glial-specific maker, was identified by mass spectrometry. This finding was also confirmed by Western blot analysis. Using proteomic analysis, we identified eight GFAP protein spots that were up-regulated in the dorsal horn of morphine-tolerant rat spinal cords. This up-regulation was partly inhibited by N-methyl-D-aspartate receptor antagonist MK-801 co-infusion, which suggests that GFAP protein can be considered to be a pathogenesis marker of morphine tolerance.


Educational inequality in adult mortality: an assessment with death certificate data from Michigan.
Education was added to the U.S. Standard Certificate of Death in 1989. The current study uses Michigan's 1989-1991 death certificates, together with the 1990 Census, to evaluate the quality of data on education from death certificates and to examine educational differences in mortality rates. With log-rates modeling, we systematically analyze the variability in educational differences in mortality by race and sex across the adult life cycle. The relative differences in mortality rates between educational levels decline with age at the same pace for all sex and race categories. Women gain a slightly greater reduction in mortality than men by reaching the secondary-education level, but a modestly smaller reduction by advancing beyond it. Blacks show a reduction in predicted mortality rates comparable to whites' by moving from the secondary to the postsecondary level of education but experience less reduction than whites by moving from the primary to the secondary level. Thus, the secular decline in mortality rates that generally accompanies historical improvements in education might actually be associated with an increase in the relative differences between blacks' and whites' mortality. We discuss limitations of the data and directions for future research.


Screening of endocrine organ-specific humoral autoimmunity in 47,XXY Klinefelter's syndrome reveals a significant increase in diabetes-specific immunoreactivity in comparison with healthy control men.
The aim of this study was to evaluate the frequency of humoral endocrine organ-specific autoimmunity in 47,XXY Klinefelter's syndrome (KS) by investigating the autoantibody profile specific to type 1 diabetes (T1DM), Addison's disease (AD), Hashimoto thyroiditis (HT), and autoimmune chronic atrophic gastritis (AG). Sixty-one adult Caucasian 47,XXY KS patients were tested for autoantibodies specific to T1DM (Insulin Abs, GAD Abs, IA-2 Abs, Znt8 Abs), HT (TPO Abs), AD (21-OH Abs), and AG (APC Abs). Thirty-five of these patients were not undergoing testosterone replacement therapy TRT (Group 1) and the remaining 26 patients started TRT before the beginning of the study (Group 2). KS autoantibody frequencies were compared to those found in 122 control men. Six of 61 KS patients (9.8 %) were positive for at least one endocrine autoantibody, compared to 6.5 % of controls. Interestingly, KS endocrine immunoreactivity was directed primarily against diabetes-specific autoantigens (8.2 %), with a significantly higher frequency than in controls (p = 0.016). Two KS patients (3.3 %) were TPO Ab positive, whereas no patients were positive for AD- and AG-related autoantigens. The autoantibody endocrine profile of untreated and treated KS patients was not significantly different. Our findings demonstrate for the first time that endocrine humoral immunoreactivity is not rare in KS patients and that it is more frequently directed against type 1 diabetes-related autoantigens, thus suggesting the importance of screening for organ-specific autoimmunity in clinical practice. Follow-up studies are needed to establish if autoantibody-positive KS patients will develop clinical T1DM.


Disentangling Independent and Mediated Causal Relationships Between Blood Metabolites, Cognitive Factors, and Alzheimer's Disease.
Education and cognition demonstrate consistent inverse associations with Alzheimer's disease (AD). The biological underpinnings, however, remain unclear. Blood metabolites reflect the end point of biological processes and are accessible and malleable. Identifying metabolites with etiological relevance to AD and disentangling how these relate to cognitive factors along the AD causal pathway could, therefore, offer unique insights into underlying causal mechanisms. Using data from the largest metabolomics genome-wide association study (N ≈ 24,925) and three independent AD cohorts (N = 4725), cross-trait polygenic scores were generated and meta-analyzed. Metabolites genetically associated with AD were taken forward for causal analyses. Bidirectional two-sample Mendelian randomization interrogated univariable causal relationships between 1) metabolites and AD; 2) education and cognition; 3) metabolites, education, and cognition; and 4) education, cognition, and AD. Mediating relationships were computed using multivariable Mendelian randomization. Thirty-four metabolites were genetically associated with AD at p < .05. Of these, glutamine and free cholesterol in extra-large high-density lipoproteins demonstrated a protective causal effect (glutamine: 95% confidence interval [CI], 0.70 to 0.92; free cholesterol in extra-large high-density lipoproteins: 95% CI, 0.75 to 0.92). An AD-protective effect was also observed for education (95% CI, 0.61 to 0.85) and cognition (95% CI, 0.60 to 0.89), with bidirectional mediation evident. Cognition as a mediator of the education-AD relationship was stronger than vice versa, however. No evidence of mediation via any metabolite was found. Glutamine and free cholesterol in extra-large high-density lipoproteins show protective causal effects on AD. Education and cognition also demonstrate protection, though education's effect is almost entirely mediated by cognition. These insights provide key pieces of the AD causal puzzle, important for informing future multimodal work and progressing toward effective intervention strategies.


A Low-Cost Open-Source Acoustic Recorder for Bioacoustics Research.
Acoustic recorders are the primary tool used in marine bioacoustics; however, available devices are either expensive or lack self-calibration capabilities that are critical for high-quality measurements. Moreover, the software used in proprietary designs can be inflexible and may involve unknown processing steps. To address this, we have designed a miniature low-cost yet high-performance acoustic recorder that features open-source hardware and software. Circuitry is included for self-calibration, making it possible to evaluate device performance in situ. Our intention is that the design will develop in conjunction with the needs of the bioacoustics community.


Integration of single-cell sequencing and bulk expression data reveals chemokine signaling pathway in proliferating cells is associated with the survival outcome of osteosarcoma.
Osteosarcoma, as the most common primary bone malignancy, is urgent to be well-studied on the biomarkers and therapeutic targets to improve the five-year survival rate. Transcriptomic analysis using single-cell RNA or bulk RNA sequencing has been developed to detect biomarkers in various cancer types. We applied Scissor to combine single-cell RNA-seq data and bulk transcriptome data of osteosarcoma, providing cell-level information and sample phenotypes to identify the survival-associated cell subpopulations. By investigating the differences between the survival-associated cell subpopulations, we identified CCL21, CCL22, CCL24, CXCL11, CXCL12, CXCL13, GNAI2, and RAC2 in the proliferating cells that are significantly associated with osteosarcoma patient outcome. Then we assigned the risk score for each sample based on the cell proportion-normalized gene expression and validated it in the public dataset. This study provides the clinical insight that chemokine signaling pathway genes (CCL21, CCL22, CCL24, CXCL11, CXCL12, CXCL13, GNAI2, and RAC2) in proliferating cells might be the potential biomarkers for treatment of osteosarcoma.


Protective effect of apigenin on Freund's complete adjuvant-induced arthritis in rats via inhibiting P2X7/NF-κB pathway.
To evaluate the effect of apigenin (AP) on arthritis in rats stimulated by Freund's complete adjuvant (FCA) was the main purpose of the investigation. Arthritis model was established by the administration of 0.1 ml FCA in the palmar surface. AP and diclofenac sodium (DS) were administered to explore and evidence the protective effects against adjuvant-induced arthritis (AA). Cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) were detected to assess the anti-inflammatory effect of AP. Besides, pathological conditions were examined in rat paws. Related-proteins of nuclear factor kappa B (NF-κB) signal pathway activated by P2X7 were investigated to determine the molecular mechanism of AP and their expressions were measured by western blot. The data showed that AP significantly suppressed the expressions of P2X7/NF-κB signal-related proteins and alleviated inflammatory reactions. Therefore, it was assumed that AP might be a potential therapeutic candidate to treat arthritis.


Evolution of MIR159/319 genes in Brassica campestris and their function in pollen development.
MIR159/319 have conserved evolution and diversified function after WGT in Brassica campestris, both of them can lead pollen vitality and germination abnormality, Bra-MIR319c also can function in flower development. MiR159 and miR319 are extensively studied highly conserved microRNAs which play roles in vegetative development, reproduction, and hormone regulation. In this study, the effects of whole-genome triplication (WGT) on the evolution of the MIR159/319 family and the functional diversification of the genes were comprehensively investigated in Brassica campestris. We identified 11 MIR159/319 genes in B. campestris, which produced five mature sequences. After analyzing the precursor sequences and phylogenetic tree, we found that Bra-MIR159/319 have evolutionary conservatism. Furthermore, Bra-MIR159/319 show functional diversification after WGT, as indicated by their expression patterns and the cis-element in their promoter. GUS signal showed that Bra-MIR159a and Bra-MIR319c can be expressed in anther but in different development stages. In B. campestris, overexpressed MIR159a and MIR319c contribute to late anther development and promote pollen abortion. Moreover, Bra-MIR319c can partially assume the function of MIR319a in flower development.


Comparison of norfloxacin with cotrimoxazole for infection prophylaxis in acute leukemia. The trade-off for reduced gram-negative sepsis.
A total of 63 neutropenic patients receiving cytotoxic therapy for acute leukemia were randomly allocated to receive norfloxacin (400 mg every 12 hours) or cotrimoxazole (160/800 mg every 12 hours) to prevent bacterial infection. Compliance was more than 95 percent and no adverse effects attributable to the study drugs were observed. The overall incidence of febrile illness (67 percent) was similar between the groups; however, no gram-negative bacillary infections were observed in 31 norfloxacin recipients compared with four of 32 cotrimoxazole recipients. Furthermore, nine norfloxacin recipients had 17 gram-positive bacteremias compared with two in two cotrimoxazole recipients (p = 0.0034). Norfloxacin was more effective than cotrimoxazole for preventing acquisition of aerobic gram-negative bacilli in surveillance cultures. Neither study drug allocation nor the presence of an indwelling central venous catheter influenced outcome among the 42 patients who subsequently received empiric systemic antibiotics for suspected infection. Although gram-positive infection remains an unsolved problem, norfloxacin appears to be a safe, effective, well-tolerated alternative to cotrimoxazole for preventing gram-negative infection in neutropenic patients with acute leukemia.


Cold hardiness and overwintering strategy of the pink maize stalk borer,Sesamia nonagrioides Lef (lepidoptera, noctuidae).
The cold-hardening capacity of larvae of the pink maize stalk borer,Sesamia nonagrioides Lef., was examined. Supercooling points (SCPs) of field collected diapausing larvae from south-east and south-west France and non-diapausing and diapausing laboratory-reared larvae did not differ and ranged between -5 and -8°C. Thus, this insect possesses sufficient supercooling ability to avoid freezing over its normal environmental temperature ranges. Despite this, we found thatSesamia presents paradoxical cold reactions. Mortality of cold acclimated diapausing larvae after short-term exposure to temperatures above the SCP is high, supporting the view thatSesamia is cold-sensitive. On the other hand,Sesamia could survive freezing for at least 24 h to temperatures close to the SCP. This ability does not seem to be related to haemolymph trehalose, the sole cold-accumulated compound detected by gas chromatography and mass spectrometry. Despite the mildness of the winter 1990-1991, only 5% of the field population survive and pupate in April. The main part of the population died from November to January, the period during which larvae were mainly located in the part of the corn stem above the ground and experienced air temperatures. After January, all surviving larvae were excuusively located in the root, 10 cm below the soil, where they experienced milder temperatures than air. They exhibited a constant low rate of mortality, possibly independent of the cold. In their current distribution area, survival of overwintering larvae ofS. nonagrioides is only related to the microclimate of the overwintering site and freezing tolerance capacity seems to be irrelevant. This study allows us to propose a non-pollutant pest control method based on the "behavioral strategy" of this insect.


[Osteoid osteoma of the talus and simple bone cyst of the homolateral calcaneus. A rare association].
Osteoid osteoma and simple bone cyst are readily observed in long bones, but are much less common in the short bones of the foot. The association of these two tumors in the same foot is exceptional. We report the case of a 15-year-old girl who presented an osteoid osteoma of the talus and a simple bone cyst of the calcaneus of the left foot. The patient complained of pain in the rear foot for four months which worsened at night and was of the inflammatory type. The physical examination was normal. Standard x-rays revealed a simple bone cyst in the calcaneus which could not explain the nighttime inflammatory pain. Scintigraphy and computed tomography of the left foot revealed an osteoid oseoma of the talus. Biopsy total resection of the osteoid osteoma with curettage and filling with cancellous bone of the simple bone cyst were performed. The patient has been free of recurrence at three years follow-up.


Heart rate time series: decreased chaos after intravenous lactate and increased non-linearity after isoproterenol in normal subjects.
In this study, we reanalyzed our previous heart rate time series data on the effects of intravenous sodium lactate (n=9) and intravenous isoproterenol (n=11) using non-linear techniques. Our prior findings of significantly higher baseline non-linear scores (NL: S(netGS)) and significantly lower largest Lyapunov exponents in supine posture in patients with panic disorder compared to control subjects prompted this study. We obtained the largest Lyapunov exponent (LLE), and a measure of non-linearity (NL: S(netGS)) of heart rate time series. LLE quantifies predictability and NL quantifies the deviation from linear processes. There was a significant increase in NL score, (S(netGS)) after isoproterenol infusions and a significant decrease in LLE (an increase in predictability indicating decreased chaos), after intravenous lactate in supine posture in normal control subjects. Increased NL scores in supine posture after intravenous isoproterenol may be due to a relative increase in cardiac sympathetic activity or a decrease in vagal activity at least in certain circumstances, and an overall decrease in LLE may indicate an impaired cardiac autonomic flexibility after intravenous sodium lactate, as LLE is diminished by autonomic blockade by atropine. Band analysis of LLE (LF/HF) (LF: 0.04-0.15 Hz and HF: 0.15-0.5 Hz) showed an increase of these ratios during either condition with a higher sympathovagal interaction after the drug administration. These findings may throw new light on the association of anxiety and significant cardiovascular events.


Evaluation of the prognostic meaning of C-reactive protein (CRP) in children and adolescents with classical Hodgkin's lymphoma (HL).
In adult cancer patients the negative predictive value of elevated CRP levels has been described for several malignancies. Only few studies have analyzed the prognostic role of CRP in children and adolescents with classical HL. In these studies elevated CRP levels correlate with the presence of classical risk factors and adverse outcome. The prognostic role of CRP for patients with classical HL admitted to the GPOH-HD-2002 study was analyzed retrospectively. CRP levels were documented for 369 of 573 patients. Significant (p<0.05) increased median CRP levels were found in the presence of B-Symptoms (25.7 vs. 5.1 mg/l), extranodal involvement (21.5 vs. 7.5 mg/l), elevated erythrocyte sedimentation rate (ESR, 13.0 vs. 1.0 mg/l) and stage III/IV disease (15.5 vs. 5.3 mg/l). 83.9% of patients with elevated and 45.8% of patients with normal CRP had an ESR >30 mm/h. Elevated CRP levels were associated with classical risk factors of HL. CRP and ESR may reflect different biological processes. CRP was prognostic within early stage TG-1 patients treated with reduced treatment, but not within advanced stage TG-2+3.


Differences in the number of embryonic and pseudo-beta-globin genes between HbA and HbB sheep.
DNA samples obtained from 8 goats, 1 moufflon, and 84 sheep with HbA, HbAB, and HbB belonging to different breeds were digested with BamHI, EcoRI, HindIII and PstI and probed with the 5' end of the goat epsilon IV- and psi beta Z-globin genes. Sheep homozygous for HbA show a different restriction pattern than sheep homozygous fo HbB with each of these endonucleases. The main difference is that HbB sheep lack the epsilon II and psi beta X genes. These results, in addition to those previously obtained using a probe specific for beta-globin genes, suggest that HbB sheep probably lack the preadult four-gene set. The DNAs from moufflon and sheep homozygous for HbA show indistinguishable restriction patterns. Furthermore, a number of restriction fragment length polymorphisms (RFLPs) are detected in the epsilon IV and psi beta Z DNA regions, and one HindIII RFLP in the epsilon VI DNA region.


[Primary mucinous carcinoma of the eyelid. Case report].
Primary cutaneous mucinous carcinoma, a tumor of the sweat glands, is a rare tumor localized to the eyelid in 40% of cases. We report a case of a primary cutaneous mucinous carcinoma of the upper eyelid in a 53-year-old Caucasian male who appeared to have a chalazion. Histology showed rows and lobules of epithelial cells with discretely anisonucleotic nuclei and few mitotic figures scattered throughout the tumor cells, surrounded by a mucoid substance. Immunohistochemical analysis was cytokeratin 7 positive and cytokeratin 20 negative, and imaging and endoscopic screening were negative for metastasis, favoring the diagnosis of primary cutaneous mucinous carcinoma. Despite a high recurrence rate of about 35%, this type of tumor displays an indolent course, and metastatic spread is very rare.


Photosynthesis in relation to leaf nitrogen and phosphorus content in Zimbabwean trees.
CO2 assimilation in relation to light intensity and the relationship between leaf nitrogen and phosphorus concentrations and CO2 assimilation in 14 species of ecologically important Zimbabwean trees were examined. Eight of the species are members of the Fabaceae (Leguminosae). In the majority of Zimbabwean climax woodlands, the dominant trees are non-nodulating members of the sub-family Caesalpinioideae. The species examined have higher light saturation points (>700 μmol m-2 s-1) than woody species from temperate areas; one species, Acacia nigrescens, did not reach saturation at photon fluxes greater than 1500 μmol m-2 sec-1. Higher leaf nitrogen content was found to correlate positively with higher CO2 assimilation rates (r=0.85; P≦0.0003); there was no correlation between leaf phosphorus content and CO2 uptake rates. There were no significant differences between sites in terms of leaf nitrogen or phosphorus content, but the mean photosynthetic rate at one of the sites (Chizedzi) was lower. Taxa from the nodulating legumes were found to have higher leaf nitrogen contents (309.1±SD 22 mmol m-2) than those of the non-nodulating species (239±33); the lowest nitrogen contents were found in nonleguminous trees (179±42), with the exception of Ziziphus mucronata. This species may form an association with an N2-fixing actinomycete.


Synthesis and evaluation of 2-pyridinone derivatives as specific HIV-1 reverse transcriptase inhibitors. 3. Pyridyl and phenyl analogs of 3-aminopyridin-2(1H)-one.
In an ongoing effort to develop novel nonnucleoside, specific human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitors, a series of 3-[(pyridylmethyl)amino]- and 3-[(phenylmethyl)amino]-2-pyridinone derivatives was synthesized and tested for HIV-1 RT inhibitory activity. The more potent compounds have a 2'-methoxy group and 4'- and/or 5'-aliphatic substituents on the pyridyl and phenyl rings. Several of the more potent compounds were also evaluated for antiviral activity in MT-4 cell culture. From this series of compounds, 3-[N-[(5-ethyl-2-methoxy-6-methyl-3-pyridyl)methyl]amino]-5-ethyl-6- methylpyridin-2(1H)-one (6) was selected for clinical evaluation.


A physical tug-of-war and the evolution of immune cells.
Antibodies form an important component of our immune response to pathogens. A robust antibody response can lead to the swift clearance of infection. The protection offered by COVID-19 vaccines has been attributed in large measure to the antibodies they elicit (Padmanabhan et al. 2022). Yet, with other pathogens like HIV-1, vaccines that elicit potent antibodies have remained elusive despite intense efforts over decades (Burton 2019). It is important, therefore, to understand how our body mounts a robust antibody response specific to an invading pathogen or vaccine. A remarkable manifestation of Darwinian evolution happens to be at the heart of such a response.


Daily Relations Between Stress and Electroencephalography-Assessed Sleep: A 15-Day Intensive Longitudinal Design With Ecological Momentary Assessments.
Recent studies have found bi-directional relations between stress and sleep. However, few studies have examined the daily associations between stress and electroencephalography (EEG) measured sleep. This study examined the temporal associations between repeated ecological momentary assessments of stress and EEG-estimated sleep. Ninety-eight international or interstate undergraduate students (Mage = 20.54 ± 1.64, 76.5% female, 84.7% Asian) reported their stress levels four times daily at morning awakening, afternoon, evening, and pre-bedtime across 15 consecutive days (>4,000 total observations). Next-day stress was coded as an average of morning, afternoon, and evening stress. Z-Machine Insight+ recorded over 1,000 nights EEG total sleep time (TST), sleep onset latency, wake after sleep onset, sleep efficiency (SE), slow-wave sleep (SWS), and rapid eye movement (REM) sleep duration. Multilevel models, adjusted for covariates (i.e., sociodemographic, health factors, and daily covariates) and lagged outcomes, tested the daily within- and between-level stress-sleep associations. After adjusting for covariates, within-person shorter TST (b = -0.11 [-0.21, -0.01], p = .04), lower SE (b = -0.02 [-0.03, 0.00], p = .04), less SWS (b = -0.38 [-0.66, -0.10], p = .008), and less REM sleep (b = -0.32 [-0.53, -0.10], p = .004) predicted higher next-day stress. Pre-bedtime stress did not predict same-night sleep. No significant results emerged at the between-person level. These findings demonstrate that poor or short sleep, measured by EEG, is predictive of higher next-day stress. Results for sleep architecture support the role of SWS and REM sleep in regulating the perception of stress. Given that only within-person effects were significant, these findings highlight the importance of examining night-to-night fluctuations in sleep affecting next-day stress and its impact on daytime functioning.


Distinct Clinical Features of Plasma Cell Myeloma Patients Exhibiting Dysmorphic Plasma Cells: Association with More Plasma Cells at Diagnosis.
Dysmorphic plasma cells are occasionally found in bone marrow (BM) aspirates of plasma cell myeloma (PCM) patients. We retrospectively analyzed the incidences of significant dysmorphic plasma cells (SDPC) presentations and their associations with clinical features in PCM patients. Total 91 PCM patients diagnosed from January 2013 to December 2017 at author's institution were enrolled. SDPC presentation was determined as ≥ 5% (SDPC5) or ≥ 10% (SDPC10) among total PC and clinical features of PCM patients were compared with respect to SDPC presentation status. Incidence of SDPC5/SDPC10 presentation was 39.6%/18.7%. Patients with SDPC5/SDPC10 showed significantly more BM PC (P = 0.004/0.020) and higher incidences of CKS1B gains (P = 0.022/0.001) and RB1 loss (P = 0.032 for SDPC10 only) at diagnosis than those without SDPC5/SDPC10. Patients with SDPC5/SDPC10 also showed significantly greater absolute BM PC (P = 0.007/0.034 and 0.047/0.049 for 1st and 2nd follow-up, respectively) and serum M-protein (P = 0.041/0.044 and 0.039/0.049 for 1st and 2nd follow-up, respectively) reductions after chemotherapy than those without SDPC5/SDPC10. SDPC5/SDPC10 presentation was confirmed as an independent predictor of BM PC ≥ 37.7% [hazard ratio (HR) 4.649/2.613, P = 0.005/0.039]. Our present study demonstrated that SDPC presentation would be an independent predictor of more BM PC at diagnosis in PCM patients. Associations between SDPC presentation and higher incidence of CKS1B gains and RB1 loss, greater PC/serum monoclonal protein reductions after chemotherapy were also identified. Association between SDPC presentation and favorable treatment response should be evaluated in more comprehensive study.


Effect of hydrogen peroxide on potassium currents in inner hair cells isolated from guinea pig cochlea.
Hydrogen peroxide (H₂O₂) is a ubiquitous reactive oxygen species that can induce several inner ear disorders. In this study, we recorded the potassium (K) currents in acutely isolated inner hair cells of guinea pig cochlea, and investigated the effects of H₂O₂. We also observed the morphological changes in inner hair cells induced by H₂O₂. In the H₂O₂ solutions, the amplitude of outward K currents (I(K,f) and I(K,s)) clearly decreased after perfusion for approximately 15 min. Despite the decrease in outward currents, small inward currents (I(K,n)) did not show any reduction. H₂O₂ induced morphological changes in the inner hair cells. All the inner hair cells in the H₂O₂ solutions showed shrinkage and granularity of the cell body and led to loss of viability. These results showed the vulnerability of inner hair cells to reactive oxygen species-induced inner ear disorders.


The effect of clinical pathways for bariatric surgery on perioperative quality of care.
Bariatric surgery demands a multidisciplinary approach and enhanced recovery schemes. Such schemes are complex and cumbersome to introduce into practice. This study evaluates if a clinical pathway (CP) facilitates implementation of an enhanced recovery scheme in bariatric surgery with the goal of improving perioperative quality of care. We compared 65 consecutive patients who underwent bariatric surgery in 2009 and were treated with a CP (CP group) with 64 consecutive patients treated without CP in 2007/2008 (pre-CP group). Process quality indicators were catheter management, postoperative mobilization, spirometer training, vitamin B supplementation, diet resumption, intake of supplement drinks, and length of stay. Outcome quality was measured through morbidity, mortality, re-operations, and re-admissions. In the CP group, foley catheters were removed earlier (p < 0.0001), patients were mobilized more often on the surgery day (CP group 92.3% vs. pre-CP group 78.1%, p = 0.03), used spirometers more often (56.9% vs. 28.1%, p = 0.002), were more often supplemented with vitamin B (100% vs. 31.3%, p < 0.0001), and received oral supplement nutrition more often (100% vs. 59.4%, p < 0.0001). Median length of stay was shorter in the CP group (6 vs. 7 days, p = 0.007). There was no significant difference in mortality, morbidity, re-operations, and re-admissions. Following implementation of an enhanced recovery CP for bariatric surgery, several indicators of process quality improved while outcome quality remained unchanged. A CP seems useful for optimizing treatment of bariatric surgery patients according to enhanced recovery principles. However, future studies are required to better determine which elements of care can be improved most.


Optimization of a sandwich sol particle immunoassay for human chorionic gonadotrophin.
Colloidal gold particles coated with rabbit anti-HCG (Au-(anti-HCG)) were used in a spectrophotometric 'sandwich' SPIA for HCG. The effects of several reagent properties and assay variables were investigated in order to optimize the assay. Best results were obtained with 55 nm particles. Optimum assay conditions involved a sample incubation period of 2 h followed by aspiration of the sample and two washings. A suitable Au-(anti-HCG) concentration corresponded to a value of A1cm540nm = 2.0. The steepest dose-response curves were obtained with an Au-(anti-HCG) incubation period of 16 h at 37 degrees C. The test procedure was suitable for preparing dose-response curves for HCG in buffer, urine and serum. The practical measuring range for HCG dissolved in these media was 30-250 IU/l. The within-run coefficient of variation varied between approx. 4 and 12%. The detection limit for HCG (in buffer) was about 1 IU/l.


RNA aptamers with specific binding affinity to CD40 (CD40Apt) represents a promising antagonist of the CD40-CD40L signaling for thyroid-associated ophthalmopathy (TAO) treatment in mouse.
Thyroid-associated ophthalmopathy (TAO) is the most common autoimmune inflammatory diseases of the orbit. The CD40-CD40L pathway has been regarded as a potential molecular mechanism contributing to the development and progression of TAO, and RNA aptamers with specific binding affinity to CD40 (CD40Apt) represents a promising inhibitor of the CD40-CD40L signaling in TAO treatment. In this study, CD40Apt was confirmed to specifically recognize mouse CD40-positive ortibtal fibroblast. Mouse orbital fibroblasts were isolated from TAO mice model orbital tissues and validated. In TGF-β-induced orbital fibroblast activation model in vitro, CD40Apt administration inhibited TGF-β-induced cell viability, decreased TGF-β-induced α-SMA, Collagen I, Timp-1, and vimentin levels, and suppressed TGF-β-induced phosphorylation of Erk, p38, JNK, and NF-κB. In TAO mice model in vivo, CD40Apt caused no significant differences to the body weight of mice; furthermore, CD40Apt improved the eyelid broadening, ameliorated inflammatory infiltration and the hyperplasia in orbital muscle and adipose tissues in model mice. Concerning orbital fibroblast activation, CD40Apt reduced the levels of CD40, collagen I, TGF-β, and α-SMA in orbital muscle and adipose tissues of model mice. Finally, CD40Apt administration significantly suppressed Erk, p38, JNK, and NF-κB phosphorylation. In conclusion, CD40Apt, specifically binds to CD40 proteins in their natural state on the cell surface with high affinity, could suppress mouse orbital fibroblast activation, therefore improving TAO in mice model through the CD40 and downstream signaling pathways. CD40Apt represents a promising antagonist of the CD40-CD40L signaling for TAO treatment.


Prostacyclin protects against elevated blood pressure and cardiac fibrosis.
Specific inhibitors of COX-2 have been associated with increased risk for cardiovascular complications. These agents reduce prostacyclin (PGI2) without affecting production of thromboxane (Tx) A2. While this abnormal pattern of eicosanoid generation has been implicated in the development of vascular disease associated with COX-2 inhibition, its role in the development of hypertension, the most common cardiovascular complication associated with COX-2 inhibition, is not known. We report here that mice lacking the receptor for PGI2 (IPKOs) develop salt-sensitive hypertension, cardiac hypertrophy, and severe cardiac fibrosis. Coincidental deletion of the TxA2 (TP) receptor does not prevent the development of hypertension, but cardiac hypertrophy is ameliorated and fibrosis is prevented in IPTP double knockouts (DKOs). Thus, deletion of the IP receptor removes a constraint revealing adverse cardiovascular consequences of TxA2. Our data suggest that adjuvant therapy that blocks unrestrained Tx actions might protect against end-organ damage without affecting blood pressure in patients taking COX-2 inhibitors.


The FUTUREPAIN study: Validating a questionnaire to predict the probability of having chronic pain 7-10 years into the future.
The FUTUREPAIN study develops a short general-purpose questionnaire, based on the biopsychosocial model, to predict the probability of developing or maintaining moderate-to-severe chronic pain 7-10 years into the future. This is a retrospective cohort study. Two-thirds of participants in the National Survey of Midlife Development in the United States were randomly assigned to a training cohort used to train a predictive machine learning model based on the least absolute shrinkage and selection operator (LASSO) algorithm, which produces a model with minimal covariates. Out-of-sample predictions from this model were then estimated using the remaining one-third testing cohort to determine the area under the receiver operating characteristic curve (AUROC). An optimal cut-point that maximized sensitivity and specificity was determined. The LASSO model using 82 variables in the training cohort, yielded an 18-variable model with an out-of-sample AUROC of 0.85 (95% Confidence Interval (CI): 0.80, 0.91) in the testing cohort. The sum of sensitivity (0.88) and specificity (0.76) was maximized at a cut-point of 17 (95% CI: 15, 18) on a 0-100 scale where the AUROC was 0.82. We developed a short general-purpose questionnaire that predicts the probability of an adult having moderate-to-severe chronic pain in 7-to-10 years. It has diagnostic ability greater than 80% and can be used regardless of whether a patient is currently experiencing chronic pain. Knowing which patients are likely to have moderate-to-severe chronic pain in the future allows clinicians to target preventive treatment.


Frequencies for radio astronomy.
At present the scope of research in radio astronomy is limited by the allocation of frequencies, some of which have to be shared with other radio services. When the International Telecommunications Union reconsiders all frequency allocations next year, astronomers are hoping for an improvement.


Sexual quality of life in women who have undergone female genital mutilation: a case-control study.
To investigate the sexual quality of life of women who have undergone female genital mutilation (FGM) and compare them with a similar group who has not undergone FGM. Case-control study. A large central London teaching hospital. A total of 73 women who had undergone FGM and 37 control women, who had not undergone FGM but were from a similar cultural background where FGM is practiced. The women completed a questionnaire containing the Sexual Quality of Life-Female (SQOL-F) questionnaire. SQOL-F score. Women who have undergone FGM of any type have a significantly lower (P < 0.001) overall SQOL-F score than control women (mean = 62.44, SD = 27.93 versus mean = 88.84, SD = 13.73). Women who were sexually active and had undergone FGM type III differed the most from sexually active controls (P < 0.05) in their SQOL-F score. Women who were sexually inactive but who had undergone FGM reported significantly lower overall SQOL-F scores (P = 0.015) than sexually inactive controls, but were not differentiated by type of FGM. FGM significantly reduces women's sexual quality of life, based on the results of the SQOL-F questionnaire.


Erlotinib Versus Etoposide/Cisplatin With Radiation Therapy in Unresectable Stage III Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer: A Multicenter, Randomized, Open-Label, Phase 2 Trial.
This study aimed to compare erlotinib (E) and etoposide/cisplatin (EP) with concurrent radiation therapy (RT) for patients with stage IIIA/B unresectable advanced non-small cell lung cancer with activating epidermal growth factor receptor mutation (EGFRm+). This was a multicenter, randomized, open-label, phase 2 trial conducted across 19 institutions in China (December 2012 to January 2016). Enrolled patients were randomized (1:1) to E + RT (oral erlotinib 150 mg/d for 2 years or until disease progression or intolerable toxicity and RT 200 cGy/d, 5 d/wk for 6 weeks from the first day of erlotinib) or EP + RT (etoposide 50 mg/m2 intravenously on days 1-5 and 29-33; cisplatin 50 mg/m2 intravenously on days 1, 8, 29 and 36; and RT as for E + RT). The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate and safety. Two hundred fifty-two patients were screened, and 20 patients with EGFRm+ in each group received the allocated E + RT or EP + RT treatment. Patient characteristics were well balanced between groups. Compared with EP + RT, median PFS with E + RT was significantly longer (24.5 vs 9.0 months [hazard ratio, 0.104; 95% confidence interval, 0.028-0.389; P < .001]). Objective response rate in the E + RT and EP + RT groups was 70% and 61.9%, respectively (P = .744). The incidence of adverse events (any grade) was similar between E + RT and EP + RT groups (88.9% and 84.2%). The primary endpoint of PFS was met, and the data showed that E + RT might provide PFS improvement compared with EP + RT, with similar tolerability. However, definitive statements regarding the efficacy of concurrent E + RT in patients with unresectable stage III non-small cell lung cancer with activating EGFRm+ cannot be made, and slow patient accrual will likely make it infeasible to conduct a phase 3 study.


Behavior of concentrated emulsions prepared by acid-hydrolyzed insoluble microalgae proteins from Chlorella protothecoides.
Microalgae are a promising alternative source to meet the increasing global demand for protein. The insoluble microalgae protein fraction that makes up over half of the protein composition of the biomass has shown potential to serve as a functional emulsifier after acidic hydrolysis. However, creaming was observed due to the flocculation of emulsion droplets, suggesting a preferable use in concentrated emulsions. In this study, we examined the emulsifying behavior of the untreated insoluble microalgae protein fraction and two of its hydrolysates obtained in 0.5 mol L-1 HCl for 4 h at 65 °C (Hydrolysates 65) or 85 °C (Hydrolysates 85), at a concentration of 3% (w/w), and elevated levels of oil (50-70%). The results showed an increase in droplet size and apparent viscosity with increasing oil content in the emulsions. The emulsions made with Hydrolysates 85 had the smallest droplet size and the highest apparent viscosity. The gravitational separation was hindered when oil content was increased. The Hydrolysates 85 stabilized emulsions had a gel-like structure and were stable against coalescence or creaming during a 7 day storage test. The results suggest that the thermal acid-treated fraction Hydrolysates 85 may, in particular, be a good emulsifier to formulate concentrated emulsion-based foods with oil content over 50%, such as mayonnaise, salad dressings, or dips. © 2020 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


The property distance index PD predicts peptides that cross-react with IgE antibodies.
Similarities in the sequence and structure of allergens can explain clinically observed cross-reactivities. Distinguishing sequences that bind IgE in patient sera can be used to identify potentially allergenic protein sequences and aid in the design of hypo-allergenic proteins. The property distance index PD, incorporated in our Structural Database of Allergenic Proteins (SDAP, http://fermi.utmb.edu/SDAP/), may identify potentially cross-reactive segments of proteins, based on their similarity to known IgE epitopes. We sought to obtain experimental validation of the PD index as a quantitative predictor of IgE cross-reactivity, by designing peptide variants with predetermined PD scores relative to three linear IgE epitopes of Jun a 1, the dominant allergen from mountain cedar pollen. For each of the three epitopes, 60 peptides were designed with increasing PD values (decreasing physicochemical similarity) to the starting sequence. The peptides synthesized on a derivatized cellulose membrane were probed with sera from patients who were allergic to Jun a 1, and the experimental data were interpreted with a PD classification method. Peptides with low PD values relative to a given epitope were more likely to bind IgE from the sera than were those with PD values larger than 6. Control sequences, with PD values between 18 and 20 to all the three epitopes, did not bind patient IgE, thus validating our procedure for identifying negative control peptides. The PD index is a statistically validated method to detect discrete regions of proteins that have a high probability of cross-reacting with IgE from allergic patients.


Synthesis and assembly of barium-doped iron oxide nanoparticles and nanomagnets.
A facile organic-phase synthesis of monodisperse barium-doped iron oxide (Ba-Fe-O) nanoparticles (NPs) is reported. The Ba-Fe-O NPs can be converted into hexagonal barium ferrite NPs at 700 °C, showing strong ferromagnetic properties with H(c) reaching 5260 Oe and M(s) at 54 emu g(-1). Moreover, the Ba-Fe-O NPs can be assembled into densely packed magnetic arrays, providing a unique model system for studying nanomagnetism and for nanomagnetic applications.


The Genetic Basis of Pigmentation Differences Within and Between Drosophila Species.
In Drosophila, as well as in many other plants and animals, pigmentation is highly variable both within and between species. This variability, combined with powerful genetic and transgenic tools as well as knowledge of how pigment patterns are formed biochemically and developmentally, has made Drosophila pigmentation a premier system for investigating the genetic and molecular mechanisms responsible for phenotypic evolution. In this chapter, we review and synthesize findings from a rapidly growing body of case studies examining the genetic basis of pigmentation differences in the abdomen, thorax, wings, and pupal cases within and between Drosophila species. A core set of genes, including genes required for pigment synthesis (eg, yellow, ebony, tan, Dat) as well as developmental regulators of these genes (eg, bab1, bab2, omb, Dll, and wg), emerge as the primary sources of this variation, with most genes having been shown to contribute to pigmentation differences both within and between species. In cases where specific genetic changes contributing to pigmentation divergence were identified in these genes, the changes were always located in noncoding sequences and affected cis-regulatory activity. We conclude this chapter by discussing these and other lessons learned from evolutionary genetic studies of Drosophila pigmentation and identify topics we think should be the focus of future work with this model system.


Two new species of Ectobiidae (Blattaria) collected in the Santa Lúcia Biological Reserve, Espírito Santo, Brazil.
This contribution describes and illustrates the male genitalia of two new species of Ectobiidae belonging to Pseudophyllodromiinae, Chorisoneura Brunner von Wattenwyl, and Blattellinae, Xestoblatta Hebard. Both species were collected in the Santa Lúcia Biological Reserve in the state of Espírito Santo, Brazil.


Improvement of the aerodynamic behaviour of the passenger car by using a combine of ditch and base bleed.
The current study investigates different methods to minimize the drag coefficient (CD) without ignoring the safety factor related to the stability of a vehicle, i.e., the lift coefficient (CL). The study was carried out by employing an SUV car analyzed numerically using one of the CFD software, Ansys. Four different models such as realizable k-ε, standard k-ω, shear stress transport k-ω, and Reynolds stress model (RSM). The considered models have been validated with experimental data and found in good agreement. The considered inlet velocity varies from 28 to 40 m/s, the results showed that the drag coefficient and the stability are both improved by applying a modification on the roof of the considered car.


Direct in vivo gene introduction into rat kidney.
We established a simple and highly efficient method for in vivo gene transfer using HVJ (Sendai virus) and liposomes. Plasmid DNA and high mobility group 1 (HMG1) protein were co-encapsulated in liposomes by agitation and sonication and were co-introduced into cells by HVJ-mediated membrane fusion. pACT SVT DNA, as a reporter gene, was introduced into the kidney of intact rats through a cannula in the renal artery, and SV40 large T antigen was detected by enzyme immunohistochemistry in glomerular cells 4 days after its introduction. This newly developed kidney-directed gene transfer method should be useful not only in basic research but also in potential gene therapeutics of renal diseases.


Application of an artificial intelligence ensemble for detection of important secondary findings on lung ventilation and perfusion SPECT-CT.
Single-photon-emission-computerized-tomography/computed-tomography(SPECT/CT) is commonly used for pulmonary disease. Scant work has been done to determine ability of AI for secondary findings using low-dose-CT(LDCT) attenuation correction series of SPECT/CT. 120 patients with ventilation-perfusion-SPECT/CT from 9/1/21-5/1/22 were included in this retrospective study. AI-RAD companion(VA10A,Siemens-Healthineers, Erlangen, Germany), an ensemble of deep-convolutional-neural-networks was evaluated for the detection of pulmonary nodules, coronary artery calcium, aortic ectasia/aneurysm, and vertebral height loss. Accuracy, sensitivity, specificity was measured for the outcomes. Inter-rater reliability were measured. Inter-rater reliability was measured using the intraclass correlation coefficient (ICC) by comparing the number of nodules identified by the AI to radiologist. Overall per-nodule accuracy, sensitivity, and specificity for detection of lung nodules were 0.678(95%CI 0.615-0.732), 0.956(95%CI 0.900-0.985), and 0.456(95%CI 0.376-0.543), respectively, with an intraclass correlation coefficient (ICC) between AI and radiologist of 0.78(95%CI 0.71-0.83). Overall per-patient accuracy for AI detection of coronary artery calcium, aortic ectasia/aneurysm, and vertebral height loss was 0.939(95%CI 0.878-0.975), 0.974(95%CI 0.925-0.995), and 0.857(95%CI 0.781-0.915), respectively. Sensitivity for coronary artery calcium, aortic ectasia/aneurysm, and vertebral height loss was 0.898(95%CI 0.778-0.966), 1 (95%CI 0.958-1), and 1 (95%CI 0.961-1), respectively. Specificity for coronary artery calcium, aortic ectasia/aneurysm, and vertebral height loss was 0.969(95% CI 0.893-0.996), 0.897 (95% CI 0.726-0.978), and 0.346 (95% CI 0.172-0.557), respectively. AI ensemble was accurate for coronary artery calcium and aortic ectasia/aneurysm, while sensitive for aortic ectasia/aneurysm, lung nodules and vertebral height loss on LDCT attenuation correction series of SPECT/CT.


Hyperthermic therapy for HIV infection.
The objective of this paper is to review what is known about the antiviral effects of fever and to highlight the scientific evidence supporting the hypothesis that hyperthermic therapy may prove to be a beneficial treatment modality for persons infected with HIV. Our hyperthermic hypothesis is based upon the mutant escape, quasispecies theory of HIV antigenic diversity. We propose that, if initiated during the asymptomatic stage of HIV infection, hyperthermia may prove to decrease the number of mutant HIV strains arising due to evolutionary pressures created by the patient's immune system, with a resultant prolongation of the asymptomatic period of infection. A review of the literature from three areas of investigation: the immune response to fever, heat as a tumor killing agent, and preliminary studies with fever and retroviral infections, strongly suggests that there is a good scientific basis for the use of hyperthermic therapy in a multimodal treatment approach to HIV infection.


Large scale transient expression with COS cells.
We demonstrate here that transient expression with COS cells can be performed at the one litre scale for a period of more than 10 days. Cells grown in T225 flasks were transfected by electroporation, transferred into spinners, and then grown either in suspension or on microcarriers. A daily medium change significantly extented culture life and production time, compared with standard protocols.Concentrations of the product, the secreted fusion protein CD40-Fc, were comparable in microcarrier and suspension culture. Cultures were started in fetal calf serum containing medium and the subsequent production process was performed in a low protein serum free medium which allowed easy downstream processing. 10 litres of supernatant, collected from one transfected batch of cells, yielded 30 mg of purified and biologically active protein.In addition to developing a simplified protocol for generation of cells we also reduced the material (DNA, cuvettes) required for electroporation. Our results show that scale up of transient expression to the litre scale can be successfully acieved. This provides a new tool to generate milligram quantities of protein within weeks of gene cloning.


The spectrum of neurological presentations in an outpatient clinic of rural Zimbabwe.
Previous studies to estimate burden of neurological disorders in Africa are limited to inpatients in urban hospitals. The spectrum of neurological conditions in rural Africa remains unclear. To determine the spectrum of neurological presentations in an outpatient setting in rural Zimbabwe. Clinical data was collected from outpatient records at Karanda Mission Hospital, a rural community hospital in Northern Zimbabwe from February 2013 to February 2014. Each patient visit was entered in an outpatient record book by a registered nurse or a nurse trainee. Demographic details such as age, sex, weight and address of the patient, and clinical details such as diagnosis on discharge and medications prescribed were recorded in the record book following assessment by a physician or nurse practitioner. Each visit corresponded to a separate entry in the study. We recorded a total of 19,206 visits in the outpatient registry. The average age was 46.41 years (standard deviation=21.46), and there were more visits from women (57.81%). 11.63% (2233) of all visits had a neurological diagnosis at discharge. The most common neurological diagnoses were epilepsy/seizures (24.38%), followed by neuropathies (13.63%), headaches (11.4%) and strokes (4.6%). One in ten cases in an outpatient setting in rural Zimbabwe were neurologically related. Further studies are required to determine the public health burden of neurological disorders in rural Africa. The development and funding of educational initiatives in resource-limited areas is needed to improve neurological diagnosis and care.