Innate and adaptive immune responses to tick-borne flavivirus infection in sheep.
The flaviviruses tick-borne encephalitis virus (TBEV) and louping ill virus (LIV) are closely-related genetically and antigenically, have broadly similar host ranges that include rodents and other mammals (including sheep), and are both transmitted by the same tick species, Ixodes ricinus. Although human infection with TBEV results in a febrile illness followed in some cases by encephalitis, humans appear to be much less susceptible to infection with LIV. However, these viruses demonstrate different susceptibilities in sheep; LIV infection causes encephalitic disease, whereas TBEV infection generally does not. To investigate the role of the immune response in this mixed outcome, groups of sheep were inoculated with either virus, or with a primary inoculation with one virus and secondary inoculation with the other. Markers of both adaptive and innate immune responses were measured. In each group studied, infection resulted in seroconversion, demonstrated by the detection of virus specific neutralising antibodies. This appeared to control infection with TBEV but not LIV, which progressed to a febrile infection, with transient viraemia and elevated levels of serum interferon. This was followed by neuroinvasion, leading to up-regulation of innate immune transcripts in discrete areas of the brain, including interferon inducible genes and chemokines. Prior inoculation with TBEV did not prevent infection with LIV, but did appear to reduce disease severity and viraemia. We postulate that LIV has adapted to replicate efficiently in sheep cells, and disseminate rapidly following infection. By contrast, TBEV fails to disseminate in sheep and is controlled by the immune response.


[Effect of ischemia and recirculation on the ultrastructure of the ventral horns of the rabbit spinal cord and accumulation of calcium in motoneurons].
The effect of 40-min ligation of the abdominal aorta and 60-min recirculation was investigated with the use of pyroantimonate. All the motoneurons were markedly damaged. Vacuolized mitochondria and basal membrane of capillaries contained calcium deposits.


Agrobacterium-mediated transformation of the ascomycete mushroom Morchella importuna using polyubiquitin and glyceraldehyde-3-phosphate dehydrogenase promoter-based binary vectors.
Morchella importuna is a worldwide distributed edible mushroom with high ecological and economic values, but the molecular and genetic research about this mushroom has been hindered due to lack of an efficient transformation method. Here, we report for the first time the successful transformation of M. importuna by using a hypervirulent Agrobacterium tumefaciens strain bearing the constructed binary plasmid p1391-U-GUS. The selectable markers used were the genes for hygromycin resistance under the control of the polyubquitin promoter from M. importuna. The reporter genes were those for enhanced green fluorescent protein (EGFP) and the β-Glucuronidase (GUS) under the control of glyceraldehyde-3-phosphate dehydrogenase promoter and polyubquitin promoter respectively. The presence of the reporter gene EGFP in the transformants was confirmed by the fluorescence and confocal microscope and molecular analysis and that of the reporter gene GUS was verified by enzyme activity and molecular analysis. The analysis results of both reporter genes indicated that Agrobacterium-mediated transformation was successfully performed in M. importuna.


Validation of the Japanese version of the Roland-Morris Disability Questionnaire.
The study was designed to validate a translated, culturally adapted questionnaire. We examined the reliability, validity, and responsiveness of the Japanese version of the Roland-Morris Questionnaire (RDQ) when assessing disability in Japanese patients with low back pain. The RDQ is a reliable, validated scale used to measure disability caused by low back pain. However, no validated Japanese version of this questionnaire is available. A series of 214 outpatients with low back pain participated in this validation study. The patients were given the RDQ and the SF-36, and assessed their pain and global rating of health. Among them, 57 who were clinically stable were given the RDQ again 2 weeks later. The reliability was examined based on the test-retest method and internal consistency. Sufficient reliability was demonstrated with a Chronbach's. coefficient of 0.85, and the reproducibility for the 30 patients was r = 0.91. The principal component analysis showed unidimensionality. The RDQ score of the 133 patients was significantly improved after treatment. The Japanese version of the RDQ is a useful scale that is easy to use with reliability, validity, and responsiveness when assessing patients with low back pain.


Alterations in beta-amyloid production and deposition in brain regions of two transgenic models.
Mutations in the amyloid precursor protein (APP) gene are associated with altered production and deposition of amyloid beta (Abeta) peptide in the Alzheimer's disease (AD) brain. The pathways that regulate APP processing, Abeta production and Abeta deposition in different tissues and brain regions remain unclear. To address this, we examined levels of various APP processing products as well as Abeta deposition in a genomic-based (R1.40) and a cDNA-based (Tg2576) transgenic mouse model of AD. In tissues, only brain generated detectable levels of the penultimate precursor to Abeta, APP C-terminal fragment-beta. In brain regions, holoAPP levels remained constant, but ratios of APP C-terminal fragments and levels of Abeta differed significantly. Surprisingly, cortex had the lowest steady-state levels of Abeta compared to other brain regions. Comparison of Abeta deposition in Tg2576 and R1.40 animals revealed that R1.40 exhibited more abundant deposition in cortex while Tg2576 exhibited extensive deposition in the hippocampus. Our results suggest that AD transgenic models are not equal; their unique characteristics must be considered when studying AD pathogenesis and therapies.


Perceptions and practices of aged care pharmacists regarding osteoporosis management: a qualitative study.
Osteoporosis is a common but sub-optimally managed disease among aged care residents. Although pharmacists are one of the key healthcare providers responsible for osteoporosis medication management there is limited research on their involvement. This study explored the perceptions and practices of Australian pharmacists regarding osteoporosis management for aged care residents. Semi-structured interviews were conducted with aged care pharmacists. Interviews were recorded, transcribed, and analysed using a constructivist grounded theory approach. Twenty-one aged care pharmacists were interviewed. Three main themes were identified: osteoporosis is highly prevalent but given low priority, factors affecting pharmacists' management of osteoporosis, and optimism for the future role of pharmacists in osteoporosis management. The complexity of aged care residents' healthcare needs and the silent, insidious nature of osteoporosis contribute to the low priority it is afforded. Barriers identified by pharmacists included their current practice model, limited access to residents' medical histories and difficulties accessing bone mineral density (BMD) testing. Interdisciplinary collaboration and education regarding osteoporosis management were seen as facilitators. Pharmacists were optimistic that an embedded practice model would improve their capacity to influence osteoporosis management. The high prevalence and low priority of osteoporosis in the aged care setting presents pharmacists with an opportunity to improve medication management and reduce fracture risk. Barriers to osteoporosis management identified by pharmacists can be addressed by interdisciplinary collaboration and education. Pharmacists being embedded in aged care could enable more opportunities to contribute to the interdisciplinary team and become champions of osteoporosis management.


Special microanatomical features surrounding the intracorpora cavernosa nerves and their probable function during erection.
The nerves of the corpora cavernosa have anatomical characteristics different from other nerves. The intracavernous nerves are located in fibrous tunnels into which numerous fibrous bundles establish attachments. These bundles are part of the fibrous meshwork included in the corpora cavernosa. We suspect that during erection, when the corpora fill with blood and high intracavernous pressure develops, the aforementioned meshwork of fibrous bundles attached to all fibrous elements of the corpora, including the tunica albuginea and the perineural fibrous tunnels, stretches and prevents compression of the intracavernous nerves.


Fasting and two-hour post-load glucose levels for the diagnosis of diabetes. The relationship between glucose levels and complications of diabetes in the Pima Indians.
The frequency distributions of both the fasting and two-hour post-load plasma glucose levels were bimodal in the Pima Indian population aged 25 years and over. The hyperglycaemic component of this distribution represents those with diabetes mellitus, as some 30 percent of this group had evidence of the specific vascular complications of the disease, whereas these abnormalities were virtually absent in those with lower glucose levels. The bimodal characteristics of the frequency distributions were utilized to define optimal criteria to separate those with and without diabetes. The sensitivity and specificity of these criteria for fasting and two-hour glucose levels were compared and were found to be similar. The fasting glucose determination, however, was more reproducible and stable, as well as being easier to obtain, indicating that it is the better measurement for diagnostic purposes. The optimal level for diagnosis of 7.5 mmol/l (136 mg/dl) for the fasting glucose and the equivalent two-hour value of 14 mmol/l (250 mg/dl), were higher than many previously recommended diagnostic levels. Nevertheless, there was no evidence that subjects with lower levels were at appreciable risk of developing the specific complications of diabetes. Subjects with impaired glucose tolerance (IGT), but without fasting hyperglycaemia, should not be diagnosed as having diabetes mellitus.


Neuropsychological functions and psychiatric symptoms in late-onset manifestation of pantothenate kinase-associated neurodegeneration: a clinical case report.
Purpose of the study: Pantothenate Kinase-associated Neurodegeneration (PKAN) is a form of Neurodegeneration with brain iron accumulation (NBIA) due to gene mutations. Classical phenotype showed progressive neurological symptoms associated to a characteristic pattern of basal ganglia iron deposits. The atypical case, with adult-onset manifestation, could have neuropsychiatric symptoms with behavioral deficits. We described an adult-onset case of Pantothenate Kinase-associated Neurodegeneration.Materials and methods: The patient underwent neuropsychological and psychiatric evaluation and Magnetic Resonance Imaging, respectively for cognitive and behavioral assessment and to confirm the characteristic findings of this syndrome.Results: The patient showed atypical phenotype of Pantothenate Kinase-associated Neurodegeneration, characterized by language deficits, dixesecutive, and psychiatric manifestations, such as obsessive ideation, impulsivity, and disinhibition.Conclusions: This description could be helpful to a more correct diagnosis and clinical management.


[Direct renal pelvic puncture in the bacteriologic study in patients with uretero-intestinal urinary diversion (a new technic for diagnosis of upper urinary tract infection)].
The renal pelvis of ten patients with ileal or colonic conduit was punctured with a 22G spinal needle under fluoroscopic guidance. Renal pelvic urine was obtained from nine patients. Two patients temporarily developed gross hematuria as a complication due to this procedure. The obtained renal pelvic urine was investigated bacteriologically. Direct renal pelvic puncture was concluded to be a useful and safe technique for locating urinary tract infection. Reflux of infected urine into the renal pelvis did not occur in any of the nine patients who had no obstruction of the ileal or colonic conduit.


Collective nostalgia and political ideology.
Collective nostalgia is a form of nostalgia that is contingent upon thinking of oneself in terms of a particular social identity. Research has focused in particular on collective nostalgia for a nation's past. Here, I propose that conservatives and others on the right side of the political spectrum experience stronger collective nostalgia for their nation's past than liberals and those on the left. I first explain the roots of this prediction in conservative political philosophy, review empirical evidence in favor of that idea, and summarize findings that show the significance of this link for policy support. Finally, I review and discuss evidence that qualifies the link between conservatism and collective nostalgia.


Comparison of Solid-Water Partitions of Radiocesium in River Waters in Fukushima and Chernobyl Areas.
Adsorption of radiocesium (RCs) on particulate matters in aquatic environment is important to understand its mobility and bioavailability. We here focused on factors controlling partition of RCs on particulate matters and sediments in Kuchibuto (Fukushima) and Pripyat (Chernobyl) Rivers, though RCs level in water was much smaller than WHO guideline. Moreover, Cs speciation and organic matter-clay mineral interaction were studied: (i) extended X-ray absorption fine structure showed that the contribution of outer-sphere complex of Cs on particulate matters is larger in Chernobyl than in Fukushima and (ii) scanning transmission X-ray microscope revealed larger association of humic substances and clay minerals in Chernobyl partly due to high [Ca2+] in the Pripyat River. Consequently, RCs is more soluble in the Pripyat River due to weaker interaction of RCs with clay minerals caused by the inhibition effect of the adsorbed humic substances. In contrast, particulate matters and sediments in the Kuchibuto River display high adsorption affinity with lesser inhibition effect of adsorbed humic substances. This difference is possibly governed by the geology and soil type of provenances surrounding both catchments (Fukushima: weathered granite; Chernobyl: peat wetland and carbonate platform) which leads to high concentrations of organic matter and Ca2+ in the Pripyat River.


Immunoelectron microscopic studies on the cell surface location of the thyroid microsomal antigen.
The cell surface location of the thyroid microsomal antigen was studied by immunoelectron microscopy. Isolated, open human thyroid follicles were incubated with patient sera containing high titers of microsomal autoantibodies. Cell surface-bound antibodies were detected by the immunogold technique using IgG-coated colloidal gold particles (10 or 15 nm). Immunocytochemical incubations were performed at 4 degrees C. Gold particles were concentrated at the apical cell surface of the follicle cells, while the basolateral cell surface was almost completely unlabelled. Quantitative evaluation of four experiments with follicle cells prepared from different patients showed that about 90% of the gold particles at the apical cell surface was associated with microvilli and that the concentration of gold particles at the microvillus membrane was, although with great intercellular variation, several times higher than that at smooth portions of the apical plasma membrane. This suggests that the microsomal antigen is organized in microdomains in the apical plasma membrane. In follicles labelled immunocytochemically at 4 degrees C and then incubated at 37 degrees C, gold particles were slowly internalized. The particles appeared in smooth and coated pits of the apical plasma membrane as well as in vesicles, vacuoles and lysosomes in the apical part of the cytoplasm. Membranes of TSH-induced pseudopods were always unlabelled. Our observations indicate that thyroid microsomal antigen immunoreactivity is present in the apical but not in the basolateral plasma membrane. The antigen with bound antibodies is internalized by micropinocytosis but not by macropinocytosis. The selective location of bound microsomal antibodies at the apical plasma membrane and their absence from the membrane of TSH-induced pseudopods are compatible with the idea that the microsomal antigen and thyroperoxidase are identical.


HEMO2 life® improves renal function independent of cold ischemia time in kidney recipients: A comparison with a large multicenter prospective cohort study.
M101 is an extracellular hemoglobin isolated from a marine lugworm and is present in the medical device HEMO2 life®. The clinical investigation OXYOP was a paired kidney analysis (n = 60) designed to evaluate the safety and performance of HEMO2 life® used as an additive to preservation solution in renal transplantation. The secondary efficacy endpoints showed less delayed graft function (DGF) and better renal function in the HEMO2 life® group but due to the study design cold ischemia time (CIT) was longer in the contralateral kidneys. An additional analysis was conducted including OXYOP patients and patients from the ASTRE database (n = 6584) to verify that the decrease in DGF rates observed in the HEMO2 life® group may not be due solely to the shorter CIT but also to HEMO2 life® performance. Kaplan-Meier estimate curves of cumulative probability of achieving a creatinine level below 250 µmol/L were generated and compared in both groups. A Cox model was used to test the effect of the explanatory variables (use of HEMO2 life® and CIT). Finally, a bootstrap strategy was used to randomly select smaller samples of patients and test them for statistical comparison in the ASTRE database. Kaplan-Meier estimate curves confirmed the existence of a relation between DGF and CIT and Cox analysis showed a benefit in the HEMO2 life® group regardless of the associated CIT. Boostrap analysis confirmed these results. The present study suggested that the better recovery of renal function observed among kidneys preserved with HEMO2 life® in the OXYOP study is a therapeutic benefit of this breakthrough innovative medical device.


Absence of parallelism between polyamine and nucleic acid contents during induced growth of cucumber cotyledons.
The cytokinins (benzyladenine or benzyladenosine) decreased spermidine and spermine contents despite increasing putrescine content, when administered to isolated cotyledons of Cucumis sativus L. var. Guntur in organ culture. KCl decreased putrescine contents, although marginally increasing polyamine contents. The cytokinins and/or KCl augmented nucleic acid biosynthesis and accumulation, resulting in enhanced growth and differentiation of the isolated cotyledons. These observations show that polyamine accumulation and growth are not always coupled.


Treatment of posttraumatic syringomyelia: evidence from a systematic review.
Following spinal cord injury (SCI), the routine use of magnetic resonance imaging (MRI) resulted in an incremental diagnosis of posttraumatic syringomyelia (PTS). However, facing four decades of preferred surgical treatment of PTS, no clear consensus on the recommended treatment exists. We review the literature on PTS regarding therapeutic strategies, outcomes, and complications. We performed a systematic bibliographic search on ("spinal cord injuries" [Mesh] AND "syringomyelia" [Mesh]). English language literature published between 1980 and 2020 was gathered, and case reports and articles examining syrinx due to other causes were excluded. The type of study, interval injury to symptoms, severity and level of injury, therapeutic procedure, duration of follow-up, complications, and outcome were recorded. Forty-three observational studies including 1803 individuals met the eligibility criteria. The time interval from SCI to the diagnosis of PTS varied between 42 and 264 months. Eighty-nine percent of patients were treated surgically (n = 1605) with a complication rate of 26%. Symptoms improved in 43% of patients postoperatively and in 2% treated conservatively. Stable disease was documented in 50% of patients postoperatively and in 88% treated conservatively. The percentage of deterioration was similar (surgery 16%, 0.8% dead; conservative 10%). Detailed analysis of surgical outcome with regard to symptoms revealed that pain, motor, and sensory function could be improved in 43 to 55% of patients while motor function deteriorated in around 25%. The preferred methods of surgery were arachnoid lysis (48%) and syrinx drainage (31%). Even diagnosing PTS early in its evolution with MRI, to date, no satisfactory standard treatment exists, and the present literature review shows similar outcomes, regardless of the treatment modality. Therefore, PTS remains a neurosurgical challenge. Additional research is required using appropriate study designs for improving treatment options.


[Clinical and radiological assessment of the results of using grafts of allogenic lyophilized spongy bone for filling of large postoperative jaw bone defects].
The authors describe the method of filling large bone defects in the maxilla and mandible with blocks of allogenic spongy bone enriched with biologically active substances. This method was used during 2 years in 21 cases with good results. Two-year clinical and radiological observations are reported, with detailed radiological documentation of 3 cases.


Synthesis, characterization and pharmacological evaluation of amide prodrugs of ketorolac.
Ketorolac (KC) suffers from the general side effects of NSAIDs, owing to presence of free carboxylic acid group. The study aimed to retard the adverse effects of gastrointestinal origin. Ten prodrugs of KC were synthesized by amidation with ethyl esters of amino acids, namely, glycine, l-phenylalanine, l-tryptophan, l-valine, l-isoleucine, l-alanine, l-leucine, l-glutamic acid, l-aspartic acid and beta-alanine. Purified synthesized prodrugs were characterized by m.p., TLC, solubility, partition coefficients, elemental analyses, UV, FTIR, NMR and MS. Synthesized prodrugs were subjected for biopharmaceutical studies, analgesic, anti-inflammatory activities and ulcerogenic index. Marked reduction of ulcerogenic index and comparable analgesic, anti-inflammatory activities were obtained in all cases as compared to KC. Among synthesized prodrugs, viz. AR-11, AR-19 and AR-20 showed excellent pharmacological response and encouraging hydrolysis rate both in SIF and in 80% human plasma. Prodrugs with increased aliphatic side chain length or introduction of aromatic substituent showed enhanced partition coefficient but diminished dissolution and hydrolysis rates. Such prodrugs can be considered for sustained release purpose.


Wearable Power-Assist Locomotor (WPAL) for supporting upright walking in persons with paraplegia.
Due to physical and psychosocial issues associated with long-term sitting in a wheelchair, devising new ways to facilitate upright mobility is a key issue in rehabilitation medicine. Wearable Power-Assist Locomotor (WPAL) is a motorized orthosis and is developed for providing independent and comfortable walking for paraplegic patients. The WPAL consists of a wearable robotic orthosis and custom walker. To facilitate alternate usage with a wheelchair, the wearable robotic orthosis is based on a medial system with motors located at the bilateral hip, knee and ankle joints to reduce the increase in heart rate during gait. The gait parameters include stride length, toe clearance height, swing time, double support time, etc. (gait speed: up to 1.3 km/h). Independent gait with the walker can be learned through a five-stage gait exercise sequence. The first two stages are stepping and gait exercises with parallel bars. The third stage is gait exercise on treadmill. The subsequent two stages are gait exercise with walker. Seven motor-complete paraplegic patients (spinal cord functional levels: T6-T12) participated. Through a series of exercises, all users achieved independent gait on a level floor (Functional Ambulation Categories: 4). The mean duration and distance of consecutively walking were 14.1 ± 11.4 minutes and 165.6 ± 202.6 m, respectively. The most competent user was able to walk continuously for as long as 40 minutes and 640 m whereas only for 6 minutes and 107 m with a conventional orthosis. These results suggest that WPAL might be useful device for supporting upright walking in persons with paraplegia.


HSP90 inhibitor (NVP-AUY922) enhances the anti-cancer effect of BCL-2 inhibitor (ABT-737) in small cell lung cancer expressing BCL-2.
Small cell lung cancer (SCLC) cannot be efficiently controlled using existing chemotherapy and radiotherapy approaches, indicating the need for new therapeutic strategies. Although ABT-737, a B-cell lymphoma-2 (BCL-2) inhibitor, exerts anticancer effects against BCL-2-expressing SCLC, monotherapy with ABT-737 is associated with limited clinical activity because of the development of resistance and toxicity. Here, we examined whether combination therapy with ABT-737 and heat shock protein 90 (HSP90) inhibitor NVP-AUY922 exerted synergistic anticancer effects on SCLC. We found that the combination of ABT-737 and NVP-AUY922 synergistically induced the apoptosis of BCL-2-expressing SCLC cells. NVP-AUY922 downregulated the expression of AKT and ERK, which activate MCL-1 to induce resistance against ABT-737. The synergistic effect was also partly due to blocking NF-κB activation, which induces anti-apoptosis protein expressions. However, interestingly, targeting BCL-2 and MCL-1 or BCL2 and NF-κB did not induce the cytotoxicity. In conclusion, our study showed that combination of BCL2 inhibitor with HSP90 inhibitor increased activity in in vitro and in vivo study in only BCL-2 expressing SCLC compared to either single BCL2 inhibitor or HSP inhibitor. The enhanced activity might be led by blocking several apoptotic pathways simultaneously rather than a specific pathway.


Incidence and mortality trends of neglected tropical diseases and malaria in China and ASEAN countries from 1990 to 2019 and its association with the socio-demographic index.
People in China and the countries in the Association of Southeast Asian Nations (ASEAN) are affected by neglected tropical diseases and malaria (NTDM). In this study, we aimed to assess the current status and trends of NTDM burden from 1990 to 2019 in China and ASEAN countries, and also explore the association of NTDM burden with socio-demographic index (SDI). The data from the Global Burden of Diseases Study 2019 (GBD 2019) results were used. Absolute incidence and death number, and age-standardized incidence and mortality rate (ASIR and ASMR) of NTDM in China and ASEAN were extracted. The estimated annual percentage change (EAPC) and join-point regression in the rates quantified the trends. Nonlinear regression (second order polynomial) was used to explore the association between SDI and ASRs. The ASIR of NTDM increased in China, Philippines, Singapore and Brunei, at a speed of an average 4.15% (95% CI 3.83-4.47%), 2.15% (1.68-2.63%), 1.03% (0.63-1.43%), and 0.88% (0.60-1.17%) per year. Uptrends of ASIR of NTDM in recent years were found in China (2014-2017, APC = 10.4%), Laos (2005-2013, APC = 3.9%), Malaysia (2010-2015, APC = 4.3%), Philippines (2015-2019, APC = 4.2%), Thailand (2015-2019, APC = 2.4%), and Vietnam (2014-2017, APC = 3.2%, all P < 0.05). Children < 5 had relatively low incidences but unexpectedly high mortality rates of NTDM in most ASEAN countries. Both incidence and mortality rates of NTDM were higher in older people. ASIR and ASMR of NTDM had a U-shaped association with SDI. The burden of NTDM in China and ASEAN countries was still huge and affects vulnerable and impoverished populations' livelihoods, including children under the age of 5 and people aged 60 and older. Facing with the large burden and complex situation of NTDM in China and ASEAN countries, regional cooperating strategies are needed to reduce the burden of NTDM, so as to achieve the goal of elimination in the world.


Null alleles of ABCG2 encoding the breast cancer resistance protein define the new blood group system Junior.
The breast cancer resistance protein, also known as ABCG2, is one of the most highly studied ATP-binding cassette (ABC) transporters because of its ability to confer multidrug resistance. The lack of information on the physiological role of ABCG2 in humans severely limits cancer chemotherapeutic approaches targeting this transporter. We report here that ABCG2 comprises the molecular basis of a new blood group system (Junior, Jr) and that individuals of the Jr(a-) blood type have inherited two null alleles of ABCG2. We identified five frameshift and three nonsense mutations in ABCG2. We also show that the prevalence of the Jr(a-) blood type in the Japanese and European Gypsy populations is related to the p.Gln126* and p.Arg236* protein alterations, respectively. The identification of ABCG2(-/-) (Jr(a-)) individuals who appear phenotypically normal is an essential step toward targeting ABCG2 in cancer and also in understanding the physiological and pharmacological roles of this promiscuous transporter in humans.


Obstructive rectal intramural hematoma caused by a foreign body.
Intramural hematoma of the alimentary tract is a rare condition, which usually results from blunt injury. It can spontaneously occur in patients with coagulopathy or on anticoagulants. Although it may be seen anywhere in the alimentary tract, duodenum is the most common site of the intestinal intramural hematomas. Intramural hematoma caused by a foreign body is rarely seen. Patients with intramural hematoma are usually encountered with obstructive symptoms after an isolated injury. Intramural hematomas are often self-limited at the site of occurrence and can be managed conservatively. They rarely cause progressive obstruction and need surgical drainage. In this article, we report a 51-year-old male patient with foreign body used for masturbation causing rectal intramural hematoma and perforation at the rectosigmoid junction. Because of the intestinal perforation, the patient was managed surgically. In the diagnosis of intramural hematoma of the alimentary tract, beside the clinical history and physical examination, the findings at imaging modalities such as conventional radiography, ultrasonography, and computed tomography are often useful. Patients with rectal intramural hematoma usually do not give diagnostic clues to the physicians in the clinical history. Therefore, radiologists must be familiar with the imaging findings. In this article, we aimed to present a patient with rectal intramural hematoma caused by foreign body and obliterating the rectal lumen.


Composition of extrafloral nectar influences interactions between the myrmecophyte Humboldtia brunonis and its ant associates.
Ant-plant interactions often are mediated by extrafloral nectar (EFN) composition that may influence plant visitation by ants. Over a 300 km range in the Indian Western Ghats, we investigated the correlation between the EFN composition of the myrmecophytic ant-plant Humboldtia brunonis (Fabaceae) and the number and species of ants visiting EFN. EFN composition varied among H. brunonis populations and between plant organs (floral bud vs. young leaf EFN). In general, EFN was rich in sugars with small quantities of amino acids, especially essential amino acids, and had moderate invertase activity. In experiments at the study sites with sugar and amino acid solutions and with leaf or floral bud EFN mimics, dominant EFN-feeding ants differentiated between solutions as well as between mimics. The castration parasite Crematogaster dohrni (northern study site) was the least selective and did not exhibit any clear feeding preferences, while the largely trophobiont-tending non-protective Myrmicaria brunnea (middle study site) preferred higher sucrose concentrations and certain essential/non-essential amino acid mixtures. The mutualistic Technomyrmex albipes (southern study site) preferred sucrose over glucose or fructose solutions and consumed the leaf EFN mimic to a greater extent than the floral bud EFN mimic. This young leaf EFN mimic had low sugar concentrations, the lowest viscosity and sugar:amino acid ratio, was rich in essential amino acids, and appeared ideally suited to the digestive physiology of T. albipes. This preference for young leaf EFN may explain the greater protection afforded to young leaves than to floral buds by T. albipes, and may also help to resolve ant-pollinator conflicts. The differential response of dominant ants to sugar, amino acids, or solution viscosity suggests that plants can fine-tune their interactions with local ants via EFN composition. Thus, EFN can mediate local partner-choice mechanisms in ant-plant interactions.


Enhancement of barium- and cesium-induced adrenal catecholamine release by lidocaine.
Catecholamine release evoked from isolated perfused bovine adrenals by Ba+2 or Cs+ is enhanced by lidocaine or by a calcium-free medium. The action of Cs+ therefore differs from that of K+ or Rb+ in adrenal medulla. Divalent and monovalent metallic cations of relatively large atomic weight like Ba+2 and Cs+, probably penetrate the cell more easily than small highly charged ions and act intracellularly to cause adrenal catecholamine release. Local anesthetics and calcium-free media may allow greater influx of Ba+2 and Cs+ into adrenomedullary cells.


Factors that influence continuing professional development over a nursing career: A scoping review.
Systematically synthesize research about factors that influence CPD over a nursing career. Continuing professional development (CPD) in nursing is defined as 'a life-long process of active participation in learning activities that assist in developing and maintaining continuing competences, enhancing professional practice and supporting achievement of career goals'. Research has shown that inability to access resources and activities for CPD influences quality of care and adversely affects nurses' satisfaction, recruitment and retention. Although more and more research regarding CPD is done, a comprehensive overview about the needs of nurses for successful CPD is missing. Scoping review, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews ensuring all quality standards are met. Between February and April 2020 the electronic databases CINAHL, PubMed, Scopus, Psychinfo and Eric were searched as well as reference lists of included papers. Papers published in peer-reviewed journals were included without restrictions on publication date, design or setting. Thematic analysis was done to synthesize the data. The search yielded 2673 papers of which 60 papers were included. Analyses showed that factors that influence CPD differ over a nursing career, which led to the identification of three groups: newly graduated nurses; experienced nurses; and experienced nurses with ambitions for advanced roles. Furthermore, analyses showed that factors for all three groups are related to personal and contextual facilitators and barriers. Newly graduated nurses find it important to be an accepted member of the team. They experience barriers when integrating into the nursing profession, where they for instance experience workplace incivility. Experienced nurses experience contextual barriers related to a lack of supportive structures and inaccessibility of CPD resources. There is limited time and availability of role models and a lack of support from managers and other colleagues. Moreover, the clinical care dynamics influence their ability to pursue CPD. For the experienced nurses with ambitions for advanced roles, an important barrier is that nursing culture emphasizes direct patient care. Often it is unclear what the value is of new nursing roles which makes it difficult for them to develop these. All nurses strive for CPD. However, organizations need to recognize nurses' personal goals and unique strategies as this leads to different needs in CPD. In addition, resources must be made available and accessible before CPD can be successfully pursued by all nurses.


Anatomy of melancholia: focus on hypothalamic-pituitary-adrenal axis overactivity and the role of vasopressin.
Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis characterized by hypercortisolism, adrenal hyperplasia and abnormalities in negative feedback is the most consistently described biological abnormality in melancholic depression. Corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are the main secretagogues of the HPA/stress system. Produced in the parvicellular division of the hypothalamic paraventricular nucleus the release of these peptides is influenced by inputs from monoaminergic neurones. In depression, anterior pituitary CRH1 receptors are down-regulated and response to CRH infusion is blunted. By contrast, vasopressin V3 receptors on the anterior pituitary show enhanced response to AVP stimulation and this enhancement plays a key role in maintaining HPA overactivity.


Narrow Complex Tachycardia With Intermittent 2:1 Atrioventricular Relationship.
Narrow QRS complex tachycardia has a broad differential diagnosis. We present a series of rhythm strips with representative onset, transition from 2:1 AV conduction to 1:1 AV conduction, and offset of tachycardia. By analyzing these rhythm strips, we can identify the electrophysiologic mechanism and diagnosis. (Level of Difficulty: Intermediate.).


Liquid crystalline nanoparticles enable a multifunctional approach for topical psoriasis therapy by co-delivering triptolide and siRNAs.
Liquid crystalline nanoparticles (LCNs) are an attractive drugs topical delivery system due to the great internal ordering, wide interfacial area and structural similarities with the skin. In this work, LCNs were designed to encapsulate triptolide (TP) and to complex on its surface small interfering RNAs (siRNA) targeting TNF-α and IL-6, aiming at topical co-delivery and regulating multi-targets in psoriasis. These multifunctional LCNs showed appropriate physicochemical properties for topical application, such as a mean size of 150 nm, low polydispersion, TP encapsulation greater than 90% and efficient complexation with siRNA. The internal reverse hexagonal mesostructure of LCNs was confirmed by SAXS while their morphology was assessed by cryo-TEM. In vitro permeation studies revealed an increase of more than 20-fold in the distribution of TP through the porcine epidermis/dermis was achieved after the application of LCN-TP or LCN TP in hydrogel. In cell culture, LCNs showed good compatibility and rapid internalization, which was attributed to macropinocytosis and caveolin-mediated endocytosis. Anti-inflammatory potential of multifunctional LCNs was assessed by reducing of TNF-α, IL-6, IL-1β and TGF-β1 levels in LPS-stimulated macrophages. These results support the hypothesis that the co-delivery of TP and siRNAs by LCNs may be a new strategy for psoriasis topical therapy.


ANGPTL4, IL-6 and TNF-α as regulators of lipid metabolism during a marathon run.
The aim of the study was to reveal whether marathon running influences regulators of lipid metabolism i.e. angiopoietin-like protein 4 (ANGPTL4), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α). Plasma concentration of ANGPTL4, IL-6, TNF-α and lipids were determined in samples collected from 11 male runners before the marathon, immediately after the run and at 90 min of recovery. Plasma ANGPTL4 increased during exercise from 55.5 ± 13.4 to 78.1 ± 15.0 ng/ml (P < 0.001). This was accompanied by a significant increase in IL-6, TNF-α, free fatty acids (FFA) and glycerol (Gly) and a decrease in triacylglycerols (TG). After 90 min of recovery ANGPTL4 and TG did not differ from the exercise values, while plasma IL-6, TNF-α, FFA and Gly concentration were significantly lower. The exercise-induced increase in plasma concentration of ANGPTL4 correlated positively with the rise in plasma IL-6, TNF-α, FFA and Gly and negatively with the duration of the run. The increase in plasma IL-6 and TNF-α correlated positively with the rise in Gly. Summarizing, marathon running induced an increase in plasma ANGPTL4 and the value was higher in faster runners. The increase in plasma FFA, IL-6 and TNF-α concentration during a marathon run may be involved in plasma ANGPTL4 release, which could be a compensatory mechanism against FFA-induced lipotoxicity and oxidative stress. All of the analyzed cytokines may stimulate lipolysis during exercise.


Exenatide prevents high-glucose-induced damage of retinal ganglion cells through a mitochondrial mechanism.
Exenatide (exendin-4 analogue) is widely used in clinics and shows a neuroprotective effect. The main objectives of the present study were to prove that retinal ganglion cells (RGC-5) express GLP-1R, to ascertain whether exenatide prevents a high-glucose-induced RGC-5 impairment, to determine the appropriate concentration of exenatide to protect RGC-5 cells, and to explore the neuroprotective mechanisms of exenatide. Immunofluorescence and Western blot analyses demonstrated that RGC-5 cells express GLP-1R. We incubated RGC-5 cells with 25 mM glucose prior to incubation with either 25 mM glucose, 55 mM glucose (high), high glucose plus exenatide or high glucose plus a GLP-1R antagonist. The survival rates of the cells were measured by CCK-8, and cellular injury was detected by electron microscopy. There were statistical differences between the high-glucose group and the control group (P<0.05). Exenatide improved the survival rate of the cells and suppressed changes in the mitochondrial morphology. The optimum concentration of exenatide to protect the RGC-5 cells from high-glucose-induced RGC injury was 0.5 μg/ml, and this protective effect could be inhibited by exendin (9-39). To further study the mechanism underlying the beneficial effects of exenatide, the expression levels of cytochrome c, Bcl-2, Bax and caspase-3 were analysed by Western blot. The present study showed that treatment with exenatide significantly inhibited cytochrome c release and decreased the intracellular expression levels of Bax and caspase-3, whereas Bcl-2 was increased (P<0.05). These results suggested that GLP-1R activation can inhibit the cellular damage that is induced by high glucose. A mitochondrial mechanism might play a key role in the protective effect of exenatide on the RGC-5 cells, and exenatide might be beneficial for patients with diabetic retinopathy.


Temperature-Dependent Dynamic Characteristics of Carbon-Fiber-Reinforced Plastic for Different Spectral Loading Patterns.
The dynamic properties of carbon-fiber-reinforced plastic (CFRP) can be efficiently estimated through a modal damping coefficient and a resonance frequency, and the modal parameters can be calculated using a frequency response function (FRF). The modal parameters used in an CFRP FRF are influenced by the carbon fiber direction, temperature, and spectral loading pattern, as well as the operating conditions. In this study, three parameters-temperature, spectral loading pattern, and carbon fiber direction-were selected as the influential factors for CFRP dynamics, and the sensitivity index formulation was derived from the parameter-dependent FRF of the CFRP structure. The derivatives of the parameter-dependent FRF over the three considered parameters were calculated from the measured modal parameters, and the dynamic sensitivity of the CFRP specimens was explored from the sensitivity index results for five different directional CFRP specimens. The acceleration response of a simple CFRP specimen was obtained via a uniaxial excitation test at temperatures ranging from -8 to 105 °C for the following two spectral loading cases: harmonic and random.


RNF186 impairs insulin sensitivity by inducing ER stress in mouse primary hepatocytes.
RING finger 186 (RNF186) is involved in the process of endoplasmic reticulum (ER)-stress-mediated apoptosis and inflammation of different cell types, such as HeLa cells and colon epithelial cells. However, the physiological and functional roles of RNF186 in peripheral tissues remain largely unknown. In the current study, we investigate the physiological function of RNF186 in the regulation of ER stress with respect to its biological roles in regulating insulin sensitivity in mouse primary hepatocytes. RNF186 expression is induced in the livers of diabetic, obese and diet-induced obese (DIO) mice. Mouse primary hepatocytes were isolated and treated with Ad-RNF186 or Ad-GFP. The results suggest that overexpression of RNF186 increases the protein levels of the ER stress sensors inositol requiring kinase 1 (IRE1) and C/EBP homologous protein (CHOP) protein, as well as the phosphorylation level of eukaryotic initiation factor 2α (eIF2α), in mouse primary hepatocytes. This effect impedes the action of insulin through c-Jun N-terminal kinase (JNK)-mediated phosphorylation of insulin receptor substrate 1 (IRS1). Furthermore, overexpression of RNF186 also significantly increases the levels of proinflammatory cytokines, including TNFα, IL-6 and MCP1. In addition, tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, alleviates the expression of ER stress markers induced by RNF186 overexpression. Taken together, the results of the present study show that overexpression of RNF186 induces ER stress and impairs insulin signalling in mouse primary hepatocytes, suggesting that RNF186 merits further investigation as a potential therapeutic target for treatment of insulin-resistance-associated metabolic diseases.


Physiological and comparative proteome analyses reveal low-phosphate tolerance and enhanced photosynthesis in a maize mutant owing to reinforced inorganic phosphate recycling.
The low-phosphate-tolerant maize mutant Qi319-96 was obtained from Qi319 through cellular engineering. To elucidate the molecular mechanisms underlying the low-phosphate tolerance of this mutant, we performed comparative proteome analyses of the leaves of Qi319-96 and Qi319 under inorganic phosphate (Pi)-sufficient and Pi-deficient conditions. Low-phosphorus levels limit plant growth and metabolism. Although the overall phosphorus contents of shoots were not significantly different between Qi319 and Qi319-96, the Pi level of Qi319-96 was 52.94 % higher than that of Qi319. Under low phosphorus conditions, Qi319-96 had increased chlorophyll levels and enhanced photosynthesis. The changes in starch and sucrose contents under these conditions also differed between genotypes. The proteomic changes included 29 (Pi-sufficient) and 71 (Pi-deficient) differentially expressed proteins involved in numerous metabolic processes. Proteome and physiological analyses revealed that Qi319-96 could better remodel the lipid composition of membranes and had higher V-ATPase activity levels than Qi319 under low-phosphate starvation, which enhanced the recycling of intracellular Pi, as reflected by its increased Pi levels. Chlorophyll biosynthesis was improved and the levels, and activities, of several Calvin cycle and "CO2 pump" enzymes were greater in Qi319-96 than in Qi319, which led to a higher rate of photosynthesis under low-phosphate stress in this line compared with in Qi319. Our results suggest that the increased tolerance of the maize mutant Qi319-96 to low-phosphate levels is owing to its ability to increase Pi availability. Additionally, inbred lines of maize with low-P-tolerant traits could be obtained effectively through cellular engineering.


Effect of biogenic iron species and copper ions on the reduction of carbon tetrachloride under iron-reducing conditions.
In this study, the cell-mediated and abiotic reduction of carbon tetrachloride (CCl(4)) by biogenic iron species produced from the reductive dissolution of ferrihydrite in the presence of Geobacter sulfurreducens and copper ions (Cu(II)) were investigated. 9,10-Anthraquinone-2,6-disulfonate (AQDS), serving as a surrogate of natural organic matters and an electron shuttling compound, was added to enhance the efficiency of biological reduction of the solid Fe(III) minerals. G. sulfurreducens drove the reduction of CCl(4), primarily through the formation of biogenic surface-bound iron species produced from the reductive dissolution of ferrihydrite, in the presence of 10microM AQDS. The pseudo-first-order rate constant (k(obsCT)) for CCl(4) transformation in the presence of ferrihydrite was 3.0 times higher than that resulting from the use of G. sulfurreducens alone. Addition of 0.5mM Cu(II) slightly inhibited both the growth of G. sulfurreducens and the production of biogenic Fe(II). However, the k(obsCT) values for CCl(4) transformation in ferrihydrite suspensions containing G. sulfurreducens and 0.3-0.5mM Cu(II) were 2.1-4.2 times higher than that observed in the absence of Cu(II). X-Ray powder diffraction analysis indicated that the added Cu(II) reacted with the biogenic Fe(II) ions to produce catalytic cuprous ions (Cu(I)) and secondary iron oxide minerals such as magnetite and goethite, resulting in accelerating the chemical transformation efficiency and rate of CCl(4) under iron-reducing conditions.


Trends in ICD-10-CM-Coded Administrative Datasets for Injury Surveillance and Research.
Accurate injury surveillance depends on data quality in administrative datasets created for billing and reimbursement. Significant effort has been devoted to testing the ability of candidate injury case definitions to identify injury cases accurately in these datasets. We used interviews with experienced coders, informed by a review of the current literature, to identify three clinical coding trends that may affect the consistency of surveillance data: "clinical documentation improvement or clinical documentation integrity" (CDI), coding by treating clinicians, and certain electronic health record features. An extensive literature review informed interviews with coding experts to identify potential issues in coding practice. To determine whether physician coding was associated with information loss, we analyzed data from two hospitals serving the same geographic area. One hospital had used physician coding of emergency department data for the past decade; the other used professional coders. We compared the proportion of emergency department records missing external cause of injury codes and assessed the variation for statistical significance. CDI audits review patient records to ensure that billing information includes every relevant International Classification of Diseases, Tenth Revision, Clinical Modification code. This approach has increased payment rates awarded to Medicare Advantage plans because additional codes increase the patient acuity level and case mix index. The impact of CDI audits on injury data needs further investigation. The pilot analysis addressing information loss with physician coding found a higher level of external cause coding with clinician self-coding, possibly because of the coding software. Finally, widespread "copy and paste" in patient electronic health records has the potential to increase reported injuries. Injury surveillance relies on billing and reimbursement records. Financial motivations may interfere with the consistency of surveillance findings and mislead injury epidemiologists. Further investigation is essential to ensure the integrity of surveillance findings.


A randomized, open-label, multicenter comparative study of the efficacy and safety of piperacillin-tazobactam and cefepime for the empirical treatment of febrile neutropenic episodes in patients with hematologic malignancies.
The empirical treatment of febrile, neutropenic patients with cancer requires antibacterial regimens active against both gram-positive and gram-negative pathogens. This study was performed to demonstrate the noninferiority of monotherapy with piperacillin-tazobactam, compared with cefepime. We conducted a randomized-controlled, open-label, multicenter clinical trial among high-risk patients from 34 university-affiliated tertiary care medical centers in the United States, Canada, and Australia who were undergoing treatment for leukemia or hematopoietic stem cell transplantation and were hospitalized for empirical treatment of febrile neutropenic episodes. Patients received piperacillin-tazobactam (4.5 g every 6 h) or cefepime (2 g every 8 h) intravenously. The primary outcome was success (defined by defervescence without treatment modification) at 72 h of treatment, end of treatment, and test of cure in the modified intent-to-treat analysis. Secondary outcomes included time to defervescence, microbiological efficacy, the additional use of glycopeptide antibiotics, emergence of resistant bacteria, and safety. For 528 subjects (265 received piperacillin-tazobactam and 263 received cefepime), success rates were 57.7% and 48.3%, respectively (P = .04) at the 72-h time point, 39.6% and 31.6% (P = .06) at end of treatment, and 26.8% and 20.5% (P = .11) at the test-of-cure visit. The analyses demonstrated noninferiority for piperacillin-tazobactam at all time points (P< or = .0001). Treatment with piperacillin-tazobactam was independently associated with treatment success in multivariate analysis (odds ratio, 1.65; 95% confidence interval, 1.04-2.64; P = .035). Both regimens were well tolerated. This study demonstrates the noninferiority and safety of piperacillin-tazobactam monotherapy, compared with cefepime, for the empirical treatment of high-risk febrile neutropenic patients with cancer.


Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis.
We evaluated the effectiveness and safety of stereotactic ablative radiotherapy (SABR) delivered using Cyberknife in patients with stage I non-small-cell lung cancer. The clinical results of 153 patients with 161 lung cancers treated with CyberKnife between May 2014 and August 2020 at the Osaka University Hospital were retrospectively analyzed. The median age was 80 years (range=48-99 years). Nine patients (5.6%) had interstitial pneumonia. The median radiation dose was 52 Gy (range=40-70 Gy) in 4-10 fractions, and the median follow-up extended to 21.4 months (range=0-68.9 months). The 2-year local control, progression-free, and overall survival rates were 91.9%, 61.7%, and 84.8%, respectively. Toxicities of grade ≥3 were observed in 13 (8.1%) patients; one patient with interstitial pneumonia developed grade 5 radiation pneumonitis and one patient developed grade 5 bronchopulmonary hemorrhage. In patients with stage I non-small-cell lung cancer, SABR using Cyberknife was effective with acceptable toxicity.


T-cell lymphoma developing in Hodgkin's disease: evidence for two clones.
A case of peripheral T-cell lymphoma (PTL) occurring in a patient with Hodgkin's disease (HD) in relapse is described. The second neoplasm developed 25 months after the diagnosis of HD. Cytogenetic analysis on the lymph node biopsy at the time of diagnosis of PTL revealed the co-existence of two distinct, abnormal cell clones. The first clone was characterized by a reciprocal translocation t(5;7)(q13;q35) involving 7q35, namely the TCR-beta gene, as expected in T-cell lymphomas. The second cell clone carried trisomies for chromosomes 2, 5, 7, and 14. By immunophenotypic and molecular analysis as well as by in situ hybridization, it was possible to prove that the malignant T-cells and the Reed-Sternberg cells corresponded to different cell clones, one carrying the structural chromosome abnormalities and one carrying the numerical chromosome anomalies. These results indicate that the present case represented a true composite lymphoma.


[3H]spiperone binding in the nigrostriatal system in human brain.
The characteristics of [3H]spiperone binding in human brain were compared in three areas of the nigrostriatal pathway: areas containing the nerve terminals (caudate nucleus, putamen and pallidum); the area containing the cell bodies (substantia nigra pars compacta); the area containing the dendrites (pars reticulata). The affinity constants were calculated from saturation binding curves and from the kinetics of association and dissociation. The pharmacological profiles of the receptors was also established by displacement studies. The affinity constants and pharmacological profiles were similar in the striatum and the substantia nigra, although the latter contained a much smaller number of sites. In the substantia nigra, however, curved Scatchard plots were obtained, indicating that a second lower affinity site binding [3H]spiperone was also present. A considerable proportion (50%) of [3H]spiperone binding to nigral membranes could be displaced by the serotonin antagonist cinanserine , compared to the striatum (20%). The effect of post-mortem conditions on binding levels was studied in the rat. A loss of 20% occurred during the first hours after death, but was stable by 6 h until at least 24 h.


Nitrofurantoin not surface active agent in rabbit urinary bladder.
It has been recently suggested that nitrofurantoin may induce symptoms of interstitial cystitis by acting as a surface active agent that destroys glycosaminoglycan (GAG) on the bladder surface. Evidence accumulated over the past decade has demonstrated that the bladder surface GAG prevents bacterial adherence. In this experiment, exposure of the bladder lumen to nitrofurantoin at more than twice the therapeutic concentration did not destroy the bladder GAG layer (as evidenced by periodic acid-Schiff histochemistry) nor increase bacterial adherence as did a true surface active agent (Triton X-100). Acid treatment as well as all tested organic solvents except 50% dimethyl sulfoxide (DMSO) also removed the bladder GAG layer and increased bacterial adherence. These results indicate that neither nitrofurantoin nor 50% DMSO has adverse effects on the bladder surface and thus is unlikely to initiate the interstitial cystitis symptom complex by means of surfactant activity.


Effects of estrogens and progesterone on the catecholaminergic activity of the adrenal medulla in female rats.
Some reports in the literature allow to suspect the existence of an effect of sexual steroids on the adrenal catecholamines. To test this possibility, we have examined the catecholaminergic activity in the adrenal medulla of normal cycling rats in three phases of estrous cycle and of ovariectomized (OVX) rats injected with pharmacological doses of estradiol (ES), 2-hydroxyestradiol (HE) and/or progesterone (P). Adrenomedullary content of norepinephrine (NE) was similar during the estrous cycle, while epinephrine (E) content was increased during diestrous. This increase was concomitant with an increased phenylethanolamine-N-methyltransferase (PNMT) activity. Moreover, the monoamine oxidase (MAO) activity was significantly increased during proestrous, while the catechol-O-methyltransferase (COMT) activity was significantly decreased during estrous. In addition to these observations, ovariectomy caused a significant reduction of the E/NE ratio and of COMT and MAO activities. Administration of ES to OVX rats increased the E content, the E/NE ratio and the COMT activity as compared to vehicle-treated OVX rats. Administration of P to OVX animals led also to a significant increase of the E/NE ratio and of the COMT activity but not of the E content, while the administration of this steroid to OVX rats previously treated with ES only increased the COMT activity. Finally, administration of HE caused non-significant changes in NE and E contents and in MAO, COMT and PNMT activities. We can conclude that sexual steroids seem to be able to modify the catecholamine metabolism in the adrenal medulla and, hence, they could alter the ability of this gland to store and release these amines.


Radioimmunoassay of thromboxane B2 in horse plasma.
A radioimmunoassay for thromboxane B2 (TXB2) in unextracted horse plasma was evaluated. Sensitivity of the assay was 14.0 (SD 5.6) pg ml-1 of plasma. Interassay and intra-assay variation were 21.3 per cent and 4.3 per cent, respectively. The percentage of tracer bound in unextracted plasma in the absence of TXB2 was often higher than that in buffer. Therefore standard curves were obtained using standards diluted in plasma from horses treated with aspirin or in charcoal treated TXB2-free plasma. Standard curves determined in plasma and buffer were parallel. This assay was used to determine the half-life of exogenous TXB2 in horses. The mean value of 20.7 minutes (n = 3) is similar to that determined in other species. Storage of plasma samples at -20 degrees C for four months was found to alter the TXB2 levels in an unpredictable manner. Mean recovery was 102.4 per cent (SD 44.1). Effect of variability in sample collection and handling was assessed, but no consistent source of artifactual generation of TXB2 was found.


Polychlorinated biphenyls and their different level metabolites as inhibitors of glutathione S-transferase isoenzymes.
Research on the effects of polychlorinated biphenyl (PCB) toxicity tends to focus on commercial PCB congeners and parent PCBs themselves. However, studies have suggested that PCB metabolites may be more interesting than the parent compounds because of their high reactivity. As a key metabolic enzyme, glutathione S-transferases (GSTs) are responsible for detoxification by catalyzing the conjugation reaction of glutathione (GSH) to xenobiotics. Inhibition of GST activity indicates reduced detoxification ability. We investigated the inhibition of chicken liver GSTs by parent PCBs and their metabolites and observed dose-dependent inhibition in vitro; inhibitory efficiency declined in the order GSH-conjugate > mono-hydroxyl ≈ quinone ≈ hydroquinone > parent PCB. Structure-inhibitory activity relationship studies indicated that with the inhibitory activity greatly increases with the number of GSH moieties or chlorine substituents on the quinone ring. However, no significant linear relationship was observed for chlorine pattern changes on the phenyl ring. The reversibility of PCB metabolite inhibition of GSTs is discussed. PCB mono-hydroxyl, hydroquinone and quinone forms showed irreversible inhibition of GSTs, which suggests a mechanism involving covalent binding to cysteine residues in the GST active site. PCB glutathionyl conjugates showed reversible GST inhibition, implying non-covalent binding. Furthermore, reactive oxygen species did not significantly affect GST activity.


Progress in Imaging the Human Torso at the Ultrahigh Fields of 7 and 10.5 T.
Especially after the launch of 7 T, the ultrahigh magnetic field (UHF) imaging community achieved critically important strides in our understanding of the physics of radiofrequency interactions in the human body, which in turn has led to solutions for the challenges posed by such UHFs. As a result, the originally obtained poor image quality has progressed to the high-quality and high-resolution images obtained at 7 T and now at 10.5 T in the human torso. Despite these tremendous advances, work still remains to further improve the image quality and fully capitalize on the potential advantages UHF has to offer.


Purification of mouse myelin basic proteins by immunoaffinity chromatography.
The preparation of two immunosorbent columns specific for mouse myelin basic proteins (BPs) is described. The columns were prepared from either affinity purified mouse 14K-antibodies or bovine BP fragment (residues 1-115) antibodies. The column prepared from mouse 14K-antibodies bound 216-441 micrograms of mouse BPs within its working range at pH 4.5. The second column, prepared from antibodies specific for bovine fragment 1-115, bound 245-442 micrograms of mouse BPs under similar conditions. The ratios of 14K to 18.5 K proteins present in the immunopurified BPs reflected those in the samples originally applied onto the column. Therefore, both columns were equally effective for the small scale isolation of mouse BPs from whole brain. Because it is easier to prepare large quantities of bovine BP fragment 1-115 than the mouse 14K protein, it is less difficult to obtain antibodies against the bovine fragment. As a result, the use of immunosorbent columns containing immobilized bovine BP fragment 1-115-antibodies to purify mouse BPs represents a practical alternative to using immunosorbent columns prepared with mouse 14K-antibodies.


Antigenic variation in visna virus.
Two antigenic variants of visna virus were isolated sequentially from a single sheep inoculated with a plaque-purified strain of virus designated 1514. The genetically stable variants, LV1-1 and LV1-4, are of two classes: LV1-1 is partially neutralized by antibody to the inoculum strain 1514, while LV1-4 is not neutralized by antibody to 1514. The genetic mechanism responsible for generating the antigenic variants was investigated by comparing the chymotryptic and tryptic maps of the envelope glycoprotein gp135 and core polypeptides (p30, p16, p14), and by comparing the pattern of large oligonucleotides produced by digestion of the RNAs by T1 ribonuclease. We show that only the peptide maps of gp135 differ among strains, that the number of peptide fragments altered is small and that gp135 is the polypeptide that elicits neutralizing antibody. The maps of the RNAs are identical. We conclude that mutation in the glycoprotein gene rather than recombination is more probably responsible for antigenic variation, and speculate on the special aspects of visna virus replication relevant to this phenomenon.


Recovery of fuel from real waste oily sludge via a new eco-friendly surfactant material used in a digital baffle batch extraction unit.
This study focused on developing a new cocktail extraction agent (CEA) composed of solvent and a new surfactant material (SM) for enhancing the efficiency of fuel recovery from real waste oil sludge (WSO). The effects of different solvents (e.g. methyl ethyl ketone (MEK), naphtha, petrol and kerosene), SMs (Dowfax and sodium thiosulfate), extraction time (10-20 min), extraction temperatures (20-60 °C) and CEA/sludge ratios (1-4) on the extraction performance were investigated. SMs and DBBE design enhanced the extraction efficiency by increasing the dispersion of solvent in WSO and enhancing the mixing and mass transfer rates. Results proved that Dowfax was the best SM for oil recovery under various conditions. The best CEA (e.g. MEK and Dowfax) provides the maximum fuel recovery rate of 97% at a period of 20 min, temperature of 60 °C and 4:1 CEA/sludge ratio. The produced fuel was analysed and fed to the distillation process to produce diesel oil. The characteristics of diesel oil were measured, and findings showed that it needs treatment processes prior its use as a finished fuel.


Reversible cerebral vasoconstriction syndrome and dissection in the setting of COVID-19 infection.
The current COVID-19 pandemic has recently brought to attention the myriad of neuro- logic sequelae associated with Coronavirus infection including the predilection for stroke, particularly in young patients. Reversible cerebral vasoconstriction syndrome (RCVS) is a well-described clinical syndrome leading to vasoconstriction in the intracra- nial vessels, and has been associated with convexity subarachnoid hemorrhage and oc- casionally cervical artery dissection. It is usually reported in the context of a trigger such as medications, recreational drugs, or the postpartum state; however, it has not been described in COVID-19 infection. We report a case of both cervical vertebral ar- tery dissection as well as convexity subarachnoid hemorrhage due to RCVS, in a pa- tient with COVID-19 infection and no other triggers.


cdc and prt Mutants of Saccharomyces cerevisiae with increased sensitivity to diepoxybutane and ultraviolet.
The sensitivity to UV and DEB of nine temperature-sensitive mutants was investigated. All prt and four cdc mutants (cdc4, cdc7, cdc8, cdc28) showed a higher level of sensitivity to UV than the wild type strain. Three mutants cdc7, cdc9 and prt1 are more sensitive than the wild type to DEB, but only two cdc7 and prt1 are sensitive to UV and DEB. Treatment with restrictive temperature increases the sensitivity after UV treatment of cdc9, cdc21, prt1, prt3 and after DEB treatment of cdc28 and all prt mutants.


Baicalein alleviates doxorubicin-induced cardiotoxicity via suppression of myocardial oxidative stress and apoptosis in mice.
Doxorubicin is a widely used anthracycline derivative anticancer drug. Unfortunately, the clinical use of doxorubicin has the serious drawback of cardiotoxicity. In this study, we investigated whether baicalein, a bioflavonoid, can prevent doxorubicin-induced cardiotoxicity in vivo and we delineated the possible underlying mechanisms. Male BALB/c mice were treated with either intraperitoneal doxorubicin (15 mg/kg divided into three equal doses for 15 days) and/or oral baicalein (25 and 50 mg/kg for 15 days). Serum markers of cardiac injury, histology of heart, parameters related to myocardial oxidative stress, apoptosis and inflammation were investigated. Treatment with baicalein reduced doxorubicin-induced elevation of serum creatine kinase-MB isoenzyme (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and ameliorated the histopathological damage. Baicalein restored the doxorubicin-induced decrease in both enzymatic and non-enzymatic myocardial antioxidants and increased the myocardial expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1). Further studies showed that baicalein could inverse the Bax/Bcl-2 ratio, suppress doxorubicin-induced p53, cleaved caspase-3 and PARP expression and prevented doxorubicin-induced DNA damage. Baicalein treatment also interferes with doxorubicin-induced myocardial NF-κB signaling through inhibition of IκBα phosphorylation and nuclear translocation of p65 subunit. Doxorubicin elevated iNOS and nitrites levels were also significantly decreased in baicalein treated mice. However, we did not find any significant change (p>0.05) in the myocardial TNF-α and IL-6 levels in control and treated animals. Our finding suggests that baicalein might be a promising molecule for the prevention of doxorubicin-induced cardiotoxicity.


Non-invasive recording of His bundle activity in patients with Wolff-Parkinson-White syndrome.
Ten patients with Wolff-Parkinson-White syndrome underwent external His bundle recording using an advanced signal-averaging technique. Surface ECG waveforms were recorded and digitized at 1.28 kHz (10 bit resolution) and then averaged with a CDC-6600 computer. A cross-correlation function, operating in the frequency domain (using the Fast Fourier Transform algorithm) was employed to extract fiducial synchronizing marks for the waveform alignment. Using this technique, reliable His bundle activity could be recorded in nine of ten patients. There was a good correlation between the HQ and HV intervals obtained during external and internal His bundle recordings, respectively, in seven patients who underwent both recordings. Administration of ajmaline enabled to obtain the His bundle activity using a digital filter with low frequency cut-off of 30 Hz as compared to the cut-off of 150 Hz which was necessary during control to reduce the electrical activity of the delta wave. We conclude that using a computerized cross-correlation signal-averaging technique enables the external His bundle recording in patients with WPW syndrome.


The impact of a partially effective HIV vaccine on a population of intravenous drug users in Bangkok, Thailand: a dynamic model.
Because of the variability of HIV, the first AIDS vaccine is likely to be only partially effective. There is some concern among scientists that a low-efficacy vaccine could worsen the HIV epidemic if vaccinated individuals increase their risk behavior under the false assumption of immunity. To address this concern, we constructed a dynamic compartmental model that simulated the course of the HIV/AIDS epidemic in a population of injection drug users in Bangkok, Thailand. The model calculated long-term HIV prevalence, number of AIDS cases, and total population size for two scenarios: vaccination program versus no vaccination program. We used sensitivity analyses to evaluate the impact of postvaccination risk behavior change on HIV prevalence. A 75% effective vaccine led to a 40-year HIV prevalence of 37% with vaccination and 50% without vaccination. Postvaccination behavior change had only a limited effect on the results with a 75% effective vaccine but a significant effect with a 30% effective vaccine. If 90% of low-risk individuals responded to a 30% effective vaccine with increased high-risk behavior, the benefit of vaccination disappeared. These results agree with analyses of the epidemic among gay men. If injection drug behavior is indeed modifiable, our findings have significant policy and planning implications.


Mortality and morbidity risks vary with birth weight standard deviation score in growth restricted extremely preterm infants.
To assess whether the mortality and morbidity risks vary with birth weight standard deviation score (BWSDS) in growth restricted extremely preterm infants. This was a multicenter retrospective cohort study using the database of the Neonatal Research Network of Japan and including 9149 infants born between 2003 and 2010 at <28 weeks gestation. According to the BWSDSs, the infants were classified as: <-2.0, -2.0 to -1.5, -1.5 to -1.0, -1.0 to -0.5, and ≥-0.5. Infants with BWSDS≥-0.5 were defined as non-growth restricted group. After adjusting for covariates, the risks of mortality and some morbidities were different among the BWSDS groups. Compared with non-growth restricted group, the adjusted odds ratio (aOR) for mortality [aOR, 1.69; 95% confidence interval (CI), 1.35-2.12] and chronic lung disease (CLD) (aOR, 1.28; 95% CI, 1.07-1.54) were higher among the infants with BWSDS -1.5 to <-1.0. The aOR for severe retinopathy of prematurity (ROP) (aOR, 1.36; 95% CI, 1.09-1.71) and sepsis (aOR, 1.72; 95% CI, 1.32-2.24) were higher among the infants with BWSDS -2.0 to <-1.5. The aOR for necrotizing enterocolitis (NEC) (aOR, 2.41; 95% CI, 1.64-3.55) was increased at a BWSDS<-2.0. Being growth restricted extremely preterm infants confer additional risks for mortality and morbidities such as CLD, ROP, sepsis and NEC, and these risks may vary with BWSDS.


Sulfur-aided aerobic biostabilization of swine manure and sawdust mixture: Humification and carbon loss.
To investigate how sulfur addition affects humification and carbon loss during swine manure (SM) biostabilisation, various proportions of sulfur, i.e., 0 (CK), 0.2%-0.8% (S1-S4) were added to SM in a 70-day pilot-scale test. Compared to CK (16.07%), sulfur addition resulted in the mineralization of 17.05%-24.27% of the total organic carbon. Sulfur addition also reduced CH4 emissions, which were 3.7%-29.3% lower than that of CK. The total global warming potential values were in the range of 913.1-968.2 g CO2 eq kg-1 for all treatments. Although the sulfur-added treatments showed lower HA/FA ratios than CK after 70 days, no significant impact on the maturity of the final products was observed. Sulfur addition impacted the microbial community, CH4, CO2, N2O emissions, and affected the variation of temperature in biowaste biostabilization. These discoveries provided an important basis for understanding the function of sulfur in regulating the aerobic bio-decomposition of organic waste.


IoT Contextual Factors on Healthcare.
With the emergence of the Internet of Things, new services in healthcare will be available and existing systems will be integrated in the IoT framework, providing automated medical supervision and efficient medical treatment. Context awareness plays a critical role in realizing the vision of the IoT, providing rich contextual information that can help the system act more efficiently. Since context in healthcare has its unique characteristics, it is necessary to define an appropriate context aware framework for healthcare IoT applications. We identify this context as perceived in healthcare applications and describe the context aware procedures. We also present an architecture that connects the sensors that measure biometric data with the sensory networks of the environment and the various IoT middleware that reside in the geographical area. Finally, we discuss the challenges for the realization of this vision.


Analysis of alkylphenols, bisphenols and alkylphenol ethoxylates in microbial-fermented functional beverages and bottled water: Optimization of a dispersive liquid-liquid microextraction protocol based on natural hydrophobic deep eutectic solvents.
In this work, the analysis of alkylphenols, bisphenols and alkylphenol ethoxylates in bottled waters, kombuchas and water kefir was performed through a vortex-assisted dispersive liquid-liquid microextraction method based on a natural hydrophobic eutectic solvent. For this purpose, mixtures of monoterpenes and fatty acids were employed. Different factors affecting extraction were optimized and the method was validated in terms of matrix effect, linearity, limits of detection and recovery. Recovery values varied between 70.0 and 124.3% (except for 4-tert-butylphenol: 67.0% and 4-n-nonylphenol: 60.8% in water kefir) and limits of detection were in the range 0.10 ng/L - 2.99 µg/L. Finally, 8 bottled waters, 8 kombuchas and 4 water kefirs were analyzed and 4-tert-octylphenol monoethoxylate was detected in water (20.28 ± 0.99 - 62.08 ± 3.63 µg/L). This is the first application analyzing xenobiotic contaminants in kombucha and water kefir and the first time in which the three types of compounds are simultaneously extracted by dispersive liquid-liquid microextraction.


A prediction model for cesarean delivery based on the glycemia in the second trimester: a nested case control study from two centers.
Maternal glycemia is associated with the risk of cesarean delivery (CD); therefore, our study aims to developed a prediction model based on glucose indicators in the second trimester to earlier identify the risk of CD. This was a nested case-control study, and data were collected from the 5th Central Hospital of Tianjin (training set) and Changzhou Second People's Hospital (testing set) from 2020 to 2021. Variables with significant difference in training set were incorporated to develop the random forest model. Model performance was assessed by calculating the area under the curve (AUC) and Komogorov-Smirnoff (KS), as well as accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). A total of 504 eligible women were enrolled; of these, 169 underwent CD. Pre-pregnancy body mass index (BMI), first pregnancy, history of full-term birth, history of livebirth, 1 h plasma glucose (1hPG), glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), and 2 h plasma glucose (2hPG) were used to develop the model. The model showed a good performance, with an AUC of 0.852 [95% confidence interval (CI): 0.809-0.895]. The pre-pregnancy BMI, 1hPG, 2hPG, HbA1c, and FPG were identifies as the more significant predictors. External validation confirmed the good performance of our model, with an AUC of 0.734 (95%CI: 0.664-0.804). Our model based on glucose indicators in the second trimester performed well to predict the risk of CD, which may reach the earlier identification of CD risk and may be beneficial to make interventions in time to decrease the risk of CD.


Discovery of curcumin inspired sulfonamide derivatives as a new class of carbonic anhydrase isoforms I, II, IX, and XII inhibitors.
A series of curcumin inspired sulfonamide derivatives was prepared from various chalcones and 4-sulfamoyl benzaldehyde via Claisen-Schmidt condensation. All new compounds were assayed as inhibitors of four human isoforms of the metalloenzyme carbonic anhydrase (hCA, EC 220.127.116.11) isoforms hCA I, II, IX and XII. Interesting inhibitory activities were observed against all these isoforms. hCA I, an isoform involved in several eye diseases was inhibited moderately with KIs in the range of 191.8-904.2 nM, hCA II, an antiglaucoma drug target was highly inhibited by the new sulfonamides, with KIs in the range of 0.75-8.8 nM. hCA IX, a tumor-associated isoform involved in cancer progression and metastatic spread was potently inhibited by the new sulfonamides, with KIs in the range of 2.3-87.3 nM, whereas hCA XII, and antiglaucoma and anticancer drug target, was inhibited with KIs in the range of 6.1-71.8 nM. It is noteworthy that one of the new compounds, 5d, was found to be almost 9 times more selective against hCA II (KI = 0.89 nM) over hCA IX and hCA XII, whereas 5e was 3 and 70 times more selective against hCA II (KI = 0.75 nM) over hCA IX and hCA XII, respectively.


Hypogonadotropic secondary amenorrhea in diabetes: effects of central opiate blockade and improved metabolic control.
The effect of improving diabetic control on secondary hypogonadotropic amenorrhea was investigated in patients with insulin-dependent diabetes mellitus (IDDM). Second, the hypothesis that increased central (hypothalamic) opiate inhibition may have been responsible for the suppression of gonadotropin-releasing hormone (GnRH) was tested by observing the effect of a four-hour naloxone infusion (1.4 mg/hour) on serum gonadotropin levels. All known causes of secondary amenorrhea were excluded before patients were eligible for the study. The median duration of amenorrhea was six years, and median body weight was 101 percent of ideal. After six months of improved metabolic control (n = 5) using intensified conventional therapy or continuous subcutaneous insulin infusion, the level of glycosylated hemoglobin dropped from 11.8 +/- 0.9 percent to 8.5 +/- 0.5 percent (p less than 0.005), and body weight increased from 60.5 +/- 1.8 kg to 64.7 +/- 1.4 kg (p less than 0.02). Menses did not, however, return in any patient. There was no significant change in serum levels of estradiol, progesterone, dihydroxyepiandrosterone, testosterone, prolactin, basal or GnRH-stimulated luteinizing hormone, or follicle-stimulating hormone. There was no change in the levels of luteinizing hormone or follicle-stimulating hormone during the naloxone infusion either during poor metabolic control or after six months of improved metabolic control. In conclusion, a form of secondary hypogonadotropic amenorrhea was identified in patients with IDDM that did not remit with sustained improvements in metabolic control. It did not appear to be mediated through increased central opiate tone.


Alkaline induction of a novel gene locus, alx, in Escherichia coli.
A novel pH-regulated locus inducible over 100-fold in alkaline media was identified in Escherichia coli through screening of 93,000 Mu dI1734 (lacZ Kmr) operon fusions at pH 6.5 and pH 8.5. Four lacZ fusions that showed expression only at the higher pH were mapped at 67.5 min by P1 transduction crosses. The locus was designated alx.


Intraoperative Three-dimensional Imaging of Ventricular Septal Defects in Children Using Epicardial Echocardiography: A Novel Approach.
To assess the feasibility and accuracy of intraoperative three-dimensional (3D) epicardial en face images of ventricular septal defects (VSD) in children using the 3D transesophageal echocardiography (TEE) probe as an epicardial probe. This was a prospective nonrandomized blinded observational study. The study was conducted at a single tertiary cardiac care center. Fifty pediatric patients, weighing between 5.0 kg and 20 kg, who were scheduled for elective surgical closure of their VSDs, prospectively were recruited for this study. Epicardial 3D images were acquired using the full-volume mode. VSD location and size were determined from the 3D data sets using multiplanar reconstruction mode (QLAB 9) by a blinded investigator. The accuracy in terms of location and size was compared with surgical findings. In 50 study subjects, 54 VSDs were located by epicardial 3D echocardiography (3DE): 12 perimembranous, 17 inlet, eight muscular, 15 malaligned, and two outlet. Average image acquisition time was 4.96 (±1.47) minutes. Average image reconstruction time was 6.18 (±1.93) minutes. Good en face views of the VSD could be rendered in all patients (100% feasibility). The highest image quality was for perimembranous and malaligned VSDs. The location of VSD by 3DE corresponded precisely with surgical findings (100% accuracy). With linear regression analysis, excellent correlation was observed between the diameters measured by surgery and that measured by 3DE from the right ventricle side (r2 = 0.97, p < 0.001). The authors' study demonstrated that diagnostic quality 3D en face images of VSD can be obtained intraoperatively using 3D epicardial echocardiography. The short acquisition and reconstruction times make this technique clinically applicable.


Distribution and possible roles of the highly polysialylated neural cell adhesion molecule (NCAM-H) in the developing and adult central nervous system.
The neural cell adhesion molecule (NCAM) is a cell surface glycoprotein which is thought to mediate cell adhesion and recognition. During developmental stages, NCAM is highly polysialylated (NCAM-H) by a unique alpha-2,8-linked polysialic acid chain (PSA), and this PSA portion of NCAM-H has been found to be closely associated with various developmental processes of the nervous system. Further, recent immunohistochemical investigations have revealed that even in the adult nervous system, a persistent PSA expression has been found confined to several regions: the olfactory bulb, the piriform cortex, the hippocampal dentate gyrus, the hypothalamus, some nuclei of the medulla and the dorsal horn of the spinal cord, which are related directly or indirectly to sensory systems. Moreover, in the dentate gyrus and olfactory bulb the expression is connected with adult neurogenesis that may add new neuronal circuits to the adult neural tissue. Therefore, the possible role of NCAM-H in the central nervous system may be associated not only with neural development, but also with adult functions, such as the processing system of sensory information and neuronal plasticity.


Governance and funding best practices for embedded research programs.
Health systems are increasingly embracing embedded research (ER) program models that allow researchers to integrate into operational and clinical practices. Successful ER programs rely on unique funding streams and bidirectional relationships with health system operational and executive leaders. This commentary summarizes current practices and recommendations for funding and governing ER programs. Three funding best practices are recommended: a mixed portfolio of short-term and long-term projects funded through a combination of internal and external sources; leveraging the community benefit requirement of non-profit hospitals and forming connections in the development office; and a research and implementation franchise model. Governance best practices include a strong relationship between researchers, operational and executive leaders and an external advisory committee to ensure that research topics are relevant to the needs of patients, the health system, and other stakeholders. These recommended best practices can help lay the foundation for early attempts to identify shared challenges and successes as health systems establish new ER programs and existing programs continue to mature.


Serine proteinase inhibitors in the Compositae: distribution, polymorphism and properties.
Multiple molecular forms of inhibitors of trypsin (TI) and chymotrypsin (CI), which are typical digestive enzymes of insects, mammals and micro-organisms, and subtilisin (SI), a proteinase of many bacteria and phytopathogenic fungi, were identified in seeds and vegetative organs of the majority of 128 wild and cultivated species representing 65 genera of three of the subfamilies of the Compositae. Inhibitors with M(r) ranging from 7450 to 7800 and combining activities towards subtilisin and trypsin and/or chymotrypsin (T/C/SI) had the widest distribution and may be involved in plant defense mechanisms. They were found in many species of the subfamilies Carduoideae (genera Carthamus, Centaurea, Cirsium), Cichorioideae (Lactuca, Taraxacum) and Asteroideae (Helianthus, Cosmos, Bidens). Partial amino acid sequencing showed that the safflower (Carthamus tinctorius) T/C/SI and Cosmos bipinnatus T/C/SI, T/SI and C/SI belonged to the potato I inhibitor family. The most active, variable and heterogeneous inhibitors were found in species of the tribe Heliantheae, which is placed in the evolutionary advanced subfamily Asteroideae. Seeds of Helianthus species, Eclipta prostrata, Gailardia aristata, Zinnia elegans and Silphium perfoliatum contained various TI with M(r) ranging from 1500 to 14,750, with some also containing SI. H. annuus seeds contain a unique cyclic TI of M(r) 1514 and similar TI were also present in other Helianthus spp. and the related species Tithonia diversifolia. Zinnia elegans contained a TI with M(r) 11,350 which appeared to represent a novel type of inhibitor distantly related to the cereal subgroup of Bowman-Birk inhibitors. TI and T/SI varied widely in H. annuus lines and wild Helianthus species in their presence or absence and composition. Similar T/SI components were found in the cultivated diploid H. annuus and annual diploid species with the B genome but not in perennials with the A genome. Some T/SI, SI and TI were detected in vegetative organs of sunflower and other Compositae. Studies of the polymorphism and distribution of proteinase inhibitors are relevant to the evolution of protective protein systems and the mechanisms of resistance to pathogenic organisms in the Compositae and other plants.


Biweekly carboplatin/gemcitabine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: report of efficacy, quality of life and geriatric assessment.
We evaluated safety and efficacy of first-line gemcitabine/carboplatin in unfit-for-cisplatin patients with advanced urothelial carcinoma and the effect on the quality of life and functional status of elderly patients (aged >70). Unfit patients had ECOG performance status (PS) > or =2, creatinine clearance <50 ml/min or comorbidities precluding cisplatin administration. Carboplatin at area under the curve of 2.5 and gemcitabine 1,250 mg/m(2) were administered biweekly. Elderly patients were stratified into group 1 (no activities of daily living (ADL) or instrumental ADL dependency and no comorbidities), group 2 (instrumental ADL dependency or 1-2 comorbidities) and group 3 (ADL dependency or > or =2 comorbidities). Thirty-four patients were enrolled: 68% had PS 2-3, 69% a creatinine clearance <50 ml/min and 65% had 1 or more comorbidities. There were 3 cases of grade 3 toxicity (9%). Response rate was 24% [95% confidence interval (CI) 11-41]. Median follow-up was 8 months, median progression-free survival 4.4 months (95% CI 1.03-7.75) and median overall survival 9.8 months (95% CI 4.7-14.9). Patients in geriatric assessment groups 1 and 2 had a significantly longer median progression-free survival compared to group 3 [6.9 months (95% CI 1.3-12.4) vs. 1.9 months (95% CI 0.5-3.2); p = 0.005]. First-line gemcitabine/carboplatin combination is active in unfit-for-cisplatin patients with advanced urothelial carcinoma. Pretreatment quality of life and geriatric assessment may be useful in selecting patients likely to benefit from this treatment.


Relation of white-matter microstructure to reading ability and disability in beginning readers.
[Correction Notice: An Erratum for this article was reported in Vol 31(5) of Neuropsychology (see record 2017-22816-001). Errors in the dataset owing to two incorrect scores have skewed results. In the 2nd paragraph of the Results section, the 2nd sentence should read: "Within the typical reader group, FA in the left AF correlated negatively with pseudoword reading (WRMT-III Word Attack: rs = .37, p = .064), but not real-word reading (WRMT-III Word Identification: rs = .07, p = .75)." The 4th sentence of the 3rd paragraph should read: "The negative correlation between FA and Word Attack in the typical reader group was driven by Daxial (Dradial: rs = .19, p = .373, Daxial: rs = .38, p = .060)." The 2nd sentence of the 4th paragraph should read: "Results of this analysis replicated those of the larger reading disability group, with a statistically greater reduction of FA in this more severely affected group (p = .008) that was associated with a significant increase in Dradial (p = .008) and no difference in Daxial (p = .47)." In Table 1, for the typical reader group, the resulting values should read: age, 94.00 ± 7.66; KBIT-2-Matrices, 118.31 ± 15.24; WRMT-III-Word Identification, 119.00 ± 9.33; WRMT-III-Word Attack, 114.04 ± 9.31; and TOWRE-2-Sight Word Efficiency, 114.48 ± 8.07. For the reading disability group, the resulting values for age and TOWRE-2- Phonemic Decoding Efficiency should be 93.65 ± 7.81 and 81.76 ± 9.33, respectively. The p values for age and KBIT-2-Matrices should be .87 and .172, respectively. In Figure 3, the image for the typical reader group has been replaced. All versions of this article have been corrected.] Objective: We examined the white-matter microstructure of the left arcuate fasciculus, which has been associated with reading ability, in beginning readers with or without reading disability. Groups were typically reading children (n = 26) or children with reading disability (n = 26), Ages 6-9, and equated on nonverbal cognitive abilities. Diffusion-weighted images were collected and TRACULA was used to extract fractional anisotropy measures from the left arcuate fasciculus. White-matter microstructure was altered in children with reading disability, who exhibited significantly reduced fractional anisotropy in the left arcuate fasciculus. Among typically reading children, lower fractional anisotropy of the left arcuate fasciculus was associated with superior pseudoword reading performance. Both the group differences and variation in reading scores among the children with reading disability were associated with radial diffusivity (but not axial diffusivity), whereas variation in reading scores among typically reading children was associated with axial diffusivity (but not radial diffusivity). The paradoxical findings that lower fractional anisotropy was associated both with reading disability and also with better phonological awareness in typical reading development suggest that there are different maturational trajectories of white-matter microstructure in typical readers and children with reading disability, and that this difference is unique to the beginning stages of reading acquisition. The finding that reading disability was associated with radial diffusivity, but that variation in ability among typically developing readers was associated with axial diffusivity, suggests that different neural mechanisms may be associated with reading development in children with or without reading disability. (PsycINFO Database Record


Reactive oxygen species, essential molecules, during plant-pathogen interactions.
Reactive oxygen species (ROS) are continually generated as a consequence of the normal metabolism in aerobic organisms. Accumulation and release of ROS into cell take place in response to a wide variety of adverse environmental conditions including salt, temperature, cold stresses and pathogen attack, among others. In plants, peroxidases class III, NADPH oxidase (NOX) locates in cell wall and plasma membrane, respectively, may be mainly enzymatic systems involving ROS generation. It is well documented that ROS play a dual role into cells, acting as important signal transduction molecules and as toxic molecules with strong oxidant power, however some aspects related to its function during plant-pathogen interactions remain unclear. This review focuses on the principal enzymatic systems involving ROS generation addressing the role of ROS as signal molecules during plant-pathogen interactions. We described how the chloroplasts, mitochondria and peroxisomes perceive the external stimuli as pathogen invasion, and trigger resistance response using ROS as signal molecule.


Lifespan of subcutaneous glucose sensors and their performances during dynamic glycaemia changes in rats.
Performances of a glucose sensor have been investigated during dynamic variations of plasma glucose levels. Subcutaneous glucose concentrations measured by the sensors were calculated by a one-point calibration, performed in basal conditions. A first group of sensors were chronically implanted in the subcutaneous tissue of normal rats. The animals were submitted to glucagon and insulin injection, in order to induce rapid modifications of their glycaemia. This test was repeated at different days after implantation in order to investigate the lifespan and the performance of the sensors. All the sensors were working 1 or 2 days after implantation, and 70% adequately responded to glycaemia variations at day 3 or 4. The quality of the sensors' performance remained constant as a function of the time. With a second group of sensors, we demonstrated that an efficient sterilization procedure did not alter the sensors' characteristics. At the day of implantation, the sterilized sensors' performance, during dynamic variations of plasma glucose levels, was closely similar to that of the non-sterilized sensors. The animals bearing the sterilized devices were rendered diabetic by streptozotocin (STZ) injection. Once the rats had developed a severe hyperglycaemia (1-3 days after STZ), they were injected with intravenous insulin. The subcutaneously implanted glucose sensors correctly followed the decline in plasma glucose levels. We therefore conclude that our sensor could represent a useful tool for short-term continuous blood monitoring.


Local delivery of magnetic resonance (MR) contrast agent in kidney using thermosensitive liposomes and MR imaging-guided local hyperthermia: a feasibility study in vivo.
To investigate the feasibility of local delivery of a magnetic resonance (MR) contrast agent in vivo using paramagnetic thermosensitive liposomes and infrared (IR) laser-induced local hyperthermia under real-time MR thermometry on rabbit kidney. Respiratory gated, radio frequency (RF)-spoiled gradient-echo sequences were used for precise MR temperature mapping (SD = 1 degrees C). In vivo heating experiments confirmed local release of MR contrast agent from liposomes. T1 decreased from 800 msec to about 500 msec, as measured after tissue cooling, in those locations where the renal parenchyma was heated above the phase transition temperature of the liposome membrane. The release of MR contrast agent has been demonstrated in rabbit kidney in vivo. This may be used as a reporter for simultaneous release of therapeutic agents.