Fine-needle aspiration and surgical pathology of infectious lesions. Morphologic features and the role of the clinical microbiology laboratory for rapid diagnosis.
There has been a renewed interest in the use of imprint smears at the time of frozen section in surgical pathology and FNA biopsy for the diagnosis of infectious disease because of the increasing need for rapid diagnosis of opportunistic infections in immunocompromised patients. Moreover, the use of FNA biopsy for the evaluation of superficial and deep masses has become more widespread. The critical step in the FNA biopsy and in evaluation of imprint smears from surgical specimens is immediate interpretation of the slides that have been stained by rapid methods as the Diff-Quik technique. This quick interpretation can identify as infectious case that may need ancillary studies such as a separate pass or more tissue for microbiologic examination and special stains on the aspirated smears, sections, or cell block. An infectious case may be suspected when the basic cytologic inflammatory patterns are identified including acute inflammation, chronic inflammation, granulomatous inflammation, or necrosis. There have been numerous reports describing the cytomorphologic features of several organisms seen in FNA and tissue specimens. The pathologist also needs to be aware of the potential for a false-negative diagnosis of neoplasms in those lesions having a prominent inflammatory component as well as the potential for false-positive diagnosis of malignancy when inflammatory atypia and a repair reaction is present. The interaction of anatomic pathologists and clinical microbiologists is essential for appropriate workup of specimens with an infectious disease etiology. Thus, pathologists need to be well versed in both the anatomic and clinical pathology features of infectious diseases. Finally, those involved with FNA biopsy and handling of surgical pathology specimens should use universal precautions, since all patients are potentially infectious with the HIV virus and other communicable agents.


The solution of an integral equation with its application to human joints.
The fundamental fluid transport mechanisms in a cavity of a joint and the deformation of the bearing surfaces are important for the understanding of the bio-mechanical process involved in the physiology of normal and pathological synovial joints. We present here a study of elasto-rheodynamic lubrication of a self-acting dynamically loaded bearing which employs a porous, elastic material (articular cartilage) and a visco-elastic non-linear lubricant (synovial fluid). The tangible solution of the model is, finally, subjected to the resolution of a non-linear integral equation. Important conclusion is drawn from the results obtained for bearing characteristics which show the self-adjusting nature of human joints.


Exploring food waste during the COVID-19 pandemic among Malaysian consumers: The effect of social media, neuroticism, and impulse buying on food waste.
The amount of food being thrown away despite being in an edible condition has become alarming in countries with populations with medium and high incomes. Changes in consumer behaviour, such as overbuying, are some of the major impetuses of food waste. This study aimed to examine the relationship between food waste and social media usage, neuroticism, and impulse buying. The mediating role of impulse buying and the moderating role of neuroticism on food waste during the coronavirus (COVID-19) pandemic were also uncovered in this study. A self-administered online survey was distributed to a total of 274 consumers who had experienced a lockdown during the COVID-19 outbreak and were also regular buyers of food. Empirical findings supported the fact that social media usage, neuroticism, and impulse buying were positively related to food waste. Impulse buying mediates the relationship between social media usage and food waste, as well as between neuroticism and food waste. The study results also revealed that neuroticism positively moderates the relationship between social media usage and food waste. This paper offers new insights into efforts for sustainable food consumption to tackle the issue of food waste.


Messages conveyed by spinocerebellar pathways during scratching in the cat. I. Activity of neurons of the lateral reticular nucleus.
(1) Signals transmitted to the cerebellum by the spino-reticulocerebellar pathway (SRCP) during scratching were studied. For this purpose, the activity of neurons of the lateral reticular nucleus (LRN), which are the last-order neurons of the SRCP, was recorded during scratching in thalamic cats. Scratching was evoked by stimulation of the pinna. LRN neurons were identified antidromically by stimulation of the hindlimb area in the cerebellar anterior lobe. In most experiments, animals were immobilized with Flaxedil, and stimulation of the pinna resulted in fictitious scratching, i.e., in periodical reciprocal activity of flexor and extensor motoneurons typical of actual scratching. (2) During both actual and fictitious scratching, the discharge frequency of LRN neurons was rhythmically modulated in relation with the scratch cycle. Most LRN neurons fired in short high-frequency bursts of spikes which coincided (completely or partly) with the extensor phase of the cycle. In this respect the SRCP differs from the ventral spinocerebellar tract (VSCT) which is maximally active in the flexor phase of the cycle. (3) The firing pattern of LRN neurons during fictitious scratching was similar to that during actual scratching. Therefore, the rhythmical burst firing of LRN neurons is determined mainly by the central mechanisms and not by the rhythmical sensory input. (4) Rhythmical modulation of LRN neurons disappeared after transection of the ipsilateral lateral funiculus of the spinal cord in which spinoreticular fibers are located. On the other hand, considerable reduction of rhythmical activity in descending brainstem-spinal pathways after contralateral hemisection of the spinal cord did not affect the discharge pattern of LRN neurons. These two facts indicate that the SRCP conveys mainly messages about activity of the central spinal mechanisms, and that influences of supraspinal motor centers.on LRN neurons and on spinoreticular neurons are of minor importance. (5) Axonal terminations of LRN neurons are distributed rather evenly over the hindlimb area in the anterior lobe of the cerebellum. Therefore, messages about the events, which happen within the spinal cord in the vicinity of the extensor phase of the cycle, arrive at every point of the hindlimb area.


Possibility of selection against mtDNA mutations in tumors.
Several studies of tumors have revealed substantial numbers of clonally expanded somatic mutations in mitochondrial DNA (mtDNA), not observed in adjacent intact tissues. These findings were interpreted as indicating the involvement of mtDNA mutations in tumorigenesis. Such comparisons, however, ignore an important confounding factor: the monoclonal origin of tumors as opposed to the highly polyclonal nature of normal tissues. Analysis of recently published data on the incidence of somatic mutations in nontumor monoclonal cells suggests that, contrary to the prevailing view, the process of tumorigenesis may be accompanied by active selection against detrimental mtDNA mutations.


Emotionally unskilled, unaware, and uninterested in learning more: reactions to feedback about deficits in emotional intelligence.
Despite the importance of self-awareness for managerial success, many organizational members hold overly optimistic views of their expertise and performance-a phenomenon particularly prevalent among those least skilled in a given domain. We examined whether this same pattern extends to appraisals of emotional intelligence (EI), a critical managerial competency. We also examined why this overoptimism tends to survive explicit feedback about performance. Across 3 studies involving professional students, we found that the least skilled had limited insight into deficits in their performance. Moreover, when given concrete feedback, low performers disparaged either the accuracy or the relevance of that feedback, depending on how expediently they could do so. Consequently, they expressed more reluctance than top performers to pursue various paths to self-improvement, including purchasing a book on EI or paying for professional coaching. Paradoxically, it was top performers who indicated a stronger desire to improve their EI following feedback.


Comparison of perioperative morbidity of anterior cruciate ligament autografts versus allografts.
We present a retrospective report of 50 patients (31 autograft and 19 allograft patients) who underwent arthroscopic bone-patellar tendon-bone anterior cruciate ligament (ACL) reconstructions between August 1988 and September 1990. All patients were followed for a minimum of 2 years. The purpose of this study was to analyze each group regarding hospital stay, swelling, thigh atrophy, laxity, strength, endurance, range of motion, patellofemoral symptoms, and complications. We found no statistical difference between autograft or allograft ACL reconstructions with regard to perioperative morbidity.


Malignant melanoma cells acquire resistance to DNA interstrand cross-linking chemotherapeutics by p53-triggered upregulation of DDB2/XPC-mediated DNA repair.
Malignant melanoma is a cancer characterized by high chemoresistance although p53 is rarely mutated. Here, we show that p53 wild-type melanoma cells acquire resistance to cell death induced by fotemustine (FM), which is a representative of alkylating DNA interstrand cross-linking agents used in melanoma therapy. We show that drug-induced resistance is a result of p53-dependent upregulation of the nucleotide excision repair (NER) genes xeroderma pigmentosum complementation group C (XPC) and damaged DNA-binding protein 2 (DDB2), which stimulate the repair of DNA interstrand cross-links (ICLs) arising from O(6)-chloroethylguanine. Consequently, TP53 mutated cells are unable to repair ICLs, leading to prolonged ATM, ATR and checkpoint kinase 1 (CHK1) activation, and finally apoptosis. The roles of p53 and NER in ICL-triggered cell death were confirmed by knockdown of p53 and XPC. Upregulation of XPC and DDB2 in p53wt cells following a single drug treatment is a robust and sustained response that lasts for up to 1 week. Pretreatment with an inducing dose followed by a high and toxic dose of FM provoked an adaptive response as the killing outcome of the challenge dose was reduced. Upregulation of XPC and DDB2 was also observed in a melanoma mouse xenograft model following systemic administration of FM. Additionally, XPC and DDB2 induction occurred upon treatment with other cross-linking anticancer drugs, such as cisplatin and mafosfamide, indicating it is a general response of cancer cells to this group of chemotherapeutics. Collectively, the data indicate that p53-dependent upregulation of XPC and DDB2 is a key mechanism upon genotoxic stress, whereby melanoma cells acquire resistance towards DNA cross-linking agents. To our knowledge, this is the first demonstration of upregulation of NER following a single dose of a DNA interstrand cross-linker, which is a robust and long-lasting effect that impacts the killing response of cancer cells to subsequent treatments.


Predictors of respiratory bacterial co-infection in hospitalized COVID-19 patients.
The primary objectives were to determine the prevalence of and identify variables associated with respiratory bacterial co-infection in COVID-19 inpatients. Secondary outcomes included length of stay and in-hospital mortality. Eighty-two (11.2%) of 735 COVID-19 inpatients had respiratory bacterial co-infection. Fifty-seven patients met inclusion criteria and were matched to three patients lacking co-infection (N = 228 patients). Patients with co-infection were more likely to receive antibiotics [57 (100%) vs 130 (76%), P < 0.0001] and for a longer duration [19 (13-33) vs 8 (4-13) days, P < 0.0001]. The multi-variable logistic regression model revealed risk factors of respiratory bacterial co-infection to be admission from SNF/LTAC/NH (AOR 6.8, 95% CI 2.6-18.2), severe COVID-19 (AOR 3.03, 95% CI 0.78-11.9), and leukocytosis (AOR 3.03, 95% CI 0.99-1.16). Although respiratory bacterial co-infection is rare in COVID-19 inpatients, antibiotic use is common. Early recognition of respiratory bacterial coinfection predictors in COVID-19 inpatients may improve empiric antibiotic prescribing.


Molecular cloning and expression of Octamer-binding transcription factor (Oct4) in the large yellow croaker, Larimichthys crocea.
Octamer-binding transcription factor 4 (Oct4) is a crucial pluripotent transcription factor in controlling pluripotency of embryonic stem cells (ESCs), formation of primordial germ cells (PGCs), early embryonic development, and gonadal germ cells. To understand the roles of Oct4 in the large yellow croaker (Larimichthys crocea) (Lc-Oct4), the full-length cDNA of Oct4 was cloned and analyzed. Lc-Oct4 includes a 104-bp 5' untranslated region (UTR), a 567-bp 3' UTR and a 1431-bp coding region encoding a protein of 476 amino acids (aa) with a predicted molecular mass (Mm) of 52.40 kDa and an isoelectric point (PI) of 6.34. Quantitative real time PCR (qRT-PCR) in tissues showed that Lc-Oct4 was only expressed in ovary. During ovarian development, the expression level in 635 days post hatching (635-dph) ovary was about 6.3-fold higher than in 270-dph and 1000-dph ovary. The in situ hybridization analysis showed that Lc-Oct4 had a high expression in the different developmental stages of oocytes with the highest level in stages II (later) and III oocytes. Lc-Oct4 was also expressed in spermatogonia and primary spermatocytes. Furthermore, the qRT-PCR analysis of Lc-Oct4 in different developmental embryos revealed that the expression from high to low was multiple-cell stage > mid-blastula stage = mid-gastrula stage, and the expression in multiple-cell stage was at less 1.6-fold higher than in other stages. Accordingly, the whole mount in situ hybridization (WISH) in embryos demonstrated that Lc-Oct4 was expressed only in early embryonic development from 2-cell stage to early-gastrula stage with the peak at 16-cell stage, but not detected in PGCs area. In conclusion, Lc-Oct4 participated in the oogenesis and early embryonic development in large yellow croaker. Overall, this study provided better understanding of Lc-Oct4 gene and lay the foundation for its function research in the large yellow croaker.


Dipylidium caninum (Cyclophyllidea, Dipylidiidae) in a wild carnivore from Brazil.
We report Dipylidium caninum for the first time in a wild carnivore in Brazil, the crab-eating fox (Cerdocyon thous). Presence of the cestode could be the consequence of anthropogenic expansion into natural habitats of this host, as this parasite has only previously been reported in domestic hosts in Brazil.


Glycolaldehyde induces sensory neuron death through activation of the c-Jun N-terminal kinase and p-38 MAP kinase pathways.
Glycolaldehyde (GA) is a highly reactive hydroxyaldehyde and one of the glycolytic metabolites producing advanced glycation endproducts (AGEs), but its toxicity toward neurons and Schwann cells remains unclear. In the present study, we found that GA exhibited more potent toxicity than other AGE precursors (glyceraldehyde, glyoxal, methylglyoxal and 3-deoxyglucosone) against immortalized IFRS1 adult rat Schwann cells and ND7/23 neuroblastoma × neonatal rat dorsal root ganglion (DRG) neuron hybrid cells. GA affected adult rat DRG neurons and ND7/23 cells more severely than GA-derived AGEs, and exhibited concentration- and time-dependent toxicity toward ND7/23 cells (10 < 100 < 250 < 500 µM; 6 h < 24 h). Treatment with 500 µM GA significantly up-regulated the phosphorylation of c-jun N-terminal kinase (JNK) and p-38 mitogen-activated kinase (p-38 MAPK) in ND7/23 cells. Furthermore, GA-induced ND7/23 cell death was significantly inhibited due to co-treatment with 10 µM of the JNK inhibitor SP600125 or the p-38 MAPK inhibitor SB239063. These findings suggest the involvement of JNK and p-38 MAPK-signaling pathways in GA-induced neuronal cell death and that enhanced GA production under diabetic conditions might be involved in the pathogenesis of diabetic neuropathy.


The neural systems of tool and action semantics: a perspective from functional imaging.
This review discusses the contributions of functional imaging (fMRI/PET) to our understanding of how action and tool concepts are represented and processed in the human brain. Category-selective deficits in neuropsychological patients have suggested a fine-grained functional specialization within the neural systems of semantics. However, the underlying principles of semantic organization remain controversial. The feature-based account of semantic memory (or 'sensory-motor theory') predicates category-selective effects (e.g. tool vs. animals) on anatomical segregation for different semantic features (e.g. action vs. visual). Within this framework, we will review functional imaging evidence that semantic processing of tools and actions may rely on activations within the visuo-motor system.


How Might Patients and Physicians Use Transparent Health Care Prices to Guide Decisions and Improve Health Care Affordability?
Many Americans face high cost-sharing demands from their health insurers. While there is hope that prices for health services are becoming more and more transparent, even increased availability of price information will not always translate into optimal, equitable health and financial outcomes for patients. This commentary on a case argues why transparent pricing is an ethical imperative and identifies steps that health sector stakeholders should take to help patients and clinicians use pricing information to inform health decision making.


Somatostatin, an In Vivo Binder to Aβ Oligomers, Binds to βPFOAβ(1-42) Tetramers.
Somatostatin (SST14) is strongly related to Alzheimer's disease (AD), as its levels decline during aging, it regulates the proteolytic degradation of the amyloid beta peptide (Aβ), and it binds to Aβ oligomers in vivo. Recently, the 3D structure of a membrane-associated β-sheet pore-forming tetramer (βPFOAβ(1-42) tetramer) has been reported. Here, we show that SST14 binds selectively to the βPFOAβ(1-42) tetramer with a KD value of ∼40 μM without binding to monomeric Aβ(1-42). Specific NMR chemical shift perturbations, observed during titration of SST14, define a binding site in the βPFOAβ(1-42) tetramer and are in agreement with a 2:1 stoichiometry determined by both native mass spectroscopy and isothermal titration calorimetry. These results enabled us to perform driven docking and model the binding mode for the interaction. The present study provides additional evidence on the relation between SST14 and the amyloid cascade and positions the βPFOAβ(1-42) tetramer as a relevant aggregation form of Aβ and as a potential target for AD.


Long-Term Assessment of Pancreatic Function After Pancreatectomy for Cystic Neoplasms.
With advances in cross-sectional imaging, pancreatic cysts are more frequently diagnosed and have become a common indication for pancreatectomy. The impact of pancreatectomy in these patients is important. The purpose of this study was to assess short-term outcomes, long-term nutritional status, quality of life (QOL), and pancreas function after pancreatectomy for cystic neoplasms. At a single institution, patients at least 3 y post-pancreatectomy for benign cystic neoplasms were identified. Using a validated questionnaire, short-term outcomes, long-term outcomes including endocrine and exocrine insufficiency, long-term nutritional status, and preoperative and postoperative QOL were compared based on operation and indication for resection. Among 102 eligible patients, 70 had valid contact information and 51 (72.9%) agreed to participate. Median follow-up was 6 (4-8) y. Patients undergoing pancreatoduodenectomy for benign cysts had higher morbidity than a similar cohort resected for pancreatic adenocarcinoma (patients with at least 1 ≥ grade 2 complication [49.0% versus 31.6%, P = 0.038]). After long-term follow-up, pancreatectomy did not significantly affect perceived QOL. Half of patients had mild-moderate or severe malnourishment, but pancreatic enzyme replacement was reported by only 4 (7.8%) patients. New-onset diabetes was present in 15 (29.4%) patients with median time-to-diagnosis of 6 (1-12) mo after resection. Pancreatectomy for benign cysts did not negatively impact patients' perceived QOL. However, after long-term follow-up, malnutrition and pancreatic insufficiency occurred in a significant percentage and may be greater than previously estimated. Consideration of short- and long-term outcomes should factor into preoperative counseling, especially in cysts with minimal risk of progression to malignancy.


Graduate training in community psychology.
The results of a 1975 survey of graduate training programs in community psychology and community mental health are presented. For 62 programs offering master's or doctoral training, formal curriculum components in each of five content areas (community systems and behavior, prevention or promotion of effectiveness, practice of community mental health, research and evaluation, and administration) are reported. Availability of training in six sites (community mental health centers, state hospitals, schools, legal, public health, and social service systems) is also indicated for each program. The number of faculty primarily involved in community psychology or community mental health training and principal sources of financial support for graduate students are described. A list of the 62 programs is provided.


Evaluation of cryogen spray cooling exposure on in vitro model human skin.
Cryogen spray cooling (CSC) is commonly used during dermatologic laser surgery. The epidermal and dermal effects of CSC have not been adequately evaluated. To study the potential for epidermal and dermal injury after CSC using an in vitro model of human skin (RAFT). RAFT specimens were exposed to continuous CSC spurt durations of 10, 20, 40, 80, 100, 200, or 500 milliseconds. Biopsies were taken acutely, 3 and 7 days post-CSC exposure. Sections were stained with hematoxylin and eosin for evaluation of possible injury, Ki-67 to determine keratinocyte viability, and Melan-A, to identify and evaluate melanocytes. Minimal, transient epidermal changes were noted in specimens exposed to continuous CSC spurts of 80 milliseconds or less. Keratinocytes and melanocytes remained viable. Continuous CSC spurts of 100, 200, or 500 milliseconds (much longer than recommended for clinical use) resulted in significant epidermal injury acutely, with partial or full thickness epidermal necrosis at 7 days. Only the 500 milllisecond specimen demonstrated dermal change, decreased fibroblast proliferation at 3 days. Continuous CSC spurts of 80 milliseconds or less induce minimal, if any, epidermal or dermal damage and are unlikely to produce cryo-injury when used during dermatologic laser surgery.


The osteogenic activity of human mandibular fracture haematoma-derived cells is stimulated by low-intensity pulsed ultrasound in vitro.
Low intensity pulsed ultrasound (LIPUS) stimulation is a clinically established treatment method used to accelerate long bone fracture healing; however, this method is currently not applied to mandibular fractures. In this study, we investigated the effects of LIPUS on human mandibular fracture haematoma-derived cells (MHCs) in order to explore the possibility of applying LIPUS treatment to mandibular fractures. MHCs were isolated from five patients. The cells were divided into two groups: (1) LIPUS (+) group: MHCs cultured in osteogenic medium with LIPUS treatment; and (2) LIPUS (-) group: MHCs cultured in osteogenic medium without LIPUS treatment. The osteogenic differentiation potential and proliferation of the MHCs were compared between the two groups. The waveform used was equal to the wave conditions of a clinical fracture healing system. The gene expression levels of ALP, OC, Runx2, OSX, OPN, and PTH-R1 and mineralization were increased in the LIPUS (+) group compared to the LIPUS (-) group. There were no significant differences in cell proliferation between the two groups. These findings demonstrate the significant effects of LIPUS on the osteogenic differentiation of MHCs. This study provides significant evidence for the potential usefulness of the clinical application of LIPUS to accelerate mandibular fracture healing.


Derailed B cell homeostasis in patients with mixed connective tissue disease.
Mixed connective tissue disease (MCTD) is a systemic autoimmune disorder, characterized by the presence of antibodies to U1-RNP protein. We aimed to determine phenotypic abnormalities of peripheral B cell subsets in MCTD. Blood samples were obtained from 46 MCTD patients, and 20 controls. Using anti-CD19, anti-CD27, anti-IgD and anti-CD38 monoclonal antibodies, the following B cell subsets were identified by flow cytometry: (1) transitional B cells (CD19+CD27-IgD+CD38(high)); (2) naive B cells (CD19+CD27-IgD+CD38(low)); (3) non-switched memory B cells (CD19+CD27+IgD+); (4) switched memory B cells (CD19+CD27+IgD-); (5) double negative (DN) memory B cells (CD19+CD27-IgD-) and (6) plasma cells (CD19+CD27(high)IgD-). The proportion of transitional B cells, naive B cells and DN B lymphocytes was higher in MCTD than in controls. The DN B cells were positive for CD95 surface marker. This memory B cells population showed a close correlation with disease activity. The number of plasma cells was also increased, and there was an association between the number of plasma cells and the anti-U1RNP levels. Cyclophosphamide, methotrexate, and corticosteroid treatment decreased the number of DN and CD27(high) B cells. In conclusion, several abnormalities were found in the peripheral B-cell subsets in MCTD, which reinforces the role of derailed humoral autoimmune processes in the pathogenesis.


Phencyclidine inhibits epinephrine-stimulated platelet aggregation independently of high affinity N-methyl-D-aspartate (NMDA)-type glutamatereceptors.
The psychotomimetic analgesic phencyclidine (PCP), which binds to a high affinity site on the neuronal N-methyl-D-aspartate (NMDA)-sensitive glutamate receptor, has previously been found to bind to platelets with high affinity and to specifically delay the onset of epinephrine-stimulated platelet aggregation (Jamieson et al. (1992) Biochem. J. 285, 35-39). We have now shown that the rank order of binding affinities of 14 synthetic PCP analogs at the high affinity binding site on platelets does not parallel the rank order of their affinities in binding to rat brain membranes, indicating that the high affinity PCP binding sites in platelets is distinct from the neuronal NMDA receptor. The order of potency of six of these analogs in delaying the onset of epinephrine-stimulated platelet aggregation also did not parallel the rank order of their binding affinities for platelet or brain binding sites. These data indicate that the ability of PCP analogs to inhibit epinephrine-stimulated aggregation is not related to their ability to bind to the high affinity platelet PCP binding site. Furthermore, (+)MK-801, which binds to the same high affinity binding site in neurons as does PCP, failed to inhibit epinephrine-stimulated platelet aggregation, further suggesting that the site at which PCP acts in platelets is not related to the NMDA-type glutamate receptor. Further studies showed that 5-HT2 receptors and effects on platelet secretion are not involved in PCP-mediated inhibition of epinephrine-induced platelet aggregation.


Synthesis and characterization of new diiodocoumarin derivatives with promising antimicrobial activities.
A series of 6,8-diiodocoumarin-3-N-carboxamides (4-11) were prepared. Treatment of ethyl 6,8-diiodocoumarin-3-carboxylate (1) with ethyl cyanoacetate/NH(4)OAc gave ethyl 2-(3-carbamoyl-6,8-diiodocoumarin-4-yl)-2-cyanoacetate (12) and 2-amino-4-hydroxy-7,9-diiodocoumarino[3,4-c]pyridine-1-carbonitrile (13), and treatment with acetone in the presence of NH(4)OAc or methylamine gave the ethyl 4-oxo-2,6-methano-2-methyl-3,4,5,6-tetrahydro-8,10-diiodobenzo[2,1-g]-2H-1,3-oxazocine-5-carboxylate derivatives 14a,b. All compounds were evaluated for their antimicrobial activity and the compounds 12-14a,b exhibited a pronounced effect on all tested microorganisms.


Role of L-type Ca(2+) channels, sarcoplasmic reticulum and Rho kinase in rat basilar artery contractile properties in a new model of subarachnoid hemorrhage.
We have previously described that L-type Ca(2+) channels' (LTCCs) activation and metabotropic Ca(2+) release from the sarcoplasmic reticulum (SR) regulate RhoA/Rho kinase (ROCK) activity and sustained arterial contraction. We have investigated whether this signaling pathway can be altered in a new experimental model of subarachnoid hemorrhage (SAH). For this purpose, arterial reactivity was evaluated on days 1 to 5 after surgery. A significant increase of basal tone, measured 4 and 60min after normalization, was observed on day 5 after SAH and at 60min on days 2 and 3 after SAH. This phenomenon was suppressed with LTCCs and ROCK inhibitors. We have also studied arterial rings vasoreactivity in response to high K(+) solutions. Interestingly, there were no significant differences in the phasic component of the high K(+)-induced contraction between sham and SAH groups, whereas a significant increase in the sustained contraction was observed on day 5 after SAH. This latter component was sensitive to fasudil, and selectively reduced by low nifedipine concentration, and phospholipase C and SR-ATPase inhibitors. Therefore, our data suggest that the metabotropic function of LTCCs is potentiated in SAH. Our results could provide a new strategy to optimize the pharmacological treatment of this pathological process.


Fibrinolysis and antifibrinolytic drugs in the growth and spread of tumours.
In the last few years increased release of fibrinolytic enzymes from malignant cells has been observed, but the significance of this property in relation to malignant growth is still not fully understood. Antifibrinolytic drugs decrease the growth rate of some experimental tumours and might have a similar effect on human malignant tumours. Antifibrinolytic drugs might also decrease the intravascular shedding of tumour cells from primary tumours, but might on the other hand enhance the lodgement of those metastatic tumour cells already in the vascular bed of recipient organs.


Characterization of a new strain of leptospira isolated from surface water in India.
A new strain of Leptospira, isolated from surface water in India, is studied and classified. It shows, in the biological tests, a behaviour like that of saprophytic leptospirae; further serovar it represents a new serovar which we named poona.


Generating solutions to far analogies makes individuals tend to categorize information based on thematic relations.
This study aimed to explore whether solving distant analogies makes individuals tend to categorize information based on either taxonomic or thematic relations. In the study, one group of participants solved far analogies (far analogy group), while another group solved near analogies (near analogy group). Then, all participants completed the triad task which is the task of measuring the propensity to classify. The research findings revealed that, regardless of whether the object of classification was the artifact or natural object, the far analogy group exhibited a higher percentage of thematic responses than the near analogy and control group in the triad task. The present study demonstrated that solving far analogies could make individuals tend to categorize information based on thematic relations.


A randomized controlled pilot study of the effects of 6-week high intensity hatha yoga protocol on health-related outcomes among students.
Modern hatha yoga exercises (YE) provide an alternative form of physical activity which may reduce stress, facilitate recovery and improve health. This study investigated the short-term effects of high intensity hatha yoga exercises (HIY) on health-related outcomes. A 6-week randomized controlled study was performed to compare HIY with a control group not changing their exercise behavior. Healthy students (N = 44; median age: 25 years, range 20-39 years; HIY: n = 21, including 3 men; control group: n = 23, including 3 men) novice to yoga participated in the intervention which included one weekly class and recommended home training. Participants provided self-reports in questionnaires before and after the intervention. Self-reports included anxiety and depression (Hospital Anxiety and Depression Scale), stress (Perceived Stress Scale), sleep quality (Pittsburgh Sleep Quality Index), insomnia (Insomnia Severity Index), subjective health complaints (Common Symptoms in General Practice Index) and self-rated health (single-item). After the 6-week intervention, there were no between-group differences in anxiety, depression, stress, sleep or self-rated health. However, when investigating associations within the HIY-group, a higher HIY-dose was related to less depression (r = 0.47; p = 0.03), improved sleep quality (r = 0.55; p = 0.01), and less insomnia (r = 0.49; p = 0.02). There were no short-term between-group effects of HIY on mental distress, sleep or self-rated health. However, within the HIY-group, a higher dose was associated with improved mental health in terms of depression and with improved sleep. Although future studies with larger samples are needed, these preliminary findings suggest short-term positive effects of HIY on health-related outcomes among students. NCT01305096.


[Competence Network Stroke. A successful model for stroke research].
In 1999 the German Ministry of Education and Research initiated a funding initiative for competence networks in health research in order to improve research and health care for major diseases with high morbidity and relevance to public health. All major players in a given field were invited to cooperate. The aims were to improve horizontal as well as vertical networking in order to improve research quality and the transfer of new results into general clinical practice. Another aim was to establish sustainable structures for lasting cooperation. After a highly competitive application round, the Competence Network Stroke was among the very first to be funded. The incidence of stroke in Germany is about 250,000 new patients per year, it is the leading cause of adult impairment and its societal impact is dramatic.This article describes how the Competence Network Stroke managed to meet the above-mentioned goals and how cooperation among stroke researchers and caregivers in Germany has improved. Furthermore it provides examples of researcher achievements in the network, which have advanced research and benefited patients.


Imaging of uretero-pelvic junction obstruction with stimulated diuresis. With consideration of the reliability of ultrasonography.
Eighty-nine kidneys of 81 infants and children with uretero-pelvic junction obstruction were investigated using ultrasonography (US), diuretic urography (DUR) and diuretic renography (DREN). Results of the US were false-negative in 14%. This can be avoided by ensuring that the patients get an amount of fluid appropriate to their age before the examination or by performing diuretic ultrasonography with frusemide. False-positive results were found with US in 15%, but obstruction was excluded by using the DUR and/or the DREN. During post-operative follow up the DUS is useful and after 6 months the clearance with 123-iodine hippurate combined with the DREN should be performed. The performance of the Whitaker-test is unnecessary.


A novel technique of endoscopic submucosal dissection for circumferential ileocecal valve adenomas with terminal ileum involvement: the "doughnut resection" (with videos).
Ileocecal valve (ICV) lesions are difficult to resect endoscopically and patients are often referred for laparoscopic colectomy. ICV involvement has been shown to be related to technical failure and tumor recurrence after endoscopic mucosal resection (EMR) and represents a challenge for endoscopic submucosal dissection (ESD). Few publications have focused specifically on endoscopic management of ICV lesions. We developed a novel ESD technique, the "doughnut resection," for circumferential ICV adenomas with terminal ileum involvement. Two circumferential mucosal incisions are performed, one in the ileum and the other in the cecum, followed by submucosal dissection of the disk of tissue between the two incisions around a guiding stent placed across the valve that helps guide the dissection as it crosses the valve orifice. The lesion is removed en bloc in the shape of a "doughnut" with two concentric assessable lateral margins. The underwater ESD technique and a gastroscope were used to facilitate the resection. Seven patients received the doughnut resection. The median patient age was 67 years. All patients had prior biopsy and three had prior endoscopic resection (1-6 times). The median specimen diameter was 4.5 cm (range 3-8). All resections were en bloc and R0. There was no perforation, delayed bleeding, or other clinically significant adverse events. After a median follow-up of 21 months (range 12-32), there was no tumor recurrence. The "doughnut resection" is a feasible, safe, and effective method to remove circumferential ICV lesions endoscopically even for patients with multiple prior tumor manipulations.


Clinical utility of ultrasonography, pulse oximetry and arterial line derived hemodynamic parameters for predicting post-induction hypotension in patients undergoing elective craniotomy for excision of brain tumors - A prospective observational study.
Hypotension, which is a common adverse effect of induction of anesthesia, may be especially detrimental in neurosurgical patients. Hence, it is important to investigate hemodynamic parameters which may be useful in identifying patients at risk of hypotension, following induction. Our study was designed to assess the utility of parameters derived from ultrasonography, pulse oximeter and arterial line for predicting post-induction hypotension. The study was designed as a prospective, observational trial. Written informed consent was obtained from 100 American Society of Anesthesiologists (ASA) 1 and 2 patients, between 18-60 years of age, scheduled for elective craniotomy for brain tumors. Arterial cannula was inserted before induction of anesthesia and connected to Vigileo cardiac output monitor. Baseline stroke volume variation (SVV), stroke volume (SV), cardiac index (Ci), cardiac output (CO) and pulse pressure variation (PPV) were recorded. Plethysmography variability index (PVI) and perfusion index (PI) were obtained from the Masimo rainbow SET® Radical-7® pulse oximeter. Ultrasonographic assessment of the inferior vena cava (IVC) was performed before induction of anesthesia and again within 15 min after induction. Maximum and minimum IVC diameters (dIVCmax and dIVCmin) and collapsibility index (CI) were measured. All the other aforementioned parameters were recorded every minute starting at induction, until the 15th minute following induction. PI, CI and dIVCmax were found to have the largest AUCROC for the prediction of post-induction hypotension (AUCROC 0.852, 0.823 and 0.781 respectively). Multiple logistic regression analysis revealed CI to be the most significant independent factor for the prediction of post-induction hypotension. Non-invasively derived hemodynamic parameters like dIVCmax, CI and PI were more accurate for the prediction of post-induction hypotension, compared to invasively derived parameters.


The effect of amputation level and age on outcome: an analysis of 135 amputees.
In this retrospective study, the impact of age, amputation level and the cause of amputation were examined using the Hospital Anxiety and Depression Scale (HADS) and Medicare K scores of amputees with unilateral lower-limb amputation. In total, 135 patients with unilateral transfemoral (TF) or (TT) transtibial amputations were examined. All data were collected using questionnaires that were either self-administered or administered during an interview. The HADS was developed as a self-reporting questionnaire to detect adverse anxiety and depressive status. K code is used to describe the functional abilities of amputees. The mean age at the time of surgery was 52.79 ± 13.08 years. The mean time since amputation was 59.20 ± 24.41 months for TT, and 60.89 ± 22.09 months for TF amputation. The HADS-A scores of the transfemoral amputation group were determined as significantly high compared to those of the transtibial group (p < 0.05). The K index of the group aged 35 years and below was significantly higher than that of the other groups (p 0.002, p 0.001, p < 0.01). The data show higher HADS-A scores with traumatic transfemoral amputation. Therefore, adequate psychiatric evaluation and rehabilitation should be applied to all amputees, especially in cases of young, traumatic, transfemoral amputations. Level 3, retrospective comparative cohort study.


Role of commissural projections in the representation of bilateral auditory space in the barn owl's inferior colliculus.
The central nucleus of the barn owl's inferior colliculus (ICc) contains a representation of both the ipsilateral and contralateral auditory hemifields. The representation of ipsilateral space is found in the "core" of the ICc, a subdivision defined by the terminal field of nucleus laminaris, the avian analogue of the medial superior olivary nucleus. The representation of contralateral space is found in the lateral portion of the "shell" of the ICc. The shell surrounds the core and is defined by the terminal field of the nucleus angularis, one of the cochlear nuclei. The representation of ipsilateral space in the core of the ICc may be accounted for by the crossed projection from the nucleus laminaris because most of the nucleus laminaris is devoted to a representation of contralateral space. We present evidence to suggest that the representation of contralateral space is due to a commissural projection from the core of one side to the lateral shell of the opposite side. Injection of horseradish peroxidase (HRP) into the lateral portion of the ICc shell produced retrogradely labeled somata in the core of the opposite side. Injection of tritiated proline into the core produced anterograde label confined to the lateral shell, thus confirming the observations made with HRP. Thus, for example, the left ICc core, which contains predominantly a representation of the left hemifield, innervates the right lateral shell, endowing it with a representation of the left, or contralateral hemifield. The representation of contralateral space in the lateral shell is ultimately conveyed to the external nucleus of the inferior colliculus where it contributes the horizontal axis to a two-dimensional map of space.


Dynamics of Acute Postsurgical Pain over the Last Decade: A Bibliometric Analysis.
Minimizing acute postsurgical pain (APSP) remains a challenge, despite extensive research about it. This study comprehensively analyzed the literature on APSP to assess how the field has developed and where it may go in the future. Studies on APSP indexed in the Web of Science Core Collection and published from 2012 to 2021 were assessed for eligibility. Data from included studies were analyzed using CiteSpace, Python, and Microsoft. Analysis of 5,236 publications on APSP showed that the number of articles per year has increased linearly. The United States leads other countries in terms of the number and centrality of publications. Cocitation analysis suggests that the field focused earlier on the incidence and risk factors of APSP, shifting later to a focus on the reduction and management of adverse outcomes due to APSP. The top-ranked keyword cluster during the study period was "short-term outcomes" (#0), followed by "risk factors" (#1). The strongest burst occurred for the keyword "combination," followed by "multimodal analgesia." The most recent burst occurred for the keywords "regional analgesia," "opioid use," "erector spinae plane block," and "infiltration." Hotspots in APSP research since 2012 have been incidence, risk factors, and control of negative outcomes. Future research is likely to concentrate on the use of opioids and technological innovations in regional anesthesia. Our findings may help APSP researchers and clinicians understand their field, optimize clinical practice, and plan future research.


Age-related changes of serum mitochondrial uncoupling 1, rumen and rectal temperature in goats.
Thermoregulatory processes are induced not only by exposure to cold or heat but also by a variety of physiological situations including age, fasting and food intake that result in changes in body temperature. The aim of the present study was to evaluate the differences in serum mitochondrial uncoupling protein 1 (UCP1), rumen temperature (TRUMEN) and rectal temperature (TRECTAL) values between adult and kids goats. Ten adult male Maltese goats aged 3-5 years old (Group A) and 30 male kids, raised for meat, were enrolled in this study. The kids were equally divided into 3 groups according to their age: Group B included kids aged 3 months, Group C included kids aged 4 months and Group D included kids aged 5 months. Blood samples and measurements of TRUMEN and TRECTAL were obtained from each animal. One-way repeated measures analysis of variance (ANOVA) was applied to evaluate the effect of age on the studied parameters. Statistically significant higher serum UCP1 levels (P<0.001) were found in Group A as compared to Groups B, C and D. Higher TRUMEN values (P<0.001) were found in Group A than in Groups B, C and D, and in Group B than in Groups C and D. Group A showed lower TRECTAL values (P<0.001) than Groups B, C and D. The Pearson's Correlation test was applied to assess significant relationship among studied parameters showing a statistically significant negative correlation between the values of TRECTAL and serum UCP1 in all studied Groups (P<0.001). These results indicate that goats have good control of body temperature suggesting that further details about the thermogenic capacity and the function of UCP1 in kids and adult goats are worth exploring.


Penetrating nail-gun injury of the thoracic descending aorta.
Penetrating injury of the descending aorta due to accidental discharge of a nail gun.


Cultured heart cell reaggregate model for studying cardiac toxicology.
This review represents a summary of the technique of using cultured heart cells as a model system for studying the physiology, pharmacology, biochemistry and toxicology of myocardial cells. The general techniques and types of culture preparations commonly used are given and some of the advantages and disadvantages of working with cultured heart cells are summarized.


Revision allograft reconstruction of the lateral collateral ligament complex in elbows with previous failed reconstruction and persistent posterolateral rotatory instability.
Primary reconstruction of the lateral collateral ligament complex (LCLC) using graft tissue restores elbow stability in many, but not all, elbows with acute or chronic posterolateral rotatory instability (PLRI). Revision reconstruction using a tendon allograft is occasionally considered for persistent PLRI, but the outcome of revision ligament reconstruction in this setting is largely unknown. We determined whether revision allograft ligament reconstruction can (1) restore the stability and (2) result in improved elbow scores for patients with persistent PLRI of the elbow after a previous failed primary reconstructive attempt and in the context of the diverse pathology being addressed. Between 2001 and 2011, 160 surgical elbow procedures were performed at our institution for the LCLC reconstruction using allograft tissue. Only patients undergoing revision allograft reconstruction of the LCLC for persistent PLRI with a previous failed primary reconstructive attempt using graft tissue and at least I year of followup were included in the study. Eleven patients (11 elbows) fulfilled our inclusion criteria and formed our study cohort. The cohort consisted of six female patients and five male patients. The mean age at the time of revision surgery was 36 years (range, 14-59 years). The revision allograft reconstruction was carried out after a mean of 3 years (range, 2.5 months to 9 years) from a failed attempted reconstruction of the LCLC. Osseous deficiency to some extent was identified in the preoperative radiographs of eight elbows. Mean followup was 5 years (range, 1-12 years). Revision allograft reconstruction of the LCLC restored elbow stability in eight of the 11 elbows; two of the three elbows with persistent instability were operated on a third time (at 6 and 7 months after allograft revision reconstruction). For elbows with no persistent instability, the mean Mayo Elbow Performance Score at most recent followup was 83 points (range, 60-100 points), and six elbows were rated with a good or excellent result. All patients with persistent instability had some degree of preoperative bone loss. Revision allograft reconstruction of the LCLC is an option for treating recurrent PLRI, although this is a complex and resistant problem, and nearly ½ of the patients in this cohort either had persistent instability and/or had a fair or poor elbow score. Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.


Condition-dependent transcriptome reveals high-level regulatory architecture in Bacillus subtilis.
Bacteria adapt to environmental stimuli by adjusting their transcriptomes in a complex manner, the full potential of which has yet to be established for any individual bacterial species. Here, we report the transcriptomes of Bacillus subtilis exposed to a wide range of environmental and nutritional conditions that the organism might encounter in nature. We comprehensively mapped transcription units (TUs) and grouped 2935 promoters into regulons controlled by various RNA polymerase sigma factors, accounting for ~66% of the observed variance in transcriptional activity. This global classification of promoters and detailed description of TUs revealed that a large proportion of the detected antisense RNAs arose from potentially spurious transcription initiation by alternative sigma factors and from imperfect control of transcription termination.


Successful in utero treatment of an oral teratoma via operative fetoscopy: case report and review of the literature.
The prenatal diagnosis of a nasopharyngeal teratoma carries a very grave prognosis. Although these tumors constitute only 9% of all teratomas, all previous cases diagnosed antenatally have been associated with either fetal demise or emergent surgery at birth. Of the fetuses that survive to birth, delivery can be associated with airway obstruction and multiple postnatal surgeries. These complications could be averted if the tumor could be safely treated in utero. We hereby report the successful treatment of an oral teratoma via operative fetoscopy, with the birth of a healthy infant at term.


Transport of N-acetyl-D-galactosamine in Escherichia coli K92: effect on acetyl-amino sugar metabolism and polysialic acid production.
The N-acetyl-D-galactosamine (GalNAc) transport system of Escherichia coli K92 was studied when the bacterium was grown in a chemically defined medium containing GalNAc as a carbon source. Kinetic measurements were carried out in vivo at 37 degrees C in 25 mM phosphate buffer, pH 7.0. Under these conditions, the uptake rate was linear for at least 3 min and the calculated Km for GalNAc was 3 microM. The transport system was strongly inhibited by sodium arsenate (70%), potassium cyanide (62%) and 2,4-dinitrophenol (75%). Analysis of bacterial GalNAc phosphotransferase activity revealed in vitro GalNAc phosphorylation activity only when phosphoenolpyruvate was present. These results strongly support the notion that GalNAc uptake depends on a specific phosphotransferase system. Study of activity regulation showed that N-acetylglucosamine and mannosamine specifically inhibit the transport of GalNAc in this bacterium. Analysis of expression revealed that the GalNAc transport system is specifically induced by GalNAc but not by N-acetylglucosamine (GlcNAc) or N-acetylmannosamine (ManNAc), two intimately related sugars. Moreover, full induction of GalNAc transport required the presence of both cAMP and GalNAc. Comparative studies revealed that E. coli K92 has developed a regulation mechanism that specifically induces the appropriate permease based on the presence of each respective phospho-amino sugar (GlcNAc, ManNAc and GalNAc). In this regulation system, GlcNAc is the preferred amino sugar as the carbon source. Finally, when E. coli K92 was grown using GalNAc, capsular polysialic acid production was strongly affected. The presence of intracellular phosphoderivative acetylamino sugars, generated by the action of the phosphotransferase transport system, can be responsible for this effect.


Determination of Three Acetylator Phenotypes in a Mexican Population Using Sulfamethazine Metabolic Ratio.
Eighty-six Mexican young healthy volunteers received a 500-mg oral sulfamethazine dose. Urine was collected 0--6 h after medication and acetylated, and unchanged sulfamethazine were determined by the Bratton--Marshall method. The frequency distribution of acetylated/unchanged sulfamethazine, determined by probit analysis, appeared to be trimodal, allowing the discrimination of three acetylator phenotypes. The frequencies of rapid, intermediate, and slow acetylators were 28%, 42%, and 30% respectively, being consistent with the Hardy-Weinberg law.


Local Therapy Indications in the Management of Patients with Oligometastatic Non-Small Cell Lung Cancer.
Advances in surgical, radiation, and interventional radiology therapies carry a reduction in morbidity associated with therapy. Aggressive management of patients with oligometastatic non-small cell lung cancer offers the potential for improved disease-free survival and quality of life compared with traditional systemic therapy alone.


OR expansion--a journey into the unknown.
WATCHING A CONSTRUCTION PROJECT mature from concept to culmination is a journey of both professional and personal growth. EFFECTIVE PLANNING and communication are essential for a project to be successful. SUCCESSES AND FAILURES provide learning experiences.


Intracellular glutathione in stretch-induced cytokine release from alveolar type-2 like cells.
Ventilator-induced lung injury (VILI) is characterized by release of inflammatory cytokines, but the mechanisms are not well understood. We hypothesized that stretch-induced cytokine production is dependent on oxidant release and is regulated by intracellular glutathione (GSH) inhibition of nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1) binding. Type 2-like alveolar epithelial cells (A549) were exposed to cyclic stretch at 15% strain for 4 h at 20 cycles/min with or without N-acetylcysteine (NAC) or glutathione monoethylester (GSH-e) to increase intracellular GSH, or buthionine sulfoximine (BSO), to deplete intracellular GSH. Cyclic stretch initially caused a decline in intracellular GSH and a rise in the levels of isoprostane, a marker of oxidant injury. This was followed by a significant increase in intracellular GSH and a decrease in isoprostane. Stretch-induced IL-8 and IL-6 production were significantly inhibited when intracellular GSH was further increased by NAC or GSH-e (P < 0.0001). Stretch-induced IL-8 and IL-6 production were augmented when intracellular GSH was depleted by BSO (P < 0.0001). NAC blocked stretch-induced NF-kappa B and AP-1 binding and inhibited IL-8 mRNA expression. We conclude that oxidant release may play a role in lung cell stretch-induced cytokine release, and antioxidants, which increase intracellular GSH, may protect lung cells against stretch-induced injury.


Isolation of microorganisms for biological detoxification of lignocellulosic hydrolysates.
Acid pretreatment of lignocellulosic biomass releases furan and phenolic compounds, which are toxic to microorganisms used for subsequent fermentation. In this study, we isolated new microorganisms for depletion of inhibitors in lignocellulosic acid hydrolysates. A sequential enrichment strategy was used to isolate microorganisms from soil. Selection was carried out in a defined mineral medium containing a mixture of ferulic acid (5 mM), 5-hydroxymethylfurfural (5-HMF, 15 mM), and furfural (20 mM) as the carbon and energy sources, followed by an additional transfer into a corn stover hydrolysate (CSH) prepared using dilute acid. Subsequently, based on stable growth on these substrates, six isolates--including five bacteria related to Methylobacterium extorquens, Pseudomonas sp, Flavobacterium indologenes, Acinetobacter sp., Arthrobacter aurescens, and one fungus, Coniochaeta ligniaria--were chosen. All six isolates depleted toxic compounds from defined medium, but only C. ligniaria C8 (NRRL 30616) was effective at eliminating furfural and 5-HMF from CSH. C. ligniaria NRRL 30616 may be useful in developing a bioprocess for inhibitor abatement in the conversion of lignocellulosic biomass to fuels and chemicals.


Pathophysiology, diagnosis, and clinical assessment of asthma in the adult.
Asthma is a chronic inflammatory disorder that is characterized by 3 distinct responses in the airways: inflammation, hyperresponsiveness, and remodeling. Clinical diagnosis of asthma is often based on the presence of symptoms, such as cough, wheeze, breathlessness, and chest tightness; but the presence of these symptoms is not exclusive to asthma, and clinical correlation with spirometry and other diagnostic testing is essential. Once a diagnosis of asthma is established, the focus of care should be toward control of the disease. This article discusses the pathophysiology, diagnosis, and clinical assessment of asthma in the adult patient population.


Performance of the heart failure risk scores in predicting 1 year mortality and short-term readmission of patients.
The aim of this study was to assess the performance of these main scores in predicting prognosis in patients with heart failure (HF). A total of 2008 patients who were admitted to the Fourth People's Hospital of Zigong, Sichuan, from December 2016 to June 2019 and diagnosed with HF were included in the study. We compared the prognostic predictive performance of Seattle Heart Failure Model (SHFM), Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC-HF) risk score, Get With the Guidelines-Heart Failure programme (GWTG-HF), Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND) risk scores, the Acute Decompensated Heart Failure National Registry (ADHERE) model, Barcelona Bio-Heart Failure (BCN-Bio-HF) risk calculator, and Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico-Heart Failure (GISSI-HF) for the endpoints. The primary endpoint was 1 year all-cause mortality and the secondary endpoint was the incidence of 28 day readmission post-discharge. At 1 year follow-up, 44 (2.21%) patients with HF died. Discrimination analyses showed that all risk scores performed reasonably well in predicting 1 year mortality, with areas under the receiver operating characteristic curve (AUCs) fluctuating between 0.757 and 0.822. GISSI-HF showed the best discrimination with the AUC of 0.822 (0.768-0.876), followed by MAGGIC-HF, BCN-Bio-HF, ASCEND, SHFM, GWTG-HF, and ADHERE with AUCs of 0.819 (0.756-0.883), 0.812 (0.758-0.865), 0.802 (0.742-0.862), 0.787 (0.725-0.849), 0.762 (0.684-0.840), and 0.757 (0.681-0.833), respectively. All risk scores were similarly predictive of 28 day emergency readmissions, with AUCs fluctuating between 0.609 and 0.680. Overestimation of mortality occurred in all scores except the ASCEND. The risk scores remained with good prognostic discrimination in patients with biventricular HF and in the subgroup of patients taking angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker. Currently assessed risk scores have limited clinical utility, with fair accuracy and calibration in assessing patients' 1 year risk of death and poor accuracy in assessing patients' risk of readmission. There is a need to incorporate more patient-level information, use more advanced technologies, and develop models for different subgroups of patients to achieve more practical, innovative, and accurate risk assessment tools.


Living on the margin: a salutogenic model for socio-economic differentials in health.
Research into health inequalities shows that socio-economic position (SEP) is strongly associated with differentials in health. Yet at present there is no adequate model to explain the causal link between the social and the biological variables: in particular why the association between SEP and health is found in all societies; and why inequalities are not simply a reflection of poverty causing sickness, but are also seen among the wealthiest classes in the wealthiest societies. In this paper we propose a model which brings together many diverse strands of research, and helps to explain how stratification by socio-economic position may be seen in terms of differentials in the margin of resources. Resource differentials lead to stratified health outcomes owing to the differential capacity of individuals and groups to realise 'universal' psychological aspirations of a broadly 'health promoting' nature. The margin model builds upon a previously described salutogenic theory of health. On average, the relative size of the margin will predict differential health outcome. This prediction is empirically testable and opens up a new agenda for research on health differentials; it also provides a framework for understanding, planning and evaluating health promotion.


Influence of sporting activity and smoking on peripheral lymph nodes in patients with melanoma analyzed by high-resolution ultrasound.
The sonographic examination of peripheral lymph nodes (LNs) plays an important role in the preoperative treatment and in the follow-up of patients with melanoma. A prospective study including 200 consecutive patients with a history of invasive cutaneous melanoma was performed at the Department of Dermatology and Allergy, University of Bonn, Germany, to examine the influence of sporting activity, physical workload, interferon alfa therapy, smoking habits, and infections of the upper respiratory tract on morphology and number of LNs analyzed by high-resolution ultrasound. Between May 2010 and June 2011, 106 men and 94 women (mean age 51.1 ± 12.8 years) were included in this study. During their follow-up visits for cutaneous melanoma, high-resolution ultrasound examination of cervical, axillary, and inguinal LN regions were performed. LN diameters and volumes were measured and correlated with the above given factors. Sports-active patients had more LNs in inguinal regions, a higher volume and a larger LN diameter, and a higher maximum width of the hypoechoic LN margin in comparison with the nonactive patients. Patients with a hard physical workload in their occupations had a significantly higher volume of the biggest LN. Compared with nonsmoking patients smokers presented higher values in the total quantity of the LNs, in the greatest volume of LN, and in the greatest diameter of LN in the cervical regions. The other factors had no significant influence on the LN parameters. Our study population was too small to comment on influencing factors in more detail especially the influences of different sporting activities or smoking habits. Sporting activity, physical workload, and smoking habits as associated cofactors influencing sonomorphologic aspects in patients with cutaneous melanoma should always be considered.


Characteristics and international comparability of the Finnish matrix sentence test in cochlear implant recipients.
The first Finnish sentence-based speech test in noise--the Finnish matrix sentence test--was recently developed. The aim of this study was to determine the characteristics of the new test with respect to test-retest reliability, speech recognition curve, and international comparability in Finnish cochlear implant (CI) recipients. The speech reception thresholds (SRT) were measured by means of an adaptive test procedure and compared with the results of the traditional Finnish word test. Additional measurements for concurrent slope and SRT estimation were conducted to determine the speech recognition curve and to check the test-retest reliability. The measurements were performed on 78 Finnish CI recipients. In a subset of 25 patients, additional measurements for test-retest reliability and slope determination were performed. The mean SRT was -3.5 ± 1.7 dB SNR, with only a weak correlation with the Finnish word test. Test-retest reliability was within ± 1 dB and the mean slope of the speech recognition curve was 14.6 ± 3.6 %/dB. The rehabilitation results were similar to the results published for the German matrix test. The Finnish matrix test was found to be suitable and efficient in CI recipients with similar characteristics as the German matrix test.


Anti-inflammatory effect of Ruta graveolens L. in murine macrophage cells.
Ruta graveolens L. (Rutaceae) is used for several therapeutic purposes worldwide. The present study is designed to investigate the effect of plant extract of Ruta graveolens on murine macrophage cells (J-774) challenged with lipopolysaccharide (LPS). LPS induces inflammatory response by stimulating the production of nitric oxide and other mediators. Significant inhibition (p=0.01 to p<0.002) of the LPS-induced nitric oxide production was observed in cells treated with plant extract in a concentration dependent manner. The inhibition observed for the extract was significantly higher than that observed for rutin, a flavonoid constituent of the plant. At 40 microM rutin, a comparable concentration of this flavonoid in the highest concentration (500 microg/ml) of plant extract was used in this study; a 20% inhibition (p=0.058) was observed. Inhibition in inducible nitric oxide synthase (inos) gene expression in the cells treated with the plant extract suggests an inhibition at the transcription level. Interestingly, a concomitant decrease in transcription of cyclooxygenase-2 (COX-2) gene has also been observed in cells treated with the plant extract and this inhibition is significantly higher than that observed with the highest concentration of rutin (80 microM) used in the study. As an inflammatory response, upregulation of nitric oxide synthase (iNOS) and COX-2 enzymes leads to production of pro-inflammatory mediators, namely nitric oxide and prostaglandins, respectively. Hence, the significant inhibitory effects on both of these inflammatory mediators unravel a novel anti-inflammatory action of this plant.


Appropriate electrode placement site for electric pulp testing first molar teeth.
Twenty volunteers with first molars free of restorations and caries were recruited. One molar from each arch was selected, and rubber dam was applied. Seven sites on each crown were electric pulp tested 4 times with an Elements Diagnostic Unit, and lowest threshold responses were recorded. Data were analyzed with one-way analysis of variance and the Tukey test at the .01 level. The lowest response for both the maxillary and mandibular teeth was with the probe on the mesiobuccal cusp tip. Other sites showed an increase in level from the mesiobuccal cuspal surface, mesiobuccal gingival surface, and the center of the supporting cusps (palatal of maxillary molar, buccal of mandibular molar). No significant difference in responses was found between male and female subjects; however, male subjects responded at higher thresholds than female subjects on all test sites except the mesiobuccal cusp tip. The optimum site for pulp testing first molars is the mesiobuccal cusp tip.


Effects of chronic NMDA-NR2b inhibition in the median eminence of the reproductive senescent female rat.
Gonadotrophin-releasing hormone (GnRH) neurones of the hypothalamic-pituitary-gonadal (HPG) axis drive reproductive function and undergo age-related decreases in activation during the transition to reproductive senescence. Decreased GnRH secretion from the median eminence (ME) partially arises from attenuated glutamatergic signalling via the NMDA receptor (NMDAR) and may be a result of changing NMDAR stoichiometry to favour NR2b over NR2a subunit expression with ageing. We have previously shown that the systemic inhibition of NR2b-containing receptors with ifenprodil, an NR2b-specific antagonist, stimulates parameters of luteinising hormone (used as a proxy for GnRH) release in both young and middle-aged females. In the present study, we chronically administered ifenprodil, an NR2b-specific antagonist, at the site of GnRH terminals in the ME or at GnRH perikarya in the preoptic area, in reproductively senescent middle-aged female rats, aiming to determine whether NR2b antagonism could restore aspects of reproductive functionality. Effects on oestrous cyclicity, serum hormones, and protein expression of GnRH, NR2b and phosphorylated NR2b (Tyr-1472) in the ME were measured. Chronic ifenprodil treatment in the ME (but not the preoptic area) altered oestrous cyclicity by increasing the percentage of days spent in pro-oestrus. This was accompanied by increased GnRH fluorescence intensity in the external ME zone and a greater proportion of GnRH terminals that co-labelled with pNR2b with treatment. We also observed changes in the relationships between protein immunofluorescence, serum hormone levels and other aspects of reproductive physiology in acyclic females, as revealed by bionetwork analysis. Together, these data support the hypothesis that NMDAR-NR2b expression and phosphorylation state play a role in reproductive senescence and highlight the ME as a major player in reproductive ageing.


Antithrombotic effect of indobufen in an experimental model of arterio-arterial microanastomosis in the rat.
Using an end-to-side microanastomosis of the left common carotid into the right common carotid of rats, implementing a potentially thrombogenic situation, we have investigated the possible antithrombotic effect of indobufen, a new antiplatelet drug. In eight of 15 untreated rats the anastomosis was totally obstructed by a single thrombus growing from the anastomotic wall. Indobufen treatment prevented thrombus formation completely in 14 of 15 rats (p less than 0.02). In treated animals indobufen also produced a statistically significant reduction of ADP-induced platelet aggregation relative to basal values. Platelet count were not influenced by drug treatment. Our experimental results suggest the potential usefulness of indobufen as an antithrombotic agent.


Author Correction: Structure of full-length wild-type human phenylalanine hydroxylase by small angle X-ray scattering reveals substrate-induced conformational stability.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


A stucy of enflurane biotransformation and fluoride ion nephrotoxicity.
Enflurane, like methoxyflurane, has been reported by some to cause renal failure, secondard to inorganic fluoride ion metabolism. In this article, the author examines some of the evidence both for and against these findings.


Multilocus genotyping of Giardia duodenalis in Malaysia.
Giardia duodenalis is considered the most common intestinal parasite in humans worldwide. In Malaysia, many studies have been conducted on the epidemiology of giardiasis. However, there is a scarcity of information on the genetic diversity and the dynamics of transmission of G. duodenalis. The present study was conducted to identify G. duodenalis assemblages and sub-assemblages based on multilocus analysis of the glutamate dehydrogenase (gdh), beta-giardin (bg) and triose phosphate isomerase (tpi) genes. Faecal specimens were collected from 484 Orang Asli children with a mean age of 7 years and examined using light microscopy. Specimens positive for Giardia were subjected to PCR analysis of the three genes and subsequent sequencing in both directions. Sequences were edited and analysed by phylogenetic analysis. G. duodenalis was detected in 17% (84 of 484) of the examined specimens. Among them, 71 were successfully sequenced using at least one locus. Genotyping results showed that 30 (42%) of the isolates belonged to assemblage A, 32 (45%) belonged to assemblage B, while discordant genotype results were observed in 9 specimens. Mixed infections were detected in 43 specimens using a tpi-based assemblage specific protocol. At the sub-assemblages level, isolates belonged to assemblage A were AII. High nucleotide variation found in isolates of assemblage B made subtyping difficult to achieve. The finding of assemblage B and the anthroponotic genotype AII implicates human-to-human transmission as the most possible mode of transmission among Malaysian aborigines. The high polymorphism found in isolates of assemblage B warrants a more defining tool to discriminate assemblage B at the sub-assemblage level.


Glans Preservation in Surgical Treatment of Distal Urethral Strictures With Dorsal Buccal Mucosa Graft Onlay by Subcoronal Approach.
To describe dorsal onlay buccal mucosa graft urethroplasty technique by subcoronal approach and glans preservation in distal penile urethral strictures with fossa navicularis involvement and to report safety, effectiveness, and cosmetic outcomes. Retrospective review of a prospective database of patients treated at Hospital Italiano de Buenos Aires between January 2011 and December 2019. Main surgical steps: ventral subcoronal incision, dorsal dissection of glandelar urethra until piercing the tip of the glans, dorsal urethrotomy, and graft transposition. Low urinary tract symptoms, uroflowmetry, and urinalysis were assessed at follow-up. Simplified International Index Erectile Function and Hypospadias Objective Scoring Evaluation were applied 1 year after surgery. Sixteen patients with a median age of 56.5 years (IQR 35.7-66.7) were included. Median stricture length was 5.5 cm (IQR 4-8.7). In 3 patients, Clavien-Dindo grade I-II complications were reported. At 1 year, median peak flow was 18 mL/seg (IQR 12.7-27.4) and median mean flow 7.8 mL/seg (IQR 6.1-9.9). At 41.5 months follow-up (IQR 13.2-74), all patients were stricture free and had no changes in erectile function. Hypospadias Objective Scoring Evaluation score ≥14 points was achieved by 14 patients (87.5%). For treatment of distal penile urethral strictures with fossa navicularis involvement, dorsal onlay buccal mucosa graft by subcoronal approach and glans preservation is a feasible technique with excellent functional outcomes, minimal complications, and substantial cosmetic results.


Editorial for the Molecular Genetics and Genomics of Metabolic Disorders in Cardiovascular and Cerebrovascular Diseases Special Issue: June 2023.
Cardiovascular and cerebrovascular diseases are the leading causes of the mortality of humans in the 21st century [...].


Three-year clinical outcome after chondrocyte transplantation using a hyaluronan matrix for cartilage repair.
Repair of articular cartilage represents a significant clinical problem and although various new techniques - including the use of autologous chondrocytes - have been developed within the last century the clinical efficacy of these procedures is still discussed controversially. Although autologous chondrocyte transplantation (ACT) has been widely used with success, it has several inherent limitations, including its invasive nature and problems related to the use of the periosteal flap. To overcome these problems autologous chondrocytes transplantation combined with the use of biodegradable scaffolds has received wide attention. Among these, a hyaluronan-based scaffold has been found useful for inducing hyaline cartilage regeneration. In the present study, we have investigated the mid-term efficacy and safety of Hyalograft C grafts in a group of 36 patients undergoing surgery for chronic cartilage lesions of the knee. Clinical Outcome was assessed prospectively before and at 12, 24, and 36 months after surgery. No major adverse events have been reported during the 3-year follow-up. Significant improvements of the evaluated scores were observed (P < 0.02) at 1 year and a continued increase of clinical performance was evident at 2 and 3 years follow-up. Patients under 30 years of age with single lesions showed statistically significant improvements at all follow-up visits compared to those over 30 with multiple defects (P < 0.01). Hyalograft C compares favorably with classic ACT and is particularly indicated in younger patients with single lesions. The graft can be implanted through a miniarthrotomy and needs no additional fixation with sutures except optional fibrin gluing at the defect borders. These results suggest that Hyalograft C is a valid alternative to ACT.


Chromosomal and histological changes in the reproductive organs of infertile men.
The chromosomal changes in the process of spermatogenesis in 27 infertile men have been examined. Normal chromosomal meiotic activity was found in 44% of cases, various chromosomal anomalies were seen in 18%, and no cells in meiosis were detected in 37% of cases.


The inhibitory effect of adenovirus-mediated p16INK4a gene transfer on the proliferation of lung cancer cell line.
Abnormalities in the p16INK4a tumor suppressor gene are found in many lung cancer cell lines and primary lung cancer tissue. To examine its tumor suppressor function and potential adequacy in cancer gene replacement therapy, wild-type p16INK4a gene was inserted in an adenovirus derived gene delivery system and introduced into lung cancer cell lines (NCI-H441 and NCI-H157) that did not express p16INK4a. Western blot assay and immunocytochemistry demonstrated production of wild-type p16 protein in these cell lines. The biological function of exogenous p16 protein was confirmed by the inhibition of pRB phosphorylation. The expression of exogenous p16 protein via recombinant adenovirus significantly inhibited cancer cell growth and colony formation in vitro of NSCLC that can not express endogenous p16. The flow cytometric analysis showed these results correlated with G1 cell cycle arrest. These observations suggest the value of adenovirally-mediated p16INK4a gene replacement therapy for lung cancer.


New p-terphenyl and benzoquinone metabolites from the bioluminescent mushroom Neonothopanus nambi.
Two new p-terphenyls, neonambiterphenyls A and B (1-2), a new benzoquinone, neonambiquinone A (3), together with six known sesquiterpenes (4-9), were isolated from the bioluminescent mushroom Neonothopanus nambi PW3. The isolated compounds were identified by mass, IR and spectroscopic analyses (1D and 2D NMR). Compounds 1-3 and 5-7 showed cytotoxicity against cancer cell lines such as KB, NCI-H187 and MCF-7 with IC50 values ranging from 1.45 to 49.31 µg/mL. In addition, compounds 1 and 5 showed cytotoxicity against Vero cells with IC50 values of 38.72 and 32.90 µg/mL, respectively.


HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial.
There is a growing body of evidence that HER2 status can change during disease recurrence or progression in breast cancer patients. In this context, re-evaluation of HER2 status by assessment of HER2 expression on circulating tumor cells (CTCs) is a strategy with potential clinical application. The aim of this trial was to determine the HER2 status of CTCs in metastatic breast cancer patients comparing two CTC assays. A total of 254 patients with metastatic breast cancer from nine German university breast cancer centers were enrolled in this prospective study. HER2 status of CTCs was assessed using both the FDA-approved CellSearch® assay and AdnaTest BreastCancer™. Using the CellSearch assay, 122 of 245 (50%) patients had ≥5 CTCs, and HER2-positive CTCs were observed in 50 (41%) of these patients. Ninety of 229 (39%) patients were CTC positive using AdnaTest BreastCancer, and HER2 positivity rate was 47% (42 of 90). The rate of breast cancer patients with HER2-negative primary tumors but HER2-positive CTCs was 32% (25 of 78) and 49% (28 of 57) using the CellSearch assay and AdnaTest BreastCancer, respectively. Considering only those patients who had CTCs on both tests (n = 62), concordant results regarding HER2 positivity were obtained in 50% of the patients (31/62) (P = 0.96, κ = -0.006). HER2-positive CTCs can be detected in a relevant number of patients with HER2 negative primary tumors. Therefore, it will be mandatory to correlate the assay-dependent HER2 status of CTCs to the clinical response on HER2-targeted therapies.


The efficacy and safety of pegylated liposomal doxorubicin monotherapy and combination therapy with carboplatin in Korean patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer: a single-institution experience.
This study aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) with or without carboplatin in Korean patients with recurrent ovarian cancer (ROC), fallopian tube, or primary peritoneal cancer. This retrospective study included 52 patients with ROC, fallopian tube, or primary peritoneal cancer who received PLD (50 mg/m2) between 1st December 2014 and 31th July 2016. The mean number of chemotherapy cycles was 3.8 (range, 2 to 9) in the PLD monotherapy group and 7 (range, 2 to 13) in the PLD combined with carboplatin (PLD-C) group. In overall response rates and clinical beneficial rates, PLD monotherapy group shows 5.0% and 17.5%, and PLD-C group shows 33.3% and 75.0%. The mean progression-free survival (PFS) was 5 and 13 months in the PLD monotherapy and PLD-C groups, respectively. At 6 months after treatment initiation, absence of disease progression was confirmed in 6 (15%) and 10 (83.3%) patients in the PLD monotherapy and PLD-C groups. Hematological adverse events (e.g., neutropenia and thrombocytopenia) were more common in the PLD-C group (P<0.001, P=0.004). The incidence of anemia and non-hematological adverse events, including mucositis, hand-foot syndrome, and allergic reactions, was similar in both groups. This study demonstrated the efficacy and safety of PLD monotherapy and PLD-C combination in Korean patients with ROC. This study would be helpful to consider the degree of worry about side effects and treatment expectations after treatment. Further retrospective studies with larger samples are required to confirm the efficacy of PLD monotherapy in Asian patients with platinum-resistant ROC.


Heart failure update.
The RUSSLAN study, which randomised 504 patients with post-infarction heart failure in whom intravenous inotropic support might be deemed appropriate, was presented for the first time in a hotline session at the annual meeting of the Working Group on Heart Failure of the European Society of Cardiology. The study suggested that levosimendan, a new calcium sensitising agent, could be used safely in patients with post-infarction heart failure in the absence of severe hypotension and that it appeared to improve symptoms and survival. If these results can be confirmed it would render it unique among intravenous inotropic agents.


High-performance liquid chromatography of sialooligosaccharides and gangliosides.
Glycans were cleaved from gangliosides and separated by high-performance liquid chromatography (HPLC). The columns were packed with bonded stationary phases made of microparticulate, macroporous silica with serotonin, phenylpropanolamine or tryptamine as the biogenic amine ligate. The ganglioside oligosaccharides were eluted in the order of increasing number of sialic acid residues in the molecule and their retention decreased with the ionic strength of the mobile phase. Best selectivity was obtained in the pH range from 3.0 to 4.0. The two major sialic acids, N-acetylneuraminic and N-glycolylneuraminic acids, were separated by lectin affinity chromatography using an HPLC column packed with silica-bound wheat germ agglutinin and 10 mM phosphate buffer, pH 4.0, as the eluent. Throughout this study, isocratic elution was used and the column effluent was monitored at 195 nm.


Robotic partial nephrectomy for complex renal tumors: surgical technique.
Laparoscopic partial nephrectomy requires advanced training to accomplish tumor resection and renal reconstruction while minimizing warm ischemia times. Complex renal tumors add an additional challenge to a minimally invasive approach to nephron-sparing surgery. We describe our technique, illustrated with video, of robotic partial nephrectomy for complex renal tumors, including hilar, endophytic, and multiple tumors. Robotic assistance was used to resect 14 tumors in eight patients (mean age: 50.3 yr; range: 30-68 yr). Three patients had hereditary kidney cancer. All patients had complex tumor features, including hilar tumors (n=5), endophytic tumors (n=4), and/or multiple tumors (n=3). Robotic partial nephrectomy procedures were performed successfully without complications. Hilar clamping was used with a mean warm ischemia time of 31 min (range: 24-45 min). Mean blood loss was 230 ml (range: 100-450 ml). Histopathology confirmed clear-cell renal cell carcinoma (n=3), hybrid oncocytic tumor (n=2), chromophobe renal cell carcinoma (n=2), and oncocytoma (n=1). All patients had negative surgical margins. Mean index tumor size was 3.6 cm (range: 2.6-6.4 cm). Mean hospital stay was 2.6 d. At 3-mo follow-up, no patients experienced a statistically significant change in serum creatinine or estimated glomerular filtration rate and there was no evidence of tumor recurrence. Robotic partial nephrectomy is safe and feasible for select patients with complex renal tumors, including hilar, endophytic, and multiple tumors. Robotic assistance may facilitate a minimally invasive, nephron-sparing approach for select patients with complex renal tumors who might otherwise require open surgery or total nephrectomy.


Non-conventional respiratory support modalities applicable in the older child. High frequency ventilation and liquid ventilation.
HFV, LV, and several other novel therapies offer promise to adults and children that the mortality associated with respiratory failure may be affected. Although there are several forms of HFV, HFOV is presently gaining favor in the treatment of severe respiratory failure and has generally supplanted HFJV in pediatric critical care. HFOV has the advantage of having an active expiratory phase, which helps to minimize air trapping and better modulate mean lung volume. Ventilators with sufficient power to perform HFOV in adults are currently under investigation, although there is a growing experience in using current ventilators in larger patients. To date, however, demonstration of lowered mortality with HFOV is lacking although intermediate outcome indicators are improved. PLV also offers promise in the treatment of ARF through its drastic ability to improve oxygenation, ventilation, and compliance in many lung injury models. Human trials are presently underway, but the optimal delivery of this novel therapy still necessitates extensive investigation. TLV is likely even more removed from general clinical application given the necessity of developing a new generation of ventilators for the delivery of liquid tidal volumes. How these and other modalities may piece together to improve the condition of our patients who have respiratory failure remains to be seen, but certainly, present and future investigation will be intriguing for years to come.


Associative learning of response inhibition affects perceived duration in a subsequent temporal bisection task.
Interval timing, the ability to discern the duration of an event, is integral to appropriately navigating the world, from crossing the road to catching a ball. Several features of an event can affect its perceived duration, for example it has previously been shown that a large stimulus is perceived to last longer than a small stimulus. In the current article, participants performed either a Go/No-Go or variable foreperiod task prior to performing a temporal bisection task. In both the Go/No-Go and variable foreperiod tasks, participants learned an association between a particular response and a particular stimulus. Subsequently, the perceived duration of these stimuli was tested in a temporal bisection task. Our findings indicated that associating a stimulus with response inhibition (i.e. a No-Go stimulus) decreased perceived duration compared to a stimulus associated with a response (a Go stimulus). Associating a stimulus with either a short or long foreperiod, on the other hand, did not affect perceived duration. We relate this finding back to the coding efficiency theory and the processing principle. A No-Go stimulus requires more cognitive processing than a Go stimulus and would thus be predicted to increase, rather than decrease, perceived duration in both these time perception theories. Finally, we suggest how our findings might be used in future investigations of interval timing.


Size fractionation of oligosaccharides by liquid chromatography on a cation-exchange column.
Oligosaccharides, labelled with 2-aminopyridine at their reducing ends, were satisfactorily fractionated according to the sugar sizes on Shodex RSpak DC-613, a cation-exchange resin column (Na+ form), with water-acetonitrile as the eluent in the presence of sodium acetate or triethylammonium acetate buffer. For the fractionation of sugar samples, dextran hydrolyzates, chitin oligomers and oligosaccharide moieties of ovomucoid were used. The oligosaccharides were strongly adsorbed to the resin column with solvents containing less water and at lower temperature, and were eluted in order of increasing molecular size above the critical concentration of acetonitrile. Baseline separation of a dextran hydrolyzate up to oligomers having 20 glucose units was observed by gradient elution. The separation efficiency and elution pattern were investigated by changing the buffer concentration, mobile phase pH and temperature.


Hyaluronate-alginate combination for the preparation of new biomaterials: investigation of the behaviour in aqueous solutions.
With the aim of producing a biomaterial for surgical applications, the alginate-hyaluronate association has been investigated. Crossed techniques were used to assess the existence of polymer interactions in aqueous solutions up to 20 mg/ml. Alginate was obtained from algae and hyaluronate was purified from rooster comb. Viscometry measurements using the capillary technique or the Couette flow, together with circular dichroism investigations, evidenced the moderate significance of interactions between the two polysaccharides in dilute solutions. In addition, the case of more concentrated solutions and containing 20 mg/ml alginate was approached by rheological measurements in the flow mode; the behaviour of the polymer associations appeared as a compromise between those of individual polysaccharides.


An open-source application for the standardized burst identification from the integrated muscle sympathetic neurogram.
Muscle sympathetic nerve activity (MSNA) can be acquired from humans using the technique of microneurography. The resulting integrated neurogram displays pulse-synchronous bursts of sympathetic activity, which undergoes processing for standard MSNA metrics including burst frequency, height, area, incidence, total activity, and latency. The procedure for detecting bursts of MSNA and calculating burst metrics is tedious and differs widely among laboratories worldwide. We sought to develop an open-source, cross-platform web application that provides a standardized approach for burst identification and a tool to increase research reproducibility for those measuring MSNA. We compared the performance of this web application against a manual scoring approach under conditions of rest, chemoreflex activation (n = 9, 20-min isocapnic hypoxia), and metaboreflex activation (n = 13, 2-min isometric handgrip exercise and 4-min postexercise circulatory occlusion). The intraclass correlation coefficient (ICC) indicated good to strong agreement between scoring approaches for burst frequency (ICC = 0.92-0.99), incidence (ICC = 0.94-0.99), height (ICC = 0.76-0.88), total activity (ICC = 0.85-0.99), and latency (ICC = 0.97-0.99). Agreement with burst area was poor to moderate (ICC = 0.04-0.67) but changes in burst area were similar with chemoreflex and metaboreflex activation. Scoring using the web application was highly efficient and provided data visualization tools that expedited data processing and the analysis of MSNA. We recommend the open-source web application be adopted by the community for the analysis of MSNA.NEW & NOTEWORTHY The basic analysis of muscle sympathetic nerve activity (MSNA) requires the identification of pulse-synchronous bursts from the integrated neurogram before standard MSNA metrics can be quantified. This process is a time-consuming task requiring an experienced microneurographer to visually identify and manually label bursts. We developed an open-source, cross-platform application permitting a standardized approach for sympathetic burst identification and present the performance of this application against a manual scorer under basal conditions and during sympathoexcitatory stresses.


Repurposing a rare opportunity: a brief insight into how implicit bias towards biomedicine impacts the care received by patients with a rare illness.
Medical students automatically couple rare illnesses with biomedical minutiae. Upon meeting CS (pseudonym), a 5-year-old boy with Worster Drought Syndrome, I became inadvertently caught in the trap of focusing on his diagnosis rather than CS as a patient. I fumbled around CS's past medical history by fervently asking about all the different types of seizures he was plagued by. It was only after CS's mother, TS (pseudonym), volunteered the psychosocial challenges she faced caring for CS that I realised the strong implicit bias I had towards biomedical aspects of patient care. I discovered that TS was robbed of being able to celebrate CS's developmental milestones, as they posed unique challenges with very serious risks. Having learned the extent of such psychosocial challenges, I searched to understand the origin of biases towards biomedicine, within myself and within the medical system. I attribute my own biases in part to the current state of medical education, which disproportionately focuses on the scientific, rather than psychosocial and humanistic factors. Systemically, there is a large commercial driving force behind scientific research into rare illnesses. The interest in rare illnesses displayed by pharmaceutical industries only after the incentivisation by various countries highlight the socio-political constraints that bind research in this field. These biases, along with the marginalisation of patients and families with rare illnesses, means there is a very real risk that the goals of all stakeholders are incongruous. As such, it is imperative that we give these patients and families a voice.


The promise and perils of CNS drug delivery: a video debate.
Neurodegenerative and infectious disorders related to host genetics, aging, and environment are rapidly increasing. Drugs, vaccines, or regenerative proteins offer "real" possibilities for positively affecting disease outcomes but are limited by access across the blood-brain barrier. New developments in nanomedicine and cell based drug delivery are becoming available. These discoveries can lead to improved neurological disease outcomes. Such obstacles include the toxicities inherent in the delivery systems de novo such as immuno- and neurological dysfunctions and perturbations of blood-brain barrier function. This debate by leading experts in the field highlights the promise and perils of CNS drug delivery. Click on Supplemental HTML to watch the streaming video.


Toxocara canis infection induces antigen-specific IL-10 and IFNgamma production in pregnant dogs and their puppies.
Toxocara canis (T. canis) is originally a parasite of canine bitches and their pups. The pathogenicity of T. canis infection is enhanced during pregnancy and puppyhood. The aim of this study was to investigate if modification of IFNgamma and IL-10 secretion occurs during infection in pregnant dogs and puppies. Analysis of cytokines secreted could let us hypothesize a role for IL-10 and/or IFNgamma in T. canis infection. We tested T. canis-specific production of IFNgamma and IL-10 by lymphocytes of pregnant dogs and their puppies after in vitro re-exposure to purified excretory/secretory antigen (ESAg) from T. canis. Blood mononuclear cells (BMC) isolated from pregnant dogs and their puppies were cultured in the presence of ESAg. Cultures' supernatants were tested for cytokine levels by ELISA. Results obtained showed that IL-10 concentrations increased during pregnancy in infected animals and in the meantime IFNgamma production decreased. In puppyhood, we observed that, IL-10 concentration decreased with the age of puppies mainly in infected animals while IFNgamma increased. In conclusion, our data suggests that BMC of infected dogs have a particular modification of IL-10 and IFNgamma synthesis. These data could be the basis to design immunotherapeutic approaches.