Hysterical stridor: a benign cause of upper airway obstruction.
We present the cases of three patients with stridor that resolved spontaneously. Paradoxical vocal cord motion was documented in one patient. Normal vocal cord motion was present in the other two patients, but stridor had resolved in both cases. Many different terms have been used to describe this entity in the literature. Emergency physicians must recognize the subtle signs of hysterical stridor. Once more serious etiologies are ruled out, sedation and reassurance instead of aggressive airway intervention are required for this benign condition.


On the reproductive energetics of chorusing males: Energy depletion profiles, restoration and growth in two sympatric species of Ranidella (Anura).
The reproductive activity of males of two species of Ranidella was recorded for four years. Linear densities and vocal activity were monitored, and correlated with rainfall. Energy and ash content of somatic tissue were examined during the course of breeding seasons. Depletions of energy reserves in somatic tissue, fat-bodies and livers were charted through each breeding season. Allometric equations linking these energetic quantities with snout-vent length were used to estimate the growth between breeding seasons of soma, fat-bodies and livers. Males invest heavily in current reproduction and relatively little in growth. Virtually all of a male's reproductive expenditure is directed to mechanisms of intrasexual competition for matings rather than investment in gonads, gametes or parental behavior.


Looking Back on Philanthropy in a Pandemic Foundation Colleagues Share Common Perspectives from Across the Pond.
Over the past year, the pandemic caused havoc globally touching the lives of most people. This included emerging challenges for nonprofits on the front lines of escalating need while at the same time limiting fundraising. Scaling up to meet needs in an extreme resource constrained environment pushed many nonprofits to the brink of insolvency. Many foundations have responded effectively to this circumstance by increasing grant making, reducing red tape, and extending greater flexibility for nonprofits. In doing so, foundations have exercised unusual humility in how they positioned themselves relative to nonprofits in protecting capacity to serve intended beneficiaries. This op-ed explores the relaxing of traditional tensions between foundations and grant seekers in ways that enabled more adequate and timely responses to pressing human needs in the face of the pandemic.


Effect of NaCl and KCl salts on the cytomorphology of pars distalis of the frog Rana cyanophlyctis (Schneider).
The effect of salts on the pars distalis of R. cyanophlyctis was studied by placing them in sodium chloride, potassium chloride (0.5%), distilled water and tapwater (control) for 15 days. In frogs kept in NaCl solution basophil type 3 cells (B3) showed marked hypertrophy and degranulation, whereas the B3 cells of frogs kept in KCl solution showed the hypertrophy and accumulation of secretory granules inside their cytoplasm. The B3 cells of frogs kept in distilled water or tapwater showed no changes. The other cell types of the pars distalis (A1 and A2 acidophils; B1 and B2 basophils) remained unaffected. It is concluded that the B3 cells are the probable source of adrenocorticotrophin and that the adenohypophyseal hormone(s) play a role in the maintenance of water and salt balance in R. cyanophlyctis.


The effectiveness of chemoprophylaxis against malaria for non-immune migrant workers in eastern Thailand.
A randomized, double-blind field trial was carried out to compare the effectiveness of mefloquine plus sulfadoxine-pyrimethamine (MSP) with that of sulfadoxine-pyrimethamine (SP) in chemoprophylaxis against malaria. The study was conducted in 193 migrant workers in the eastern rural areas of Thailand which are known to be highly endemic for multidrug-resistant Plasmodium falciparum infection. MSP was found to be more effective than SP in the suppression of both P. falciparum and P. vivax parasitaemias, when administered weekly for 12 weeks (P = 0.0014). Complete suppression of P. falciparum was achieved by MSP while 8 subjects receiving SP developed parasitaemia. One subject in the MSP group developed P. vivax parasitaemia, compared with 4 in the SP group. However, in view of the reported complications associated with the use of long-acting sulphonamides, some of which can be life threatening, prophylactic regimens containing sulfadoxine, though proved efficacious, must be used with extreme caution.


Bacterial autofluorescence in infected perineal wounds: A prospective cohort study.
Diagnosis of perineal wound infection based solely on clinical signs and symptoms is subjective, and often incorrectly identifies wounds with clinically significant bacterial loads. New advances in wound care such as bacterial fluorescence imaging allow point-of -care assessment of bacterial burden. This single-center, prospective observational study included 80 women with perineal wound infection and aimed to determine the incidence of significant bacterial colonization identified with bacterial fluorescence imaging. Also, to evaluate the diagnostic accuracy of bacterial fluorescence imaging. 30 women (37.5%) had fluorescence in their wounds despite antibiotic therapy. The sensitivity of bacterial fluorescence imaging in the diagnosis of wounds with a clinically significant bacterial burden was 83% and specificity was 90%. The positive predictive value was 92% and negative predictive value was 80%. Overall, diagnostic accuracy was substantial. The results of this study demonstrate that bacterial fluorescence imaging can provide real-time information surrounding the bacterial burden of perineal wounds. ClinicalTrials.gov NCT04480684.


Associations between gut microbiota and Parkinson disease: A bidirectional Mendelian randomization analysis.
Parkinson disease (PD)-associated alterations in the gut microbiome have been observed in clinical and animal studies. However, it remains unclear whether this association reflects a causal effect in humans. We performed two-sample bidirectional Mendelian randomization using summary statistics from the international consortium MiBioGen (N = 18,340), the Framingham Heart Study (N = 2076), and the International Parkinson's Disease Genomics Consortium for PD (33,674 cases and 449,056 controls) and PD age at onset (17,996 cases). Twelve microbiota features presented suggestive associations with PD risk or age at onset. Genetically increased Bifidobacterium levels correlated with decreased PD risk (odds ratio = 0.77, 95% confidence interval [CI] = 0.60-0.99, p = 0.040). Conversely, high levels of five short-chain fatty acid (SCFA)-producing bacteria (LachnospiraceaeUCG010, RuminococcaceaeUCG002, Clostridium sensustricto1, Eubacterium hallii group, and Bacillales) correlated with increased PD risk, and three SCFA-producing bacteria (Roseburia, RuminococcaceaeUCG002, and Erysipelatoclostridium) correlated with an earlier age at PD onset. Gut production of serotonin was associated with an earlier age at PD onset (beta = -0.64, 95% CI = -1.15 to -0.13, p = 0.013). In the reverse direction, genetic predisposition to PD was related to altered gut microbiota composition. These results support a bidirectional relationship between gut microbiome dysbiosis and PD, and highlight the role of elevated endogenous SCFAs and serotonin in PD pathogenesis. Future clinical studies and experimental evidence are needed to explain the observed associations and to suggest new therapeutic approaches, such as dietary probiotic supplementation.


Retention of brivaracetam in adults with drug-resistant epilepsy at a single tertiary care center.
Brivaracetam (BRV) is licensed as an adjunctive treatment for focal epilepsy. We describe our clinical experience with BRV at a large UK tertiary center. Adults initiated on BRV between July 2015 and July 2020 were followed up until they discontinued BRV or September 2021. Data on epilepsy syndrome, duration, seizure types, concomitant and previous antiseizure medication (ASM) use, BRV dosing, efficacy, and side effects were recorded. Efficacy was categorized as temporary (minimum three months) or ongoing (at last follow-up) seizure freedom, ≥50% seizure reduction, or other benefits (e.g., no convulsions or daytime seizures). Brivaracetam retention was estimated using Kaplan-Meier survival analysis. Two-hundred people were treated with BRV, of whom 81% had focal epilepsy. The mean (interquartile range [IQR]) follow-up time was 707 (688) days, and the dose range was 50-600 mg daily. The mean (IQR) of the previous number of used ASMs was 6.9 (6.0), and concomitant use was 2.2 (1.0). One-hundred and eighty-eight people (94%) had previously discontinued levetiracetam (LEV), mainly due to side effects. 13/200 (6.5%) were seizure free for a minimum of six months during treatment, and 46/200 (23%) had a ≥50% reduction in seizure frequency for six months or more. Retention rates were 83% at six months, 71% at 12 months, and 57% at 36 months. Brivaracetam was mostly discontinued due to side effects (38/75, 51%) or lack of efficacy (28/75, 37%). Concomitant use of carbamazepine significantly increased the hazard ratio of discontinuing BRV due to side effects (p = 0.006). The most commonly reported side effects were low mood (20.5%), fatigue (18%) and aggressive behavior (8.5%). These side effects were less prevalent than when the same individuals took LEV (low mood, 59%; aggressive behavior, 43%). Intellectual disability was a risk factor for behavioral side effects (p = 0.004), and a pre-existing mood disorder significantly increased the likelihood of further episodes of low mood (p = 0.019). Brivaracetam was effective at a broad range of doses in managing drug-resistant epilepsy across various phenotypes, but less effective than LEV in those who switched due to poor tolerability on LEV. There were no new tolerability issues, but 77% of the individuals experiencing side effects on BRV also experienced similar side effects on LEV.


Structure and functions of a multireplicon genome of Antarctic Psychrobacter sp. ANT_H3: characterization of the genetic modules suitable for the construction of the plasmid-vectors for cold-active bacteria.
Among Psychrobacter spp., there are several multireplicon strains, carrying more than two plasmids. Psychrobacter sp. ANT_H3 carries as many as 11 extrachromosomal replicons, which is the highest number in Psychrobacter spp. Plasmids of this strain were subjected to detailed genomic analysis, which enables an insight into the structure and functioning of this multireplicon genome. The replication and conjugal transfer modules of ANT_H3 plasmids were analyzed functionally to discover their potential for being used as building blocks for the construction of novel plasmid-vectors for cold-active bacteria. It was shown that two plasmids have a narrow host range as they were not able to replicate in species other than Psychrobacter, while remaining plasmids had a wider host range and were functional in various Alpha- and Gammaproteobacteria. Moreover, it was confirmed that mobilization modules of seven plasmids were functional, i.e., could be mobilized for conjugal transfer by the RK2 conjugation system. Auxiliary genes were also distinguished in ANT_H3 plasmids, including these encoding putative DNA-protecting protein DprA, multidrug efflux SMR transporter of EmrE family, glycine cleavage system T protein, MscS small-conductance mechanosensitive channel protein, and two type II restriction-modification systems. Finally, all genome-retrieved plasmids of Psychrobacter spp. were subjected to complex genome- and proteome-based comparative analyses showing that Antarctic replicons are significantly different from plasmids from other locations.


A scoping review of studies exploring physical activity and cognition among persons with cancer.
This scoping review aimed to identify and synthesize published studies on physical activity (PA) and cognition among persons with cancer and elucidate knowledge gaps. Articles were identified through electronic and manual searches (02/21 and 03/22) using the following inclusion criteria: (1) empirical, peer-reviewed publication in English, (2) sample comprised persons with cancer, and (3) reported at least one statistical association between PA and cognition. Multiple reviewers independently performed study selection and data extraction, and results were mapped in tabular and narrative form. Ninety-seven articles were eligible; these were largely published from 2017 to 2022 (54.6%), conducted in high-income countries (96.9%), and presented (quasi-)experimental studies (73.2%). Samples predominantly comprised women with breast cancer (48.5%), and recruitment often occurred post-treatment (63.9%). PA interventions included: aerobic (32.3%), resistance (4.8%), combined aerobic/resistance (38.7%), mind-body (19.4%), or other PA (4.8%). Most (66%) articles reported inconclusive findings; 32% were positive (in support of PA promoting cognition or vice versa), and 2.1% were negative. Diverse samples and studies with long-term follow-up were scarce. The state of knowledge is insufficient and more rigorous, large-scale studies are required to provide definitive conclusions about the cognitive benefits of PA among persons with cancer. Cancer-related cognitive impairment (CRCI) thwarts quality of life. This review summarizes what is known about the association between PA and cognition among persons with cancer and concludes that the evidence is currently equivocal. Hence, it remains uncertain if PA interventions can reduce CRCI, and large-scale PA intervention trials explicitly designed to promote cognition are greatly needed.


Amino-terminal pro-brain natriuretic peptide as a predictor of outcome in patients admitted to intensive care. A prospective observational study.
Amino-terminal pro-brain-type natriuretic peptide is known to predict outcome in patients with heart failure, but its role in an intensive care setting is not yet fully established. To assess the incidence of elevated amino-terminal pro-brain natriuretic peptide (NT-pro-BNP) on admission to intensive care and its relation to death in the ICU and within 30 days. Prospective, observational cohort study. A mixed non-cardiothoracic tertiary ICU in Sweden. NT-pro-BNP was collected from 481 consecutive patients on admission to intensive care, in addition to data on patient characteristics and outcome. A receiver-operating characteristic curve was used to identify a discriminatory level of significance, a stepwise logistic regression analysis to correct for other clinical factors and a Kaplan-Meier analysis to assess survival. The correlation between Simplified Acute Physiology Score (SAPS) 3, Sequential Organ Failure Assessment score (SOFA) and NT-pro-BNP was analysed using Spearman's correlation test. Quartiles of NT-pro-BNP elevation were compared for baseline data and outcome using a logistic regression model. An NT-pro-BNP more than 1380 ng -l on admission was an independent predictor of death in the ICU and within 30 days [odds ratio (OR) 2.6; 95% confidence interval (CI), 1.5 to 4.4] and was present in 44% of patients. Thirty-three percent of patients with NT-pro-BNP more than 1380 ng -1, and 14.6% of patients below that threshold died within 30 days (log rank P=0.005). NT-pro-BNP correlated moderately with SAPS 3 and with SOFA on admission (Spearman's ρ 0.5552 and 0.5129, respectively). In quartiles of NT-pro-BNP elevation on admission, severity of illness and mortality increased significantly (30-day mortality 36.1%; OR 3.9; 95% CI, 2.0 to 7.3 in the quartile with the highest values, vs. 12.8% in the lowest quartile). We conclude that NT-pro-BNP is commonly elevated on admission to intensive care, that it increases with severity of illness and that it is an independent predictor of mortality.


RRP1B is a metastasis modifier that regulates the expression of alternative mRNA isoforms through interactions with SRSF1.
RRP1B (ribosomal RNA processing 1 homolog B) was first identified as a metastasis susceptibility gene in breast cancer through its ability to modulate gene expression in a manner that can be used to accurately predict prognosis in breast cancer. However, the mechanism(s) by which RRP1B modulates gene expression is currently unclear. Many RRP1B binding candidates are involved in alternative splicing, a mechanism of gene expression regulation that is increasingly recognized to be involved in cancer progression and metastasis. One such target is SRSF1 (serine/arginine-rich splicing factor 1) (SF2/ASF, splicing factor 2/alternative splicing factor), an essential splicing regulator that also functions as an oncoprotein. Earlier studies demonstrated that splicing and transcription occur concurrently and are coupled processes. Given that RRP1B regulates transcriptional activity, we hypothesized that RRP1B also regulates the expression of alternative mRNA isoforms through its interaction with SRSF1. Interaction between RRP1B and SRSF1 was verified by coimmunoprecipitation and coimmunofluorescence. Treatment of cells with transcriptional inhibitors significantly increased this interaction, demonstrating that the association of these two proteins is transcriptionally regulated. To assess the role of RRP1B in the regulation of alternative isoform expression, RNA-sequencing data were generated from control and Rrp1b-knockdown cells. Knockdown of Rrp1b induced a significant change in isoform expression in over 600 genes compared with control cell lines. This was verified by quantitative reverse-transcription PCR using isoform-specific primers. Pathway enrichment analyses identified cell cycle and checkpoint regulation to be those most affected by Rrp1b knockdown. These data suggest that RRP1B suppresses metastatic progression by altering the transcriptome through its interaction with splicing regulators such as SRSF1.


Treatment of a case of septic tibial nonunion by the Capanna technique.
This report presents the case of a 25-year-old male with an infected tibial diaphyseal nonunion caused by a bone transport procedure carried out to treat an open fracture the patient had sustained 10 years before referral to our hospital. After an initial radical debridement, a bone defect was created, which was subsequently obliterated by placement of an antibiotic-impregnated cement spacer and Stimulan beads and covered by an anterolateral thigh flap. As the patient refused to wear an external fixator and his osseous biology was not amenable to a Masquelet procedure, a decision was made to apply the Capanna technique as soon as the infection healed. The second debridement resulted in a 12-cm-long bone defect that was filled with a tibial allograft and a vascularized fibular graft. At six months, the patient had regained full knee function and was able to bear his full weight, without pain or the need of support equipment. At one year, the bone had healed completely, the infection had subsided and the patient was able to resume his everyday activities. Although the Capanna technique was initially developed to reinforce reconstructions at risk of fracture or nonunion as a result of chemotherapy, its use in post-traumatic cases has been shown to be successful in a selected group of patents. Our study demonstrated that increasing the stability of a reconstruction with an allograft can accelerate the time to heal, and that using a vascularized fibular graft can enhance incorporation of the whole construct. It can be concluded that the Capanna technique is a valid treatment option for managing infected segmental bone defects in selected patients.


A phase 1b/2 study of duvelisib in combination with FCR (DFCR) for frontline therapy for younger CLL patients.
Fludarabine, cyclophosphamide, and rituximab (FCR) is highly effective initial therapy for younger patients with chronic lymphocytic leukemia (CLL); however, most eventually relapse. Duvelisib is a delta/gamma PI3K inhibitor approved for relapsed/refractory CLL. We conducted an investigator-initiated, phase 1b/2 study of duvelisib + FCR (DFCR) as initial treatment for CLL patients aged ≤65. A standard 3 + 3 design included two dose levels of duvelisib (25 mg qd and 25 mg bid). Duvelisib was given for 1 week, then with standard FCR added for up to six 28-day cycles, then up to 2 years of duvelisib maintenance. Thirty-two patients were enrolled. The phase 2 dose of duvelisib was identified as 25 mg bid. Hematologic toxicity was common, and all-grade non-hematologic toxicities included transaminitis (28%), febrile neutropenia (22%), pneumonia (19%), and colitis (6%). The best overall response rate by ITT was 88% (56% CR/CRi and 32% PR). The best rate of bone marrow undetectable minimal residual disease (BM-uMRD) by ITT was 66%. The rate of CR with BM-uMRD at end of combination treatment (primary endpoint) was 25%. Three-year PFS and OS are 73 and 93%, respectively. DFCR is active as initial therapy of younger CLL patients. Immune-mediated and infectious toxicities occurred and required active management.


Effects of motilin and octapeptide of cholecystokinin on antral and duodenal myoelectric activity in the interdigestive state and during inhibition by secretin and gastric inhibitory polypeptide.
In conscious dogs prepared with gastric cannulae and antral and duodenal electrodes, intravenous administration of synthetic porcine motilin and CCK-OP in varying doses resulted in significant increases in the mean percent frequency of spike potentials on slow waves. Motilin was a more potent stimulant than CCK-OP. Motilin-stimulated spike potentials in both antrum and duodenum were significantly suppressed by either natural porcine secretin or synthetic porcine GIP. Secretin suppressed the spike potentials of the antrum stimulated by CCK-OP but not those of the duodenum. The spike potentials stimulated by CCK-OP could not be suppressed by GIP in the dosages employed.


The Conserved VPS-50 Protein Functions in Dense-Core Vesicle Maturation and Acidification and Controls Animal Behavior.
The modification of behavior in response to experience is crucial for animals to adapt to environmental changes. Although factors such as neuropeptides and hormones are known to function in the switch between alternative behavioral states, the mechanisms by which these factors transduce, store, retrieve, and integrate environmental signals to regulate behavior are poorly understood. The rate of locomotion of the nematode Caenorhabditis elegans depends on both current and past food availability. Specifically, C. elegans slows its locomotion when it encounters food, and animals in a food-deprived state slow even more than animals in a well-fed state. The slowing responses of well-fed and food-deprived animals in the presence of food represent distinct behavioral states, as they are controlled by different sets of genes, neurotransmitters, and neurons. Here we describe an evolutionarily conserved C. elegans protein, VPS-50, that is required for animals to assume the well-fed behavioral state. Both VPS-50 and its murine homolog mVPS50 are expressed in neurons, are associated with synaptic and dense-core vesicles, and control vesicle acidification and hence synaptic function, likely through regulation of the assembly of the V-ATPase complex. We propose that dense-core vesicle acidification controlled by the evolutionarily conserved protein VPS-50/mVPS50 affects behavioral state by modulating neuropeptide levels and presynaptic neuronal function in both C. elegans and mammals.


Components of relative growth rate and sensitivity to nitrogen availability in annual and perennial species of Bromus.
Two grass species, the annual Bromus sterilis and the perennial Bromus erectus, were grown from seeds for 28 days in a hydroponic culture system at 1 and 100 μM NO3- in the nutrient solution. At 100 μM NO3-, the relative growth rate (RGR) of the perennial was 30% lower than that of the annual. This was only the consequence of the higher specific mass of its leaves, since its leaf mass ratio was higher than that of the annual and the unit leaf rates (ULR), calculated on an area basis, were similar for the two species. At 1 μM, the RGR of the annual was 50% lower than at 100 μM, while that of the perennial was not significantly lower. This was due mainly to a lower ULR for the annual. while for the perennial ULR was the same in both treatments. These differences between the two species were all the more striking in that the differences in total nitrogen concentrations and nitrate reductase activities between the two treatments were very similar for both species. These different responses together with differences in the nitrogen productivity of the two species suggest that the level of nutrient availability may play an important role in the distribution of these Bromus species in natural habitats.


Projected structure of the pore-forming OmpC protein from Escherichia coli outer membrane.
A single-projection structure analysis of a bacterial outer membrane protein, OmpC, has been carried out by electron microscopy of frozen hydrated specimens. Two distinct crystal polymorphs have been observed in the frozen-hydrated samples, and projection structures of both forms have been obtained to a resolution of 13.5 A. Preliminary examination of negatively stained samples revealed the expected, trimeric appearance of pores in the OmpC specimens. Electron microscopy of unstained, frozen-hydrated OmpC reveals the trimeric pore structure with equal clarity. In addition, the overall molecular envelope of the protein is readily discerned, and a major lipid-containing domain can also be seen. Because of the small coherent patch size, mosaic disorder, and unpredictable polymorphism of the presently available specimens, three-dimensional reconstruction of frozen-hydrated OmpC has not been carried out.


On the overestimation of early wall thickening at the carotid bulb by black blood MRI, with implications for coronary and vulnerable plaque imaging.
Black blood MRI is an attractive tool for monitoring normal and pathological wall thickening; however, limited spatial resolutions can conspire with complex vascular geometries to distort the appearance of the wall in ways hitherto unclear. To elucidate this, a thin-walled cylinder model was developed to predict the composite effects of obliqueness, in-plane resolution and voxel anisotropy on the accuracy of MRI-derived wall thickness measurements. These predictions were validated by means of imaging of a thin-walled carotid bifurcation phantom. Typical thick-slice axial acquisitions were found to result in artifactual wall thickening at the carotid bulb, owing to its obliqueness to the nominal imaging plane. Obliqueness was less problematic for near-isotropic resolutions; however, the obligatory reduction of in-plane resolution served to inflate wall thicknesses uniformly by up to 50%. Moreover, the nonlinear relationship between wall thickness and its overestimation served to mask genuine differences in wall thickness, an effect predicted to be worse for thinner coronary artery walls and plaque caps. Therefore, care must be taken when interpreting black blood MRI wall thickness measurements in the presence-or absence-of observed differences within or between individuals.


P-coumaric acid ameliorates fipronil induced liver injury in mice through attenuation of structural changes, oxidative stress and inflammation.
Fipronil is a broad-spectrum phenylpyrazole insecticide and has been used effectively in the agriculture. Due to its widespread use and bioaccumulation in the environment, it possesses significant threat to human and animals. P-coumaric acid is a natural dietary polyphenolic compound that has anti-oxidant and anti-inflammatory property. The present study was aim to investigate the ameliorative effect of p-coumaric acid on fipronil induced liver injury. The mice were divided into five groups (SHAM, FPN, FPN/PCA/50, FPN/PCA/100 and PCA/100) and challenged with fipronil @ 25 mg/kg bw (half of LD50). Haematological, liver function biomarkers (ALT, AST, ALP, GGT), biochemical parameters (MPO, oxidative, nitrosative stress and anti-oxidant enzyme activity), levels of serum and liver inflammatory cytokines (TNF-α, IL-1β and IL-10), histopathology were monitored. Fipronil administration caused a significant increase in liver enzymes with concomitant significant increase in inflammatory cytokines (TNF-α, IL-1β, IL-10) and myeloperoxidase activity. A significant increase in oxidative stress (lipid peroxidation, nitric oxide) as well as down regulation of anti-oxidant enzymes like superoxide dismutase (SOD) and catalase (CAT) along with histopathological changes such as microsteatosis, hypertrophy of the hepatocytes and necrosis were observed on fipronil administration. Administration of p-coumaric acid against fipronil caused decreased serum liver enzymes, inflammatory cytokines, myeloperoxidase activity and oxidative stress along with improvement in anti-oxidant enzyme levels and structural changes induced by fipronil. Thus p-coumaric acid ameliorates the FPN induced liver injury in mice through attenuation of structural changes, oxidative stress, and inflammation.


A novel microtiter plate assay for the quantitation of procoagulant activity on adherent monocytes, macrophage and endothelial cells.
The interaction of monocytes, macrophages and endothelial cells with inflammatory agents induces cell surface changes resulting in the activation of the coagulation cascade. A large volume 96 well plate microtiter assay has been developed which permits the quantitation of procoagulant activity on endotoxin stimulated cells without requiring the use of purified coagulation factors. Procoagulant activity is measured through a two stage amidolytic assay using commercially available Proplex as a source of factors VII and X and the chromogenic substrate S2222. The assay is rapid, linear, and sensitive as procoagulant activity can be detected on as few as 5 X 10(3) monocytes or macrophages and 3 X 10(2) endothelial cells.


Gastric carcinoma resected 95 months after being diagnosed: report of a case.
It is usually assumed that patients with gastric carcinoma will almost certainly die within 5 years if they do not receive treatment. We report herein a rare case of curative gastrectomy being performed 95 months after gastric carcinoma was diagnosed. A 37-year-old Japanese man had an upper gastrointestinal endoscopy with biopsy which revealed moderately differentiated adenocarcinoma of the stomach. This was diagnosed as type IIc early gastric carcinoma with ulceration but he refused surgery. At 45 years of age, 95 months later, he presented to our hospital with melena, at which time lesions in an identical location had enlarged to Borrmann type 3 advanced gastric carcinoma. Thus, a total gastrectomy with regional lymph node dissection was performed. Although there was no liver or peritoneal metastasis, the regional lymph nodes were involved; however, the patient recovered well and is still alive without any further recurrence roughly 4 years postoperatively. The natural history of gastric carcinoma and the malignant cycle are discussed following the presentation of this case.


Extending greedy feature selection algorithms to multiple solutions.
Most feature selection methods identify only a single solution. This is acceptable for predictive purposes, but is not sufficient for knowledge discovery if multiple solutions exist. We propose a strategy to extend a class of greedy methods to efficiently identify multiple solutions, and show under which conditions it identifies all solutions. We also introduce a taxonomy of features that takes the existence of multiple solutions into account. Furthermore, we explore different definitions of statistical equivalence of solutions, as well as methods for testing equivalence. A novel algorithm for compactly representing and visualizing multiple solutions is also introduced. In experiments we show that (a) the proposed algorithm is significantly more computationally efficient than the TIE* algorithm, the only alternative approach with similar theoretical guarantees, while identifying similar solutions to it, and (b) that the identified solutions have similar predictive performance.


CRISPR/Cas9-edited triple-fusion reporter gene imaging of dynamics and function of transplanted human urinary-induced pluripotent stem cell-derived cardiomyocytes.
To investigate the post-transplantation behaviour and therapeutic efficacy of human urinary-induced pluripotent stem cell-derived cardiomyocytes (hUiCMs) in infarcted heart. We used clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR/Cas9) technology to integrate a triple-fusion (TF) reporter gene into the AAVS1 locus in human urine-derived hiPSCs (hUiPSCs) to generate TF-hUiPSCs that stably expressed monomeric red fluorescent protein for fluorescence imaging, firefly luciferase for bioluminescence imaging (BLI) and herpes simplex virus thymidine kinase for positron emission tomography (PET) imaging. Transplanted cardiomyocytes derived from TF-hUiPSCs (TF-hUiCMs) engrafted and proliferated in the infarcted heart as monitored by both BLI and PET imaging and significantly improved cardiac function. Under ischaemic conditions, TF-hUiCMs enhanced cardiomyocyte (CM) glucose metabolism and promoted angiogenic activity. This study established a CRISPR/Cas9-mediated multimodality reporter gene imaging system that can determine the dynamics and function of TF-hUiCMs in myocardial infarction, which is helpful for investigating the application of stem cell therapy.


Quinolones in the treatment of gonorrhoea and Chlamydia trachomatis infections.
The results of two therapeutic trials in female patients with uncomplicated urogenital gonorrhoea (A) and in male patients with uncomplicated urethral gonorrhoea (B) treated with either 200 mg and 400 mg enoxacin orally, of one therapeutic trial in male patients with uncomplicated urogenital gonorrhoea treated with either 250 mg or 500 mg ciprofloxacin orally (C) and of one therapeutic trial in male patients with non-gonococcal urethritis (NGU) treated with ciprofloxacin 1 g daily during seven days (D) are presented and compared with the results of other investigators. The cure rate in study A was 100% (n = 40) in the 400 mg group and 95.7% (n = 46) in the 200 mg group. The cure rate in study B was 92% (n = 78) in the 400 mg group and 90% (n = 77) in the 200 mg group. In both studies no antichlamydial effect of enoxacin was observed. The cure rates in study C were 100% with 250 and 500 mg. An antichlamydial effect seemed to be present. In studies A, B and C side effects were minor and rare and were mainly nausea and headache. In study D (100 patients suffering from NGU) disappearance of Chlamydia trachomatis and Ureaplasma urealyticum one day after the end of treatment was observed in 29 of 32 (91%) and 28 of 32 (88%) cases, respectively. Pyuria disappeared in 44% and 74% of the patients showed clinical cure. However, two weeks after the end of treatment Chlamydia trachomatis and Ureaplasma urealyticum were observed in respectively six and eight cases. In 30% pyuria was still absent. Side effects were only minor.(ABSTRACT TRUNCATED AT 250 WORDS)


Alkali-induced reduction of the beta-cytochromes in purified complex III from beef heart mitochondria.
Approx. 40-50% of the cytochrome b in purified Complex III is reduced by ascorbate plus N,N,N',N'-tetramethyl-p-phenylenediamine or phenazine methosulfate at neutral pH. The remaining cytochrome b, including cytochrome b-565, is reduced by increasing the pH. The apparent pK for this reduction is between pH 10 and 11, and is more than two pH units higher than a similar alkali-induced transition in Mg-ATP particles. Alkali-induced reduction of cytochrome b occurs concomitantly with the exposure of hydrophobic tyrosine and tryptophan residues to a more hydrophilic environment. The relationship of these findings to the presence of a substrate accessibility barrier in Complex III is discussed.


Aspergillus fumigatus infection of the maxillary sinus. A case report.
The diagnosis and radiological findings in a 48-year-old woman with paranasal sinus Aspergillus fumigatus infection is described. The patient had had chronic post-nasal discharge and sinusitis for 7 years. She was treated by total removal of all infected material.


Field measurements of photosynthesis, water-use efficiency, and growth inAgropyron smithii (C3) andBouteloua gracilis (C4) in the Colorado shortgrass steppe.
Field measurements of gas exchange and growth were conducted on a C3 grass,Agropyron smithii, and a C4 grass,Bouteloua gracilis, in order to further establish the adaptive significance of the C4 pathway under natural conditions. Maximum rates of leaf area expansion in tillers and maximum seasonal photosynthesis rates of both species occurred during the cool, early summer month of June. The occurrence of maximum growth and photosynthesis inB. gracilis during this cool period was apparently related to its occupation of warm microenvironments next to the ground surface. As temperatures increased during the midsummer, photosynthesis rates decreased to 47% and 55% of the seasonal maximum inB. gracilis andA. smithii, respectively. Water-use efficiencies in both species were similar or slightly higher forB. gracilis during June, the period of maximum growth. By mid-July, however, leaves of the C3 grass,A. smithii, exhibited water-use efficiencies approximately half as high asB. gracilis. These differences in water-use efficiency were the result of differences in stomatal conductance, rather than differences in daily CO2 uptake rates which were similar in both species. The results demonstrate that in certain environments there are no offset periods of growth and maximum photosynthesis during the growing season in these C3 and C4 species. The greater amounts of daily water use inA. smithii during the midsummer might contribute to its much greater abundance in lowland sites in the shortgrass steppe. The C4 grass,B. gracilis, occurs in dry upland sites in addition to the more mesic lowland sites.


Partitioning behaviour of organic compounds between ionic liquids and supercritical fluids.
Applications and prospects of two-phase, tuneable solvent systems composed of ionic liquids (ILs) and supercritical fluids with an emphasis on supercritical carbon dioxide (scCO(2)) are reviewed. The IL-scCO(2) biphasic systems have increasingly been used in diverse fields of chemistry and technology, and some examples of these applications are mentioned here. Rational design of such applications can obviously benefit from pertinent data on phase equilibria including the partition coefficients of the prospective products and reactants between the two phases. Therefore, a reliable technique to measure the limiting partition coefficients would be of value. Here, the pros and cons of supercritical fluid chromatography in this respect are discussed. An overview of methods for predictive thermodynamic modelling of binary (IL-scCO(2)) and ternary (solute-IL-scCO(2)) systems is also included.


How do primary care physicians use long-term acid suppressant drugs? A population-based analysis of Dutch general practices.
A considerable proportion of the medication budget of Dutch general practitioners is spent on prescribed long-term acid suppressant drugs. We investigated the magnitude of long-term prescription of acid suppressant drugs in general practice and the frequency and means of confirming the primary working diagnosis. We used a retrospective descriptive study of 24 general practices in the Amsterdam region. We identified those receiving long-term acid suppressant therapy (12 or more weeks/year) from a total of 46,813 patients by extracting data from pharmacy databases. We measured the amount and duration of prescriptions for each medication, indications for prescription, and investigations performed by general practitioners. Of the 46,813 patients, 922 (2%) received long-term acid suppressant therapy. The duration of prescription varied from 12 weeks in 8% of patients to &gt 52 weeks in 23% of patients (mean = 33 weeks). In 25% of patients, no investigations were performed; 75% of patients underwent endoscopy or ingested a barium meal. The predominant diagnoses in investigated patients were ulcer disease (39%), gastroesophageal reflux disease (49%), and functional dyspepsia (gastritis, normal aspect; 18%). Helicobacter pylori status was available in 29% of patients with ulcer disease. Eradication therapy was reported in 44% of these patients. Among patients of physicians in general practice in the Amsterdam region, 2% used long-term acid suppressants. Patients with ulcer disease may stop taking acid suppressants after apparent successful H pylori eradication. Tapering strategies must be developed for patients with mild reflux disease or functional dyspepsia.


Fungal associations of roots of dominant and sub-dominant plants in high-alpine vegetation systems with special reference to mycorrhiza.
Types of root infection were analysed in healthy dominant and sub-dominant plants of zonal and azonal vegetation above the timberline in the Central and Northern Calcareous Alps of Austria. In the open nival zone vegetation, infection by fungi of the Rhizoctonia type was predominant, vesicular-arbuscular mycorrhizal infection, which was mostly of the fine endophyte (Glomus tenuis) type, being light and mainly restricted to grasses in closed vegetation patches. More extensive Glomus tenuis infection was found in the alpine grass heath, but in Carex, Rhizoctonia was again the most important fungus. The ericaceous plants of the dwarf shrub heath have typical ericoid infection, but quantitative analysis reveals a decrease of infection intensity with increase of altitude. The possible function of the various types of root infection are discussed, and the status of Rhizoctonia as a possible mycorrhizal fungus is considered.


Cancer development, chemoresistance, epithelial to mesenchymal transition and stem cells: A snapshot of IL-6 mediated involvement.
Interleukin-6 (IL-6) is a cytokine present in tumor microenvironment. Elevated level of IL-6 is associated with cancer cell proliferation, angiogenesis and metastasis through fueling STAT3, MAPK and Akt signaling. It promotes epithelial to mesenchymal transition (EMT) through altered expression of N-cadherin, vimentin, snail, twist and E-cadherin leading to cancer metastasis. IL-6 boosts mammosphere formation, self-renewal of stem cells, stemness properties of cancer cells and recruitment of mesenchymal stem cells. IL-6 is also a contributing factor for multidrug resistance in cancer due to gp130/MAPK/STAT3 mediated activation of transcription factors C/EBPβ/δ, overexpression of p-glycoprotein, EMT transition and expansion of stem cells. The in-depth investigation of IL-6 mediated cellular effects and its signaling pathway can provide the new window for future research and clinical development of IL-6 targeted therapy in cancer. Thus, an overview is delivered in this review deciphering the emerging aspect of the predominant influence of IL-6 in malignant transformation, EMT, cancer-associated stem cells and chemoresistance.


Predicting zebrafish spatial avoidance triggered by discharges of dairy wastewater: An experimental approach based on self-purification in a model river.
Wastewater discharges from dairy industries can cause a range of harmful effects in aquatic ecosystems, including a decline in biodiversity due to species evasion. Therefore, it is important to know the purification potential of rivers for the removal of pollutants released in dairy wastewater (DWW). The hypothesis adopted in this work was that the release of DWW into stretches of the Ribeirão dos Pombos River (São Paulo State, Brazil) might trigger an avoidance response, resulting in fish migrating to other regions, with the response being greater when the self-cleaning potential of the river is smaller. Therefore, the goals of the present study were to: (i) investigate how land use and seasonality of the rainfall regime influence the quality of the water in different areas of the river (P1: river source; P2: urban region; P3: rural region); (ii) assess the potential of the river to purify DWW; and (iii) evaluate the potential toxicity and repellency of DWW to the freshwater fish Danio rerio, using acute toxicity (mortality) and non-forced avoidance tests, respectively. P1 was shown to be the most preserved area. The chemical composition of the river varied seasonally, with higher concentrations of Cl- and SO42- at P3 during the rainy period. The river purification potential for DWW was higher at P2, due to greater microbiological activity (associated with higher BOD). The DWW was more acutely toxic in water from P2. The avoidance response was strongly determined by the concentration of DWW, especially for water from P2. The high capacity for self-cleaning at P2 did not seem sufficient to maintain the stability of the ecosystem. Finally, the non-forced exposure system proved to be a suitable approach that can assist in predicting how contaminants may affect the spatial distributions of organisms.


Would an anatomically shaped lumbar interbody cage provide better stability? An in vitro cadaveric biomechanical evaluation.
A biomechanical cadaveric study of lumbar spine segments. To compare the immediate stability provided by parallel-shaped and anatomically shaped carbon fiber interbody fusion I/F cages in posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) constructs with posterior pedicle screw instrumentation. Few biomechanical data are available on the anatomically shaped cages in PLIF and TLIF constructs. Twenty human lumbar segments were tested in flexion-extension (FE) (8 N m flexion, 6 N m extension), lateral bending (LB) (± 6 N m), and torsional loading (± 5 N m). Each segment was tested in the intact state and after insertion of interbody cages in one of 3 constructs: PLIF with 2 parallel-shaped or anatomically shaped cages and TLIF with 1 anatomically shaped cage. All cages received supplementary pedicle screw fixation. The range-of-motion (ROM) values after cage insertion and posterior fixation were compared with the intact specimen values using analysis of variance and multiple comparisons with Bonferroni correction. All constructs significantly reduced segmental motion relative to intact (P < 0.001). The motion reductions in FE, LB, and axial rotation were 85 ± 15%, 83 ± 18%, and 67 ± 6.8% for the PLIF construct using parallel cages, 79 ± 5.5%, 87 ± 10%, and 66 ± 20% for PLIF using anatomically shaped cages, and 90 ± 6.8%, 87 ± 12%, and 77 ± 22% for TLIF with an anatomically shaped cage. In FE and LB, the reductions in the ROM caused between the 3 constructs were equivalent (P > 0.05). In axial rotation, the TLIF cage provided significantly greater limitation in the ROM compared with the parallel-shaped PLIF cage (P = 0.01). The parallel-shaped and anatomically shaped I/F cages provided similar stability in a PLIF construct. The greater stability of the TLIF construct was likely due to a more anterior placement of the TLIF cage and preservation of the contralateral facet joint.


Full-length ureteral avulsion caused by ureteroscopy: report of one case cured by pyeloureterostomy, greater omentum investment, and ureterovesical anastomosis.
The aim of this report was to look for a good solution to full-length ureteral avulsion. This report retrospectively analyzed the data of the patient. The patient underwent ureteroscopic management. Full-length avulsion of ureter occurred during ureteroscopy. Pyeloureterostomy plus greater omentum investment outside the avulsed ureter and ureterovesical anastomosis were performed immediately. The patient was followed-up 25 months. After the first operation, the patient developed hydronephrosis because of press of fibrosis tissue outside ureter and anastomotic atresia of ureter-bladder. When we finished the second operation, the renal function recovered well. Full-length avulsion of ureter is a severe complication. Pyeloureterostomy plus greater omentum investment outside the avulsed ureter and ureterovesical anastomosis are probably a good choice.


Characterization of a superoxide dismutase gene from the archaebacterium Methanobacterium thermoautotrophicum.
A gene encoding superoxide dismutase (SOD) was cloned from the archaebacterium Methanobacterium thermoautotrophicum, the first example from an anaerobic bacterium. The deduced amino acid sequence showed overall similarity to sequences of known Mn- and Fe-SODs from aerobic organisms. Judging from a detailed sequence comparison, the cloned SOD gene is classified as Mn-SOD. By comparison of Mn-SOD sequences among various species it was suggested that archaebacterial superoxide dismutase is a direct descendant of a primordial enzyme. Between a putative promoter and the start codon there is an inverted repeat sequence which is also found in the counterpart of Halobacterium halobium.


A novel dimorphic microsporidian Ameson iseebi sp. nov. infecting muscle of the Japanese spiny lobster, Panulirus japonicus, in western Japan.
Japanese spiny lobsters (Panulirus japonicus) exhibiting white opaque abdominal muscle were found in Mie and Wakayama prefectures, in mid-Western Japan. Microscopically, two types of microsporidian spores, ovoid and rod-shaped, were observed infecting the muscle. Histologically, both types of spore were detected inside myofibers of the abdomen, appendages, and cardiac muscles and were often both observed in a single myofiber simultaneously. Transmission electron microscopy revealed that ovoid spores have villous projections on the surface, and that ovoid and rod-shaped spores have a polar filament with 12 coils and 6 to 8 coils respectively. Merogonic and sporogonic stages were observed around ovoid spores, but rarely around rod-shaped spores. The small subunit ribosomal DNA sequences obtained from both spore types were identical to each other, indicating that this microsporidian exhibits a clear spore dimorphism. Phylogenetic analysis based on the rDNA sequences indicates that this microsporidian is part of a clade consisting of the genera Ameson and Nadelspora, with the most closely related species being A. herrnkindi found in the Caribbean spiny lobster P. argus. Based on ultrastructural features, molecular phylogenetic data, host type and geographical differences among known species in these genera, the species found in whitened abdominal muscles of the Japanese spiny lobster is described as Ameson iseebi sp. nov.


Beamline P02.1 at PETRA III for high-resolution and high-energy powder diffraction.
Powder X-ray diffraction techniques largely benefit from the superior beam quality provided by high-brilliance synchrotron light sources in terms of photon flux and angular resolution. The High Resolution Powder Diffraction Beamline P02.1 at the storage ring PETRA III (DESY, Hamburg, Germany) combines these strengths with the power of high-energy X-rays for materials research. The beamline is operated at a fixed photon energy of 60 keV (0.207 Å wavelength). A high-resolution monochromator generates the highly collimated X-ray beam of narrow energy bandwidth. Classic crystal structure determination in reciprocal space at standard and non-ambient conditions are an essential part of the scientific scope as well as total scattering analysis using the real space information of the pair distribution function. Both methods are complemented by in situ capabilities with time-resolution in the sub-second regime owing to the high beam intensity and the advanced detector technology for high-energy X-rays. P02.1's efficiency in solving chemical and crystallographic problems is illustrated by presenting key experiments that were carried out within these fields during the early stage of beamline operation.


Spin in abstracts of randomized controlled trials in dentistry: A cross-sectional analysis.
Spin in randomized controlled trial (RCT) abstracts can misguide clinicians. In this cross-sectional analysis, the authors assessed the prevalence of spin in RCT abstracts and explored the factors potentially influencing it. In this cross-sectional analysis, the authors conducted a systematic search in top 10 dental journals based on Eigenfactor score and selected RCTs published in 2015 with statistically nonsignificant primary outcomes. The dentistry disciplines covered in these journals include general dentistry, dental research, oral implantology, endodontics, oral surgery, periodontology, and oral oncology. In these RCT abstracts, the authors assessed the prevalence of 3 different categories of spin and factors that could influence its presence using the t test and χ2 test. Spin assessment performed in the included 75 RCTs revealed the existence of spin in 23 abstracts (30.7%). Associations between the presence of spin in abstracts and the variables international collaborations, commercial support type, number of treatment arms, and journal impact factor were found to be statistically nonsignificant (P ≥ .05). Approximately one-third of the 75 RCT abstracts published in high-impact dental journals in 2015 with nonsignificant outcomes presented with some form of spin, irrespective of funding type and journal impact factor. Clinicians should be aware of the potential existence of spin in abstracts and be diligent in reading and appraising the full trial before incorporating its recommendations in clinical practice.


Nanobodies for Accurate Recognition of Iso-tenuazonic Acid and Development of Sensitive Immunoassay for Contaminant Detection in Foods.
The accurate analysis of chemical isomers plays an important role in the study of their different toxic effects and targeted detection of pollutant isomers in foods. The Alternaria mycotoxins tenuazonic acid (TeA) and iso-tenuazonic acid (ITeA) are two isomer mycotoxins with the lack of single analysis methods due to the similar structures. Antibody-based immunoassays exhibit high sensitivity and superior application in isomer-specific determination. Previously, various kinds of antibodies for TeA have been prepared in our group. Herein, highly specific nanobodies (Nbs) against ITeA mycotoxin were selected from immune nanobody phage display library, and one of Nbs, namely Nb(B3G3) exhibited excellent affinity, thermal stability as well as organic solvent tolerance. By molecular simulation and docking technology, it was found that stronger interaction between Nb(B3G3) and ITeA lead to higher affinity than that for its isomer TeA. Furthermore, a sensitive indirect competitive enzyme-linked immunosorbent assay (icELISA) was established with a limit of detection (LOD) of 0.09 ng/mL for ITeA mycotoxin. The recovery rate of ITeA in spiked samples was analyzed with 84.8%-89.5% for rice, 78.3%-96.3% for flour, and 79.5%-90.7% for bread. A conventional LC-MS/MS method was used to evaluate the accuracy of this proposed icELISA, which showed a satisfactory consistent correlation. Since the convenient strategy for nanobody generation by phage display technology, this study provide new biorecognition elements and sensitive immunoassay for analysis of ITeA in foods.


Effect of prolactin on tolerance and dependence to acute administration of morphine.
The effect of exogenous prolactin on the development of acute tolerance to and dependence on morphine was studied. As described elsewhere, analgesia induced by prolactin was subject to tolerance. Pretreatment with prolactin enhanced the development of tolerance to analgesia induced by morphine while it effectively suppressed the withdrawal symptoms. These results indicate that prolactin behaves like an opioid agonist and suggest that it may have therapeutic implications in the management of opioid dependence.


First appropriate use of automated external defibrillator in an infant.
Automated external defibrillators (AEDs) are currently not recommended for use in children under 1 year of age. We report the first description of successful AED defibrillation in an infant using a 50 J shock and provide rationale for employing these life-saving devices in infants at risk for sudden cardiac death.


Persistent organic pollutants and trace elements detected in New Zealand fur seals (long-nosed fur seal; Arctocephalus forsteri) from New South Wales, Australia, between 1998 and 2019.
Environmental pollution is a growing threat to wildlife health and biodiversity. The relationship between marine mammals and pollutants is, however, complex and as new chemicals are introduced to ecosystems alongside concomitant, interacting threats such as climate change and habitat degradation, the cumulative impact of these stressors to wildlife continues to expand. Understanding the health of wildlife populations requires a holistic approach to identify potential threatening processes. In the context of environmental pollution in little studied wildlife species, it is important to catalogue the current exposome to develop effective biomonitoring programs that can support diagnosis of health impacts and management and mitigation of pollution. In New South Wales, Australia, the New Zealand fur seal (Arctocephalus forsteri) is a resident species experiencing population growth following devastating historic hunting practices. This study presents a retrospective investigation into the exposure of New Zealand fur seals to a range of synthetic organic compounds and essential and non-essential trace elements. Liver tissue from 28 seals were broadly analyzed to assess concentrations of organochlorine and organophosphate pesticides, polychlorinated biphenyls, per- and polyfluoroalkyl substances, and essential and non-essential trace elements. In addition to contributing extensive pollution baseline data for the species, the work explores the influence of sex, age, and body condition on accumulation patterns. Further, based on these findings, it is recommended that a minimum of 11 juvenile male New Zealand fur seals are sampled and analyzed annually in order to maintain a holistic biomonitoring approach for this population.


An electronic processor for use with a whole body plethysmograph to determine specific airways conductance.
The panting manoeuvre traces produced by a whole body plethysmograph during the measurement of specific airways conductance (sGaw) are traditionally analysed by hand. Since this technique is tedious and time consuming it is prone to error, as well as suffering from considerable inter-observer variability. We describe a new inexpensive analogue electronic processor which rapidly produces readouts of sGaw and overcomes many of the problems associated with hand analysis. The system takes as its inputs the mouth flow and plethysmograph volume outputs from a pressure-corrected flow-displacement whole body plethysmograph, but it could be adapted for use with other types of plethysmograph. Since the processor is intended mainly for use during serial measurements of sGaw it does not carry out an unnecessary correction for flowmeter resistance. Using an electronic simulator of sGaw signals the output of the processor was found to be linear to better than 2% of full scale and to be insensitive to drift on the volume signal. The system has been comprehensively evaluated using signals from both normal subjects and patients. The processor output was found to agree well with the results of hand analysis, an agreement which was comparable with that obtained from computer based systems. For the normal subjects the equal value line adequately described the relationship between the processor and hand estimates of sGaw. However, for patients the slope of the best fit line was 18% less than unity but the correlation coefficient was high: 0.95. Reproducibility was found to be better than 3%.(ABSTRACT TRUNCATED AT 250 WORDS)


Visual outcomes after toric intraocular lens implantation in pediatric eyes undergoing cataract surgery.
To evaluate long-term visual outcomes and complications after toric intraocular lens (IOL) implantation in children with preexisting corneal astigmatism undergoing cataract surgery. Iladevi Cataract & IOL Research Center, Ahmedabad, India. Prospective, interventional case series. Children with regular corneal astigmatism of at least 1.5 diopters (D) were included. A standardized surgical technique with in-the-bag implantation of a toric IOL was performed. All children were followed up on postoperative day 1 and periodically thereafter, until 36 months postoperatively. The uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and residual refractive astigmatism were documented 36 months postoperatively. Rotational stability of toric IOL was also evaluated through the follow-up duration. Complications, particularly visual axis obscuration (VAO) and glaucoma, were documented. In total, 76 eyes (51 children) were included in the study. Mean age at surgery was 7.41 ± 2.82 years (SD) and mean preoperative keratometric astigmatism was 1.56 ± 2.13 D. The CDVA (logarithm of the minimum angle of resolution [logMAR]) improved significantly from 0.59 ± 0.43 preoperatively to 0.23 ± 0.27 36 months postoperatively (P = .03). Mean postoperative UDVA was 0.32 ± 0.26 logMAR. Mean refractive astigmatism at final follow-up was -0.55 ± 0.40 D, with 74% patients having a UDVA of at least 20/40; 5% of eyes needed VAO treatment and none developed glaucoma. No eye required repositioning of toric IOL until final follow-up. Toric IOL implantation reduced postoperative refractive astigmatism and gave excellent UDVA at 36 months follow-up in pediatric eyes undergoing nontraumatic cataract surgery.


Efficacy of microsurgical epididymal sperm aspiration (MESA) and intracytoplasmic sperm injection (ICSI) in obstructive azoospermia.
Our purpose was to test whether micromanipulation using subzonal insemination and intracytoplasmic sperm injection could improve the poor fertilization and pregnancy rates obtained when attempting in vitro fertilization in patients with congenital absence of the vas deferens and unreconstructable obstructive azoospermia with microsurgically retrieved epididymal spermatozoa. Conventional in vitro fertilization (group A; 14 cycles), subzonal insemination (group B; 13 cycles), and intracytoplasmic sperm injection (group C; 28 cycles) were carried out in 55 treatment cycles. Fertilization rates for groups A, B, and C were 16.1, 31.4, and 48.6%, respectively (P < 0.05). Clinical pregnancy rates for groups A, B, and C were 7.1, 7.7, and 32.1% (P < 0.05), respectively. In five cycles, intracytoplasmic sperm injection using epididymal sperm from alloplastic spermatoceles was performed and two clinical pregnancies (40%) were obtained. The combined microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection procedure is highly effective in improving the fertilization and pregnancy rate in congenital absence of the vas deferens and unreconstructable obstructive azoospermia. Furthermore, alloplastic spermatoceles may be useful for repeat sperm aspirations.


NFTs and asset class spillovers: Lessons from the period around the COVID-19 pandemic.
In this paper, we analyze the connectedness between returns for non-fungible tokens (NFTs) and other financial assets (equities, bonds, currencies, gold, oil, Ethereum) during the period from January 2018 to June 2021. By using the Time-Varying Parameter Vector Autoregressions (TVP-VAR) approach, we show that the overall connectedness between the returns for financial assets increased during the COVID-19 period. Our static analysis shows that the behavior of the majority of NFT returns is attributable to endogenous shocks and only a small portion of this variation resulted from the impact of innovation in other assets. The results suggest that NFTs are mainly independent of shocks from common assets classes and even from their close relation, Ethereum. The dynamic analysis across time reveals that during normal times, NFTs act as transmitters of systemic risk to some degree, but during stressful times, their role shifts, and they act as absorbers of risk spillovers. This suggests that NFTs may have diversification benefits during turbulent times, as apparent during the COVID-19 crisis, and especially around the great March 2020 market plunge.


Atrial and ventricular rat coronary arteries are differently supplied by noradrenergic, cholinergic and nitrergic, but not sensory nerve fibres.
The present immunohistochemical study set out to determine the extent of perivascular innervation in the rat heart, using markers for noradrenergic sympathetic fibres (tyrosine hydroxylase = TH), cholinergic parasympathetic fibres (vesicular acetylcholine transporter = VAChT), nitrergic fibres (neuronal NO synthase = nNOS), and peptidergic sensory fibres (calcitonin gene-related peptide = CGRP). For each of these antigens, the vascular innervation density was assessed separately in the atria, the basal and the apical parts of the ventricles, and was correlated to the inner vascular diameter. The four major findings are: (1) Each of these neurochemically defined populations shows an individual distribution pattern significantly different from the others with respect to correlation with vascular diameter and occurrence along atrial versus ventricular vessels. (2) Among autonomic efferent axons, nNOS-containing fibres are far less numerous than cholinergic and noradrenergic fibres. (3) Autonomic efferent axons (noradrenergic, cholinergic, nitrergic) are much more abundant around atrial than ventricular vessels, whereas perivascular CGRP-immunoreactive sensory nerve fibres are equally distributed in the various parts of the heart. (4) Noradrenergic and cholinergic axons preferentially innervate small-diameter vessels (negative linear correlation between index of innervation and vascular diameter), whereas the supply with CGRP-immunoreactive sensory nerve fibres does not change with vascular diameter. Collectively, the present study shows individual distribution patterns for each of the neurochemically defined populations of perivascular axons along the atrial and ventricular coronary arteries, indicating a highly differentiated nervous regulation of atrial versus ventricular, and large-diameter versus resistance vessels.


Anaesthetic management and non-invasive monitoring for caesarean section in a patient with cardiomyopathy.
This paper describes the anaesthetic management of a 29-year-old woman for an elective repeat Caesarean section. A diagnosis of peripartum cardiomyopathy (PPCM) had been made after her first delivery by Caesarean section three years earlier. Although the patient was currently asymptomatic, recent echocardiography demonstrated persistent left ventricular dilatation. The choice of haemodynamic monitors and the clinical significance of PPCM in this situation are discussed.


Immunoglobulin G subclasses and lymphocyte stimulatory responses to cytomegalovirus in transplant patients with primary cytomegalovirus infections.
The early activation of T- and B-cell responses to cytomegalovirus was studied in immunosuppressed patients. Primary lymphocyte stimulation to cytomegalovirus (CMV) antigen, a measure of T-helper activity, and anti-CMV IgG subclass responses were analyzed. Ten patients suffering from primary CMV infection following renal transplantation were studied. Of the ten, nine became positive for CMV induced lymphocyte proliferation 5-40 weeks after transplantation. Nine showed an almost simultaneous appearance of anti-CMV IgG1 and three at 3-32 weeks after transplantation, while one patient synthesized only low levels of anti-CMV IgG1. The lymphocyte proliferation assays have limited diagnostic value for primary CMV infection in renal transplant patients. The humoral and cellular immune responses seemed to be independent of each other.


Momentum conservation and some problems of metagalactic astronomy.
This article explains that bodies of plasma in active galactic nuclei and quasi-stellar objects-"magnetoids"-will attain large momenta because of anisotropy in the generation of relativistic particles and in the synchrotron emission. Magnetoids may therefore be expected to be ejected from the nuclei with high velocities, thus accounting for several puzzling observations in astronomy.


Re-evaluation of pectoralis major height as an anatomic reference for humeral height in fracture hemiarthroplasty.
Shoulder replacement may be indicated for complex proximal humeral fractures. The primary reason for disappointing results is the nonanatomic position of the prosthesis because the normal anatomic landmarks are disrupted when fractured. An anatomic reference outside of the zone of injury may facilitate proper positioning of fracture arthroplasty reconstructions. It is unknown whether the measurement from the top of the pectoralis major tendon (PMT) to the top of the humeral head is related to patient height. PMT measurements were performed on 21 pairs of cadaveric shoulders. A second group of PMT measurements was performed on 107 patients receiving a shoulder magnetic resonance imaging scan. A third PMT comparison group was included using historical measurements from 20 pairs of cadaveric shoulders. All heights, sexes, and ages were known. Statistical analysis used mixed-effects linear regression models. A consistent association between patient height and PMT was found, with a mean distance from the top of the PMT to the top of the humeral head of 58.9 mm in men and 55.2 mm in women. For every 10-mm increase in patient height over 1.7 m, there is a 1.7-mm increase in PMT (P = .01). Age was not associated with PMT distance (P > .5). A predictable measurement from the upper portion of the PMT to the top of the humeral head exists to guide implant height in fracture hemiarthroplasty and may be approximated by use of patient height and sex.


Adenosine 3',5'-cyclic monophosphate levels in normal and IAA-induced tumours in bean (Phaseolus vulgaris L.) embryos.
Endogenous levels of adenosine 3',5'-cyclic monophosphate in indole-3-acetic acid induced tumours, and control bean embryos were measured with Gilman protein binding assay. No significant differences in cAMP concentrations were found in IAA-induced tumours, which suggests that IAA does not mediate cAMP synthesis in bean embryos.


Clinicopathological characteristics and outcomes of synchronous renal cell carcinoma and urothelial carcinoma: A population-based analysis.
To better understand the characteristics, and survival outcomes of synchronous renal cell carcinoma (RCC) and urothelial carcinoma (UC), we described and analyzed the clinical features, factors, and prognosis of patients with synchronous RCC and UC using a large population-based database. Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2016), we identified patient with concurrent RCC and UC at initial diagnosis. Their clinicopathological features and prognosis were evaluated. A logistic regression model was used to examine risk factors for the occurrence of concomitant RCC and UC, and Kaplan-Meier survival curves were used to estimate overall survival. A total of 61,454 RCC patients were identified from the SEER database, 704 (1.1%) patients presented with synchronous RCC and UC. Among these patients, concurrent bladder tumors (566/704) are more common. Subsequently, subgroup analysis based on the location of UC indicated that patients with concurrent RCC and upper tract urothelial carcinoma (UTUC) had unfavorable UC characteristics (higher tumor stage and grade), compared with patients with concomitant bladder cancer. An increased risk of concurrent UC was observed among older age, male sex, and white race. Meanwhile, papillary RCC histology [odds ratio (OR) 3.23; 95% confidence interval (CI) 2.13-4.90], and smaller tumor (OR 6.63; 95% CI 4.46-9.87) were independent risk factors for concomitant UTUC. In addition, we found that synchronous RCC and UTUC was associated with worse survival by using Kaplan-Meier and multivariable analysis [hazard ratio (HR) 2.36, 95% CI 1.89-2.95]. However, concomitant bladder cancer did not affect survival outcomes of patients with RCC (HR 1.00, 95% CI 0.86-1.17). We found that synchronous concurrent RCC and UC is relatively uncommon and mostly located in the bladder. Older age, male sex, and white race increase the risk of synchronous RCC and UC. Meanwhile, patients with papillary RCC histology, and smaller tumors are more likely to have concomitant RCC and UTUC. Furthermore, our findings suggest that synchronous RCC and UTUC has a worse prognosis, while, concomitant bladder tumor did not affect the oncological outcomes of RCC.


Melatonin Treatment Alters Biological and Immunomodulatory Properties of Human Dental Pulp Mesenchymal Stem Cells via Augmented Transforming Growth Factor Beta Secretion.
Melatonin is an endogenous neurohormone with well-reported anti-inflammatory and antioxidant properties, but the direct biological and immunomodulatory effects of melatonin on human dental pulp stem cells (hDPSCs) has not been fully elucidated. The aim of this study was to evaluate the influence of melatonin on the cytocompatibility, proliferation, cell migration, odontogenic differentiation, mineralized nodule formation, and immunomodulatory properties of hDPSCs. To address the melatonin biological effects on hDPSCs, the cytocompatibility, proliferation, cell migration, odontogenic differentiation, mineralized nodule formation, and immunomodulatory properties of hDPSCs after melatonin treatment were evaluated. The statistical differences were evaluated using 1-way analysis of variance with the Tukey multiple comparison test. We found that melatonin did not alter hDPSC immunophenotype or cell viability, even at the highest concentrations used. However, using intermediate melatonin concentrations (10-300 μmol/L), a significantly higher proliferation rate (P < .05 and P < .01) and migration of hDPSCs (P < .01) were observed. Importantly, melatonin treatment (100 μmol/L) significantly increased the secretion of the anti-inflammatory cytokine transforming growth factor beta (P < .05 and P < .01) and provoked a more robust antiproliferative effect on mitogen-stimulated T cells (P < .05). Finally, and unlike previous results found with mesenchymal stem cells from other sources, melatonin fails to induce or accelerate the spontaneous osteogenic differentiation of hDPSCs. Together, these findings provide key data on the bioactivity of melatonin and its effects on hPDSC biological and immunomodulatory properties.


The utility and limitations of (18)F-fluorodeoxyglucose positron emission tomography with computed tomography in patients with primary mediastinal B-cell lymphoma: single institution experience and literature review.
There are limited data regarding the role of (18)F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET-CT) scanning in primary mediastinal B-cell lymphoma (PMBL). We analyzed 28 patients with PMBL treated with chemotherapy, of whom 25 (89%) also received rituximab and 17 (61%) radiotherapy. PET-CT scans were interpreted using visual analysis and a 5-point scale. After a median follow-up of 2.6 years, four patients relapsed and two died. The 2-year progression-free survival and overall survival were 86% and 94%. PET-CT has excellent negative predictive value (interim, 86-87%; end of treatment, 95%) but limited positive predictive value due to the high frequency of positive scans. Several patients with persistent metabolically active masses underwent biopsies, which showed necrosis but no lymphoma. Thus a negative PET-CT is an excellent predictor of subsequent outcome. However, residual metabolically active masses after treatment should be biopsied to confirm viable lymphoma prior to salvage therapy.


Tissue Repair: Guarding against Friendly Fire.
Following tissue injury, cells produce reactive molecules that fight off invading pathogens, but these factors might also damage the host tissue. A new study has characterized a network of defense pathways that synergize to protect cells from collateral damage and drive repair.


The role of Streptococcus pneumoniae sortase A in colonisation and pathogenesis.
Sortase enzymes are found throughout Gram-positive bacteria and are responsible for the covalent attachment of specific proteins to the cell wall. Through the anchoring of these cell wall proteins, sortase enzymes are important in the ability of several Gram-positive pathogens to cause disease. Previously, deletion of srtA from Streptococcus pneumoniae (the pneumococcus) was shown to disturb the localisation of surface proteins, and decrease bacterial adherence to human pharyngeal cells in vitro. Here we present data demonstrating, for the first time, a role for srtA as a pneumococcal fitness factor in experimental models of pneumonia and bacteraemia. In addition, srtA contributed to nasopharyngeal colonisation in vivo. Furthermore, we find that the contribution of srtA varied between two pneumococcal strains. We show that the known role of srtA in adherence in vitro is dependent on capsule expression, the role of SrtA in adherence to human cells only being apparent in the absence of the pneumococcal capsule. The srtA gene was detected by PCR in all 82 clinical isolates examined and sequencing of the gene from 20 strains showed srtA to be highly conserved. The ubiquitous distribution of srtA was in contrast to the other known pneumococcal sortase genes, srtB, C and D, which were found in only 14 of the 82 tested strains (17%).


Efficacy of low dose rituximab in treatment-resistant CIDP with antibodies against NF-155.
We herein to describe the response and the potential treatment mechanism of low dose rituximab in patients with treatment-resistant chronic inflammatory demyelinating polyneuropathy (CIDP) with antibodies against neurofascin-155 (NF-155). Patients received 100 mg rituximab once weekly for 4 weeks followed by 100 mg per month for 2 additional doses. Clinical function scores, Fahn- Tolosa-Marin Tremor Rating Scale (FTMTRS) and flow cytometry of peripheral blood were scheduled before and at 1, 3, 6 months after rituximab treatment. All clinical function score including MRC, INCAT, Hughes, mRS, ODSS and FTMTRS scores showed obvious improvement at the post-treatment follow-up 1,3,6 months in comparison with baseline values. The proportion of CD19 + CD27+, CD19 + CD38+ and CD138 in lymphocytes of all patients declined at 1,3,6 month and the proportion of CD19 + CD24hiCD38hi in one patient was increased at 6 months after rituximab treatment. Low dose rituximab can significant improve disease severity and disabling tremor of CIDP patients with anti-NF155 antibody by the powerful role of B cell depletion within six months and subsequent reestablishment of B-cell subsets including increasing regulatory B cells, inhibiting memory B cells and reducing plasmablasts.


Three Types of Intimate Relationships among Individuals with Chronic Pain and a History of Trauma Exposure.
Individuals with chronic pain often have psychiatric disorders, such as depression and posttraumatic stress disorder (PTSD), which can affect their intimate relationship satisfaction and stability. Little is known about the nature of support stemming from chronic pain patients' intimate relationships, and therefore, this study sought to: (1) use cluster modeling to construct specific intimate relationship groups based on types of support patients receive, and (2) determine if there is a relationship between support type and PTSD, chronic pain, anxiety, and depression. Ward's method of cluster analysis in Stata was used to create groups based on the level of informational, affirmation, confident, emotional, and fun support received from chronic pain patients' most intimate relationship. Three types of support were identified: high (type 1, n = 17), high emotional/low instrumental (type 2, n = 9), and unstable (type 3, n = 15). Types 1 and 3 included more family members (Type 1: 100%, Type 2: 93%), than type 2 (77%). Type 2 patients experienced more trauma (Mean = 9.4 ± 1.7 vs. 7.5 ± 0.88 for types 1 and 3) and were significantly more likely to have PTSD (X² = 7.91, p < 0.05. Patients with low familial support may also benefit from PTSD screening and referral but further study is needed.


The effects of Wechsler Intelligence Scale for Children-Fourth Edition cognitive abilities on math achievement.
This study used structural equation modeling to examine the effect of Stratum III (i.e., general intelligence) and Stratum II (i.e., Comprehension-Knowledge, Fluid Reasoning, Short-Term Memory, Processing Speed, and Visual Processing) factors of the Cattell-Horn-Carroll (CHC) cognitive abilities, as operationalized by the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV; Wechsler, 2003a) subtests, on Quantitative Knowledge, as operationalized by the Wechsler Individual Achievement Test, Second Edition (WIAT-II; Wechsler, 2002) subtests. Participants came from the WISC-IV/WIAT-II linking sample (n=550). We compared models that predicted Quantitative Knowledge using only Stratum III factors, only Stratum II factors, and both Stratum III and Stratum II factors. Results indicated that the model with only the Stratum III factor predicting Quantitative Knowledge best fit the data.


Coronaviruses and their therapy.
Coronaviruses may cause respiratory, enteric and central nervous system diseases in many species, including humans. Until recently, the relatively low burden of disease in humans caused by few of these viruses hampered development of coronavirus specific therapeutics. However, the emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) has prompted the discovery of such drugs. Subsequent studies in animal models demonstrated the efficacy of SARS-CoV specific monoclonal antibodies, pegylated-interferon-alpha and siRNAs against SARS-CoV. Furthermore, several antivirals shown to be effective against other viruses were tested in vitro. Because of availability and shown efficacy, the use of interferons may be considered should SARS-CoV or a related coronavirus (re)-emerge. The more recent design of wide-spectrum inhibitors targeting the coronavirus main proteases may lead to the discovery of new antivirals against multiple coronavirus induced diseases.


Roles of Sema4D and Plexin-B1 in tumor progression.
Sema4D, also known as CD100, is a protein belonging to class IV semaphorin. Its physiologic roles in the immune and nervous systems have been extensively explored. However, the roles of Sema4D have extended beyond these traditionally studied territories. Via interaction with its high affinity receptor Plexin-B1, Sema4D-Plexin-B1 involvement in tumor progression is strongly implied. Here, we critically review and delineate the Sema4D-Plexin-B1 interaction in many facets of tumor progression: tumor angiogenesis, regulation of tumor-associated macrophages and control of invasive growth. We correlate the in vitro and in vivo experimental data with the clinical study outcomes, and present a molecular mechanistic basis accounting for the intriguingly contradicting results from these recent studies.


Differences in white matter fiber tract development present from 6 to 24 months in infants with autism.
Evidence from prospective studies of high-risk infants suggests that early symptoms of autism usually emerge late in the first or early in the second year of life after a period of relatively typical development. The authors prospectively examined white matter fiber tract organization from 6 to 24 months in high-risk infants who developed autism spectrum disorders (ASDs) by 24 months. The participants were 92 high-risk infant siblings from an ongoing imaging study of autism. All participants had diffusion tensor imaging at 6 months and behavioral assessments at 24 months; a majority contributed additional imaging data at 12 and/or 24 months. At 24 months, 28 infants met criteria for ASDs and 64 infants did not. Microstructural properties of white matter fiber tracts reported to be associated with ASDs or related behaviors were characterized by fractional anisotropy and radial and axial diffusivity. The fractional anisotropy trajectories for 12 of 15 fiber tracts differed significantly between the infants who developed ASDs and those who did not. Development for most fiber tracts in the infants with ASDs was characterized by higher fractional anisotropy values at 6 months followed by slower change over time relative to infants without ASDs. Thus, by 24 months of age, those with ASDs had lower values. These results suggest that aberrant development of white matter pathways may precede the manifestation of autistic symptoms in the first year of life. Longitudinal data are critical to characterizing the dynamic age-related brain and behavior changes underlying this neurodevelopmental disorder.


Accuracy of fatal occupational injury registration in a high-income country: A comparison of two-source capture-recapture estimates with the number of cases identified in four register systems in Norway, 2000-2003.
Globally, work-related deaths (injuries and diseases) are a major social and public health problem. Register data on fatal occupational injuries in high-income countries may be considered to have high quality, especially when reporting is mandatory and regulated by law. We aimed to assess the accuracy of work-related injury death statistics in Norway, with reference to the Labour Inspection Authority and three other on-going registration systems (the cause-specific mortality register, the register for governmental compensations, and the register for insurance companies). In this register-based study, we used the capture-recapture technique to adjust for undercounting. We investigated whether the capture-recapture method using two or three sources gave a valid estimate of fatal occupational injuries as compared with the number of cases identified in four registers administrated by the Norwegian Labour Inspection Authority, Statistics Norway, the Labour and Welfare Administration, and Finance Norway. The inclusion criteria were fatal unintentional injuries among residents of Norway between 2000 and 2003 that occurred while working for income in private and public land-based industries. We obtained ethical and legal approvals. In a period of four years (2000-2003), the Labour Inspection Authority registered 171 occupational injury deaths among residents employed in land-based industries. Two combinations of data sources gave capture-recapture estimates of 246 [95% CI 216; 279] and 265 [95% CI 234; 299] deaths. In total, 246 cases were identified in the four registration systems, which was 44% higher than the number of deaths registered by the Labour Inspection Authority. The Labour Inspection Authority had the most complete register out of the four registration systems. The capture-recapture method used on two overlapping data sources gave highly valid estimates of the total deaths. We demonstrated the existence of significant weaknesses in the registration systems in a country considered to have high-quality register data.


Metabolic specialization in itaconic acid production: a tale of two fungi.
Some of the oldest and most established industrial biotechnology processes involve the fungal production of organic acids. In these fungi, the transport of metabolites between cellular compartments, and their secretion, is a major factor. In this review we exemplify the importance of both mitochondrial and plasma membrane transporters in the case of itaconic acid production in two very different fungal systems, Aspergillus and Ustilago. Homologous and heterologous overexpression of both types of transporters, and biochemical analysis of mitochondrial transporter function, show that these two fungi produce the same compound through very different pathways. The way these fungi respond to itaconate stress, especially at low pH, also differs, although this is still an open field which clearly needs additional research.


Delayed perihematomal hypoperfusion is associated with poor outcome in intracerebral haemorrhage.
The aim of this study was to characterize the temporal evolution and prognostic significance of perihematomal perfusion in acute intracerebral haemorrhage (ICH). A single-centre prospective cohort of patients with primary spontaneous ICH receives computed tomography perfusion (CTP) within 6 h from onset (T0) and at 7 days (T7). Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the manually outlined perihematomal low-density area. Poor functional prognosis (modified Rankin Scale 3-6) at 90 days was the outcome of interest, and predictors were explored with multivariable logistic regression. A total of 150 patients were studied, of whom 52 (34.7%) had a mRS 3-6 at 90 days. Perihematomal perfusion decreased from T0 to T7 in all patients, but the magnitude of CBF and CBV reduction was larger in patients with unfavourable outcome (median CBF change -7.8 vs. -6.0 ml/100 g/min, p < .001, and median CBV change -0.5 vs. -0.4 ml/100 g, p = .010, respectively). This finding remained significant after adjustment for confounders (odds ratio [OR] for 1 ml/100 g/min CBF reduction: 1.33, 95% confidence interval [CI] (1.15-1.55), p < .001; OR for 0.1 ml/100 g CBV reduction: 1.67, 95% CI 1.18-2.35, p = .004). The presence of CBF < 20 ml/100 g/min at T7 was then demonstrated as an independent predictor of poor functional outcome (adjusted OR: 2.45, 95% CI 1.08-5-54, p = .032). Perihaemorrhagic hypoperfusion becomes more severe in the days following acute ICH and is independently associated with poorer outcome. Understanding the underlying biological mechanisms responsible for delayed decrease in perihematomal perfusion is a necessary step towards outcome improvement in patients with ICH.


Selectively peeling of spent LiFePO4 cathode by destruction of crystal structure and binder matrix for efficient recycling of spent battery materials.
Impurity Fe could severely damage the performance of resynthesized cathode material, and therefore, LiFePO4 cathode should be removed from the mixed spent LIBs for materials recycling. In this research, a non-hydrometallurgy method has been developed to separate LiFePO4 by selectively peeling-off the LiFePO4 cathode material and the peeling-off process was well explained by theoretical modeling. The peeling-off efficiency of LiFePO4 was approximate 100 % and that of LiMn2O4/LiCoO2/Li(Ni, Co, Al)O2/Li(Ni, Mn, Co)O2 was only 0.08 %. That is, the separating selectivity was 1250. Mechanism study revealed that the peeling-off was achieved through selective destruction of the LiFePO4 crystal and the matrix of polyvinylidene fluoride (PVDF) binder. Particularly, the crystal structure of LiFePO4 was firstly destructed by sulfide, thus LiFePO4 particles were detached from the matrix of PVDF binder. Then, the PVDF binder without LiFePO4 particles filling were more susceptible to be brittlely peeled off by the micro-explosion force of hydrogen from the reaction of Al foil with water due to the weakened mechanical strength. The process is suitable for recycling varied types of spent LIBs, having a strong potential for industrial application.


Increased exon-trapping efficiency through modifications to the pSPL3 splicing vector.
Exon trapping allows for the rapid identification and cloning of coding regions from cloned eukaryotic DNA. In preliminary experiments, we observed two phenomena which limited the exon-trapping efficiency of pSPL3-based systems. The first factor that affected performance was revealed when we found that up to 50% of the putative trapped exons contained sequences derived from the intron of the pSPL3 trapping vector. Removal of the DNA sequences responsible for the cryptic splice event from the original splicing vector resulted in a new vector, pSPL3B. We demonstrate that pSPL3B virtually eliminates pSPL3-only spliced products while maximizing the proportion of exon traps containing genomic DNA (> 98%). The other step which impacted performance was our observation that a majority of the ampicillin-resistant (APR) clones produced after shotgun subcloning from ApR cosmids into pSPL3 were untrappable, pSPL3-deficient, recircularized cosmid vector fragments. Replacement of the pSPL3 ApR gene with the CmR cassette encoding chloramphenicol (Cm) acetyltransferase enabled selection for only pSPL3-containing CmR clones. We show a 30-40-fold increase in the initial subcloning efficiency of cosmid-derived fragments with pSPL3-CAM, when compared to pSPL3. The collective vector alterations described improve the overall exon-trapping efficiency of the pSPL3-based trapping system.


Conformational change of human lens insoluble alpha-crystallin.
Human lens alpha-crystallin becomes progressively insoluble with age and is the major crystallin component in the water-insoluble (WI) fraction. The mechanism that causes the originally water-soluble (WS) alpha-crystallin to become insoluble is unknown. A conformational change by chemical modification may be the cause, but the nature of insolubility renders it impossible to study protein conformation in the WI fraction by most spectroscopic measurements. In the present study, alpha-crystallin in the WI fraction was extracted by urea and reconstituted to a folded protein by dialysis. The refolded urea-soluble (US) alpha-crystallin was compared with WS alpha-crystallin. The US alpha-crystallin has a greater amount of polymeric species, but fewer degraded subunits than the WS alpha-crystallin as shown by SDS-PAGE and Western blot. Circular dichroism (CD) measurements indicate that they have the same secondary structure but a different tertiary structure, possibly a partial unfolding in the US alpha-crystallin. This is supported by fluorescence measurements: Trp residues are more exposed and protein has a more-hydrophobic surface in the US than in the WS alpha-crystallin. Blue fluorescence further indicates that the US alpha-crystallin has a greater amount of pigment than the WS alpha-crystallin. Together, these results indicate that the US alpha-crystallin is a chemically and conformationally modified protein.


Response Strategies for Emerging Infectious Diseases: More Efforts Are Needed.
In recent years, emerging infectious disease outbreaks have placed significant health and socioeconomic burdens upon the population [...].


Mirror asymmetry of Category and Letter fluency in traumatic brain injury and Alzheimer's patients.
In this study we contrasted the Category fluency and Letter fluency performance of 198 normal subjects, 57 Alzheimer's patients and 57 patients affected by traumatic brain injury (TBI). The aim was to check whether, besides the prevalence of Category fluency deficit often reported among Alzheimer's patients, the TBI group presented the opposite dissociation. According to some recent claims, in fact, the deficit of TBI would be equally severe for both fluency types. The inquiry followed different approaches for data analysis, including the evaluation of a unique index (Fluency Type Index or FTI), independent of the overall fluency and aimed at expressing at individual subject level the relationship between Category and Letter fluency. The results confirmed that Alzheimer's patients are more defective on Category than Letter fluency, and also clearly indicated that an opposite pattern applies to TBI patients. TBI seems to cause a relatively more severe impairment of Letter than Category fluency, probably due to its impact on the frontal lobe structures. We discuss whether, on the basis of the statistical distribution of our data, it is worth considering as homogeneous populations broadly defined groups as Alzheimer's or TBI patients.


[Neonatal presentation of Prader-Willi syndrome: A report of five cases].
Prader-Willi syndrome (PWS) is a fingerprint disease caused by the loss of paternally inherited chromosome 15q11.2-q13. In several populations studied, prevalence is estimated to be from 1/10,000 to 1/25,000 births. The disease initially manifests by neonatal hypotonia associated with orality disorders. Secondly, hyperphagia appears with significant obesity and hypogonadism. Motor milestones and language development are delayed, and all individuals have variable degrees of cognitive disability during childhood. Frequently, the most prominent features do not become evident until the later childhood stage, which can lead to underdiagnosis or late diagnosis in early childhood. Because of the long-term implications of this syndrome, it is important to recognize its features as soon as possible so that early counseling of parents and the affected child is possible. The diagnosis is suspected on clinical grounds and confirmed by genetic analysis. Prenatal diagnosis is possible and can be considered in polyhydramnios, decreased fetal active movements, malpresentation, oddly positioned hands and feet, and abnormal fetal heart rhythm. Since PWS can also lead to complications in both pregnancy and labor, proper prenatal diagnosis can also help optimize perinatal care for affected children. We report a series of five newborns for whom PWS was diagnosed in the neonatal period over 6 years. During this period, no prenatal signs of PWS were detected. The incidence in our population was 1/7937 births. The disease was diagnosed on clinical criteria: severe hypotonia, failure to thrive with poor sucking, and dysmorphic and abnormalities of the genitalia. Polyhydramnios was observed in only one case. The delivery was normal for only one patient. All except one were term newborns. There were three males and two females. We noted abnormal fetal heart rate for 80 % of the patients. The birth weight was close to the 10th percentile for two patients, less than the 3rd percentile for two others. All individuals had eutrophic cranial perimeter and four presented peculiar position of fingers. Genetic analyses found a deletion of the paternal chromosome 15 in three patients (60 %) and maternal uniparental disomy for the two others (40 %). The distribution by sex, weight, cranial perimeter, and mutations are those reported in the literature. PWS should be sought in cases of severe neonatal hypotonia, most particularly if it combines dysmorphism, hypogonadism, malposition of the fingers, and suggestive prenatal history. An early diagnosis provides better multidisciplinary care for the patient and family. We have no explanation for the higher incidence of the disease than in the general population. It is possible that this incidence is only fortuitous, but further studies would help to identify potential risk factors for the disease.