Enhancing short-term ethanol-type fermentation of waste activated sludge by adding saccharomycetes and the implications for bioenergy and resource recovery.
Ethanol-type sludge fermentation has recently attracted much attention because it can enhance direct interspecies electron transfer and thus improve the anaerobic digestion of waste activated sludge (WAS). In this paper, the enhancement of short-term ethanol-type fermentation of WAS via adding Saccharomyces was investigated. The experimental results show that the maximum ethanol production of 1030.8 ± 20.6 mg/L was achieved, with the optimum fermentation conditions of a pH of 5.1, temperature of 26.0 ℃ and time of 8.0 hr. Although the content of volatile fatty acid (VFA) increased within 10 hr, it is one order of magnitude lower than the content of ethanol, indicating that the VFA generation did not affect the efficient production of ethanol. The analyses of changes in the microbial community during the fermentation process demonstrate that the greatest Saccharomyces activity occurred in the first 8 hr and it can play an important role in ethanol production even at a very low relative abundance. Meanwhile, most typical acid-producing bacteria were inhibited, but the hydrogenotrophic methanogens (i.e., Methanobacterium) were enriched to a certain extent. Further statistical analyses reveal that the Rhodobacter, Thermomonas, Terrimonas and Saccharomyces are responsible for ethanol production during the fermentation. However, these findings not only provide a reference for the development of enhancing ethanol-type fermentation of sludge, but also are expected to provide a new way of thinking for the efficient bioenergy and resource recovery from sludge.


Prediction of critical properties of sulfur-containing compounds: New QSPR models.
In this study, new models have been proposed for the prediction of different critical properties (critical temperature (TC), critical pressure (PC), critical volume (VC), and acentric factor (ω)) of the sulfur-containing compounds based on quantitative structure-property relationship (QSPR). An extensive data set containing experimental data of over 130 different sulfur-containing compounds was employed. Enhanced Replacement Method (ERM) was applied for subset variable selection. Based on ERM selected descriptors, two different models, including linear model and genetic programming (GP) based non-linear model have been proposed for each critical property. The predicted values of each target were in good agreement with the experimental data. For GP-based models, the values of the coefficient of determination (R2) were 0.936, 0.976, 0.990, and 0.917 for TC, PC, VC, and ω, respectively. After revisiting the available QSPR models, it was found that the domain of applicability of new models has been expanded.


Genotypic detection of acyclovir-resistant HSV-1: characterization of 67 ACV-sensitive and 14 ACV-resistant viruses.
Infections due to herpes simplex virus (HSV) resistant to acyclovir (ACV) represent an important clinical concern in immunocompromised patients. In order to switch promptly to an appropriate treatment, rapid viral susceptibility assays are required. We developed herein a genotyping analysis focusing on thymidine kinase gene (TK) mutations in order to detect acyclovir-resistant HSV in clinical specimens. A total of 85 HSV-1 positive specimens collected from 69 patients were analyzed. TK gene could be sequenced directly for 81 clinical specimens (95%) and 68 HSV-1 specimens could be characterized as sensitive or resistant by genotyping (84%). Genetic characterization of 67 susceptible HSV-1 specimens revealed 10 polymorphisms never previously described. Genetic characterization of 14 resistant HSV-1 revealed 12 HSV-1 with either TK gene additions/deletions (8 strains) or substitutions (4 strains) and 2 HSV-1 with no mutation in the TK gene. DNA polymerase gene was afterwards explored. With this rapid PCR-based assay, ACV-resistant HSV could be detected directly in clinical specimens within 24 h.


Relevance of compartmental anatomic guidelines for biopsy of musculoskeletal tumors: retrospective review of 363 biopsies over a 6-year period.
To retrospectively assess percutaneous core needle biopsies performed by radiologists and the association with tumor seeding along the biopsy tract when anatomic compartment guidelines are not consistently observed. Retrospective data from computerized patient records and digital images from 363 consecutive computed tomography-guided biopsies of the lower extremity (thigh and leg) performed by radiologists at a single institution from August 2002 to August 2008 were analyzed for breaches of biopsy guidelines. Of the 363 biopsies, 243 (67%) were of soft tissue lesions and 120 (33%) were of bony lesions. There were 188 (52%) malignant and 175 (48%) benign lesions. The following biopsy breaches were observed: 13 (3.6%) of anatomic compartment, 42 (11.6%) of "vital structures," and 82 (68.3%) of needle path for bony tumors. Vital structures as defined by the literature included, but were not limited to, the following: knee joint capsule, greater trochanteric bursa, rectus femoris and vastus intermedius muscles, tibial tubercle, peroneus brevis and peroneus longus distal tendons, and neurovascular bundles. No cases of tumor recurrences could be attributed to needle seeding along a biopsy tract for any of these biopsy guideline breaches. The concern for needle tract seeding with musculoskeletal tumors is more widespread than the evidence supporting it as a significant or frequent complication. In this study, breaching anatomic compartment, vital structures (other than neurovascular structures), and suggested exact needle path guidelines were not associated with needle tract seeding in the lower extremity.


Impact of baseline PR interval on cardiac resynchronization therapy outcomes in patients with narrow QRS complexes: an analysis of the ReThinQ Trial.
Heart failure (HF) is a major cause of morbidity and mortality, and ventricular dyssynchrony is an important contributor. The ReThinQ trial reported no improvement with cardiac resynchronization therapy (CRT) in HF patients with left ventricular ejection fraction (LVEF) <35%, narrow QRS (<130 ms), New York Heart Association (NYHA) class III, and echocardiographically detected dyssynchrony, in spite of echocardiographic optimization. We investigated whether a subset of narrow QRS patients might derive benefit from CRT, based on baseline PR interval. We retrospectivelyanalyzed the 87 patients from ReThinQ who were randomized to CRT. Patients were divided into two groups: baseline PR interval <180 ms and baseline PR interval ≥180 ms. The primary outcome was change in VO2 max at 6 months; secondary outcomes were change in LVEF, 6-min walk distance, and change in NYHA class. Forty-six patients had PR < 180 ms and 41 had PR ≥ 180 ms. The baseline characteristics were similar in the two groups. As compared to patients with a short PR interval, at 6 months, only patients with PR ≥ 180 ms showed a statistically significant increase in VO2 max from 12.2 to 13.6 mL/kg min (P = 0.045). Similarly, LVEF was significantly improved only in the long PR group (0.26 to 0.28, P = 0.038). A greater percentage of patients in the long PR group showed improvement by at least one NYHA class (59 vs. 35%, P = 0.033). A longer baseline PR interval may allow more efficacious delivery of CRT by allowing programming of physiologic AV delays. A short baseline PR interval may contribute to LV under-filling and CRT non-response.


Diagnosis of cerebrotendinous xanthomatosis (CTX) and effect of chenodeoxycholic acid therapy by analysis of urine using capillary gas chromatography.
By means of capillary gas chromatography urine samples of patients with cerebrotendinous xanthomatosis (CTX) were investigated before and during treatment by oral administration of chenodeoxycholic acid. The occurrence of various conjugated bile alcohols, presumably glucuronides, was demonstrated, the major compound being 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 23 xi, 25-pentol. In the bile acid fraction norcholic acid and hydroxycholic acid were shown to be present in considerable amounts. In this way the presence of CTX can be demonstrated conclusively. After chenodeoxycholic acid therapy the excretion of both abnormal bile acids as well as of bile alcohols rapidly decreased within a few weeks, showing the effectiveness of the treatment. By early discovery and subsequent therapy it may be possible to prevent the onset of the detrimental symptoms such as mental deficiency, caused by the accumulation of cholestanol and cholesterol in CTX patients.


The effect of fluorocitrate on urinary calcium and citrate excretion.
The renal handling of calcium and citrate was studied in dogs after the administration of fluorocitrate. The drug produced a significant increase in urinary calcium and citrate excretion. Net renal secretion of citrate occurred during the infusion of fluorocitrate since citrate clearances exceeded the glomerular filtration rate.


The association of HIV viral load with indirect markers of liver injury.
This study assessed the association of HIV RNA with indirect markers of liver injury including FIB-4 index, liver enzymes and platelet counts in a high-risk Hispanic population. The data were derived from a prospective study that included 138 HIV/hepatitis C (HCV)-coinfected and 68 HIV-infected participants without hepatitis C or B co-infection (mono-infected). In unadjusted analyses, detectable HIV viral load (vs undetectable, <400 copies/mL) was associated with a 40% greater odds (OR 1.4, 95% CI: 1.1-1.9, P = 0.016) of FIB-4 > 1.45 in the HIV/HCV-coinfected group and 70% greater odds of FIB-4 > 1.45 (OR 1.7, 95% CI: 1.0-2.8; P = 0.046) in the HIV-mono-infected group. In multivariable analyses, a 1 log(10) increase in HIV RNA was associated with a median increase in FIB-4 of 12% in the HIV/HCV-coinfected group and 11% in the HIV-mono-infected group (P < 0.0001). Among the HIV/HCV-coinfected group, the elevating effect of HIV RNA on FIB-4 was strongest at low CD4 counts (P = 0.0037). Among the HIV-mono-infected group, the association between HIV RNA and FIB-4 was independent of CD4 cell counts. HIV RNA was associated with alterations in both liver enzymes and platelet counts. HIV antiretroviral therapy was not associated with any measure of liver injury examined. This study suggests that HIV may have direct, injurious effects on the liver and that HIV viral load should be considered when these indirect markers are used to assess liver function.


Clinical efficiency of 2% chlorhexidine gel in reducing intracanal bacteria.
This study evaluated the clinical efficacy of 2% chlorhexidine (CHX) gel on intracanal bacteria reduction during root canal instrumentation. The additional antibacterial effect of an intracanal dressing (Ca[OH](2) mixed with 2% CHX gel) was also assessed. Forty-three patients with apical periodontitis were recruited. Four patients with irreversible pulpitis were included as negative controls. Teeth were instrumented using rotary instruments and 2% CHX gel as the disinfectant. Bacterial samples were taken upon access (S1), after instrumentation (S2), and after 2 weeks of intracanal dressing (S3). Anaerobic culture was performed. Four samples showed no bacteria growth at S1, which were excluded from further analysis. Of the samples cultured positively at S1, 10.3% (4/39) and 8.3% (4/36) sampled bacteria at S2 and S3, respectively. A significant difference in the percentage of positive culture between S1 and S2 (p < 0.001) but not between S2 and S3 (p = 0.692) was found. These results suggest that 2% CHX gel is an effective root canal disinfectant and additional intracanal dressing did not significantly improve the bacteria reduction on the sampled root canals.


Mucormycosis are infrequent filamentous fungal infections, but severe and with high mortality (20 to 50%). Symptoms are very common, like necrosis, and burn/polytrauma patients have a higher risk of mucormycosis than the general population. We report here the history of a 38-year-old man, polytraumatized and burned because of a tractor incident. During the first two weeks two haemorrhagic shock episodes occurred because of necrosis of the humeral artery. Analysis of vascular fragment identified Lichteimia spp. The diagnosis of invasive infection was established after identifying Lichteimia spp. in blood cultures also. We treated the patient with intravenous liposomal amphotericin, oral posaconazole and surgical debridement according to the gold standard. The wound mucormycosis was also treated with a humeral bypass with vascular allograft and a latissimus dorsi pedicled flap. Furthermore, mucormycosis was treated with local instillations of amphotericin B in the dressings twice a day with 1% (1 mg/100mL) solution of non-liposomal amphotericin. Early diagnosis and treatment is very important for mucormycosis healing and to minimize morbimortality. With burn and polytrauma patients necrosis and bad local evolution have to be carefully screened and analyzed.


Growth inhibition of imatinib-resistant CML cells with the T315I mutation and hypoxia-adaptation by AV65--a novel Wnt/β-catenin signaling inhibitor.
We investigated the effect of a novel Wnt/β-catenin signaling inhibitor, AV65 on imatinib mesylate (IM)-sensitive and -resistant human chronic myeloid leukemia (CML) cells in vitro. AV65 inhibited the proliferation of various CML cell lines including T315I mutation-harboring cells. AV65 reduced the expression of β-catenin in CML cells, resulting in the induction of apoptosis. Moreover, AV65 inhibited the proliferation of hypoxia-adapted primitive CML cells that overexpress β-catenin. The combination of AV65 with IM had a synergistic inhibitory effect on the proliferation of CML cells. These findings suggest that AV65 could be a novel therapeutic agent for the treatment of CML.


How to mimic a type A intramural hematoma: A case of IgG4-related aortitis associated with cerebral hemorrhage.
IgG4-related aortitis is an inflammatory condition of the aorta, characterized by aortic wall thickening and periaortic soft-tissue involvement. Therefore, this condition can mimic an aortic intramural hematoma (IMH), due to similar radiological findings. We hereby report the case of an IgG4-related aortitis misdiagnosed as an IMH, associated with cerebral hemorrhage, possibly due to cerebral vascular system involvement.


Distribution of amikacin in serum, muscle, and fat in children after a single intramuscular injection.
Amikacin concentrations in serum, muscle, and fat were determined in 41 children after intramuscular administration of 7.5 mg/kg of body weight. At 1.5 h amikacin reached peak concentrations in serum (mean value, 14.9 mug/ml) as well as in muscle (2.2 mug/g) and fat (1.89 mug/g) tissue; from then on all concentrations declined. Amikacin concentrations exceeded 1 mug/g in muscle for at least 3 h and in fat for at least 4 h.


Very-low-dose ketamine for the management of pain and sedation in the ICU.
Management of pain in critically ill patients can be very difficult. In the attempt to provide comfort with adequate levels of opioids and sedatives, respiratory depression and cardiovascular instability may become difficult to control in patients with labile hemodynamics and poor cardiopulmonary reserve. The use of medications like ketamine, an anesthetic agent that in subanesthetic doses has been reported to be effective in preventing opioid-induced tolerance and to have analgesic properties, may be of help, especially in patients who develop tolerance, leading to rapidly escalating doses of opioids and sedatives. The case report presented here shows how a very low dose of ketamine can be helpful for the management of pain and sedation in critically ill patients, especially when they are ready to be weaned from mechanical ventilation, and very high doses of opiods and sedatives do not permit it.


The bull's-eye sign of extracranial cervical aneurysms.
Extracranial, cervical aneurysms and arterial thrombosis are uncommon entities. In most cases, they have diagnostic clinical presentations. However, on occasion the history and physical findings do not clearly suggest their presence. In these cases, postcontrast computed tomography scans can aid in rapidly establishing the correct diagnosis by revealing a "bull's-eye" appearance within the mass (vessel lumen). The diagnosis is less difficult to make when the involved vessel is the carotid artery, because this artery is routinely identified on postcontrast computed tomography scans and the lesion can be easily placed along its course. The vascular origin of such a lesion is not usually evident on computed tomography if the process does not lie along the course of a major vessel. In these cases, the bull's-eye sign can establish the diagnosis so that prompt consideration can be given to angiography and therapy.


High-pressure paint gun injury to the orbit and ocular adnexa.
High-pressure injection injury to the orbit and adnexa is a rare but potentially blinding type of trauma. Few cases of such injury have been reported in the literature. A 27-year-old Indian man accidentally injected paint material from a high-pressure nozzle gun into his left eye. Radiological investigation revealed the presence of paint material in the orbital tissues and the ethmoidal sinuses. The patient underwent two orbital surgeries to remove the paint material. He later developed signs suggestive of limbal stem cell failure and was treated with limbal stem cell autografting. He also has ophthalmoplegia with a compensatory anomalous head posture that was managed conservatively. We report the clinical course and outcome of this unfortunate patient to highlight the complexity of such an injury and the need for a multidisciplinary approach in its management.


Evaluation of emergency department derived delirium prediction models using a hospital-wide cohort.
Delirium is acute disorder of attention and cognition. We conducted an observational study using a hospital-wide database to validate three delirium prediction models that were developed to predict prevalent delirium within the first day of hospitalization after ED visit. This was a retrospective cohort study at the academic medical center to evaluate the predictive ability of three previously developed prediction models for delirium from 2014 to 2017. We included patients aged 65 years and older who were hospitalized from ED. Nurses used the Delirium Observation Screening Scale (DOSS) twice daily while hospitalized. We extracted variables to examine the three prediction models with a positive DOSS screen within the first day of admission. The predictive ability was summarized using the area under the curve (AUC). We identified 2582 visits with a positive DOSS screen and 877 visits with a diagnosis of delirium from ICD9/10 codes among 12,082 encounters. The AUC of these prediction models ranged from 0.71 to 0.80 when predicting a positive DOSS screen, and 0.68 to 0.72 when predicting a ICD9/10 diagnosis of delirium. In our cohort, the delirium risk score which uses the cutoff of positive or negative predicted DOSS positive delirium with the AUC of 0.8 (p < .0001). The model demonstrated the sensitivity and the specificity of 91.2 (95% CI 90.0-92.3) and 50.3 (95% CI 49.3-51.3). In this study, the delirium risk score had the highest predictive ability for prevalent delirium defined by a positive DOSS within the first day of hospitalization.


Mechanical allodynia in human glabrous skin mediated by low-threshold cutaneous mechanoreceptors with unmyelinated fibres.
We recently showed that C-tactile fibres (CTs) in human hairy skin (anterior leg) mediate crossover between innocuous touch and noxious touch, i.e. mechanical allodynia. Although there is no evidence for existence of a phenotypically identical class of CTs in human glabrous skin, the 'qualia' of affective stimuli are comparable across skin types. In 42 healthy subjects, muscle pain was induced by infusing hypertonic saline (5 %) into flexor carpi ulnaris muscle. Concurrently, sinusoidal vibration (200 Hz-200 μm) was applied to glabrous skin of little finger. The neural substrate of allodynia was determined by employing conduction blocks of myelinated (ulnar nerve compression) and unmyelinated (low-dose intra-dermal anaesthesia) fibres. In order to compare the expression of allodynia across spinal segments and skin types, vibration was also applied to glabrous skin of index finger and hairy skin of dorsal forearm. In addition, high-precision brushing stimuli were applied at speeds of 1.0 and 3.0 cm s(-1) to digital glabrous skin with absent myelinated fibres. During muscle pain, vibration caused a significant and reproducible increase in pain (allodynia). This effect persisted during blockade of myelinated fibres, but was abolished by inactivation of unmyelinated cutaneous fibres. The vibration-evoked effects were found to be comparable across spinal segments and skin types. Furthermore, brushing produced a near-identical expression of C-fibre-mediated allodynia. Prior to induction and upon cessation of muscle pain, vibration and brushing were reported as non-painful. Based on these results, we postulate that a functional homologue of the CTs (hairy skin) mediates allodynia in human glabrous skin.


Double-pulse stimulation of startle-like responses in rats: refractory periods and temporal summation.
A startle-like response was evoked by electrical stimulation with one pulse in several brainstem sites of the primary acoustic startle circuit. If a second pulse was delivered 0.4-10 ms after the first pulse, a stronger response or a decreased current threshold resulted. The facilitatory effect of the second pulse increased as interpulse (C-T) interval increased from 0.4 to 2.0 ms in cochlear nucleus or ventral lateral lemniscus sites. In caudal pontine reticular formation sites, the effect of the second pulse increased sharply from 0.3 to 0.5 ms. These results suggest that very short refractory period axons mediate electrically elicited startle in reticular formation, and that longer refractory period axons mediate startle in cochlear nucleus or ventral lateral lemniscus. In reticular formation sites, the effect of the second pulse declined nearly exponentially from 2.0 to 50 ms with a time constant of about 4 ms. Stimulation of similar reticular formation sites in cats evokes monosynaptic EPSPs in spinal motoneurons with an almost identical time course, as reported by other investigators. This suggests that the startle response evoked from the reticular formation results from monosynaptic activation of spinal motoneurons. Temporal summation declined more slowly and irregularly in cochlear nucleus and ventral lateral lemniscus sites, suggesting that these sites are not monosynaptically connected with spinal motoneurons, a conclusion consistent with anatomical data. In reticular formation sites near the facial nerve, a second peak in the two-pulse curve was observed at a C-T interval of 10 ms. The second peak was blocked by local anesthesia of the face ipsilateral to the stimulating electrode, suggesting that a single twitch of facial muscles facilitates startle.


pH and temperature stability of (-)-epigallocatechin-3-gallate-β-cyclodextrin inclusion complex-loaded chitosan nanoparticles.
The oxidative stability of (-)-epigallocatechin-3-gallate (EGCG) incorporated as inclusion complexes (ICs) in sulfobutylether-β-cyclodextrin sodium (SBE-β-CD) and then ionotropically crosslinked with chitosan hydrochloride (CSH) into nanoparticles were investigated. EGCG-loaded CSH-SBE-β-CD nanoparticles (CSNs) were physically unstable at higher pH and temperature. The particle size of CSNs was unchanged in the pH range of 3-5, but the microenvironment of EGCG-IC appeared to be intact until the pH increased to 6.5 by fluorescence spectroscopy. The physical structure of EGCG-ICs was also affected during storage in addition to CSNs, which was further affected as temperature increased from 25 to 55°C. The decrease in antioxidant activities of EGCG-ICs and free EGCG with increasing pH, storage time and temperature were modest compared to the prominent decreases in antioxidant activities of EGCG-loaded CSNs. The extreme entrapment of EGCG-ICs and/or free EGCG in the aggregated CSNs restricted the release of EGCG, thus inhibiting the antioxidant activities.


Decoding nociceptor-DC dialogues.
Neuro-immune interactions link physiological and immune responses in host defense. Hanč et al.1 report that nociceptors attract dendritic cells (DCs) via the chemokine (C-C motif) ligand 2 (CCL2), initiate a "sentinel" DC program via the neuropeptide calcitonin gene-related peptide (CGRP), and enhance DC inflammatory responses through direct connections. These neuroimmune units integrate nociceptors' rapid responsiveness with DCs' immune coordination, functioning as an advanced warning system.


Validity of self-reported eye disease and treatment in a population-based study: the Los Angeles Latino Eye Study.
To examine the validity of self-reported eye disease, including cataract, age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR), and self-reported surgical treatment for cataract and DR in the Los Angeles Latino Eye Study (LALES). Population-based, cross-sectional study. A total of 6357 Latinos aged 40+ years from the LALES. Participants underwent a detailed interview, including survey questions about ocular health, diagnoses, and timing of last eye examination, and a standardized clinical examination. Self-report was compared with examination to determine sensitivity and specificity by length of time since last eye examination. Stepwise logistic regression was used to determine factors associated with inaccurate self-report. Sensitivity and specificity were calculated for 4 self-reported eye diseases (cataract, AMD, glaucoma, and DR) and for surgical treatment of cataract and DR. Odds ratios (ORs) were determined for factors associated with inaccurate self-report underestimating eye disease and treatment. For each disease, sensitivity and specificity in those who reported their last eye examination as <1 year ago were 36.8% and 92.5% for cataract, 37.7% and 96.3% for glaucoma, 5.1% and 98.9% for AMD, and 25.7% and 94.2% for DR, respectively. Self-report was less accurate with increasing time since last eye examination. Inaccurate self-report was independently associated with better visual acuity (OR, 2.4), <2 comorbidities (OR, 1.7), last eye examination/visit 1 to 5 years ago and ≥ 5 years ago (OR, 2.3 and 4.9, respectively), and less education (OR, 1.3 for 7-12 years and 1.7 for <7 years). Of 88 participants surgically treated for cataract who reported an eye examination <1 year ago, sensitivity and specificity of self-reported surgical history were 90.9% and 99.9%, respectively. Of the 31 participants treated for DR (laser/surgery) and reporting an eye examination <1 year ago, sensitivity and specificity of self-reported surgical history were 19.4% and 99.6%, respectively. Among Latinos, self-reporting of eye disease and surgical history provides a significant underestimate of the disease burden. This may lead to significant misclassification in vision research if self-report alone is used to identify persons with eye disease.


Current treatment and future directions in the management of chronic hepatitis B viral infection.
The World Health Organization places hepatitis B virus (HBV) in the top 10 causes of death worldwide. It is estimated that there are over 400 million carriers of HBV as well. At least 20% to 30% of hepatitis B surface antigen (HBsAg) carriers will die of complications of chronic liver disease, including cirrhosis and liver cancer. The serious consequences of end-stage liver disease and liver cancer occur in 30% of chronic carriers and confront patients and physicians throughout the world. Vaccination is the major form of treatment (prevention) that may eventually eliminate HBV worldwide. This article discusses the currently available treatments as well as evolving treatments for chronic HBV infection.


Whole-genome resequencing from bulked-segregant analysis reveals gene set based association analyses for the Vibrio anguillarum resistance of turbot (Scophthalmus maximus).
Many achievements have been made to develop quantitative trait loci (QTLs) and gene-associated single nucleotide polymorphisms (SNPs) to facilitate practical marker-assisted selection (MAS) in aquatic animals. However, the systematic studies of SNPs associated with extreme threshold traits were poor in populations lacking of parental genomic information. Coupling next generation sequencing with bulked segregant analysis (BSA) should allow identification of numerous associated SNPs with extreme phenotypes. In the present study, using combination of SNP frequency difference and Euclidean distance, we conducted linkage analysis of SNPs located in genes involved in immune responses, and identified markers associated with Vibrio anguillarum resistance in turbot (Scophthalmus maximus). A total of 221 SNPs was found as candidate SNPs between resistant and susceptible individuals. Among these SNPs, 35 loci located in immune related genes were genotyped in verification population and 7 of them showed significant association with V. anguillarum resistance in both alleles and genotypes (P < 0.05). Among these 7 genes, PIK3CA-like, CYLD, VCAM1, RhoB and RhoGEF are involved in PI3K/Akt/mTOR pathway and NF-κB pathway, which influence the efficiency of bacteria entering the host and inflammation. SNP-SNP interaction analysis was performed by generalized multifactor dimensionality reduction (GMDR). The combination of SNP loci in RhoB, PIK3CA-like and ADCY3 showed a significant effect on V. anguillarum resistance with the verification rate in the sequencing population up to 70.8%. Taken all, our findings demonstrated the feasibility of BSA-seq approach in identifying genes responsible for the extreme phenotypes and will aid in performing MAS in turbot.


A prospective, observational, multicenter study on risk factors and prophylaxis for low emetic risk chemotherapy-induced nausea and vomiting.
The incidence of and the risk factors for nausea and vomiting in patients undergoing low emetic risk chemotherapy (LEC) are unclear. The aim of the study was to provide information on these topics by performing a multicenter, observational, prospective study. The study consisted of patients who were administered first-time LEC that was consistent or inconsistent with current guidelines. Using the visual analog scale, patients recorded their daily food intake and the occurrence and severity of nausea over a 5-day treatment period. The overall incidence of chemotherapy-induced nausea and vomiting did not differ significantly between patients undergoing guideline-consistent (n = 89) or guideline-inconsistent (n = 121) prophylaxis (30.3 vs. 22.3%, respectively; P = 0.19). Logistic regression analysis identified a history of nausea and LEC other than taxanes as independent risk factors associated with nausea and vomiting in patients undergoing LEC. The mean daily visual analog scale scores for nausea severity and a decrease in food intake were <25 mm throughout the entire observation period. Guideline-consistent prophylaxis appeared to control nausea and vomiting effectively in patients undergoing LEC. However, patients with a history of nausea and receiving LEC other than taxanes should be carefully observed and treatment should be adjusted according to their symptoms.


Elevated serum FGF21 predicts the major adverse cardiovascular events in STEMI patients after emergency percutaneous coronary intervention.
Although there have been several studies related to serum fibroblast growth factor 21 (FGF21) levels and acute myocardial infarction, the value of serum FGF21 levels in ST-segment elevation myocardial infarction (STEMI) patients after emergency percutaneous coronary intervention (PCI) has not been previously investigated. A total of 348 STEMI patients who underwent emergency PCI were enrolled from January 2016 to December 2018. The primary endpoint was the occurrence of major adverse cardiovascular events (MACEs), with a median follow-up of 24 months. Eighty patients with stable angina (SA) who underwent selective PCI served as the control group. Serum FGF21 levels were measured by ELISA. Serum FGF21 levels were significantly higher in the STEMI group than in the SA group (225.03 ± 37.98 vs. 135.51 ± 34.48, P < 0.001). Multiple linear regression analysis revealed that serum FGF21 levels were correlated with NT-proBNP (P < 0.001). According to receiver operating characteristic (ROC) analysis, the areas under the ROC curve (AUCs) of FGF21 and NT-proBNP were 0.812 and 0.865, respectively. The Kaplan-Meier curves showed that STEMI patients with lower FGF21 levels had an increased MACE-free survival rate. Cox analysis revealed that high FGF21 levels (HR: 2.011, 95% CI: [1.160-3.489]) proved to be a powerful tool in predicting the risk of MACEs among STEMI patients after emergency PCI. Elevated FGF21 levels on admission have been shown to be a powerful predictor of MACEs for STEMI patients after emergency PCI.


Combined PD-L1 and TIM3 blockade improves expansion of fit human CD8+ antigen-specific T cells for adoptive immunotherapy.
Antigen-specific T cell expansion ex vivo followed by adoptive transfer enables targeting of a multitude of microbial and cancer antigens. However, clinical-scale T cell expansion from rare precursors requires repeated stimulation, which may lead to T cell dysfunction and limited therapeutic potential. We used a clinically compliant protocol to expand Epstein-Barr virus (EBV) and Wilms tumor 1 (WT1) antigen-specific CD8+ T cells, and leveraged T cell exhaustion-associated inhibitory receptor blockade to improve T cell expansion. Several inhibitory receptors were expressed early by ex vivo-expanded antigen-specific CD8+ T cells, including PD-1 and TIM3, with co-expression matching evidence of T cell dysfunction as the cultures progressed. Introduction of anti-PD-L1 and anti-TIM3 blockade in combination (but not individually) to the culture led to markedly improved antigen-specific T cell expansion without inducing T cell dysfunction. Single-cell RNA sequencing (RNA-seq) and T cell receptor (TCR) repertoire profiling revealed that double blockade does not impart specific transcriptional programs in T cells or alterations in TCR repertoires. However, combined blockade may affect gene expression in a minority of clonotypes in a donor-specific fashion. We conclude that antigen-specific CD8+ T cell manufacturing can be improved by using TIM3 and PD-L1/PD-1 axis blockade in combination. This approach is readily applicable to several adoptive immunotherapy strategies.


D-Dopachrome tautomerase is a candidate for key proteins to protect the rat liver damaged by carbon tetrachloride.
Carbon tetrachloride (CCl4) is known to induce liver damage. Animal experiments with CCl4 injections have revealed many findings, especially mechanisms of liver damage and liver regeneration. Recently, proteomic approaches have been introduced in various studies to evaluate the quantitative and qualitative changes in the comprehensive proteome level. The aim of this research is to elucidate the key protein for liver damage, liver protection and liver regeneration by using proteomic techniques. 50 % (v/v) CCl4 in corn oil was administered intraperitoneally to adult male rats at a dose of 4ml/kg body weight. Approximately 24h after the injection, the liver was removed and extracted proteins were analyzed with cleavable isotope coded affinity tag (cICAT) reagents, two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). A twelvefold increase in D-dopachrome tautomerase (DDT) was indicated. This enzyme has been reported to be involved in the biosynthesis of melanin, an antioxidant. According to the histological analysis, melanin levels were increased in un-damaged hepatocytes of CCl4-treated rats. These results suggest that the increase in DDT is a response to liver damage, accelerates melanin biosynthesis and protects the liver from oxidative stress induced by CCl4.


Comparative analysis of animal growth: a primate continuum revealed by a new dimensionless growth rate coefficient.
The comparative analysis of animal growth still awaits full integration into life-history studies, partially due to the difficulty of defining a comparable measure of growth rate across species. Using growth data from 50 primate species, we introduce a modified "general growth model" and a dimensionless growth rate coefficient β that controls for size scaling and phylogenetic effects in the distribution of growth rates. Our results contradict the prevailing idea that slow growth characterizes primates as a group: the observed range of β values shows that not all primates grow slowly, with galago species exhibiting growth rates similar or above the mammalian average, while other strepsirrhines and most New World monkeys show limited reduction in growth rates. Low growth rate characterizes apes and some papionines. Phylogenetic regressions reveal associations between β and life-history variables, providing tests for theories of primate growth evolution. We also show that primate slow growth is an exclusively postnatal phenomenon. Our study exemplifies how the dimensionless approach promotes the integration of growth rate data into comparative life-history analysis, and demonstrates its potential applicability to other cases of adaptive diversification of animal growth patterns.


Analysis of gene expression profile induced by hepatocyte nuclear factor 4alpha in hepatoma cells using an oligonucleotide microarray.
Hepatocyte nuclear factor 4alpha (HNF-4alpha), a liver-specific transcription factor, plays a significant role in many liver-specific functions, including lipid, glucose, drug, and ammonia metabolism, and also in embryonal liver development. However, its functions and regulation are not yet clearly understood. In this study, we constructed an adenovirus vector carrying rat HNF-4alpha cDNA and transfected the adenovirus to human hepatoma cells, HuH-7, to enforce expression of the exogenous HNF-4alpha gene. We analyzed HNF-4alpha-induced genes using cDNA microarray technology, which included over 9000 genes. As a result, 62 genes showed a greater than 2.0-fold change in expression level after the viral transfection. Fifty-six genes were consistently induced by HNF-4alpha overexpression, and six genes were repressed. To assess HNF-4alpha function, we attempted to classify the genes, which had been classified by their encoding protein functions in a previous report. We could classify 45 genes. The rest of the HNF-4alpha-sensitive genes were unclassified (4 genes) or not identified (13 genes). Among the classified genes, almost half of the induced genes (26 of 40) were related to metabolism genes and particularly to lipid metabolism-related genes. This cDNA microarray analysis showed that HNF-4alpha is one of the central liver metabolism regulators.


Changes in autophagy in rats after spinal cord injury and the effect of hyperbaric oxygen on autophagy.
The purpose of this study was to explore the effects of Hyperbaric oxygen (HBO) on the autophagic changes after induction of spinal cord injury (SCI) in rats. A total of 75 rats were randomly divided into the sham-operated group, the spinal cord injury group, and the SCI+HBO group. We found that at 7 d and 14 d after surgery, the BBB scores were higher in the SCI+HBO group in comparison to the SCI group. The expression of Beclin-1 and LC3II was upregulated in the SCI and SCI+HBO groups after SCI. Fluorescently stained Beclin-1 and LC3II proteins were barely detectable in the sham group. In contrast, Beclin-l and LC3II expression was observed in neurons and glial cells from the SCI and SCI+HBO groups. Beclin-1 and LC3II expression appeared at 6h after SCI. At each time point, Beclin-1 and LC3II expression was significantly higher in the SCI+HBO group compared to the SCI group. These results suggest that autophagy is activated in rats after SCI and sustained over a period of time. HBO treatment enhances autophagy expression in rats after SCI and accelerates cell repair rate, which may represent one of the mechanisms of action of HBO in the treatment of SCI.


Effects of semantic cues on mathematical modeling: evidence from word-problem solving and equation construction tasks.
Mathematical solutions to textbook word problems are correlated with semantic relations between the objects described in the problem texts. In particular, division problems usually involve functionally related objects (e.g., tulips-vases) and rarely involve categorically related objects (e.g., tulips-daisies). We examined whether middle school, high school, and college students use object relations when they solve division word problems (WP) or perform the less familiar task of representing verbal statements with algebraic equations (EQ). Both tasks involved multiplicative comparison statements with either categorically or functionally related objects (e.g., "four times as many cupcakes [commuters] as brownies [automobiles]"). Object relations affected the frequency of correct solutions in the WP task but not in the EQ task. In the latter task, object relations did affect the structure of nonalgebraic equation errors. We argue that students use object relations as "semantic cues" when they engage in the sense-making activity of mathematical modeling.


Visualization of folate transport proteins by covalent labeling with fluorescein methotrexate.
Fluorescein-methotrexate (F-MTX) has been synthesized by an improved procedure and separated via chromatography on DEAE-Trisacryl into the alpha- and gamma-isomers. Purity of each isomer was verified by TLC, HPLC, and absorbance spectra. Identity of the alpha- and gamma-isomers was established by the following biological criteria: the gamma-isomer inhibited dihydrofolate reductase and was hydrolyzed by carboxypeptidase G2 (at the pteroate-glutamate linkage). The alpha-isomer, conversely, was unreactive in both systems, which is consistent with the specificity of these enzymes. Based upon these results, the gamma-isomer was selected for covalent labeling of proteins. Fluorescent bands were observed when the 22 kDa human dihydrofolate reductase and the 18 kDa folate transporter from Lactobacillus casei were treated with gamma-F-MTX (activated by N-hydroxysuccinimide) and subjected to SDS-PAGE. The probe was also useful for visualizing in situ the micromolar folate transport protein in L1210 cells.


Periorbital marginotomies: anatomy and applications.
The application of craniofacial techniques has led to a greater variety of methods for operative exposure. In the orbital region, the inferior marginotomy of Tessier is a valuable adjunct in the reconstruction of severe orbital floor fractures and their sequelae. This concept has been extended to the superior, lateral, and medial orbital rims to improve the exposure of the respective orbital wall. These marginotomies have been used for a variety of problems. There have been no complications related to the inclusion of a periorbital marginotomy, and its use in appropriate patients is strongly recommended.


Corrigendum: Helicobacter pylori cagA+ Is Associated with Milder Duodenal Histological Changes in Chilean Celiac Patients.
[This corrects the article on p. 376 in vol. 7, PMID: 28879170.].


[Value and limits of computed tomography in processes of the skull base (author's transl)].
Among 750 skull bases studied with CT, 137 were pathologic cases. Findings in intracranial tumors, in primarily extracranial tumors with intracranial extension, and malformations are described. The value and some limitations of CT in this pathology are described.


Pediatric Cardiac Intensive Care Society 2014 Consensus Statement: Pharmacotherapies in Cardiac Critical Care Anticoagulation and Thrombolysis.
Thrombotic complications are increasingly being recognized as a significant cause of morbidity and mortality in pediatric and congenital heart disease. The objective of this article is to review the medications currently available to prevent and treat such complications. Online searches were conducted using PubMed. Studies were selected for inclusion based on their scientific merit and applicability to the pediatric cardiac population. Pertinent information from each selected study or scientific review was extracted for inclusion. Four classes of medications were identified as potentially beneficial in this patient group: anticoagulants, antiplatelet agents, thrombolytic agents, and novel oral anticoagulants. Data on each class of medication were synthesized into the follow sections: mechanism of action, pharmacokinetics, dosing, monitoring, reversal, considerations for use, and evidence to support. Anticoagulants, antiplatelet agents, and thrombolytic agents are routinely used successfully in the pediatric patient with heart disease for the prevention and treatment of a wide range of thrombotic complications. Although the novel oral anticoagulants have been approved for a limited number of indications in adults, studies on the safety and efficacy of these agents in children are pending.


Occurrence of androgens and progestogens in wastewater treatment plants and receiving river waters: comparison to estrogens.
Research has shown that exposure to androgens and progestogens can cause undesirable biological responses in the environment. To date, however, no detailed or direct study of their presence in wastewater treatment plants has been conducted. In this study, nine androgens, nine progestogens, and five estrogens were analyzed in influent and final effluent wastewaters in seven wastewater treatment plants (WWTPs) of Beijing, China. Over a period of three weeks, the average total hormone concentrations in influent wastewaters were 3562 (Wujiacun WWTP)-5400 ng/L (Fangzhuang WWTP). Androgens contributed 96% of the total hormone concentrations in all WWTP influents, with natural androgen (androsterone: 2977±739 ng/L; epiandrosterone: 640±263 ng/L; and androstenedione: 270±132 ng/L) being the predominant compounds. The concentrations of synthetic progestogens (megestrol acetate: 41±25 ng/L; norethindrone: 6.5±3.3 ng/L; and medroxyprogesterone acetate: 6.0±3.2 ng/L) were comparable to natural ones (progesterone: 66±36 ng/L; 17α,20β-dihydroxy-4-progegnen-3-one: 4.9±1.2 ng/L; 21α-hydroxyprogesterone: 8.5±3.0 ng/L; and 17α-hydroxyprogesterone: 1.5±0.95 ng/L), probably due to the wide and relatively large usage of synthetic progestogens in medical therapy. In WWTP effluents, androgens were still the dominant class accounting for 60% of total hormone concentrations, followed by progestogens (24%), and estrogens (16%). Androstenedione and testosterone were the main androgens detected in all effluents. High removal efficiency (91-100%) was found for androgens and progestogens compared with estrogens (67-80%), with biodegradation the major removal route in WWTPs. Different profiles of progestogens in the receiving rivers and WWTP effluents were observed, which could be explained by the discharge of a mixture of treated and untreated wastewater into the receiving rivers.


A novel organic-rich meteoritic clast from the outer solar system.
The Zag meteorite which is a thermally-metamorphosed H ordinary chondrite contains a primitive xenolithic clast that was accreted to the parent asteroid after metamorphism. The cm-sized clast contains abundant large organic grains or aggregates up to 20 μm in phyllosilicate-rich matrix. Here we report organic and isotope analyses of a large (~10 μm) OM aggregate in the Zag clast. The X-ray micro-spectroscopic technique revealed that the OM aggregate has sp2 dominated hydrocarbon networks with a lower abundance of heteroatoms than in IOM from primitive (CI,CM,CR) carbonaceous chondrites, and thus it is distinguished from most of the OM in carbonaceous meteorites. The OM aggregate has high D/H and 15N/14N ratios (δD = 2,370 ± 74‰ and δ15N = 696 ± 100‰), suggesting that it originated in a very cold environment such as the interstellar medium or outer region of the solar nebula, while the OM is embedded in carbonate-bearing matrix resulting from aqueous activities. Thus, the high D/H ratio must have been preserved during the extensive late-stage aqueous processing. It indicates that both the OM precursors and the water had high D/H ratios. Combined with 16O-poor nature of the clast, the OM aggregate and the clast are unique among known chondrite groups. We further propose that the clast possibly originated from D/P type asteroids or trans-Neptunian Objects.


Free-ranging dogs assess the quantity of opponents in intergroup conflicts.
In conflicts between social groups, the decision of competitors whether to attack/retreat should be based on the assessment of the quantity of individuals in their own and the opposing group. Experimental studies on numerical cognition in animals suggest that they may represent both large and small numbers as noisy mental magnitudes subject to scalar variability, and small numbers (≤4) also as discrete object-files. Consequently, discriminating between large quantities, but not between smaller ones, should become easier as the asymmetry between quantities increases. Here, we tested these hypotheses by recording naturally occurring conflicts in a population of free-ranging dogs, Canis lupus familiaris, living in a suburban environment. The overall probability of at least one pack member approaching opponents aggressively increased with a decreasing ratio of the number of rivals to that of companions. Moreover, the probability that more than half of the pack members withdrew from a conflict increased when this ratio increased. The skill of dogs in correctly assessing relative group size appeared to improve with increasing the asymmetry in size when at least one pack comprised more than four individuals, and appeared affected to a lesser extent by group size asymmetries when dogs had to compare only small numbers. These results provide the first indications that a representation of quantity based on noisy mental magnitudes may be involved in the assessment of opponents in intergroup conflicts and leave open the possibility that an additional, more precise mechanism may operate with small numbers.


Ambulatory care provision versus first admission to psychiatric hospital: 5 years follow up.
Ambulatory care for subjects with severe mental problems has been clearly shown to be a valid alternative to hospitalisation. However, very few studies have considered the fate of patients over several years. Ambulatory care services are often experimental set-ups, for small groups, and their impact on subsequent treatment has only been assessed over the first few months of treatment. The value of developing this practice therefore remains unclear. We investigated the possible consequences of generalising ambulatory care services by a mobile crisis intervention team (ERIC) to all requests for the first hospitalisation in a psychiatric department. The principal aim was to determine whether systemic intervention by the crisis intervention team could provide a true alternative to hospitalisation. We also investigated whether problem-resolving approaches and ambulatory care led, in the long term, to fewer prolonged or repeated periods of hospitalisation than practices in which hospitalisation was considered as an ordinary solution. We carried out a prospective, comparative, cohort study over a 5-year period beginning with the creation of ERIC by one of the hospital departments. All patients arriving at this department for the first time were offered immediate ambulatory care by this team for 1 month. Their hospitalisation record (duration of hospital stay, number of days in hospital) was compared with that of subjects hospitalised in the same conditions but in other departments of the hospital. This study included most of the subjects referred for the first time to the psychiatric hospital, in our department. Regardless of their diagnosis, intensive follow-up at home, based on systemic crisis intervention work, was found to be an effective and well-accepted alternative to hospitalisation. Indeed, a highly significant immediate decrease in both the number of admissions and the duration of hospital stay was observed for the experimental group, with no subsequent increase in the number of days of hospitalisation. From the second year onwards, the use of hospitalisation did not seem to be influenced by the type of care initially given to the patient. Rehospitalisation was rare in both groups. One third of the patients in the experimental group benefited from another intervention of the ambulatory emergency team from the second year onwards, highlighting the value placed on this type of care by the patients and their families. Our results support the development of ambulatory crisis intervention services, including those from psychiatric hospitals. Clinical studies following the treatment paths of patients in a more exhaustive manner would almost certainly distinguish more precisely between the "natural" course of the disease and the impact of the care provided. In any case, the prevention of hospitalisation must be based as much on a possible alternative at the time of the crisis as on subsequent access to ambulatory care.


Variable dual carbon-bromine stable isotope fractionation during enzyme-catalyzed reductive dehalogenation of brominated ethenes.
The potential of compound-specific stable isotope analysis (CSIA) to characterize biotransformation of brominated organic compounds (BOCs) was assessed and compared to chlorinated analogues. Sulfurospirillum multivorans and Desulfitobacterium hafniense PCE-S catalyzed the dehalogenation of tribromoethene (TBE) to either vinyl bromide (VB) or ethene, respectively. Significantly lower isotope fractionation was observed for TBE dehalogenation by S. multivorans (εC = -1.3 ± 0.2‰) compared to D. hafniense (εC = -7.7 ± 1.5‰). However, higher fractionation was observed for dibromoethene (DBE) dehalogenation by S. multivorans (εC = -16.8 ± 1.8‰ and -21.2 ± 1.6‰ for trans- and cis-1,2- (DBE) respectively), compared to D. hafniense PCE-S (εC = -9.5 ± 1.2‰ and -14.5 ± 0.7‰ for trans-1,2-DBE and cis-1,2-DBE, respectively). Significant, but similar, bromine fractionation was observed for for S. multivorans (εBr = -0.53 ± 0.15‰, -1.03 ± 0.26‰, and -1.18 ± 0.13‰ for trans-1,2-DBE, cis-1,2-DBE and TBE, respectively) and D. hafniense PCE-S (εBr = -0.97 ± 0.28‰, -1.16 ± 0.36‰, and -1.34 ± 0.32‰ for cis-1,2-DBE, TBE and trans-1,2-DBE, respectively). Variable CBr dual-element slopes were estimated at Λ (εC/εBr) = 1.03 ± 0.2, 17.9 ± 5.8, and 29.9 ± 11.0 for S. multivorans debrominating TBE, cis-1,2-DBE and trans-1,2-DBE, respectively, and at 7.14 ± 1.6, 8.27 ± 3.7, and 8.92 ± 2.4 for D. hafniense PCE-S debrominating trans-1,2-DBE, TBE and cis-1,2-DBE, respectively. A high variability in isotope fractionation, which was substrate property related, was observed for S. multivorans but not D. hafniense, similar as observed for chlorinated ethenes, and may be due to rate-limiting steps preceding the bond-cleavage or differences in the reaction mechanism. Overall, significant isotope fractionation was observed and, therefore, CSIA can be applied to monitor the fate of brominated ethenes in the environment. Isotope effects differences, however, are not systematically comparable to chlorinated ethenes.


An autopsy case of commotio cordis from a motor scooter accident.
A motor scooter carrying two 15-year-old boys collided with the back of an open, parked truck. The tailgate of the truck was down and in a horizontal position. At the autopsy of the driver, horizontal tramline bruises were found on the anterior chest, but the thoracic cage was intact. There was a transverse tear of the ascending aorta with adventitial hematoma, but significant bleeding was not found in the pericardial sac or the thoracic cavities. Therefore, it was obvious that cardiovascular collapse occurred immediately after the accident. Neither injuries nor diseases that would cause the instantaneous death were found on examination of the whole body. We determined that the driver died of commotio cordis due to blunt force to the anterior chest.


Economic Burden of Cancer Treatment in a Region in South India: A Cross Sectional Analytical Study.
The rising cost of cancer diagnosis and treatment has imposed a huge financial burden on the affected households. Understanding the nature of this burden will help us to formulate plans to avoid financial distress among the same. The study aims to estimate the Out of Pocket Expenditure (OOPE) for the management of selected solid cancers among the Out-Patient Department (OPD) of Regional Cancer Centre in South India and to determine the proportion of families experiencing Catastrophic Health Expenditure (CHE) due to the same. A hospital based cross sectional analytical study was undertaken in the authors' institute in South India. 474 solid cancer patients were interviewed in OPD of Radiation Oncology by a trained data collector. Sociodemographic variables, costs incurred under various headings and expenditure details of participants were obtained. Direct Medical and Direct Non-Medical costs were calculated, and its total was used as the OOPE. Costs were presented as mean with its standard error. Incidence of CHE was calculated using the 40% threshold on the Capacity to pay and was expressed as proportions with 95% confidence interval. Appropriate statistical tests were used to look for statistically significant differences in the study groups. The average OOP expenditure incurred by a cancer patient was INR 35,817 (USD 523.6) for male and INR 20,496 (USD 299.6) for female. Males had a significantly higher OOPE than females. The prevalence of catastrophic health expenditure (CHE) was 61.6% at the 40% CTP threshold. Patients who used insurance schemes had higher prevalence of CHE than those who did not use insurance schemes (65.5% vs 60.7%, p value 0.351). Cancer care provided through public institutions had a low direct medical cost, but the indirect cost seemed to be extremely high. Public based financial assistance is the need of the hour to help the cancer affected families.


Altered contractile response due to increased beta3-adrenoceptor stimulation in diabetic cardiomyopathy: the role of nitric oxide synthase 1-derived nitric oxide.
In the diabetic heart, the positive inotropic response to beta-adrenoceptor stimulation is altered and beta1 and beta2 adrenoceptors are down-regulated, whereas beta3 adrenoceptor is up-regulated. In heart failure, beta3-adrenoceptor stimulation induces a negative inotropic effect that results from endothelial nitric oxide synthase (NOS3)-derived nitric oxide production. The objective of our study was to investigate the role of beta3-adrenoceptor in diabetic cardiomyopathy. beta-Adrenergic responses were investigated in vivo (dobutamine echocardiography) and in vitro (left ventricular papillary muscle) in healthy and streptozotocin-induced diabetic rats. The effect of beta3-adrenoceptor inhibition on the inotropic response was studied in vitro. Immunoblots and NOS activities were performed in heart homogenates (electron paramagnetic resonance) and isolated cardiomyocytes. Data are mean percentage of baseline +/- SD. The impaired positive inotropic effect was confirmed in diabetes both in vivo (121 +/- 15% vs. 160 +/- 16%; P < 0.05) and in vitro (112 +/- 5% vs. 179 +/- 15%; P < 0.05). In healthy rat, the positive inotropic effect was not significantly modified in presence of beta3-adrenoceptor antagonist (174 +/- 20%), nonselective NOS inhibitor (N -nitro-l-arginine methylester [l-NAME]; 183 +/- 19%), or selective NOS1 inhibitor (vinyl-l-N-5-(1-imino-3-butenyl)-l-ornithine [l-VNIO]; 172 +/- 13%). In diabetes, in parallel with the increase in beta3-adrenoceptor protein expression, the positive inotropic effect was partially restored by beta3-adrenoceptor antagonist (137 +/- 8%; P < 0.05), l-NAME (133 +/- 11%; P < 0.05), or l-VNIO (130 +/- 13%; P < 0.05). Nitric oxide was exclusively produced by NOS1 within diabetic cardiomyocytes. NOS2 and NOS3 proteins were undetectable. beta3-Adrenoceptor is involved in altered positive inotropic response to beta-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by NOS1-derived nitric oxide in diabetic cardiomyocyte.


Reference charts of gestation-specific tissue Doppler imaging indices of systolic and diastolic functions in the normal fetal heart.
Assessment of fetal cardiac function is difficult because of limited accessibility. Tissue Doppler imaging (TDI) is a promising technique in assessing diastolic function in adults. There has been sparseness concerning the use of TDI in assessing fetal cardiac function. The aim of this study was to construct reference charts of TDI indices of systolic and diastolic functions of the normal fetal heart. Ventricular myocardial velocities at the left ventricular (LV) wall, right ventricular (RV) wall, and interventricular septum (IVS) were assessed by TDI in 302 subjects. From 19 to 37 weeks of gestation, peak myocardial velocities during early diastole (Em) increased from 3.3 to 7.2, 3.9 to 8.3, and 3.2 to 5.0 m/s at the LV wall, RV wall, and IVS, respectively. Peak myocardial velocities during atrial contraction (Am) also increased throughout gestation, but the magnitude of increase was smaller (6.3 to 7.9, 7.7 to 10.6, and 5.5 to 5.9 m/s for the LV wall, RV wall, and IVS, respectively). As a consequence, the Em/Am ratio increased from 0.51 to 0.61 at midtrimester to 0.76 to 0.91 at term. Similar to Em, peak myocardial velocities during systole (Sm) also increased by almost 2 times from 18 to 37 weeks of gestation (3.8 to 6.0, 4.2 to 7.6, and 3.3 to 5.6 for the LV wall, RV wall, and IVS, respectively). Reference charts of gestation-specific Em, Am, Em/Am ratio, Sm, and E/Em were constructed accordingly. In midtrimester, fetal diastolic function is predominantly contributed by atrial contraction. As gestation advances, ventricular relaxation becomes increasingly mature. Reference charts for TDI indices were constructed, these will allow identification of fetuses with an abnormal diastolic function.


Evaluation of hepatocellular carcinoma size using two-dimensional and volumetric analysis: effect on liver transplantation eligibility.
Milan criteria recommends selection of candidates with hepatocellular carcinoma (HCC) for liver transplantation based on strict tumor size thresholds. The purpose of this study is to compare the effect of two-dimensional and three-dimensional tumor measurements on the selection of candidates for liver transplantation using Milan criteria. This retrospective Health Insurance Portability and Accountability Act-compliant study was approved by our institutional review board. Patient-informed consent was waived. Forty-five HCCs in 19 patients, evaluated with triphasic multidetector row computed tomography scans, were included in the analysis. The largest diameters in each two-dimensional orthogonal plane (Max2D) and within three-dimensional tumor boundaries (Max3D) were calculated for each lesion. Diameters were compared and the eligibility based on lesion size for liver transplantation was assessed. The mean Max2D diameter of HCC was 3.2 ± 0.9 cm and the mean Max3D diameter was 3.5 ± 1.2 cm. There was a significant difference between the mean Max2D and Max3D diameters (P < .001). Among the 45 lesions, 22 of them (48.9%) were ineligible for transplantation according to Max2D diameter, whereas 29 of them (64.44%) were ineligible when Max3D diameter was applied (P < .001). HCC diameter based on 3D measurements is significantly different than the conventional 2D measurements and may affect eligibility for liver transplantation.


Validating an image segmentation program devised for staging lymphoma.
Hybrid positron emission tomography-computed tomography (PET-CT) imaging systems are an important tool for assessing the progression of lymphoma. PET-CT systems offer the ability to quantitatively assess lymphocytic bone involvement throughout the body. There is no standard methodology for staging lymphoma patients using PET-CT images. Automatic image segmentation algorithms could offer medical specialists a means to evaluate bone involvement from PET-CT images in a consistent manner. To devise and validate an image segmentation program that may assist staging lymphoma by determining the degree of bone involvement based from PET-CT studies. A custom-made program was developed to segment regions-of-interest from images by utilising an enhanced fuzzy clustering technique that incorporates spatial information. The program was subsequently tested on digital and physical phantoms using four different performance metrics before being employed to extract the bony regions of clinical PET-CT images acquired from 248 patients staged for lymphoma. The algorithm was satisfactorily able to delineate regions-of-interest within all phantoms. When applied to the clinical PET-CT images, the algorithm was capable of accurately segmenting bony regions in less than half of the subjects (n = 103). The performance of the algorithm was adversely affected by the presence of oral contrast, metal implants and the poor image quality afforded by low dose CT images in general. Significant changes are necessary before the algorithm can be employed clinically in an unsupervised fashion. However, with further work performed, the algorithm could potentially prove useful for medical specialists staging lymphoma in the future.


[Determination of longistylin A and longistylin C in Cajanus cajan].
To establish quality control criteria for medicinal herb Cajanus cajan based on the determination of longistylin A and longistylin C, two bioactive and specific stilbenes of the plant. Longistylin A and longistylin C were obtained from the leaves of C. cajan by silica gel column chromatography and identified as marker compounds of this plant by spectroscopic analysis. A RP-HPLC method was established to determine the two compounds. Longistylin A and longistylin C were well separated on a Thermo BDS Hypersil C18 column (4.6 mm x 250 mm, 5 microm) with a mobile phase methanol-water (8:2), and showed good linearity in the range of 0.00288 - 0.0576 microg and 0.0112 - 0.224 microg, respectively. The average recoveries were 98.9% and 97.2% with RSD of 2.4% and 2.2% for these two compounds, respectively. The established analysis method is simple and accurate, whicn can be used for quality control of C. cajan.


New horizons of biomaterials in treatment of nerve damage in diabetes mellitus: A translational prospective review.
Peripheral nerve injury is a serious concern that leads to loss of neuronal communication that impairs the quality of life and, in adverse conditions, causes permanent disability. The limited availability of autografts with associated demerits shifts the paradigm of researchers to use biomaterials as an alternative treatment approach to recover nerve damage. The purpose of this study is to explore the role of biomaterials in translational treatment approaches in diabetic neuropathy. The present study is a prospective review study. Published literature on the role of biomaterials in therapeutics was searched for. Biomaterials can be implemented with desired characteristics to overcome the problem of nerve regeneration. Biomaterials can be further exploited in the treatment of nerve damage especially associated with PDN. These can be modified, customized, and engineered as scaffolds with the potential of mimicking the extracellular matrix of nerve tissue along with axonal regeneration. Due to their beneficial biological deeds, they can expedite tissue repair and serve as carriers of cellular and pharmacological treatments. Therefore, the emerging research area of biomaterials-mediated treatment of nerve damage provides opportunities to explore them as translational biomedical treatment approaches. Pre-clinical and clinical trials in this direction are needed to establish the effective role of several biomaterials in the treatment of other human diseases.


Socioeconomic Status Disparities in Cognitive and Physical Functional Impairment among Older Adults: Comparison of Asians with other Major Racial/Ethnic Groups.
This study investigated to what extent socioeconomic status (SES) disparity associates with cognitive and physical impairment within older Asian Americans in comparison with other races/ethnicities. Data were from the National Health and Nutrition Examination Survey 2011-2018 that included 3,297 White, 1,755 Black, 1,708 Hispanic, and 730 Asian Americans aged ≥ 60. Physical functioning was measured by activities of daily living (ADL) or instrumental activities of daily living (IADL). Memory and language fluency were evaluated using the Alzheimer's Disease Word List Memory Task and Animal Fluency Tests, respectively. Multivariate logistic regressions were conducted to investigate the association between SES and physical and cognitive impairment within racial/ethnic groups, and seemingly unrelated regressions compared coefficients across subgroups. Asians with ≤ high school education had the highest prevalence of age- and sex-adjusted memory impairment among all races/ethnicities, while no difference was observed for those with > high school education. ADL/IADL disability odds did not differ between Asians and Whites, but Asians were more likely to exhibit impaired verbal fluency. Education disparity for ADL disability (OR, 3.40; 95% CI, 2.20-5.25) and memory impairment (OR, 11.57; 95% CI, 6.59-20.31) were largest among Asians compared to Whites, Blacks, and Hispanics. Income disparity for function impairment showed no significant difference across racial/ethnic groups (all P > 0.05). Asians experienced the highest burden of physical functioning and memory impairment due to education disparity. Efforts should focus on strengthening research infrastructure and creating targeted programs and services to improve cognitive and physical health for racially/ethnically underrepresented older adults with lower education attainment.


Hypoxic-hypercapnic ventilatory interaction at the carotid body of awake goats.
Neurophysiological studies have demonstrated that a positive interaction between hypoxic and hypercapnic stimuli occurs at the carotid body (CB). The present study was designed to confirm that this interaction at the CB was translated into a similar interaction in the ventilatory response. By utilizing an awake goat model in which the CB could be selectively perfused using an extracorporeal circuit we avoided confounding central effects. In six goats the CB was stimulated by progressively decreasing PcbO2 from 160 to 40 Torr at two constant levels of PcbCO2, 36 and 61 Torr. The animals breathed room air with supplemental CO2 to maintain systemic isocapnia. The response to CB hypoxia was significantly greater in CB hypercapnia than in CB normocapnia for minute ventilation, tidal volume, respiratory frequency, and mean inspiratory flow rate. We conclude that the hypercapnic-hypoxic interaction at the CB is reflected in the ventilatory responses of the animal.


[Washing liquid cytology examination of operative wound in patients with breast tumor].
To study the relation between exfoliated tumor cells in operative wound and clinical pathologic classification and to provide theory for killing exfoliated tumor cells in operation. Washing liquid cytology examination of the operative wound was done in 262 patients with breast tumor. The relation between cytology examination and pathological classification was analyzed. In the 262 patients, exfoliated tumor cells were found in 63 patients, (24%). The detection rate in patients with I, II, III and IV stage was 5.3%, 27.1%, 79.3% and 100% respectively; The rate for T(1), T(2), T(3) stage was 6.1%, 18.9% and 51.3% respectively. The detection rate was 58.6% when the number of metastasis lymph node beyond 3; the rate was 14.3% and 14.1% respectively when the number below 3 or no lymphatic metastasis. The detection rate of exfoliated tumor cells is related to tumor advance, and it is necessary to kill exfoliated tumor cells in operation.


The mechanism of the release of hepatic enzymes in various liver diseases. 1. Alterations in cytoplasmic and mitochondrial enzyme activities in serum.
Serum glutamic oxaloacetic transaminase (GOT), mitochondrial GOT (GOTm), glutamic-pyruvic transaminase (GPT) and glutamate dehydrogenase activities were determined in 43 healthy controls and in 280 cases of liver diseases. A simplified column chromatographic method coupled with UV assay was employed for separation of GOTm. The activity was measured by following decrease in abosrbance of NADH at 340 nm. The lowest activity of GOTm determined with a coefficient of variation below 10% was 6 mIU/ml. High GOTm activities were found in acute hepatitis (acute stage), subacute hepatitis and primary biliary cirrhosis and were generally associated with high total GOT (GOTt) activities. The activity ratio of GOTm/GOTt varied depending on the stage and severity of liver diseases. The GOTm/GOTt ratio was decreased in acute, fulminant and subacute hepatitides. No significant reduction in the ratio was found in bile duct obstruction, alcoholic liver injury or metastatic liver cancer. Although relatively high GOTm/GOTt ratios were found in some patients with severe hepatic injury, they had no definite association with poor prognosis. These results indicate that the marked elevation in GOTt over GPT in advanced chronic hepatitis, liver cirrhosis and primary hepatoma was mainly due to preferential leakage of cytoplasmic GOT (GOTs).


Administration of prostaglandin F2alpha for the recovery of fertilized eggs from the vaginas of rabbits.
Nonsurgical recovery of fertilized eggs from the vaginas of prostaglandin F2alpha (PGF2alpha)-treated rabbits was attempted. Eighty-two eggs were collected by the vaginal washing method, and the earliest egg was recovered 20 hours after mating. Twenty eggs recovered vaginally 24 to 107 hours after mating were transferred to six synchronized, pseudopregnant rabbits to test the viability of the eggs; four newborns, two fetuses, and one implantation site were obtained. These results indicate that some viable eggs are discharged into the vaginas of rabbits treated with PGF2alpha.


The effects of domain knowledge and event structure on event processing.
Research suggests that domain knowledge facilitates memory for domain-specific information through two mechanisms: differentiation, which involves the ability to identify meaningful, fine-grained details within a sequence, and unitization, which involves binding individual components from a sequence into functional wholes. This study investigated the extent to which individuals engaged in differentiation and unitization when parsing continuous events into discrete, meaningful units (i.e., event segmentation) and recalling them. Participants watched and segmented basketball videos. They then rewatched the videos and provided descriptions afterward. Videos were coded for the presence of higher order goals (A2 actions) and the individual sub-actions that comprised them (A1 actions). Results suggested that event segmentation behavior for participants with less knowledge was more aligned with changes in basic actions (A1 actions) than for participants with greater knowledge. When describing events, participants with greater knowledge were more likely than participants with less knowledge to use statements that reflected unitization.


Neurocognitive deficits increase risk of poor retention in care among older adults with newly diagnosed HIV infection.
To evaluate the role of neurocognitive impairment on retention in care across the lifespan in antiretroviral-naïve persons newly diagnosed with HIV. A prospective observational study of 138 antiretroviral-naive newly diagnosed HIV-positive participants who presented to an urban clinic between August 2010 and April 2013. All participants underwent a baseline evaluation that included a neuromedical examination and brief neuropsychological test battery. Retention in care was operationalized as attending at least two visits separated by more than 90 days during the 12-month follow-up period. Fifty-five per cent of participants were retained in care over the study observation period. In a logistic regression controlling for ethnicity, there was a significant interaction between age and neurocognitive impairment in predicting retention in care (P = 0.009). Planned post-hoc analyses showed that neurocognitive impairment was associated with a significantly lower likelihood of retention in care among participants aged 50 years and older (P = .007), but not among younger participants (P > 0.05). Extending prior research on antiretroviral adherence and medication management, findings from this study indicate that neurocognitive impairment may be an especially salient risk factor for poor retention in care among older adults with newly diagnosed HIV infection.


Promoter recognition by sigma-37 RNA polymerase from Bacillus subtilis.
Bacillus subtilis possesses at least five different forms of RNA polymerase holoenzyme which are distinguished by their sigma subunit and their promoter recognition specificity. Sigma-37 RNA polymerase, a minor form of RNA polymerase, recognizes a class of promoters, which includes promoters for genes transcribed early during endospore formation. We have used site-directed bisulfite mutagenesis to construct a series of single and multiple base substitutions in a promoter recognized by sigma-37 RNA polymerase. In vitro transcription analysis of this series of mutant promoters demonstrated that single base substitutions at positions -36, -16, -15 and -14 most dramatically reduced the efficiency of promoter utilization by sigma-37 RNA polymerase. These results support a model in which sigma-37 RNA polymerase recognizes its cognate promoters by interacting with a sequence of nucleotides near the -10 region and the -35 region of the promoter--a sequence not recognized by B. subtilis sigma-55 RNA polymerase or Escherichia coli RNA polymerase.


Clinically useful smartphone ophthalmic imaging techniques.
Imaging devices in ophthalmology are numerous, and most of them are sophisticated and specialized for specific regions of the eye. In addition, these are fixed and involve close interaction of the patient and the examiner; therefore, simple, portable and tele facility-imbibed imaging tools can be considered optimal alternatives to routine exercises. In the last 10 years, utility of smartphones in ophthalmology is being continuously explored to unearth their potential benefits. In this direction, a smartphone device with/without simple attachments has been noted to aid in detailed, high-quality imaging of the ocular adnexa, cornea, angle, iris, lens, optic disc, and the retina including its periphery. In addition, such utility has also been extended in strabismology workup and intraocular pressure measurements. Hence, using these clinician friendly tools and techniques or by devising newer and more comprehensive tool kits, ophthalmic care can be well-managed with apt use of technology. Also, the smartphone companies are encouraged to collaborate with the medical experts to endeavor more, and help and serve the people better.


Morphology and structure of in situ FeS affect Cr(VI) removal by sulfidated microscale zero-valent iron with short-term ultrasonication.
The properties of sulfidated zero-valent iron (S-ZVI) are considered to be determined by the entire structure of Fe0 and FexSy as a whole, but few studies focus on the influence of the morphology and structure of the external FexSy layer on the performance of S-ZVI. In this study, after the sulfidation of microscale ZVI in acetate (HAc-NaAc) and 2-(N-morpholino) ethanesulfonic acid (MES) buffer solution, the S-mZVIHAc-NaAc surface presented the in situ growth of the FeS nanosheet, while the S-mZVIMES surface was dominated by agglomerated FeS sub-micron particles. Under short-term ultrasonication, S-mZVIHAc-NaAc was superior to removing Cr(VI) than S-mZVIMES, and the clearance of the passivation layer by ultrasound maximized the conductivity of the FeS nanosheet to strengthen the sulfidation contribution. However, agglomerated FeS particles were easily separated from S-mZVIMES by ultrasonication, resulting in the suppression of its sulfidation contribution. The removal of Cr(VI) by S-ZVI increased linearly with FeS content, and the chemical combination of FeS with ZVI had more significant synergy than their physical mixture. The FeS nanosheet with excellent conductivity and large vertical space benefited the generation of dissolved and surface-associated Fe(II) as electron donors and structural Fe(II) as the electron shuttle. Understanding the relationship between FeS structure and S-ZVI performance will pave a way for optimizing the synthesis of S-ZVI.


Superior prognosis stratification for stage III colon cancer using log odds of positive lymph nodes (LODDS) compared to TNM stage classification: the Japanese study group for postoperative follow-up of colorectal cancer.
The aim of this study is to examine whether prognosis stratification in staging of Stage III colon cancer using T factor and log odds of positive lymph nodes (LODDS) categories is superior to that of the TNM staging system. The subjects were 5,919 patients with Stage III colon cancer who underwent curative resection at 24 Japanese institutions. Univariate analysis of LODDS categories and clinicopathologic factors was conducted using a Cox proportional hazards regression model for cancer-specific survival (CSS). Independent prognostic factors for CSS were extracted in multivariate analysis using factors with significance in univariate analysis. Effect sizes of risk factors for CSS were compared using the LogWorth statistic. Combinations of T factor and LODDS categories were used to create L-stage subgroups A, B and C. Stratification of prognosis with L-stage and TNM was compared using the Akaike information criterion (AIC). In multivariate analysis, LODDS was identified as an independent prognostic factor, together with age, maximum tumor diameter, histopathological grade, L, V, pT, and pN. The LogWorth of LODDS was 17.149, which was the second highest after pT (31.562), and that of pN was 7.434. The 5-year CSS was 96.5%, 88.5%, and 66.6% in TNM stages IIIA, IIIB, and IIIC, respectively, and 96.0%, 87.6%, and 59.3% in L-stage A, B, and C, respectively (p < 0.0001). AICs for TNM and L-stage were 14,795.5 and 14,707.8, respectively. Prognosis stratification of the stage classification for Stage III colon cancer was superior with L-stage compared to TNM stage classification.


Lipopolysaccharide-binding protein as a new and reliable infection marker after kidney transplantation.
The early and reliable differentiation of rejections, viral infections and bacterial infections is one of the main problems after organ transplantation. One promising solution to this problem is the lipopolysaccharide-binding protein (LBP), which is regulated upwards in gram-negative sepsis and related conditions. Therefore, the aim of our study was to explore the diagnostic potential of LBP serum levels in well-defined, non-infectious and infectious events after kidney transplantation (KTx). In a retrospective study the LBP serum levels were measured in a total of 686 serum samples from 52 kidney graft recipients. In all pre-KTx sera tested, the mean LBP level was 8.8+/-3.5 microg/ml (reference range: 2.0-15.2 microg/ml). In 7 of 52 recipients without intraoperative T-cell depletion, the mean LBP level was significantly ( P<0.01) increased (13.0+/-1.5 microg/ml) at post-KTx day 1, but was within the reference range. In contrast, the intraoperative T-cell depletion by antilymphocyte antibodies resulted in a significant ( P<0.01) increase to 25.8+/-11.4 microg/ml (range: 13.3-47.2 microg/ml). In recipients with immediate ( n=14) or delayed ( n=9) graft function without any other complications, all post-KTx values (except the post-KTx peak) were within the reference range. In 10 recipients with steroid-sensitive rejections and in 11 recipients with steroid-resistant rejections, no rejection-associated changes of the LBP levels could be shown. In six recipients with cytomegalovirus infection, the detection of an antigenemia (pp65) also was not associated with alterations of the LBP levels. In addition, there was no correlation between LBP levels and the number of pp65-positive leukocytes in peripheral blood. In contrast, a strong elevation of LBP levels was seen in five recipients with gram-positive bacteremia as well as in other severe bacterial infections (e.g., purulent extravasate, heavily infected grafts, bacterial pneumonia and contaminated hematoma). In two recipients with superinfected (bacterial and mycotic or viral) Pneumocystis carinii pneumonias requiring assisted ventilation, LBP levels were elevated, too. Thus, in our study only systemic non-viral infections and massive lymphocytolysis were associated with elevated LBP serum levels.


Alternatives to restraints: what patients and caregivers should know.
Current nursing practice mandates that patients be provided safe care in the least restrictive environment possible. This article discusses specific unsafe patient behaviors, their possible causes, and alternatives to the use of restraints in the home. The role of the home care and hospice professional is presented.


Focal Dermal Hypoplasia: Case Series.
Focal dermal hypoplasia (Goltz syndrome) is a genetic multisystem disorder characterized primarily by involvement of the skin associated to face, skeletal, and eyes anomalies. The objective of the present series is to shed light on this rare syndrome and these atypical manifestations. Our study reports the case of five Moroccan patients who present typical clinical picture of the Goltz syndrome with some rare manifestations. A total of 5 patients with Goltz syndrome were evaluated. All of them are female with one familial case. The age ranged from 8 months to 35 years. A characteristic Blaschkoid hypo- and hyper-pigmented skin lesions, congenital nodular fat herniation, and skin atrophy were present in all patients. Ocular manifestations were present in 80% of patients. Cranio-facial deformity was seen in 80% of patients. Short stature and intellectual delay were documented in 80% and 40% of patients, respectively. Limb abnormality was found in all patients. Two patients had a cleft lip, one of which unusual lateral facial cleft. Genetic testing could not be performed in the present series. Through this work we will discuss the different clinical signs and genetic aspects of Goltz syndrome and the interest of a good clinical expertise.


Habitat-Specific variation in eyespot size of a benthic cladoceran.
Pigmented eyespot size of the benthic cladoceran Simocephalus exspinosus was measured in individuals sampled from four freshwater ponds that differed in the extent of visually-oriented predation. In ponds with such predation (from fish, salamander larvae, and dragonfly nymphs), eyespot size was found to be significantly smaller, relative to body size, than in a pond without visually-oriented predation. Reduction in pigmented eyespot size may represent an adaptation to reduce vulnerability to predation.


Initial blood cultures in pediatric patients with central line infections and short bowel syndrome can direct a treatment plan that can reduce hospital length of stay.
Children with short bowel syndrome requiring parenteral nutrition are at high risk of recurrent central line-associated bloodstream infections requiring inpatient admission. Predicting responses to treatment at admission could help revise our current treatment algorithm and reduce the length of stay. We conducted a retrospective study of all intestinal rehabilitation clinic patients admitted for central line-associated bloodstream infections at our academic hospital between January 2018 and June 2021. Demographic, blood culture, and treatment response data were analyzed. There were 180 separate admissions for central line-associated bloodstream infections, involving 24 patients who met the inclusion and exclusion criteria. The average length of stay was 9.4 days, and 77.1% of the admissions exceeded the predicted length of stay. All patients were treated according to the standard protocols. In the initial blood cultures, 64.4%, 10.6%, and 25% grew a single bacterium, a single fungus, and multiple organisms, respectively. After treatment initiation, 73.3% of single bacterial infections did not show additional positive cultures. However, 78.9% and 48.9% of fungal and multiple organism infections, respectively, had multiple positive cultures, even after initiating treatment. All positive repeat cultures were treated with an ethanol lock for 24 hours in addition to continued treatment. The treatment preserved 90.5% of the catheters. Patients experiencing short bowel syndrome admitted for central line-associated bloodstream infections with initial cultures growing fungi or multiple organisms frequently had multiple positive cultures, whereas those with a single bacterial organism did not. Discharging patients who grew a single bacterial organism and placing an initial ethanol lock on those with multiple or fungal organisms could reduce the average length of stay, even if some of these patients would require readmission for line removal.


Attenuation of corticotropin releasing factor-induced hypotension in anesthetized rats with the CRF antagonist, alpha-helical CRF9-41; comparison with effect on ACTH release.
The effect of pretreatment with the corticotropin releasing factor (CRF-41) antagonist, alpha-helical CRF(9-41), on the hypotensive response obtained on peripheral administration of CRF-41 has been assessed in anesthetized Wistar rats. A single IV bolus dose of rat CRF-41 (2 nmol, at 0 min) produced a hypotensive effect which was rapid in onset (-52 mmHg at +1 min) and sustained throughout the 60-min study period (-42, -40, -26 and -16 mmHg at +3, +10, +30 and +60 min, respectively). The antagonist [alpha CRF(9-41)] was administered in consecutive bolus doses of 12.5, 25 and 50 nmol at -15, -10 and -5 min, respectively. This had no effect on mean arterial blood pressure (MABP) or heart rate, nor did it change significantly the magnitude of the initial rapid fall in MABP when CRF-41 was administered (-45 mmHg at +1 min). However, following pretreatment with alpha CRF(9-41), MABP returned to control values within 3 min and the sustained period of hypotension was completely blocked. Administration of CRF-41 resulted in 44% and 142% increases in norepinephrine and epinephrine measured at +60 min. Pretreatment with the antagonist attenuated the rise in circulating catecholamine levels observed after CRF-41 administration. In comparison, pretreatment with the antagonist did not alter the ACTH response to CRF-41 at +1 and +3 min and only reduced ACTH levels by 28% (p less than 0.05), 43% (p less than 0.001) and 41% (p less than 0.01) at 10, 30 and 60 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Motile cells lacking hyaluronidase can penetrate the hamster oocyte cumulus complex.
Sperm hyaluronidase is thought to assist in penetration of the extracellular matrix (ECM) between the cumulus and corona radiata cells surrounding mammalian oocytes. The question was asked: Can motile cells which lack hyaluronidase penetrate the hamster oocyte cumulus complex (OCC)? Sea urchin (Strongylocentrotus purpuratus) and frog (Rana catesbeiana) sperm and the unicellular, biflagellated, green alga Chlamydomonas reinhardtii were extracted and found to contain no hyaluronidase activity. Moreover, none of these cells was able to disperse the cumulus cells of hamster OCC, nor did they affect the ultrastructure of the ECM between cells. Fresh hamster OCC were challenged with suspensions of each cell type. Frog and sea urchin sperm penetrated to the zona pellucida surface in less than 5 min. A cell wall-less mutant of Chlamydomonas also penetrated to the zona surface but required longer than 5 min. Wild-type Chlamydomonas penetrated only halfway to the zona, perhaps because its cell wall adhered to the ECM between the cumulus cells and retarded its movement. The motility of the frog and sea urchin sperm was not affected by the ECM of the OCC. Frog sperm exhibited slow lethargic motility yet had no difficulty penetrating to the zona; this indicates that hyperactivated motility is not required for penetration of the ECM. None of the challenge cells penetrated the zona pellucida, although the frog sperm did compress the weave of the zona. These data show that motile cells which lack the enzyme hyaluronidase can readily penetrate the ECM of the hamster cumulus and corona radiata and suggest that the significance of hyaluronidase in fertilization should be reevaluated.


Regulatory mechanisms of mitogen-activated kinase signaling.
MAP kinases (MAPKs) are evolutionarily conserved regulators that mediate signal transduction and play essential roles in various physiological processes. There are three main families of MAPKs in mammals, whose functions are regulated by activators, inactivators, substrates and scaffolds, which together form delicate signaling cascades in response to different extracellular or intracellular stimulation. MAPK signaling is tightly regulated so that optimal biological activities are achieved and health is maintained. However, how the specificity of the signaling flow along each cascade is achieved is still relatively unclear. In this review, we summarize recent advances in understanding the regulation of MAPK cascades and the roles of MAP kinases and their regulators in development and in immune responses.


Continuous Thermodilution Method to Assess Coronary Flow Reserve.
Coronary flow reserve (CFR) is a well-validated flow-based physiological parameter that has shown value in clinical risk stratification. CFR can be invasively assessed, classically by Doppler and, more recently, by thermodilution with saline boluses (CFRthermo-bolus). Alternatively, continuous thermodilution is a novel operator-independent, highly-reproducible technique to invasively quantify maximum absolute coronary flow (AF). This study aimed to assess the feasibility of this method to quantify resting AF and to determine CFR (CFRThermo-infusion) as compared with CFRthermo-bolus. Sixty-two consecutive patients with suspicion of coronary disease and absence of significant epicardial lesions were prospectively investigated. AF at maximal hyperemia (20 mL/min) and at lower infusion rates (6-8-10-12 mL/min) were systematically measured using a dedicated catheter and a temperature/pressure guidewire. The absence of baseline Pd/Pa decrease at 6 (0.15 ± 0.2%), 8 (0.17 ± 0.18%) and 10 mL/min (0.2 ± 0.12%) demonstrated absence of hyperemia at ≤10 mL/min (all p = NS). However, at 12 mL/min hyperemia was confirmed by a significant decrease in Pd/Pa (1.3 ± 1.5%, p <0.01) and increase in AF from 10 mL/min to 12 mL/min (31.4 ± 28.1 mL, p <0.05). All curve tracings at 10 mL/min (129/129, 100%) were adequate versus only (7/15, 53%) and (15/18, 17%) at 6 mL/min, and 8 mL/min, respectively, and this infusion-rate was considered to determine resting-AF. CFRThermo-infusion was determined as the ratio of hyperemic-AF (20 mL/min) by resting-AF (10 mL/min). Mean CFRThermo-infusion was 2.56 ± 0.9 and CFRthermo-bolus 2.49 ± 1. Both parameters showed a good correlation (r = 0.76; p <0.001) and intraclass agreement (ICC = 0.76; p <0.001).The continuous thermodilution method enables to quantify resting-AF providing a novel clinical tool to determine CRF. CFRThermo-infusion shows a good correlation with CFRthermo-bolus..


Many‑objective meta-heuristic methods for solving constrained truss optimisation problems: A comparative analysis.
Many-objective truss structure problems from small to large-scale problems with low to high design variables are investigated in this study. Mass, compliance, first natural frequency, and buckling factor are assigned as objective functions. Since there are limited optimization methods that have been developed for solving many-objective truss optimization issues, it is important to assess modern algorithms performance on these issues to develop more effective techniques in the future. Therefore, this study contributes by investigating the comparative performance of eighteen well-established algorithms, in various dimensions, using four metrics for solving challenging truss problems with many objectives. The statistical analysis is performed based on the objective function best mean and standard deviation outcomes, and Friedman's rank test. MMIPDE is the best algorithm as per the overall comparison, while SHAMODE with whale optimisation approach and SHAMODE are the runners-up.•A comparative test to measure the efficiency of eighteen state-of-the-practice methods is performed.•Small to large-scale truss design challenges are proposed for the validation.•The performance is measured using four metrics and Friedman's rank test.


Ca2+ potentiates corticotropin-induced, but not isoproterenol-induced, [3H]guanosine diphosphate release in rat adipocyte membranes.
EGTA abolished corticotropin (ACTH)-stimulated adenylate cyclase in rat adipocyte membranes. In contrast, the potency of guanosine triphosphate (GTP) stimulation of adenylate cyclase activated with ACTH was greater in the presence of Ca2+ (1 mmol/L). EGTA (1 mmol/L) powerfully inhibited ACTH-stimulated [3H]guanosine diphosphate (GDP) release from membranes prelabeled with [3H]GTP in the presence of isoproterenol (ISO) or ACTH, whereas Ca2+ significantly increased it. In contrast, neither EGTA nor Ca2+ affected ISO-stimulated [3H]GDP release. These data clearly show that Ca2+ is necessary for the binding of ACTH to its receptor, and that Ca2+ stimulates the interaction of the ACTH-occupied receptor with GTP-binding proteins.