Electrophysiological effects of encainide (MJ9067) on canine subendocardial Purkinje fibers surviving infarction.
The electrophysiological effects of encainide (MJ9067) on canine subendocardial Purkinje fibers surviving infarction were examined 22-24 h after coronary artery ligation, using standard microelectrode techniques at pH 7.4. Encainide (5 and 10 microM) shortened APD50, decreased the action potential amplitude and overshoot, caused a 2-3 mV depolarization of the cell, and decreased the maximum rate of phase 0 depolarization. All these effects were dose dependent. APD90 was slightly, but not significantly, shortened. Encainide had a greater effect on APD50 and APD90 at longer (1,000 ms) stimulation cycle lengths than at shorter (400 ms) cycle lengths. There was a significant interaction between the effects of stimulation rate and encainide concentration on APD90, APD50, amplitude, and overshoot. The same parameters measured at a lower pH (7.1) gave similar results. There was a significant correlation (r = -0.540, p less than 0.001) between the control APD90 and the degree and direction of change of APD90 after 10 microM encainide. Automaticity of the infarcted preparations was eliminated or slowed in a dose-dependent fashion by 5 and 10 microM encainide. The curve relating membrane potential and the maximum rate of phase 0 depolarization was shifted down and toward higher potentials by 5 microM encainide. The results show that encainide produces similar changes in the action potentials of Purkinje fibers surviving infarction as in normal Purkinje fibers, and is effective in lowering the rate of spontaneous depolarization in infarcted tissue. Furthermore, encainide appears to be the only antiarrhythmic drug which has been shown to increase and decrease APD90, depending on the initial APD90 of the cell.


Median Nerve Ultrasonography Measurements Correlate With Electrodiagnostic Carpal Tunnel Syndrome Severity.
The purpose of this study was to assess whether median nerve ultrasonography (US) measurements correlate with the severity scale of electrodiagnostic studies (EDS) of carpal tunnel syndrome (CTS). A retrospective review was conducted of patients aged ≥18 years who underwent both median nerve US and EDS. US measurements of the median nerve cross-sectional area at the distal wrist crease and forearm were used to calculate the median nerve wrist-to-forearm ratio. EDS severity was classified according to guidelines from the American Association of Electrodiagnostic Medicine. A total of 112 wrists (n = 112) in 78 consecutive patients with a mean age of 59 (range, 26 to 88) years were included. Increased cross-sectional area at the distal wrist crease and wrist-to-forearm ratio were significantly correlated with increased EDS severity (P < 0.0001). Median nerve US measurements not only distinguished between normal and abnormal EDS but also correlated with the category of EDS severity. Diagnostic III.


The Stockholm trial on adjuvant tamoxifen in early breast cancer. Correlation between estrogen receptor level and treatment effect.
The paper presents interim results of an on-going randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no endocrine adjuvant therapy in postmenopausal women with early breast cancer. A total of 1407 patients were included in the study between November 1976 through June 1984. Estrogen receptor (ER) data were available on 1184 patients (84%). The median follow-up was 53 months. Adjuvant tamoxifen increased the recurrence-free interval (P less than 0.01) but had no significant effect on overall survival. Treatment failures were reduced by 25% (P less than 0.01) and deaths by 7% (P greater than 0.05). Tamoxifen mainly decreased the frequency of loco-regional recurrence whereas distant metastases were less affected. The treatment effect was independent of tumor stage but was significantly related to the estrogen receptor (ER) content of the primary tumor. Tamoxifen appeared ineffective among ER negative patients, and the greatest effect was seen among those with high levels of ER. The results indicate that the main mechanism of action of adjuvant tamoxifen is similar to that suggested in advanced disease, i.e. an interaction with the estrogen receptor.


Semantic memory in schizophrenia: association with cell membrane essential fatty acids.
Semantic memory and language deficits are associated with schizophrenia. Understanding how these systems operate in this disorder will likely require a multi-factorial model that explains their linkages with cognition and modulation by dopamine. A biological factor that may provide causal convergence for these connections is cell membrane composition and dynamics. N400 is an electrophysiological measure of semantic memory and language that is sensitive to deficits in schizophrenia. Relationships among N400, cognition, dopamine, and cell membrane polyunsaturated fatty acids (PUFAs) were examined for patients tested under medicated (haloperidol only) and unmedicated (placebo) conditions. Relationships between these factors and clinical symptoms were also evaluated. The sample included 37 male schizophrenia inpatients and 34 male normal controls. The N400 priming effect was measured from visual event-related potentials recorded during a semantic priming-lexical decision task, in which semantic association (related versus unrelated words) and presentation rate (Stimulus Onset Asynchrony/SOAs: 350 and 950 ms) were varied. N400 was associated with cognition (speed, visuoperception, attention) in patients and controls. These relationships were influenced by SOA in both groups, and by pharmacological condition in patients. Levels of total PUFAs and arachidonic acid were associated with N400 in unmedicated patients. Clinical symptoms (paranoia, thought disturbance) were associated with N400, but not with cognition or PUFAs. Results suggest cell membrane fatty acids are associated with semantic memory and language in schizophrenia. Findings also suggest a series of linkages that are modulated by dopamine: cell membrane fatty acids are associated with N400 semantic priming; N400 semantic priming is associated with clinical symptoms.


A compound radial artery forearm flap for the reconstruction of lip and chin defect.
This report presents a successful case of lip and chin reconstruction by a compound radial artery forearm free flap. This was a versatile source of tissue in the absence of local tissue for reconstruction.


Anti-inflammatory and analgesic activities of the hydrolyzed sasanquasaponins from the defatted seeds of Camellia oleifera.
The defatted seeds of Camellia oleifera (Abel.) are used for stopping itching and pain in old days, the effective compounds need to be investigated. Sasanquasaponin as a rich fraction was extracted with 70% ethanol, purified by AB-8 macro-reticular resin, crystallized in 80% ethanol, and further hydrolyzed by 4% hydroxyl potassium or 2 M hydrochloride. Anti-inflammatory activities of the extracts were measured by carrageenan-induced paw edema in rats and croton oil induced ear inflammation in mice; the analgesic activities were analyzed by hot plate test, acetic acid induced writhing in mice; the levels of pain mediators of IL-1β, TNF-α and PGE₂ were determined; the antioxidative activities in vivo were evaluated by MDA, SOD and GSH-Px in serum of rats. The extracts showed significant (p < 0.01) anti-inflammatory and analgesic activities, remarkably (p < 0.01) inhibited production of pro-inflammatory cytokines and PGE2, decreased MDA and increased SOD and GSH-Px in serum. Inhibition of IL-1β, TNF-α and PGE2 may contribute to their anti-inflammatory and analgesic effects; elimination of free radicals is also involved. The sapogenin and acid hydrolyzed product have better anti-inflammatory, analgesic effects, and stronger antioxidative activity than sasanquasaponin and alkaline hydrolyzed product, and they are better candidate medicines for inflammation and pain.


[Antibodies to double-helical RNA and several viruses in medical personnel caring for systemic lupus erythematosus patients].
An average level of antibody to double-stranded RNA in patients with systemic lupus erythematosus and medical staff taking care of these patients is higher than that in physicians from other institutions and donors. The level of antibodies to antigens of various viruses in lupus patients is elevated in comparison with that in the medical staff. No statistically significant differences in the levels of antibody to viruses in the staff of various institutions were found.


Monoacylglycerol O-acyltransferase 1 lowers adipocyte differentiation capacity in vitro but does not affect adiposity in mice.
Monoacylglycerol O-acyltransferase 1 (Mogat1), a lipogenic enzyme that converts monoacylglycerol to diacylglycerol, is highly expressed in adipocytes and may regulate lipolysis by re-esterifying fatty acids released during times when lipolytic rates are low. However, the role of Mogat1 in regulating adipocyte fat storage during differentiation and diet-induced obesity is relatively understudied. Here, adipocyte-specific Mogat1 knockout mice were generated and subjected to a high-fat diet to determine the effects of Mogat1 deficiency on diet-induced obesity. Mogat1 floxed mice were also used to develop preadipocyte cell lines wherein Mogat1 could be conditionally knocked out to study adipocyte differentiation in vitro. In preadipocytes, it was found that Mogat1 knockout at the onset of preadipocyte differentiation prevented the accumulation of glycerolipids and reduced the differentiation capacity of preadipocytes. However, the loss of adipocyte Mogat1 did not affect weight gain or fat mass induced by a high-fat diet in mice. Furthermore, loss of Mogat1 in adipocytes did not affect plasma lipid or glucose concentrations or insulin tolerance. These data suggest Mogat1 may play a role in adipocyte differentiation in vitro but not adipose tissue expansion in response to nutrient overload in mice.


A high-sampling-rate automated continuous-flow fluorometric technique for the analysis of nanogram levels of histamine in biological samples.
An automated continuous-flow technique of the modified fluorometric method of Shore was devised to obtain a high sampling rate (60/h) and a sensitive measurement of the histamine content of biological samples. The volumes of samples range from 50 to 500 microliter. A linear relationship is obtained from 0 to 5 micrograms/ml (histamine base) with a good specificity. The limit of detection is 25 pg (actual amount). The coefficient of variation is less than or equal to +/- 5% for concentrations of less than 2 ng/ml and from +/- 0.2 to +/- 2% for higher concentrations. With this technique more sensitive, more specific, and twice as fast as similar ones, histamine content in 350-400 unknowns can be measured routinely in a working day. It has been used for more than 4 years and has proven to be a reliable and useful tool for the numerous research studies in which histamine is involved: immunology, allergy, pharmacology, dermatology, cancer, nutrition.


Analgesia after otoplasty: regional nerve blockade vs local anaesthetic infiltration of the ear.
Children scheduled to undergo otoplasty experience severe pain postoperatively. Nausea and vomiting is also a problem. This study was designed to compare two analgesic techniques (i) regional nerve blockade (ii) local anaesthetic infiltration, with respect to quality and duration of analgesia, opioid requirements and the incidence of postoperative nausea and vomiting (PONV). Forty three children, ASA I-II, aged 3-15 yr, were studied and followed for 24 hr postoperatively. Patients were randomised into two groups. Patients in Group A received local infiltration with lidocaine 1% with adrenaline 1:200,000 0.4 ml.kg-1 (n = 21). Patients in Group B (n = 22) received nerve blockade, bupivacaine 0.5%, 0.4 ml.kg-1. No other form of analgesia was used intraoperatively. Quality and duration of analgesia were assessed using pain and sedation scores recorded by a blinded observer at 0, 5, 10, 15, 30, 45 min with Recovery Room, and at 0, 30, 60, 90, 120, 180, 240, 360, 480 min on the ward. Pain score > 6 was treated with fentanyl 1 microgram.kg-1 iv (recovery) and morphine 0.2 mg.kg-1 im or mefenamic acid 8 mg.kg-1 po on the ward. Time to first supplemental analgesia was noted. Mean duration of analgesia was 8.6 (1.1-24) hr, Group A and 10.5 (1.3-24) hr, Group B (P > 0.7). 24% per cent of children (Group A) and 27% (Group B) required no supplemental analgesia (P > 0.6). The degree of pain control resulted in a low requirement for opioids, Group A: 24%, Group B: 14% (P:NS). The overall incidence of PONV was 43% (Group A) and 36% (Group B) (P:NS): PONV correlated with opioid use. There were no differences between the groups with regard to pain/sedation scores, quality/duration of analgesia, opioid requirements and incidence of PONV. Both techniques provided excellent postoperative analgesia. Lidocaine 1% infiltration (adrenaline 1:200,000) has the added advantage of improving surgical field and haemostasis. Thus, we advocate use of the simpler technique.


Specimen-driven intraoperative assessment of resection margins should be standard of care for oral cancer patients.
With an incidence of 350.000 new cases per year, cancer of the oral cavity ranks among the 10 most common solid organ cancers. Most of these cancers are squamous cell carcinomas. Five-year survival is about 50%. It has been shown that clear resection margins (>5 mm healthy tissue surrounding the resected tumor) have a significant positive effect on locoregional control and survival. It is not uncommon that the resection margins of oral tumors are inadequate. However, when providing the surgeon with intraoperative feedback on the resection margin status, it is expected that obtaining adequate resection margins is improved. In this respect, it has been shown that specimen-driven intraoperative assessment of resection margins is superior to defect-driven intraoperative assessment of resection margins. In this concise report, it is described how a specimen-driven approach can increase the rate of adequate resections of oral cavity squamous cell carcinoma as well as that it is discussed how intraoperative assessment can be further improved with regard to the surgical treatment of oral cavity squamous cell carcinoma.


The Descriptor Differential Scale of Pain Intensity: an evaluation of item and scale properties.
Improved methods for pain measurement have both theoretical and clinical importance. This study evaluated the Descriptor Differential Scale (DDS) of Pain Intensity, a recent methodology designed for assessing pain reports in clinical samples. Experiment 1 evaluated the sensitivity of the measure to small changes in electrocutaneous stimulation relative to a traditional visual analogue scale (VAS) of pain intensity. Additionally, direct psychophysical scaling methods were employed to determine ratio-scale values for the DDS sensory items in relation to the electrocutaneous stimuli. This ratio scale was cross-validated by comparison with previously published ratio-scaled data from cross-modality matching pain intensity judgement studies. Experiment 2 evaluated the performance of the measure in both experimental and clinical pain samples, as well as the similarity of item-response patterns in each of these samples. Results indicate that the DDS of Pain Intensity is sensitive to small changes in electrocutaneous stimulation, has consistent ratio-scale properties across two different psychophysical methods, and demonstrates similar item-response patterns across divergent experimental and clinical samples. The results support the validity of the sensory DDS as a measure of pain intensity.


High-resolution array comparative genomic hybridization analysis of human bronchial and salivary adenoid cystic carcinoma.
Adenoid cystic carcinoma (ACC) is a rare but distinctive tumor. Oligonucleotide array comparative genomic hybridization has been applied for cataloging genomic copy number alterations (CNAs) in 17 frozen salivary or bronchial tumors. Only four whole chromosome CNAs were found, and most cases had 2-4 segmental CNAs. No high level amplification was observed. There were recurrent gains at 7p15.2, 17q21-25, and 22q11-13, and recurrent losses at 1p35, 6q22-25, 8q12-13, 9p21, 12q12-13, and 17p11-13. The minimal region of gain at 7p15.2 contained the HOXA cluster. The minimal common regions of deletions contained the CDKN2A/CDKN2B, TP53, and LIMA1 tumor suppressor genes. The recurrent deletion at 8q12.3-13.1 contained no straightforward tumor suppressor gene, but the MIRN124A2 microRNA gene, whose product regulates MMP2 and CDK6. Among unique CNAs, gains harbored CCND1, KIT/PDGFRA/KDR, MDM2, and JAK2. The CNAs involving CCND1, MDM2, KIT, CDKN2A/2B, and TP53 were validated by FISH and/or multiplex ligation-dependent probe amplification. Although most tumors overexpressed cyclin D1 compared with surrounding glands, the only case to overexpress MDM2 had the corresponding CNA. In conclusion, our report suggests that ACC is characterized by a relatively low level of structural complexity. Array CGH and immunohistochemical data implicate MDM2 as the oncogene targeted at 12q15. The gain at 4q12 warrants further exploration as it contains a cluster of receptor kinase genes (KIT/PDGFRA/KDR), whose products can be responsive to specific therapies.


Myopic change after transconjunctival blepharoplasty using carbon dioxide laser: case report.
The case of a patient who experienced temporary myopic change after transconjunctival blepharoplasty using the carbon dioxide (CO(2)) laser is reported. Transconjunctival lower lid blepharoplasty using the CO(2) laser, one of the most frequent laser procedures performed in aesthetic surgery, is considered to be a safe and reliable approach that does not incur significant complications. This report describes temporary myopia in a 38-year-old woman as a rare complication after this procedure. As for the possible etiology of the postoperative myopia, the authors strongly suspect a temporary mild deformity of the eyeball leading to the change in refraction, including scleral edematization and/or retinal indentation attributable to thermal injury as a result of CO(2) laser irradiation adjacent to the eyeball. The purpose of this case report is to inform others of the complication the authors encountered and to discuss the possible etiology.


Congenital bifid sternum. Report of an unusual case.
This article presents the case of a child with an unusual type of cleft sternum characterized by fusion superiorly between the clavicles and inferiorly at the xiphoid with wide intervening separation. The defect was successfully corrected at age 17 months by surgical closure of the cleft primarily, which had not been achieved previously in a patient at this late age.


No Survival Benefit for Patients with Treatment in Certified Breast Centers-A Population-based Evaluation of German Cancer Registry Data.
Much time and money has been spent on the establishment and preservation of certified breast centers (CBCs), but up to now there is almost no evidence for whether certification results in an improved outcome for breast cancer patients. The aim of this evaluation was to assess, whether the certification of specialized units had any influence on their patients' outcomes and if a survival difference between CBC patients and non-CBC patients can be shown. This population-based analysis included cancer registry data from 32,789 operated breast cancer patients with no prior cancer diagnosis and with active follow-up. They were diagnosed between 2004 and 2010 in four different regions in Germany. Survival was investigated using the Kaplan-Meier method and multivariate Cox regression analysis. A survival difference was found neither between patients with treatment before and after certification of specialized units nor between CBC patients and non-CBC patients aged up to 75 years. Only for patients older than 75 years, an improved survival could be seen for CBC patients (adjusted hazard ratio 0.77; 95% confidence interval 0.68-0.87). The improved survival of elderly CBC patients is most likely caused by selection effects concerning health status differences and not by processes attributable to certification. Thus, this study found that as of yet, certification has not influenced survival of breast cancer patients.


Production of cellulosic ethanol from sugarcane bagasse by steam explosion: Effect of extractives content, acid catalysis and different fermentation technologies.
The production of cellulosic ethanol was carried out using samples of native (NCB) and ethanol-extracted (EECB) sugarcane bagasse. Autohydrolysis (AH) exhibited the best glucose recovery from both samples, compared to the use of both H3PO4 and H2SO4 catalysis at the same pretreatment time and temperature. All water-insoluble steam-exploded materials (SEB-WI) resulted in high glucose yields by enzymatic hydrolysis. SHF (separate hydrolysis and fermentation) gave ethanol yields higher than those obtained by SSF (simultaneous hydrolysis and fermentation) and pSSF (pre-hydrolysis followed by SSF). For instance, AH gave 25, 18 and 16 g L(-1) of ethanol by SHF, SSF and pSSF, respectively. However, when the total processing time was taken into account, pSSF provided the best overall ethanol volumetric productivity of 0.58 g L(-1) h(-1). Also, the removal of ethanol-extractable materials from cane bagasse had no influence on the cellulosic ethanol production of SEB-WI, regardless of the fermentation strategy used for conversion.


Mitigating Moral Distress: Pediatric Critical Care Nurses' Recommendations.
In pediatric critical care, nurses are the primary caregivers for critically ill children and are particularly vulnerable to moral distress. There is limited evidence on what approaches are effective to minimize moral distress among these nurses. To identify intervention attributes that critical care nurses with moral distress histories deem important to develop a moral distress intervention. We used a qualitative description approach. Participants were recruited using purposive sampling between October 2020 to May 2021 from pediatric critical care units in a western Canadian province. We conducted individual semi-structured interviews via Zoom. A total of 10 registered nurses participated in the study. Four main themes were identified: (1) "I'm sorry, there's nothing else": increasing supports for patients and families; (2) "someone will commit suicide": improving supports for nurses: (3) "Everyone needs to be heard": improving patient care communication; and (4) "I didn't see it coming": providing education to mitigate moral distress. Most participants stated they wanted an intervention to improve communication among the healthcare team and noted changes to unit practices that could decrease moral distress. This is the first study that asks nurses what is needed to minimize their moral distress. Although there are multiple strategies in place to help nurses with difficult aspects of their work, additional strategies are needed to help nurses experiencing moral distress. Moving the research focus from identifying moral distress towards developing effective interventions is needed. Identifying what nurses need is critical to develop effective moral distress interventions.


Engineering rhizobacteria for sustainable agriculture.
Exploitation of plant growth promoting (PGP) rhizobacteria (PGPR) as crop inoculants could propel sustainable intensification of agriculture to feed our rapidly growing population. However, field performance of PGPR is typically inconsistent due to suboptimal rhizosphere colonisation and persistence in foreign soils, promiscuous host-specificity, and in some cases, the existence of undesirable genetic regulation that has evolved to repress PGP traits. While the genetics underlying these problems remain largely unresolved, molecular mechanisms of PGP have been elucidated in rigorous detail. Engineering and subsequent transfer of PGP traits into selected efficacious rhizobacterial isolates or entire bacterial rhizosphere communities now offers a powerful strategy to generate improved PGPR that are tailored for agricultural use. Through harnessing of synthetic plant-to-bacteria signalling, attempts are currently underway to establish exclusive coupling of plant-bacteria interactions in the field, which will be crucial to optimise efficacy and establish biocontainment of engineered PGPR. This review explores the many ecological and biotechnical facets of this research.


A comparison of dynamic coronal plane excursion between matched male and female athletes when performing single leg landings.
Despite recent evidence supporting the use of neuromuscular training to reduce anterior cruciate ligament injury risk, female athletes continue to show an increased anterior cruciate ligament injury rate in collegiate basketball and soccer when compared to males. The purpose of the current study was to identify gender and task differences in measures that may increase the risk of anterior cruciate ligament injury in female basketball and soccer athletes. Eleven female and 11 male collegiate basketball and soccer athletes were height (female mean 176 (SD 8 cm), male mean 176 (SD 8 cm)) and weight (female mean 73 (SD 7 kg), male mean 74 (SD 6 kg)) matched. Three-dimensional motion analysis was used to calculate differences in total coronal plane angular joint excursion (maximum-minimum) between male and female athletes when performing a series of medially and laterally directed drop landings. Female athletes demonstrated increased total coronal plane excursion for the hip, knee and ankle (P < 0.05) during the medial drop landing. During the lateral drop landing females displayed increased excursion at the hip and knee. When comparing tasks, the lateral drop landing resulted in greater coronal plane excursion at the hip (P < 0.05) while the knee showed no differences between movements. In contrast, females demonstrated increased ankle excursion during the medial drop task (P < 0.05). Female athletes demonstrate increased lower extremity coronal plane excursion when performing single leg drop landing in both the medial and lateral direction when compared to height/weight matched male athletes. This increased coronal plane oscillation of lower extremity joints may be related to the increased risk of anterior cruciate ligament injury for female basketball and soccer athletes.


Invasive pressure monitoring of patients during magnetic resonance imaging.
The purpose of this paper is to describe a system for monitoring patients who require general anaesthesia, profound sedation or intensive care while undergoing high field (> or = 1.5 T) magnetic resonance (MR) imaging. Continuous evaluation of invasive and noninvasive pressures, inspired and end-tidal respiratory gas concentrations, body temperature, heart rate, ECG and pulse oximetry were measured successfully during the MR examination. Diagnostic quality MR images were acquired on all 15 monitored patients. The calculated signal-to-noise ratios were not different between the control and monitored patients. Commonly encountered technical problems and their solutions are described. This study demonstrates that invasive monitoring can be safely performed in critically ill patients who are undergoing high field MR examinations.


Use of ultrasound in antenatal diagnosis of large-for-gestational age infants in diabetic gravid patients.
Near-term ultrasonograms of 44 diabetic gravid patients and 47 nondiabetic gravid patients were retrospectively analyzed. The mean values of abdominal diameter to femur length ratios and abdominal diameter to biparietal diameter ratios in diabetic gravid patients with large-for-gestational age fetuses were significantly different from those values in diabetic patients with appropriate-for-gestational age fetuses and in nondiabetic patients. Glycosylated hemoglobin values were above 7.4% (mean +/- 2 SD) in 79% of diabetic patients with large-for-gestational age infants and abdominal diameter to femur length ratio exceeding 1.385. Glycosylated hemoglobin values were less than or equal to 7.4% in 69% of diabetic gravid patients with appropriate-for-gestational age fetuses and abdominal diameter to femur length ratio less than 1.385. These findings suggest that large-for-gestational age infants have a different growth characteristic with a disproportionate enlargement of the abdomen. This possibly results from a long period of elevated levels of maternal plasma glucose (as shown by elevated values of glycosylated hemoglobin).


Optimization of medium formulation and seed conditions for expression of mature PsaA (pneumococcal surface adhesin A) in Escherichia coli using a sequential experimental design strategy and response surface methodology.
PsaA, a candidate antigen for a vaccine against pneumonia, is well-conserved in all Streptococcus pneumoniae serotypes. A sequence of two-level experimental designs was used to evaluate medium composition and seed conditions to optimize the expression of soluble mature PsaA in E. coli. A face-centered central composite design was first used to evaluate the effects of yeast extract (5 and 23.6 g/L), tryptone (0 and 10 g/L), and glucose (1 and 10 g/L), with replicate experiments at the central point (14.3 g/L yeast extract, 5 g/L tryptone, 5.5 g/L glucose). Next, a central composite design was used to analyze the influence of NaCl concentration (0, 5, and 10 g/L) compared with potassium salts (9.4 g/L K(2)HPO(4)/2.2 g/L KH(2)PO(4)), and seed growth (7 and 16 h). Tryptone had no significant effect and was removed from the medium. Yeast extract and glucose were optimized at their intermediate concentrations, resulting in an animal-derived material-free culture medium containing 15 g/L yeast extract, 8 g/L glucose, 50 μg/mL kanamycin, and 0.4% glycerol, yielding 1 g/L rPsaA after 16 h induction at 25°C in shake flasks at 200 rpm. All the seed age and salt conditions produced similar yields, indicating that no variation had a statistically significant effect on expression. Instead of growing the seed culture for 16 h (until saturation), the process can be conducted with 7 h seed growth until the exponential phase. These results enhanced the process productivity and reduced costs, with 5 g/L NaCl being used rather than potassium salts.


Gene expression profiling of single bovine embryos uncovers significant effects of in vitro maturation, fertilization and culture.
In vitro production (IVP) has been shown to affect embryonic gene expression and often result in large offspring syndrome (LOS) in cattle and sheep. To dissect the effects of in vitro maturation, fertilization and culture on bovine embryos, we compared the expression profiles of single blastocysts generated by: (1) in vitro maturation, fertilization and culture (IVF); (2) in vivo maturation, fertilization and in vitro culture (IVD); and (3) in vivo maturation, fertilization and development (AI). To conduct expression profiling, total RNA was isolated from individual embryos, linearly amplified and hybridized to a custom bovine cDNA microarray containing approximately 6,300 unique genes. There were 306, 367, and 200 genes differentially expressed between the AI and IVD, IVF and IVD, and AI and IVF comparisons, respectively. Interestingly, 44 differentially expressed genes were identified between the AI embryos and both the IVF and IVD embryos, making these potential candidates for LOS. There were 60 genes differentially expressed between the IVF embryos and the AI and IVD embryos. The Gene Ontology category "RNA processing" was over-represented among the genes that were down-regulated in the IVF embryos, indicating an effect of in vitro oocyte maturation/fertilization on the ability to transcribe maternal RNA stores. A culture effect on the expression of genes involved in translation was also observed by the comparison of AI with IVD embryos.


Association between syphilis seroprevalence and age among blood donors in Southern China: an observational study from 2014 to 2017.
This study investigated the association between syphilis seroprevalence and age among blood donors, and described the distribution of serological titres among syphilis-infected donors, aiming to confirm the syphilis epidemic characteristics and to promote effective interventions for older adults. Data were obtained from the Shenzhen Programme for Syphilis Prevention and Control in 2014-2017. Blood samples were screened using the ELISAs, and confirmed using the Treponema pallidum particle agglutination assay (TPPA) and toluidine red unheated serum test (TRUST). Among 394 792 blood donors, 733 tested TPPA and TRUST positive (active infection), and 728 tested only TPPA positive (historical infection). The overall prevalence of syphilis seropositivity was 370.1 per 100 000 (95% CI 351.1 to 389.0 per 100 000); the prevalence of active infection was 185.7 per 100 000 (95% CI 172.2 to 199.1 per 100 000). People aged ≥45 years displayed a prevalence of 621.8 per 100 000 in syphilis seropositivity and 280.5 per 100 000 in active infection, which were 3.8 times and 2.4 times higher than that for people aged <25 years, respectively. The prevalence of syphilis seropositivity (χ2trend=311.9, p trend<0.001) and active infection (χ2trend=72.1, p trend<0.001) increased significantly with age. After stratification by gender and year of donation, the increasing trend of prevalence with age remained (p trend<0.05), except for the prevalence of active infection in males and females in 2014. About 16.3% of donors with active infection and aged ≥45 years had a TRUST titre of ≥1∶8, lower than that of patients aged <25 years (51.3%) and 25-34 years (34.1%). The findings confirm the high prevalence of syphilis among older adults, and suggest the need to increase awareness among healthcare providers and deliver more targeted prevention interventions for older adults to promote early testing.


Diffusion-weighted MR imaging histogram analysis in HIV positive and negative patients with primary central nervous system lymphoma as a predictor of outcome and tumor proliferation.
Ki-67 expression, a marker of tumor proliferation, is considered a prognostic factor in primary CNS lymphoma (PCNSL). Apparent diffusion coefficient (ADC) parameters have also been proposed as imaging biomarkers for tumor progression and proliferative activity in various malignancies. The aim of this study is to investigate the correlation between ADC parameters, Ki-67 expression, overall survival (OS) and progression free survival (PFS) in PCNSL. Patients diagnosed with PCNSL at MD Anderson Cancer Center between Mar 2000 and Jul 2016 and at Ben Taub Hospital between Jan 2012 and Dec 2016 were retrospectively studied. Co-registered ADC maps and post-contrast images underwent whole tumor segmentation. Normalized ADC parameters (nADC) were calculated as the ratio to normal white matter. Percentiles of nADC were calculated and were correlated with Ki-67 using Pearson's correlation coefficient and clinical outcomes (OS and PFS) using Cox proportional hazards models. Selection criteria yielded 90 patients, 23 patients living with HIV (PLWH) and 67 immunocompetent patients. Above median values for nADCmean, nADC15, nADC75 and nADC95 were associated with improved OS in all patients (p < 0.05). Above median values for nADCmin, nADCmean, nADC1, nADC5 and kurtosis were associated with improved PFS in all patients (p < 0.05). In patients with available Ki-67 expression data (n = 22), nADCmean, nADC15 and nADC75 inversely correlated with Ki-67 expression (p < 0.05). For PLWH, there was no correlation between ADC parameters and Ki-67 expression or clinical outcomes. ADC histogram analysis can predict tumor proliferation and survival in immunocompetent patients with PCNSL, but with limited utility in PLWH.


Increased risk of cholecystectomy in users of supplemental estrogen.
We report the results of an analysis of information from a prospective cohort study of women examining the association between cholecystectomy and use of supplemental estrogens (never, current, and past use). There were 55 cases of cholecystectomy in those who had never used estrogen and 105 cases in those who had ever used estrogen. After adjustment for age, the relative risk of cholecystectomy in those who had ever used estrogen was 2.1 (95% confidence interval, 1.5-3.0). In women classified as current users based on information available in 1977, the relative risk of gallbladder disease was 2.7 (95% confidence interval, 1.8-4.0) and in past users as of this date, it was 1.6 (95% confidence interval, 1.1-2.5). When cases known to have reinitiated estrogen use after 1977 are removed from the numerator for past users and added to the numerator for current users, the relative estimate for past use decreased to 1.1 (95% confidence interval, 0.7-1.8), and the risk estimate for current use increased to 3.9 (95% confidence interval, 2.6-5.9). Although an increase in the risk of gallbladder disease in women using supplemental estrogens has been consistently observed in previous studies, the risk after cessation of use has received little attention but could be important. Our data suggest the possibility that the risk of gallbladder disease in estrogen users persists after use of the drug ceases. An increase in the risk of cholecystectomy in estrogen users that persists after drug use ends is plausible if estrogen-induced increases in the lithogenicity of bile cause gallstones to form during drug use and if these gallstones fail to dissolve even after bile lithogenicity returns to normal upon cessation of use. The effect of estrogen use on the gallbladder should be considered in weighing the net risk-benefit ratio of these drugs.


The complexity of verifying population protocols.
Population protocols (Angluin et al. in PODC, 2004) are a model of distributed computation in which indistinguishable, finite-state agents interact in pairs to decide if their initial configuration, i.e., the initial number of agents in each state, satisfies a given property. In a seminal paper Angluin et al. classified population protocols according to their communication mechanism, and conducted an exhaustive study of the expressive power of each class, that is, of the properties they can decide (Angluin et al. in Distrib Comput 20(4):279-304, 2007). In this paper we study the correctness problem for population protocols, i.e., whether a given protocol decides a given property. A previous paper (Esparza et al. in Acta Inform 54(2):191-215, 2017) has shown that the problem is decidable for the main population protocol model, but at least as hard as the reachability problem for Petri nets, which has recently been proved to have non-elementary complexity. Motivated by this result, we study the computational complexity of the correctness problem for all other classes introduced by Angluin et al., some of which are less powerful than the main model. Our main results show that for the class of observation models the complexity of the problem is much lower, ranging from Π 2 p to PSPACE.


Risk factors for serious underlying pathology in adult emergency department nontraumatic low back pain patients.
Nontraumatic low back pain (LBP) is a common emergency department (ED) complaint and can be caused by serious pathologies that require immediate intervention or that lead to death. The primary goal of this study is to identify risk factors associated with serious pathology in adult nontraumatic ED LBP patients. We conducted a health records review and included patients aged ≥ 16 years with nontraumatic LBP presenting to an academic ED from November 2009 to January 2010. We excluded those with previously confirmed nephrolithiasis and typical renal colic presentation. We collected 56 predictor variables and outcomes within 30 days. Outcomes were determined by tracking computerized patient records and performance of univariate analysis and recursive partitioning. There were 329 patients included, with a mean age of 49.3 years; 50.8% were women. A total of 22 (6.7%) patients suffered outcomes, including one death, five compression fractures, four malignancies, four disc prolapses requiring surgery, two retroperitoneal bleeds, two osteomyelitis, and one each of epidural abscess, cauda equina, and leaking abdominal aortic aneurysm graft. Risk factors identified for outcomes were: anticoagulant use (odds ratio [OR] 15.6; 95% confidence interval [CI] 4.2-58.5), decreased sensation on physical examination (OR 6.9; CI 2.2-21.2), pain that is worse at night (OR 4.3; CI 0.9-20.1), and pain that persists despite appropriate treatment (OR 2.2; CI 0.8-5.6). These four predictors identified serious pathology with 91% sensitivity (95% CI 70-98%) and 55% specificity (95% CI 54-56%). We successfully identified risk factors associated with serious pathology among ED LBP patients. Future prospective studies are required to derive a robust clinical decision rule.


Management of ruptured or symptomatic abdominal aortic aneurysms.
During the past 15 years, the operative mortality for elective repair of abdominal aortic aneurysms has declined; this favorable trend has very likely resulted from simplified operative technique and improved perioperative management. Unfortunately, however, there has been no comparable decline in the mortality associated with repair of ruptured abdominal aortic aneurysms. The management of these patients remains a challenge to even the most skilled and experienced vascular surgeon.


Thiobacillus as a key player for biofilm formation in oligotrophic groundwaters of the Fennoscandian Shield.
Biofilm formation is a common adaptation for microbes in energy-limited conditions such as those prevalent in the vast deep terrestrial biosphere. However, due to the low biomass and the inaccessible nature of subsurface groundwaters, the microbial populations and genes involved in its formation are understudied. Here, a flow-cell system was designed to investigate biofilm formation under in situ conditions in two groundwaters of contrasting age and geochemistry at the Äspö Hard Rock Laboratory, Sweden. Metatranscriptomes showed Thiobacillus, Sideroxydans, and Desulforegula to be abundant and together accounted for 31% of the transcripts in the biofilm communities. Differential expression analysis highlighted Thiobacillus to have a principal role in biofilm formation in these oligotrophic groundwaters by being involved in relevant processes such as the formation of extracellular matrix, quorum sensing, and cell motility. The findings revealed an active biofilm community with sulfur cycling as a prominent mode of energy conservation in the deep biosphere.


NGSpop: A desktop software that supports population studies by identifying sequence variations from next-generation sequencing data.
Next-generation sequencing (NGS) is widely used in all areas of genetic research, such as genetic disease diagnosis and breeding, and it can produce massive amounts of data. The identification of sequence variants is an important step when processing large NGS datasets; however, currently, the process is complicated, repetitive, and requires concentration, which can be taxing on the researcher. Therefore, to support researchers who are not familiar enough with bioinformatics to identify sequence variations regularly from large datasets, we have developed a fully automated desktop software, NGSpop. NGSpop includes functionalities for all the variant calling and visualization procedures used when processing NGS data, such as quality control, mapping, filtering details, and variant calling. In the variant calling step, the user can select the GATK or DeepVariant algorithm for variant calling. These algorithms can be executed using pre-set pipelines and options or customized with the user-specified options. NGSpop is implemented using JavaFX (version 1.8) and can thus be run on Unix-like operating systems such as Ubuntu Linux (version 16.04, 18.0.4). Although several pipelines and visualization tools are available for NGS data analysis, most integrated environments do not support batch processes; thus, variant detection cannot be automated for population-level studies. The NGSpop software developed in this study has an easy-to-use interface and helps in rapid analysis of multiple NGS data from population studies. According to a benchmark test, it effectively reduced the carbon footprint in bioinformatics analysis by expending the least central processing unit heat and power. Additionally, this software makes it possible to use the GATK and DeepVariant algorithms more flexibly and efficiently than other programs by allowing users to choose between the algorithms. As a limitation, NGSpop currently supports only the sequencing reads in fastq format produced by the Illumina platform. NGSpop is freely available at https://sourceforge.net/projects/ngspop/.


New algorithm for post-radial keratotomy intraocular lens power calculations based on rotating Scheimpflug camera data.
To provide an algorithm to calculate intraocular lens (IOL) power for post-radial keratometry (RK) eyes based on data extracted from the Pentacam Scheimpflug camera and to compare calculations with those from an existing standard. Private practice, Mesa, Arizona. Case series. Relevant IOL calculation and postoperative refractive data were obtained for eyes that had previous RK but no additional keratorefractive procedures or subsequent cataract surgery. Various Scheimpflug measurements from examinations before cataract surgery over a range of zone diameters were used to calculate IOL power using an Aramberri double-K-modified Holladay 1 formula. Results were compared with actual postsurgical data and IOL calculations based on the mean of the 1.0 mm to 4.0 mm rings from the Atlas topography system. Data were obtained for 83 eyes of 57 patients, including more than 120 different measures per eye from the Scheimpflug system. The mean pupil-centered sagittal front power over the central 4.0 mm zone provided the best results after adjustment for central corneal thickness (CCT). Results were similar to those obtained when the IOL power was calculated using the topography system; 42% of eyes were within ± 0.50 diopter (D) of the target, and 76% of eyes were within ± 1.00 D. In this large series of eyes, the calculation of IOL power after RK using sagittal front-surface power and CCT from the Scheimpflug system produced results equivalent to the multizone approach with the topography system.


Endoplasmic Reticulum Calcium Regulates Epidermal Barrier Response and Desmosomal Structure.
Ca(2+) fluxes direct keratinocyte differentiation, cell-to-cell adhesion, migration, and epidermal barrier homeostasis. We previously showed that intracellular Ca(2+) stores constitute a major portion of the calcium gradient especially in the stratum granulosum. Loss of the calcium gradient triggers epidermal barrier homeostatic responses. In this report, using unfixed ex vivo epidermis and human epidermal equivalents we show that endoplasmic reticulum (ER) Ca(2+) is released in response to barrier perturbation, and that this release constitutes the major shift in epidermal Ca(2+) seen after barrier perturbation. We find that ER Ca(2+) release correlates with a transient increase in extracellular Ca(2+). Lastly, we show that ER calcium release resulting from barrier perturbation triggers transient desmosomal remodeling, seen as an increase in extracellular space and a loss of the desmosomal intercellular midline. Topical application of thapsigargin, which inhibits the ER Ca(2+) ATPase activity without compromising barrier integrity, also leads to desmosomal remodeling and loss of the midline structure. These experiments establish the ER Ca(2+) store as a master regulator of the Ca(2+) gradient response to epidermal barrier perturbation, and suggest that ER Ca(2+) homeostasis also modulates normal desmosomal reorganization, both at rest and after acute barrier perturbation.


Myosin light chain kinase is a potential target for hypopharyngeal cancer treatment.
Hypopharyngeal cancer is squamous cell carcinoma (SCC) with the worst prognosis among the head and neck cancers. Overall, the 5-year survival rate remains poor although diagnostic imaging, radiation, chemotherapy, and surgical techniques have been improved. The mortality of patients with hypopharyngeal cancer is partly due to an increased likelihood of developing a second primary malignancy and metastasis. In this study, we found that MLCK expression, compared to healthy tissue, was up-regulated in hypopharyngeal tumor tissue. Of particular interest, a low 5-year survival rate was positively correlated with MLCK expression. We hypothesized that MLCK might be a target for hypopharyngeal cancer prognosis and treatment. In order to explore the function of MLCK in the development of cancer, we knockdown MLCK in hypopharyngeal cancer FaDu cells. The results showed that MLCK knockdown reduced the migration and invasion of FaDu cells. 4-amino-2-trifluoromethyl-phenyl retinate (ATPR) is the derivative of all-trans retinoic acid (ATRA), which was able to reduce both MLCK expression and activity in FaDu cells. ATPR induced FaDu cells apoptosis in a dose-dependent manner and also inhibited cell growth both in vivo and in vitro. Further experiments showed that overexpression of MLCK reduced ATPR induced-migration inhibition while increase of ATPR induced apoptosis, which suggested that MLCK was involved in ATPR's anti-cancer function. In conclusion, MLCK is a novel prognostic marker and therapeutic target for hypopharyngeal cancer. By targeting MLCK, ATPR exhibits its potential application in the treatment of this type of cancer.


Transcutaneous electrical acupoint stimulation for stage 1 hypertension: protocol for a randomized controlled pilot trial.
Hypertension is a major pathogenic factor of cardiovascular diseases. Insufficient blood pressure control rate and sub-optimal medication adherence remain challenges for effective management of hypertension. Transcutaneous electrical acupoint stimulation (TEAS) has been used to treat various diseases, including hypertension, but the scientific evidence for its benefit remains insufficient. Therefore, we will perform a randomized, controlled clinical trial in patients with stage 1 hypertension to evaluate the effect of TEAS. The study will be a two-arm parallel, randomized controlled trial. Sixty patients with stage 1 hypertension will be randomly assigned to the TEAS group and the control group in a 1:1 ratio. The participants in the TEAS group will receive non-invasive acupoint electrical stimulation for 30 min at four acupoints in the upper and lower extremities at home, 4 times weekly for 12 weeks for a total of 48 sessions. Participants in the control group will not receive any form of acupoint stimulation. All participants in both groups will receive lifestyle education on how to control high blood pressure, including diet, weight control, and exercise. The primary outcome measure will be the change of the mean systolic blood pressure from baseline to 12 weeks. Secondary outcomes include the change of mean diastolic blood pressure, quality of life, body mass index, and physical activity level. This pilot, randomized, controlled trial will explore the feasibility of TEAS. It will also provide potential clinical evidence for the efficacy and safety of TEAS in the treatment of patients with stage 1 hypertension. The results of this study will be published in peer-reviewed journals. Furthermore, this pilot trial as the precursor of a large scale randomized controlled trial will inform the sample size of the subsequent trial. Chinese clinical trial registry, ChiCTR1900025042, Registered on 8 August 2019 (http://www.chictr.org.cn/showproj.aspx?proj=41496).


Loop Diuretics in the Treatment of Hypertension.
Loop diuretics are not recommended in current hypertension guidelines largely due to the lack of outcome data. Nevertheless, they have been shown to lower blood pressure and to offer potential advantages over thiazide-type diuretics. Torsemide offers advantages of longer duration of action and once daily dosing (vs. furosemide and bumetanide) and more reliable bioavailability (vs. furosemide). Studies show that the previously employed high doses of thiazide-type diuretics lower BP more than furosemide. Loop diuretics appear to have a preferable side effect profile (less hyponatremia, hypokalemia, and possibly less glucose intolerance). Studies comparing efficacy and side effect profiles of loop diuretics with the lower, currently widely prescribed, thiazide doses are needed. Research is needed to fill gaps in knowledge and common misconceptions about loop diuretic use in hypertension and to determine their rightful place in the antihypertensive arsenal.


A novel tracheobronchial reconstruction for right upper lung carcinoma involving the lower trachea: preliminary results.
We developed a novel technique for tracheobronchial reconstruction after resection of carcinoma of the right upper lung involving the right main bronchus and lower trachea. Preliminary results of the technique are reported. Between December 2007 and October 2011, 9 patients underwent treatment with our new technique. The right upper lobe was resected together with the involved right main bronchus and right lateral wall of the lower trachea. Closure of the trachea was started at the level of the carina and continued upward, leaving an oval opening at the upper end of the tracheal defect, to which the bronchus intermedius was reimplanted. The sutured lower trachea became the extension of the left main bronchus. The procedure was completed successfully in all 9 patients. Two patients underwent partial carinal resection, 2 underwent replacement of the superior vena cava by interposition graft, 2 underwent partial resection of the superior vena cava, and 1 underwent partial resection of the esophageal wall. There were no perioperative deaths. No major complications, including dehiscence, stenosis, and adult respiratory distress syndrome, were observed. Arrhythmia occurred in 2 patients, and vocal cord paresis and pneumonia occurred in 1 patient. One patient died 31 months after operation, and 1 patient was lost to follow-up 28 months after operation, without tumor recurrence. The other 7 are alive to date. Despite this being a small series and short follow-up, this tracheobronchial reconstruction shows encouraging preliminary results with low mortality and morbidity, and could be an alternative to other methods for the treatment of carefully selected patients with advanced carcinoma of the right upper lobe.


Sugar-substituted 2-azetidinone cholesterol absorption inhibitors: enhanced potency by modification of the sugar.
A glucuronide conjugate of the potent 2-azetidinone cholesterol absorption inhibitor Sch 58235 was synthesized to confirm the structure of a metabolite isolated from in vivo sources. A series of 2-azetidinone glycosides was prepared via Schmidt trichloroimidate methodology. Enhanced cholesterol absorption inhibition was achieved by modification of the sugar moiety.


Diphtheria toxin receptor. Identification of specific diphtheria toxin-binding proteins on the surface of Vero and BS-C-1 cells.
The biochemical characteristics of specific receptor molecules for diphtheria toxin on the surface of two toxin-sensitive cell lines (Vero and BS-C-1) were examined. Diphtheria toxin was found to bind to a number of different proteins in Nonidet P-40 solubilized extracts of 125I-labeled cells. In contrast, permitting diphtheria toxin to bind first to labeled intact cells, which were subsequently solubilized and subjected to immunoprecipitation with anti-diphtheria toxin, resulted in a far more restricted profile of diphtheria toxin-binding proteins that possessed Mrs in the range of 10,000-20,000. Direct chemical cross-linking of radioiodinated diphtheria toxin to cell surface proteins resulted in the appearance of several predominant bands possessing Mrs of approximately 80,000. The Mr approximately 80,000 complexes were shown to be composed of radiolabeled diphtheria toxin (Mr 60,000) and unlabeled Mr approximately 20,000 cellular proteins. These complexes were judged to be a result of specific binding in that their appearance could be preferentially inhibited by the addition of a 100-fold excess of unlabeled diphtheria toxin. The formation of the Mr approximately 80,000 complexes was sensitive to prior trypsin treatment of the cells and to known inhibitors of diphtheria toxin binding. Furthermore, prior incubation of the cells with diphtheria toxin at 37 degrees C ("down regulation") markedly and specifically reduced the subsequent formation of the Mr approximately 80,000 cross-linked complexes, and these down-regulated cells were less sensitive to diphtheria toxin in cytotoxicity assays. Further incubation of down-regulated cells at 37 degrees C restored their ability to form Mr approximately 80,000 complexes; this regeneration requires protein synthesis and restores the cells' sensitivity to diphtheria toxin-mediated cytotoxicity. These results strongly suggest that a Mr 10,000-20,000 cell surface protein is, or constitutes a portion of, the functional diphtheria toxin receptor.


Human continuous glucose monitors for measurement of glucose in dairy cows.
If validated for use in dairy cattle, interstitial continuous glucose monitors (CGMs) could be easily implemented, informative tools for research, clinical, and perhaps even on-farm applications. To evaluate their efficacy, 2 experiments were conducted, during which lactating Holstein cows were fit with indwelling jugular catheters, as well as FreeStyle Libre (FSL; Abbott) and Dexcom G6 (DexCom Inc.) CGMs secured either behind their polls, lateral to their ears, or beneath their pin bones on their upper rear legs. During the first experiment, blood (measured with a handheld glucometer) and interstitial glucose measurements were collected from 13 cows every 4 h for 96 h. In the second experiment, the same measurements were collected from 8 cows every 15 min for 6 h. At the mid-point of the sampling period (3 h), cows received a bolus dose of dextrose to facilitate comparisons across a broad range of glucose concentrations. Results from both experiments determined that functional longevity of the sensors was greatest for those sensors secured near the ear. Likewise, interstitial measurements from the ear sensors were most closely correlated with blood glucose concentrations (r = 0.82 and r = 0.71 for FSL ear and Dexcom G6 ear, respectively). Unfortunately, accuracy calculated as absolute relative error was low, at 60.7% or less. As a result of the low accuracy, even though both ear sensors detected an increase in glucose concentrations following the bolus dose, neither produced results exactly matching blood glucose measurements. The results of this work indicate that the FSL and Dexcom G6 CGMs are not currently capable of replacing blood-based glucose measurements.


Cochlear implantation outcomes in children with global developmental delay.
As the number of hearing loss cochlear implant candidates who suffer from global developmental delay has dramatically increased, we aimed to study the prognosis of implantation in this group. In this cross-sectional case-control study, we utilized the Ages and Stages Questionnaire third edition (ASQ-3) to investigate the prognosis of cochlear implantation and its rehabilitation in 26 congenitally deaf children who suffered from global developmental delay compared with those in 25 non-delayed cases with the same conditions in two time periods, namely the first diagnosis of hearing loss and 18 months after the surgery and rehabilitation program. The data were analyzed using Statistical Package for Social Sciences, version 21 (SPSS-21). By the time of hearing loss diagnosis (six months old), the performance of all the global developmentally delayed hearing loss children in five subtests of the ASQ-3 scale was significantly lower than that of their non-delayed peers. Meanwhile, they improved significantly in two gross motor and social development subtests 18 months after the surgery and rehabilitation. Along with the general improvement of delay developed children with sensorineural hearing loss after cochlear implantation, global developmental assessment in the process of candidacy and after implantation is an essential factor that needs to be considered.


NMR study of manganese(II) binding by a new versatile peroxidase from the white-rot fungus Pleurotus eryngii.
Nuclear magnetic resonance spectroscopy has been used to characterize the versatile peroxidase from Pleurotus eryngii, both in the resting state and in the cyanide-inhibited form. The assignment of most of the hyperfine-shifted resonances has been achieved by two-dimensional NMR, allowing the comparison of the present system with other ligninolytic peroxidases. This information has enabled a detailed analysis of the interaction of the enzyme with one of its reducing substrates, Mn(II). Furthermore, comparison with the data collected on a mutant in the putative Mn(II) binding site, and an analysis of the enzyme kinetic properties, shed light on the factors affecting the function of this novel peroxidase.


Optimisation of gene transfer into vascular endothelial cells using electroporation.
We have examined the conditions required to obtain optimum transfection efficiencies for human umbilical vein endothelial cells by transduction with a plasmid conferring neomycin resistance. Preliminary studies examined the effects of electric discharges using the Biorad Gene Pulser on endothelial cells. Post-electroporation, there was a significant decrease in cell survival with increasing voltages (100-400 volts; p = 0.03), capacitances [125-960 microFarads (microF); p = 0.02], number of electric pulses (1-2; p = 0.03) and decreasing cell concentrations (p = 0.01). The optimal cell concentration was 3 x 10(6) cells/ml. Transfection studies utilised the neomycin resistance expressing plasmid, pTCF; transfectants were selected with the neomycin analogue G-148. Electro-transfection was optimised with increasing voltages (p = 0.02) and capacitances (p = 0.01) using a single pulse. Optimal transfection was obtained using 400 volts with a capacitance of 960 microF using a single pulse; the median transfection efficiency was 10%. Transduced endothelial cells stably expressed the plasmid for 12 days and at least two cell passages. The results indicate that endothelial cells can be efficiently transduced by electroporation to stably express an introduced gene. This may have important implications in vascular surgery.


Exposure to Air Pollution Disrupts Circadian Rhythm through Alterations in Chromatin Dynamics.
Particulate matter ≤2.5μm (PM2.5) air pollution is a leading environmental risk factor contributing disproportionately to the global burden of non-communicable disease. We compared impact of chronic exposure to PM2.5 alone, or with light at night exposure (LL) on metabolism. PM2.5 induced peripheral insulin resistance, circadian rhythm (CR) dysfunction, and metabolic and brown adipose tissue (BAT) dysfunction, akin to LL (with no additive interaction between PM2.5 and LL). Transcriptomic analysis of liver and BAT revealed widespread but unique alterations in CR genes, with evidence for differentially accessible promoters and enhancers of CR genes in response to PM2.5 by ATAC-seq. The histone deacetylases 2, 3, and 4 were downregulated with PM2.5 exposure, with increased promoter occupancy by the histone acetyltransferase p300 as evidenced by ChIP-seq. These findings suggest a previously unrecognized role of PM2.5 in promoting CR disruption and metabolic dysfunction through epigenetic regulation of circadian targets.


Chronic limb threatening ischemia and diabetes mellitus: the severity of tibial atherosclerosis and outcome after infrapopliteal revascularization.
Diabetes mellitus associates with poor outcomes in chronic limb threatening ischemia but data on different hypoglycemic regimens and outcomes are lacking. We analyzed insulin-treated diabetes mellitus, non-insulin-treated diabetes mellitus, and patients without diabetes mellitus. All patients with peripheral artery disease and/or diabetes mellitus and infrapopliteal revascularization in the Department of Vascular Surgery, Turku University Hospital during 2007-2015 were included. Tibial atherosclerosis was categorized into crural index classes of I-IV. Of the 497 patients, 180 were insulin-treated diabetes mellitus, 94 non-insulin-treated diabetes mellitus, and 223 patients without diabetes mellitus groups (diabetes mellitus 55.1%). Insulin-treated diabetes mellitus was the most ill, youngest (insulin-treated diabetes mellitus-median: 72.4, interquartile range: 64.0-79.5 versus non-insulin-treated diabetes mellitus-76.0, interquartile range: 67.9-83.6 versus patients without diabetes mellitus-77.3, interquartile range: 68.5-83.7, p < 0.001), had the highest body mass index (insulin-treated diabetes mellitus-median: 27.7, interquartile range: 24.0-31.8 versus non-insulin-treated diabetes mellitus-26.3, interquartile range: 23.2-30.3 versus patients without diabetes mellitus-23.9, interquartile range: 21.5-26.9, p < 0.001), and Charlson comorbidity index (insulin-treated diabetes mellitus-65.6% versus non-insulin-treated diabetes mellitus-46.8% versus patients without diabetes mellitus-10.8%, p < 0.001). After endovascular revascularization, limb salvage was poorer for insulin-treated diabetes mellitus (p = 0.046) and non-insulin-treated diabetes mellitus groups (p = 0.011) compared to surgery, but not for patients without diabetes mellitus (p = 0.15). Patients with crural index IV in insulin-treated diabetes mellitus (p = 0.001) and non-insulin-treated diabetes mellitus (p = 0.013) had higher mortality after revascularization. Crural index IV was a risk factor for limb loss (hazard ratio: 1.37, 95% confidence interval: 1.08-1.74, p = 0.008). Limb salvage after bypass is better for insulin and non-insulin diabetics, compared to the endovascular approach. Extensive tibial atherosclerosis is an independent risk factor for limb loss. It associates with increased mortality in both insulin and non-insulin diabetics.


Pharmacotherapeutic friendly fire in the intensive care unit: high stakes seeking high calibre.
Increasing numbers of patients are surviving the intensive care unit. Concordant with our shifting focus to minimizing intensive care unit-acquired morbidity, in the present issue of Critical Care Moyen, Camire, and Stelfox describe the importance of quality pharmacotherapy. They describe challenges and potential solutions to this source of iatrogenic injury in our vulnerable patients. Their article reminds us not to understate the importance of medication error, to avoid overstating the benefits of incompletely proven methods to prevent medication error, and to distinguish harmful medication errors from other types of medication error.


Mifepristone-induced abortion and birth weight in the first subsequent pregnancy.
To assess the effect of a medically induced abortion (MA) on birth weight in the first subsequent pregnancy. Pregnant women who had had a MA, a surgical abortion (SA), or primigravidas with no history of abortion (NA), were recruited for a prospective cohort study between July 1998 and February 2001. The sample for the present analysis included 12995 singleton live births at term. The overall incidence rate of low birth weight (LBW) was 1.0%. The rates of LBW in the MA, SA, and NA groups were 1.0%, 0.9%, and 1.2, respectively. There were no significant differences in LBW rates between the MA and SA groups, neither between the MA and NA. Logistic regression analysis was used to estimate the effects of MA on birth weight, and we found no relationship between risk of LBW and MA. We did not find a statistically significant relationship between a history of one medically induced abortion and LBW for the first subsequent term pregnancy.


MFO induction potential of fish species native to the Swan-Canning Estuary, Western Australia.
The use of mixed function oxygenase (MFO) enzymes as a potential biomarker of pollution in the Swan-Canning Estuary was investigated in four indigenous fish species, Perth herring (Nematalosa vlaminghi), sea mullet (Mugil cephalus), yellowtail trumpeter (Amniataba caudavittata), and black bream (Acanthopagrus butcheri). Each experimental fish was intraperitoneally injected with 10 micrograms/kg of 3,3',4,4',5-pentachlorobiphenyl per kilogram of fish using corn oil as a carrier. Controls were injected with 1 mL corn oil per kilo. Induction of the hepatic ethoxyresorufin-O-deethylase (EROD) activity was measured 10 days post injection. Perth herring did not survive the experimental period due to the poor ability of this fish to endure captivity and handling. Yellowtail trumpeter demonstrated a low EROD induction response (2-fold relative to controls), while sea mullet displayed a moderate EROD induction potential (3.5-fold relative to controls). Because of their lower EROD induction potential, yellowtail trumpeter and sea mullet were not considered the most suitable bioindicator species for Western Australian estuarine waters. Black bream has desirable population traits and had a relatively high MFO induction potential response (9-fold relative to controls). From the results it was concluded that, when using EROD induction as a biomarker, black bream is a suitable fish to use as a bioindicator species for investigations into the health of the Swan-Canning Estuary.


Next-generation sequencing as means to retrieve tick systematic markers, with the focus on Nuttalliella namaqua (Ixodoidea: Nuttalliellidae).
Nuclear ribosomal RNA (18S and 28S rRNA) and mitochondrial genomes are commonly used in tick systematics. The ability to retrieve these markers using next-generation sequencing was investigated using the tick Nuttalliella namaqua. Issues related to nuclear markers may be resolved using this approach, notably, the monotypic status of N. namaqua and its basal relationship to other tick families. Four different Illumina datasets (∼55 million, 100 bp reads each) were generated from a single tick specimen and assembled to give 350k-390k contigs. A genome size of ∼1 Gbp was estimated with low levels of repetitive elements. Contigs (>1000 bp, >50-fold coverage) present in most assemblies (n=69), included host-derived 18S and 28S rRNA, tick and host-derived transposable elements, full-length tick 18S and 28 rRNA, the mitochondrial genome in single contig assemblies and the histone cassette. Coverage for the nuclear rRNA genes was above 1000-fold confirming previous sequencing errors in the 18S rRNA gene, thereby maintaining the monotypic status of this tick. Nuclear markers for the soft tick Argas africolumbae were also retrieved from next-generation data. Phylogenetic analysis of a concatenated 18S-28S rRNA dataset supported the grouping of N. namaqua at the base of the tick tree and the two main tick families in separate clades. This study confirmed the monotypic status of N. namaqua and its basal relationship to other tick families. Next-generation sequencing of genomic material to retrieve high quality nuclear and mitochondrial systematic markers for ticks is viable and may resolve issues around conventional sequencing errors when comparing closely related tick species.


Granzyme M as a novel effector molecule for human cytolytic fusion proteins: CD64-specific cytotoxicity of Gm-H22(scFv) against leukemic cells.
Immunotoxins are promising targeted therapeutic agents comprising an antibody-based ligand that specifically binds to diseased cells, and a pro-apoptotic protein. Toxic components from bacteria or plants can trigger a neutralizing immune response, so that human effector molecules are more suitable. In this context, the protease granzyme B has been successfully tested in cytotoxicity assays against different cancer cells in vitro and in vivo. Our aim here was to introduce granzyme M as an alternative and novel component of human cytolytic fusion proteins. We fused it to the humanized single-chain antibody fragment (scFv) H22 which specifically binds to CD64, an FcγRI receptor overexpressed on activated myeloid cells and leukemic cells. We show that the humanized cytolytic fusion protein Gm-H22(scFv) specifically targets the acute myeloid leukemia cell line HL60 in vitro and is cytotoxic with an IC50 between 1.2 and 6.4 nM. These findings were confirmed ex vivo using leukemic primary cells from patients, which were killed by granzyme M despite the presence of the granzyme B inhibitor serpin B9. In conclusion, granzyme M is a promising new cell-death inducing component for hCFPs because it specifically and efficiently kills target cells when fused to a targeting component.


Transcriptional Profiling of Xenogeneic Transplants: Examining Human Pluripotent Stem Cell-Derived Grafts in the Rodent Brain.
Human pluripotent stem cells are a valuable resource for transplantation, yet our ability to profile xenografts is largely limited to low-throughput immunohistochemical analysis by difficulties in readily isolating grafts for transcriptomic and/or proteomic profiling. Here, we present a simple methodology utilizing differences in the RNA sequence between species to discriminate xenograft from host gene expression (using qPCR or RNA sequencing [RNA-seq]). To demonstrate the approach, we assessed grafts of undifferentiated human stem cells and neural progenitors in the rodent brain. Xenograft-specific qPCR provided sensitive detection of proliferative cells, and identified germ layer markers and appropriate neural maturation genes across the graft types. Xenograft-specific RNA-seq enabled profiling of the complete transcriptome and an unbiased characterization of graft composition. Such xenograft-specific profiling will be crucial for pre-clinical characterization of grafts and batch-testing of therapeutic cell preparations to ensure safety and functional predictability prior to translation.


Dermatofibrosarcoma protuberans (DFSP): predictors of recurrence and the use of systemic therapy.
Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue malignancy that typically presents with local invasion but rarely metastasizes. We examine clinicopathologic factors associated with disease-free survival (DFS) in patients with primary and recurrent DFSP and evaluate responses to multimodality therapy. Patients treated for DFSP were identified in a prospectively maintained database. Clinicopathologic factors associated with DFS were analyzed using univariate and multivariate analysis. A total of 244 patients with DFSP were identified. Median follow-up was 50 months. A total of 14 patients had local recurrence (LR), and 2 patients had distant recurrence (DR), with a median time to recurrence of 35 months. At time of last follow-up, 70% and 47% of patients showed no evidence of disease (NED) in the primary (n = 197) and recurrent groups (n = 47), respectively. On univariate analysis, tumor location and depth were associated with DFS in the primary group, while margin status (R1 vs. R0) was associated with DFS in the LR group. On multivariate analysis, only depth (primary group) and margin status (LR group), remained significant. Also, 22 patients had therapy other than surgical resection: 14 radiotherapy, 4 tyrosine kinase inhibitor (TKI) only, 2 conventional chemotherapy only, and 2 chemotherapy plus TKI. Responses to other therapies were variable. DFS after treatment for DFSP is strongly predicted by tumor depth in the primary setting and margin status in recurrent tumors. The treatment for DFSP in the primary or recurrent setting is excision with negative margins, resulting in low recurrence rates and infrequent metastatic spread. Multimodality treatment, especially TKI use, can be effective, but is not curative.


Two-stage procedure for the management of massive hydronephrosis.
A case of congenital unilateral massive hydronephrosis containing 42.5 l. clear urine is reported. Treatment consisted of a 2-stage procedure that is described. The consequences of sudden decompression, which occurs after a 1-stage operation, are discussed. The rationale of the 2-stage procedure is that gradual decompression helps to restore the normal anatomical and physiological base lines so that the definitive operation of removal of the sac can be accomplished with minimum risk to the patient. This 2-stage technique is a relatively safe procedure based on sound principles.


Biocompatibility and hemocompatibility of hydrothermally derived reduced graphene oxide using soluble starch as a reducing agent.
Graphene-based nanomaterials (GBNs) have many applications as biomedical materials in tissue engineering and regenerative medicine. We report on the preparation of starch-(functionalized) reduced graphene oxide nanosheets (SRGO) using soluble starch as a reducing agent in a hydrothermal method, and their in vitro interactions with human skin fibroblasts and red blood cells (RBCs). Our results indicate that soluble SRGO nanosheets were prepared using graphene oxide (GO) as a raw material. SRGO-1 and -10, which were prepared using different concentrations of soluble starch after hydrothermal treatment, were characterized by ultraviolet-visible spectroscopy and showed a peak shift at 260 nm corresponding to the deoxygenation of GO and restoration of the conjugated aromatic structure. Dynamic light scattering and zeta potential measurements were used to determine Z-average sizes and surface charges of GO and SRGOs. X-ray diffractometry, attenuated total reflectance Fourier-transform infrared spectroscopy, and Raman spectroscopy revealed the progressive elimination of labile oxygen functional groups during hydrothermal treatment and restoration of the π-conjugated network. X-ray photoelectron spectroscopy showed de-oxidation of SRGOs, which had high carbon to oxygen ratios (C/O) as compared with GO. Interactions of SRGO-1 and -10 with skin fibroblasts showed excellent biocompatibility even at a concentration of 200 μg/ml with cell viabilities up to 88% and 90%, respectively, whereas notable cytotoxicity was observed for GO at 20 μg/ml. Similarly, SRGO-1 and -10 did not exhibit toxicity to RBCs compared to GO. Biofilm formation and metabolic activities of biofilm by the bacterium Staphylococcus aureus were also evaluated using a crystal violet and a tetrazolium reduction assay, respectively. The described hydrothermal method used to synthesize SRGO provides a cheap, facile, and environmentally friendly means of producing water-dispersible, biocompatible and hemocompatible reduced GOs for the fabrication of novel GBNs for various biomedical applications.


Rat cortical morphology following crowded-enriched living conditions.
This experiment studied cerebral cortical morphology in rats living in a crowded-enriched condition. Three groups of 60-day-old, male Long-Evans rats were divided accordingly: 12 rats, 3 per small cage (32 X 20 X 20 cm), standard colony condition; 12 rats in a single, large, enrichment cage with "toys" (70 X 70 X 45 cm), enriched condition; and 36 rats in a large, single, enrichment cage with "toys", crowded-enriched condition. Matched toys for the two enriched cages were changed twice a week at the time of cage cleaning. Measurements on 20-micron, transverse brain sections showed that in both the crowded-enriched and enriched groups the thickness of the medial occipital cortex increased by 4 to 6% compared with the cortex from animals in the standard colony condition. In addition, the crowded-enriched group demonstrated a 4% (P less than 0.05) increase in thickness in area 39 in the left hemisphere compared with the standard control. However, the thickness in area 39 in the crowded group was not significantly different from that of the enriched area 39. These results indicate that the cortex increases in thickness as much with "crowding" and enrichment as with enrichment alone. We hypothesize that diversion through interaction with "toys" mitigates the stress of crowded conditions.


Morphological changes in submandibular lymph nodes after subcutaneous implantation of gold alloys.
Functional activity of cells in regional lymph nodes of the major salivary glands was studied in rats after subcutaneous implantation of gold alloys. Alloy 900 modified the function of regional lymph nodes.


A Qualitative Study of Sleep-Wake Disturbance Among Veterans With Post-Acute Moderate to Severe Traumatic Brain Injury.
Examine sleep-wake disturbance (SWD) characteristics, factors, consequences, and management strategies from the perspective of veterans with chronic stage, moderate/severe traumatic brain injury (TBI). VA Medical Center, Rocky Mountain. Nineteen male veterans with post-acute TBI and SWD in the VA Health Administration. Qualitative descriptive. Semistructured interviews, Ohio State University TBI-Identification Method, Insomnia Severity Index. Two main dimensions emerged: "Messed up sleep" and Surviving and Managing SWD. Sleep-wake disturbance has long-term multidimensional features, etiology, consequences, and practice implications. Although SWD may not be consistently discussed with providers, the problem appears to be pervasive in many aspects of the lives of the informants. Difficulty falling asleep, frequent awakenings, and poor sleep quality were common symptoms that were described as intrusive, isolating, and difficult to self-manage. Veterans discussed a host of physical symptoms, mental health issues, environmental, and behavioral factors that contributed to SWD. Medications, sleep apnea treatment, and self-imposed isolation were frequent management strategies. Veterans expressed a willingness to try new approaches and work with providers. Sleep-wake disturbance among veterans with chronic stage TBI is a multidimensional phenomenon with interplay between comorbidities, contributing factors, effects on functioning, and sleep management strategies. Implications for practice include early and routine evaluation, monitoring, and treatment of SWD. Research is needed to test interventions that address SWD and common TBI comorbidities.


Paleoclimate-conditioning reveals a North Africa land-atmosphere tipping point.
While paleoclimate records show that the Earth System is characterized by several different tipping points, their representation within Earth System models (ESMs) remains poorly constrained. This is because historical observations do not encompass variations large enough to provoke such regime changes, and paleoclimate conditions are rarely used to help develop and tune ESMs, which potentially ignores a rich source of information on abrupt climate change. A critical example is the early to mid-Holocene "greening" and subsequent rapid desertification of the Sahara, which most ESMs fail to reproduce, casting doubt on the representation of land-atmosphere coupling and monsoon dynamics. Here, we show that this greening and abrupt termination can be successfully simulated with one ESM after optimizing uncertain model components using both present-day observations and crucially mid-Holocene (6,000 y before present) reconstructions. The optimized model displays abrupt threshold behavior, which shows excellent agreement with long paleoclimate records that were not used in the original optimization. These results suggest that in order to realistically capture climate-system thresholds, ESMs first need to be conditioned with appropriate paleoclimate information.


Nomograms to predict isolated loco-regional or distant recurrence among women with uterine cancer.
While there is ample literature on prognostic factors for uterine cancer, currently there are nomeans to estimate an individual's risk for recurrence or to differentiate the risk of loco-regional recurrence from distant recurrence. We addressed this gap by developing nomograms to individualize the risk of recurrence. A total of 2097 consecutive patients who underwent primary surgery between 1997 and 2007 were included. Sixteen covariates were evaluated for their prognostic significance and modeled using multivariable competing risks regression to predict three-year outcomes as part of a nomogram. Each covariate in the nomogram is assigned a value, and a sum of these values form the overall risk score from which three-year incidence probabilities can be predicted for each individual. Predictive accuracy was assessed with concordance index and then corrected for optimism. The median follow-up time (inter-quartile range, IQR) was 50.0 (28.3-77.5) months and 221 patients developed a recurrence (127 patients with isolated loco-regional recurrence, 94 patients with distant recurrence). The nomograms included the following covariates: age at diagnosis, FIGO stage (2009), grade, lymphovascular invasion, histological type, depth of myometrial invasion, and peritoneal cytology. Concordance indices for isolated loco-regional and distant recurrences were 0.73 and 0.86, respectively. Our nomograms quantify an individual patient's risk of isolated loco-regional and distant recurrence, using factors that are routinely collected. They may assist clinicians to assess an individual's prognosis, individualize treatment and also assist in the risk stratification in prospective randomized clinical trials evaluating the effectiveness of treatments for uterine cancer.


Decreased early diastolic function after indomethacin administration in premature infants.
The effect of indomethacin on systolic and diastolic cardiac function was assessed in 15 premature infants. Seven infants (group 1) received indomethacin to treat a clinically significant patent ductus arteriosus (PDA), and eight infants (group 2) received indomethacin prophylactically at 24 hours of age because of their high risk for PDA. Diastolic cardiac function was assessed using instantaneous rates of change of left ventricular (LV) cavity dimension, derived from M-mode echocardiography. The maximum velocity of lengthening of the LV cavity dimension, an index of early diastolic function, fell from 63 +/- 19 mm/sec before indomethacin to 48 +/- 16 mm/sec 1 hour after indomethacin in group 1 (P less than 0.01), with the ductus still patent and the LV chamber still dilated, and also decreased in group 2, from 52 +/- 7 mm/sec to 38 +/- 6 mm/sec (P less than 0.01). This index, when normalized for loading conditions, was decreased 1 hour after indomethacin at 12 +/- 2 sec-1 and 12 +/- 1 sec-1 for groups 1 and 2, respectively, compared with values before indomethacin of 15 +/- 3 sec-1 and 15 +/- 2 sec-1. There was no effect of indomethacin on the indices of systolic function. We conclude that indomethacin decreases early diastolic function in premature infants.


Material coefficients of the strain energy function of pulmonary arteries in normal and cigarette smoke-exposed rats.
The effect of cigarette smoke on the stress-strain relationship of pulmonary arteries was studied in 2- and 3-month smoke-exposed rats. The animals were exposed to cigarette smoke in a smoke-generating system 10 times daily with one cigarette each time. The smoke density and the puffing duration and frequency of the system were regulated in accordance with reference values measured from human smokers. The mechanical properties of the pulmonary arteries about 450 microns in external diameter (at zero pressure) were determined in vitro by inflation and deflation tests. The average stress and middle-wall strain of the selected pulmonary arteries were determined on the basis of experimental data including inflation and deflation pressures during loading and unloading processes, respectively, and vessel diameter and length at various pressure levels, and vessel circumferential and longitudinal lengths at zero-stress state. A constitutive equation for the pulmonary arteries was derived from an energy function depending on circumferential and longitudinal Green's strains. The coefficients of the strain energy function of the pulmonary arteries were determined in both the smoke-exposed and control rats by fitting the experimental stress-strain data with the constitutive equation. It was found that the wall stress of the pulmonary arteries at a given strain and most of the coefficients of the strain energy function were increased in both the 2- and 3-month smoke-exposed rats in comparison with those in the corresponding controls. These results indicated that cigarette smoke induced an increase in the wall stiffness of the pulmonary arteries in the rats.


How social policies can improve financial accessibility of healthcare: a multi-level analysis of unmet medical need in European countries.
The article explores in how far financial accessibility of healthcare (FAH) is restricted for low-income groups and identifies social protection policies that can supplement health policies in guaranteeing universal access to healthcare. The article is aimed to advance the literature on comparative European social epidemiology by focussing on income-related barriers of healthcare take-up. The research is carried out on the basis of multi-level cross-sectional analyses using 2012 EU-SILC data for 30 European countries. The social policy data stems from EU-SILC beneficiary information. It is argued that unmet medical needs are a reality for many individuals within Europe - not only due to direct user fees but also due to indirect costs such as waiting time, travel costs, time not spent working. Moreover, low FAH affects not only the lowest income quintile but also the lower middle income class. The study observes that social allowance increases the purchasing power of both household types, thereby helping them to overcome financial barriers to healthcare uptake. Alongside healthcare system reform aimed at improving the pro-poor availability of healthcare facilities and financing, policies directed at improving FAH should aim at providing a minimum income base to the low-income quintile. Moreover, categorical policies should address households exposed to debt which form the key vulnerable group within the low-income classes.


Variants of the myosin interacting-heads motif.
Under relaxing conditions, the two heads of myosin II interact with each other and with the proximal part (S2) of the myosin tail, establishing the interacting-heads motif (IHM), found in myosin molecules and thick filaments of muscle and nonmuscle cells. The IHM is normally thought of as a single, unique structure, but there are several variants. In the simplest ("canonical") IHM, occurring in most relaxed thick filaments and in heavy meromyosin, the interacting heads bend back and interact with S2, and the motif lies parallel to the filament surface. In one variant, occurring in insect indirect flight muscle, there is no S2-head interaction and the motif is perpendicular to the filament. In a second variant, found in smooth and nonmuscle single myosin molecules in their inhibited (10S) conformation, S2 is shifted ∼20 Å from the canonical form and the tail folds twice and wraps around the interacting heads. These molecule and filament IHM variants have important energetic and pathophysiological consequences. (1) The canonical motif, with S2-head interaction, correlates with the super-relaxed (SRX) state of myosin. The absence of S2-head interaction in insects may account for the lower stability of this IHM and apparent absence of SRX in indirect flight muscle, contributing to the quick initiation of flight in insects. (2) The ∼20 Å shift of S2 in 10S myosin molecules means that S2-head interactions are different from those in the canonical IHM. This variant therefore cannot be used to analyze the impact of myosin mutations on S2-head interactions that occur in filaments, as has been proposed. It can be used, instead, to analyze the structural impact of mutations in smooth and nonmuscle myosin.


Tooth Resorption - Part 1: The evolvement, rationales and controversies of tooth resorption.
In 1966, Andreasen and Hjørting-Hansen were the first to describe a relationship between tooth resorption and dental trauma. However, Andreasen's original classification did not include other resorptive processes which have since been identified. Numerous articles have been published suggesting new terminology and definitions for tooth resorption. A uniform language with universally accepted terminology is crucial to eliminate the multiplicity of terms and definitions which only cause confusion within the profession. An electronic literature search was carried out in the PubMed database using the following keywords for articles published in English: "root resorption," "inflammatory root resorption," "replacement resorption," "cervical resorption," "trauma," "ankylosis," "surface resorption," and "internal resorption." The search also included textbooks and glossaries that may not have surfaced in the online search. This was done to identify articles related to tooth resorption and its etiology in dentistry. The aim of this review was to present the history that has led to the variety of terms and definitions for resorption. This review emphasizes the need for a clearer, simpler, and more comprehensive nomenclature for the various types of tooth resorption which are presented in Part 2 of this series.


The impact of COVID-19 pandemic on patients receiving orthodontic treatment: An online questionnaire cross-sectional study.
The spread of Coronavirus Disease 2019 (COVID-19) has led to a major public health issue; most dental clinics were closed and millions of orthodontic patients were unable to complete their treatment. This study aimed to assess the challenges faced by patients receiving orthodontic treatment and their preferred solutions to overcoming these challenges during this pandemic. An online questionnaire was developed and sent to patients receiving orthodontic treatment at a public or private clinic. A total of 388 responses were analyzed: mean age 20.4 ± 4 years, 75% (291) female, and 58% (226) received their treatment at a public clinic. Of all participants, 27.3% (106) were still unable to attend their appointments and 69% (244) stated that closing of the clinic was the main reason for missing their appointments. Depending on their type of appliance, the patients faced different problems and chose multiple ways to deal with them. Most participants had fixed appliances, 84% (327), and only 21% (64) of them stated that they had no problem compared with 39% (11) and 36% (8) for removable appliance and clear aligner groups, respectively. The COVID-19 pandemic has had a significant impact on orthodontic treatments. Almost every orthodontic patient had to stop attending their appointments, which put them in complicated situations and in fear of delayed treatment. Patients from a public clinic and patients with fixed appliances reported more problems than others. More attention should be giving to teleorthodontics; also orthodontists should prepare their patients to deal with some of the problems related to their appliances when possible.


Detection of erythrocytes in patient with elliptocytosis complicating ITP using atomic force microscopy.
The pathological changes of erythrocytes were detected at the nanometer scale, which was important for revealing the onset of diseases, early diagnosis, and effective therapies. Diseases may disturb the morphology and function of erythrocytes at molecular scale. There were dramatic surface deformations in topography of erythrocytes from a patient with elliptocytosis complicating idiopathic thrombocytopenic purpura (ITP). The overall shape and surface membrane of the healthy, pre- and post-therapeutic erythrocytes have been studied by high-resolution atomic force microscopy imaging. The results showed that we can detect healthy and pathological erythrocytes by the morphologic parameters of the length, width, ratio of length to width, peak, valley, valley-to-peak, surface fluctuation, and standard deviations of the erythrocytes. Therefore, the morphologic information of erythrocytes is very important indictor for diagnosing the healthy and disease, as well as evaluating therapeutic effect.


[Albrecht von Graefe and the beginning of modern ophthalmology : Graefe year 2020].
After almost 4000 years of history, ophthalmology became independent between 1850 and 1900. The decisive founder of modern ophthalmology was Albrecht von Graefe (1828-1870), who founded both his archive (1854), which still exists today and is named after him, and the German Ophthalmological Society (1857). There are still numerous Graefe sites today, especially in Berlin. Thanks to his timeless values, Albrecht von Graefe can be described as the conscience of ophthalmology in Germany.


Host factor DUSP5 potently inhibits dengue virus infection by modulating cytoskeleton rearrangement.
Cytoskeleton has been reported to play an essential role in facilitating the viral life cycle. However, whether the host can exert its antiviral effects by modulating the cytoskeleton is not fully understood. In this study, we identified that host factor DUSP5 was upregulated after dengue virus (DENV) infection. In addition, we demonstrated that overexpression of DUSP5 remarkably inhibited DENV replication. Conversely, the depletion of DUSP5 led to an increase in viral replication. Moreover, DUSP5 was found to restrain viral entry into host cells by suppressing F-actin rearrangement via negatively regulating the ERK-MLCK-Myosin IIB signaling axis. Depletion of dephosphorylase activity of DUSP5 abolished its above inhibitory effects. Furthermore, we also revealed that DUSP5 exhibited broad-spectrum antiviral effects against DENV and Zika virus. Taken together, our studies identified DUSP5 as a key host defense factor against viral infection and uncovered an intriguing mechanism by which the host exerts its antiviral effects through targeting cytoskeleton rearrangement.


Aortic elastic properties in Takayasu arteritis.
We describe the case of a female patient with Takayasu arteritis. The aortic elastic properties were improved after the administration of diltiazem, as assessed by the aortic pressure-diameter relation. Consequently, the patient was treated with diltiazem at a dose of 270 mg/day for three years. During this follow-up period, there have been no life-threatening events related to Takayasu arteritis.