Closed Versus Open Supracondylar Fractures of the Humerus in Children: A Comparison of Clinical and Radiographic Presentation and Results.
The purpose of this investigation was to compare the presentation and postoperative results of children treated for open and closed, completely displaced type III supracondylar humerus fractures (SCFs). Thirty patients with open and 66 patients with closed, completely displaced type III SCFs were evaluated. Open fractures underwent irrigation and debridement, and all patients were treated by open or closed reduction and pin fixation. Medical records were reviewed to obtain demographic information as well as preoperative and postoperative clinical data regarding mechanism of injury, neurovascular status, associated injuries, postoperative range of motion, infections, and pain. Radiographs were evaluated to quantify displacement, Baumann's angle, humeral capitellar angle, position of the anterior humeral line, and adequacy of reduction. Outcomes were assessed using Flynn criteria. Mean clinical follow-up for the open and closed fracture groups was 8.9 and 5.7 months, respectively. Both groups were similar with respect to age, sex distribution, weight and body mass index, laterality of involvement, and mechanism of injury. At presentation, 35% of closed SCFs and 23% of open SCFs presented with abnormal neurovascular status. There was a higher prevalence of diminished/absent pulses or distal limb ischemia in patients with open injuries (27%) compared with closed fractures (18%). Conversely, severely displaced closed fractures were more commonly associated with nerve injury/palsy at presentation (35%) than those with open fractures (23%). Spontaneous nerve recovery was seen in 87% within 3 to 6 months. Postoperative loss of reduction and malunion were more common in the closed fracture group. However, 84% of patients achieved good-to-excellent results by Flynn criteria, with no appreciable difference based upon open versus closed fractures. With timely wound and fracture treatment, the clinical and radiographic results of children treated for open SCFs is similar to those with closed type III injuries, with little increased risk for infection, malunion, or neurovascular compromise. Level III.


Using surveys of Affymetrix GeneChips to study antisense expression.
We have used large surveys of Affymetrix GeneChip data in the public domain to conduct a study of antisense expression across diverse conditions. We derive correlations between groups of probes which map uniquely to the same exon in the antisense direction. When there are no probes assigned to an exon in the sense direction we find that many of the antisense groups fail to detect a coherent block of transcription. We find that only a minority of these groups contain coherent blocks of antisense expression suggesting transcription. We also derive correlations between groups of probes which map uniquely to the same exon in both sense and antisense direction. In some of these cases the locations of sense probes overlap with the antisense probes, and the sense and antisense probe intensities are correlated with each other. This configuration suggests the existence of a Natural Antisense Transcript (NAT) pair. We find the majority of such NAT pairs detected by GeneChips are formed by a transcript of an established gene and either an EST or an mRNA. In order to determine the exact antisense regulatory mechanism indicated by the correlation of sense probes with antisense probes, a further investigation is necessary for every particular case of interest. However, the analysis of microarray data has proved to be a good method to reconfirm known NATs, discover new ones, as well as to notice possible problems in the annotation of antisense transcripts.


The Role of Physicians in Digitalizing Health Care Provision: Web-Based Survey Study.
Digitalization affects all areas of society, including the health care sector. However, the digitalization of health care provision is progressing slowly compared to other sectors. In the professional and political literature, physicians are partially portrayed as digitalization sceptics. Thus, the role of physicians in this process requires further investigation. The theory of "digital natives" suggests a lower hurdle for younger generations to engage with digital technologies. The objective of this study was to investigate the role of physicians in the process of digitalizing health care provision in Germany and to assess the age factor. We conducted a large-scale study to assess the role of this professional group in the progress of the digital transformation of the German health care sector. Therefore, in an anonymous online survey, we inquired about the current digital penetration of the personal working environment, expectations, attitude toward, and concerns regarding digitalization. Based on these data, we studied associations with the nominal variable age and variations across 2 age groups. The 1274 participants included in the study generally showed a high affinity towards digitalization with a mean of 3.88 on a 5-point Likert scale; 723 respondents (56.75%) stated they personally use mobile apps in their everyday working life, with a weak tendency to be associated with the respondents' age (η=0.26). Participants saw the most noticeable existing benefits through digitalization in data quality and readability (882/1274, 69.23%) and the least in patient engagement (213/1274, 16.72%). Medical practitioners preponderantly expect further improvements through increased digitalization across almost all queried areas but the most in access to medical knowledge (1136/1274, 89.17%), treatment of orphan diseases (1016/1274, 79.75%), and medical research (1023/1274, 80.30%). Respondents defined their role in the digitalization of health care provision as ambivalent: "scrutinizing" on the one hand but "active" and "open" on the other. A gap between willingness to participate and digital sovereignty was indicated. Thus, education on digitalization as a means to support health care provision should not only be included in the course of study but also in the continuing process of further and advanced training.


[Carcinoma inside of an amygdaloid cyst. Apropos of a case].
The authors report one case of tonsillar cyst with area of dysplasia in the epithelium, in situ carcinoma, and invasive carcinoma which are peculiar to branchiogenic carcinoma. A tonsillarectomy made ten month after the operation contradict this diagnosis. The criteria for making the diagnosis of branchiogenic carcinoma are discussed so as the clinical sensibility of this cysts. Present imagery is not able to assert the primarity of such lesion. Removing of the tonsil would be made systematically.


Examining Bias in Published Surgical Glaucoma Clinical Trials.
Our results demonstrate that, among randomized clinical trials examining the use of surgical treatments for glaucoma, the majority were not registered. Publication bias was less likely. More than one third of registered trials presented outcome reporting bias. Despite the optimum of quality evidence provided by randomized controlled trials (RCTs), biases may be introduced and hinder their application. The primary objective of this study was to investigate outcome reporting bias (ORB) and publication bias (PB) in RCTs assessing surgical treatments of glaucoma, as well as their registration status. A literature review was conducted in MEDLINE, EMBASE and CENTRAL databases. Inclusion criteria were RCTs published in English between 2007 and 2021 that focused on surgical treatments of patients of all ages with glaucoma or elevated intraocular pressure. Exclusion criteria included cadaveric and animal studies. Registration status was correlated with entries from clinical trial registries. PB was determined by the proportion of trials presenting statistically significant results. ORB was evaluated by comparing the study's primary outcome with that listed in the trial registry. Trials quality was assessed using the Jadad score. After deleting duplicates, 7,561 citations were screened. 161 RCTs were eligible and included between 13 and 556 participants. Ninety one percent studied an adult population and 71% included patients suffering from primary open-angle glaucoma. Among included studies, 63% were not registered and 47% had statistically significant results. An upward trend in registration was observed with time. However, 37% of the studies showed discrepancies between objectives in cited clinical trial registries and the published results. Publication bias in surgical glaucoma trials was not obvious. Among the minority of trials that were registered, more than a third presented outcome reporting bias. Unregistered trials had lower quality. RCT registration is crucial for transparent interpretation of studies, improved patient care in surgery and informed decision-making.


Application of PCR to the identification of dermatophyte fungi.
Infection of the keratinised tissues (skin, hair and nails) in man and animals by keratinophilic fungi (dermatophytes) results in dermatophytosis (also known as tinea or ringworm). As conventional laboratory procedures for the identification of dermatophytes are either slow or lack specificity, improved diagnostic methods are required. The application of nucleic acid amplification technology has made rapid and precise identification of dermatophytes possible. Recent studies have shown that when one of the four random primers (OPAA11, OPD18, OPAA17 and OPU15) was used in arbitrarily primed PCR (AP-PCR), up to 20 of the 25 dermatophyte species or subspecies under investigation could be distinguished on the basis of characteristic band patterns detected in agarose gel electrophoresis. A combination of two random primers (OPD18 and OPAA17) used in separate reaction tubes identified 23 of the 25 dermatophyte species or subspecies examined. AP-PCR provides a rapid and practical tool for identification of dermatophyte isolates that is independent of morphological and biochemical characteristics and thus enhances laboratory diagnosis of dermatophytosis.


Plasma amine oxidase and genetic vulnerability to schizophrenia.
Plasma amine oxidase (PAO) activity was studied in 52 chronic schizophrenics, 130 first-degree relatives, and 36 normal control subjects. Enzyme activity was shown to be a heritable and stable characteristic. Age and sex effects were not present. Patients had lower PAO activity than did control subjects, although the difference fell short of statistical significance. Within families, reduced PAO activity was associated with schizophrenia spectrum disorders.


[Characterization of endothelial progenitor cells and putative strategies to improve their expansion].
Injection of endothelial progenitor cells (EPC) expanded ex vivo has been shown to increase neovascularization in preclinical models of ischemia and in adult patients, but the precise origin and identity of the cell population responsible for these clinical benefits are controversial. Given the potential usefulness of EPC as a cell therapy product, their thorough characterization is of major importance. This review describes the two cell populations currently called EPC and the means to find differential phenotypic markers. We have shown that BMP2/4 are specific markers of late EPC and play a key role in EPC commitment and outgrowth during neovascularization. Several authors have attempted to expand EPC ex vivo in order to obtain a homogeneous cell therapy product. One possible mean of expanding EPC ex vivo is to activate the thrombin receptor PAR-1 with the specific peptide SFLLRN. Indeed, PAR-1 activation increases angiogenic properties of EPC through activation of SDF-1, angiopoietin and IL-8 pathways. This review summarizes the characterization of EPC and different methods of ex vivo expansion.


Acne: hormonal concepts and therapy.
Acne vulgaris is the most common skin condition observed in the medical community. Although we know that hormones are important in the development of acne, many questions remain unanswered regarding the mechanisms by which hormones exert their effects. Androgens such as dihydrotestosterone (DHT) and testosterone, the adrenal precursor dehydroepiandrosterone sulfate (DHEAS), estrogens such as estradiol, and other hormones, including growth hormone and insulin-like growth factors (IGFs), may be important in acne. It is not known whether these hormones are taken up from the serum by the sebaceous gland, whether they are produced locally within the gland, or whether a combination of these processes is involved. Finally, the cellular and molecular mechanisms by which these hormones exert their influence on the sebaceous gland have not been fully elucidated. Hormonal therapy is an option in women with acne not responding to conventional treatment or with signs of endocrine abnormalities.


The employment of adults with spina bifida.
Information on employment was obtained from 157 adults with spina bifida aged 18-26 years. Ninety were given an additional interview, 43% had been employed at some time, but only 19% currently. They mainly did routine, non-manual work for average working hours, but below average pay. They enjoyed their jobs, principally for the social contact, and were well accepted by employees and work-mates. Unfortunately, job retention was poor. The 81% who were unemployed largely hoped to find a job, but suitable ones were not available. They considered that they should have more help to find jobs. Their days were mainly spent at home or at day centres. They had no doubts that being unemployed had many disadvantages, of which the principal one was lack of social contact, but financial hardship was also mentioned.


Effect of cumin (Cuminum cyminum) seed essential oil on biofilm formation and plasmid Integrity of Klebsiella pneumoniae.
Seeds of the cumin plant (Cuminum cyminum L.) have been used since many years in Iranian traditional medicine. We assessed the effect of cumin seed essential oil on the biofilm-forming ability of Klebsiella pneumoniae strains and on the integrity of a native resistance plasmid DNA from K. pneumoniae isolates, treated with essential oil. Antibacterial coaction between the essential oil and selected antibiotic disks were determined for inhibiting K. pneumoniae. The essential oil of the cumin seeds was obtained by hydrodistillation in a Clavenger system. A simple method for the formation of biofilms on semiglass lamellas was established. The biofilms formed were observed by scanning electron microscopy (SEM). The effect of essential oil on plasmid integrity was studied through the induction of R-plasmid DNA degradation. The plasmid was incubated with essential oil, and agarose gel electrophoresis was performed. Disk diffusion assay was employed to determine the coaction. The essential oil decreased biofilm formation and enhanced the activity of the ciprofloxacin disk. The incubation of the R-plasmid DNA with essential oil could not induce plasmid DNA degradation. The results of this study suggest the potential use of cumin seed essential oil against K. pneumoniae in vitro, may contribute to the in vivo efficacy of this essential oil.


Short- and long-term outcome following laparoscopic versus open resection for carcinoma of the rectum in the multimodal setting.
Laparoscopic resection for rectal cancer has remained controversial because of the lack of level 1 evidence regarding oncologic safety and long-term survival. The aim of this study was to assess the impact of laparoscopic versus open resection for rectal cancer on clinical and oncologic outcome in the multimodal setting. This is a review of prospectively gathered data from a single-institution rectal cancer database. This study was conducted in the Central Hospital of Central Finland. From January 1999 to December 2006, 191 selected patients were included. One hundred patients underwent laparoscopic resection, and 91 patients, also suitable for laparoscopic surgery, underwent open major rectal resection in the multimodal setting. The main measures of outcome were early recovery and short- and long-term morbidity; local recurrence and survival were secondary outcomes. This is not a randomized study. The study groups were balanced for baseline characteristics. Conversion rate to open surgery was 22%. Laparoscopic surgery resulted in significantly less bleeding (175 mL vs 500 mL, p < 0.001), 1 day earlier recovery of normal diet (3 days vs 4 days, p = 0.001), and shorter postoperative hospital stay (7 days vs 9 days, p < 0.001). Postoperative 30-day mortality (1% vs 3%), morbidity (31% vs 43%), readmission (11% vs 15%), and reoperation (6% vs 9%) rates were similar in the 2 groups, but significantly fewer patients in the laparoscopic group had long-term complications (19% vs 36%, p = 0.033). The 5-year disease-free survival (78% vs 80%, p = 0.74) and local recurrence (5% vs 6%, p = 0.66) rates were similar in the laparoscopic and open group for those 175 patients treated for cure. Laparoscopic surgery resulted in faster postoperative recovery and fewer long-term complications than open surgery without apparently compromising the long-term oncologic outcome. Our results indicate that laparoscopic rectal resection is an acceptable alternative to open surgery in selected patients with rectal cancer.


The beneficial effect of icaritin on osteoporotic bone is dependent on the treatment initiation timing in adult ovariectomized rats.
Epimedium-derived flavonoids (EFs) have a potential to treat established osteoporosis in postmenopausal women. However, one of the main disadvantages of the compound is the high volume and dosage during long-term administration period. Meanwhile, the beneficial effect of EFs on osteoporotic bone depends greatly on the intervention timing. Whether icaritin (ICT), an active molecular compound from EFs, can exert beneficial effect on osteoporotic bone and whether the beneficial effect is also dependent on the intervention timing remain unknown. The objective of this study was to evaluate the effect of the early and late ICT treatment on bone turnover markers, trabecular architecture, bone remodeling, biomechanics, colony formation of bone marrow stromal cells and osteoblast, adipocyte and osteoclast-related gene expression in adult ovariectomized rats. Eighty 9-month-old female rats (n=8/group) were sham-operated (Sham) or ovariectomized (OVX). The OVX rats were subjected to ICT treatment initiation at 1 month (early treatment) and 3 months (late treatment) post-operation, respectively. The vehicle-treated Sham and OVX rats starting at month 1 and month 3 post-operation served as the corresponding controls (Sham and OVX controls) for early and late ICT treatment, respectively. Those Sham and OVX rats sacrificed immediately before early and late ICT treatment served as the pretreatment baseline controls. Both ICT and vehicle treatments lasted for 2 months. The bone turnover markers, trabecular architecture, bone remodeling and bone biomechanical properties were analyzed with biochemistry, microCT, histomorphometry and mechanical testing, respectively. The population of bone marrow stromal cells (BMSCs) and osteoblasts were evaluated with colony formation assays, respectively. The expression levels of osteoblast, adipocyte and osteoclast-related genes in bone marrow were assessed by real-time polymerase chain reaction (PCR), respectively. At the tissue level, early ICT treatment remarkably restored the trabecular bone mass, trabecular architecture and bone biomechanical properties towards pretreatment Sham levels, and significantly increased bone formation from pretreatment OVX level and markedly inhibited bone resorption towards pretreatment Sham level, whereas late ICT treatment failed to have any effect. At the cellular and molecular level, early ICT treatment significantly increased the number of osteoblastic colonies and the level of osteoblast-related gene expression compared to pretreatment OVX levels and remarkably decreased adipocyte and osteoclast-related gene expression towards pretreatment Sham levels. Late ICT treatment failed to have beneficial effect on any of these parameters. ICT can exert anabolic and anti-resorptive effect on osteoporotic bone. The beneficial effect of ICT treatment is dependent on the intervention timing in established osteoporosis induced by estrogen depletion.


Telehealth is here to stay but not without challenges: a consultation of cardiac rehabilitation clinicians during COVID-19 in Victoria, Australia.
Delivery of cardiac rehabilitation (CR) was challenged during the pandemic caused by the Coronavirus disease (COVID-19), due to government stay-at-home directives which restricted in-person programmes. The Australian state of Victoria experienced the longest and most severe COVID-19 restrictions and was in lockdown for ∼6 months of 2020. We aimed to explore (i) clinicians' experiences and perceptions and (ii) identify barriers and enablers, for delivering CR during the COVID-19 pandemic. Victorian members of the Australian Cardiovascular Health and Rehabilitation Association (ACRA) were invited to attend an exploratory qualitative online consultation in November 2020. An inductive thematic analysis was undertaken, before deductively applying the Non-adoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework to identify barriers and enablers for technology adoption in CR. Thirty members participated in a 106-min consultation. Seventeen members who provided demographics represented multiple disciplines (nursing n = 13, exercise physiology n = 3, and physiotherapy n = 1) and geographical settings (metropolitan n = 10, regional n = 4, and rural n = 3). Four main themes were inductively identified: consequences of change; use of technology; capacity; and the way forward. The deductive NASSS analysis demonstrated the main challenges of continuing remotely delivered CR lie with adopters (staff, patients, and carers) and with organizations. The COVID-19 pandemic expedited significant changes to CR delivery models. While clinicians are eager to retain technology-enabled delivery in addition to resuming in-person CR, it is now timely to review remote models of care, tools used and plan how they will be integrated with traditional in-person programmes.


[Microbiological characterization of candidate vaccine strains of Ballum serogroup Leptospira interrogans].
Two candidate vaccines of Ballum serogroup Leptospira interrogans were microbiologically characterized as part of the work directed to the obtention of new antileptospirosis vaccine formulations for human use. The growth kynetics of both strains was evaluated in EMJH protein medium and in 3 protein free media. The virulence was estimated in hamsters by the calculation of the mean lethal dose. The cellular and extracellular antigenic profiles were analyzed by unidimensional SDS-PAGE and compared with those from strains of Canicola, Icterohaemorrhagiae and Pomona serogroups. The antigenic homology among heterologous groups was analyzed by western blotting with serun from hasterms vaccinated with vax-SPIRAL. The results obtained showed a fastidious growth of both strains of Ballum in the studied media, a high virulence in the animal model and a large antigenic homology with strains from other serogroups of Lepstospira prevailing in Cuba.


Differential expression of metabolic genes essential for glucose and lipid metabolism in skeletal muscle from spinal cord injured subjects.
Skeletal muscle plays an important role in the regulation of energy homeostasis; therefore, the ability of skeletal muscle to adapt and alter metabolic gene expression in response to changes in physiological demands is critical for energy balance. Individuals with cervical spinal cord lesions are characterized by tetraplegia, impaired thermoregulation, and altered skeletal muscle morphology. We characterized skeletal muscle metabolic gene expression patterns, as well as protein content, in these individuals to assess the impact of spinal cord injury on critical determinants of skeletal muscle metabolism. Our results demonstrate that mRNA levels and protein expression of skeletal muscle genes essential for glucose storage are reduced, whereas expression of glycolytic genes is reciprocally increased in individuals with spinal cord injury. Furthermore, expression of genes essential for lipid oxidation is coordinately reduced in spinal cord injured subjects, consistent with a marked reduction of mitochondrial proteins. Thus spinal cord injury resulted in a profound and tightly coordinated change in skeletal muscle metabolic gene expression program that is associated with the aberrant metabolic features of the tissue.


Interatrial conduction measured during biventricular pacemaker implantation accurately predicts optimal paced atrioventricular intervals.
Optimizing atrioventricular (AV) delay during biventricular (BiV) pacemaker implantation can require substantial resources. Hence, a simpler method is desirable. We hypothesized that interatrial conduction time (IACT), measured at the time of BiV device implant, could be a surrogate value for the optimal AV delay. This study determined the relationship between paced IACT and the optimal paced AV delay (PAV), as determined by echocardiography. Consecutive subjects (N = 25; age = 66 +/- 10 years; M/F: 17/8) undergoing BiV pacemaker implantation and in sinus rhythm were included. Cannulation of the coronary sinus (CS) was at the operator's discretion. A quadripolar electrophysiology catheter was inserted via the guiding sheath into the inferiolateral CS to measure left atrial depolarization. The IACT was calculated as the interval between right atrial stimulation artifact and earliest deflection on the coronary sinus catheter electrogram. Subsequently, during atrial pacing the PAV was determined using transmitral pulsed wave Doppler echocardiography (iterative method). The relationship between paced IACT and PAV was then determined. The mean +/- SD paced IACT and PAV were 126 +/- 25 msec and 157 +/- 23 msec, respectively. There was a strong positive correlation between the paced IACT and PAV (r = 0.73, P < 0.001). The equation describing the relationship was PAV = 0.68 * (IACT + 104) msec. The paced IACT has a strong correlation with the echo derived optimal PAV. This method may be used to program PAV intervals without need for echocardiography in patients undergoing BiV pacemaker implantation.


Potential treatment of Parkinson's disease with omega-3 polyunsaturated fatty acids.
Parkinson's disease (PD) is characterized by dysfunction of the nigrostriatal system, loss of dopamine neurons and intracellular aggregation of α-synuclein. Recently, both clinical and experimental studies have reported that neuroinflammation and oxidative stress markedly contribute to the etiology of PD. Current clinical pharmacotherapies only temporarily relieve the symptoms of PD, accompanied by many side effects. Hence, searching for natural anti-inflammatory, anti-oxidative and neuroprotective agents has received great attention. Polyunsaturated fatty acids (PUFAs), especially omega (n)-3, are essential lipid nutrients in the human diet and important components of cell membranes. Together by competing with the production of n-6 PUFAs, the precursors of inflammatory mediators, n-3 PUFAs can inhibit microglial activity and neuroinflammation, protect astrocyte function to produce neurotrophins, thereby normalizing neurotransmission and improving neurodegeneration. Thus, with regard to the hypotheses of PD, our and other's recent studies have demonstrated that n-3 PUFAs may improve PD by inhibiting proinflammatory cytokine release, promoting neurotrophic factor expression, recovering mitochondrial function and membrane fluidity, decreasing the levels of oxidant production, maintaining α-synuclein proteostasis, calcium homeostasis, axonal transport, and reducing endoplasmic reticulum stress. This review mainly introduces and analyzes the effect of n-3 PUFA treatments on PD-related behavioral and neuropathological abnormalities in clinical patients and different cellular and animal models of PD. Finally, the limitations and future work in n-3 PUFAs anti-PD area are discussed.


The reactive serine residue in phosphoglucomutase of Micrococcus lysodeikiticus.
1. Phosphoglucomutase of Micrococcus lysodeikticus was labelled at the active site by exchange with (32)P-labelled substrates of high specific radioactivity. 2. Partial acid hydrolysis gave rise to radioactive peptides; serine phosphate was identified as one of the derivatives. 3. Comparison of the other (32)P-labelled peptides with the peptides obtained from the (32)P-labelled rabbit muscle phosphoglucomutase indicates that the sequence around the reactive serine residue is identical in both enzymes.


Selective killing of p53-deficient cancer cells by SP600125.
The genetic or functional inactivation of p53 is highly prevalent in human cancers. Using high-content videomicroscopy based on fluorescent TP53(+/+) and TP53(-/-) human colon carcinoma cells, we discovered that SP600125, a broad-spectrum serine/threonine kinase inhibitor, kills p53-deficient cells more efficiently than their p53-proficient counterparts, in vitro. Similar observations were obtained in vivo, in mice carrying p53-deficient and -proficient human xenografts. Such a preferential cytotoxicity could be attributed to the failure of p53-deficient cells to undergo cell cycle arrest in response to SP600125. TP53(-/-) (but not TP53(+/+) ) cells treated with SP600125 became polyploid upon mitotic abortion and progressively succumbed to mitochondrial apoptosis. The expression of an SP600125-resistant variant of the mitotic kinase MPS1 in TP53(-/-) cells reduced SP600125-induced polyploidization. Thus, by targeting MPS1, SP600125 triggers a polyploidization program that cannot be sustained by TP53(-/-) cells, resulting in the activation of mitotic catastrophe, an oncosuppressive mechanism for the eradication of mitosis-incompetent cells.


Phylogenetically informed analysis of the allometry of Mammalian Basal metabolic rate supports neither geometric nor quarter-power scaling.
The form of the relationship between the basal metabolic rate (BMR) and body mass (M) of mammals has been at issue for almost seven decades, with debate focusing on the value of the scaling exponent (b, where BMR is proportional to M(b)) and the relative merits of b= 0.67 (geometric scaling) and b= 0.75 (quarter-power scaling). However, most analyses are not phylogenetically informed (PI) and therefore fail to account for the shared evolutionary history of the species they consider. Here, we reanalyze the most rigorously selected and comprehensive mammalian BMR dataset presently available, and investigate the effects of data selection and phylogenetic method (phylogenetic generalized least squares and independent contrasts) on estimation of the scaling exponent relating mammalian BMR to M. Contrary to the results of a non-PI analysis of these data, which found an exponent of 0.67-0.69, we find that most of the PI scaling exponents are significantly different from both 0.67 and 0.75. Similarly, the scaling exponents differ between lineages, and these exponents are also often different from 0.67 or 0.75. Thus, we conclude that no single value of b adequately characterizes the allometric relationship between body mass and BMR.


Inoculation with Bacillus amyloliquefaciens and mycorrhiza confers tolerance to drought stress and improve seed yield and quality of soybean plant.
The present study aimed to evaluate the effect of Bacillus amyloliquefaciens and/or Arbuscular Mycorrhizal Fungi (AMF) as natural biofertilizers on biomass, yield, and seed nutritive quality of soybean (Giza 111). The conditions investigated include a well-watered (WW) control and irrigation withholding at the seed development stage (R5, after 90 days from sowing) (DS). Co-inoculation with B. amyloliquefaciens and AMF, resulted in the highest plant biomass and yield under WW and DS conditions. The nuclear DNA content analysis suggested that co-inoculation with B. amyloliquefaciens and AMF decreased the inhibition of drought stress on both the size and granularity of seed cells, which were comparable to the normal level. The single or co-inoculation with B. amyloliquefaciens and AMF increased the primary metabolites content and alleviated the drought-induced reduction in soluble sugars, lipids, protein and oil contents. Plant inoculation induced the expression of genes involved in lipid and protein biosynthesis, whereas an opposite trend was observed for genes involved in lipid and protein degradation, supporting the observed increase in lipid and protein content. Plant inoculated with B. amyloliquefaciens showed the highest α-amylase and β-amylase activities, indicating improved osmolyte (soluble sugar) synthesis, particularly under drought. Interestingly, single or co-inoculation further strengthen the positive effect of drought on the antioxidant and osmoprotectant levels, i.e. phenol, flavonoid, glycine betaine contents, and glutathione-S-transferase (GST) activity. As a result of stress release, there was a decrease in the level of stress hormones (abscisic acid, ABA) and an increase in gibberellin (GA), trans-zeatin-riboside (ZR), and indole acetic acid (IAA) in the seeds of inoculated plants. Additionally, the ATP content, hydrolytic activities of plasma membrane H+ -ATPase, Ca2+ -ATPase, and Mg2+ -ATPase were also increased by the inoculation.


Identification and characteristics of microRNAs from army worm, Spodoptera frugiperda cell line Sf21.
microRNAs play important regulatory role in all intrinsic cellular functions. Amongst lepidopteran insects, miRNAs from only Bombyx mori have been studied extensively with a little focus on Spodoptera sp. In the present study, we identified a total of 226 miRNAs from Spodoptera frugiperda cell line Sf21. Of the total, 116 miRNAs were well conserved within other insects, like B. mori, Drosophila melanogaster and Tribolium castenum while the remaining 110 miRNAs were identified as novel based on comparative analysis with the insect miRNA data set. Landscape distribution analysis based on Sf21 genome assembly revealed clustering of few novel miRNAs. A total of 5 miRNA clusters were identified and the largest one encodes 5 miRNA genes. In addition, 12 miRNAs were validated using northern blot analysis and putative functional role assignment for 6 Sf miRNAs was investigated by examining their relative abundance at different developmental stages of Spodoptera litura and body parts of 6th instar larvae. Further, we identified a total of 809 potential target genes with GO terms for selected miRNAs, involved in different metabolic and signalling pathways of the insect. The newly identified miRNAs greatly enrich the repertoire of insect miRNAs and analysis of expression profiles reveal their involvement at various steps of biochemical pathways of the army worm.


Lymphoproliferative disorders of the ocular adnexa.
Immunodysregulation appears to play a prominent role in the evolution of some lymphomas, as evidenced by the strong associations between congenital and acquired immunodeficiencies and lymphoid neoplasia, and abnormal ratios of helper T cells in lymphoid proliferations. Lympho-proliferative diseases of the ocular adnexa encompass a spectrum of lesions that may present with similar clinical and radiological features. Most primary lymphoid proliferations of the ocular adnexa consist of small lymphocytes of B-cell origin. Employing morphological, immunohistochemical, and molecular genetic criteria, proliferations may be separated into polyclonal and monoclonal categories. Increased insight into the biology and behavior of these tumors tells us that seemingly benign, as well as frankly malignant proliferations, might disseminate to nodal or extranodal sites. The diagnosis of lymphoproliferative disease of any type necessitates a complete workup for systemic lymphoma. Major prognostic criteria for lymphomas are anatomical site, stage, and histological features. Radiotherapy is employed for localized lymphoid proliferations, with chemotherapy recommended for disseminated disease. Long-term follow-up with semiannual examination is recommended. A significant percentage of primary ocular adnexal lymphoid lesions are MALT-type lymphomas, extranodal low-grade B-cell lymphomas usually associated with mucosal tissues or glandular epithelia. The pathogenesis of this lymphoma in orbital soft tissue, which normally is devoid of lymphoid tissue, lymphatic vessels, and epithelium, is unclear. MALT-type lymphomas of the ocular adnexa follow an indolent course, with long periods between relapses, and are responsive to therapy. Dissemination, when it occurs, preferentially affects other extranodal sites.


Management of Acute Respiratory Failure Due to Community-Acquired Pneumonia: A Systematic Review.
Community-acquired pneumonia (CAP) is a leading cause of mortality worldwide. CAP mortality is driven by the development of sepsis and acute respiratory failure (ARF). We performed a systematic review of the available English literature published in the period 1 January 1997 to 31 August 2017 and focused on ARF in CAP. The database searches identified 189 articles-of these, only 29 were retained for data extraction. Of these 29 articles, 12 addressed ARF in CAP without discussing its ventilatory management, while 17 evaluated the ventilatory management of ARF in CAP. In the studies assessing the ventilatory management, the specific treatments addressed were: high-flow nasal cannula (HFNC) (n = 1), continuous positive airway pressure (n = 2), non-invasive ventilation (n = 9), and invasive mechanical ventilation (n = 5). When analyzed, non-invasive ventilation (NIV) success rates ranged from 20% to 76% and they strongly predicted survival, while NIV failure led to an increased risk of adverse outcome. In conclusion, ARF in CAP patients may require both ventilatory and non-ventilatory management. Further research is needed to better evaluate the use of NIV and HFNC in those patients. Alongside the prompt administration of antimicrobials, the potential use of steroids and the implementation of severity scores should also be considered.


Critical role of dopant in NiOx hole transport layer for mitigating redox reactivity at NiOx/absorber interface in mixed cation perovskite solar cells.
Redox chemistry transpiring at the interface of NiOx hole transport layer (HTL) and perovskite absorber is a critical phenomenon leading to relatively low values of open circuit voltage (VOC) and fill factor (FF), in turn hampering the overall device performance and stability. In this work, for the first time, the hard acid electronic nature of vanadium (V) dopant in nickel oxide HTL is opportunely exploited to mitigate the undesirable Lewis acid-base reactions occurring at the HTL/mixed-cation perovskite interface. The findings of the study show that vanadium doping results in improved interfacial energetics along with decreased VOC loss, confirming that despite the increase in Ni3+/Ni2+ ratio with the vanadium dopant, the redox reaction catalyzed by Ni3+ ions is kept under check. Vanadium doping also aided in the realization of superior perovskite films with lower Urbach energy, which translated into one order increase in maximum photoinduced carrier generation rate per unit volume. Carrier dynamics investigations show fewer defect states (lower VTFL) and trap-assisted recombination (lower diode ideality factor), which optimize the devices' photovoltaic performance. These benefits collectively contribute to low-loss charge transfer across the NiOx/mixed-cation perovskite interface, which increases the relative efficiency by ∼30% for 5 wt% V-doped NiOx devices compared to pristine NiOx devices, augmented by an increase in device J-V parameters like open circuit voltage (VOC), short circuit current density (JSC), and fill factor (FF).


NADPH oxidase-derived oxidant stress is critical for neutrophil cytotoxicity during endotoxemia.
Neutrophils can cause liver injury during endotoxemia through generation of reactive oxygen species. However, the enzymatic source of the oxidant stress and the nature of the oxidants generated remain unclear. Therefore, we investigated the involvement of NADPH oxidase in the pathophysiology by using the NADPH oxidase inhibitor diphenyleneiodonium chloride (DPI) in the galactosamine/endotoxin (700 mg/kg Gal:100 microg/kg ET) model of liver injury. In addition, we measured chlorotyrosine as indicator for hypochlorous acid formation by myeloperoxidase. Gal/ET treatment of male C3HeB/FeJ mice resulted in sinusoidal neutrophil accumulation and parenchymal cell apoptosis (14 +/- 3% of cells) at 6 h. At 7 h, 35% of neutrophils had transmigrated. The number of apoptotic cells increased to 25 +/- 2%, and the overall number of dead cells was 48 +/- 3%; many of them showed the characteristic morphology of necrosis. Hepatocytes, which colocalized with extravasated neutrophils, stained positive for chlorotyrosine and 4-hydroxynonenal (4-HNE) protein adducts. In contrast, animals pretreated with DPI (2.5 mg/kg) were protected against liver injury at 7 h (necrosis = 20 +/- 2%). These livers showed little chlorotyrosine or 4-HNE staining, but apoptosis and neutrophil accumulation and extravasation remained unaffected. However, DPI-treated animals showed serious liver injury at 9 h due to sustained apoptosis. The results indicate that NADPH oxidase is responsible for the neutrophil-derived oxidant stress, which includes formation of hypochlorous acid by myeloperoxidase. Thus NADPH oxidase could be a promising therapeutic target to prevent neutrophil-mediated liver injury. However, the long-term benefit of this approach needs to be investigated in models relevant for human liver disease.


Confocal scanning laser ophthalmoscopy in high myopic eyes in a population-based setting.
To compare the parameters of confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph [HRT] II; Heidelberg Engineering, Heidelberg, Germany) in high myopia with those in age-matched emmetropia. A population-based study in which HRT II data were analyzed from 135 healthy subjects with high myopia (spherical equivalent [SE] from -6 to -12 D) and 135 age-matched subjects with emmetropia (SE from -1 to +1 D). The HRT parameters, the correlation between disc area and ovality, and asymmetry between the right and left eyes were evaluated. High myopia was associated with greater disc ovality, smaller cup areas and cup volumes, higher rim volumes, height variation contour (HVC), and the mean retinal nerve fiber layer (RNFL) thickness compared with those parameters in emmetropia (P < or = 0.003). The intergroup differences in the rim volume and mean RNFL thickness remained significant (P = 0.003) after adjustment for the disc area and ovality. The disc area was correlated significantly (P < or = 0.002) with most parameters in both groups. The disc ovality was significantly (P = 0.005) negatively correlated with the disc area only in high myopia and significantly (P < or = 0.003) positively correlated with the rim volume, HVC, and mean RNFL thickness in both groups. Asymmetry of the mean RNFL thickness was significantly (P = 0.003) greater in high myopia than in emmetropia. The characteristics of the HRT parameters in highly myopic eyes involved smaller cup parameters and greater rim and RNFL parameters compared with emmetropic eyes. The effects of disc area and ovality on the HRT parameters in highly myopic eyes differed from those in emmetropic eyes.


Continuous lines of basophil/mast cells derived from normal mouse bone marrow.
Nonadherent tissue culture cell lines were established from normal bone marrow of a variety of mouse strains. The lines possessed morphological and histochemical markers of the basophil/mast cell and contained committed stem cells for metachromatic cells. Their derivation from normal marrow and their lack of tumorigenicity despite long-term culture makes these cell lines potentially important for studies of the mechanisms of allergic reactions and inflammation as well as the differentiation pathways involving this subset of hematopoietic cells.


Nephrotic syndrome: immunological mechanisms.
Nephrotic Syndrome (NS) is a rare diseases (around 2-7 cases per 100.000 children per year) characterized by proteinuria ≥50 mg/kg/day (or ≥40 mg/m2/h) or a proteinuria/creatininuria ratio >2 (mg/mg); hypoalbuminaemia less than 25 g/l and edema. The protein leakage, with the consequent hypoalbunaemia and edema, due to podocyte alterations may be caused by genetic diseases, immunological mechanisms, infections, toxins or malignancy. However, most commonly the exact etiology is unknow. The idiopathic NS may be classified based on response to corticosteroid therapy or the hytological appearance. The first classification identifies steroid-resistant NS (no response after 4 weeks of steroid therapy); frequently relapsing NS (≥ 2 relapses in first 6 months or ≥4 relapses in 1-year); steroid dependent NS (relapses during steroid decalage or within 2 weeks from steroid therapy interruption). The hystological classification is based on light and electron microscopy after renal biopsy, which is indicated in case of onset disease before 1 year or after 12 years of age. Macroscopic hematuria: persistent hypertension and/or microscopic hematuria and/or low plasma C3 renal failure not related to hypovolemia; steroid resistence: secondary or relatedsyndromes NS. Minimal change disease (MCD) is the most common form of idiopahtic NS in children, with good response to steroid treatment, and it is characterized by normal glomerular appearance on light microscopy and evidence of podocyte foot alterations on electron microscopy, due to immunological related damage. Focal segmental glomerulosclerosis (FSGS) is described inidiopahtic NS, particularly in steroiddependent or steroid-resistant forms, and is characterized by evidence of focal glomerular damage with secondary sclerosis and adhesion with Bowman's capsule; the electron appearance is the same of MCD one. Recent authors hypotizethat the FSGS is an evolution of MCD. These 2 idiopathic NS forms may be expression of the same immunological disease, with 2 different severity grades; so they may be considered different moments of the same disease spectrum. Less common idiopathic NS forms are membrano proliferative glomerulonephritis; membranous nephropathy; IgM-nephropathy; C1q nephropathy and thin basement membrane disease (1, 2, 3).


Global comparison of multiple-segmented viruses in 12-dimensional genome space.
We have recently developed a computational approach in a vector space for genome-based virus classification. This approach, called the "Natural Vector (NV) representation", which is an alignment-free method, allows us to classify single-segmented viruses with high speed and accuracy. For multiple-segmented viruses, typically phylogenetic trees of each segment are reconstructed for discovering viral phylogeny. Consensus tree methods may be used to combine the phylogenetic trees based on different segments. However, consensus tree methods were not developed for instances where the viruses have different numbers of segments or where their segments do not match well. We propose a novel approach for comparing multiple-segmented viruses globally, even in cases where viruses contain different numbers of segments. Using our method, each virus is represented by a set of vectors in R(12). The Hausdorff distance is then used to compare different sets of vectors. Phylogenetic trees can be reconstructed based on this distance. The proposed method is used for predicting classification labels of viruses with n-segments (n ⩾ 1). The correctness rates of our predictions based on cross-validation are as high as 96.5%, 95.4%, 99.7%, and 95.6% for Baltimore class, family, subfamily, and genus, respectively, which are comparable to the rates for single-segmented viruses only. Our method is not affected by the number or order of segments. We also demonstrate that the natural graphical representation based on the Hausdorff distance is more reasonable than the consensus tree for a recent public health threat, the influenza A (H7N9) viruses.


Genetic management of Dutch golden retriever dogs with a simulation tool.
Excessive inbreeding rates and small effective population sizes are an important problem in many populations of dogs. Proper genetic management of these populations can decrease the problem, and several measures are available. However, the effectiveness of these measures is not clear beforehand. Therefore, a simulation model was developed to test measures that aim to decrease the rate of inbreeding. The simulation program was used to evaluate inbreeding restriction measures in the Dutch golden retriever dog population. This population consisted of approximately 600 dams and 150 sires that produce 300 litters each year. The five most popular sires sire approximately 25% of the litters in a year. Simulations show that the small number of popular sires and their high contribution to the next generation are the main determinants of the inbreeding rates. Restricting breeding to animals with a low average relatedness to all other animals in the population was the most effective measure and decreased the rate of inbreeding per generation from 0.41 to 0.12%. Minimizing co-ancestry of parents was not effective in the long run, but decreased variation in inbreeding rates. Restricting the number of litters per sire generally decreased the generation interval because sires were replaced more quickly, once they met their restriction. In some instances, this lead to an increase in inbreeding rates because the next generations were more related. The simulation tool proved to be a powerful and educational tool for deciding which breeding restrictions to apply, and can be effective in different breeds and species as well.


The effects of 4-MEI on cell proliferation, DNA breaking and DNA fragmentation.
4-Methylimidazole (4-MEI) is a color widely found in cola drinks, roasted foods, grilled meats, coffee and other foods. This study was aimed to investigate the 4-MEI effects on the cell proliferation, purified circular DNA and DNA from cells of rats treated with the 4-MEI.In this study, mouse 3T3-L1 cell line was treated with 4-MEI at concentrations of 300, 450, 600 and 750 µg/mL for 24 hours and 48 hours periods, after that cytotoxic effect of the 4-MEI was studied by MTT test. Also, the effect of 4-MEI on purified circular DNA (pET22b) was investigated by treating of the DNA with 4-MEI concentrations of 300, 450, 600 and 750 µg/ml. DNA was extracted from liver cells of rats that have been treated with 4-MEI doses of 25 and 50 mg/kg for 10 week and it was subjected to agarose gel electrophoreses analyses.4-MEI significantly inhibited cell proliferation of 3T3-L1 cell line at highest concentration for 24 h and at all concentration for 48 h treatment time. DNA fragmentation assay showed that 4-MEI at 50 mg/kg concentration clearly produced characteristic DNA smear and no DNA laddering (200bp) was observed when mouse was exposed to 4-MEI. The results obtained from plasmid DNA damaging assay showed that 4-MEI has noeffect on the DNA, because the electrophoretic pattern of DNA treated with 4-MEI showed three bands on agarose gel electrophoresis as it was for untreated control. 4-MEI showed cytotoxic effect on 3T3-L1 cells but no effect on plasmid DNA breaking. According to DNA fragmentation assay 4-MEI has necrosis effects on mouse liver cells (Tab. 1, Fig. 4, Ref. 27).


Mutagenic damage among bronchiectasis patients attending in the pulmonology sector of a hospital in southern Brazil.
Bronchiectasis is a chronic respiratory disease characterized by inflammation, irreversible dilation of the bronchi, and recurrent pulmonary infections, with a high morbidity and mortality rate, but is less studied from the point of view of its prevalence and associated factors not directly related to respiratory prognosis. As it is a disease related to the exacerbation of the inflammatory process and oxidative stress, this study searched to investigate the micronucleus frequency in patients with and without bronchiectasis treated at a specialized pulmonology service in a hospital in the extreme south of Brazil. Patients with a confirmed tomographic diagnosis of bronchiectasis were defined as cases. Mutagenicity was evaluated by the micronucleus test in patients' oral mucosa cells. Data collection was performed through a questionnaire containing socioeconomic, demographic, lifestyle, and health condition information. Of the 95 patients involved in this study, 21 (22.1%) were diagnosed with bronchiectasis aged between 12 and 89 years. There was no significant difference in the frequency of micronucleus between patients with and without bronchiectasis. There was a significant positive association between age and frequency of micronucleus among patients with bronchiectasis, but this association does not occur among patients without the disease. This is the first study to investigate data on the prevalence and clinical and epidemiological aspects of this chronic disease in Brazil, especially those related to the genotoxicity outcome.


Measurement-to-measurement blood pressure variability is related to cognitive performance: the Maine Syracuse study.
The objective was to investigate the association between variability in blood pressure (BP) and cognitive function for sitting, standing, and reclining BP values and variability derived from all 15 measures. In previous studies, only sitting BP values have been examined, and only a few cognitive measures have been used. A secondary objective was to examine associations between BP variability and cognitive performance in hypertensive individuals stratified by treatment success. Cross-sectional analyses were performed on 972 participants of the Maine Syracuse Study for whom 15 serial BP clinic measures (5 sitting, 5 recumbent, and 5 standing) were obtained before testing of cognitive performance. Using all 15 measures, higher variability in systolic and diastolic BP was associated with poorer performance on multiple measures of cognitive performance, independent of demographic factors, cardiovascular risk factors, and pulse pressure. When sitting, reclining, and standing systolic BP values were compared, only variability in standing BP was related to measures of cognitive performance. However, for diastolic BP, variability in all 3 positions was related to cognitive performance. Mean BP values were weaker predictors of cognition. Furthermore, higher overall variability in both systolic and diastolic BP was associated with poorer cognitive performance in unsuccessfully treated hypertensive individuals (with BP ≥140/90 mm Hg), but these associations were not evident in those with controlled hypertension.


[Sickle cell disease in childhood in 2004].
Sickle cell disease is a genetic autosomal recessive disease of hemoglobin. The disease results from a mutation of the sixth codon of the beta-globin gene, which induces the synthesis of an abnormal hemoglobin called hemoglobin S (HbS). The polymerisation of deoxy HbS molecules causes a chronic hemolytic anemia and vaso-occlusive phenomena. The disease affects mainly people from West Indies and Sub Saharan Africa. Due to recent movements of these populations over the past years, sickle cell disease has spread across all continents. Painful crises, severe infections such as septicemia, meningitis, osteomyelytis, acute anemia episodes, and severe vaso-occlusive events, mainly neurological, are the most frequent complications affecting children. Recent progresses in the care of patients have deeply modified the prognosis. The mean life expectancy of patients is now above 40 years. The conventional treatment includes antibiotics and immunizations, analgesics, and blood transfusion. The effects of chronic blood transfusion, hydroxyurea and bone marrow transplantation are the subject of current comparative evaluations.


Using expression genetics to study the neurobiology of ethanol and alcoholism.
Recent simultaneous progress in human and animal model genetics and the advent of microarray whole genome expression profiling have produced prodigious data sets on genetic loci, potential candidate genes, and differential gene expression related to alcoholism and ethanol behaviors. Validated target genes or gene networks functioning in alcoholism are still of meager proportions. Genetical genomics, which combines genetic analysis of both traditional phenotypes and whole genome expression data, offers a potential methodology for characterizing brain gene networks functioning in alcoholism. This chapter will describe concepts, approaches, and recent findings in the field of genetical genomics as it applies to alcohol research.


Color Perspectives in Aquatic Explorations: Unveiling Innate Color Preferences and Psychoactive Responses in Freshwater Crayfish.
Color preference assay is a test for an animal's innate and adaptive response to differentiate colors and can be used as an endpoint for psychoactive activity evaluation. Several color preference test methods in aquatic animals that can be used to perform behavioral screening have been established. However, the color preference test conditions have yet to be extensively studied and standardized in aquatic invertebrates. This study aimed to replicate and optimize the previously published method to evaluate the potential color preference in freshwater crayfish based on four different approaches: species, life stages, sex, and pharmaceutical exposure. Using the optimized setup, two crayfish species display color preferences to some specific colors. P. clarkii displays more dominant color preference behavior than C. quadricarinatus in terms of color preference ranking and index. P. clarkii prefers the red color compared to other colors (red > green > blue > yellow), while C. quadricarinatus dislikes yellow compared to other colors (blue = green = red > yellow). Since P. clarkii has a more obvious color index ranking and several advantages compared to C. quadricarinatus, we conducted further tests using P. clarkii as an animal model. In the juvenile and adult stages of P. clarkii, they prefer red and avoid yellow. However, the juvenile one did not display a strong color preference like the adult one. Different sex of crayfish displayed no significant differences in their color preference responses. In addition, we also evaluated the potential effect of the antidepressant sertraline on color preference in P. clarkii and found that waterborne antidepressant exposure can significantly alter their color preference. This fundamental information collected from this study supports the crayfish color preference test as a good behavioral test to address environmental pollution.


Non-alkaloids extract from Stemona sessilifolia enhances the activity of chemotherapeutic agents through P-glycoprotein-mediated multidrug-resistant cancer cells.
One of the major impediments to the successful treatment of cancer is the development of resistant cancer cells, which could cause multidrug resistance (MDR), and overexpression of ABCB1/P-glycoprotein (P-gp) is one of the most common causes of MDR in cancer cells. Recently, natural products or plant-derived chemicals have been investigated more and more widely as potential multidrug-resistant (MDR) reversing agents. The current study demonstrated for the first time that non-alkaloids extract from Stemona sessilifolia significantly reversed the resistance of chemotherapeutic agents, adriamycin, paclitaxel and vincristine to MCF-7/ADR cells compared with MCF-7/S cells in a dose-dependent manner. The results obtained from these studies indicated that the non-alkaloids extract from S. sessilifolia plays an important role in reversing MDR of cancer as a P-gp modulator in vitro and may be effective in the treatment of multidrug-resistant cancers.


Patient-specific pediatric silicone heart valve models based on 3D ultrasound.
Patient-specific heart and valve models have shown promise as training and planning tools for heart surgery, but physically realistic valve models remain elusive. Available proprietary, simulation-focused heart valve models are generic adult mitral valves and do not allow for patient-specific modeling as may be needed for rare diseases such as congenitally abnormal valves. We propose creating silicone valve models from a 3D-printed plastic mold as a solution that can be adapted to any individual patient and heart valve at a fraction of the cost of direct 3D-printing using soft materials. Leaflets of a pediatric mitral valve, a tricuspid valve in a patient with hypoplastic left heart syndrome, and a complete atrioventricular canal valve were segmented from ultrasound images. A custom software was developed to automatically generate molds for each valve based on the segmentation. These molds were 3D-printed and used to make silicone valve models. The models were designed with cylindrical rims of different sizes surrounding the leaflets, to show the outline of the valve and add rigidity. Pediatric cardiac surgeons practiced suturing on the models and evaluated them for use as surgical planning and training tools. Five out of six surgeons reported that the valve models would be very useful as training tools for cardiac surgery. In this first iteration of valve models, leaflets were felt to be unrealistically thick or stiff compared to real pediatric leaflets. A thin tube rim was preferred for valve flexibility. The valve models were well received and considered to be valuable and accessible tools for heart valve surgery training. Further improvements will be made based on surgeons' feedback.


Involvement of Host ATR-CHK1 Pathway in Hepatitis B Virus Covalently Closed Circular DNA Formation.
The covalently closed circular (CCC) DNA of hepatitis B virus (HBV) functions as the only viral transcriptional template capable of producing all viral RNA species and is essential to initiate and sustain viral replication. CCC DNA is converted from a relaxed circular (RC) DNA, in which neither of the two DNA strands is covalently closed. As RC DNA mimics damaged cellular DNA, the host cell DNA damage repair (DDR) system is thought to be responsible for HBV CCC DNA formation. The potential role of two major cellular DDR pathways, the ataxia telangiectasia mutated (ATM) pathway and the ATM and Rad3-related (ATR) pathway, in HBV CCC DNA formation was thus investigated. Inhibition, or expression knockdown, of ATR and its downstream signaling factor CHK1, but not of ATM, decreased CCC DNA formation during de novo HBV infection, as well as intracellular CCC DNA amplification, when RC DNA from extracellular virions and intracellular nucleocapsids, respectively, is converted to CCC DNA. Furthermore, a novel RC DNA processing product with 5' truncated minus strands was detected when the ATR-CHK1 pathway was inhibited, further indicating that this pathway controls RC DNA processing during its conversion to CCC DNA. These results provide new insights into how host cells recognize and process HBV RC DNA in order to produce CCC DNA and have implications for potential means to block CCC DNA production.IMPORTANCE Hepatitis B virus (HBV) chronically infects hundreds of millions of people and remains a major cause of viral hepatitis, cirrhosis, and liver cancer. HBV persistence is sustained by a viral nuclear episome that directs all viral gene expression needed to support viral replication. The episome is converted from an incomplete DNA precursor in viral particles in an ill-understood process. We report here that the incomplete DNA precursor is recognized by the host cell in a way similar to the sensing of damaged cellular DNA for subsequent repair to form the nuclear episome. Intense efforts are ongoing to develop novel antiviral strategies to eliminate CCC DNA so as to cure chronic HBV infection. Our results here provide novel insights into, and suggest novel ways of perturbing, the process of episome formation. Furthermore, our results inform mechanisms of cellular DNA damage recognition and repair, processes essential for normal cell growth.


The Physician Anesthesia Workforce in Canada From 1996 to 2018: A Longitudinal Analysis of Health Administrative Data.
A robust anesthesia workforce is essential to the provision of safe surgical, obstetrical, and critical care but information describing the physician anesthesia workforce and volume of clinical services delivered in Canada is limited. This study examines the Canadian physician anesthesia workforce, exploring trends in physician characteristics and activity levels over time. Practice patterns of specialist anesthesiologists and family physician anesthetists (FPAs) working in urban and rural communities were of particular interest. Physicians who provided anesthesia care between 1996 and 2018 were identified using health administrative data from the Canadian Institute of Health Information (CIHI). In addition, data from the Canadian Post-MD Education Registry (CAPER) were used to characterize physicians pursuing postgraduate anesthesia training (1996-2019). Descriptive analyses of physician demographics, training, location, specialty designations, and volume of clinical services were undertaken. Between 1996 and 2018, the anesthesia workforce grew 1.8-fold to 3681 physicians, including 536 FPAs. Over the same time, nerve block services increased 7-fold, and payments for other anesthesia services increased 5-fold. The average age of the anesthesiology workforce increased by 2.3 years and the annual retirement rate was 3%. The workforce has become more gender balanced but remains predominantly male (73% in 2018). The proportion of physicians who were trained internationally (about 30%; 38% in rural areas) remained stable (and higher than that in the overall physician workforce). FPAs provided most anesthesia care in rural Canada and their attrition rate was generally 2- to 3-fold higher than specialists. Physicians in the rural anesthesia workforce provided anesthesia services more intensively over time. Relatively few FPAs who left the anesthesia workforce entered full retirement and they instead contributed other medical services to their communities. This study provides foundational information regarding anesthesia workforce capacity over a 22-year period, including insights into demographics, locations of practice, and clinical volumes. The results do not quantify the gap between service capacity and need; however, they support the need for a national workforce strategy to achieve equitable access to sustainable anesthesia services in Canada, particularly for rural communities.


Impaired beta-cell responses improve when fasting blood glucose concentration is reduced in non-insulin-dependent diabetes.
Pancreatic beta-cell responses to a controlled intravenous glucose stimulus in 18 untreated non-insulin-dependent diabetic patients were compared with those in seven healthy control subjects. The patients' first-and second-phase responses were only 10 to 20 per cent of those of the normal subjects. However, when normal subjects had been hyperglycaemic for two hours, their first-phase responses were similar to those of the patients. Six patients were subsequently treated by diet alone, six by diet and tolbutamide and six by diet and metformin. There was no improvement in first-phase responses after treatment, but second-phase responses doubled. Improved responses were seen with all treatments, and correlated with the fall in fasting blood glucose concentration during treatment. This study supports the view that hyperglycaemia impairs beta-cell function and suggests that first-phase responses are more sensitive to hyperglycaemia than second-phase responses.


[Study on the application of methybenzeneazosalicylfluorone to spectrophotometric determination of microelement molybdenum modality distributions in soy hydrolysate hydrolyzed by enzymes].
A new method has been developed for spectrophotometric determination of molybdenum modality distributions in soy hydrolysate hydrolyzed by enzymes, based on the study on the color reaction of methybenzeneazosalicylfluorone (abbreviated as MBASF) with molybdenum (VI). In hydrochloric acid medium, MBASF reacts with molybdenum (VI) sensitively to form a stable red complex, its apparent molar absorptivity is 1.54 L x mol(-1) x cm(-1), and 0-12 microg of molybdenum obeys Beer's law in 25 mL of solution. Besides normal metal ions, protein, peptide and amino acid also have high tolerance limits. Soy hydrolysate hydrolyzed by enzyme (A) was precipitated at its isoelectric point, and the filtrate (B) was obtained. Subsequently, B was transferred to the chromatogram column with D301R resin. The column was purged by using 20 mL of HAc-NaAc (pH 3.6) and NH4Cl-NH3 x H2O buffer solution(pH 9) orderly and the effluent solutions C and D were obtained. A, B, C and D solutions were used for the spectrophotometric determination of total molybdenum, hydrolyzed molybdenum, chelated molybdenum by peptide or amino acid, and dissociative molybdenum, respectively.


Current trends in dental implants.
Tooth loss is very a very common problem; therefore, the use of dental implants is also a common practice. Although research on dental implant designs, materials and techniques has increased in the past few years and is expected to expand in the future, there is still a lot of work involved in the use of better biomaterials, implant design, surface modification and functionalization of surfaces to improve the long-term outcomes of the treatment. This paper provides a brief history and evolution of dental implants. It also describes the types of implants that have been developed, and the parameters that are presently used in the design of dental implants. Finally, it describes the trends that are employed to improve dental implant surfaces, and current technologies used for the analysis and design of the implants.


Construction and demonstration of a multispectral tomographic scanning imager (TOSCA).
This work presents the first experimental demonstrator of an imager based on a tomographic scanning (TOSCA) principle. The device described generates a stream of multispectral images of a scene or target using simple conical scan optics and a simple patterned reticle, followed by collecting optics and one or several single pixel detectors. Tomographic processing techniques are then applied to the one-dimensional signals to reproduce two-dimensional images. Various aspects of the design and construction are described, and resulting images and movies are shown.


Vertebral hemangioma: an important differential in the evaluation of locally aggressive spinal lesions.
A case report and a discussion of recent published data. To highlight the importance of vertebral hemangioma (VH) as a differential diagnosis in the evaluation of locally aggressive spinal lesions. VH commonly occur as incidental findings, however, locally aggressive VH have been described. Difficulties in diagnosing these lesions are well reported and relate to changes in fat content causing uncharacteristic appearances on imaging. The management options for these lesions include a combination of observation, embolization, sclerotherapy, surgical decompression, or stabilization and radiotherapy. A 45-year-old patient who was previously well presented with back pain and rapidly progressive paraparesis. Imaging confirmed the presence of an extensive lesion centered within the right T3 vertebral pedicle with intrusion into the spinal canal. Urgent surgical decompression was undertaken and was complicated by extensive intraoperative hemorrhage requiring massive transfusion. Histologically, the lesion was shown to be a cavernous VH with no evidence of malignancy. Following radiation oncology review, he was offered adjuvant radiotherapy to minimize the risks of recurrence. He achieved a near full neurologic recovery within 2 weeks and had a full recovery by 12 months. VH should be considered in the evaluation of locally aggressive spinal lesions. Angiography is a useful adjunct in the evaluation of these lesions, both as a diagnostic and therapeutic tool. After diagnosed correctly a wide range of treatment options exist that may prevent the patient from undergoing major surgical resection and reconstruction procedures, which may be associated with high rates of morbidity.


Small joint involvement: a systematic roentgenographic study in rheumatoid arthritis.
Standard hand and foot roentgenograms from 200 consecutively hospitalised patients with definite or classical rheumatoid arthritis (RA) were read for marginal erosions by three independent observers. For each joint or group of joints analysed the degree of symmetry (S = absolute symmetry, U = unilateral, PS = partial symmetry) was determined. The total number of joints affected significantly correlated only with disease duration; symmetry of erosions and number of affected patients were not influenced by seropositivity. Metatarsophalangeal erosions (in 70%) were the most common and were classified as S in 16%, U in 21%, and PS in 63%. Metacarpophalangeal erosions (in 68%) were also common, with a symmetry pattern of S in 19%, U in 21%, and PS in 60%. Proximal finger interphalangeal erosions (in 42%) were unilateral in 42% (S in 8% and PS in 50%). The only site where symmetry was usual (90%) was the wrist, but radiocarpal and intercarpal joints were considered together. Erosions also occurred in about 16% of the finger distal interphalangeal and 28% of the great toe interphalangeal joints. In RA roentgenographic asymmetry is usual and unilateral involvement common.


A simulation study to rescue the Na+/Ca2+ exchanger knockout mice.
The Na(+)/Ca(2+) exchanger (NCX) is the major Ca(2+) efflux system in cardiac myocytes, and thereby its global knockout is embryonically lethal. However, Henderson et al. (2004) found that mice with the cardiospecific knockout of NCX1 lived to adulthood. No adaptation was detected in expression levels of other proteins except for a 50% reduction in the L-type Ca(2+) current (I(CaL)) as revealed in electrophysiological studies. To predict mechanisms of survival, we simulated cardiac myocyte activity in the absence of NCX using a mathematical model of guinea pig ventricular myocytes. The NCX knockout resulted in contracture of the model cell because of a rise in the cytoplasmic Ca(2+) ([Ca(2+)](i)). However, up-regulation of the sarcolemmal Ca(2+) pump (PMCA) and/or down-regulation of I(CaL) enables steady rhythmic contractions even if NCX is totally excluded. The simulation predicted that the steady activities are maintained by a functional up-regulation of PMCA by about 2.3 times in addition to the down-regulation of I(CaL) to a half, as observed in the experiment. However, the model analysis predicted that the myocyte depending on PMCA for Ca(2+) extrusion is unstable against any changes in ionic fluxes and energetically unfavorable in comparison with the control. The reason for the instability is that the activity of PMCA driven by the ATP hydrolysis is hardly affected by changes in [Ca(2+)](i), but NCX has a reversal potential in the middle level of the action potential and is immediately affected by the Ca(2+) flux via NCX itself. The source code of the model is available at http://www.sim-bio.org/.


On the Anglocentricities of current reading research and practice: the perils of overreliance on an "outlier" orthography.
In this critique of current reading research and practice, the author contends that the extreme ambiguity of English spelling-sound correspondence has confined reading science to an insular, Anglocentric research agenda addressing theoretical and applied issues with limited relevance for a universal science of reading. The unique problems posed by this "outlier" orthography, the author argues, have focused disproportionate attention on oral reading accuracy at the expense of silent reading, meaning access, and fluency, and have significantly distorted theorizing with regard to many issues-including phonological awareness, early reading instruction, the architecture of stage models of reading development, the definition and remediation of reading disability, and the role of lexical-semantic and supralexical information in word recognition. The dominant theoretical paradigm in contemporary (word) reading research--the Coltheart/Baron dual-route model (see, e.g., J. Baron, 1977; M. Coltheart, 1978) and, in large measure, its connectionist rivals--arose largely in response to English spelling-sound obtuseness. The model accounts for a range of English-language findings, but it is ill-equipped to serve the interests of a universal science of reading chiefly because it overlooks a fundamental unfamiliar-to-familiar/novice-to-expert dualism applicable to all words and readers in all orthographies.


Association Between Marijuana Use and Cardiovascular Disease in US Adults.
Introduction The prevalence of marijuana use has increased by about 16% since 2006, translating to approximately 200 million people worldwide. Being so widely used, long-term effects of marijuana use on cardiovascular health are largely unknown. Previous studies have had conflicting results, either showing marijuana use having a negative impact or no significant impact on cardiovascular health. This study aims to add evidence regarding the impact marijuana use has on the prevalence of cardiovascular disease. Methods This retrospective study was conducted using the Behavioral Risk Factor Surveillance System (BRFSS) database. Patients who completed the questionnaire and answered all questions in relation to marijuana use and the diagnosis of cardiovascular disease in 2017 were a part of this study. Subjects were excluded if they were children (<18 years old) or had missing data for marijuana use or cardiovascular disease. Age, gender, race/ethnicity, body mass index (BMI), income, exercise, tobacco use, alcohol use, and depression were all considered as potential confounders. Bivariate analysis was conducted to find an initial association between marijuana use and cardiovascular disease, which was followed by a multivariate regression analysis to adjust for confounders. Odds ratios and 95% confidence intervals were calculated. Results A total of 56,742 subjects were included in the analysis. The unadjusted bivariate analysis showed a reduced prevalence of cardiovascular disease in individuals using marijuana (OR 0.65, 95%CI [0.50-0.84]). After adjustment with all additional variables, an adjusted model showed a similar odds ratio, but statistical significance of the association was lost (OR 0.74, 95%CI [0.54-1.01]). Discussion A systematic review by Ravi et al in 2018, which looked at marijuana use, cardiovascular risk factors, and clinical outcomes concluded that there was insufficient data to make conclusions regarding the effect of marijuana use and negative long-term cardiovascular effects. Our study lends support to the notion that marijuana use does not have an association with cardiovascular disease. A limitation in our study was that there was missing data from the BRFSS questionnaire due to participants not fully answering all questions concerning cardiovascular disease and marijuana use. This decreased our sample size from 67,974 to 56,742 subjects. The missing participants led to a decrease in the power of our odds ratio, which may have impacted statistical significance of our results. Conclusion Although previous literature has shown that marijuana use has a negative impact on cardiovascular health, our study suggests that users and non-users of marijuana did not have an association with the prevalence of cardiovascular disease. Varying levels of support within the literature highlights the need for further research of this association.


Responses of the Necrotrophic Fungus Alternaria brassisicola to the Indolic Phytoalexin Brassinin.
Alternaria brassicicola causes black spot disease in Brassicaceae. During host infection, this necrotrophic fungus is exposed to various antimicrobial compounds, such as the phytoalexin brassinin which is produced by many cultivated Brassica species. To investigate the cellular mechanisms by which this compound causes toxicity and the corresponding fungal adaptive strategies, we first analyzed fungal transcriptional responses to short-term exposure to brassinin and then used additional functional approaches. This study supports the hypothesis that indolic phytoalexin primarily targets mitochondrial functions in fungal cells. Indeed, we notably observed that phytoalexin treatment of A. brassicicola disrupted the mitochondrial membrane potential and resulted in a significant and rapid decrease in the oxygen consumption rates. Secondary effects, such as Reactive oxygen species production, changes in lipid and endoplasmic reticulum homeostasis were then found to be induced. Consequently, the fungus has to adapt its metabolism to protect itself against the toxic effects of these molecules, especially via the activation of high osmolarity glycerol and cell wall integrity signaling pathways and by induction of the unfolded protein response.


The macrophage as a production site for hematopoietic regulator molecules: sensing and responding to normal and pathophysiological signals.
Several functional capacities of the macrophage enable it to act as an "administrator" cell for normal and pathophysiological hemopoietic regulation. Its capacity of sensing and responding to physiso-chemical, cellular and humoral signals indicates that it can regulate myelomonocytopoiesis and erythropoiesis. This occurs by modulating colony stimulating factor and erythropoietin production in response to lactoferrin and oxygen tension respectively. Detection of erythropoietin gene expression in macrophages, both in vitro and in vivo, implies that the macrophage is an "active" member of the hemopoietic cellular microenvironment. Since a subpopulation of macrophages is responsible for this function, a model is proposed in which other hemopoietic regulator molecules may be produced by distinct subpopulations of macrophages under steady-state conditions.


cDNA cloning and characterization of human monocyte/macrophage serine esterase-1.
Human monocyte/macrophage serine esterase (HMSE), commonly known as acid esterase or alpha-naphthylacetate esterase, comprises a group of five enzyme variants that can be distinguished by their isoelectric points from esterase variants of the other normal human blood cell populations. A cDNA for one of the monocytic enzyme variants (HMSE1) was cloned from a U-937 lambda gt11 cDNA library by screening with an oligonucleotide mixture designed according to amino acid sequence data of the purified enzyme. The cDNA contains 1,727 bp with an open reading frame of 1,512 bp coding for a protein of 503 amino acid residues. HMSE1 cDNA represents the first cloned monocyte/macrophage-specific serine esterase and its sequence shows up to 77% homology to other known serine esterases of different species. The amino acid composition of the putative active site of HMSE1 as deduced from the nucleotide sequence corresponds with the active sites of other serine esterases but not with the active sites of serine proteases. Hybridization of the cDNA with RNA of separated normal blood cell populations and hematopoietic cell lines shows restricted expression within the monocyte/macrophage lineage.


Mutants of Escherichia coli unable to make protein at 42 C.
Members of a collection of mutants of Escherichia coli unable to form colonies on nutrient agar at 42 C have been characterized on the basis of their growth response to a shift from 32 to 42 C in liquid medium. Forty-four mutants, which show an abrupt, nonlethal cessation of growth when moved to the restrictive temperature, have been characterized with respect to the effect of the mutation responsible for temperature sensitivity on deoxyribonucleic acid, ribonucleic acid, and protein synthesis. In 12 mutants, the mutation causing temperature sensitivity of growth primarily affects protein synthesis, in each case through an altered aminoacyl-transfer ribonucleic acid synthetase. Mutants with temperature-sensitive glutamyl-, phenylalanyl-, and valyl-transfer ribonucleic acid synthetases have been obtained, and the genes specifying these enzymes have been mapped by conjugation and transduction. Another mutant has been shown to possess a temperature-sensitive tryptophanyl-transfer ribonucleic acid synthetase, but this is not responsible for inability to grow at 42 C on media containing tryptophan.


Ultrasound assessment of scald scars in Asian children receiving pressure garment therapy.
Scar formation after scald injury in children is managed commonly by application of pressure garment. The duration of the treatment depends on clinical assessment. The objective of the study was to evaluate the efficacy of the pressure garment therapy and to correlate the clinical assessment scar thickness with ultrasound measurement. Prospective study of children with hypertrophic scars receiving pressure garment therapy was carried out between 1993 and 1998. The scars were mapped with paper cutting. Representative scar sites were scored clinically according to Vancouver General Hospital Burn Assessment Scale (pigmentation, vascularity, pliability, height, pain, itchiness). Blind to the clinical results, 2 radiologists measured the scar thickness of the same sites with ultrasonography (5 to 10 MHz transducer, General Electric LOGIQ 500). The correlation between the clinical scores and ultrasound measurement of scar thickness were analysed using analysis of variance (ANOVA). The median age of 58 children with scald injury (M:F = 36:22) was 2.8 years (0.5 to 15.8 years). The mean percentage of scald was 8.8% (24% had scald area >10%). In addition, there were 5 children with burn from naked flame and 9 children with keloid secondary to surgical incisions. With pressure garment therapy, the scar thickness reached a plateau 1 (1/2) years after the injury and began to decline gradually thereafter. The clinical estimation of scar thickness correlated well with the ultrasound measurement (ANOVA, P =.003, Adjusted R square = 0.99). The accuracy rate of clinical thickness estimation was 67%. Overestimation and underestimation accounted for 15% and 18%, respectively. There also was good correlation between total clinical score and the ultrasound measurement (ANOVA, P <.001). In children with scald injury, the pressure garment needs to be continued for a minimum of 1 year. Ultrasound measurement correlates well with overall score of the Vancouver General Hospital Burn Assessment Scale but not individual components of the scoring system except wound height.


[Scanning electron microscopical observations on Pagumogonimus skrjabini metacercaria and juveniles].
The present paper reports on the results of scanning electron microscopical observations on seven excysted metacercariae and twelve juveniles of Pagumogonimus skrjabini. The former were from the naturally excysted metacercariae in fresh water in Ningquang District of Shaanxi Province and the latter were collected from the dogs and rats experimentally infected with metacercariae from the District mentioned above. Both excysted metacercariae and juveniles have tegumental ridges or folds on the surface of the body. The anterior two-thirds of the body surface are covered with many dome-shaped sensory papillae. There are rings of this kind of papillae on the rim of oral and ventral suckers. The papillae being obviously in decreasing number in the 30-40-day-old juveniles and adult worms. Except for the suckers and excretory pores, the whole body surface of the metacercariae and the juveniles are covered with posteriorly pointing tegumental spines which are relatively denser in the forebody than in the hindbody. Spines around the oral sucker are bayonet-shaped, and those on the rest part of the body surface are basically chisel-shaped. The authors considered it important that spines of P. skrjabini can be arranged singly or in groups.


Arsenic methylation capacity is associated with breast cancer in northern Mexico.
Exposure to environmental contaminants, dietary factors and lifestyles may explain worldwide different breast cancer (BC) incidence. Inorganic arsenic (iAs) in the drinking water is a concern in many regions, such as northern Mexico. Studies in several countries have associated the proportion of urinary monomethylarsenic (%MMA) with increased risks for many As-related diseases, including cancer. To investigate the potential relationships between the risk of BC and the capacity to methylate iAs, a hospital-based case-control study (1016 cases/1028 controls) was performed in northern Mexico. Women were directly interviewed about their reproductive histories. The profile of As metabolites in urine was determined by HPLC-ICP-MS and methylation capacity was assessed by metabolite percentages and indexes. Total urinary As, excluding arsenobetaine (TAs-AsB), ranged from 0.26 to 303.29μg/L. Most women (86%) had TAs-AsB levels below As biological exposure index (35μg/L). Women with higher %MMA and/or primary methylation index (PMI) had an increased BC risk (%MMA ORQ5vs.Q1=2.63; 95%CI 1.89,3.66; p for trend <0.001; PMI ORQ5vs.Q1=1.90; 95%CI 1.39,2.59, p for trend <0.001). In contrast, women with higher proportion of urinary dimethylarsenic (%DMA) and/or secondary methylation index (SMI) had a reduced BC risk (%DMA ORQ5vs.Q1=0.63; 95%CI 0.45,0.87, p for trend 0.006; SMI ORQ5vsQ1=0.42, 95%CI 0.31,0.59, p for trend <0.001). Neither %iAs nor total methylation index was associated to BC risk. Inter-individual variations in iAs metabolism may play a role in BC carcinogenesis. Women with higher capacity to methylate iAs to MMA and/or a lower capacity to further methylate MMA to DMA were at higher BC risk.


Quadrilateral space syndrome: the Mayo Clinic experience with a new classification system and case series.
Quadrilateral space syndrome (QSS) arises from compression or mechanical injury to the axillary nerve or the posterior circumflex humeral artery (PCHA) as they pass through the quadrilateral space (QS). Quadrilateral space syndrome is an uncommon cause of paresthesia and an underdiagnosed cause of digital ischemia in overhead athletes. Quadrilateral space syndrome can present with neurogenic symptoms (pain and weakness) secondary to axillary nerve compression. In addition, repeated abduction and external rotation of the arm is felt to lead to injury of the PCHA within the QSS. This often results in PCHA thrombosis and aneurysm formation, with distal emboli. Because of relative infrequency, QSS is rarely diagnosed on evaluation of athletes with such symptoms. We report on 9 patients who presented at Mayo Clinic with QSS. Differential diagnosis, a new classification system, and the management of QSS are discussed, with a comprehensive literature review. The following search terms were used on PubMed: axillary nerve, posterior circumflex humeral artery, quadrilateral space, and quadrangular space. Articles were selected if they described patients with symptoms from axillary nerve entrapment or PCHA thrombosis, or if related screening or imaging methods were assessed. References available within the obtained articles were also pursued. There was no date or language restriction for article inclusion; 5 studies in languages besides English were reported in German, French, Spanish, Turkish, and Chinese.


Type II non-ribosomal peptide synthetase proteins: structure, mechanism, and protein-protein interactions.
Covering: 1990 to 2019 Many medicinally-relevant compounds are derived from non-ribosomal peptide synthetase (NRPS) products. Type I NRPSs are organized into large modular complexes, while type II NRPS systems contain standalone or minimal domains that often encompass specialized tailoring enzymes that produce bioactive metabolites. Protein-protein interactions and communication between the type II biosynthetic machinery and various downstream pathways are critical for efficient metabolite production. Importantly, the architecture of type II NRPS proteins makes them ideal targets for combinatorial biosynthesis and metabolic engineering. Future investigations exploring the molecular basis or protein-protein recognition in type II NRPS pathways will guide these engineering efforts. In this review, we consolidate the broad range of NRPS systems containing type II proteins and focus on structural investigations, enzymatic mechanisms, and protein-protein interactions important to unraveling pathways that produce unique metabolites, including dehydrogenated prolines, substituted benzoic acids, substituted amino acids, and cyclopropanes.


Is there an irritable bladder in the irritable bowel syndrome?
In this prospective case controlled study 16 premenopausal women with documented irritable bowel syndrome were recruited from the gastroenterology clinic and 16 premenopausal controls without symptoms of irritable bowel syndrome were recruited from the gynaecology clinic. All women answered a standardised bowel and urinary symptom questionnaire and underwent twin channel subtracted cystometry. Women with irritable bowel syndrome also underwent oesophageal balloon distension studies for perception and pain. Oesophageal and bladder sensory thresholds were compared. Urinary frequency and urgency and the urodynamic finding of detrusor instability were significantly more common in women with irritable bowel syndrome (P < 0.05). We were unable to demonstrate a relationship between first sensation of bladder fullness and oesophageal perception or between maximum bladder capacity and oesophageal pain thresholds. These findings suggest that there is an irritable bladder in the irritable bowel syndrome and support the concept that irritable bowel syndrome is part of a generalised disorder of smooth muscle.


Acetabular and femoral reconstruction with impacted graft and cement.
Loosening of primary cemented and noncemented components of total hip arthroplasties always is accompanied by a loss of bone stock. There are several options for reconstruction of the acetabular and femoral defects. The authors' treatment of choice is a standardized cemented revision procedure with tight impaction of morsellized cancellous autograft or allograft chips in acetabular and femoral reconstructions. In this study, the clinical and radiographic evaluation of acetabular defects reconstructed with impacted morsellized allograft femoral heads was described. A cemented cup supplemented with morsellized cancellous grafts and wire meshes in cases of segmental defects was sufficiently stable to allow for complete graft consolidation. After a mean followup of 70 months of 88 hips, 4 cases of clinical failures (including 1 infection) and 6 cases of radiologic failure of the reconstructions were observed, resulting in a failure percentage of 11.4% after 5 years. Autografts and allografts were equally effective. Because the clinical success of the technique also was supported by the results of histologic and biomechanic studies in animals, the authors were encouraged to continue this technique, not only in the acetabulum, but also in the femur.


Factors influencing the chemical stability of carotenoids in foods.
In recent years, a number of studies have produced evidence to suggest that consuming carotenoids may provide a variety of health benefits including a reduced incidence of a number of cancers, reduced risk of cardiovascular disease, and improved eye health. Evolving evidence on the health benefits of several carotenoids has sparked interest in incorporating more carotenoids into functional food products. Unfortunately, the same structural attributes of carotenoids that are thought to impart health benefits also make these compounds highly susceptible to oxidation. Given the susceptibility of carotenoids to degradation, particularly once they have been extracted from biological tissues, it is important to understand the major mechanisms of oxidation in order to design delivery systems that protect these compounds when they are used as functional food ingredients. This article reviews current understanding of the oxidation mechanisms by which carotenoids are degraded, including pathways induced by heat, light, oxygen, acid, transition metal, or interactions with radical species. In addition, several carotenoid delivery systems are evaluated for their potential to decrease carotenoid degradation in functional food products.


Mutation of nonessential cysteines shows that the NF-κB essential modulator forms a constitutive noncovalent dimer that binds IκB kinase-β with high affinity.
NEMO (NF-κB essential modulator) associates with catalytic subunits IKKα and IKKβ to form the IκB kinase (IKK) complex and is a key regulator of NF-κB pathway signaling. Biochemical and structural characterization of NEMO has been challenging, however, leading to conflicting data about basic biochemical properties such as the oligomeric state of active NEMO and its binding affinity for IKKβ. We show that up to seven of NEMO's 11 cysteine residues can be mutated to generate recombinant full-length NEMO that is highly soluble and active. Using a fluorescence anisotropy binding assay, we show that full-length NEMO binds a 44-mer peptide encompassing residues 701-745 of IKKβ with a K(D) of 2.2 ± 0.8 nM. The IKKβ binding affinities of mutants with five and seven Cys-to-Ala substitutions are indistinguishable from that of wild-type NEMO. Moreover, when expressed in NEMO -/- fibroblasts, the five-Ala and seven-Ala NEMO mutants can interact with cellular IKKβ and restore NF-κB signaling to provide protection against tumor necrosis factor α-induced cell death. Treatment of the NEMO-reconstituted cells with H₂O₂ led to the formation of covalent dimers for wild-type NEMO and the five-Ala mutant, but not for the seven-Ala mutant, confirming that Cys54 and/or Cys347 can mediate interchain disulfide bonding. However, the IKKβ binding affinity of NEMO is unaffected by the presence or absence of interchain disulfide bonding at Cys54, which lies within the IKKβ binding domain of NEMO, or at Cys347, indicating that NEMO exists as a noncovalent dimer independent of the redox state of its cysteines. This conclusion was corroborated by the observation that the secondary structure content of NEMO and its thermal stability were independent of the presence or absence of interchain disulfide bonds.