Worldwide scientific productions with immunotherapy of sepsis: a bibliometric analysis.
Sepsis represents a significant healthcare problem worldwide and causes a high number of deaths every year but remains to be fully understood. During and after sepsis, the host immune response is complex and involves an initial excessive host inflammatory response to infection that is closely related to tissue damage and leads to organ failure. Over the past three decades, immunotherapy for sepsis has vastly improved, but in this area, the most influential articles, journals, authors, and countries have not yet been completely summarized and analyzed. Performed a bibliometric analysis on all the articles concerning immunotherapy for sepsis from 1962 to 2019 was our objective, and we also explored the potential correlations between publications of different countries and their gross domestic product (GDP). All articles about immunotherapy for sepsis were extracted from the Scopus database and analyzed. We also retrieved GDP data from all the countries that have published information from the World Bank. In summary, we have retrieved 1,483 related articles from the Scopus database starting from the first publication on immunotherapy for sepsis in 1962 through March 16, 2019. Over the past decade, the number of the articles published has increased year by year to reach 866 in total, which accounts for about 58% of all publications, with 2017 being the most prolific year when 179 articles were published. The US published 604 articles (41%), followed by China (n = 163, 11%), and Germany (n = 158, 11%). In terms of publishing media, the journal that published the highest number of the articles was Journal of Critical Care Medicine with 65 articles (4%), followed by Shock with 55 articles (4%), and Critical Care with 35 articles (2%). There was a strong correlation between the GDP of the different countries and their publication numbers (r = 0.811, P < 0.001). Our present study analyzed all types of articles concerning immunotherapy for sepsis over the past 57 years and countries with high GDP tends to make more contributions to the medical field of this field. In the meantime, these studies highlight the importance of immunotherapy in the treatment of sepsis patients. The recognition of the historical status and development trend of this field can promote inter-agency cooperation, guide future research, and ultimately provide the basis for clinical practice guidelines.


Pro-NGF secreted by astrocytes promotes motor neuron cell death.
It is well established that motor neurons depend for their survival on many trophic factors. In this study, we show that the precursor form of NGF (pro-NGF) can induce the death of motor neurons via engagement of the p75 neurotrophin receptor. The pro-apoptotic activity was dependent upon the presence of sortilin, a p75 co-receptor expressed on motor neurons. One potential source of pro-NGF is reactive astrocytes, which up-regulate the levels of pro-NGF in response to peroxynitrite, an oxidant and producer of free radicals. Indeed, motor neuron viability was sensitive to conditioned media from cultured astrocytes treated with peroxynitrite and this effect could be reversed using a specific antibody against the pro-domain of pro-NGF. These results are consistent with a role for activated astrocytes and pro-NGF in the induction of motor neuron death and suggest a possible therapeutic target for the treatment of motor neuron disease.


Delivery of midinfrared (6 to 7-microm) laser radiation in a liquid environment using infrared-transmitting optical fibers.
Ablation at wavelengths near lambda = 6.45 microm results in tissue ablation with minimal collateral damage (< 40 microm) yet yields a high ablation rate that is useful for human surgery. However, delivery of this wavelength has been limited to that in air and thus to applications in which the target tissue can be readily exposed. The goal of this study is to investigate the potential of a pulsed infrared laser at lambda = 6.45 microm for noncontact ablation in a liquid environment. To this end we investigated fiber delivery in combination with the use of infrared transparent liquids. Transmission characteristics and damage thresholds for two types of fiber materials (silver halide and arsenic sulfide), for high-power pulsed laser radiation were determined using the Mark III free electron laser. Both fibers had comparable bulk losses (0.54 dB/m and 0.62 dB/m, respectively) while the arsenic sulfide fibers showed more coupling losses (37 versus 27%). Damage thresholds were higher in arsenic sulfide fibers than in silver halide fibers (1.12 GW/cm2 versus 0.54 GW/cm2), but both fibers were sufficient to deliver radiant exposures well above the ablation threshold in tissue. Seven different perfluorocarbon liquids (PFCLs), known for their transparency at lambda = 2.94 microm, were investigated and their optical transmission was determined using Fourier transform infrared and direct Beer's law measurements. All of the PFCLs tested had similar values for an absorption coefficient mu(a) at a given wavelength (mu(a) = 0.05 mm(-1) at lambda = 2.94 microm and mu(a) is approximately 3 mm(-1) at lambda = 6.45 microm). Pump-probe imaging showed the ablation sequence (lambda = 6.45 microm) at the fiber tip in a water environment, which revealed a fast expanding and collapsing bubble. In contrast, the volatile PF-5060 showed no fast bubble expansion and collapse, but rather formation of nontransient gas bubbles. Perfluorodecalin did not show any bubble formation at the radiant exposures used. It was shown that using the lambda = 6.45 microm wavelength delivered via fiber optics in combination with perfluorodecalin allows a noncontact laser surgical procedure. Deeper structures, however, are effectively shielded because the radiant exposure of the beam will fall below the ablation threshold owing to the absorption by perfluorodecalin. This may optimize the efficacy and safety of laser-based vitreoretinal surgery.


Levodopa-refractory hyperprolactinemia and pituitary findings in inherited disorders of biogenic amine metabolism.
Elevated serum prolactin concentrations occur in inherited disorders of biogenic amine metabolism because dopamine deficiency leads to insufficient inhibition of prolactin secretion. This work from the International Working Group on Neurotransmitter Related Disorders (iNTD) presents the results of the first standardized study on levodopa-refractory hyperprolactinemia (LRHP; >1000 mU/L) and pituitary magnetic resonance imaging (MRI) abnormalities in patients with inherited disorders of biogenic amine metabolism. Twenty-six individuals had LRHP or abnormal pituitary findings on MRI. Tetrahydrobiopterin deficiencies were the most common diagnoses (n = 22). The median age at diagnosis of LRHP was 16 years (range: 2.5-30, 1st-3rd quartiles: 12.25-17 years). Twelve individuals (nine females) had symptoms attributed to hyperprolactinemia: menstruation-related abnormalities (n = 7), pubertal delay or arrest (n = 5), galactorrhea (n = 3), and decreased sexual functions (n = 2). MRI of the pituitary gland was obtained in 21 individuals; six had heterogeneity/hyperplasia of the gland, five had adenoma, and 10 had normal findings. Eleven individuals were treated with the dopamine agonist cabergoline, ameliorating the hyperprolactinemia-related symptoms in all those assessed. Routine monitoring of these symptoms together with prolactin concentrations, especially after the first decade of life, should be taken into consideration during follow-up evaluations. The potential of slow-release levodopa formulations and low-dose dopamine agonists as part of first-line therapy in the prevention and treatment of hyperprolactinemia should be investigated further in animal studies and human trials. This work adds hyperprolactinemia-related findings to the current knowledge of the phenotypic spectrum of inherited disorders of biogenic amine metabolism.


Complex, high-risk, and indicated percutaneous coronary angioplasty in essentially calcified stented coronary lesions using excimer laser coronary atherectomy with contrast mix injection.
Complex, coronary stenosis remains a technical challenge that may be responsible for in-stent restenosis and vessel thrombosis. Here we investigated the efficacy and safety of excimer laser coronary atherectomy (ELCA) with contrast mix injection for improving vessel wall stent apposition in undilatable, mostly calcified lesions. To assess ELCA with contrast mix injection in complex, stented, calcified coronary lesions. This prospective single-center observational study enrolled 52 consecutive patients (73 lesions), with suboptimal stents implanted in de novo lesions and lesions requiring in-stent restenosis (ISR) due to stent underexpansion using all available means to achieve an optimal result. Patients presenting with ST-segment elevation myocardial infarction were excluded. All patients underwent coronary angiography 6 months after ELCA with intravascular ultrasound or optical coherence tomography study. We used contrast media mixed with saline (25-75%) to supply maximum laser energy output when a standard approach was unsuccessful. Procedural success was defined as relative stent expansion of > 80% minimal stent area (MSA) divided by average reference lumen area. Procedural success was achieved in all cases. The cross-sectional area measured in treated segment improved significantly from 2.9 (0.72) mm2 to 7.3 (0.79) mm2 after ELCA. The in-hospital device-oriented major adverse cardiac event (DOCE) rate was 9.6%. No vessel perforation occurred during ELCA. After 6 months, the DOCE rate was 13.4%, while the rate of target lesion revascularization (TLR) was 8.2%. This registry confirms the efficacy and safety of ELCA with contrast mix injection as a possible approach for stent expansion/ISR in failed PCI.


Cutaneous and systemic vasculitis: cellular players and pathogenetic aspects.
Vascular wall damage, inflammatory cell recruitment and subsequent structural remodelling define a vasculitic process. Histopathological classification of vasculitis is based on the caliber of the vessel involved and on the prevalent type of inflammatory cells (neutrophils in acute forms, lymphocytic for chronic, histiocytic for granulomatous). A large amount of information is emerging from the literature on the complex pathophysiology of the cellular components of vessel wall. For instance, endothelial cells not only have the task to cover the inner surface of the vascular system but they also play an active role in tuning the immunological response in a very sophisticated way. Neutrophils are not only terminally differentiated cells sacrificed for a valuable cause. Cellular types of the perivascular microenvironment play roles one time not expected. The spread of the inflammatory process into the vascular wall is not necessarily inside-out. These and other selected concepts will be discussed in this paper.


Extraintestinal salmonellosis in a children's hospital.
An increase in the number of patients presenting with extraintestinal salmonellosis has occurred at our institution. The purpose of this study was to review the extraintestinal salmonellosis cases in our institution and to investigate the possible reasons for this increase. A retrospective review of patients from 1985 through 1996 was carried out to identify patients with extraintestinal infections with Salmonella. Demographic data were gathered and statistical evaluations comparing differences among groups (1985 to 1989, 1989 to 1992, 1993 to 1996) was done using the G statistic, adjusted (maximum likelihood) chi square or the Fisher's exact test. Thirty-nine patients were identified with extraintestinal salmonellosis and although the number of cases had increased from 8 in 1985 to 1988 to 18 in 1989 to 1992 and 13 from 1993 to 1996, the percentage of cases that were extraintestinal were similar (3.3%, 6%, 4.9%; P > 0.1). Seventy-two percent of patients had underlying risk factors with the most common being age < 3 months (44%), sickle cell anemia (13%) and gastrointestinal surgery (10%). Fever and diarrhea were more common presenting symptoms in patients < 3 months of age than in older patients (P < 0.05). Salmonella typhimurium and Salmonella heidelberg were the most common serotypes isolated and an increasing trend of ampicillin resistance was noted from 0% in 1985 to 1988 to 39% from 1989 to 1992 and 23% from 1993 to 1996. The reasons for an increasing trend in extraintestinal cases of human salmonellosis at our institution were not identified. This illness continues to occur in infants and children with well-recognized risk factors.


Social presence and dynamics of group communication: An analysis of a health professionals WhatsApp group chats.
WhatsApp has become a medium of communication with the potential of promoting collaborative environment with peers, patients and general population. Till date, no analysis of professional WhatsApp groups' activities exists in physiotherapy. The official WhatsApp group chats of the Association of Clinical and Academic Physiotherapists of Nigeria (ACAPN) was analyzed. A total of 20760 chats were gleaned from July 2020 to June 2021. Videos, audios and emoticons were excluded in the analysis. Administrative permission to conduct was obtained from ACAPN leadership. Two consenting physiotherapists who had never deleted their ACAPN group chats shared and exported all chats to a Gmail. The social presence theory for group communication was used as the framework of analysis. Thematic content analysis was used to analyze qualitative data. Descriptive statistics of frequency and percentages were used to summarize data. Based on social presence theory classifications, interactive messages (64.5%) followed by cohesive messages (30%) were predominant. Members used the platform more for expression of emotions affectively (100%), referring explicitly to others' messages interactively (56.6%) and for greetings (phatic and salutation) cohesively (61.8%). Qualitative themes indicate that all three categories of social presence theory communications were present sufficiently with interactive category being the most common, as members used the WhatsApp platform to interact, construct and share knowledge. Group WhatsApp platform is a veritable means of communication and an indicator of level of social presence among Nigerian physiotherapists. Communication among Nigerian physiotherapists is mostly interactive, then cohesive and affective in terms of dynamics.


Temporal and kinetic analysis of unilateral jumping in the vertical, horizontal, and lateral directions.
The aims of this study were to: (1) assess the reliability of various kinetic and temporal variables for unilateral vertical, horizontal, and lateral countermovement jumps; (2) determine whether there are differences in vertical ground reaction force production between the three types of jumps; (3) quantify the magnitude of asymmetry between limbs for variables that were established as reliable in a healthy population and whether asymmetries were consistent across jumps of different direction; and (4) establish the best kinetic predictor(s) of jump performance in the vertical, horizontal, and lateral planes of motion. Thirty team sport athletes performed three trials of the various countermovement jumps on both legs on two separate occasions. Eccentric and concentric peak force and concentric peak power were the only variables with acceptable reliability (coefficient of variation = 3.3-15.1%; intra-class correlation coefficient = 0.70-0.96). Eccentric and concentric peak vertical ground reaction force (14-16%) and concentric peak power (45-51%) were significantly (P < 0.01) greater in the vertical countermovement jump than in the horizontal countermovement jump and lateral countermovement jump, but no significant difference was found between the latter two jumps. No significant leg asymmetries (-2.1% to 9.3%) were found in any of the kinetic variables but significant differences were observed in jump height and distance. The best single predictors of vertical countermovement jump, horizontal countermovement jump, and lateral countermovement jump performance were concentric peak vertical power/body weight (79%), horizontal concentric peak power/body weight (42.6%), and eccentric peak vertical ground reaction force/body weight (14.9%) respectively. These findings are discussed in relation to monitoring and developing direction-specific jump performance.


[The application of PS II model for the analysis of fluorescence yield transients induced by actinic single turnover flash in the time range from 100 ns to 10 s].
Changes in flash-induced fluorescence yield in preparations of thermophilic Chlorella pyrenoidosa Chick cells (native and in the presence of DCMU) were investigated in the time range from 100 ns to 10 s using a new measuring system. The results were analyzed by mathematical modeling of processes in photosystem II. It was shown that the detailed description of recombination (including nonradiative) processes in photosystem II is important to simulate the fluorescence yield transients induced by an actinic single turnover flash. The model photosystem II parameters were modified to describe the light-induced effects in the presence of DCMU. By comparing the theoretical fluorescence curves with experimental ones, we obtained the values of relative fluorescence yield and the FM/F0 ratio, which is typical for experimental data. As a result of simulation, the values of the model parameters (rate constants of electron transfers at the donor and acceptor sites of photosystem II, pH in stroma, initial redox state of the plastoquinone pool, the rate of plastoquinol oxidation, and the rate constants of nonradiative recombination processes) were determined.


Pulmonary Intravascular Large B-cell Lymphoma (IVLBCL) Disguised as an Asthma Exacerbation in a Patient with Asthma.
A 62-year-old man with asthma presented with a 1-month history of wheezing and exertional dyspnea. Although the wheezing symptoms disappeared after systemic corticosteroid therapy, the exertional dyspnea and hypoxemia did not improve. A diagnosis of intravascular large B-cell lymphoma (IVLBCL) with pulmonary involvement was suspected because of the increased serum lactic dehydrogenase (LDH) and soluble interleukin-2 receptor (sIL-2R) level, increased alveolar-arterial oxygen difference (AaDO2), decreased pulmonary diffusing capacity for carbon monoxide (DLCO) and scintigraphic, computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT findings. The patient was diagnosed as having IVLBCL with pulmonary involvement based on a pathological analysis of a random skin biopsy and a transbronchial lung biopsy. IVLBCL should be considered in patients with symptoms of asthma that are refractory to corticosteroid treatment.


Women taking the "blue pill" (sildenafil citrate): such a big deal?
For years, phosphodiesterase type 5 inhibitors have been used for the treatment of erectile dysfunctions. Due to the similarities between male and female sexual response, several studies have assessed the effects of sildenafil citrate (Viagra(®)) in women affected by female sexual arousal disorder. The results are still conflicting and the drug is not devoid of adverse effects. Furthermore, female sexual arousal disorder is a heterogeneous condition whose underlying causes are difficult to diagnose and appropriate treatment requires a thorough sexual, psychological, and medical history along with specialist consultations. The clinician should pursue a global approach to the patient with sexual difficulties, while non-hormonal treatment such as phosphodiesterase type 5 inhibitors (ie, sildenafil citrate) should be kept as the last option.


The new place of enterohormones in intestinal failure.
Since the approval of teduglutide, a glucagon-like peptide-2 (GLP-2) analog, for the treatment of patients with short bowel syndrome (SBS) associated with intestinal failure, enterohormone therapy has received significant interest and is becoming the first choice of treatment in selected patients. As such, it is paramount to assess and understand the new place of hormonal therapy in the algorithm of treatments in SBS-intestinal failure. Specialized intestinal failure units have recently reported their outcomes with teduglutide to evaluate if they are consistent with the phase III trials results. SBS-intestinal failure patients are very heterogenous including their response to this treatment, hence the importance of real-life studies beyond the context of clinical trials. Moreover, it is essential to find a consensus on criteria identifying candidate patients for teduglutide. In addition, the impact of teduglutide on quality of life and its cost-effectiveness are emerging as well as new enterohormone treatments are being studied whether it is long action GLP-2 analog or other ileocolonic break hormones like glucagon-like peptide-1 analog. Hormonotherapy is currently modifying the natural history of patients with SBS-intestinal failure by decreasing their need for parenteral support and possibly even complications associated with long-term parenteral support. Enterohormone treatment is now the cornerstone in SBS-intestinal failure and should be offered as a first-line therapy to selected patients.


Care of the patient with adult congenital heart disease.
The adult congenital heart disease (ACHD) patient population has numerous and distinctive needs and comprise a rapidly growing group within the modern day healthcare arena. Current treatment provisions along with recommendations for future specialized multidisciplinary ACHD teams are discussed. The exclusive needs of this patient population have forced professional groups to reconsider the availability and appropriateness of current healthcare delivery to this group of complex patients, whose survivability and life expectancy have continued to improve as a direct result of enhanced research, technology, medical, surgical, and nursing care. General care considerations including psychosocial issues and patient education are presented, and reveal the challenges and strengths of caring for this adult patient population within a pediatric facility. Congenital heart disease is a lifelong illness that requires a dedicated, consistent approach to healthcare delivery in order to guarantee quality care throughout the lifespan.


Dysarthria and aphagia: a case study of neuromuscular treatment.
This case study involves a 44-year-old man with flaccid dysarthria, right hemiparesis, left facial paresis, left vocal fold paralysis, and aphagia following multiple gunshot wounds. He was treated surgically with a tracheostomy, feeding gastrostomy, left temporalis muscle sling, left cricopharyngeal myotomy, hypoglossal nerve anastomosis, and left true vocal fold Teflon injection. After seven years, the patient was referred for speech therapy. The areas of glottic closure, velopharyngeal closure, and tongue strength and mobility were stressed initially in speech therapy. Since these mechanisms were related to his aphagia, it was hypothesized that the oral motor activities used for speech would also aid in swallowing. After nine weeks of intensive practice, gains were noted in strength and movement for the tongue, velum and larynx. Shortly thereafter, he swallowed blender-texture food.


Consumption of addictive substances in mariners.
For many years, studies have confirmed that there is a high prevalence of addiction amongst seafarers. The effect of this is even more serious when one considers their isolated and even hostile living environment presenting risks which require vigilance and rapid reactions. The purpose of this article is to determine the extent of knowledge about addiction among seafarers. This is a review of the literature between 1993 and 2013 with respect to the prevalence of consumption of alcohol, tobacco, cannabis, cocaine, heroin, and other drugs amongst seafarers. Total prevalence was calculated using the virtual population represented by the subjects of each article, when drug consumption definition was the same between articles and when mariners studied were different. 63.1% (range 38.4-96.3%) of seafarers smoked tobacco. 14.5% (range 8.8-75%) of seafarers drank alcohol. 3.4% (range 9-45%) had used cannabis during the previous month. Few studies concerned other drugs; 3-10% of seafarers used drugs on board. The prevalence of tobacco and alcohol consumption amongst seafarers was higher than that in the general population. Further studies on the use of drugs at work would be valuable for this population who are subject to significant occupational risk.


Pd-catalyzed cross-coupling of aryllithium reagents with 2-alkoxy-substituted aryl chlorides: mild and efficient synthesis of 3,3'-diaryl BINOLs.
Palladium-catalyzed cross-coupling of aryllithium reagents with 2-alkoxy-substituted aryl chlorides is described. The reactions proceed under mild conditions with short reaction times and provide a wide range of 2-alkoxy-substituted biaryls. This new methodology is applied to the efficient preparation of 3,3'-diaryl BINOLs and represents the first synthesis of this important class of chiral compounds from the corresponding 3,3'-dichloro BINOLs.


Using Twitter to investigate opinions about multiple sclerosis treatments: a descriptive, exploratory study.
Multiple sclerosis (MS) is a common complex disorder, with new treatment options emerging each year. Social media is being increasingly used to investigate opinions about drugs, diseases and procedures. In this descriptive exploratory study, we sought to investigate opinions about currently available MS treatments. The Twitter resource Topsy was searched for tweets mentioning the following MS treatments: Aubagio, Avonex, Betaferon or Betaseron, Copaxone, Extavia, Gilenya, Lemtrada, Novantrone, Rebif, Tysabri and Tecfidera between 1 Jan 2006 to 31 Jul 2014. Tweets were normalised and sentiment analysis performed. In total, there were 60037 unique tweets mentioning an MS treatment. About half of the tweets contained non-neutral sentiment. Mean sentiment scores were different for treatments ranging from -0.191to 0.282 when investigating all tweets. These differences in sentiment scores between treatments were statistically significant (P<0.001). Sentiment scores tended to be higher for oral MS treatments than injectable treatments. Many tweets about MS treatments have a non-neutral sentiment. The analysis of social media appears to be a potential avenue for exploring patient opinion about MS treatments.


Use of xinfeng capsule to treat abarticular pathologic changes in patients with rheumatoid arthritis.
To observe the influence of Xinfengcapsule (XFC) on abarticular pathologic changes (APCs) and other indices of patients with rheumatoid arthritis (RA) and explore the mechanism of action of XFC in improving such changes. Three-hundred RA patients were divided randomly into a treatment group (n = 150) and control group (n = 150). A normal control (NC) group (n = 90) was also created. Changes in cardiac function, pulmonary function, anemia indices and platelet parameters of RA patients were measured. Curative effects of the two groups were compared, and comparison carried out with the NC group. In 300 RA patients, late diastolic peak flow velocity (A peak) was much higher (P < 0.01) and early diastolic peak flow velocity (E peak), E/A, and left ventricular fraction shortening much lower(P < 0.01) than those in the NC group. Vital capacity (VC), forced vital capacity in one second, forced vitalcapacity (FVC), maximal voluntary ventilation (MVV), maximal expiratory flow in 50% of VC (FEF50) and FEF75 were lowered remarkably (P < 0.05 or P < 0.01). Platelet count (PLT), plateletcrit (PCT) and mean platelet volume (MPV) increased markedly (P < 0.05 or P < 0.01), and hemoglobin (Hb) level decreased significantly (P < 0.05). After XFC treatment, the A peak and PLT and PCT were much lower (P < 0.05), and E/A and the number of red blood cells as well as Hb level were much higher (P < 0.05), as were FVC, MVV and FEF50 (P < 0.05 or P < 0.01), in the treatment group than those in the NC group. Total score of pain and swelling in joints, uric-acid level and high-sensitivity C-reactive protein level were much lower, and superoxide dismutase level as well as the number of CD4 + CD25+ regulation T cells (Treg) and CD4+ CD25+ CD127- Treg were much higher (P < 0.05 or P < 0.01) in the treatment group than those in the NC group. RA patients with pathologic changes in joints also suffer from lower cardiac and pulmonary functions and from parameters of anemia and platelet factors. XFC can improve the symptoms of RA patients, ameliorate their cardiac and pulmonary functions and reduce the parameters of anemia and platelet factors. XFC lowers the immune inflammatory reaction to improve APCs in RA patients.


Differential action of 13-HPODE on PPARalpha downstream genes in rat Fao and human HepG2 hepatoma cell lines.
In rats, oxidized fats activate the peroxisome proliferator-activated receptor alpha (PPARalpha), leading to reduced triglyceride concentrations in liver, plasma and very low density lipoproteins. Oxidation products of linoleic acid constitute an important portion of oxidized dietary fats. This study was conducted to check whether the primary lipid peroxidation product of linoleic acid, 13-hydroperoxy-9,11-octadecadienoic acid (13-HPODE), might be involved in the PPARalpha-activating effect of oxidized fats. Therefore, we examined the effect of 13-HPODE on the expression of PPARalpha target genes in the rat Fao and the human HepG2 hepatoma cell lines. In Fao cells, 13-HPODE increased the mRNA concentration of the PPARalpha target genes acyl-CoA oxidase (ACO), cytochrome P450 4A1 and carnitine-palmitoyltransferase 1A (CPT1A). Furthermore, the concentration of cellular and secreted triglycerides was reduced in Fao cells treated with 13-HPODE. Because PPARalpha mRNA was not influenced, we conclude that these effects are due to an activation of PPARalpha by 13-HPODE. In contrast, HepG2 cells seemed to be resistant to PPARalpha activation by 13-HPODE because no remarkable induction of the PPARalpha target genes ACO, CPT1A, mitochondrial HMG-CoA synthase and delta9-desaturase was observed. Consequently, cellular and secreted triglyceride levels were not changed after incubation of HepG2 cells with 13-HPODE. In conclusion, this study shows that 13-HPODE activates PPARalpha in rat Fao but not in human HepG2 hepatoma cells.


Use of cerebral oximetry to detect and manage cerebral desaturation with a rapidly expanding neck hematoma.
We report a case in which cerebral oximetry was used to successfully demonstrate when cerebral oxygen saturation is dangerously low. In a 60-year-old-man with end-stage multiple myeloma and hyperviscosity syndrome, a rapidly expanding hematoma developed after insertion of an internal jugular central venous catheter. As the hematoma expanded, the patient became lethargic and disoriented (Glasgow Coma Score of E2/M4-5/V2-ETT). His platelet count was 17,000.mm(-3), hemoglobin was 4.5 g/dl, partial thromboplastin time was 51 s, and his international ratio was 1.7. Although carotid pulses became unpalpable, blood pressure and heart rate remained stable. Cerebral oximeter probes positioned on the patient's forehead showed that cerebral oxygen saturation was 22-26% bilaterally. The surgery team was advised to surgically evacuate the hematoma. The hematoma was evacuated and a small needle hole in the right internal jugular vein adjacent to the central-venous catheter was found and repaired. Cerebral oxygen saturation increased to 56-58% within 1 h and stabilized near 60%. The patient awoke with normal cognitive function. This case demonstrates how cerebral oximetry can be used to give quantitative evidence of cerebral hypoxia, thus showing that immediate surgical intervention is necessary.


Estimating risk curves for first-degree relatives of patients with Alzheimer's disease: the REVEAL study.
The REVEAL study is a randomized, controlled study of the psychological and behavioral impact of APOE disclosure in a risk assessment protocol provided to first degree relatives of patients with Alzheimer's disease. The protocol presents risk information as cumulative incidence curves. This article describes how these curves were estimated. Curves were calculated using Bayes' rule to compute the posterior survival curves incorporating APOE information. A combination of survival data from the MIRAGE study and gender- and age-specific APOE odds ratios were used to create risk curves for males and females within each of the 6 APOE genotypes. Utilizing comparative genotype relative risk information and survival data from family studies, estimates of gender-, age-, and genotype-specific risk can be generated for use in a risk assessment research study that features genotype disclosure.


Spatial extent and figural factors in backward masking.
Spatial and figural characteristics of backward masking were studied, with two collinear arcs presented end-to-end and serving as target and mask, respectively. Stimulus onset asynchrony was 50 ms while interstimulus interval was 0 ms. Mask exposure duration required for masking was determined as a function of target length with mask length as a parameter. The exposure duration of the mask required for complete masking varied directly with target length, but inversely with mask length. The fact that masking strength increased with mask duration while all other parameters were kept constant suggests that masking depended on stimulus termination asynchrony. Maximal masking occurred for target arcs as long as 5.0 deg of visual angle, exceeding previously reported distances. Misaligned or differently shaped stimuli produced less masking, suggesting that figural factors play a role in long-range backward masking.


Potent Antibacterial Activity of Copper Embedded into Silicone and Polyurethane.
A simple, easily up-scalable swell-encapsulation-shrink technique was used to incorporate small 2.5 nm copper nanoparticles (CuNPs) into two widely used medical grade polymers, polyurethane, and silicone, with no significant impact on polymer coloration. Both medical grade polymers with incorporated CuNPs demonstrated potent antimicrobial activity against the clinically relevant bacteria, methicillin-resistant Staphylococcus aureus and Escherichia coli. CuNP-incorporated silicone samples displayed potent antibacterial activity against both bacteria within 6 h. CuNP-incorporated polyurethane exhibited more efficacious antimicrobial activity, resulting in a 99.9% reduction in the numbers of both bacteria within just 2 h. With the high prevalence of hospital-acquired infections, the use of antimicrobial materials such as these CuNP-incorporated polymers could contribute to reducing microbial contamination associated with frequently touched surfaces in and around hospital wards (e.g., bed rails, overbed tables, push plates, etc.).


Painful oculomotor nerve palsy - A presenting sign of internal carotid artery stenosis.
We report a 72-year-old patient presenting acute painful partial left IIIrd nerve palsy with pupillary involvement. Due to the patient's age and mild hyperlipidemia a microangiopathic ischemic origin was assumed after a compressive or inflammatory cause had been excluded by magnetic resonance imaging, blood and cerebrospinal fluid analyses. Carotid ultrasound examination disclosed a high-grade stenosis of the ipsilateral internal carotid artery (ICA). In the absence of diabetes mellitus, other significant vascular risk factors and leukoencephalopathy indicative of advanced arteriosclerotic disease, we suggest a pathogenetic role of the ICA stenosis in ischemic IIIrd nerve palsy. The frequency of a IIIrd nerve palsy as the presenting symptom in patients with ICA stenosis as well as the frequency of an ICA stenosis being the cause in patients with isolated IIIrd nerve palsy is not well documented in the literature. Both seem to be rare but may be underestimated. We advocate cervicocerebral ultrasound examination in patients presenting IIIrd nerve palsy with no obvious or a presumed ischemic cause.


Phase II study of fludarabine phosphate in multiple myeloma. A Southwest Oncology Group study.
Thirty-one patients with multiple myeloma refractory to therapy or relapsing after response to initial therapy were treated with Fludarabine Phosphate utilizing a daily intravenous schedule for five consecutive days. There were no objective responses seen and only one patient showed clinical improvement. Myelosuppression manifest as leucopenia and granulocytopenia was the primary toxicity seen. Fludarabine Phosphate is inactive in previously treated myeloma patients when given by the daily intravenous route.


Deriving disyllabic word variants from a Chinese conversational speech corpus.
Motivated by the quasi-categorical reduced forms of disyllabic words produced in Chinese conversational speech, a frequency-based selection procedure of typical pronunciation by disyllabic word type and reduction degree is proposed in this paper. This variant-selection algorithm utilizes techniques of free phone recognition and phonetic similarity score calculation to account for Chinese syllable structure. Four reduction types are suggested by considering the presence of a within-word syllable boundary: Citation form-like reduction, marginal segment deletion, nuclei merger, and syllable merger. The results show that the most frequent reduction types for disyllabic words in Chinese conversation are citation form-like reduction and syllable merger. In particular, high-frequency disyllabic words preferentially take the extreme syllable-merger form. As shown in the analysis, segmental reduction in Chinese disyllabic words is morphology-dependent. It is also related to the prosodic position at which a disyllabic word is produced as well as the temporal quality of the word. Finally, in the automatic speech recognition experiments, the performance was improved by adding a small number of variants selected by the algorithm to the pronunciation dictionary of the system.


Mechanotransduction map: simulation model, molecular pathway, gene set.
Mechanotransduction--the ability to output a biochemical signal from a mechanical input--is related to the initiation and progression of a broad spectrum of molecular events. Yet, the characterization of mechanotransduction lacks some of the most basic tools as, for instance, it can hardly be recognized by enrichment analysis tools, nor could we find any pathway representation. This greatly limits computational testing and hypothesis generation on mechanotransduction biological relevance and involvement in disease or physiological mechanisms. We here present a molecular map of mechanotransduction, built in CellDesigner to warrant that maximum information is embedded in a compact network format. To validate the map's necessity we tested its redundancy in comparison with existing pathways, and to estimate its sufficiency, we quantified its ability to reproduce biological events with dynamic simulations, using Signaling Petri Networks. SMBL language map is available in the Supplementary Data: core_map.xml, basic_map.xml. Supplementary data are available at Bioinformatics online.


In vivo efficacy and bioavailability of lumefantrine: Evaluating the application of Pheroid technology.
The oral absorption of compounds with low aqueous solubility, such as lumefantrine, is typically limited by the dissolution rate in the gastro-intestinal tract, resulting in erratic absorption and highly variable bioavailability. In previous studies we reported on the ability of Pheroid vesicles to improve the bioavailability of poorly soluble drugs. In the present study a Pro-Pheroid formulation, a modification of the previous formulation, was applied to improve the solubility of lumefantrine after oral administration and compared to lumefantrine in DMSO:water (1:9 v/v) solution (reference solution). A bioavailability study of lumefantrine was conducted in a mouse model in fed and fasted states. When using the reference solution, the bioavailability of the lumefantrine heavily depended on food intake, resulting in a 2.7 times higher bioavailability in the fed state when compared to the fasted state. It also showed large between-subject variability. When formulated using Pro-Pheroid, the bioavailability of lumefantrine was 3.5 times higher as compared to lumefantrine in the reference solution and fasting state. Pro-Pheroid also dramatically reduced the effects of food intake and the between-subject variability for bioavailability observed with the reference. In vivo antimalarial efficacy was also evaluated with lumefantrine formulated using Pro-Pheroid technology compared to the reference solution. The results indicated that lumefantrine in Pro-Pheroid formulation exhibited improved antimalarial activity in vitro by 46.8%, when compared to the reference. The results of the Peters' 4-day suppressive test indicated no significant difference in the efficacy or mean survival time of the mice in the Pro-Pheroid formulation and reference test groups when compared to the positive control, chloroquine. These findings suggest that using the Pro-Pheroid formulation improves the bioavailability of lumefantrine, eliminates the food effect associated with lumefantrine as well as significantly reduces the between subject variability in bioavailability when compared to the reference solution.


Plasma/Serum Zinc Status During Aerobic Exercise Recovery: A Systematic Review and Meta-Analysis.
Exercise and the subsequent recovery processes have been proposed to induce disturbances in zinc homeostasis. We previously reported acute increase in serum zinc concentration immediately after aerobic exercise; the change in the indices of zinc status during exercise recovery was not explored. The aim of the current analysis is to determine the changes in zinc biomarkers during recovery from an aerobic exercise bout. We conducted a systematic literature search on PubMed, Web of Science, Scopus and SPORTDiscus electronic databases from inception to 20 December 2014 to identify studies that investigated the acute effects of exercise on selected indices of zinc status. Meta-analyses were conducted to determine the change in serum zinc concentration during exercise recovery, defined as up to 4 h following exercise cessation, compared to pre-exercise levels. Forty-five studies were included in the systematic literature review, of which 12 studies (providing 18 comparisons) reported serum zinc levels after the cessation of exercise. During exercise recovery, serum zinc concentration was significantly lower than pre-exercise values (-1.31 ± 0.22 μmol/L, P < 0.001; mean ± SE). Secondary analyses showed a significant decrease of serum zinc levels in all categories of participants' training status, mode of exercise and time of blood collection. Insufficient data were available for meta-analysis of other zinc biomarkers. The present analysis showed that serum zinc levels decrease significantly during exercise recovery, compared to pre-exercise levels. This extends our previous report of an increase in serum zinc immediately after exercise. We postulate that the exercise-induced fluctuations in zinc homeostasis are linked to the muscle repair mechanisms following exercise; the potential for zinc to enhance the exercise recovery process remains to be determined.


[In vitro effects of low-molecular weight heparin and dexamethasone on the hemolysis of red blood cells from paroxysmal nocturnal hemoglobinuria patients].
To study the in vitro effects of low-molecular weight heparin (LMWH) and dexamethasone on the hemolysis of red blood cells from paroxysmal nocturnal hemoglobinuria (PNH) patients. By Ham's test and micro-complement lysis sensitive test (mCLST), the changes of hemolysis of red blood cells from 6 PNH patients were tested by adding different doses of LMWH and dexamethasone into the test mixture. The effects of LMWH and dexamethasone on the coagulation of the tested blood samples were also studied by activated partial thromboplastin time (APTT). (1) Either LMWH or dexamethasone could dose-dependently inhibit the hemolysis of PNH red blood cells, and the effects were synergistic when added together. The same dose of LMWH induced a less than 100% prolongation of APTT. (2) Dexamethasone could inhibit the hemolysis in Ham's test and had different effects on the hemolysis by different adding methods in mCLST. LMWH could inhibit the hemolysis in both Ham's test and mCLST. Both LMWH and dexamethasone could inhibit the hemolysis of PNH red cells and showed a synergistic effect. The mechanisms of the inhibition of hemolysis were different. Furthermore, a tolerable dose of LMWH induced only a limited prolongation of APTT, which might be useful for controlling acute hemolysis and reducing the dose of dexamethasone.


The plasmid-encoded outer-membrane proteins of Yersinia pestis.
The yersinial plasmid-encoded outer-membrane proteins (Yops) are encoded by the low-Ca++ response virulence plasmid present in the yersiniae pathogenic for humans. It has been shown that in Yersinia pestis KIM there are 11 of these proteins, which are expressed maximally during growth at 37 degrees C in the absence of Ca++. To recover these proteins in outer membranes, it was necessary to transfer the Y. pestis low-Ca++ response plasmid to Yersinia pseudotuberculosis. However, two of these proteins (Yops M and N) were present in the culture medium after growth of Y. pestis; no other Yops were released by the bacteria. This raises the possibility of multiple roles for Yops in the virulence of Y. pestis.


Thawing procedures and the time course of clotting factor activity in fresh-frozen plasma: a controlled laboratory investigation.
In this study, we evaluated the effects of the thawing process of 2 commercially available devices on the activity of clotting factors, inhibitors and activation markers of the hemostatic system in fresh-frozen plasma (FFP). In an experimental procedure, FFP was thawed under running warm water at 42 degrees C. Plasma of 20 healthy donors was sampled, separated, and distributed in 3 plasma bags. Within 2 h after sampling plasma bags was frozen at a temperature of -30 degrees C to -40 degrees C and stored for at least 8 wk. After sampling (baseline) as well as immediately and 1, 2, 4, and 6 h after thawing, the activity of FV, FVII, FVIII, fibrinogen, fibrin monomers (FM), d-dimers (DD), alpha2-antiplasmin (alpha2-AP), and protein S (PS) was determined from each plasma bag. From 1 h to 6 h after thawing, no significant differences in the activity of the investigated coagulation markers dependent on the thawing procedure were found. However, immediately after thawing and independent of the thawing procedure, the activity of FVII was significantly decreased (P < 0.01), whereas FM were significantly increased (P = 0.001). The thawing procedures studied exhibited no significant influence on activity and stability of the investigated markers of coagulation over the study period. The decreased activity of FVII and the clinical significance of the increase in FM require further research.


Role of direct oral anticoagulants in gastrointestinal cancer associated thrombosis "practical issues in clinical practice"-narrative review.
Direct oral anticoagulants (DOAC) are now considered an effective treatment option for cancer associated thrombosis (CAT). There are still controversies in the use of DOACs in CAT associated with gastrointestinal (GI) malignancies. Patients with GI malignancies and CAT present several unique management challenges. Factors such as the risk of bleeding from intact luminal primary, impact on absorption and efficacy of the DOACs due to altered anatomy, chemotherapy-induced nausea and vomiting, the potential drug to drug interactions need to be considered when prescribing DOACs in CAT associated with GI malignancies. The landmark randomised controlled trials (RCTs), systematic reviews and observational studies (OSs) of real-world data comparing DOACs with low molecular weight heparin (LMWH) in treating CAT comprised heterogeneous groups of tumour sites with limited numbers of patients with GI malignancies. This article reviews the available evidence on outcomes of the subset of CAT associated with GI malignancies in recent RCTs. Future prospective trials need to evaluate the impact of the factors mentioned above in the efficacy of DOACs in preventing and treating CATs in specific subsets of GI malignancies. Until more evidence is available, LMWH is a more reasonable choice in selected subgroups of CAT in GI malignancies.


IL-2 and IL-10 production by human CD4+T cells is differentially regulated by p38: mode of stimulation-dependent regulation of IL-2.
Antigenic stimulation of T cells initiates a complex series of intracellular signaling pathways that target and activate different cytokine genes. The participation of mitogen-activated protein kinases (MAPKs) in these processes has not been studied thoroughly and in some instances conflicting results have been reported. Here we have examined the role of p38 MAPK on IL-2 and IL-10 production following activation of human CD4+ T cells or of the leukemic cell line Hut-78, with either plate-bound anti-CD3 in the presence or absence of soluble anti-CD28 (plCD3, plCD3/sCD28), or with cross-linked anti-CD3 and anti-CD28 (crsCD3+CD28), or with PMA plus ionomycin. Pharmacological inhibition of the p38 pathway with either SB203580, SB202190, or SKF86002 strongly downregulated IL-10 production by T cells stimulated with any of the above treatments. In contrast the effect of p38 inhibition on IL-2 was stimulus dependent. Thus, p38 inhibition strongly upregulated IL-2 production (up to 10-fold) in the plCD3- and plCD3/sCD28-stimulated cultures while it had minimal or no effect in the other two stimulation protocols. Intracellular and mRNA levels of IL-2 and IL-10 were also upregulated and downregulated, respectively, by p38 inhibitors in the plCD3/sCD28-stimulated CD4+ T cells. Also, the induction of IL-2 and the parallel suppression of IL-10 by p38 inhibitors were independent of the balance between these two cytokines, as demonstrated by the addition of exogenous IL-10 or blocking anti-IL-10 antibody in CD4+ and Hut-78 cell cultures. These results show that p38 acts as a molecular switch that changes the balance between IL-2 and IL-10. This is especially important considering the opposing role of these cytokines in peripheral immune tolerance.


[Useful treatment modality for postoperative duodenal fistula with somatostatin analogue].
A case with leakage of duodenal stump treated by a somatostatin analogue (SMS 201-995,SMS) effectively was reported. A 39-year-old man had underwent gastric resection (Billroth I) and distal pancreaticojejunostomy for transsection of duodenal bulbus and pancreatic body. After 14 days later duodenal diverticulization was performed due to anastomotic stricture of the gastro-duodenostomy, which resulted in leakage of duodenal stump and voluminous fluids from drains were lasting about 5 weeks. Amylase (AMY) value was shown as high as 703,812 U/l in the exudate. SMS was injected by 100 micrograms, s, c, by three times a day for 24 days. The volume of exudate decreased immediately after the administration of SMS and to one-half in volume in 2 weeks. AMY also fell to 42, 378 U/l. The drain was removed two months after the third surgery. The patient was discharged on post operative day 200. SMS was known to inhibit secretion of bile and intestinal as well as pancreatic juice and its usefulness for leakage of the intestinal tract, especially of the duodenum, is suggested.


Persistent Left Superior Vena Cava: Incidence and Management in Patients Undergoing Repair of Partial Anomalous Pulmonary Venous Connection.
A association between partial anomalous pulmonary venous connection (PAPVC) and systemic venous anomalies has been described in the literature, but the true incidence is yet to be elucidated. At our institution, we sought to find the incidence of a persistent left superior vena cava (PLSVC) in patients undergoing an operation for PAPVC. A retrospective review of all pediatric and adult patients with PAPVC who underwent surgical repair from February 2006 to February 2016. All clinical, radiographic, and operative data were reviewed. Eighty-five patients underwent surgical repair. A PLSVC was identified in 15 (17.6%) patients. Every PLSVC drained/connected to the coronary sinus. A bridging vein was present in only 26.7% (4 of 15). Intraoperative management of the PLSVC consisted of direct cannulation in nine (60%) patients, temporary occlusion in one (6.7%) patient, and ligation in one (6.7%) patient. In the 15 PLSVC patients, 6 (40%) had a secundum atrial septal defect (ASD), 2 (13.3%) had a patent foramen ovale (PFO), 10 (66.6%) had a sinus venosus type defect, and 3 (20%) had both an ASD and sinus venosus-type defect. Of the 15 patients with PAPVC and PLSVC, 14 (93%) had anomalous drainage of pulmonary vein(s) on the right side, whereas 1 (7%) had veins on both sides with anomalous drainage. Persistent left superior vena cava is present in 17.6% of patients undergoing an operation for PAPVC. Awareness of this association as well as the intraoperative management of PLSVC is advised for those that perform operations for PAPVC. As improper myocardial protection and cardiopulmonary bypass strategies in the presence of a PLSVC can result in deleterious outcomes.


Empathy for positive and negative emotions in the gustatory cortex.
Anterior insula and adjacent frontal operculum (hereafter referred to as IFO) are active during exposure to tastants/odorants (particularly disgusting ones), and during the viewing of disgusted facial expressions. Together with lesion data, the IFO has thus been proposed to be crucial in processing disgust-related stimuli. Here, we examined IFO involvement in the processing of other people's gustatory emotions more generally by exposing participants to food-related disgusted, pleased and neutral facial expressions during functional magnetic resonance imaging (fMRI). We then exposed participants to pleasant, unpleasant and neutral tastants for the purpose of mapping their gustatory IFO. Finally, we associated participants' self reported empathy (measured using the Interpersonal Reactivity Index, IRI) with their IFO activation during the witnessing of others' gustatory emotions. We show that participants' empathy scores were predictive of their gustatory IFO activation while witnessing both the pleased and disgusted facial expression of others. While the IFO has been implicated in the processing of negative emotions of others and empathy for negative experiences like pain, our finding extends this concept to empathy for intense positive feelings, and provides empirical support for the view that the IFO contributes to empathy by mapping the bodily feelings of others onto the internal bodily states of the observer, in agreement with the putative interoceptive function of the IFO.


Perceived Risk of Cervical Cancer and Barriers to Screening among Secondary School Female Teachers in Al Hassa, Saudi Arabia
Background: No previous studies had addressed the perceived risk of cervical cancer (CC) and its influence on screening practices and perceived barriers in Saudi Arabia. Methods: This cross-sectional study was conducted on 506 randomly selected Saudi female secondary school teachers in Al Hassa, Saudi Arabia to assess their level of knowledge about risk factors and signs of CC in relation to perceived risk and to characterize CC screening compliance using a self-administered questionnaire. Results: Of the included female Saudi teachers, 65.4% and 63.4% were considered less-knowledgeable about CC risk factors and early signs and symptoms respectively. Only 17.2% reported being previously examined for CC. The majority of participants perceived themselves to be at an average or below average risk of CC. Residing in urban areas was the strongest predictor of CC screening (Odds ratio 'OR'= 3.39; 95% confidence intervals 'CI= 1.76-6.46; P=0.001). Awareness of risk factors was significantly associated with higher awareness of signs of CC (OR 2.5; 95% CI=, P=0.001). Exploratory factor analysis showed that personal fears (of screening being embarrassing) was the major factor that hindered CC screening with a high loading eigenvalue of 4.392, explaining 30.8% of the barriers toward utilization, followed by health care related factors. Conclusion: Secondary school teachers in Al Hassa, Saudi Arabia showed low perceived risk, poor awareness about risk factors, signs and symptoms of CC and limited uptake of screening practices. This underlines the need for education programs on CC targeting this group.


Separate roles for the DNA damage checkpoint protein kinases in stabilizing DNA replication forks.
The DNA damage checkpoint plays a crucial role in maintaining functional DNA replication forks when cells are exposed to genotoxic agents. In budding yeast, the protein kinases Mec1 (ATR) and Rad53 (Chk2) are especially important in this process. How these kinases act to stabilize DNA replication forks is currently unknown but is likely to have important implications for understanding how genomic instability is generated during oncogenesis and how chemotherapies that interfere with DNA replication could be improved. Here we show that the sensitivity of rad53 mutants to DNA-damaging agents can be almost completely suppressed by deletion of the EXO1 gene, which encodes an enigmatic flap endonuclease. Deletion of EXO1 also suppresses DNA replication fork instability in rad53 mutants. Surprisingly, deletion of EXO1 is completely ineffective in suppressing both the sensitivity and replication fork breakdown in mec1 mutants, indicating that Mec1 has a genetically separable role in replication fork stabilization from Rad53. Finally, our analysis indicates that a second downstream effector kinase, Chk1, can stabilize replication forks in the absence of Rad53. These results reveal previously unappreciated complexity in the downstream targets of the checkpoint kinases and provide a framework for elucidating the mechanisms of DNA replication fork stabilization by these kinases.


[Pulmonary alveolar proteinosis - a case report].
Pulmonary alveolar proteinosis (PAP) is a rare lung disease of unknown origin, where an amorphous lipoprotein material accumulates in the alveoli of the lungs. We describe a young male with a four month history of progressive dyspnea, low grade fever, hypoxemia and weight loss. Chest X-ray showed diffuse interstitial and alveolar infiltrates in both lungs. The diagnosis of PAP was confirmed with trans-bronchial lung biopsy. Because of a deteriorating clinical course a whole lung lavage was performed. Under general anesthesia, both lungs were lavaged with warm saline in two different sessions with good results. Two years later the patient is almost free of symptoms and lung function has markedly improved.


Primary malignant fibrous histiocytoma of the lung. Fine needle aspiration cytologic features.
A case of primary malignant fibrous histiocytoma of the lung occurring in a 71-year-old woman is presented. The preoperative aspiration cytology showed a large-cell, undifferentiated, malignant neoplasm suggestive of carcinoma. Subsequent histologic examination revealed a primary malignant fibrous histiocytoma. The diagnosis was confirmed by electron microscopic and immunohistochemical studies. Cytologic features of this rare primary pulmonary sarcoma are discussed.


[Molecular genetics principles in cystic fibrosis. An example of genetic illness in pneumology].
The generalized exocrinopathy cystic fibrosis (CF) is caused by molecular lesions in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The basic defect of this autosomal-recessive disorder manifests in decreased permeability for chloride ions across the apical epithelial membrane. Of the more than 1,000 known CFTR mutations the most frequent mutation F508del occurs on about 70% of North- and Mideuropean CF chromosomes. CFTR mutations are also causatively involved in male infertility, pancreatitis and several airway diseases like disseminated bronchiectasis. The differential diagnosis between CF, other CFTR-opathies and diseases of unrelated etiology can be achieved by the assessment of clinical symptoms, CFTR mutation analysis and electrophysiological bioassays (sweat test, nasal potential difference, intestinal current measurements).


Synergistic Effects of the Ni3B Cocatalyst and N Vacancy on g-C3N4 for Effectively Enhanced Photocatalytic N2 Fixation.
The photocatalytic fixation of N2 is a promising technology for sustainable production of ammonia, while the unsatisfactory efficiency resulting from the low electron-transfer rate, narrow light absorption range, and limited active sites of the photocatalyst seriously hinder its application. Herein, we designed a noble metal-free Schottky junction photocatalyst constructed by g-C3N4 nanosheets with N vacancies (VN-CN) and metallic Ni3B nanoparticles (Ni3B/VN-CN) for N2 reduction to ammonia. The ammonia yield rate over the optimized Ni3B/VN-CN is 7.68 mM g-1 h-1, which is 6.7 times higher than that of pristine CN (1.15 mM g-1 h-1). The superior photocatalytic N2 fixation performance of Ni3B/VN-CN can be attributed not only to the formation of Schottky junctions between Ni3B and VN-CN, which facilitates the migration and separation of photogenerated electrons, but also to the incorporation of VN into g-C3N4, which enhances visible light absorption and improves electrical conductivity. More importantly, Ni3B nanoparticles can act as the cocatalyst, which provide more active sites for the adsorption and activation of N2, thereby improving the N2 reduction activity. This work provides an effective strategy of designing noble metal-free-based cocatalyst photocatalyst for sustainable and economic N2 fixation.


Risk of Prostate Cancer in Men Treated With 5α-Reductase Inhibitors-A Large Population-Based Prospective Study.
Studies have shown that 5α-reductase inhibitors (5-ARIs) decrease the risk for low-grade prostate cancer (PC), but results are conflicting concerning high-grade PCs. The objective of the present study is to evaluate the association between 5-ARI treatment for lower urinary tract symptoms and the risk for PC. This is a population-based prospective study on all men age 40 years and older with at least one prostate-specific antigen (PSA) test in Stockholm County from January 2007 until December 2015. Data are derived from the Stockholm PSA and Biopsy Register and Prescribed Drug Register in Sweden, containing data on 5-ARI-use before diagnosis of PC. Cox proportional hazards models were used to estimate the cause-specific hazard ratios of PC for each exposure level relative to men not taking the medication. Of the 333 820 men in the cohort, 23 442 (7.0%) were exposed to 5-ARI at some time during the study period of eight years. Treatment with 5-ARI decreased the risk for overall PC, and the effect was larger with longer time of exposure (0.1 to 2 years: hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.71 to 0.93; 2 to 4 years: HR = 0.39, 95% CI = 0.32 to 0.47; 4 to 6 years: HR = 0.40, 95% CI = 0.31 to 0.52; and 6 to 8 years: HR = 0.31, 95% CI = 0.16 to 0.60). Specifically, 5-ARI decreased the risk for PC with Gleason Scores 6 and 7 but did not statistically significantly affect the long-term risk of being diagnosed with a PC with a Gleason Score of 8 to 10 with up to eight years of treatment. Treatment with 5-ARI for lower urinary tract symptoms is safe with respect to prostate cancer risk.


Technical Note: Characterization of custom 3D printed multimodality imaging phantoms.
Imaging phantoms are important tools for researchers and technicians, but they can be costly and difficult to customize. Three dimensional (3D) printing is a widely available rapid prototyping technique that enables the fabrication of objects with 3D computer generated geometries. It is ideal for quickly producing customized, low cost, multimodal, reusable imaging phantoms. This work validates the use of 3D printed phantoms by comparing CT and PET scans of a 3D printed phantom and a commercial "Micro Deluxe" phantom. This report also presents results from a customized 3D printed PET/MRI phantom, and a customized high resolution imaging phantom with sub-mm features. CT and PET scans of a 3D printed phantom and a commercial Micro Deluxe (Data Spectrum Corporation, USA) phantom with 1.2, 1.6, 2.4, 3.2, 4.0, and 4.8 mm diameter hot rods were acquired. The measured PET and CT rod sizes, activities, and attenuation coefficients were compared. A PET/MRI scan of a custom 3D printed phantom with hot and cold rods was performed, with photon attenuation and normalization measurements performed with a separate 3D printed normalization phantom. X-ray transmission scans of a customized two level high resolution 3D printed phantom with sub-mm features were also performed. Results show very good agreement between commercial and 3D printed micro deluxe phantoms with less than 3% difference in CT measured rod diameter, less than 5% difference in PET measured rod diameter, and a maximum of 6.2% difference in average rod activity from a 10 min, 333 kBq/ml (9 μCi/ml) Siemens Inveon (Siemens Healthcare, Germany) PET scan. In all cases, these differences were within the measurement uncertainties of our setups. PET/MRI scans successfully identified 3D printed hot and cold rods on PET and MRI modalities. X-ray projection images of a 3D printed high resolution phantom identified features as small as 350 μm wide. This work shows that 3D printed phantoms can be functionally equivalent to commercially available phantoms. They are a viable option for quickly distributing and fabricating low cost, customized phantoms.


Welcome to volume 3 of Future Science OA.
Happy New Year to all of our readers! Welcome to volume 3 of Future Science OA. 2016 was another excellent year, with us receiving some superb content for publication, and our becoming indexed on both Chemical Abstracts and the Emerging Sources Citation Index, meaning our content now appears on Web of Science. We thank our readers, reviewers, authors and Editorial Board members for their continued support, and look forward to working with everyone in 2017.


Ensemble statistical and subspace clustering model for analysis of autism spectrum disorder phenotypes.
Heterogeneity in Autism Spectrum Disorder (ASD) is complex including variability in behavioral phenotype as well as clinical, physiologic, and pathologic parameters. The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) now diagnoses ASD using a 2-dimensional model based social communication deficits and fixated interests and repetitive behaviors. Sorting out heterogeneity is crucial for study of etiology, diagnosis, treatment and prognosis. In this paper, we present an ensemble model for analyzing ASD phenotypes using several machine learning techniques and a k-dimensional subspace clustering algorithm. Our ensemble also incorporates statistical methods at several stages of analysis. We apply this model to a sample of 208 probands drawn from the Simon Simplex Collection Missouri Site patients. The results provide useful evidence that is helpful in elucidating the phenotype complexity within ASD. Our model can be extended to other disorders that exhibit a diverse range of heterogeneity.


Palmitoleate is a mitogen, formed upon stimulation with growth factors, and converted to palmitoleoyl-phosphatidylinositol.
Controversial correlations between biological activity and concentration of the novel lipokine palmitoleate (9Z-hexadecenoate, 16:1) might depend on the formation of an active 16:1 metabolite. For its identification, we analyzed the glycerophospholipid composition of mouse Swiss 3T3 fibroblasts in response to 16:1 using LC-MS/MS. 16:1 was either supplemented to the cell culture medium or endogenously formed when cells were stimulated with insulin or growth factors as suggested by the enhanced mRNA expression of 16:1-biosynthetic enzymes. The proportion of 1-acyl-2-16:1-sn-phosphatidylinositol (16:1-PI) was time-dependently and specifically increased relative to other glycerophospholipids under both conditions and correlated with the proliferation of fatty acid (16:1, palmitate, oleate, or arachidonate)-supplemented cells. Accordingly, cell proliferation was impaired by blocking 16:1 biosynthesis using the selective stearoyl-CoA desaturase-1 inhibitor CAY10566 and restored by supplementation of 16:1. The accumulation of 16:1-PI occurred throughout cellular compartments and within diverse mouse cell lines (Swiss 3T3, NIH-3T3, and 3T3-L1 cells). To elucidate further whether 16:1-PI is formed through the de novo or remodeling pathway of PI biosynthesis, phosphatidate levels and lyso-PI-acyltransferase activities were analyzed as respective markers. The proportion of 16:1-phosphatidate was significantly increased by insulin and growth factors, whereas lyso-PI-acyltransferases showed negligible activity for 16:1-coenzyme A. The relevance of the de novo pathway for 16:1-PI biosynthesis is supported further by the comparable incorporation rate of deuterium-labeled 16:1 and tritium-labeled inositol into PI for growth factor-stimulated cells. In conclusion, we identified 16:1 or 16:1-PI as mitogen whose biosynthesis is induced by growth factors.


Factors predicting late collapse of distal radius fractures.
Although fractures of the distal radius are a common clinical presentation, many factors affect instability of these injuries. The aim of this study was to assess the influence of age, sex, distal radial ulnar joint injury (DRUJ), ulnar styloid fracture, and dorsal displacement in late collapse of distal radius fractures. Three hundred twenty-nine patient fractures were measured for dorsal tilt, radial inclination and ulnar variance after reduction and 2 months later. Reduction loss was analysed statistically against variables like DRUJ involvement, ulnar styloid fractures, age, sex, and AO classification. After two months there was loss of reduction in 171(51.9%) cases. Loss of reduction was related to age, AO classification, involvement of DRUJ, ulnar styloid fractures and initial displacement. Factors such as age, associated DRUJ injury, ulnar styloid fracture are predictive of loss of reduction. Knowing these predictor factors, can aid in decision regarding treatment methods. Distal Radius Fracture, Radial Tilt, Ulnar Variance, Volar Tilt, Ulnar Styloid Fracture, DRUJ.


Impaired FEF25-75 may predict high exhaled nitric oxide values in children with allergic rhinitis and/or asthma.
Allergic rhinitis and asthma are closely associated. Inflammation is a common pathological characteristic shared by both disorders. The measure of the fractional concentration of exhaled nitric oxide (FeNO) may be considered a surrogate marker for airway inflammation. Forced expiratory flow between 25 and 75 percent of vital capacity (FEF25-75) has been previously demonstrated to be able to predict BHR and bronchial reversibility. The aim of this study was to evaluate whether impaired FEF25-75 values may be related to FeNO values in a pediatric cohort of allergic subjects. 850 children with allergic rhinitis, allergic asthma, or both, were evaluated. Bronchial function (FEV1, FVC, and FEF25-75), FeNO, and sensitizations were assessed. Bronchial function and FeNO were significantly different in the 3 groups (p less than 0.001). A strong inverse correlation between FeNO and FEV1was found in patients with rhinitis, asthma and asthma with rhinitis (r= -0.72, r=-0.70 and r= -0.70, respectively). Impaired FEF25-75 values (such as less than 65 percent of predicted) were significantly associated with high FeNO levels (such as =34 ppb). In conclusion, this study provided evidence that FEF25-75 is strongly and inversely related with FeNO and FEF25-75 may predict high FeNO levels in children with allergic rhinitis, asthma or both.


Bibliometric analysis of global research trends on small-cell lung cancer (2012-2021).
Small-cell lung cancer (SCLC) is a recalcitrant tumor with a poor prognosis. With the rise of SCLC research in the past decade, this study aims to analyze the foundation and frontiers of SCLC research through bibliometric analysis. Relevant publications from the Web of Science Core Collection were retrieved on January 3, 2022. R package bibliometrix and EXCEL2019 were used to analyze quantitative variables. Bibliometric mapping was constructed by VOS viewer and CiteSpace software to visualize citation, co-authorship, co-occurrence, and co-citation analysis of countries/regions, organizations, authors, references, and keywords. A total of 2,361 publications related to SCLC were identified with the total amount of articles steadily increasing, where China is the most productive country with 859 papers. Scholars and organizations from the United States, China, and Europe are primary sources of this research, among which the University of Texas MD Anderson Cancer Center made the most contribution to the field with 122 papers. Lung Cancer published the highest number of SCLC-related articles with a total of 121, while the Journal of Thoracic Oncology received the most citations totaling 3,098. Rudin, Charles M., and Sage, Julien are the most creative author. Leora, Horn, 2018, New Engl J Med and Rudin, Charles M., Nat Genet, 2012 can be categorized as classic literature owing to their high citations or strong sigma value. "Heterogeneity & Subtypes" and "Immunotherapy" may be the new frontiers in the SCLC domain. Research on SCLC showed an upward trend based on the current global situation. Moreover, the current scope of collaboration in SCLC research is chiefly regional, which should further focus on transnational cooperation in the future. More attention should be devoted to "Heterogeneity & Subtypes" and "Immunotherapy", which will be the hotspots in future research.


Evaluating the outcome of screening for glaucoma using colour fundus photography-based referral criteria in a teleophthalmology screening programme for diabetic retinopathy.
To evaluate the effectiveness of glaucoma screening using glaucoma suspect (GS) referral criteria assessed on colour fundus photographs in Singapore's Integrated Diabetic Retinopathy Programme (SiDRP). A case-control study. This study included diabetic subjects who were referred from SiDRP with and without GS between January 2017 and December 2018 and reviewed at Singapore National Eye Centre. The GS referral criteria were based on the presence of a vertical cup-to-disc ratio (VCDR) of ≥0.65 and other GS features. The final glaucoma diagnosis confirmed from electronic medical records was retrospectively matched with GS status. The sensitivity, specificity and positive predictive value (PPV) of the test were evaluated. Of 5023 patients (2625 with GS and 2398 without GS) reviewed for glaucoma, 451 (9.0%, 95% CI 8.2% to 9.8%) were confirmed as glaucoma. The average follow-up time was 21.5±10.2 months. Using our current GS referral criteria, the sensitivity, specificity and PPV were 81.6% (95% CI 77.7% to 85.1%), 50.6% (95% CI 49.2% to 52.1%) and 14.0% (95% CI 13.4% to 14.7%), respectively, resulting in 2257 false positive cases. Increasing the VCDR cut-off for referral to ≥0.80, the specificity increased to 93.9% (95% CI 93.1% to 94.5%) but the sensitivity decreased to 11.3% (95% CI 8.5% to 14.6%), with a PPV of 15.4% (95% CI 12.0% to 19.4%). Opportunistic screening for glaucoma in a lower VCDR group could result in a high number of unnecessary referrals. If healthcare infrastructures are limited, targeting case findings on a larger VCDR group with high specificity will still be beneficial.


Methamphetamine abuse: medical and dental considerations.
Amphetamines are central nervous system stimulants with high abuse potential and intense physiological and psychological effects. Abuse of methamphetamine--a methyl derivative of amphetamine--has grown to epidemic proportions across the United States. Due to the characteristic signs of methamphetamine abuse that appear in the oral cavity dentists should have a heightened awareness of the medical and dental issues surrounding this dangerous behavior. Moreover, recognition and proper referral to treatment should be a part of every provider's plan for preventing the devastating psychological, oral, and overall systemic effects of methamphetamine abuse.


Unexpected clinical features in a female patient with proopiomelanocortin (POMC) deficiency.
Loss of function mutations of proopiomelanocortin (POMC) gene results in adrenal insufficiency, early-onset hyperphagic obesity, and red hair. However, neuromotor retardation with POMC deficiency has not been reported before. We report a female patient whose initial diagnosis was neurometabolic disease because of motor mental retardation, ataxia, and bilateral hyperintense lesions in the basal ganglia in cranial magnetic resonance imaging, increased lactate-lipid peak in proton magnetic resonance spectroscopy. She was consulted due to rapid weight gain, obesity, and episodes of hypoglycemia and homozygous mutation (c.64delA) in POMC gene was found. Severe motor mental retardation and cranial magnetic resonance imagingpathology in patients with POMC deficiency have not been reported previously in the literature. Bilateral hyperintense lesions in the basal ganglia and the increased lactate-lipid peak was thought to be the result of recurrent hypoglycemia.


Utility and sufficiency of psychiatric inpatient units in general hospitals: a cross-sectional study in Tokyo.
In order to investigate the utility and sufficiency of psychiatric beds in general hospitals (GHP beds), a cross-sectional study was performed in general hospitals all over Tokyo. Reasons for admission were acute-phase treatment (43%), medical comorbidity (15%), electroconvulsive therapy (13%), differential diagnosis (12%), and others (17%). The number of patients who could not be admitted to GHP beds despite appropriate reasons for admission was estimated to be greater than that of inpatients without indispensable reasons for admission to GHP beds on the day of the survey. GHP beds played the expected roles, and were in short supply.


Chronic myocardial infarction changed the excitatory-inhibitory synaptic balance in the medial prefrontal cortex of rat.
The medial prefrontal cortex is a key area for the regulation of pain and emotion. However, the functional involvement of the medial prefrontal cortex for visceral nociception, at the neuronal or synaptic level, is obscure yet. In the present study, the properties of excitatory and inhibitory synaptic transmission within the layer II/III of rat medial prefrontal cortex after chronic myocardial infarction were studied. It is found that the excitation-inhibition ratio of the medial prefrontal cortex was greatly changed, with enhanced excitation and decreased inhibition inputs to the pyramidal cells of the medial prefrontal cortex, which largely due to decreased spike firing in gamma-aminobutyric acid-ergic neurons. Behaviorally, inhibition of gamma-aminobutyric acid-ergic synaptic transmission alleviated the visceral pain and anxiety. It is thus for the first time showing that the excitation-inhibition ratio is increased in the medial prefrontal cortex after chronic myocardial infarction, which may come from the reduced intrinsic activity of gamma-aminobutyric acid-ergic neurons and is important for regulating the angina pectoris and anxiety induced by chronic myocardial infarction.


Heart involvement in muscular dystrophies due to sarcoglycan gene mutations.
Mutations in the sarcoglycan genes cause autosomal-recessive muscular dystrophies. Because sarcoglycan genes and their protein products are highly expressed both in skeletal and cardiac muscle, patients with these mutations might be expected to be at risk to develop dilated cardiomyopathy. We therefore studied 13 patients with alpha-, beta-, gamma-sarcoglycan gene mutations by thorough cardiological assessment. Electrocardiographic or echocardiographic abnormalities were observed in about 30% of cases showing a severe course of muscular dystrophy. No correlation was found between the presence of cardiac abnormalities and the type of mutation or sarcoglycan gene involved. The cardiac involvement was never severe, but it may be detected in early stages of the muscle disease. The absence of overt cardiac dysfunction may be due to lower sarcoglycan protein expression in cardiac than skeletal muscle or to less sarcolemmal instability at the myocardial level, possibly related to the different distribution of forces generated by contraction of the myocardium with respect to proximal limb-girdle muscles.


Use of DNA fluorochromes for studying meiosis in the woody species Thryptomene calycina.
The fluorescent DNA probes DAPI and Hoechst 33258 produce superior images to the traditional acetocarmine stain of the small chromosomes of the woody shrub Thryptomene calycina at all stages of microsporocyte meiosis and microspore mitosis. Hoechst 33258 was slightly superior to DAPI because of reduced background fluorescence. Binding with the DNA-specific probes required a fixative containing chloroform to remove autofluorescent materials, a pretreatment with acetic acid and a pH of least 6 during treatment. The nucleoli did not fluoresce after treatment with DAPI or Hoechst 33258. Superior resolution of chromosomes after treatment with the fluorochromes enabled easy determination of the haploid number at metaphase I, metaphase II and at metaphase of the microspore mitosis.


The Scottish school leavers cohort: linkage of education data to routinely collected records for mortality, hospital discharge and offspring birth characteristics.
The Scottish school leavers cohort provides population-wide prospective follow-up of local authority secondary school leavers in Scotland through linkage of comprehensive education data with hospital and mortality records. It considers educational attainment as a proxy for socioeconomic position in young adulthood and enables the study of associations and causal relationships between educational attainment and health outcomes in young adulthood. Education data for 284 621 individuals who left a local authority secondary school during 2006/2007-2010/2011 were linked with birth, death and hospital records, including general/acute and mental health inpatient and day case records. Individuals were followed up from date of school leaving until September 2012. Age range during follow-up was 15 years to 24 years. Education data included all formal school qualifications attained by date of school leaving; sociodemographic information; indicators of student needs, educational or non-educational support received and special school unit attendance; attendance, absence and exclusions over time and school leaver destination. Area-based measures of school and home deprivation were provided. Health data included dates of admission/discharge from hospital; principal/secondary diagnoses; maternal-related, birth-related and baby-related variables and, where relevant, date and cause of death. This paper presents crude rates for all-cause and cause-specific deaths and general/acute and psychiatric hospital admissions as well as birth outcomes for children of female cohort members. This study is the first in Scotland to link education and health data for the population of local authority secondary school leavers and provides access to a large, representative cohort with the ability to study rare health outcomes. There is the potential to study health outcomes over the life course through linkage with future hospital and death records for cohort members. The cohort may also be expanded by adding data from future school leavers. There is scope for linkage to the Prescribing Information System and the Scottish Primary Care Information Resource.


ERS-24, a mammalian v-SNARE implicated in vesicle traffic between the ER and the Golgi.
We report the identification and characterization of ERS-24 (Endoplasmic Reticulum SNARE of 24 kD), a new mammalian v-SNARE implicated in vesicular transport between the ER and the Golgi. ERS24 is incorporated into 20S docking and fusion particles and disassembles from this complex in an ATP-dependent manner. ERS-24 has significant sequence homology to Sec22p, a v-SNARE in Saccharomyces cerevisiae required for transport between the ER and the Golgi. ERS-24 is localized to the ER and to the Golgi, and it is enriched in transport vesicles associated with these organelles.


Correlations with operative anatomy of real time three-dimensional echocardiographic imaging of congenital aortic valvar stenosis.
To define the anatomic characteristics of the congenitally malformed and severely stenotic aortic valve using trans-thoracic real time three-dimensional echocardiography, and to compare and contrast this with the valvar morphology as seen at surgery. Prospective cross-sectional observational study. Tertiary centre for paediatric cardiology. All patients requiring aortic valvotomy between December 2003 and July 2004 were evaluated prior to surgery with three-dimensional echocardiography. Full volume loop images were acquired using the Phillips Sonos 7500 system. A single observer analysed the images using "Q lab 4.1" software. The details were then compared with operative findings. We identified 8 consecutive patients, with a median age of 16 weeks, ranging from 1 day to 11 years, with median weight of 7.22 kilograms, ranging from 2.78 to 22 kilograms. The measured diameter of the valvar orifice, and the number of leaflets identified, corresponded closely with surgical assessment. The sites of fusion of the leaflets were correctly identified by the echocardiographic imaging in all cases. Fusion between the right and non-coronary leaflets was identified in half the patients. Dysplasia was observed in 3 patients, with 1 patient having nodules and 2 shown to have excrescences. At surgery, nodules were excised, and excrescences were trimmed. The dysplastic changes correlated well with operative findings, though statistically not significant. We recommend trans-thoracic real time three-dimensional echocardiography for the assessment of the congenitally malformed aortic valve, particularly to identify sites of fusion between leaflets and to measure the orificial diameter. The definition of nodularity, and the prognosis of nodules based on the mode of intervention, will need a comparative study of patients submitted to balloon dilation as well as those undergoing surgical valvotomy.


Biochar and earthworms working in tandem: Research opportunities for soil bioremediation.
Intensive use of agrochemicals is considered one of the major threats for soil quality. In an attempt to mitigate their side-effects on non-target organisms and soil functioning, many engineering and biological remediation methodologies are currently available. Among them, the use of biochar, a carbonaceous material produced from pyrolysing biomass, represents an attractive option enhancing both remediation and soil carbon storage potentials. Currently, activation of biochar with chemical or physical agents seeks for improving its remediation potential, but most of them have some undesirable drawbacks such as high costs and generation of chemical wastes. Alternatively, the use of biological procedures to activate biochar with extracellular enzymes is gaining acceptance mainly due to its eco-friendly nature and cost-effectiveness. In these strategies, microorganisms play a key role as a source of extracellular enzymes, which are retained on the biochar surface. Recently, several studies point out that soil macrofauna (earthworms) may act as a biological vector facilitating the adsorption of enzymes on biochar. This paper briefly introduces current biochar bioactivation methodologies and the mechanisms underlying the coating of biochar with enzymes. We then propose a new conceptual model using earthworms to activate biochar with extracellular enzymes. This new earthworm-biochar model can be used as a theoretical framework to produce a new product "vermichar", vermicompost produced from blended feedstock, earthworms, and biochar that can be used to improve soil quality and remove soil contaminants. This model can also be used to develop innovative in-situ "vermiremediation" technologies utilizing the beneficial effects of both earthworms and biochar. Since biochar may contain toxic chemicals generated during its production stages or later concentrated when applied to polluted soils, this paper also highlights the need for an ecotoxicological knowledge around earthworm-biochar interaction, promoting further discussion on suitable procedures for assessing the environmental risk of this conceptual model application in soil bioremediation.


A mouse homolog of the Escherichia coli recA and Saccharomyces cerevisiae RAD51 genes.
Analysis of mitotic and meiotic recombination in mammalian cells has been hampered by the complexity of the reactions involved as well as lack of mutants. Furthermore, none of the genes involved in the process has yet been identified. In budding yeast, Saccharomyces cerevisiae, the RAD51 gene is essential along with other genes of the RAD52 epistasis group for mitotic and meiotic recombination and DNA repair. The Rad51 protein is structurally similar to Escherichia coli RecA protein, which is required in homologous recombination and SOS responses in bacteria. Here we report the isolation of a mouse homolog of the yeast RAD51 gene. The amino acid sequence predicted from the gene shows 83% and 55% homology with those of the yeast RAD51 and the E. coli recA product, respectively. The mouse gene complemented a rad51 mutation of S. cerevisiae with sensitivity to methyl-methanesulfonate, which produces double-strand breaks of DNA. This gene is expressed in the thymus, testis, ovary, spleen, and intestine, suggesting that its product is involved in mitotic and meiotic recombination in addition to DNA repair.


Increased Remyelination and Proregenerative Microglia Under Siponimod Therapy in Mechanistic Models.
Siponimod is an oral, selective sphingosine-1-phosphate receptor-1/5 modulator approved for treatment of multiple sclerosis. Mouse MRI was used to investigate remyelination in the cuprizone model. We then used a conditional demyelination Xenopus laevis model to assess the dose-response of siponimod on remyelination. In experimental autoimmune encephalomyelitis-optic neuritis (EAEON) in C57Bl/6J mice, we monitored the retinal thickness and the visual acuity using optical coherence tomography and optomotor response. Optic nerve inflammatory infiltrates, demyelination, and microglial and oligodendroglial differentiation were assessed by immunohistochemistry, quantitative real-time PCR, and bulk RNA sequencing. An increased remyelination was observed in the cuprizone model. Siponimod treatment of demyelinated tadpoles improved remyelination in comparison to control in a bell-shaped dose-response curve. Siponimod in the EAEON model attenuated the clinical score, reduced the retinal degeneration, and improved the visual function after prophylactic and therapeutic treatment, also in a bell-shaped manner. Inflammatory infiltrates and demyelination of the optic nerve were reduced, the latter even after therapeutic treatment, which also shifted microglial differentiation to a promyelinating phenotype. These results confirm the immunomodulatory effects of siponimod and suggest additional regenerative and promyelinating effects, which follow the dynamics of a bell-shaped curve with high being less efficient than low concentrations.


Contemporary trends in necrotizing soft-tissue infections in the United States.
Necrotizing soft-tissue infections (NSTI) are rare, potentially fatal, operative emergencies. We studied a national cohort of patients to determine recent trends in incidence, treatment, and outcomes for NSTI. We queried the Nationwide Inpatient Sample (1998-2010) for patients with a primary diagnosis of NSTI. Temporal trends in patient characteristics, treatment (debridement, amputation, hyperbaric oxygen therapy [HBOT]), and outcomes were determined with Cochran-Armitage trend tests and linear regression. To account for trends in case mix (age, sex, race, insurance, Elixhauser index) or receipt of HBOT on outcomes, multivariable analyses were conducted to determine the independent effect of year of treatment on mortality, any major complication, and hospital length of stay (LOS) for NSTI. We identified 56,527 weighted NSTI admissions, with an incidence ranging from approximately 3,800-5,800 cases annually. The number of cases peaked in 2004 and then decreased between 1998 and 2010 (P < .0001). The percentage of female patients decreased slightly over time (38.6-34.1%, P < .0001). Patients were increasingly in the 18- to 34-year-old (8.8-14.6%, P < .0001) and 50- to 64-year-old age groups (33.2-43.5, P < .0001), Hispanic (6.8-10.5%, P < .0001), obese (8.9-24.6%, P < .0001), and admitted with >3 comorbidities (14.5-39.7%, P < .0001). The percentage of patients requiring only one operative debridement increased somewhat (43.2-46.2%, P < .0001), whereas the use of HBOT was rare and decreasing (1.6-0.8%, P < .0001). The percentage of patients requiring operative wound closure decreased somewhat (23.5-20.8%, P < .0001). Although major complication rates increased (30.9-48.2%, P < .0001), hospital LOS remained stable (18-19 days) and mortality decreased (9.0-4.9%, P < .0001) on univariate analyses. On multivariable analyses each 1-year incremental increase in year was associated with a 5% increased odds of complication (odds ratio 1.05), 0.4 times decrease in hospital LOS (coefficient -0.41), and 11% decreased odds of mortality (odds ratio 0.89). There were potentially important national trends in patient characteristics and treatment patterns for NSTI between 1998 and 2010. Importantly, though patient acuity worsened and complication rates increased, but LOS remained relatively stable and mortality decreased. Improvements in early diagnosis, wound care, and critical care delivery may be the cause.


Role of growth hormone in polycystic ovarian syndrome.
Given recent in-vitro and in-vivo evidence that insulin and growth hormone may have gonadotropin-augmenting effects, the putative endocrine role of serum growth hormone levels in women with polycystic ovarian syndrome (PCOS) has been investigated in several studies since 1990. Obesity is a disease entity in its own right and, therefore, a confounding influence on investigations of PCOS. PCOS in the absence of obesity may be viewed as the "authentic syndrome". The use of IGF-1 as a marker of growth hormone secretion is not fully adequate as there is little to no correlation between this peptide and growth hormone in women with PCOS. The development of hyposomatotropinism in obese PCOS women appears to be an obesity-dependent event. The confirmed observation in both obese and lean women with and without PCOS of serum IGF-1 and IGFBP-3 levels requires further delineation. Preliminary evidence suggest that GH may play a role in the lean woman with PCOS and that the presence of obesity dampens its effect. Future investigations of the role of growth hormone in PCOS are dependent on first elucidating the role of GH in adult women and in the disease state of obesity.


Intravascular imaging during percutaneous coronary intervention: temporal trends and clinical outcomes in the USA.
Prior trials have demonstrated that intravascular imaging (IVI)-guided percutaneous coronary intervention (PCI) results in less frequent target lesion revascularization and major adverse cardiovascular events (MACEs) compared with standard angiographic guidance. The uptake and associated outcomes of IVI-guided PCI in contemporary clinical practice in the USA remain unclear. Accordingly, temporal trends and comparative outcomes of IVI-guided PCI relative to PCI with angiographic guidance alone were examined in a broad, unselected population of Medicare beneficiaries. Retrospective cohort study of Medicare beneficiary data from 1 January 2013, through 31 December 2019 to evaluate temporal trends and comparative outcomes of IVI-guided PCI as compared with PCI with angiography guidance alone in both the inpatient and outpatient settings. The primary outcomes were 1 year mortality and MACE, defined as the composite of death, myocardial infarction (MI), repeat PCI, or coronary artery bypass graft surgery. Secondary outcomes were MI or repeat PCI at 1 year. Multivariable Cox regression was used to estimate the adjusted association between IVI guidance and outcomes. Falsification endpoints (hospitalized pneumonia and hip fracture) were used to assess for potential unmeasured confounding. The study population included 1 189 470 patients undergoing PCI (38.0% female, 89.8% White, 65.1% with MI). Overall, IVI was used in 10.5% of the PCIs, increasing from 9.5% in 2013% to 15.4% in 2019. Operator IVI use was variable, with the median operator use of IVI 3.92% (interquartile range 0.36%-12.82%). IVI use during PCI was associated with lower adjusted rates of 1 year mortality [adjusted hazard ratio (aHR) 0.96, 95% confidence interval (CI) 0.94-0.98], MI (aHR 0.97, 95% CI 0.95-0.99), repeat PCI (aHR 0.74, 95% CI 0.73-0.75), and MACE (aHR 0.85, 95% CI 0.84-0.86). There was no association with the falsification endpoint of hospitalized pneumonia (aHR 1.02, 95% CI 0.99-1.04) or hip fracture (aHR 1.02, 95% CI 0.94-1.10). Among Medicare beneficiaries undergoing PCI, use of IVI has increased over the previous decade but remains relatively infrequent. IVI-guided PCI was associated with lower risk-adjusted mortality, acute MI, repeat PCI, and MACE.