Carboxyhemoglobin levels in patients with flu-like symptoms.
Subacute carbon monoxide poisoning is commonly misdiagnosed as an influenza-like viral illness. All patients presenting to the triage nurse at University Hospital with flu-like symptoms during February 1985 were asked to give blood samples for carboxyhemoglobin determination. Fifty-five patients (10% of those eligible) with headache, dizziness, nausea, vomiting, diarrhea, weakness, general malaise, or shortness of breath were enrolled in the study. Carboxyhemoglobin levels ranged from 0 to 21%. Thirteen patients (23.6%) of this self-selected subgroup had carboxyhemoglobin levels greater than or equal to 10%. There was no statistically significant difference in carboxyhemoglobin levels between smokers and nonsmokers. More patients using wood heat had elevated carboxyhemoglobin levels than patients using any other form of heating (P less than .05). No patient with a carboxyhemoglobin level greater than or equal to 10% was diagnosed as having subacute CO poisoning by emergency physicians. Physicians must seek out the possibility of CO toxicity in patients with flu-like illness, particularly in inner-city populations during the heating months. Fundoscopy and COHb levels may be useful in selected cases to correctly diagnose patients and avoid a return to a hazardous environment with potentially fatal consequences.


Successful treatment of non-HIV progressive multifocal leukoencephalopathy: case report and literature review.
Progressive multifocal leukoencephalopathy (PML) is a subacute onset demyelinating disease caused by JC virus and characterized by multifocal involvement of the subcortical white matter and cerebellar hemispheres or peduncles on magnetic resonance imaging (MRI). However, non-HIV PML patients with brain lesions limited to the cerebellum and brainstem have not been well characterized. We report a 68-year-old man with systemic lupus erythematosus under treatment with immunosuppressants who developed non-HIV PML with brain lesions limited to the cerebellum and brainstem and successfully treated with a combination of mefloquine and mirtazapine. We performed a literature review to characterize patients with non-HIV PML with brain lesions limited to the cerebellum and brainstem. Eight cases with non-HIV brainstem/cerebellar form PML were identified including our case. All cases had compromised status related underlying diseases. Four (50%) had a good prognosis. Five cases were treated, including 3 with favourable outcomes. Between the good prognosis group (n = 4) and the poor prognosis group (n = 4), treatment status for PML and the interval between the initial manifestation and diagnosis did not differ. Among those who performed contrast-enhanced brain imaging, lesion enhancement was related to good prognosis (good prognosis group vs. poor prognosis group; 100% vs. 0%). PML should be considered in the differential diagnosis of brain lesions limited to the cerebellum and brainstem in immunocompromised patients. The presence of immune response against JC virus and inflammatory reactions may indicate good prognosis in non-HIV brainstem/cerebellar form PML.


Effects of electrical stimulation of the dorsal raphe nucleus on local cerebral blood flow in the rat.
We have studied the effects of electrical stimulation of the dorsal raphe nucleus on local cerebral blood flow (LCBF), as assessed by the quantitative [14C]-iodoantipyrine autoradiographic technique. Stimulation of the dorsal raphe nucleus in the alpha-chloralose anesthetized rat caused a significant decrease in LCBF, ranging from -13 to -26% in 24 brain structures out of 33 investigated. The most pronounced decreases (-23 to -26%) were observed in the accumbens, amygdaloid, interpeduncular nuclei and in the median raphe nucleus, limbic system relays. The decreases also concerned cortical regions and the extrapyramidal system. These results indicate that activation of ascending serotonergic system produces a vasoconstriction and that the dorsal raphe nucleus has a widespread modulatory influence on the cerebral circulation.


Functionally distinctive testicular cell lines of zebrafish to support male germ cell development.
Here we describe two testicular cell lines of zebrafish with distinct functions to support the development of male germ cells. Twelve cell lines were established by single-colony isolation from tumor-like testis-derived ZtA6 cells, and the features characteristic of Sertoli cells such as phagocytic activity and transcription both of their specific genes, sox9a and Wilms' tumor suppressor WT1, and of the vas gene of germ cells were analyzed in the lines. Six lines exhibited these three characteristics of Sertoli cells. Despite the single-colony isolation, low levels of vas expression were detected in three lines. Two lines, ZtA6-2 and ZtA6-12, showed almost the same characteristics as Sertoli cells, but exhibited distinctive features when male germ cells were cocultured with each line as feeders. The in vitro fertilization by the culture of germ cells with ZtA6-12 produced more embryos than that with ZtA6-2. In contrast, ZtA6-2 gave rise to large clumps of germ cells after a 12-day culture, while ZtA6-12 still produced only small clumps. Expression of vas, strongly expressed in spermatogonia and premeiotic spermatocytes, was prolonged in the culture with ZtA6-2, while it reduced in that with ZtA6-12. Compared with the previous results obtained on the original ZtA6 cells, these results suggested that the function of the ZtA6-2 cells was directed to stimulate the proliferation of spermatogonia, and ZtA6-12 to stimulate the differentiation into sperm. These cell lines will facilitate investigation of Sertoli cell molecules that contribute to the proliferation and differentiation of spermatogonia, and the longer culture time of male germ cells by using these lines successively.


Hypoglycemia in diabetes among children and adolescents.
Hypoglycemia is one of the most common early complications in insulin-dependent diabetes mellitus (IDDM). Hypoglycemia in children may be considered a risk factor for brain damage and later intellectual impairment, and carries with it a high degree of child and parental anxiety. Recent studies have shown that in IDDM patients, and especially in those on intensive therapy, there is a defect in glucose counter-regulation, increased frequency of hypoglycemic episodes, loss of hypoglycemic awareness and responsiveness. Autonomic neuropathy, glucagon deficiency and low catecholamine response were implied in the pathogenesis of these disorders. In addition, uncontrolled IDDM patients show hypoglycemic symptoms at a higher blood glucose level. These recent observations may suggest that attempts to improve metabolic control may increase the risk of severe hypoglycemia. If so, some alterations in our therapeutic goals must be considered.


[Central pontine myelinolysis during qualified alcohol withdrawal therapy. A case report].
Central pontine myelinolysis is a rare but severe disease that often occurs in alcohol-dependent and malnourished patients. One pathological mechanism is the rapid correction of chronic hyponatremia, even though the disease can occur independently of decreased serum sodium levels. Here, we present a patient suffering from malnutrition, alcohol dependency, and a severe depressive disorder, who presented himself to our clinic wishing for qualified withdrawal treatment. Because the patient reported significant weight loss and nocturnal sweating without fever, we performed different diagnostic investigations and examinations. Cranial MRI revealed the presence of a central pontine myelinolysis. In the clinical neurological examination, the patient only showed slight gait ataxia. The depressive symptoms had improved while the patient now showed problems in his short-term memory. At presentation, only slight hyponatremia was present, while no rapid correction occurred throughout treatment. The presented case reveals the importance of considering osmotic demyelination disorders as a differential diagnosis in patients suffering from neurological symptoms during alcohol withdrawal therapy. This is important independently of hyponatremia.


How does air pollution affect the stock market performance? Evidence from China.
Given its broad impact on human society, air pollution could become a non-economic factor affecting the stock market. But the impact of air pollution on the stock market performance has not received enough attention. This study examines the influence and potential mechanism of air pollution on stock market performance based on the panel data of 1344 A-share listed firms in China covering the period 2013-2019. The result shows that air pollution can negatively affect stock market performance. Second, heterogeneity analysis creatively points out that firms with less analysts, smaller size, stated-owned ownership, polluting related industry are more vulnerable to the negative effects of air pollution. Finally, the result also reveals a mechanism that air pollution could worsen the stock market by depressing investors' sentiments. The above findings enrich current research related to the impact of air pollution on stock market performance and also provide a new perspective for investors to make stock investment decisions.


Construction and characterization of helper-dependent adenoviral vectors for sustained in vivo gene therapy.
A helper-dependent adenoviral (HDAd) vector is the most recently developed adenoviral vector. It does not contain any viral coding sequences except the inverted terminal repeat for replication origin and the packaging signal. Its safety profile and duration of transgene expression in vivo have improved substantially compared to early generation adenoviruses. Despite its usefulness for experimental gene therapy, technical difficulties in producing the HDAd vector have hampered its wide application. This chapter illustrates important considerations in vector design, unique features of this system, and an overview of vector production, which is followed by a step-by-step protocol for vector production. Vector characterization and troubleshooting are also provided at appropriate steps.


Importance and Impact of Appropriate Radiology in the Management of Branchial Cleft Anomalies.
Branchial cleft anomalies are common differential diagnosis of neck masses. However, depending on the origin (1st, 2nd, 3rd or 4th arch), this pathology presents at different locations as cyst, sinus and fistula. Incomplete excision or incision and drainage of infected branchial cleft anomalies (cystic presentation) can lead to multiple recurrences. Appropriate radiology is imperative to make a correct diagnosis and to achieve complete excision to prevent recurrence. Our case series highlights the mode of presentation, appropriate radiology and management for each type of branchial cleft anomalies. Data of 27 patients with the diagnosis of branchial cleft anomaly and treated in the department of Otolaryngology-Head and Neck Surgery in a tertiary care referral centre in last 5 years was analysed retrospectively. Demographic data in terms of age, sex, laterality, clinical presentation, duration of symptoms and radiological investigations if any were recorded. The mean age at presentation was 22.1 years in this series of 27 cases including six (22.2%) recurrent cases. Most common clinical presentation was discharging sinus (59.25%) followed by cystic neck swelling (33.3%). Second branchial cleft anomalies were commonest (51.8%) followed by first branchial cleft anomalies (29.6%). Appropriate radiology was available for 17 (62.9%) patients. Branchial cleft anomaly is an important differential diagnosis of neck mass. Appropriate radiology helps in complete excision and prevents recurrences. Recurrent cases pose surgical challenge owing to fibrosis from previous surgery which further increases the chances of incomplete excision.


High performance liquid chromatography for simultaneous determination of xipamide, triamterene and hydrochlorothiazide in bulk drug samples and dosage forms.
A novel, simple and robust high-performance liquid chromatography (HPLC) method was developed and validated for simultaneous determination of xipamide (XIP), triamterene (TRI) and hydrochlorothiazide (HCT) in their bulk powders and dosage forms. Chromatographic separation was carried out in less than two minutes. The separation was performed on a RP C-18 stationary phase with an isocratic elution system consisting of 0.03 mol L(-1) orthophosphoric acid (pH 2.3) and acetonitrile (ACN) as the mobile phase in the ratio of 50:50, at 2.0 mL min(-1) flow rate at room temperature. Detection was performed at 220 nm. Validation was performed concerning system suitability, limits of detection and quantitation, accuracy, precision, linearity and robustness. Calibration curves were rectilinear over the range of 0.195-100 μg mL(-1) for all the drugs studied. Recovery values were 99.9, 99.6 and 99.0 % for XIP, TRI and HCT, respectively. The method was applied to simultaneous determination of the studied analytes in their pharmaceutical dosage forms.


The splicing machinery is a genetic modifier of disease severity.
Disease severity correlates with the level of correctly spliced RNA transcribed from genes carrying splicing mutations and with the ratio of alternatively spliced isoforms. Hence, a role for splicing regulation as a genetic modifier has been suggested. Here we discuss recent experiments that provide direct evidence that changes in the level of splicing factors modulate the splicing pattern of disease-associated genes. Importantly, modulation of the splicing pattern led to regulation of the protein function and modification of disease severity.


Do antidepressants prevent transition to psychosis in individuals at clinical high-risk (CHR-P)? Systematic review and meta-analysis.
Emerging meta-analytical evidence indicates that baseline exposure to antipsychotics in individuals at clinical high-risk for psychosis (CHR-P) is associated with a higher risk of an imminent transition to psychosis. Despite their tolerability profile and potential beneficial effects, baseline exposure to antidepressants (AD) in CHR-P has surprisingly received far less attention as a potential risk modulator for transition to psychosis. The current systematic review and meta-analysis were performed to fix such a knowledge gap. Systematic scrutiny of Medline and Cochrane library, performed up to 1 August 2021, searching for English-language studies on CHR-P reporting numeric data about the sample, the transition outcome at a predefined follow-up time and raw data on AD baseline exposure in relation to such outcome. Of 1942 identified records, 16 studies were included in the systematic review and meta-analysis. 26% of the participants were already exposed to AD at baseline; at the end of the follow-up 13.5% (95% CI 10.2-17.1%) of them (n = 448) transitioned to psychosis against 21.0% (18.9 to 23.3%) of non-AD exposed CHR-P (n = 1371). CHR-P participants who were already under AD treatment at baseline had a lower risk of transition than non-AD exposed CHR-P. The RR was 0.71 (95% CI 0.56-0.90) in the fixed-effects model (z = -2.79; p = 0.005), and 0.78 (0.58-1.05) in the random-effects model (z = -1.77; p = 0.096; tau-squared = 0.059). There was no relevant heterogeneity (Cochran's Q = 18.45; df = 15; p = 0.239; I2 = 18.7%). Ongoing AD exposure at inception in CHR-P is associated to a reduced risk of transition to psychosis at follow up.


Improvement of the breastfeeding self-efficacy and postpartum mental health after lactation consultations - Observational study.
Maternal self-efficacy in breastfeeding may be undermined by common mental health difficulties in the postpartum, leading to an early breastfeeding cessation. The relationship may also be the opposite: problems with effective breastfeeding and breastfeeding cessation may increase the postpartum mental health difficulties. The purpose of this study was the assessment of the effectiveness of lactation consultations in strengthening the breastfeeding self-efficacy and maternal postpartum mental health. 160 Polish women (90 consultation participants and 70 controls) completed a structured interview, the General Health Questionnaire, and the Breastfeeding Self-Efficacy Scale twice: before lactation consultation and one month later. Research was conducted in the city of Gdańsk, Poland. Study revealed that women seeking lactation support exhibited greater mental health difficulties while their breastfeeding self-efficacy was similar to the control group. Initial breastfeeding self-efficacy was negatively correlated with the severity of the postpartum mental health problems. One month after lactation consultations, a significant increase in the breastfeeding self-efficacy and significantly reduced symptoms of mental health difficulties (somatic symptoms, functional disorders, and anxiety and insomnia) were observed among mothers. Women willing to benefit from the lactation consultations may exhibit symptoms of mental health difficulties that may be associated with difficulties in breastfeeding. Strengthening the breastfeeding confidence during lactation consultations, may reflect in the improvement of the woman's mental health. Midwives and lactation consultants can make a difference in the mental health promotion by offering breastfeeding interventions which address the emotional needs of a mother.


Successive and large-scale synthesis of InP/ZnS quantum dots in a hybrid reactor and their application to white LEDs.
We report successive and large-scale synthesis of InP/ZnS core/shell nanocrystal quantum dots (QDs) using a customized hybrid flow reactor, which is based on serial combination of a batch-type mixer and a flow-type furnace. InP cores and InP/ZnS core/shell QDs were successively synthesized in the hybrid reactor in a simple one-step process. In this reactor, the flow rate of the solutions was typically 1 ml min(-1), 100 times larger than that of conventional microfluidic reactors. In order to synthesize high-quality InP/ZnS QDs, we controlled both the flow rate and the crystal growth temperature. Finally, we obtained high-quality InP/ZnS QDs in colors from bluish green to red, and we demonstrated that these core/shell QDs could be incorporated into white-light-emitting diode (LED) devices to improve color rendering performance.


Fabrication and characterization of oleogels stabilized by metal-phenolic network coatings-decorated zein nanoparticles.
Self-assembly coatings are used to functionalize the surface structures of protein. Herein, emulsion-templated approach was adopted to obtain oleogels using metal-phenolic network coatings-decorated zein nanoparticles. Two self-assembly strategies were used to decorate zein nanoparticles: 1) adding (-)-epigallocatechin-3-gallate (EGCG) first and then calcium ions (Ca2+) (zein/EGCG/Ca2+ nanoparticles). 2) adding Ca2+ first and then EGCG (zein/Ca2+/EGCG nanoparticles). The formation of nanoparticles, the stability of emulsions and the rheological behaviors of oleogels were modulated by using different adding sequences of EGCG and Ca2+. Nanoparticles prepared by two self-assembly strategies exhibited increasing diameter (340-360 nm). More Ca2+ participated in the formation of zein/EGCG/Ca2+ nanoparticles, as described by X-ray photoelectron spectroscopy analysis. Metal-phenolic network coatings facilitated the formation of well-structured emulsions and oleogels, which were candidates for fat substitutes and stable carriers. Findings confirmed metal-phenolic network coatings-decorated zein nanoparticles were effective stabilizers for emulsions and oleogels, further expanding the selectivity of oleogelators.


Hierarchical and synergistic organization of control variables during the multi-digit grasp of a free and an externally fixed object.
In the referent control theory, grip force emerges by designating the referent aperture (Ra) as a threshold position inside the object. This study quantified Ra and investigated whether the synergistic control of digit referent coordinate (RC) and apparent stiffness (k) depend on the external mechanical constraints on the hand-held object. Subjects held a motorized handle capable of adjusting the grip width and performed static multi-digit prehension tasks in which the handle was free and externally fixed in different conditions. The RC and k of individual digits were reconstructed from the changes in digit normal forces and the positions as the grip width was modulated. RCs of the thumb and virtual finger were used to calculate the width and midpoint of Ra, and synergy indices quantifying the task-specific covariation in the space of the digit normal forces and {RC, k} variables were computed. We found that the k and width of the Ra were larger when holding a free handle than the fixed handle. The higher stiffness in the free condition could be a strategy to ensure grip stability. The midpoint of Ra was skewed toward the virtual finger, reflecting different magnitudes of k for the two digits. Further, the normal forces and control variables {RC, k} displayed synergistic covariation for stabilization of the total grasping force. Finally, the synergies were weaker when the handle was externally fixed, demonstrating the dependence of synergies on external constraints. These results add to the current literature by demonstrating that grasp control involves modulation of digit apparent stiffness in addition to the referent coordinate and by identifying the synergistic organization of the control variables during static grasp.


Is the curve relating temperature to aggression linear or curvilinear? A response to Bell (2005) and to Cohn and Rotton (2005).
P. Bell recommended examining the relationship between temperature and assaults during the hottest times of day and during the hottest months of the year. The authors' analyses of these data show a linear rather than inverted U-shaped relationship between temperature and assault during the hottest times of day and in the hottest months of the year. E. Cohn and J. Rotton recommended analyzing the 6 hr with the highest assaults versus the 6 hr with the lowest assaults. During high assault periods, there is a strong positive linear relationship between temperature and assault. During low assault periods, there is no relationship between temperature and assaults. Assaults and other violent crimes might decrease when temperatures are very hot, but the Minneapolis data set does not allow for testing of this hypothesis because Minneapolis is too cold.


High-Grade Desmoplastic Foamy Gland Prostatic Adenocarcinoma.
It is important to recognize high-grade foamy gland prostatic adenocarcinoma with desmoplastic stroma given its aggressive clinical course with frequent metastases and death. To review the morphology, immunohistochemistry, and prognosis for this rare subtype of prostate adenocarcinoma. Twenty-four cases received for consultation from 2010 to 2021 were analyzed including needle biopsy (n = 21), transurethral resection (n = 2), and a cystoprostatectomy (n = 1). Patients ranged in age from 40 to 89 years (mean, 67 years). On average, 8 cores per case were involved (mean 67% core involvement). Extraprostatic extension and seminal vesicle invasion were observed in 6 of 21 (29%) and 3 of 21 (14%) needle biopsy cases, respectively. Twenty of the 24 cases (83%) were Grade Group (GG) 5 with 4 of 24 (17%) being GG4. Tumor necrosis as a component of Gleason pattern 5 was observed in 21 of 24 cases (88%). Associated intraductal adenocarcinoma (IDC) was observed in 22 of 24 cases (92%), with 4 of 24 cases (17%) demonstrating extensive IDC. Diagnostic challenges were as follows: (1) sparse isolated cancer glands embedded in the dense desmoplastic stroma; (2) fragmented glands; and (3) aberrant staining for high-molecular-weight cytokeratin in a nonbasal cell pattern in all cases. PTEN loss was observed in 9 cases, and p53 nuclear accumulation was observed in 8 cases. Three patients were lost to follow-up. Overall, of the 16 patients with meaningful follow-up, 12 (75%) either had metastases or died from prostate cancer. High-grade desmoplastic foamy gland adenocarcinoma is difficult to diagnose and grade and has a poor prognosis.


Atomic structure of a short alpha-helix stabilized by a main chain hydrogen-bond surrogate.
Herein we report the 1.15 A X-ray crystal structure of a short alpha-helix in which the N-terminal i and i + 4 main chain hydrogen bond is replaced with a carbon-carbon bond. The structure shows that the hydrogen-bond surrogate (HBS) derived alpha-helix truly resembles the structure of canonical alpha-helices and provides unequivocal support for our helix nucleation strategy.


Age and sex distribution of infections with Entamoeba histolytica and Giardia intestinalis in the Lagos population.
Stool samples were collected from 2,099 persons and examined for parasites: 9.5 percent were infected with Entamoeba histolytica, 7.9 percent were infected with Giardia intestinalis and 15.5 percent were infected with Iodamoeba butschlii. The infections with E. histolytica and I. butschlii occurred more frequently in females than in males and adults were also more frequently infected than children. Infection with G. intestinalis, on the other hand, was more prevalent in males than in females and children were more frequently infected than adults with the highest incidence of infection (13.8 percent) in the age-group 1-5 years.


Isoproterenol-induced Mg2+ uptake in liver.
Isoproterenol increased the Mg2+ content of hepatocytes after injection into rats or after addition to collagenase-dispersed hepatocytes. cAMP also the increased cellular Mg2+ content of isolated hepatocytes. This effect was prevented by staurosporine. Phorbol ester had no effect on the Mg2+ content of isolated hepatocytes, and after injection of isoproterenol into rats, protein kinase C of liver was not affected. It was concluded that isoproterenol induced long-term Mg2+ influx via the activation of protein kinase A which can be inhibited by staurosporine.


High detection rates of cryptococcal antigen in pulmonary cryptococcosis by Eiken latex agglutination test with pronase pretreatment.
Two different kits for the detection of serum cryptococcal antigen in patients with pulmonary cryptococcosis were evaluated. The Eiken test (the Eiken Co., Tokyo), which uses pronase for pretreatment of serum, was compared with the Crypto-LA test (International Biological Laboratories, Cranbury, NJ), which did not use pronase prior to testing. Cryptococcal antigen was detected in 21 of 23 patients (91%) with the Eiken test and in only 10 of 23 patients (43%) with the Crypto-LA test (p < 0.01 by McNemar test). However, the sensitivity of two tests was identical without use of pronase, as both tests could detect as little as 10(4) cells/ml of Cryptococcus neoformans and 10 ng/ml of capsular polysaccharide of C. neoformans. In those serum specimens for which both tests were positive, titers were much higher for the Eiken test, but there was a statistically significant correlation between the two tests (coefficient correlation 0.79, p < 0.01). Cryptococcal antigen titer levels measured by the Eiken test correlated well with clinical courses. There was one false-positive reaction among 82 sera of non-cryptococcal patients. Pronase enhanced the sensitivity of the Eiken test, which appeared to be useful in patients with pulmonary cryptococcal disease, and its use may prevent unneeded lung biopsies.


Escaping the shackles of law at the end of life: R (Nicklinson) v Ministry of Justice [2012] EWHC 2381 (Admin).
This commentary discusses the decision in R (Nicklinson) v Ministry of Justice;(1) it will argue that the court should have allowed the use of the defence of necessity. It argues that the official response of the law should be to outlaw euthanasia or assisted suicide, but also to recognise that in exceptional circumstances these should be permitted. The use of the defence of necessity permits this nuanced response to the issue. The commentary also argues that the treatment of suicidal and elderly people is a far more important issue than creating the correct legal response to assisted dying.


Survey of anesthesiologists' practices related to steep Trendelenburg positioning in the USA.
Steep Trendelenburg during surgery has been associated with many position-related injuries. The American Society of Anesthesiology practice advisory recommends documentation, frequent position checks, avoiding shoulder braces, and limiting abduction of upper extremities to avoid brachial plexopathy. We conducted a web-based survey to assess anesthesiologists' practices, institutional policies, and complications encountered when using steep Trendelenburg. Two thousand fifty randomly selected active members of the American Society of Anesthesiology were invited via email to participate in a 9-item web-based survey. Results are reported as absolute numbers and proportions with 95% confidence interval (CI). Survey response rate was 290 of 2050 (14.1%). 44.6% (95% CI, 38.9-50.3) of the respondents documented anesthesia start and finish, 73.9% (95% CI, 68.8-79) frequently checked positioning during surgery, 30.8% (95% CI, 25.4-36.2) reported using shoulder braces, 66.9% (95% CI, 61.5-72.3) tucked patients' arms to the side, 54.0% (95% CI, 48.2-59.8) limited fluid administration, and more than two-thirds did not limit the duration or inclination angle. Notably, 63/290 (21.7%) reported a complication and only 6/289 (2.1%) had an institutional policy. The most common complication was airway and face edema, second was brachial plexus injury, and third was corneal abrasions. Most institutional policies, when present, focused on limiting duration of steep Trendelenburg and communication with surgical team. Only 1/6 policies required avoiding use of shoulder braces. Based on survey results, practices related to steep Trendelenburg varied among USA anesthesiologists. Differences included protective measures, documentation, positioning techniques, fluid management, and institutional guidelines. The singular commonality found among all respondents was lack of institutional policies. Survey results highlighted the need for institutional policies and more education.


Comparative toxicokinetics of explosive compounds in sheepshead minnows.
Juvenile sheepshead minnows Cyprinodon variegatus were exposed to the explosive compounds 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) and to the TNT transformation products 2-aminodinitrotoluene (2-ADNT) and 2,4-diaminonitrotoluene (2,4-DANT) in five separate water-only experiments. A one-compartment model was used to characterize uptake (k(u)) and elimination (k(e)) rate constants and to estimate bioconcentration factors (BCFs). The compounds investigated in this study are weakly hydrophobic. Kinetically derived BCFs (9.6, 13.1, 0.5, 1.7, and 0.5 ml g(-1) for TNT, 2-ADNT, 2,4-DANT, RDX, and HMX, respectively) confirmed the expected low bioaccumulative potential of those compounds and the positive relationship between log BCF and log K(ow) (1.6, 2.0, 0.8, 0.9, and 0.2 for TNT, 2-ADNT, 2,4-DANT, RDX, and HMX, respectively). The uptake clearance (k(u)) was relatively slow for all compounds (7.3, 12.6, 1.3, 0.15, and 0.06 ml g(-1)h(-1) for TNT, 2-ADNT, 2,4-DANT, RDX, and HMX, respectively), and overall, it decreased with decreasing compound hydrophobicity. Elimination was extremely fast for the nitroaromatic compounds (0.77, 0.96, and 2.74 h(-1) for TNT, 2-ADNT, and 2,4-DANT, respectively), thus resulting in very short biological half-lives (<1 hour), but it was much slower for the cyclonitramines (0.09 h(-1) for RDX and 0.12 h(-1) for HMX). Although ADNTs were present in fish exposed to TNT, the parent compound was the dominant compound in tissues during the uptake and elimination exposures. The rates of metabolite formation (0.06 h(-1)) and elimination (0.16 h(-1)) were much slower than the rate of elimination of the parent compound (0.80 h(-1)). Because of the fast elimination rate of TNT and its transformation products and the exceedingly low bioaccumulative potential of RDX and HMX, exposure conditions likely associated with the presence of explosives in aquatic systems are unlikely to pose unacceptable risks to fish.


A prospective pilot study of two-session Gamma Knife surgery for large metastatic brain tumors.
The purpose of this prospective study is to evaluate the efficacy and limitations of two-session Gamma Knife radiosurgery (GKS) alone for large metastatic brain tumors. Inclusion criteria were as follows: (i) patients with large metastatic brain tumors (volume >15 cm(3) in the supratentorial region or >10 cm(3) in the infratentorial region), and (ii) tumors not causing clinical signs of impending cerebral herniation. Twenty-eight lesions in 27 consecutive patients (18 men and 9 women, age range 32 to 88 years, median age 65 years) were included in this study. The radiosurgical protocol was as follows: 20-30 Gy given in two fractions 3-4 weeks apart. The local tumor control rate and the overall survival rate were calculated by using the Kaplan-Meier method. Median tumor volumes were 17.8 cm(3) at first GKS and 9.7 cm(3) at second GKS. Median follow-up time was 8.9 months. The local control rate was 85 % at 6 months and 61 % at 12 months. The overall survival rate after GKS was 63 % at 6 months and 45 % at 12 months. The 1-year rate of prevention of neurological death was maintained at 78 %. Mean Karnofsky performance status (KPS) improved from 61 [95 % confidence interval (CI), 57-71] at first GKS to 80 (95 % CI, 74-85) at second GKS; the best follow-up mean KPS was 85 (95 % CI, 78-91) (p < 0.001). Local tumor recurrence necessitated craniotomy in two patients and repeat GKS in three patients. Seventeen patients died, and the causes of death were as follows: 3 from local progression, 2 from meningeal carcinomatosis, and 12 from progression of the primary tumor. Delayed symptomatic perilesional edema developed in one patient and eventually resolved with conservative treatment. Two-session GKS for large brain metastases appears to be an effective treatment in terms of both local tumor control and neurological palliation with minimal treatment-related morbidity. These data suggest that two-session GKS could be used as an alternative to surgical resection of large tumors in patients with significant comorbidity and/or at an advanced age. The optimum regimen for dose and fraction schedule remains to be established.


Surgical options for treating ventricular tachyarrhythmia and sudden death.
From 1981 to 1987, 62 patients with ventricular tachyarrhythmias and associated sudden death required treatment after unsuccessful initial medical therapy (51 patients) and previous surgical therapy (11 patients). Surgical options included direct revascularization (group I, 11 patients), endocardial resection (group II, 7 patients), automatic internal cardiac defibrillators (group III, 18 patients), and these combinations of operations: revascularization and endocardial resection (group IV, 18 patients), revascularization and insertion of automatic internal cardiac defibrillators (group V, 5 patients), and endocardial resection and insertion of cardiac defibrillator (group VI, 3 patients). Five underwent repeat revascularization (4) or endocardial resection (4) with mitral valve replacement (1) or papillary muscle reconstruction (2). The overall operative mortality of 8.1% (5/62) has been acceptable (2.8% or 1/36 for the simple procedures [groups I, II, and III] and 15.4% or 4/26 for the combined procedures [IV, V, and VI]; p less than 0.074). Operative risk factors included recent myocardial infarction (4/5 deaths) and depressed ejection fraction of 23% or less (5/5 deaths). These operative risks were highest in group IV and, thus, the highest mortality was in group IV (4/18 patients or 22%, p less than 0.022). Six late deaths (4 patients in group III) brought the overall survival rate to 82% or 51/62 patients at a mean follow-up of 30 months. Surgical treatment of sudden death ventricular tachyarrhythmias requires a planned, combined operative approach, since initial medical or surgical failures can occur. The optimal surgical approach requires complete revascularization, resection of the localized subendocardial arrhythmogenic focus, and ventricular reconstruction. An automatic defibrillator is a palliative alternative for less favorable surgical anatomy and for patients who are poor operative candidates for these combined or reoperative procedures.


Determination of factors affecting prevention of burns among children under five years old using PRECEDE model: A cross-sectional study in urban and rural populations.
Burns are one of the most important childhood injuries that can be controlled and prevented. Mothers play an important role in preventing child burns. Health education and promotional theories facilitate a precise recognition of the behavioral factors in mothers that help preventing burn injury in their children. Burns in children under five years old and the factors in prevention of burn by their mothers were examined using PRECEDE Model. The study environment was rural and urban areas of Kermanshah, Iran. This cross-sectional study was conducted on 330 mothers in urban and rural areas of Kermanshah County in the west of Iran. The participants were randomly selected among mothers who had at least one child younger than five years old. Data was collected through interviewing the mothers using a valid and reliable questionnaire. The questionnaire included questions on demographic characteristics, PRECEDE Model, and history of burn. The data were analyzed using SPSS-16. The mean age of the mothers in urban areas (29.33 ± 5.987) was higher than that of those in rural areas (28.77 ± 6.236). More than 90% of the mothers were housewives, both in urban and rural areas. The rate of a history of burn in rural children under the age of five (8.3%) was greater than that in urban children (5.2%). Most of the burn cases in urban areas were mild whereas those in rural areas were moderate. The majority of burn cases had happened at home in children 1-3 years' age range; this rate was higher in boys. The majority of burns cases had happened when the child was playing (urban: 64.3%, rural: 100%). In addition, liquids and hot objects were the main causes of the burns (urban: 78.5%, rural: 100%). Among the constructs of PRECEDE models in the urban areas, knowledge (P < 0.001), attitudes (P = 0.027), and environmental factors (P = 0.03) had a significant relationship with burn-preventive behaviors in mothers. In addition, in the rural areas, attitudes (P = 0.038) had a significant relationship with burn-preventive behaviors in mothers. Burn was an important injury in the study population, especially in the rural areas. The PRECEDE model can help us to identify the factors in burn injuries in children and the preventive behaviors in mothers. The findings can be used to develop preventive interventional programs to better protect this vulnerable group in society.


Infection surveillance and selective decontamination of the digestive tract (SDD) in critically ill patients--results of a controlled study.
All ICU patients were continuously monitored for infections according to a standard protocol by the physician in charge and an infection control nurse during the first quarter of five consecutive years (1980-1984). The number of patients surveyed was 1,009. The average age was 45.5 years and the average period of stay about four days. 733 patients (72.6%) were intubated and artificially ventilated for three days. A fatal outcome resulted in 13.2% of all patients, 1,129 nosocomial infections were registered in 331 patients, which means an infection rate of 32.8%. The most frequent nosocomial infections were those of the respiratory tract (24.3%). Wound infections developed in 16.6%. The urinary tract was affected in 8.8%. Nosocomial septicaemias were observed in 8.7%. Catheter-associated infections were found in 6.7% of the patients. A fatal outcome resulted in 26% of the patients with nosocomial infections and in 6.9% of the non-infected patients, respectively. There was no significant reduction in nosocomial infections over the five-year period in our ICU. Therefore, a study was designed to evaluate the concept of selective decontamination of the digestive tract (SDD) in critically ill patients in our two surgical/traumatological ICUs. A prospective, consecutive, placebo-controlled study in two ICUs was carried out during four six-month periods. 200 patients who were intubated for at least three days, required intensive care for a minimum of five days, and belonged to either class III or IV according to the "Therapeutic Intervention Scoring System" were included in the study. They received either placebo or a prophylaxis regimen, consisting of polymyxin E, tobramycin and amphotericin B.(ABSTRACT TRUNCATED AT 250 WORDS)


Cerebral venous sinus thrombosis in a neonate due to factor V Leiden deficiency.
A case is described of cerebral venous sinus thrombosis due to factor V Leiden deficiency that occurred in the neonatal period, presenting with seizures. Diagnosis was based on ultrasonography, Doppler ultrasound (US) and magnetic resonance imaging (MRI). The aetiology was only recognized after blood-clotting tests, antithrombin III, C and S protein levels and factor V Leiden were studied. This situation was treated with intravenous heparin controlled by activated partial thromboplastin time (APTT). MRI angiography and Doppler US were important in the follow-up. It is important to assess periodically the neurological development of the baby and to prevent situations such as dehydration or severe infection, which can precipitate further thrombotic events. Molecular genetics allowed the identification of this trait in other family members. In every newborn with a thrombotic episode, coagulation studies must be performed, including testing for activated protein C (APC) resistance. Doppler US flow measurement and the MRI studies provide the best tools for diagnosis and follow-up. Heparin should be given to double the initial individual APTT. It is important to prevent any risk situation such as dehydration or severe infection, which could lead to a recurrence of a thrombotic episode. Regular assessment of the child's neurodevelopment is an important aspect of further care.


Proton pump inhibitors affect sperm parameters by regulating aquaporins.
Proton pump inhibitors (PPIs) were one of the most commonly used drugs in daily life. The adverse effects of long-term use of PPIs have aroused widespread controversy. It was of great significance to explore the molecular mechanism of sperm abnormality caused by PPIs. The PPI group was given omeprazole by gavage for 28 days. After the omeprazole intervention, the caudal epididymis was dissected to obtain sperms, and the sperm was counted through the microscope, as the acrosomal integrity was observed through PNA-FITC staining. The expression of aquaporins were detected by immunofluorescence and western blot in the testis, epididymis and spermatozoa. The liver cytochrome enzyme was evaluated by immunohistochemistry and western blot. We detected the serum estrogen level by ELISA, and the level of alanine transaminase (ALT) were detected through microplate method. The sperm count in PPI group was less than control group (p < 0.05), and the sperm acrosin integrity in PPI group was lower than control group (p < 0.05). In the testis, the expression of aquaporin 3 and aquaporin 8 in PPI group was higher than control group (p < 0.05), while the expression of aquaporin 7 was lower than control group (p < 0.05). In the epididymal and sperm, the expression of aquaporin 3 and aquaporin 7 in PPI group was higher than control group (p < 0.05), while the expression of aquaporin 8 in PPI group was lower than control group (p < 0.05). Meanwhile, the liver cytochrome enzyme in PPI group were lower than control group (p < 0.05), and estrogen and ALT in PPI group were higher than control group (p < 0.05). PPI may lead to the up-regulation of estrogen by inhibiting the activity of cytochrome enzyme, and then lead to the dysfunction of sperm parameters and acrosin integrity by affecting aquaporins function.


Supervised segmentation of MRI brain images using combination of multiple classifiers.
Segmentation of different tissues is one of the initial and most critical tasks in different aspects of medical image processing. Manual segmentation of brain images resulted from magnetic resonance imaging is time consuming, so automatic image segmentation is widely used in this area. Ensemble based algorithms are very reliable and generalized methods for classification. In this paper, a supervised method named dynamic classifier selection-dynamic local training local tanimoto index, which is a member of combination of multiple classifiers (CMCs) methods is proposed. The proposed method uses dynamic local training sets instead of a full statics one and also it change the classifier rank criterion properly for brain tissue classification. Selection policy for combining the different decisions is implemented here and the K-nearest neighbor algorithm is used to find the best local classifier. Experimental results show that the proposed method can classify the real datasets of the internet brain segmentation repository better than all single classifiers in ensemble and produces significantly improvement on other CMCs methods.


Microstructure and load bearing capacity of TiN/NbN superlattice coatings deposited on medical grade CoCrMo alloy by HIPIMS.
In recent years significant progress has been made in the application of various ceramic, namely Metal nitride (MeN) functional coatings to engineer the surfaces of medical implants utilising metal-on-metal (MoM) articulation. This article reports on the load bearing capacity and structural response of TiN/NbN superlattice coatings deposited on medical grade CoCrMo alloy substrate under the application of localised load and the subsequent crack formation mechanism. The coatings have been deposited by mixed High Power Impulse Magnetron Sputtering-Unbalanced Magnetron Sputtering (HIPIMS-UBM) process. In the case of TiN/NbN coating deposited on CoCrMo substrate where Ecoating/Esubstrate is as high as 1.81 indicating that the substrate does not provide the necessary load bearing support for the brittle thin film, the utilisation of the Berkovich indentation technique proved to be a potent approach to study coating material as well as structural response to applied concentrated load. FIB/SEM analyses of the indented coatings revealed that in the hard-on-soft material systems cracks will initiate due to sub-coating substrate deformation and then propagate towards the coating surface. The FIB/SEM and low magnification XTEM analysis showed that an exceptionally strong TiN/NbN coating substrate adhesion bonding was achieved due to the utilisation of the HIPIMS pre-treatment. High resolution XTEM analyses revealed, for the first time, that during the indentation a collective rotation and alignment of the individual layers of the superlattice stack takes place without compromising coatings integrity which is clear evidence for the exeptionally high coating fracture toughness. The high toughness of the superlattice structured TiN/NbN coatings combined with their exceptionally high adhesion on madical grade CoCrMo ranks them as a strong candidate for medical implant applications.


Proliferative generation of mammalian auditory hair cells in culture.
Hair cell (HC) and supporting cell (SC) productions are completed during early embryonic development of the mammalian cochlea. This study shows that acutely dissociated cells from the newborn rat organ of Corti, developed into so-called otospheres consisting of 98% nestin (+) cells when plated on a non-adherent substratum in the presence of either epidermal growth factor (EGF) or fibroblast growth factor (FGF2). Within cultured otospheres, nestin (+) cells were shown to express EGF receptor (EGFR) and FGFR2 and rapidly give rise to newly formed myosin VIIA (+) HCs and p27(KIP1) (+) SCs. Myosin VIIA (+) HCs had incorporated bromodeoxyuridine (BrdU) demonstrating that they were generated by a mitotic process. Ultrastructural studies confirmed that HCs had differentiated within the otosphere, as defined by the presence of both cuticular plates and stereocilia. This work raises the hypothesis that nestin (+) cells might be a source of newly generated HCs and SCs in the injured postnatal organ of Corti.


The PARN, TOE1, and USB1 RNA deadenylases and their roles in non-coding RNA regulation.
The levels of non-coding RNAs (ncRNAs) are regulated by transcription, RNA processing, and RNA degradation pathways. One mechanism for the degradation of ncRNAs involves the addition of oligo(A) tails by non-canonical poly(A) polymerases, which then recruit processive sequence-independent 3' to 5' exonucleases for RNA degradation. This pathway of decay is also regulated by three 3' to 5' exoribonucleases, USB1, PARN, and TOE1, which remove oligo(A) tails and thereby can protect ncRNAs from decay in a manner analogous to the deubiquitination of proteins. Loss-of-function mutations in these genes lead to premature degradation of some ncRNAs and lead to specific human diseases such as Poikiloderma with Neutropenia (PN) for USB1, Dyskeratosis Congenita (DC) for PARN and Pontocerebellar Hypoplasia type 7 (PCH7) for TOE1. Herein, we review the biochemical properties of USB1, PARN, and TOE1, how they modulate ncRNA levels, and their roles in human diseases.


(1)H-MRS profile in MRI positive- versus MRI negative patients with temporal lobe epilepsy.
The objective of this study was to quantitate and compare ipsilateral total N-acetyl aspartate (tNAA), creatine (Cr), choline (Cho), myo-inositol (m-Ins) and glutamate plus glutamine (Glx) levels in the hippocampi of patients with temporal lobe epilepsy (TLE) with and without magnetic resonance imaging (MRI) evidence for mesial temporal sclerosis (MRI positive/negative). Twenty-three age matched healthy controls and 26 consecutive patients with unilateral TLE, based on intensive 24h video-EEG, were investigated with proton magnetic resonance spectroscopy ((1)H-MRS) (17 with unilateral hippocampal sclerosis (HS) in MRI-MRI positive; 9 MRI negative). For statistical analysis one-way analysis of variance (ANOVA) with post hoc multiple comparisons and Bonferroni correction was applied. The significance level was based on p<0.05. The mean tNAA level ipsilateral to the seizure focus was significantly decreased in MRI negative, respectively MRI positive patients in comparison to healthy controls (p<0.001). The lowest tNAA level was noticed in the MRI positive group (p<0.001). Statistical analysis highlighted a clear "tNAA cut-off" (95% confidence interval) between MRI positive- and MRI negative patients and healthy controls. Mean level of Glx and m-Ins was not significantly elevated or reduced. However, in individual cases a significant elevation was noticed for Glx in MRI negative patients, respectively for m-Ins in MRI positive patients. MRI negative TLE patients have a different MRS profile than MRI positive patients (HS) with marginal but significant decrease of tNAA. Our results reveal a clear "tNAA cut-off" between the groups. The value of m-Ins and Glx in focus detection in TLE patients remains controversy.


Cellular pathogenesis of porcine circovirus type 2 infection.
Porcine circovirus associated disease (PCVAD) and the associated histological lesions are thought to appear due to an increase in the amount of porcine circovirus type 2 (PCV2) present in an infected animal. However, examination of the cellular and molecular pathogenesis of PCVAD is complicated by the lack of a consistent cell culture model that replicates the animal phenotypes of persistent, asymptomatic infection, and acute, pathological disease typified by lymphocyte depletion. The porcine fetal retina cell line, VR1BL, shows a high permissiveness to PCV2 infection, 40 times higher than the alternative PK15 culture model, allowing for high titer viral production, with PCV2b growth higher than PCV2a growth. Cytopathic effect due to apoptosis is observed after challenge with high amounts of PCV2, but at low levels, infection is maintained in passaged cells. Thus, VR1BL cells may be used as a model system to examine both acute viral pathogenesis and cellular innate defense, as well as persistent PCV2 infection.


Spontaneous Growth of Ultra-Long SiO(x) Nanowires from SiC Thin Films by Thermal Annealing.
The use of a simple thermal treatment for growing ultra-long SiO(x) nanowires on silicon carbide (SiC) thin films is reported for the first time. SiC thin films with a thickness of 100 nm were prepared by sputtering at room temperature followed by annealing in an Ar/H2 gas atmosphere. The growth of SiO(x) nanowires started when the annealing temperature was at 1200 degrees C, and was rapidly and spontaneously grown at temperatures above 1250 degrees C. The diameters of as-grown SiO(x) nanowires with lengths up to several hundred micrometers were determined to be -1 μm.


Perioperative opioid use in paediatric inguinal hernia patients: A systematic review and retrospective audit of practice.
Opioids play a major role in postoperative pain management in children, but their administration remains an under investigated topic. This study aimed to describe perioperative opioid prescribing practices for paediatric inguinal hernia patients in the literature and at The Royal Children's Hospital (RCH) in Melbourne, Australia. A systematic review of English articles (published from 2009 to 2019) was conducted on paediatric (0-18y) inguinal hernia patients who received a postoperative or discharge opioid prescription, or both. The review was combined with a retrospective audit of RCH patients. Demographic, surgical, and analgesic details were collected from the electronic medical records. Fifteen studies (n = 1166; combined mean age 4.93y) met the systematic review criteria. The percentage of patients receiving opioids postoperatively overall ranged from 3.33-100%, and doses ranged from 0.07 to 0.35 mg/kg oMEDD. At the RCH, perioperative opioid use was analyzed from 150 inguinal hernia patients (male - 113, median age - 3 months old). Postoperatively, 26 (17.3%) patients received opioids. The most commonly administered opioids were fentanyl (0.04-0.60 mg/kg oMEDD) in the post anaesthesia care unit and oxycodone (0.14-0.40 mg/kg oMEDD) in the first 24 h postoperatively. Older age at surgery, female sex and absence of regional anaesthesia were significantly associated with higher risk of total opioid use. No patients received an opioid prescription at discharge. There is demonstratable variability in opioid prescribing practices for paediatric inguinal hernia patients as described in the literature. At our institution opioids were not used frequently in postoperative period.


In situ Self-Catalyzed Growth of Manganese-Embedded 3D Flakes-Coated Carbon Rod as an Efficient Oxygen-Reduction Reaction Catalyst of Zinc-Air Batteries.
The in situ self-catalyzed growth of manganese-embedded 3D flakes-coated carbon rods (GFC) as an efficient oxygen-reduction reaction (ORR) catalyst of Zinc-air batteries is described for the first time. By optimizing the amount of Mn in the precursor, a series of 3D graphene-like flakes-coated carbon rods were synthesized. GFC with a doping amount of Mn of 10 % (GFC-10) exhibits excellent ORR performance with an onset potential of 0.94 V (vs. reversible hydrogen electrode). The Zinc-air battery is constructed with GFC-10 as the cathode catalyst, and it exhibits a peak power density of 128.9 mW cm-2 and a cycling stability of 75 h at a current density of 10 mA cm-2 , which are superior to the commercial 20 wt% Pt/C-based Zinc-air battery. Interestingly, the introduction of Mn facilitates the self-catalyzed growth of carbon rods, and the change of Mn amount can effectively regulate the morphology of materials. The improved ORR performance of the catalyst is ascribed to the synergistic effect of unique hierarchical porous structure, high-charge transport capacity, abundant carbon defects/edges and Mn-Nx sites. This research provides a new avenue to fabricating highly active Mn-based electrocatalysts for renewable energy systems.


Oxygen Kinetics During Corneal Cross-linking With and Without Supplementary Oxygen.
To measure and simulate oxygen kinetics during corneal cross-linking at different irradiances with and without supplementary oxygen. Experimental, laboratory study. In de-epithelialized porcine eyes, a femtosecond-laser-generated tunnel was used to place a fiber probe in corneal depths of 100, 200, and 300 μm to measure the local oxygen concentration. After riboflavin imbibition, the corneas were irradiated at 3, 9, 18, and 30 mW/cm2 while the oxygen concentration was measured. All experiments were performed under normoxic (21%) and hyperoxic (>95%) conditions. The obtained data were used to identify parameters of a numerical model for oxygen consumption and diffusion. The equilibrium stromal oxygen concentration under atmospheric oxygen at 3 mW/cm2 was 2.3% in 100 μm decreasing to <1% in 300 μm. With 9, 18, and 30 mW/cm2, no oxygen was available in 200 μm, respectively, 100 μm or deeper. Using a hyperoxic environment, the concentration was 50% using 3 mW/cm2 in 100 μm, decreasing to 40% in 300 μm. At 9 mW/cm2, the concentrations were 5%, 3%, and 1% in 100, 200 and 300 μm, respectively. Using 18 and 30 mW/cm2, all oxygen was depleted at 100 μm; however, oxygen half-lives were longer at 18 mW/cm2 than at 30 mW/cm2. The oxygen model was able to reproduce the experiments and indicated an exponential decay with increasing distance to the anterior surface. Supplementary oxygen increases the oxygen availability during corneal cross-linking. At higher irradiances, supplementary oxygen is beneficial and eliminates the bottleneck of oxygen allowing a potentially more efficient cross-linking. The calibrated numerical model can quantify the spatial oxygen concentration related to different scenarios such as irradiance or environmental oxygen concentration.


The polytetrafluoroethylene (PTFE) channel model of cyclic-buildup biofilm and traditional biofilm: The impact of friction, and detergent on cleaning and subsequent high-level disinfection.
To evaluate the efficacy of detergent and friction on removal of traditional biofilm and cyclic-buildup biofilm (CBB) from polytetrafluoroethylene (PTFE) channels and to evaluate the efficacy of glutaraldehyde to kill residual bacteria after cleaning. PTFE channels were exposed to artificial test soil containing 108 CFU/mL of Pseudomonas aeruginosa and Enterococcus faecalis, followed by full cleaning and high-level disinfection (HLD) for five repeated rounds to establish CBB. For traditional biofilm, the HLD step was omitted. Cleaning with enzymatic and alkaline detergents, bristle brush, and Pull Thru channel cleaner were compared to a water flush only. Carbohydrate, protein, viable count, adenosine triphosphate (ATP) levels were analyzed and atomic force microscopy (AFM) was performed. In the absence of friction, cleaning of traditional biofilm and CBB was not effective compared to the positive control (Dunn-Bonferroni tests; P > .05) regardless of the detergent used. ATP, protein, and carbohydrate analyses were unable to detect traditional biofilm or CBB. The AFM analysis showed that fixation resulted in CBB being smoother and more compact than traditional biofilm. Friction during the cleaning process was a critical parameter regardless of the detergent used for removal of either traditional biofilm or CBB. Glutaraldehyde effectively killed the remaining microorganisms regardless of the cleaning method used.


Biomechanics of walking in adolescents with progressive pseudorheumatoid arthropathy of childhood leads to physical activity recommendations as therapeutic focus.
Progressive pseudorheumatoid arthropathy of childhood is a rare disease with an estimated prevalence of approximately 1/1,000,000. The disease manifests around the age of three to eight years and progresses with symptoms of early fatigue, muscle weakness, joint swelling and stiffness. The resulting functional limitations are often described as having a waddling gait. Walking is difficult and can be managed with multilevel compensation movements only. Aims of this study were to determine typical malpositions that arise during walking and to identify preventive strategies to reduce excessive joint damage. This study presents data of three-dimensional gait analysis of nine patients with progressive pseudorheumatoid arthropathy of childhood (♀=2; ♂=7; 13.3y; 47.0kg; 1.39m; BMI: 24.2kg/m(2)) performed with eight infrared cameras and the Plug-in-Gait Model. For comparison of spatiotemporal and kinematic parameters with age-matched healthy controls (♀=6; ♂=3; 13.4y; 49.0kg; 1.61m; BMI: 18.9kg/m(2)), the Mann-Whitney U-test was applied with a significance level of P<0.05. The patients had a significantly lower height, but higher BMI. Walking speed was reduced with wide, but short steps and significant motion anomalies in the pelvis, hips, knees and ankles. Small ranges of motion in propulsion-supporting movements were typical, especially in the sagittal plane. The gait analysis revealed dominant compensatory movements in pelvic obliquity and rotation. The deficits can be attributed to pronounced muscle weakness plus functional joint impairment and pain. Therapeutic preventive strategies therefore should consider continuous muscle power exercises, stretching programmes and restrictive weight control.


Topographical study of stereo-related potentials.
In order to estimate objectively binocular vision and especially stereopsis, random dot stereograms generated by a personal computer were used. Brain activity during stereopsis was topographically studied by visually evoked potentials (VEPs). The potentials evoked by binocular viewing of patterns without disparity, e.g. correlogram, were very similar to the potentials evoked from patterns with disparity, i.e. stereogram, as many authors have already indicated. To derive the stereo-related potentials from the VEP elicited by stereograms, the potentials evoked by correlograms were subtracted from the potentials evoked by stereograms, and the differences of topographical distribution between normal and stereoblind subjects were investigated.


New amides and gastroprotective constituents from the fruit of Piper chaba.
The 80 % aqueous acetone extract from the fruit of Piper chaba was found to show protective effects on ethanol- and indomethacin-induced gastric lesions in rats. From the aqueous acetone extract, four new amides named piperchabamides A ( 1), B ( 2), C ( 3), and D ( 4) were isolated, and their structures were determined on the basis of chemical and physicochemical evidence. In addition, the gastroprotective effects of the principal constituents, piperine ( 5), piperanine ( 6), pipernonaline ( 7), dehydropipernonaline ( 8), piperlonguminine ( 9), retrofractamide B ( 10), guineensine ( 11), N-isobutyl-(2 E,4 E)-octadecadienamide ( 12), N-isobutyl-(2 E,4 E,14 Z)-eicosatrienamide ( 13), and methyl piperate ( 14), were examined. As a result, compounds 5 - 10 and 12 - 14 significantly inhibited ethanol-induced gastric lesions at a dose of 25 mg/kg, p. o., while 5, 7, 8, 10, 12, and 13 also significantly inhibited indomethacin-induced gastric lesions at the same dose.


Epigenetic regulation of aging: implications for interventions of aging and diseases.
Aging is accompanied by the decline of organismal functions and a series of prominent hallmarks, including genetic and epigenetic alterations. These aging-associated epigenetic changes include DNA methylation, histone modification, chromatin remodeling, non-coding RNA (ncRNA) regulation, and RNA modification, all of which participate in the regulation of the aging process, and hence contribute to aging-related diseases. Therefore, understanding the epigenetic mechanisms in aging will provide new avenues to develop strategies to delay aging. Indeed, aging interventions based on manipulating epigenetic mechanisms have led to the alleviation of aging or the extension of the lifespan in animal models. Small molecule-based therapies and reprogramming strategies that enable epigenetic rejuvenation have been developed for ameliorating or reversing aging-related conditions. In addition, adopting health-promoting activities, such as caloric restriction, exercise, and calibrating circadian rhythm, has been demonstrated to delay aging. Furthermore, various clinical trials for aging intervention are ongoing, providing more evidence of the safety and efficacy of these therapies. Here, we review recent work on the epigenetic regulation of aging and outline the advances in intervention strategies for aging and age-associated diseases. A better understanding of the critical roles of epigenetics in the aging process will lead to more clinical advances in the prevention of human aging and therapy of aging-related diseases.


Equine sarcoids.
Sarcoids, the most common tumor of the horse, are fibroblastic, wart-like skin lesions that show variable manifestations. They are often invasive and recurrent, although they do not fulfill all criteria of malignancy. Due to their anatomic location, these tumors can sometimes cause loss of use of the horse. There is very strong evidence that sarcoids are caused by viruses closely related or identical to bovine papilloma viruses, and genetic studies have shown associations between genes in or near the equine major histocompatibility complex (MHC) and susceptibility to sarcoid. Several types of treatments have been successful in treating sarcoids, although the response to therapy is not consistent. Current treatment of sarcoids primarily involves antitumor therapy, but the development of preventative measures in the future may be directed against the causative papilloma virus. Sarcoid continues to be an important clinical entity for the equine practitioner.


ZNF198-FGFR1 transforms Ba/F3 cells to growth factor independence and results in high level tyrosine phosphorylation of STATS 1 and 5.
The ZNF198- FGFR1 fusion gene arises as a result of the t(8;13)(p11;q12) in the 8p11 myeloproliferative syndrome. To determine the transforming properties of this chimeric protein we transfected ZNF198-FGFR1 into the interleukin (IL)-3 dependent cell line Ba/F3. Growth factor independent subclones were obtained in which ZNF198-FGFR1, STAT1, and STAT5 were constitutively tyrosine phosphorylated, as determined by immunoprecipitation and Western blot analysis. To test the hypothesis that constitutive activation of ZNF198-FGFR1 tyrosine kinase activity is a result of self-association of the fusion protein, we in vitro transcribed and translated ZNF198-FGFR1 and a derivative construct, ZNF198- FGFR1deltaC-myc, in which the C-terminal FGFR1 epitope was replaced by a c-myc tag. As expected, an anti-FGFR1 antibody immunoprecipitated ZNF198-FGFR1 but not ZNF198-FGFRdeltaC-myc. However when both products were translated together, both were coimmunoprecipitated by anti-FGFR1 antisera. Similar results were obtained by using an anti-myc antibody and demonstrated a physical interaction between the two proteins. Analysis of COS-7 cells transfected with ZNF198-FGFR1 demonstrated that the fusion gene, in contrast to normal FGFR1, is located in the cytoplasm. We conclude that ZNF198-FGFR1 is a cytoplasmic protein that self-associates and has constitutive transformation activity. These data suggest that ZNF198-FGFR1 plays a primary role in the pathogenesis of the t(8;13) myeloproliferative syndrome and is the first report to implicate STAT proteins in FGFR1-mediated signaling.


Prediction and prophylaxis of postoperative thromboembolism--a comparison between peroperative calf muscle stimulation with groups of impulses and dextran 40.
The effects of peroperative electrical calf muscle stimulation with groups of impulses giving a short lasting tetanus of the calf muscles on postoperative deep venous thrombosis (DVT) and pulmonary embolism (PE) were compared with that of dextran 40 given per and postoperatively. The incidence of DVT and PE during the first 4-6 postoperative days was recorded. The diagnosis of DVT was based on the 125I-fibrinogen uptake test and phlebography and of PE on pre- and postoperative perfusion pulmonary scintigram and chest X-ray examination. Both methods reduced the incidence of PE. Calf muscle stimulation reduced the DVT incidence in patients with malignant disease while the reduction in DVT incidence for the whole group only was significant in the stimulation as well as the dextran 40 group. Mean values for preoperatively determined levels of antithrombin III, beta-thromboglobulin, fibrinopeptide A, plasminogen and ability to release fibrinolytic activity during venous stasis did not differ between those patients who developed or those who did not develop postoperative DVT or PE. However, antithrombin III levels below 80 per cent appeared to predispose to postoperative thromboembolism. The two prophylactic methods have similar effects on the incidence of postoperative thromboembolism. The stimulation method has certain advantages due to its safety and simplicity.


A novel mechanism of the lncRNA PTTG3P/miR-142-5p/JAG1 axis modulating tongue cancer cell phenotypes through the Notch1 signaling.
Tongue cancer is the most prevalent type of oral cancer. Our previous study revealed that JAG1 exerted an oncogenic effect on tongue carcinoma through the JAG1/Notch pathway. In this study, a lncRNA PTTG3P which was upregulated in tongue cancer, was found to be positively correlated with JAG1. In CAL-27 and SCC4 cells, PTTG3P silencing significantly decreased JAG1 proteins and the ability of tongue tumor cells to proliferate and migrate. PTTG3P overexpression exhibited the opposite effect on CAL-27 and SCC4 cells. PPTG3P directly bound miR-142-5p, and miR-142-5p directly bound 3'UTR of JAG1 and inhibited the expression levels of JAG1. As opposed to PTTG3P silencing, miR-142-5p inhibition increased JAG1 protein levels and tongue cancer cell proliferation and migration; moreover, miR-142-5p inhibition substantially reversed the effects of PTTG3P silencing. Finally, the PPTG3P/miR-142-5p axis regulated the level of NICD, Notch downstream c-myc, and cyclin D1, as well as EMT markers Snail, Twist, and Vimentin. In conclusion, the PTTG3P/miR-142-5p axis modulates tongue cancer aggressiveness through JAG1, potentially through a JAG1/Notch signaling pathway.


Morphine decreases ticagrelor concentrations but not its antiplatelet effects: a randomized trial in healthy volunteers.
Our recent drug interaction trial with clopidogrel shows that morphine decreases the concentrations and pharmacodynamic effects of clopidogrel, which could lead to treatment failure in susceptible individuals. We hypothesized that the pharmacodynamic consequences of drug-drug interactions would be less between morphine and ticagrelor. Twenty-four healthy subjects received a loading dose of 180 mg ticagrelor together with placebo or 5 mg morphine intravenously in a randomized, double-blind, placebo-controlled, crossover trial. Pharmacokinetics were determined by liquid chromatography tandem mass spectrometry, and ticagrelor pharmacodynamic effects were measured by platelet function tests (whole blood platelet aggregation: multiplate, platelet plug formation: PFA-100, vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay). Concomitant i.v. injection of morphine slows drug resorption of ticagrelor and its active metabolite (P < 0·05) by 1 h and decreases plasma levels of ticagrelor and its active metabolite by 25-31% (P ≤ 0·03) and the drug exposure (area under the curve) by 22-23% (P ≤ 0·01). Importantly, however, the pharmacodynamic effects of ticagrelor on platelet aggregation in whole blood, platelet plug formation and VASP phosphorylation are not affected by morphine. Morphine co-administration moderately decreases ticagrelor plasma concentrations but does not inhibit its pharmacodynamic effects in healthy volunteers within 6 h after drug administration. Limitations of our trial include the investigation in healthy volunteers under standardized conditions, which does not necessarily reflect a realistic emergency scenario.


Deciphering dynamic combinatorial libraries of glycoclusters with miniaturized weak affinity chromatography coupled with mass spectrometry (nano-FAC-MS).
We report an original methodology based on affinity chromatography coupled with mass spectrometry to decipher the complexity of dynamic combinatorial libraries (DCLs) of glycoclusters. Such libraries are intended to boost the design of potential therapeutic anti-infectious agents targeting Pseudomonas aeruginosa, which is responsible for numerous diseases, mostly found in hospitals as major a cause of nosocomial infections. Dynamic combinatorial chemistry provides a rapid access to an equilibrating mixture of glycocluster candidates through the formation of reversible covalent bonds under thermodynamic control. Identifying each molecule in the complex mixture overcomes challenges due to the dynamic process. Selection of glycoclusters candidates was first realized on a model lectin (Concanavalin A, ConA). Home-made affinity nanocolumns, containing covalently immobilized ConA and have volumes in the microliter range, were used to separate DCLs of glycoclusters with respect to their specific lectin binding properties under buffered aqueous conditions. Miniaturization facilitates the inline coupling with MS detection in such purely aqueous and buffered conditions and reduces target protein consumption. Monolithic lectin-affinity columns prepared by immobilization of ConA were first characterized using a known ligand. The amount of active binding immobilized lectin is 61 ± 5 pmol on 8.5-cm length column. We demonstrated the ability of our approach to evaluate individual dissociation constants of species directly in the complex mixture. The concept was then successfully applied to the screening of DCLs of more complex glycoclusters to identify (by mass spectrometry) and rank the ligands (by relative breakthrough curve delay) according to their affinity for the immobilized lectin in a single experiment.


Neurotoxicity of Mn3O4 nanoparticles: Apoptosis and dopaminergic neurons damage pathway.
Mn3O4 nanoparticles (NPs) are used increasingly in various fields due to their excellent physiochemical properties. Previous studies have documented that Mn-based nanomaterials resulted in excess reactive oxygen species (ROS) generation and dopamine (DA) reduction both in vivo and in vitro experiments. However, little is known about the mechanism of ROS production and DA decrease induced by Mn-based nanomaterials. The present study was carried out to elucidate the mechanism of the co-incubation model of dopaminergic neuron PC12 cells and the synthesized Mn3O4 NPs. The results demonstrated that exposure to Mn3O4 NPs reduced cell viability, increased level of lactate dehydrogenase (LDH), triggered oxidative stress and induced apoptosis. Notably, the level of ROS was remarkably increased (>10-fold) with Mn3O4 NPs exposure. We also found that mitochondrial calcium Ca2+ uniporter (MCU) was up-regulated and the mitochondrial Ca2+ concentration ([Ca2+]mito) increased induced by Mn3O4 NPs in PC12 cells. Furthermore, the MCU inhibitor RuR significantly attenuated Mn3O4 NPs-induced [Ca2+]mito, ROS production and apoptosis. In PC12 cells, the decrease of DA content was mainly due to the downregulation of DOPA decarboxylase (DDC) expression caused by Mn3O4 NPs treatment. The expression of proteins related to DA storage system was not significantly affected by treatment.


Obesity in black women in Soweto, South Africa: minimal effects on hypertension, hyperlipidaemia and hyperglycaemia.
Studies were made on 50 South African urban black obese women aged 25-40 years, with Body Mass Index (BMI) (Kg/m2) of 29.5 or more, and on 50 non-obese women with BMI of 25 or less. In the two groups, mean triceps skinfolds were 25.5mm and 17.8mm, respectively. Hypertension (greater than or equal to 160/95mm Hg) was present in 6 and 4 women (12% and 8%), hypercholesterolaemia (greater than or equal to 5.2mmol/l) in 5 and 3 women (10% and 6%), hypertriglyceridaemia (greater than or equal to 1.8mmol/l) in 5 and 3 (10% and 6%), and hyperglycaemia (greater than or equal to 7.8mmol/l) in 2 and 1 women (4% and 2%). One or more adverse sequelae were present in 11 (22%) obese and in 9 (18%) of non-obese women, proportions not significantly different. Dietarily, mean daily intakes were--Kcals 2273 and 2240, protein 73g and 70g (12.9% and 12.5% energy), fat 65g and 67g (25.7% and 26.9% energy), carbohydrate 349g and 330g (61.4% and 60.5% energy), and dietary fibre, 12g and 13g. In this low socioeconomic and low fat dietary context, obesity in the black women studied was not specifically evocative of deleterious sequelae of obesity.


bZIP23 interacts with NAC028 to modulate rice resistance to sheath blight disease.
Rice sheath blight disease (ShB) is a serious threat to rice production, and breeding ShB-resistance varieties is the most effective strategy for ShB control. However, the molecular mechanisms of rice resistance to ShB are largely unknown. In this study, the NAC transcription factor NAC028 was shown to be sensitive to ShB infection. ShB inoculation assays revealed that NAC028 is a positive regulator of ShB resistance. To elucidate the molecular basis of NAC028-mediated ShB resistance, another transcription factor (bZIP23) was identified as a NAC028-interacting protein. Results of the transcriptome and qRT-PCR analyses demonstrated that CAD8B, a key enzyme for lignin biosynthesis and ShB resistance, is regulated by both bZIP23 and NAC028. The combination of the yeast-one hybrid, ChIP-qPCR, and transactivation assays illustrated that both bZIP23 and NAC028 directly bind the CAD8B promoter and activate its expression. The transcriptional connection between bZIP23 and NAC028 was also investigated and the results of in vitro and in vivo assays demonstrated that NAC028 was one of the target genes of bZIP23, but not vice versa. The results presented here provide new insights into the molecular basis of ShB resistance and contribute to the potential targets for the ShB resistance breeding program.


Interactions between bacterial CpG-DNA and TLR9 bridge innate and adaptive immunity.
The astounding adjuvanticity and Th1-polarizing immunobiology of bacterial CpG-DNA and mimicking CpG-oligonucleotides continue to mirror promising therapeutic potential. The past year has witnessed some particularly impressive progress in knowledge of its molecular mode of action. Accordingly, CpG-DNA acts as a "pathogen-associated" molecular pattern that is recognized by TLR9 expressed, in particular, by dendritic cells. Interactions between CpG-DNA and TLR9 rapidly activate antigen-presenting dendritic cells through the ancient Toll/IL-1-receptor signaling pathway to upregulate co-stimulatory molecules and to produce Th1-polarizing cytokines, such as interleukin-12 and interleukin-18. Thus, interactions between CpG-DNA and TLR9 effectively bridge innate and acquired immunity.


Strain variation in Campylobacter pylori detected by numerical analysis of one-dimensional electrophoretic protein patterns.
A total of 21 clinical isolates of Campylobacter pylori from Peru and the United Kingdom and two reference strains (from Australia), including the type strain (NCTC 11637T), were characterized by high resolution one-dimensional SDS-polyacrylamide gel electrophoresis of cellular proteins. The protein patterns contained more than 40 discrete bands and the approximate molecular weights of the major bands were 22, 27, 46, 57, 60, 65 and 93 kD. The total patterns were used as the basis of numerical analysis. Most strains were clustered in four phenons at 91% similarity with the exception of six ungrouped strains. Overall similarity was high with all strains linked in the phenogram at greater than or equal to 81%. Variation among strains was attributable principally to qualitative and quantitative band differences in the 47 to 56 kD (hypervariable) region of the C. pylori protein profile. From the analysis, ten different electropherotypes (EP-types) were identified. We demonstrated that differences were detectable among isolates from widely separated geographical locations as well as from the same location, although multiple isolates from two Peruvian patients had the same electropherotype. Our results indicate that determination of protein profiles provides the basis of a reproducible method for characterization of C. pylori isolates.


Can Bottom-Up Synthetic Biology Generate Advanced Drug-Delivery Systems?
Creating a magic bullet that can selectively kill cancer cells while sparing nearby healthy cells remains one of the most ambitious objectives in pharmacology. Nanomedicine, which relies on the use of nanotechnologies to fight disease, was envisaged to fulfill this coveted goal. Despite substantial progress, the structural complexity of therapeutic vehicles impedes their broad clinical application. Novel modular manufacturing approaches for engineering programmable drug carriers may be able to overcome some fundamental limitations of nanomedicine. We discuss how bottom-up synthetic biology principles, empowered by microfluidics, can palliate current drug carrier assembly limitations, and we demonstrate how such a magic bullet could be engineered from the bottom up to ultimately improve clinical outcomes for patients.


The two-component regulators GacS and GacA influence accumulation of the stationary-phase sigma factor sigmaS and the stress response in Pseudomonas fluorescens Pf-5.
Three global regulators are known to control antibiotic production by Pseudomonas fluorescens. A two-component regulatory system comprised of the sensor kinase GacS (previously called ApdA or LemA) and GacA, a member of the FixJ family of response regulators, is required for antibiotic production. A mutation in rpoS, which encodes the stationary-phase sigma factor sigmaS, differentially affects antibiotic production and reduces the capacity of stationary-phase cells of P. fluorescens to survive exposure to oxidative stress. The gacA gene of P. fluorescens Pf-5 was isolated, and the influence of gacS and gacA on rpoS transcription, sigmaS levels, and oxidative stress response of Pf-5 was determined. We selected a gacA mutant of Pf-5 that contained a single nucleotide substitution within a predicted alpha-helical region, which is highly conserved among the FixJ family of response regulators. At the entrance to stationary phase, sigmaS content in gacS and gacA mutants of Pf-5 was less than 20% of the wild-type level. Transcription of rpoS, assessed with an rpoS-lacZ transcriptional fusion, was positively influenced by GacS and GacA, an effect that was most evident at the transition between exponential growth and stationary phase. Mutations in gacS and gacA compromised the capacity of stationary-phase cells of Pf-5 to survive exposure to oxidative stress. The results of this study provide evidence for the predominant roles of GacS and GacA in the regulatory cascade controlling stress response and antifungal metabolite production in P. fluorescens.


The quality control of MHC class I peptide loading.
The assembly of major histocompatibility complex (MHC) class I molecules is one of the more widely studied examples of protein folding in the endoplasmic reticulum (ER). It is also one of the most unusual cases of glycoprotein quality control involving the thiol oxidoreductase ERp57 and the lectin-like chaperones calnexin and calreticulin. The multistep assembly of MHC class I heavy chain with beta(2)-microglobulin and peptide is facilitated by these ER-resident proteins and further tailored by the involvement of a peptide transporter, aminopeptidases, and the chaperone-like molecule tapasin. Here we summarize recent progress in understanding the roles of these general and class I-specific ER proteins in facilitating the optimal assembly of MHC class I molecules with high affinity peptides for antigen presentation.


Primary follicular lymphoma of the epididymis positive for t(14;18)(q32;q21)/IGH-BCL2 and negative for BCL2 protein expression: a case report.
Non-Hodgkin lymphoma (NHL) can involve the paratesticular organs as the primary disease, as primary testicular lymphoma that secondarily involves the paratesticular structures, as the initial site of presentation of occult nodal disease or as the result of disease dissemination. Primary follicular lymphoma of the epididymis in an adult is extremely rare. Little is known about primary adult paratesticular/epididimal lymphomas. We report a rare case of primary follicular non-Hodgkin lymphoma of the epididymis in a 90-year-old Caucasian man who presented with a left scrotal mass. Bone marrow biopsy was negative and computed tomography of the total body revealed no evidence of extratesticular involvement. Macroscopically, the epididymis was replaced completely by a uniform mass. Histologic studies revealed a dense lymphoid infiltrate predominantly composed of centrocytes with admixed centroblasts. Immunohistochemical analyses demonstrated that neoplastic cells strongly expressed CD45RB, CD20, CD79a, bcl-6 and CD10; bcl-2 immunostaining was negative. Molecular studies showed the presence of the monoclonal IgH gene rearrangement and the IgH/BCL2 rearrangement. The lymphoma was classified as follicular lymphoma, low grade, grade 1-2. The patient subsequently underwent radical orchiectomy, did not receive chemotherapy and post-operative follow-up showed absence of disease recurrence. The case of primary follicular lymphoma of epididymis, reported here, is considered a very rare event. It is characterized by clinically indolent localized disease, a good clinical outcome, lack of expression of BCL2 protein and the presence of the t(14;18)(q32;q21)/IGH-BCL2. Even if it is a single case, the primary follicular lymphoma epididymis with t(14;18) could represent either a variant of the previously reported t(14;18)-negative primary paratesticular follicular lymphoma or a distinct biological entity. To report additional cases in the future would be helpful in resolving this question.


Continuous cultivation of microalgae yields high nutrient recovery from nitrified urine with limited supplementation.
Microalgae can play a key role in the bioeconomy, particularly in combination with the valorisation of waste streams as cultivation media. Urine is an example of a widely available nutrient-rich waste stream, and alkaline stabilization and subsequent full nitrification in a bioreactor yields a stable nitrate-rich solution. In this study, such nitrified urine served as a culture medium for the edible microalga Limnospira indica. In batch cultivation, nitrified urine without additional supplements yielded a lower biomass concentration, nutrient uptake and protein content compared to modified Zarrouk medium, as standard medium. To enhance the nitrogen uptake efficiency and biomass production, nitrified urine was supplemented with potentially limiting elements. Limited amounts of phosphorus (36 mg L-1), magnesium (7.9 mg L-1), calcium (12.2 mg L-1), iron (2.0 mg L-1) and EDTA (88.5 mg Na2-EDTA.2H2O L-1) rendered the nitrified urine matrix as effective as modified Zarrouk medium in terms of biomass production (OD750 of 1.2), nutrient uptake (130 mg N L-1) and protein yield (47%) in batch culture. Urine precipitates formed by alkalinisation could in principle supply enough phosphorus, calcium and magnesium, requiring only external addition of iron, EDTA and inorganic carbon. Subsequently, the suitability of supplemented nitrified urine as a culture medium was confirmed in continuous Limnospira cultivation in a CSTR photobioreactor. This qualifies nitrified urine as a valuable and sustainable microalgae growth medium, thereby creating novel nutrient loops on Earth and in Space, i.e., in regenerative life support systems for human deep-space missions.


Impact of random assignment on study outcome: an empirical examination.
Sixty research investigations published in the biomedical literature were analyzed to examine the effect of design attributes on outcome. All 60 studies included a controlled trial involving a pretest, a therapeutic intervention, and a posttest across at least two groups. Thirty of the trials used random assignment of participants to treatment or control conditions and 30 trials employed some nonrandom method of subject assignment. Trial results were aggregated and evaluated by comparing effect sizes for the primary statistical test of the hypothesis. Data analysis revealed that the trial results, as measured by effect size, did not vary across therapeutic trials using random assignment versus those using nonrandom allocation of subjects. The impact of design attributes in the interpretation of multiple clinical trials addressing a similar research question is examined. The argument is made that various design attributes frequently associated with methodological quality should be considered as important moderator variables and their influence on trial outcome should not be assumed a priori but rather examined empirically.


Commuting physical activity and prevalence of metabolic disorders in Poland.
The aim of this study was to examine the relationship between walking or cycling to work and prevalence of metabolic syndrome (MetS) and its components. Cross-sectional analysis of 6401 randomly selected individuals (3297 men and 3104 women) aged 20-74 years, who participated in the National Multicentre Health Survey WOBASZ, Poland (2002-2005). Commuting physical activity (PA) was assessed by asking about type and time spent on transportation to/from work using an interviewer-administered questionnaire. Weight, height, waist circumference (WC), blood pressure (BP), fasting plasma glucose (FPG), triglycerides (TG) and high-density cholesterol, (HDL-C) were measured by standard methods. MetS was defined according to the NCEP-ATP III and IDF criteria. Active commuting was associated with decreased likelihood of abdominal obesity (WC≥94 cm), lower HDL-C and elevated TG in men and abdominal obesity (WC≥80 cm) in women. In a subgroup of postmenopausal women (n=317) active commuting was favourably associated with abdominal obesity, low HDL-C and elevated FPG. Prevalence of MetS was significantly lower among those who spent above 30 min/day daily on walking/cycling to work than among other gender subgroups. Increasing of commuting PA level may have an important influence on reducing the prevalence of metabolic disorders.


Primary Thromboprophylaxis and the Risk of Venous Thromboembolic Events in Patients With Testicular Germ Cell Tumors Treated With Cisplatinum-Based Chemotherapy.
Cisplatinum-based chemotherapy is associated with an increased risk of venous thromboembolism (VTE). We hypothesized that primary thromboprophylaxis in patients with testicular germ cell tumors (GCT) undergoing cisplatinum-based chemotherapy can reduce the risk of VTE. In this single-center retrospective cohort study, we investigated the increased use of primary thromboprophylaxis between January 2000 and December 2021 at our institution and its effect on the risk of VTE. Patients with GCT undergoing adjuvant or curative cisplatinum-based chemotherapy were included. Three hundred forty-six patients with GCT initiating a cisplatinum-based therapy were included in the study, of whom 122 (35%) were treated in the adjuvant and 224 (65%) in the curative setting, respectively. VTE events occurred in 49 (14.2%) patients. In univariable competing risk analysis, a higher clinical tumor stage and large retroperitoneal lymphadenopathy (RPLND >5 cm) were the strongest predictors of an elevated VTE risk (SHR for stage IIC - IIIC: 2.6 (95%CI: 5.0-24.7, P < .001), SHR for RPLN: 2.36 (95%CI: 1.27-4.4, P < .007)). The proportion of patients receiving primary thromboprophylaxis strongly increased over time and reached 100% in CS IIC-III patients from 2019 onwards. After adjusting for tumor stage, primary thromboprophylaxis was associated with a 52% relatively lower risk of VTE (SHR = 0.48, 95% CI: 0.24-0.97; P = .032). In this retrospective cohort study, we showed that TGCT patients undergoing cisplatinum-based chemotherapy have a lower VTE risk when receiving primary thromboprophylaxis. For the duration of chemotherapy, primary thromboprophylaxis should be considered on a risk-benefit ratio.


Effects of Blood Flow Restriction Exercise and Possible Applications in Type 2 Diabetes.
Blood flow restriction resistance training (BFRT) employs partial vascular occlusion of exercising muscles via inflation cuffs. Compared with high-load resistance training, mechanical load is markedly reduced with BFRT, but induces similar gains in muscle mass and strength. BFRT is thus an effective training strategy for people with physical limitations. Recent research indicates that BFRT has beneficial effects on glucose and mitochondrial metabolism. BFRT may therefore qualify as a valuable exercise alternative for individuals with type 2 diabetes (T2D), a disorder characterized by impaired glucose metabolism, musculoskeletal decline, and exacerbated progression of sarcopenia. This review covers the effects of BFRT in healthy populations and in persons with impaired physical fitness, the mechanisms of action of this novel training modality, and possible applications for individuals with T2D.


Burned adolescents' descriptions of their coping strategies.
In an effort to describe adolescents' coping strategies after burns, eight postburn adolescents were interviewed. Their physical changes and their self-described behaviors and responses to changes in appearance, function, and potential are delineated. With the use of Lazarus' coping paradigm, mechanisms described by subjects were classified as problem focused or emotion focused. Comparison is made with coping mechanisms previously identified in adults. Subjects' problem-focused adjustments included the institution of comfort and therapeutic measures, the resumption of preburn style of dress, varied verbal responses to questioning and staring, the redirection of career goals, and adjustments to phobic neurosis. Emotion-focused adjustments included anger, acceptance of limitations, anticipation of ridicule or rejection, decreased focus on physical changes, a sense of loss, boredom with burns and their sequelae, and various defenses such as rationalization, denial, intellectualization, and humor. Identification of specific physical changes and responses permits the nurse to plan interventions and to provide anticipatory guidance accordingly.


Liposomes containing colloidal gold are a useful probe of liposome-cell interactions.
A method is described for the preparation of liposomes containing colloidal gold as an electron-dense marker to trace liposome-cell interactions. Since gold sols would precipitate at the high concentrations necessary for loading a large proportion of liposomes, gold sols were formed within preformed liposomes which had encapsulated gold chloride. The optimal conditions for encapsulating the marker were ascertained for liposomes prepared by the method of reverse-phase evaporation. Gold sols formed rapidly at ambient temperature and without organic solvent, and produced homogeneous populations of gold granules inside liposomes. Most vesicles contained the marker, allowing us to determine unambiguously the intracellular fate of liposomes and their contents. The in vitro experiments showed that gold-liposomes were internalized by African green monkey kidney cells in a manner similar to receptor-mediated endocytosis of well-characterized ligands. Preliminary in vivo studies also indicated that liposomes were endocytosed by Kupffer cells via the coated vesicle pathway.


Progestin membrane receptors involved in the meiotic maturation of teleost oocytes: a review with some new findings.
The endocrine control of oocyte maturation in fish has proven to be a valuable model for investigating rapid, nongenomic steroid actions at the cell surface. Considerable progress has been made over the last decade in identifying and characterizing progestin membrane receptors mediating these actions in fish, in understanding the hormonal regulation and physiological roles of these receptors in oocyte maturation, in elucidating the signal transduction pathways they activate, and in determining their nature. Recent advances on these topics are briefly reviewed. New data demonstrating the involvement of pertussis toxin-sensitive inhibitory G-proteins in induction of oocyte maturation by the maturation-inducing steroid (MIS) in teleosts is also presented. In addition, the cloning strategy to isolate the MIS receptor gene from spotted seatrout ovaries and the characteristics of a novel gene and protein discovered by this approach are discussed. Current evidence suggests this G-protein-coupled receptor-like protein is the long sought after MIS receptor mediating meiotic maturation of teleost oocytes.


Recent expansion of the telomeric complex in rodents: Two distinct POT1 proteins protect mouse telomeres.
Human telomeres are protected by shelterin, a complex that includes the POT1 single-stranded DNA binding protein. We found that mouse telomeres contain two POT1 paralogs, POT1a and POT1b, and we used conditional deletion to determine their function. Double-knockout cells showed that POT1a/b are required to prevent a DNA damage signal at chromosome ends, endoreduplication, and senescence. In contrast, POT1a/b were largely dispensable for repression of telomere fusions. Single knockouts and complementation experiments revealed that POT1a and POT1b have distinct functions. POT1a, but not POT1b, was required to repress a DNA damage signal at telomeres. Conversely, POT1b, but not POT1a, had the ability to regulate the amount of single-stranded DNA at the telomere terminus. We conclude that mouse telomeres require two distinct POT1 proteins whereas human telomeres have one. Such divergence is unprecedented in mammalian chromosome biology and has implications for modeling human telomere biology in mice.