Transcript and protein marker patterns for the identification of steatotic compounds in human HepaRG cells.
Non-alcoholic fatty liver disease is a major health concern especially in Western countries. Animal studies suggest that certain chemicals may contribute to hepatocellular triglyceride accumulation, among them a number of hepatotoxic pesticidal active compounds. In order to improve the identification of potential liver steatosis inducers in vitro in a human cell culture system, HepaRG cells were treated with a selection of 30 steatotic or non-steatotic pesticides. Induction of triglyceride accumulation was monitored, and changes in the expression of hepatotoxicity marker genes were measured at the mRNA and protein levels. Based on these data, transcript and protein marker signatures predictive of triglyceride accumulation in HepaRG cells were derived. The predictive transcript set consisted of POR, ANXA10, ARG1, CCL20, FASN, INSIG1, SREBF1, CD36, CYP2D6, and SLCO1B1. The predictive protein set consisted of NCPR (POR), CYP2E1, CYP1A1, ALDH3A1, UGT2B7, UGT2B15, S100P, LMNA, and PRKDC. In conclusion, the present study presents for the first time transcript and protein marker patterns to separate steatotic from non-steatotic compounds in a human liver cell line.


[Experience with the use of the CO2 laser in reconstructive and plastic gynecologic surgery in patients with uterine myoma and endometriosis].
CO2 laser has been used during reconstructive plastic surgery for uterine myoma, endometriosis of various locations, and associated gynecologic conditions in 71 patients. Comparison in patients with uterine myoma who underwent conservative myomectomy with and without the use of CO2 laser showed that treatment with CO2 laser diminished blood loss and duration of the operation, and improved postoperative progress.


Erratum to: Further analysis of selection-based instruction, lag reinforcement schedules, and the emergence of topography-based responses to interview questions.
[This corrects the article DOI: 10.1007/s40616-015-0031-5.].


Successful treatment with adalimumab for severe multifocal choroiditis and panuveitis in presumed (early-onset) ocular sarcoidosis.
Early-onset sarcoidosis (EOS) and Blau syndrome are rare auto-inflammatory diseases characterized by a triad of skin rash, granulomatous uveitis, and symmetrical polyarthritis occurring in early childhood. In this paper, we describe a case report very interesting for the multidisciplinary management (pediatric rheumatologist and ophthalmologist), the challenging diagnosis and the difficult choice of the best treatment. We describe a case report of an 8-year old with recurrent episodes of acute uveitis that developed bilateral granulomatous panuveitis initially treated with topical and systemic steroids. Genetic testing for NOD2/CARD15 revealed a heterozygous mutation on exon 4 in the NBD domain (P268S/SNP5). Therefore, an incomplete EOS was suspected. Because uveitis worsening with multifocal chorioretinitis aggravation, intravenous boluses of methylprednisolone were administered. During the steroids tapering, she flared again, and methotrexate was started along with corticosteroids pulse therapy. However, new ocular granuloma appeared, macular oedema with poor visual outcome occurred, and therefore, adalimumab was added to MTX and steroids. After 6 months since the new therapy started, she had a complete visual recovery, and she was able to stop steroid treatment. At 2 years of follow-up, she is still in remission on treatment, and her visual acuity is normal. No side effects were observed. In our patient, we found a heterozygous mutation on exon 4 in the NBD domain (P268S/SNP5) of NOD2/CARD15 gene and an incomplete EOS was hypothesized. The role of this variant is currently under study. Adalimumab use dramatically changed the course of eye disease, prompting to stop steroid treatment and preserving visual acuity.


Experimental infection of Danish Landrace/Yorkshire crossbred pigs with Schistosoma japonicum from the People's Republic of China.
This study was undertaken to assess the suitability of Danish Landrace/Yorkshire (L/Y) crossbred pigs as experimental hosts of a Chinese mainland strain of Schistosoma japonicum. Pigs were exposed to 200, 500 or 1000 cercariae and parasite burdens were determined by perfusion after either 8 or 11 weeks. All pigs became infected with onset of faecal egg excretion 6 to 7 weeks following exposure to cercariae. The pattern of faecal egg excretion differed markedly among the individual animals. Gross hepatic pathological lesions of varying degrees were noted in all of the pigs. Schistosome worm recoveries ranged from 1.5-23.4% of the cercarial exposure dose. Most schistosome eggs recovered from the tissues, expressed as eggs/g tissue, were found in the rectum (91%), caecum (3.1%) and liver (5.1%). The results show that Danish L/Y pigs may serve as appropriate experimental final hosts of the Chinese mainland strain of S. japonicum.


Focal adhesion kinase signaling promotes phagocytosis of integrin-bound photoreceptors.
Daily alphavbeta5 integrin-dependent phagocytosis of spent photoreceptor outer segment fragments by the retinal pigment epithelium (RPE) is critical for retinal function. This study identifies a key role for focal adhesion kinase (FAK) in RPE phagocytosis. Particle binding increases FAK complex formation with alphavbeta5 receptors at the apical, phagocytic RPE surface and activates FAK. Subsequent particle engulfment coincides with dissociation of activated FAK from alphavbeta5. Mutant FAK retaining focal adhesion targeting but lacking kinase activity interferes with recruitment of full-length FAK to alphavbeta5 and abrogates FAK activation in response to RPE phagocytic challenge. Such inhibition of FAK signaling has no effect on alphavbeta5-dependent binding of particles but blocks their engulfment. Conversely, FAK re-expression promotes particle engulfment by FAK null fibroblasts. Selective ligation of alphavbeta5 receptors at the apical RPE surface is sufficient to phosphorylate and mobilize FAK. Furthermore, FAK phagocytic signaling is independent of the internalization receptor MerTK. In contrast, inhibition of FAK signaling diminishes MerTK phosphorylation. These results demonstrate that FAK provides an essential link between binding and engulfment mechanisms of integrin-mediated phagocytosis.


Using DWT for ECG motion artifact reduction with noise-correlating signals.
Dealing with motion artifacts in long-term ECG recordings is a big issue. The frequency spectrum of motion artifacts is similar to the frequencies of the QRS complex--the wanted signal in the ECG. The deletion of motion artifacts often leads to a deformation of QRS complexes, too. These risks can be minimized by using a noise-correlating signal as a second channel for artifact reduction. This paper presents an approach using the electrode-skin impedance as a second channel for the reduction of motion artifacts. Using the discrete wavelet transform, motion artifacts can be deleted time and frequency selective. This filter approach leads to an improvement of the automatic QRS detection and decreases the number of false detections by 35 %.


[Comparative study of HLA-DQA1 and HLA-DRB1 allele in patients with endometriosis and adenomyosis].
To make a comparative study of HLA-DQA1 and HLA-DRB1 allele frequencies in the cases of endometriosis and adeonmyosis. The allelic types of HLA-DQA1 and HLA-DRB1 were detected by polymerase chain reaction-sequence specific primers (PCR-SSP) technique in 51 cases of endometriosis, 45 cases of adenomyosis, and 44 normal individuals as the control. The frequencies of HLA-DQA1*0401(7.8%, 10.0%) were significantly increased in the endometriosis group and the adenomyosis group (Pc=0.03, Pc=0.01), and the frequencies of HLA-DQA1*0301(8.8%, 5.6%) were significantly decreased in these two groups (Pc=0.00, Pc=0.00).There was no significant difference between the frequencies of HLA-DQA1 and HLA-DRB1 of endometriosis and adenomyosis. The results indicate that HLA-DQA1*0301 and *0401 alleles are associated with both endometriosis and adenomyosis, and there is perhaps common mechanism involved in both endometriosis and adenomyosis based on HLA-DQA1 and HLA-DRB1 allele frequencies.


Surviving severe COVID-19: Interviews with patients, informal carers and health professionals.
The COVID-19 pandemic has been associated with an unprecedented number of critical care survivors. Their experiences through illness and recovery are likely to be complex, but little is known about how best to support them. This study aimed to explore experiences of illness and recovery from the perspective of survivors, their relatives and professionals involved in their care. In-depth qualitative interviews were conducted with three stakeholder groups during the first wave of the pandemic. A total of 23 participants (12 professionals, 6 survivors and 5 relatives) were recruited from 5 acute hospitals in England and interviewed by telephone or video call. Data analysis followed the principles of Reflexive Thematic Analysis. Three themes were generated from their interview data: (1) Deteriorating fast-a downhill journey from symptom onset to critical care; (2) Facing a new virus in a hospital-a remote place; and (3) Returning home as a survivor, maintaining normality and recovering slowly. Our findings highlight challenges in accessing care and communication between patients, hospital staff and relatives. Following hospital discharge, patients adopted a reframed 'survivor identity' to cope with their experience of illness and slow recovery process. The concept of survivorship in this patient group may be beneficial to promote and explore further. All efforts should be made to continue to improve communication between patients, relatives and health professionals during critical care admissions, particularly while hospital visits are restricted. Adapting to life after critical illness may be more challenging while health services are restricted by the impacts of the pandemic. It may be beneficial to promote the concept of survivorship, following admission to critical care due to severe COVID-19.


Discovery of 3,5-substituted 6-azaindazoles as potent pan-Pim inhibitors.
Pim kinase inhibitors are promising cancer therapeutics. Pim-2, among the three Pim isoforms, plays a critical role in multiple myeloma yet inhibition of Pim-2 is challenging due to its high affinity for ATP. A co-crystal structure of a screening hit 1 bound to Pim-1 kinase revealed the key binding interactions of its indazole core within the ATP binding site. Screening of analogous core fragments afforded 1H-pyrazolo[3,4-c]pyridine (6-azaindazole) as a core for the development of pan-Pim inhibitors. Fragment and structure based drug design led to identification of the series with picomolar biochemical potency against all three Pim isoforms. Desirable cellular potency was also achieved.


A longitudinal magnetic resonance imaging study of the brain in survivors in childhood acute lymphoblastic leukemia.
The objective of this study was to evaluate changes in magnetic resonance imaging (MRI) of the brain in children with acute lymphoblastic leukemia (ALL) during the first 5 years after the cessation of therapy and to correlate MRI abnormalities with neuropsychologic outcome. Thirty-two children with ALL were studied at the end of treatment and 5 years later by brain MRI and the results were compared with the neuropsychologic findings. Fifteen patients had received chemotherapy alone and 17 had received chemotherapy plus cranial radiation. MRI of the brain was abnormal in 6 of 30 patients at the end of treatment and in 8 of 32 patients 5 years later. White matter changes (WMC) were found in 3 patients at the end of treatment and in 4 patients 5 years later. Two patients had developed new mild changes, whereas in one case WMC had normalized during the follow-up. Two patients had old hemorrhages or calcifications at each examination, with some improvement after follow-up, although one case revealed a new calcification or hemorrhage. Signs of cortical atrophy were observed in five patients at both evaluations. The patients with abnormal MRI findings did not differ significantly in their performance in the neuropsychologic tests from the patients with normal MRI findings, but the two patients with persistent WMC had a depression of verbal functions. Abnormalities in brain MRI were infrequent at the end of treatment for childhood ALL and 5 years later. They did not appear to correlate significantly with neuropsychologic outcome. Brain MRI is not very informative as a routine follow-up method during the first 5 years after treatment.


The effects of a startle on awareness of action.
The execution of a ballistic movement within a reaction time task paradigm is significantly speeded up when an unexpected startling auditory stimulus (SAS) is delivered together with the imperative signal. Using Libet's clock, we investigated whether acceleration involves also the subjective appraisal of the time of task execution. In trials containing the SAS, reaction time shortened to 68.7% of control values. However, subjective judgment of task execution remained a similar time with respect to the imperative signal as in control trials. The dissociation between task execution and its subjective perception indicates the existence of separate circuits for action execution and action awareness.


Children with Congenital Heart Disease Are Active but Need to Keep Moving: A Cross-Sectional Study Using Wrist-Worn Physical Activity Trackers.
To compare daily physical activity of children with congenital heart disease (CHD) with healthy peers measured using wearables bracelets in a large cohort. Additionally, subjectively estimated and objectively measured physical activity was compared. From September 2017 to May 2019, 162 children (11.8 ± 3.2 years; 60 girls) with various CHD participated in a self-estimated and wearable-based physical activity assessment. Step-count and moderate-to-vigorous physical activity were recorded with the Garmin vivofit jr. for 7 consecutive days and compared with a reference cohort (RC) of 96 healthy children (10.9 ± 3.8 years; 49 girls). Children with CHD were active and 123 (75.9%) achieved 60 minutes physical activity on a weekly average according to the World Health Organization criteria as 81 (84.3%) of the healthy peers did (P = .217). After correction for age, sex, and seasonal effects, only slightly lower step count (CHD: 10 206 ± 3178 steps vs RC: 11 142 ± 3136 steps; P = .040) but no lower moderate-to-vigorous physical activity (CHD: 80.5 ± 25.6 minutes/day vs RC: 81.5 ± 25.3 minutes/day; P = .767) occurred comparing CHD with RC. In children with CHD higher age (P = .004), overweight or obesity (P = .016), complex severity (P = .046), and total cavopulmonary connection (P = .027) were associated with not meeting World Health Organization criteria. Subjective estimation of daily moderate-to-vigorous physical activity was fairly correct in half of all children with CHD. Even though the majority is sufficiently active, physical activity needs to be promoted in overweight or obese patients, patients with complex CHD severity, and in particular in those with total cavopulmonary connection.


Synthesis of the 7,8-dihydro-7-deazapurine derivatives and their antibiotic activity.
The cis- and trans-diastereomers of the 7,8-dihydro-7-deazapurine derivatives were synthesized from the corresponding diastereomers of 4-trans-cyano-2-methyl-3-phenyl-5-oxopyrrolidine (5), which were reduced from the 2-cis- and 2-trans-diastereomers of 4-trans-cyano-2-hydroxymethyl-3-phenyl-5-oxopyrrolidine (2) via tosylation, iodination and following elimination, respectively. The prepared cis- and trans-diastereomers of 6-amino-2-mercapto-8-methyl-7-phenyl-7,8-dihydro-7(9H)-deazapurine (8) were transferred to the corresponding 2-methylthio-diastereomers 9 and following desulfurization with Raney-nickel leaded to the cis- and trans-diastereomers of 6-amino-8-methyl-7-phenyl-7,8-dihydro-7(9H)-deazapurine (10), respectively. The synthesized 7-deazapurine derivatives were tested for their antibiotic activity by the serial two-fold dilution method.


Membrane type 1-matrix metalloproteinase expression is regulated by E-cadherin through the suppression of mitogen-activated protein kinase cascade.
To elucidate the role of E-cadherin in matrix metalloproteinases (MMPs) expression, we transfected to squamous carcinoma cells with E-cadherin cDNA. HN5 cells and mock-transfected HN5-neo cells expressed proMMP-2 and active MMP-2. E-cadherin-transfected HN5-EC cells produced comparable proMMP-2 but low active MMP-2; and membrane type 1-MMP (MT1-MMP) mRNA declined. Phosphorylated ERK, a marker of mitogen-activated protein (MAP) kinase cascade, also declined in HN5-EC cells. The addition of anti-E-cadherin antibody resulted in the disappearance of these alterations in HN5-EC cells. These results suggest that E-cadherin suppresses MAP kinase cascade and down-regulates MT1-MMP.


Biological Pathotyping of Newcastle Disease Viruses in Sudan 2008-2013.
The biological properties and pathogenicity of seven Newcastle disease virus field isolates were studied. These isolates were recovered from different outbreaks in Sudan (5 from chickens and 2 from pigeons) during 2008-2013. Based on intracerebral pathogenicity index, four NDV isolates were characterized as velogenic (their ICPI ranged 2.0-1.6) and three isolates were characterized as mesogenic (ICPI ranged 1.2-1.3). The mean death time for all isolates ranged from 54 to 76.8 hours. The elution time of the viruses from chicken erythrocytes and the ability to haemagglutinate mammalian red blood cells differed considerably in their reactions.


Impact of Sustained Remission on the Risk of Serious Infection in Patients With Rheumatoid Arthritis.
This retrospective analysis examined how sustained remission impacted risk of serious infections in patients with rheumatoid arthritis (RA) enrolled in a clinical registry. Inclusion criteria included RA diagnosis, age ≥18 years, and ≥2 Clinical Disease Activity Index (CDAI) scores followed by a followup visit. Index date was the second of 2 visits in which a patient had sustained remission (CDAI ≤2.8), low disease activity (LDA; 2.8 < CDAI ≤10), or moderate-to-high disease activity (MHDA; CDAI >10). Followup extended from the index date until first serious infection (requiring intravenous antibiotics or hospitalization) or last followup visit. The crude incidence rate (IR) per 100 patient-years for serious infections was calculated for the sustained remission, LDA, and MHDA groups. The multivariable-adjusted incidence rate ratio (IRR) (adjusted for age, sex, and prednisone dose) compared serious infection rates across disease activity groups. Most patients were female (>70%); mean age was approximately 60 years. The crude IR (95% confidence interval [95% CI]) per 100 patient-years for serious infections was 1.03 (0.85-1.26) in the sustained remission group (n = 3,355), 1.92 (1.68-2.19) in the sustained LDA group (n = 3,912), and 2.51 (2.23-2.82) in the sustained MHDA group (n = 5,062). Compared to sustained remission, the serious infection rate was higher in sustained LDA (adjusted IRR 1.69 [95% CI 1.32-2.15]). Compared to sustained LDA, the serious infection rate was higher in sustained MHDA (adjusted IRR 1.30 [95% CI 1.09-1.56]). In this study, lower RA disease activity was associated with lower serious infection rates. This finding may motivate patients and health care providers to strive for remission rather than only LDA.


Chronic TGF-β exposure drives stabilized EMT, tumor stemness, and cancer drug resistance with vulnerability to bitopic mTOR inhibition.
Tumors comprise cancer stem cells (CSCs) and their heterogeneous progeny within a stromal microenvironment. In response to transforming growth factor-β (TGF-β), epithelial and carcinoma cells undergo a partial or complete epithelial-mesenchymal transition (EMT), which contributes to cancer progression. This process is seen as reversible because cells revert to an epithelial phenotype upon TGF-β removal. However, we found that prolonged TGF-β exposure, mimicking the state of in vivo carcinomas, promotes stable EMT in mammary epithelial and carcinoma cells, in contrast to the reversible EMT induced by a shorter exposure. The stabilized EMT was accompanied by stably enhanced stem cell generation and anticancer drug resistance. Furthermore, prolonged TGF-β exposure enhanced mammalian target of rapamycin (mTOR) signaling. A bitopic mTOR inhibitor repressed CSC generation, anchorage independence, cell survival, and chemoresistance and efficiently inhibited tumorigenesis in mice. These results reveal a role for mTOR in the stabilization of stemness and drug resistance of breast cancer cells and position mTOR inhibition as a treatment strategy to target CSCs.


Control of supraventricular tachycardia by VVI pacing in a patient with drug-induced enhanced atrioventricular conduction.
A 56-year-old male with atrial fibrillation developed rapid ventricular response up to 200 beats/min or more in the postoperative stage of emergency aortocoronary bypass surgery. Resuscitation for cardiac arrest triggered this rapid ventricular rate. The idea that retrograde conduction into atrioventricular node may prevent ventricular capture of atrial fibrillation was tested. The ventricle was then paced at rapid rate followed by a gradual decrease in the pacing rate to 120 beats/min. By this method, ventricular rate was controlled and hemodynamics stabilized, with more efficiency of intra-aortic balloon counterpulsation. VVI pacing may be used in this manner to control irregular and rapid ventricular response of atrial fibrillation.


Interaction of poly(N-isopropylacrylamide) (pNIPAM) based nanoparticles and their linear polymer precursor with phospholipid membrane models.
Poly(N-isopropylacrylamide) (pNIPAM) is a thermoresponsive polymer which has promising applications in nanomedicine for drug delivery. The cross-linking of pNIPAM based copolymer using the chain collapse method leads to the synthesis of pNIPAM based polymer nanoparticles. This study looks at the interaction of pNIPAM polymers and pNIPAM nanoparticles with biomembrane models of, (i) a dioleoyl phosphatidylcholine (DOPC) monolayer on a mercury (Hg) electrode and (ii) DOPC and dimyristoyl phosphatidylcholine (DMPC) vesicles. The following techniques were used to follow the interactions: Dynamic light scattering (DLS), differential scanning calorimetry (DSC), rapid cyclic voltammetry (RCV) and electrochemical impedance spectroscopy (EIS). Results showed that the polymers interacted more extensively than the nanoparticles with the phospholipid. The interaction of the polymer was more rapid and led to a polymer-phospholipid conjugate whereas the nanoparticle adsorbed on the phospholipid monolayer surface and penetrated the monolayer at longer contact times. The association of the linear polymer with the phospholipid can be related to the larger molecular area available with the pendant -Cl groups and the inherent polymeric flexibility compared to the nanoparticle structure. The apparent dissociation constant for nanoparticles-DOPC complex was K(d,app)=1.67 × 10(-5)±1.2 × 10(-6) mol dm(-3). The apparent kinetic constant of nanoparticle penetration through the DOPC monolayer was k(2,app)=1.054 × 10(-2)±9.1 × 10(-4) s(-1). It can be concluded therefore that the pNIPAM nanoparticle because of its lower affinity for phospholipids is more appropriate for medical applications.


Kawasaki disease complicated with shock syndrome, macrophage activation syndrome, and acute abdomen in children: Two case reports.
Kawasaki disease (KD) is an acute systemic vasculitis that can involve multiple organs. Few reports have been published about KD patients presenting with multiple complications such as acute abdomen, KD shock syndrome (KDSS), and macrophage activation syndrome (MAS). We present the cases of two males (9 and 12 years old) diagnosed with KD accompanied by rare manifestations. Case 1 is a 9-year-old male treated for acute appendicitis, KDSS, and MAS. Case 2 is a 12-year-old male who presented with KDSS, MAS, and an ileal perforation. They were treated with intravenous immunoglobulin, aspirin, high-dose corticosteroids, vasoactive drugs, and symptomatic treatment, with good outcomes. Clinicians should be aware of the possibility of KD in the presence of fever and unusual manifestations, such as severe inflammatory indicators and acute abdomen that is nonresponsive to antibiotic therapy. Meanwhile, KD-related unusual complications should be recognized, such as KDSS and MAS.


Fast and quantitative compositional analysis of hybrid cellulose-based regenerated fibers using thermogravimetric analysis and chemometrics.
Cellulose can be dissolved with another biopolymer in a protic ionic liquid and spun into a bicomponent hybrid cellulose fiber using the Ioncell® technology. Inside the hybrid fibers, the biopolymers are mixed at the nanoscale, and the second biopolymer provides the produced hybrid fiber new functional properties that can be fine-tuned by controlling its share in the fiber. In the present work, we present a fast and quantitative thermoanalytical method for the compositional analysis of man-made hybrid cellulose fibers by using thermogravimetric analysis (TGA) in combination with chemometrics. First, we incorporated 0-46 wt.% of lignin or chitosan in the hybrid fibers. Then, we analyzed their thermal decomposition behavior in a TGA device following a simple, one-hour thermal treatment protocol. With an analogy to spectroscopy, we show that the derivative thermogram can be used as a predictor in a multivariate regression model for determining the share of lignin or chitosan in the cellulose hybrid fibers. The method generated cross validation errors in the range 1.5-2.1 wt.% for lignin and chitosan. In addition, we discuss how the multivariate regression outperforms more common modeling methods such as those based on thermogram deconvolution or on linear superposition of reference thermograms. Moreover, we highlight the versatility of this thermoanalytical method-which could be applied to a wide range of composite materials, provided that their components can be thermally resolved-and illustrate it with an additional example on the measurement of polyester content in cellulose and polyester fiber blends. The method could predict the polyester content in the cellulose-polyester fiber blends with a cross validation error of 1.94 wt.% in the range of 0-100 wt.%. Finally, we give a list of recommendations on good experimental and modeling practices for the readers who want to extend the application of this thermoanalytical method to other composite materials. The online version contains supplementary material available at 10.1007/s10570-021-03923-6.


Altered expression of the growth and transformation suppressor PML gene in human hepatocellular carcinomas and in hepatitis tissues.
The promyelocytic leukaemia (PML) gene, which encodes a transformation and growth suppressor, was first identified at a chromosomal translocation break point in acute promyelocytic leukaemia. To elucidate if PML may be involved in hepatocellular carcinoma (HCC), the expression of PML was analysed using immunohistochemistry in human HCC and hepatitis tissues. Our studies demonstrated overexpression of PML protein in the PML-oncogenic domain (POD) structure in 50% of HCC (11/22). Enhanced expression and cytoplasmic localisation of PML was associated with cirrhosis. Increased expression of PML was also found in liver abscesses. However, in colon metastasis to the liver, the expression of PML was moderate to low, although strong expression was seen in the surrounding interstitial cells, macrophages and lymphocytes, an indication of the inflammation process associated with tumour growth. Most interestingly, strong expression of PML was found in neoplastic cells at the periphery of the tumours, but progressively decreased in cells at the centre of the tumours, which may be associated with an altered transform phenotype or apoptosis. The altered expression of PML indicates that this nuclear protein may play an important role in cellular response to stress and inflammation, as well as in compensatory cell growth.


AIDS under a competitive Medicaid program in a "second wave" state: Arizona's experience.
Arizona is a "second wave" state, ranking twenty-first among states in a number of reported AIDS cases. Interviews with 50 administrators and providers were used to determine how Arizona's Medicaid program, the Arizona Health Care Cost Containment System (AHCCCS), has responded to the AIDS epidemic. AHCCCS is a unique Medicaid program in which care is provided by health plans selected through competitive bidding on capitated rates. Policies that foster price competition among health plans may impede a timely and appropriate response to the AIDS epidemic, unless they take the character of this epidemic into account.


The association of RNA-binding protein Human antigen R with kidney clinicopathologic features and renal outcomes in patients with diabetic nephropathy.
RNA-binding protein Human antigen R (HuR) is closely related to diabetic nephropathy (DN) pathogenesis. However, the capacity of histological HuR level as a biomarker for DN progression remains unclear. A total of 147 patients with type 2 diabetes mellitus who had biopsy-proven DN were enrolled. Renal outcomes were defined by doubling serum creatinine level or progression to end-stage renal disease (ESRD). A nomogram was built to predict renal outcomes based on Cox proportional hazards regression. The median follow-up period was 31 months, during which 71 (48.30 %) patients confronted DN progression. Pearson's correlation indicated that histological HuR increased along with DN pathological class rising (r = 0.776, p < 0.001). Notably, multivariate Cox regression analysis showed that elevated HuR was associated with a greater risk of DN progression (HR 2.431, 95 %CI: 1.275-4.634, p = 0.007) beyond 6 months after renal biopsy. Patients in the higher HuR expression group had lower cumulative renal survival rates beyond the first 6 months. Simultaneously, a well-performed nomogram including HuR classification, was developed to predict the individual progression risk (C-index 0.828). Our findings demonstrated that the histologic HuR expression was an independent risk factor for kidney progression beyond 6 months after renal biopsy in DN.


Rest and treadmill exercise first-pass radionuclide ventriculography: validation of left ventricular ejection fraction measurements.
To assess the accuracy of rest and treadmill exercise first-pass radionuclide ventriculographic measurements of left ventricular ejection fraction (LVEF), 40 patients underwent treadmill exercise first-pass and bicycle exercise equilibrium radionuclide ventriculography. To determine the frequency of technically adequate treadmill exercise first-pass studies, an additional 128 consecutive patients undergoing treadmill exercise first-pass procedures during stress 99mTc-labeled sestamibi myocardial perfusion studies were assessed. The treadmill exercise first-pass procedure used a multicrystal camera and an 241Am point source to allow for correction of patient motion. Excellent correlations were observed between resting first-pass and resting equilibrium LVEF (r = 0.91; standard error of the estimate = 5.6). A high correlation was also observed between treadmill exercise first-pass and bicycle equilibrium exercise LVEF measurements (r = 0.85, standard error of the estimate = 7.6). Treadmill first-pass LVEF systematically underestimated the bicycle equilibrium LVEF. Intraobserver agreement for rest and exercise first-pass LVEF was high (r values of 0.98 and 0.94, respectively). Of the 168 consecutive treadmill exercise first-pass studies evaluated for technical adequacy, 21 (12.5%) were deemed technically inadequate, with most of the sources of error being avoidable. The frequency of technically adequate studies was as high (87%) in high levels of exercise (Bruce stages 3 and 4) as in lower levels (88%). The findings of this study validate the first-pass treadmill exercise LVEF measurement. This procedure now provides the option for combining the information of peak treadmill exercise LVEF with measurements of exercise myocardial perfusion from the same injection of radioactivity.


Preclinical testing of oncolytic adenovirus sensitivity in patient-derived tumor organoids.
Patient-derived organoids (PDOs) have shown the potential to reflect patient sensitivity to chemotherapeutic or targeted drugs. Recently, we showed that organoid models can also serve as a platform to screen for selectivity and potency of oncolytic adenoviruses (OAds). In this protocol, we describe the steps for tumor organoid adenoviral infection and functional assessment of patient-specific responses to OAds. We provide methods to determine OAd relative efficacy by evaluation of PDO viability after infection and adenoviral replication within cancer cells. For complete details on the use and execution of this protocol, please refer to Raimondi et al. (2020).


Evolution of myoelectrical and precentral cell activities during learning of a new amplitude of movement.
The object of these experiments was to determine if changes in precentral neuron activity may be related to learning of a new amplitude of movement. Data were obtained from two monkeys trained to stop, in a given position, an elbow flexion movement in order to get a reward. A screen prevented the animal from seeing its forearm. The terminal position was not indicated by a cue, and movements were self-initiated. Motor performance and cell activity were analyzed during the period of learning of a new amplitude of movement. The cells studied presented the reciprocal patterns of activity: they were active flexion but discharged during passive extension. Results clearly indicated that: (1) amplitude was the actual parameter which was learned; (2) the peak frequency of discharge of motor cortex neurons increased during learning, as did the frequency of reward; and (3) the peak frequency of discharge related to passive movements was not changed by conditioning. The results support the hypothesis that the increase of the activity tied to active movements which is observed during conditioning may not be related to an increase of peripheral feedback but expresses a greater 'corticalization' of the movement.


Displaced radial neck fractures in children.
Forty-eight children with displaced fractures of the radial neck were studied. Five types of injury were seen, that associated with a valgus strain being the most common. Good results were obtained in just over one-half of the cases. It is concluded that treatment of these fractures should be by closed means whenever possible. It is generally unwise to attempt operative correction unless the radial head remains displaced or the residual angulation approaches 45 degrees. Open reduction should be checked by intraoperative radiographs. Internal fixation is seldom necessary and has its complications. Late manipulation of the fracture causes additonal trauma and the results are bad. Avascular necrosis and radio-ulnar synostosis were the two most disabling complication encountered.


Combined astigmatic keratotomy and conductive keratoplasty to correct high corneal astigmatism.
To determine the safety, efficacy, and predictability of combined astigmatic keratotomy (AK) and conductive keratoplasty (CK) for treating high corneal astigmatism. University of California-Los Angeles, Los Angeles, California, USA. Retrospective case series. From January 1, 2004, to December 31, 2009, AK and CK were performed in eyes with corneal astigmatism of 5.0 diopters (D) or more after keratoplasty or trauma. The uncorrected (UDVA) and corrected (CDVA) distance visual acuities, spherical equivalent (SE), defocus equivalent, mean astigmatism, efficacy index, and complications were evaluated. In 11 eyes of 11 patients, the mean UDVA improved from 1.54 logMAR ± 0.50 (SD) preoperatively to 0.69 ± 0.62 logMAR 3 months postoperatively (P < .001) and the mean CDVA from 0.55 ± 0.62 logMAR to 0.12 ± 0.11 logMAR (P = .028). The mean SE and mean defocus equivalent decreased from -1.25 ± 5.06 D to 3.13 ± 3.06 D (P = .15) and from 7.98 ± 4.41 D to 6.97 ± 3.73 D (P = .45), respectively; these changes were not statistically significant. The mean absolute astigmatism decreased from 10.25 ± 4.71 D to 4.31 ± 2.34 D (P < .001). The mean absolute orthogonal and mean oblique astigmatism showed a statistically significant decrease. The efficacy index was 0.82. One case of wound gape after AK required suturing. No infectious keratitis, corneal perforation, or graft rejection occurred. Results indicate that combined AK and CK is safe and effective for correcting high corneal astigmatism after surgery or trauma.


The cumulative risk of false-positive results in the Norwegian Breast Cancer Screening Program: updated results.
Some false-positive results are inevitable in mammographic screening, but the impact of false-positive findings on the program and the participants is a disadvantage of screening. The objective of the current study was to estimate the cumulative risk of a false-positive result over 10 biennial screening examinations and the cumulative risk of undergoing an invasive procedure with a benign outcome in women screened between the ages of 50 years to 69 years. A retrospective cohort study was performed in 231,310 women aged 50 years to 51 years at the time of first mammography screening who underwent 715,311 screening mammograms in the Norwegian Breast Cancer Screening Program from 1996 through 2010. Generalized linear mixed models were used to estimate the probability of a false-positive screening result and to compute the cumulative false-positive risk for up to 10 biennial screening examinations. The cumulative false-positive risk after 20 years of biennial screening for women who initiated screening aged 50 years to 51 years was 20.0% (95% confidence interval [95% CI], 19.7%-20.4%). The cumulative risk of undergoing an invasive procedure with a benign outcome for the same group of women was 4.1% (95% CI, 3.9%-4.3%). The cumulative risk of undergoing a fine-needle aspiration cytology, core needle biopsy, or open biopsy with a benign outcome was 1.4% (95% CI, 1.3%-1.5%), 2.0% (95% CI, 1.9%-2.1%), and 0.16% (95% CI, 0.13%-0.19%), respectively. One in every 5 women will be recalled for further assessment with a negative outcome if they attend biennial mammographic screening between ages 50 years to 69 years. The risk of an invasive procedure with a benign outcome is approximately 4%. It is important to communicate the existence and extent of this risk to the target group and to reduce to a minimum the waiting times between screening and further assessment.


Verification of a loss of heterozygosity at the D8S1179 locus in a paternity case by the MiSeq FGx system.
Capillary electrophoresis is widely used to study short tandem repeats (STRs) in forensic genetics. However, next-generation sequencing platforms have become a new strategy for forensic DNA typing. In this study, we report a false four-step STR mutation between an alleged father (AF) and child in a paternity case. A total of 23 autosomal STR loci were evaluated using the Huaxia™ Platinum and Goldeneye™ 20A kits, revealing a single mismatch in D8S1179 between the AF (10/10) and the male child (14/14). Additional Y-STR typing of the AF and child was performed, and the results were consistent with those based on 27 Y-STR loci. To further confirm the experimental results, we sequenced the individuals using the MiSeq FGx system and detected 10/15 unbalanced alleles in the D8S1179 locus of the AF and 14/15 unbalanced alleles in the D8S1179 locus of the child. Sanger sequencing revealed that both the AF and child had the C→G point mutation in the primer binding region of D8S1179 resulting in allelic dropout. Therefore, the verification of STR typing by different sequencing systems is helpful for the interpretation of results in cases of multistep STR mutations.


Ultrahigh Throughput Protein-Ligand Docking with Deep Learning.
Ultrahigh-throughput virtual screening (uHTVS) is an emerging field linking together classical docking techniques with high-throughput AI methods. We outline mechanistic docking models' goals and successes. We present different AI accelerated workflows for uHTVS, mainly through surrogate docking models. We showcase a novel feature representation technique, molecular depictions (images), as a surrogate model for docking. Along with a discussion on analyzing screens using regression enrichment surfaces at the tens of billion scale, we outline a future for uHTVS screening pipelines with deep learning.


The localization of thromboxane synthase in normal and pathological human kidney tissue using a monoclonal antibody Tü 300.
Thromboxane, excreted in the urine in increased amounts in glomerular, vascular and tubulo-interstitial diseases, is considered to originate from the kidney. The localization of thromboxane synthase, a key enzyme of arachidonic acid metabolism, was studied in the human kidney by immunohistology using the monoclonal antibody Tü 300. In the interstitial tissue dendritic reticulum cells surrounding the tubules expressed high concentrations of the enzyme. In glomeruli the enzyme was weakly expressed in podocytes. This was confirmed by co-localization with an antiserum directed to podocalyxin, a marker of the visceral epithelial cells. In the study of various kidney diseases, massive accumulation of thromboxane synthase containing cells was observed in interstitial diseases, whereas in glomerular diseases there were no differences from normal kidney; in a case of thrombotic microangiopathy podocytes exhibited an increase in thromboxane-synthase. The thromboxane-synthase positive infiltrating interstitial cells were shown by conventional light microscopy to be mononuclear phagocytic cells. The physiological sources of renal thromboxane are dendritic reticular cells and podocytes. In interstitial renal disease infiltrating cells of the monocyte/macrophage system constitute the major site of thromboxane synthesis. In glomerular disease, a characteristic alteration of thromboxane-synthase was not found.


Disruption of a key ligand-H-bond network drives dissociative properties in vamorolone for Duchenne muscular dystrophy treatment.
Duchenne muscular dystrophy is a genetic disorder that shows chronic and progressive damage to skeletal and cardiac muscle leading to premature death. Antiinflammatory corticosteroids targeting the glucocorticoid receptor (GR) are the current standard of care but drive adverse side effects such as deleterious bone loss. Through subtle modification to a steroidal backbone, a recently developed drug, vamorolone, appears to preserve beneficial efficacy but with significantly reduced side effects. We use combined structural, biophysical, and biochemical approaches to show that loss of a receptor-ligand hydrogen bond drives these remarkable therapeutic effects. Moreover, vamorolone uniformly weakens coactivator associations but not corepressor associations, implicating partial agonism as the main driver of its dissociative properties. Additionally, we identify a critical and evolutionarily conserved intramolecular network connecting the ligand to the coregulator binding surface. Interruption of this allosteric network by vamorolone selectively reduces GR-driven transactivation while leaving transrepression intact. Our results establish a mechanistic understanding of how vamorolone reduces side effects, guiding the future design of partial agonists as selective GR modulators with an improved therapeutic index.


Photobiomodulation: An Emerging Treatment Modality for Depression.
Major depressive disorder (MDD) is considered a global crisis. Conventional treatments for MDD consist of pharmacotherapy and psychotherapy, although a significant number of patients with depression respond poorly to conventional treatments and are diagnosed with treatment-resistant depression (TRD). Transcranial photobiomodulation (t-PBM) therapy uses near-infrared light, delivered transcranially, to modulate the brain cortex. The aim of this review was to revisit the antidepressant effects of t-PBM, with a special emphasis on individuals with TRD. A search on PubMed and ClinicalTrials.gov tracked clinical studies using t-PBM for the treatment of patients diagnosed with MDD and TRD.


The spinal cord in lightning injury: a report of two cases.
We present 2 patients in whom the predominant neurological complication following lightning strike was spinal cord injury. One patient, who was followed for 5 years, showed clinical, electrophysiologic and MRI evidence of cervical spinal cord injury. This patient had significant recovery, which in part, may be related to early and intense rehabilitation. The second patient presented with the symptoms and signs of spinal shock which then evolved into a myelopathy. Follow-up several months later showed almost complete resolution of symptoms. These patients demonstrate that the prognosis of spinal cord injury complicating a lightning strike may not be uniformly poor.


Awareness about breast cancer and mammogram among women attending outpatient clinics, Ain Shams University Hospitals, Egypt.
Breast diseases in women, whether benign or malignant, are very commonly encountered. The breast is the commonest site for female cancer in Egypt (38.8%). Breast cancer screening can reduce morbidity and mortality and improve the survival rate for this malignancy. Mammogram can be used as a screening technique beside its role as diagnostic, especially in women over 40 years of age. To assess knowledge, attitude and practice regarding breast cancer and awareness about mammogram as a screening method among a group of females attending Ain Shams University outpatient clinics. A cross-sectional study was performed from August to September 2017. A systematic random sample was taken from attending females (18-70 years) in Ain Shams University outpatient clinics (Internal Medicine, Surgery, Pediatrics Hospital, and Maternity hospital). They were interviewed using a questionnaire inquiring about sociodemographic background, participants' knowledge, attitude, and practice towards breast cancer and its screening. The mean age ± SD of attending females (18-70 years) was 37 ± 11 years. Most study participants had correct information about mammography. They showed poor knowledge level about risk factors. Mass media such as TV and internet were identified as the main source of information on breast cancer by 43% and 23.9%, respectively. In general, participants had positive attitude towards breast cancer screening by mammography. Around 90% agreed that mammogram was the best way to find a very small lump in the breast, and 91.4% agreed that women who have regular screening by mammogram have better disease outcome than those who do not screen. Regarding mammography practice rate, a small percent of participants (8.1%) was advised by their doctors to conduct a screening mammography. The level of knowledge was significantly and positively correlated with their attitude towards breast cancer screening. The poor knowledge and practices of women illustrate the need for health education program directed to Egyptian females to improve their knowledge about breast cancer-especially its risk factors-and its screening. Using TV and Internet as media for spreading information about this disease is crucial.


Socioeconomic Inequalities in Heart Failure.
Prevalence and incidence of chronic heart failure (CHF) has increased during the past decades. Beyond its impact on mortality rates, CHF severely impairs quality of life, particularly with the elderly and vulnerable population. Several studies have shown that CHF takes its toll mostly on the uneducated, low-income population, who exhibit impaired access to health care systems, less knowledge regarding its pathology and poorer self-care behaviors. This review summarizes the available evidence linking socioeconomic inequalities and CHF, focusing on the modifiable factors that may explain the impaired health outcomes in socioeconomically deprived populations.


Stereotype Threat Lowers Older Adults' Self-Reported Hearing Abilities.
Although stereotype threat is a well-documented phenomenon, previous studies examining it in older adults have almost exclusively focused on objective cognitive outcomes. Considerably less attention has been paid to the impact of stereotype threat on older adults' subjective assessments of their own abilities or to the impact of stereotype threat in noncognitive domains. Older adults are stereotyped as having experienced not only cognitive declines, but physical declines as well. The current study tested the prediction that stereotype threat can negatively influence older adults' subjective hearing abilities. To test this, 115 adults (mean age 50.03 years, range 41-67) read either a positive or negative description about how aging affects hearing. All participants then answered a questionnaire in which they assessed their own hearing abilities. The impact of stereotype threat on self-reported hearing was moderated by chronological age. Participants in their 40s and early 50s were unaffected by the stereotype threat manipulation. In contrast, participants in their late 50s and 60s rated their hearing as being subjectively worse when under stereotype threat. The current study provides a clear demonstration that stereotype threat negatively impacts older adults' subjective assessments of their own abilities. It is also the first study to demonstrate an effect of stereotype threat within the domain of hearing. These results have important implications for researchers investigating age-related hearing decline. Stereotype threat can lead to overestimation of the prevalence of age-related hearing decline. It can also serve as a confounding variable when examining the psychosocial correlates of hearing loss. Because of this, researchers studying age-related hearing loss should aim to provide a stereotype threat-free testing environment and also include assessments of stereotype threat within their studies.


The association of neuraxial versus general anesthesia with inpatient admission following arthroscopic knee surgery.
Arthroscopic knee procedures are increasingly being performed in an outpatient setting. Appropriate intraoperative anesthesia is vital to prevent complications such as unanticipated hospital admission. We examined differences in complications between general (GA) vs neuraxial anesthesia (NA) as the primary anesthetic for patients undergoing arthroscopic knee procedures. This was a retrospective cohort study. We queried the National Surgical Quality Improvement Program for arthroscopic knee procedures performed between 2007 and 2016. We compared postoperative complication rates between propensity-matched cohorts (NA vs GA). The anesthesia groups were matched based on age, race, BMI, gender, diabetes, smoking history, COPD, CHF, functional status, HTN, ASA class, steroid use, bleeding disorder history, and readmission status. Univariable and multivariable logistic regression were used to compare factors associated with inpatient admission - defined as hospital length of stay >1 day. A total of 57,494 patients were included - 55,257 GA and 2237 NA patients. Among the matched cohorts, NA patients were significantly more likely to be admitted to the hospital postoperatively (p < 0.001). Neuraxial anesthesia (OR 5.93, 95% CI 4.90-7.21) use was also significant in the final multivariable regression model for inpatient admission. Additional significant predictors for inpatient admission included history of bleeding disorder (OR 5.44, 95% CI 2.14-12.76), Asian race (OR 6.47, 95% CI 4.90-8.56), COPD (OR 3.10, 95% CI 1.94-4.82), diabetes (OR 1.90, 95% CI 1.43-2.49), and increased operation time (OR 3.01, 95% CI 2.69-3.37). NA was significantly associated with inpatient admission following knee arthroscopy. Further research should focus on examining the reason for this association and methods to reduce inpatient admission for patients undergoing arthroscopic knee procedures using neuraxial anesthesia.


Environmentally friendly electroless plating for Ag/TiO2-coated core-shell magnetic particles using ultrasonic treatment.
In this work, high-reflectance brilliant white color magnetic microspheres comprising a Fe/TiO2/Ag core-shell structure with a continuous, uniform compact silver layer were successfully fabricated by TiO2-assisted electroless plating in a simple and eco-friendly method. The coating procedure for TiO2 and Ag involved a sol-gel reaction and electroless plating with ultrasound treatment. The electroless plating step was carried out in an eco-friendly manner in a single process without environmentally toxic additives. The TiO2 layer was used as a modification layer between the Fe microspheres and the silver layer to improve adhesion. A continuous and compact silver layer could be formed with a high degree of morphological control by introducing ultrasonication and adjusting the ammonium hydroxide concentration.


Temporal Lobe Surgery for Epilepsy in a Resource-Limited Vietnamese Cohort.
Epilepsy surgery is traditionally difficult to pursue in resource-limited countries but is nevertheless essential in the treatment of medication-refractory, surgically amenable epilepsy. With the help of international collaboration, a successful epilepsy program was started in Vietnam. This article comprises a retrospective chart review, combined with prospective longitudinal follow-up of 35 cases of unilateral drug-resistant epilepsy in the temporal lobe who underwent temporal lobectomy, in Viet Duc University Hospital from May 2018 to September 2022. The female/male ratio was 0.6:1, and focal seizures with impaired awareness accounted for 97.14% of patients. Of patients with focal awareness seizures, 51.41% were localized and detected by electroencephalography. Postoperatively, 80% of patients were seizure free (Engel I) at 1 year, and the remaining 20% had worthwhile seizure improvement (Engel II). Postoperative temporal lobe pathology was categorized as follows: mesial temporal sclerosis (48.57%), focal cortical dysplasia (25.71%), and low-grade neoplasms (25.71%). Of patients, 17.14% had postoperative complications (5 infections and 1 transient extremity paresis), and there were no deaths. Even in low-resource environments, effective and safe surgical care can be provided for drug-resistant epilepsy caused by temporal lobe disease. This study serves as a model of international collaboration and support for future hospitals in low-resource environments to replicate.


Methods of a Study to Assess the Contribution of Cerebral Small Vessel Disease and Dementia Risk Alleles to Racial Disparities in Vascular Cognitive Impairment and Dementia.
Background Non-Hispanic Black adults have a higher proportion of vascular cognitive impairment and Alzheimer's disease and related dementias compared with non-Hispanic White adults that may be due to differences in the burden of cerebral small vessel disease and risk alleles for Alzheimer's disease and related dementias. We describe here the methods of an ancillary study to the REGARDS (Reason for Geographic and and Racial Difference in Stroke) study, which will examine the role of magnetic resonance imaging markers of cerebral small vessel disease and vascular as well as genetic risk factors for Alzheimer's disease and related dementias in racial disparity in the prevalence and trajectory of vascular cognitive impairment and dementia in non-Hispanic White and non-Hispanic Black participants. Methods In participants with no prior history of stroke who had an incident stroke or transient ischemic attack after enrollment in the study, magnetic resonance imaging scans will be evaluated using the Standards for Reporting Vascular Changes on Neuroimaging international consensus criteria and automated analysis pipelines for quantification of cerebral small vessel disease. Participants will be genotyped for APOE ε4 and TREM2 risk alleles for Alzheimer's disease and related dementias. The 6-item screener will define global cognitive function and be the primary cognitive outcome. Conclusions With at least 426 non-Hispanic Black and 463 non-Hispanic White participants who have at least 2 prior and 2 poststroke or transient ischemic attack cognitive assessments, we will have at least 80% power to detect a minimum effect size of 0.09 SD change in Z score, with correction for as many as 20 tests (ie, at P<0.0025, after adjusting for up to 20 covariates) for cognitive decline.


The processing of the selective M1 agonist CDD-0102-J by human hepatic drug metabolizing enzymes.
The in vitro metabolism of the selective M1 muscarinic agonist CDD-0102-J was evaluated in heterologous systems expressing individual human cytochrome P-450 (CYP) isoenzymes and also in suspensions of cryopreserved human hepatocytes. In all experiments, the metabolism of CDD-0102-J was characterized based on its rate of disappearance using an HPLC assay since no metabolites have as yet been characterized. The human CYP isoenzymes used were CYP1A2, 2A6, 2B6, 2C8, 2C19, 2D6, and 3A4. Measurable decreases in CDD-0102-J concentrations over time were detectable only in systems containing either CYP2D6 or CYP2C8, although the unbound in vitro clearance was more than 20 times larger for CYP2D6 (7.6 mL h(-1) nmol(-1)) than for CYP2C8 (0.35 mL h(-1) nmol(-1)). When scaled to in vivo hepatic clearance based on just CYP2D6 and CYP2C8, the projected hepatic clearance for CDD-0102-J was 7.7 L h(-1), which corresponded closely with the hepatic clearance of 8.4 L h(-1) scaled from experiments using cryopreserved human hepatocytes.


The role of magnetic assisted capsule endoscopy (MACE) to aid visualisation in the upper GI tract.
Examination of the upper gastrointestinal tract by a standard endoscope is often thought as a daunting experience to many who have undertaken or are about to undergo the procedure. The overall perceived size of the gastroscope, unpleasantness of stimulation of the gag reflex and the need often for sedation is discouraging to many. A method to visualise the upper gastrointestinal mucosa which negates the need for sedation, the associated expensive decontamination costs and the possibility of having a community based examination would be particularly welcoming to this endoscopy field. Since the first swallow of a capsule endoscope by a human volunteer in 1999, their usage for examining the small bowel has exponentially grown to that of over a million patients worldwide. More recently, innovation in this field have shown plausibility for its use to visualise the upper gastrointestinal tract, with the integration of magnets within the capsule the most promising method.


Prospective study of nephrolithiasis occurrence in children receiving cefotriaxone.
Ceftriaxone is a commonly used antibiotic among the paediatric population. Various reports have associated high doses of Ceftriaxone with the development of nephrolithiasis; our aim was to test this association with a 5 day course of treatment. Our study group consisted of 120 patients divided into two groups. The first group included 60 patients who underwent treatment with Ceftriaxone therapy that was started empirically and continued for 5 days at the dose of 80 mg/kg per day. The second group (60 patients) who received treatment with other antibiotics (other than Ceftriaxone), as recommended by hospital protocols. Patients with urinary tract infections (UTI) were excluded as UTI may be a predisposing cause for nephrolithiasis. Baseline and follow up after 5 days were done with; abdominal ultrasound, serum urea, creatinine, serum calcium, 24 h urinary calcium and urinary calcium/ creatinine ratio. Extended metabolic tests were done for cases that developed nephrolithiasis. Five cases out of the 60 patients treated with Ceftriaxone developed calculi; that were small and were eliminated spontaneously in four cases at mean duration of 3 weeks. In these cases renal ultrasonography examinations were normal prior to treatment; and none of them had metabolic disturbances or risk factors leading to stone formation. By multiple regression analysis, only age was related to nephrolithiasis formation being higher in the group that has developed stones. Only patients who underwent Ceftriaxone therapy have developed renal stones, even with a short course of therapy (5 days), and in the absence of a known predisposing cause for nephrolithiasis. We have thus concluded that Ceftriaxone by itself maybe a predisposing factor for nephrolithiasis.


Fatigue and recovery in shiftworking nurses: A scoping literature review.
To identify factors impeding or enhancing recovery from fatigue in shiftworking nurses. Scoping literature review methodology was implemented to identify key concepts around recovery from fatigue in shiftworking nurses to provide a narrative around these paradigms. Five electronic data bases were searched: CINAHL, MEDLINE, PROQUEST Health and Medicine, ScienceDirect and PsycINFO to identify primary studies on fatigue and recovery in shiftworking nurses from 2000 to 2019 inclusive. Preliminary searches were completed between September and December 2017 and finalised in January 2020. Research was drawn from nursing only samples employed under shiftwork scheduling. 31 studies were included in this scoping review. Factors impeding and enhancing recovery at work and home are identified as impacting on fatigue outcomes. Findings indicate recovery from fatigue in shiftworking nurses are most significantly affected by high work and job demands and the 'when' and 'how' of shiftwork scheduling; all reported to impede recovery from shiftwork related fatigue. The most noteworthy facilitators of recovery were work control and control over shiftwork scheduling, break opportunities at work, age and being part of a family structure. There was a dearth of research identified around the time frames of the progression from acute to chronic fatigue and the in-depth role of recovery in this transition. As chronic or long-term fatigue can develop from an acute or recoverable fatigue this may significantly impact on shiftworking nurses' health and wellbeing. This scoping review highlights the complicated nature of shiftwork scheduling and the impact it can have on recovery from fatigue in shiftworking nurses. Multiple methods and ways of measuring fatigue, recovery and shiftwork were identified in the studies. The results describe factors impeding and enhancing recovery from fatigue as occurring within both the workplace and during time away from work. Thus, this review provides improved understanding of the barriers and facilitators in recovery from fatigue and the potential accumulation of fatigue over time. These findings are important for shiftworking nurses, nursing managers and hospital administrators, and society, who are dependant on nurses' care.


Electrodermal activity in schizophrenia: a quantitative study using a short interstimulus paradigm.
Electrodermal activity in response to short interstimulus interval (ISI) stimulation allows aspects of information processing to be examined, but such paradigms cause skin conductance responses (SCRs) to overlap. A signal decomposition method was developed and employed to score the overlapped SCRs. This is the first application of the method to the study of schizophrenia. Electrodermal activity of 30 medicated patients with schizophrenia and 50 normal controls was obtained using a conventional auditory oddball paradigm with an ISI of 1.3 sec. Tonic skin conductance level (SCL), phasic SCRs, SCR temporal dynamics, and a range of SCR variables in response to target tones were examined. The schizophrenic group showed reduced response rate, proportion of responders, SCR amplitude, rise time, peak latency, and steady-state response amplitude, over the trial compared with controls. There were no between-group differences in SCL or SCR onset time. The combined use of a conventional short ISI paradigm and the new SCR scoring method demonstrated new facets of electrodermal hyporeactivity in medicated patients with schizophrenia. The hyporeactivity could not be attributed to changes in tonic arousal or dysfunctions in peripheral sympathetic nerve conductance.


[Therapeutic and prophylactic measures in patients with dust-induced bronchitis complicated by pulmonary emphysema].
Therapeutic-prophylactic measures in 60 patients were directed to remove the main pathogenetic mechanisms of development of lung emphysema (control of the obstructive syndrome, normalization of the sputum rheology, reduction of the protease level, restoration of the surfactant system activity). The efficacy of complex treatment (broncholytic agents, mucus regulators, protease inhibitors, etc.) depended largely on the necessity of active prophylactic medical care of patients with dust-induced bronchitis at early stages of the disease.


Compressed mini-tablets as a biphasic delivery system.
Compressed mini-tablets systems are presented as a biphasic delivery system designed for zero-order sustained drug release. The outer layer that fills the void spaces between the mini-tablets was formulated to release the drug in a very short time (fast release), while the mini-tablets provided a prolonged release. Different composition (HPMC or EC) and number (10 or 21) of mini-tablets were used to obtain different drug release rates. The in vitro performance of these systems showed the desired biphasic behaviour: the drug contained in the fast releasing phase (powder enrobing the mini-tablets) dissolved within the first 2 min, whereas the drug contained in the mini-tablets was released at different rates, depending up on formulation. Based on the release kinetic parameters calculated, it can be concluded that mini-tablets containing HPMC were particularly suitable approaching to zero-order (constant) release over 8h time periods.


Predictive ability of estrogen receptor (ER), progesterone receptor (PR), COX-2, Mlh1, and Bcl-2 expressions for regression and relapse of endometrial hyperplasia treated with LNG-IUS: a prospective cohort study.
To test the predictive ability of immunohistochemical estrogen receptor(ER), progesterone receptor (PR), COX-2, Mlh1, and Bcl-2 expressions for predicting the outcomes of regression and relapse in women with endometrial hyperplasia treated with the Levonorgestrel-releasing intrauterine system (LNG-IUS). We recruited prospectively all women diagnosed with complex or atypical complex hyperplasia that underwent treatment with LNG-IUS from August 1998 until September 2008. Immunohistochemistry was performed with conventional methods and recorded using a semi-quantitative score (Q score) by two blinded assessors. Women were followed with endometrial biopsies to record regression and relapse. The biomarker predictive ability was analysed using the Cox proportional hazards model. The median follow-up was 72.1 months (IQR 59.1-89.8). The Q score agreement between assessors was 82.6% (K statistic=0.801 ± 0.036). The majority of study participants initially regressed to normal endometrium following LNG-IUS therapy (n = 164 regressed; n = 10 persisted). From the 164 women that regressed with LNG-IUS we were able to assess 152 women for relapse from which 18 relapsed. We found a weak association for persisted endometrial hyperplasia with ER and PR expressions with Q score on the 5th and 10th centiles. No associations were found for COX-2, Mlh1 and Bcl-2 protein expressions for regression and for any of the biomarkers for relapse. We found that poor expression of ER and PR is weakly associated with persisting endometrial hyperplasia and COX-2, Mlh1, and Bcl-2 expressions are not predictive. None of the biomarkers is predictive for relapse in women with endometrial hyperplasia treated with LNG-IUS.


Searching for new NO-donor aspirin-like molecules: Furoxanylacyl derivatives of salicylic acid and related furazans.
A new group of derivatives of salicylic acid containing NO-donor furoxans, and the related des-NO-furazans, were synthesized and evaluated as new aspirin-like molecules. Their stability was assessed in acid (pH 1) and physiological solutions (pH 7.4), and in human serum. No compound exhibited COX-inhibitory activity against COX-1 and COX-2 isoforms, when tested up to 100μM, respectively, on isolated platelets and on monocytes. Phenylsulfonyl- and cyano-substituted furoxans inhibited platelet aggregation induced by collagen in human platelet-rich plasma, through a cGMP dependent mechanism. Furoxan derivatives displayed cGMP-dependent vasodilator activities, tested on rat aorta strips precontracted with phenylephrine. All products showed anti-inflammatory activity similar to that of ASA, tested on rats by the carrageenan-induced paw edema assay. Unlike ASA, all products showed markedly reduced gastrotoxicity in a rat lesion model.


Haematology, weight and condition of captive red grouse (Lagopus lagopus scoticus) infected with caecal threadworm (Trichostrongylus tenuis).
Red grouse infected with the caecal threadworm Trichostrongylus tenuis developed a mild anaemia. Haemoglobin and albumin levels in the blood fell but there were no significant changes in the number of red blood cells or their size. In infected birds the numbers of circulating eosinophils and heterophils increase, as did the concentration of alpha, beta and gamma globulin. Body weights did not change but muscle masses shrank. Birds that subsequently died had the lowest concentration of haemoglobin and packed cell volumes and the highest counts of eosinophils. The survivors were affected little by worms and their haematology showed small deviations from normal.


[Mathematical model of epidemiology of an anthropozoonose: brucellosis (author's transl)].
We are trying to make a model of the epidemiology of Brucellosis by using a two-type branching process. In this text, we are studying the probability of extinction. A complete study on the theory of process with a finite number of types was made by SEVAST'YANOV (1951) [6]. The study of the behaviour of such a process is made with the help of the generating function of the number of infected animals by a single animal. To express this generating function, we start with the same hypothesis as BARTOSZYNSKI [2] (1965) when he makes an interhuman epidemic model by a simple branching process of GALTON-WATSON. However these hypothesis will be modified in order to adapt them to the types of Brucellosis contamination.


Characteristics of paraspinal muscle degeneration in degenerative diseases of the lumbar spine at different ages.
To analyze the relationship between gender, age, and the degree of lumbar degenerative disease. 290 patients with Lumbar spinal stenosis and sciatica were analyzed. Sixty patients without sciatica were collected in the control group. Patient demography including age, gender, body mass index (BMI), serum calcium, and triglyceride level was acquired. The cross-sectional area (CSA) and percentage of fat infiltration area (Intermuscular adipose tissue (IMat%) of paraspinal muscles at the L4-5 level were measured using MRI imaging. The patients were divided into five age groups: A (18-30 years old), B (31-40 years old), C (41-50 years old), D (51-60 years old), and E (> 60 years old). Analysis of variance (ANOVA) and LSD was used to analyze differences among subgroups. Student's t-test was used to compare MCSA and fat CSA in the two groups. P < 0.05 was statistically significant. The paraspinal muscle CSA (MCSA) was significantly smaller in women (P < 0.05). Older age was associated with less MCSA and greater fatty infiltration in erector spinae and multifidus (MF) muscle (P < 0.05). Serum calcium and BMI were positively correlated with CSA of erector spinae muscle (P < 0.05), but not with muscle fat infiltration (P > 0.05). Although there was no significant difference in MCSA between the two groups, the fat infiltration (IMat%) in the disease group was significantly higher than in the control group (p < 0.05). Lumbar degenerative diseases caused the degeneration of the paravertebral muscles, which mainly resulted in increased intramuscular fat infiltration, rather than changes in the overall MCSA.


Sex-hormone-binding globulin and albumin concentrations in human cerebrospinal fluid.
Polyacrylamide gel electrophoresis of plasma and concentrated cerebrospinal fluid (CSF) preincubated with tritium labelled 5 alpha-dihydrotestosterone (DHT) showed identical migration of the radioactivity, indicating the presence of sex-hormone-binding globulin (SHBG) in human CSF. The concentrations of SHBG (measured as the binding capacity) and albumin were measured in concentrated CSF (12 women and 1 man) and samples of plasma of some patients (9 women). SHBG could not be detected in 6 of the CSF samples, and the mean value of the determinable samples was 42.3 +/- 13.4 pmol/l. The mean +/- SE of the SHBG concentration in plasma was 90.8 +/- 8.9 nmol/l and the mean albumin concentrations in CSF and plasma were 3.4 +/- 0.6 mumol/l and 670 +/- 107 mumol/l respectively. The distribution ratio for SHBG over the blood-CSF barrier was 10 times higher than for albumin. It was concluded that the SHBG-binding in the CSF is negligible but that the albumin-binding may contribute to the CSF concentrations of testosterone and estradiol, which are 10-25% above the plasma unbound concentrations.


Health and safety at work in the transport industry (TRANS-18): factorial structure, reliability and validity.
In this article, we study the psychometric properties of a short scale (TRANS-18) which was designed to detect safe behaviors (personal and vehicle-related) and psychophysiological disorders. 244 drivers participated in the study, including drivers of freight transport vehicles (regular, dangerous and special), cranes, and passenger transport (regular transport and chartered coaches), ambulances and taxis. After carrying out an exploratory factor analysis of the scale, the findings show a structure comprised of three factors related to psychophysiological disorders, and to both personal and vehicle-related safety behaviors. Furthermore, these three factors had adequate reliability and all three also showed validity with regard to burnout, fatigue and job tension. In short, this scale may be ideally suited for adequately identifying the safety behaviors and safety problems of transport drivers. Future research could use the TRANS-18 as a screening tool in combination with other instruments.


Molecular mechanism of manipulating seed coat coloration in oilseed Brassica species.
Yellow seed is a desirable characteristic for the breeding of oilseed Brassica crops, but the manifestation of seed coat color is very intricate due to the involvement of various pigments, the main components of which are flavonols, proanthocyanidin (condensed tannin), and maybe some other phenolic relatives, like lignin and melanin. The focus of this review is to examine the genetics mechanism regarding the biosynthesis and regulation of these pigments in the seed coat of oilseed Brassica. This knowledge came largely from recent researches on the molecular mechanism of TRANSPARENT TESTA (tt) and similar mutations in the ancestry model plant of Brassica, Arabidopsis. Some key enzymes in the flavonoid (flavonols and proanthocyanidin) biosynthetic pathway have been characterized in tt mutants. Some orthologs to these TRANSPARENT TESTA genes have also been cloned in Brassica species. However, it is suggested that some alterative metabolism pathways, including lignin and melanin, might also be involved in seed color manifestation. Polyphenol oxidases, such as laccase, tyrosinase, or even peroxidase, participate in the oxidation step in proanthocyanidin, lignin, and melanin biosynthesis. Moreover, some researches also suggested that melanic pigment in black-seeded Brassica was several fold higher than in yellow-seeded Brassica. Although more experiments are required to evaluate the importance of lignin and melanin in seed coat browning, the current results suggest that the flavonols and proanthocyanidin are not the only roles affecting seed color.


The nursing critical thinking in clinical practice questionnaire for nursing students: A psychometric evaluation study.
To adapt and validate the N-CT-4 Practice for use with Spanish nursing students. Promoting critical thinking is one of the primary objectives of nursing education programs all over the world. Using reliable and valid instruments to measure critical thinking is essential. The Nursing Critical Thinking in Clinical Practice Questionnaire (N-CT-4 Practice) is used internationally to assess critical thinking in nursing practice. However, little is known about the possible applications of this instrument in the context of nursing education. Two-phase study: Phase I, adaptation of the N-CT-4 Practice for use with nursing students and verification of its content validity; phase 2, cross-sectional study to validate its psychometric properties in a sample of 331 nursing students from three university nursing schools. A subsample of 34 students completed the questionnaire on two occasions, with a time interval of two weeks. The construct validity and reliability of the instrument were tested using confirmatory factor analysis, convergent validity, internal consistency reliability and test-retest reliability. The STROBE guidelines and the COSMIN checklist were followed. All items obtained optimal content validity values. The model fit indices obtained from the confirmatory factor analysis supported the hypothesis of the four-dimensional structure on which the original questionnaire was based. Cronbach's alpha of 0.96 indicated high reliability. The correlations between the total score and the scores for the dimensions were statistically significant, positive and high, with values above r = 0.78 (p < 0.05). Lin's concordance correlation coefficient was 0.6 (p < 0.001). The adapted version of the N-CT-4 Practice is suitable for measuring critical thinking skills in the educational context of the degree course in nursing in Spain. Its psychometric validation yielded satisfactory results.


Brain angiotensin II: new developments, unanswered questions and therapeutic opportunities.
1. There are two Angiotensin II systems in the brain. The discovery of brain Angiotensin II receptors located in neurons inside the blood brain barrier confirmed the existence of an endogenous brain Angiotensin II system, responding to Angiotensin II generated in and/or transported into the brain. In addition, Angiotensin II receptors in circumventricular organs and in cerebrovascular endothelial cells respond to circulating Angiotensin II of peripheral origin. Thus, the brain responds to both circulating and tissue Angiotensin II, and the two systems are integrated. 2. The neuroanatomical location of Angiotensin II receptors and the regulation of the receptor number are most important to determine the level of activation of the brain Angiotensin II systems. 3. Classical, well-defined actions of Angiotensin II in the brain include the regulation of hormone formation and release, the control of the central and peripheral sympathoadrenal systems, and the regulation of water and sodium intake. As a consequence of changes in the hormone, sympathetic and electrolyte systems, feed back mechanisms in turn modulate the activity of the brain Angiotensin II systems. It is reasonable to hypothesize that brain Angiotensin II is involved in the regulation of multiple additional functions in the brain, including brain development, neuronal migration, process of sensory information, cognition, regulation of emotional responses, and cerebral blood flow. 4. Many of the classical and of the hypothetical functions of brain Angiotensin II are mediated by stimulation of Angiotensin II AT1 receptors. 5. Brain AT2 receptors are highly expressed during development. In the adult, AT2 receptors are restricted to areas predominantly involved in the process of sensory information. However, the role of AT2 receptors remains to be clarified. 6. Subcutaneous or oral administration of a selective and potent non-peptidic AT1 receptor antagonist with very low affinity for AT2 receptors and good bioavailability blocked AT1 receptors not only outside but also inside the blood brain barrier. The blockade of the complete brain Angiotensin II AT1 system allowed us to further clarify some of the central actions of the peptide and suggested some new potential therapeutic avenues for this class of compounds. 7. Pretreatment with peripherally administered AT1 antagonists completely prevented the hormonal and sympathoadrenal response to isolation stress. A similar pretreatment prevented the development of stress-induced gastric ulcers. These findings strongly suggest that blockade of brain AT1 receptors could be considered as a novel therapeutic approach in the treatment of stress-related disorders. 8. Peripheral administration of AT1 receptor antagonists strongly affected brain circulation and normalized some of the profound alterations in cerebrovascular structure and function characteristic of chronic genetic hypertension. AT1 receptor antagonists were capable of reversing the pathological cerebrovascular remodeling in hypertension and the shift to the right in the cerebral autoregulation, normalizing cerebrovascular compliance. In addition, AT1 receptor antagonists normalized the expression of cerebrovascular nitric oxide synthase isoenzymes and reversed the inflammatory reaction characteristic of cerebral vessels in hypertension. As a consequence of the normalization of cerebrovascular compliance and the prevention of inflammation, there was, in genetically hypertensive rats a decreased vulnerability to brain ischemia. After pretreatment with AT1 antagonists, there was a protection of cerebrovascular flow during experimental stroke, decreased neuronal death, and a substantial reduction in the size of infarct after occlusion of the middle cerebral artery. At least part of the protective effect of AT1 receptor antagonists was related to the inhibition of the Angiotensin II system, and not to the normalization of blood pressure. These results indicate that treatment with AT1 receptor antagonists appears to be a major therapeutic avenue for the prevention of ischemia and inflammatory diseases of the brain. 9. Thus, orally administered AT1 receptor antagonists may be considered as novel therapeutic compounds for the treatment of diseases of the central nervous system when stress, inflammation and ischemia play major roles. 10. Many questions remain. How is brain Angiotensin II formed, metabolized, and distributed? What is the role of brain AT2 receptors? What are the molecular mechanisms involved in the cerebrovascular remodeling and inflammation which are promoted by AT1 receptor stimulation? How does Angiotensin II regulate the stress response at higher brain centers? Does the degree of activity of the brain Angiotensin II system predict vulnerability to stress and brain ischemia? We look forward to further studies in this exiting and expanding field.


Searching for molecular targets in sarcoma.
Sarcoma are about 1% of cancers. Within that 1% are widely varied tumors now divided into types and subtypes. Sarcoma occur in patients of all ages with frequency spread evenly over the human age range. Although the specific cell of origin of many sarcoma remains unclear, sarcoma are all tumors of mesenchymal origin. The mesenchymal stem cell, a pluripotent cell, which gives rise to varied differentiated cells including osteocytes, adipocytes, chondrocytes, muscle cells, fibroblasts, neural cells and stromal cells, is the most likely ultimate cell of origin for sarcoma. When mesenchymal stem cell genetics go awry and malignant transformation occurs sarcoma including osteosarcoma, Ewing's sarcoma, chondrosarcoma, rhabdomyosarcoma, synovial sarcoma fibrosarcoma, liposarcoma and many others can initiate. Our knowledge of sarcoma genetics is increasing rapidly. Two general groups, sarcoma arising from chromosomal translocations and sarcoma with very complex genetics, can be identified. Genes that are frequently mutated in sarcoma include TP53, NF1, PIK3CA, HDAC1, IDH1 and 2, KDR, KIT and MED12. Genes that are frequently amplified in sarcoma include CDK4, YEATS4, HMGA2, MDM2, JUN, DNM3, FLT4, MYCN, MAP3K5, GLI1 and the microRNAs miR-214 and miR-199a2. Genes that are upregulated in sarcoma include MUC4, CD24, FOXL1, ANGPTL2, HIF1α, MDK, cMET, TIMP-2, PRL, PCSK1, IGFR-1, TIE1, KDR, TEK, FLT1 and several microRNAs. While some alterations occur in specific subtypes of sarcoma, others cross several sarcoma types. Discovering and developing new therapeutic approaches for these relentless diseases is critical. The detailed knowledge of sarcoma genetics may allow development of sarcoma subtype-targeted therapeutics.


[Determination of the diagnostic value of erythrocyte discrimination indices (Mentzer and Srivastava) and of glycerol lysis time (GLT 50) in microcytosis].
Many authors proposed erythrocytes discriminating functions to differentiate most common microcythemic hypochromic anemias (beta-thalassemia and iron deficiency). This study considers two of these discriminating functions: 1. Mentzer's index; 2. Srivastava's index; and also test GLT50 proposed by Authors with the same aim. The purpose is to quantify the percent of false positive and false negative results of such tests. As standard the test of measurement HbA2 and HbF was used to classify thalassemic patients. The results prove that the Mentzer test is the best while, not highly specific (20% false positive), but we did not find any false negatives in our study. Srivastava's method for the presence of false negatives (7% of thalassemic patients) is less reliable, and even less so the GLT50 test (30% of thalassemic patients).


Temperature and depth evaluation of the in vitro effects of femtosecond laser on oral soft tissue, with or without air-cooling.
Femtosecond laser is an effective and safe tool in many surgeries, but the studies of its effect on oral soft tissue ablation are insufficient. This study aimed to investigate the effect of soft tissue ablation with a 1030-nm femtosecond laser on temperature and depth. Twenty Sprague-Dawley rat tongue specimens were obtained and flat-mounted. The 1030-nm femtosecond laser was controlled by a computer system, with a set distance of 4.7 mm between the laser aperture and soft tissue surfaces. Ten specimens were ablated for > 1 min with or without air-cooling for temperature measurement, while the other 10 specimens were ablated for depth measurements, using the following parameters: (i) 3 W, 2000 mm/s; (ii) 3 W, 4000 mm/s; (iii) 5 W, 2000 mm/s; (iv) 5 W, 4000 mm/s; (v) 8 W, 2000 mm/s; (vi) 8 W, 4000 mm/s. Temperature changes were measured using a type-K thermocouple. The depth attained using different power and scanning speed settings was measured by a three-dimensional morphology measurement laser microscope. Laser power, scanning speed, and air-cooling effects were determined. Higher energy and lower speed induced higher temperatures (p < 0.05), which were significantly decreased by air-cooling (p < 0.05). The lowest ablation depth was obtained at 3 W and 4000 mm/s (72.63 ± 6.47 μm) (p < 0.05). The greatest incision depth was achieved at 8 W and 2000 mm/s (696.19 ± 35.37 μm), or 4000 mm/s (681.16 ± 55.65 μm) (p < 0.05). The 1030-nm femtosecond laser application demonstrates clinically acceptable ablation efficiency, without marked temperature damage, in a controlled manner.


Extranodal diffuse large B-cell lymphoma confined to liver in a kidney transplant recipient.
Posttransplant lymphoproliferative disorder (PTLD) is a well-documented complication that arises as a result of immunosuppression in the setting of solid organ or bone marrow transplantation. The disorder may be subtle and/or extranodal. We report a patient with extranodal lymphoma following kidney transplantation who had successful treatment with surgery and chemotherapy.


Corrigendum: Conformational rearrangements in the transmembrane domain of CNGA1 channels revealed by single-molecule force spectroscopy.
This corrects the article DOI: 10.1038/ncomms8093.


The effect of lipid composition on the metabolism of lignocaine by a reconstituted mixed function oxidase system from rat liver.
Hepatic microsomal preparations from male and female rats were delipidated by column chromatography following cholate solubilisation. The enzyme activities were reconstituted using known lipids and the vesicle reconstitution method. Enzyme activity was assayed using lignocaine as the substrate for the mixed function oxidase. This substrate gives two products; one which is predominantly found in the male (N-deethylated derivative) and one that is found in approximately equal amounts in both sexes (3-hydroxylated product). Reconstitution of male- but not female-derived enzyme in mixed dilauroylphosphatidylcholine (DLPC)/dilauroylphosphatidylethanolamine (DLPE) vesicles gave a higher N-deethylase activity than if the same enzyme was reconstituted in DLPC vesicles. 3-Hydroxylase activity, which is not sex-dependent, was not affected by DLPE. Microsomal lipids from male animals were more efficient than female-derived lipids in reconstituting N-deethylase activity from both male- and female-derived enzymes. Microsomal lipids were more efficient than DLPC in reconstituting N-deethylase activity from both male- and female-derived enzymes but 3-hydroxylase activity was similar in the two lipids. There is, thus, a sex- and pathway-dependent effect of the lipids: the male-specific N-deethylase pathway is more affected by lipid composition and then more so in the male-derived enzyme. It is possible, therefore, that some of the sex differences in drug metabolism may be related to changes in lipid composition.


Extended versus limited arch replacement in acute Type A aortic dissection.
The recommended extent of surgical resection and reconstruction of the arch in acute DeBakey Type I aortic dissection is an ongoing controversy. However, several recent reports indicate a trend towards a more extensive arch operation in several institutions. We have analysed the recent data from the International Registry of Acute Aortic Dissection to assess the choice of procedure over time and to evaluate the surgical outcome in a 'real-world' database. Our aim was to compare short- and mid-term outcomes of limited repairs versus complete arch surgery. Of the 1241 patients included in the 'Interventional Cohort' of the International Registry of Acute Aortic Dissection from March 1996 to March 2015, 907 underwent ascending aortic or hemiarch replacement (Group A) and 334 had extended arch replacement (Group B). An extended resection was a surgeon's 'judgement call'. Logistic regression analysis, propensity-adjusted multivariable comparisons and Kaplan-Meier curves were used for analyses. Overall in-hospital mortality was 14.2% with no difference between groups (Group A 13.1%, Group B 17.1%). Coma/altered consciousness (odds ratio 3.16, 95% confidence interval 1.60-6.25, P = 0.001), hypotension, tamponade or shock (2.03, 1.11-3.73, P = 0.022) and any pulse deficit (1.92, 1.04-3.54, P = 0.038) were predictors of in-hospital mortality in a propensity score-adjusted multivariable analysis. Overall 5-year survival was 69.4% in the ascending group and 73.1% in the total arch group (P = 0.83 by Kaplan-Meier analysis). For survivors of the index hospitalization, the 5-year freedom from death, aortic rupture and reintervention were 71.1% in Group A and 76.4% in Group B (P = 0.54 by Kaplan-Meier analysis). Selective, or 'surgeon's choice', extended arch replacement had no discernible acute downside compared with less extensive surgery. Whether extended arch replacement improves the prognosis beyond 5 years remains to be settled.


A prospective morphological study of facet joint integrity following intervertebral disc replacement with the CHARITE Artificial Disc.
In degenerative disc disease (DDD), increased loading in the posterior column increases facet joint subchondral bone density and may lead to facet joint degeneration. While spinal fusion is commonly used to treat patients with symptomatic DDD, increased stress at the levels adjacent to fusion may accelerate facet joint and adjacent segment degeneration. Artificial disc replacements have been developed as an alternative to fusion. In this prospective study, the effects of disc replacement with the CHARITE Artificial Disc on facet joint loading and integrity were evaluated. Thirteen patients aged <50 years with symptomatic DDD were recruited. Computed tomography (CT) osteoabsorptiometry was performed prior to the implantation of the CHARITE Artificial Disc and six months after. With this technique, increases or decreases in facet joint loading and integrity are indicated by corresponding changes in subchondral bone density. Changes in the distribution of load alter the distribution of the areas of maximum bone density. Clinical outcome was also assessed at pre-operative and 6 and 12 month post-operative visits using the Visual Analogue Scale back and leg pain scores, the Oswestry Disability Index and the Short Form-36 (SF-36) questionnaire. The height of the intervertebral space at the operated level was monitored by lateral X-ray. Subchondral bone density was evaluated in the facet joints of all 13 patients at the operated level, 12 patients at the level above the operated segment, and five patients at the level below the operated segment. Quantitative measurements revealed no significant increases (> or =3%) in subchondral bone density of the facet joints at any level in any patient. Significant decreases (> or =3%) in subchondral bone density were measured at the operated level in 10/13 patients, at the level above the operated segment in 6/12 patients, and at the level below the operated segment in 3/5 patients. There were no changes in the distribution of the areas of maximum bone density in any of the studied facet joints at 6 months compared with pre-operative measurements. Clinical outcome scores were improved at 6 and 12 months compared with baseline. The mean intervertebral space height at the operated level was increased following implantation of the CHARITE Artificial Disc and was 1.8 times greater than the pre-operative height at both 6 and 12 months. In this study, replacement of degenerated intervertebral discs with the CHARITE Artificial Disc was not associated with increased loading of the facet joints at the operated or adjacent levels. Decreases in subchondral bone density may indicate reduced loading in the posterior column following disc replacement compared with loading in the pre-operative degenerated spine. Further study is required to establish the baseline for healthy subchondral bone density and to compare this baseline with long-term measurements in patients undergoing disc replacement.


The influence of different copper wires on human sperm penetration into bovine cervical mucus, in vitro.
The influence of four different copper-containing intrauterine devices (IUD) (Nova-T, Multiload, Fincoid 250 and copper-T 250) on the penetration of human sperm into bovine cervical mucus were assessed. Pooled samples of predetermined sperm concentration were suspended in Earl's medium in which a copper IUD was previously incubated for periods between one hour to fourteen days. The mean copper concentration was determined for each of the medium containing IUD and was found to be between 284 +/- 93 micrograms/100 ml to 392 +/- 138 micrograms/100ml. While there was no adverse effect on sperm motility by the copper-containing medium, there was a significant reduction in the number of sperm penetrated into the bovine cervical mucus as compared to the penetration of sperm suspended in pure Earl's medium. It therefore seems that the influence of copper on sperm penetration might be by an effect on the environment or spermatozoal migration rather than by direct effect of copper on sperm motility.


A study on contagious caprine pleuropneumonia (CCPP) in goats at an export oriented abattoir, Debrezeit, Ethiopia.
300 goat serum samples from an export-oriented abattoir were tested for contagious caprine pleuropneumonia antibodies by the complement fixation test. The disease prevalence was 31% with no significant differences (P > 0.05) between the regions "Borena", "Bale", "Afar" and "Jinka" or the age of the goats (P > 0.05). Gross pathology and histopathology of the lung primary lesions were indicative of pleuropneumonia caused by Mycoplasma capricolum subsp. capripneumoniae.


Nitrogen removal from low C/N wastewater in a novel Sharon&DSR (denitrifying sulfide removal) reactor.
Denitrification reactions commonly remove nitrate and other reactive nitrogen (Nr) from wastewater. The C/N ratio indicates the sufficiency of organic carbons to drive heterotrophic denitrification; a low C/N ratio frequently leads to poor denitrification performance in wastewater treatment. This study proposed and tested a novel Sharon&DSR (denitrifying sulfide removal) process, with nitrite generated by the Sharon reactions and sulfide from sulfur-reducing reactions for promoting the following nitrite-based denitrification and denitrifying sulfide removal (DSR) process. The present reactor can remove nitrate at an efficiency of 97.7 %-93.5 % at an influent C/N ratio of 0.646-0.737 over a 96-d continuous-flow test. The microbial community study reveals the functional strains corresponding to individual groups of critical reactions. The stoichiometry analysis reveals the potential to apply the nitrite-based DSR process for Nr removal from ultra-low C/N (<0.64) wastewaters, experimentally demonstrated in the present study with a C/N ratio of 0.16-0.39.