Nasal foreign bodies: Results of a study of 260 cases.
Insertion of a foreign body in the nasal cavity is a very common incident in children. It is easily diagnosed, but the type of foreign body varies and extraction can sometimes be difficult, with risk of complications. The present study reports nasal foreign bodies seen in emergency in our ENT department, with an update on the state of knowledge. A prospective study between May and August 2011 included all patients admitted to the ENT emergency unit for nasal foreign body. Data comprised age, gender, circumstances of discovery, symptoms, type of foreign body, extraction method and complications. Two hundred and sixty cases of nasal foreign body were included, representing 4.3% of all consultations in the unit. Mean age was 3 years (range: 1-16 years); the sex ratio was 1.4 (male predominance). The incident was reported by a family member or the actual child in 76.9% of cases (n=199), or discovered following nasal symptoms in 23.1% (n=61). The main types of foreign body were non-organic synthetic beads in 18.8% of cases and vegetable forms in 17.7%. Extraction was easy, using forceps, micro-hooks or suction, in 91.53% of cases. Complications comprised infection (n=48), epistaxis (n=18) and nasal septum perforation (n=1). Nasal foreign bodies are a frequent accident in medical practice, especially in young children. They are generally harmless, but may incur complications if overlooked or when a button cell is involved, whence the importance of timely extraction. The best treatment, however, remains prevention.


Prevalence of osteoporosis using bone mineral measurements at the calcaneus by dual X-ray and laser (DXL).
Using manufacturers reference data the prevalence of osteoporosis using a T-score threshold of -2.5 for heel measurements by DXL technology was compared to dual-energy X-ray absorptiometry (DXA) measurements at the femoral neck, spine and forearm. The prevalence of osteoporosis for women aged 50 years or older was 28% for DXL measurements of the heel bone and 30, 22 and 32% for DXA measurements of the lumbar spine, femoral neck and forearm respectively. Bone mineral density (BMD) was also measured by DXL in the heel bone and by DXA in spine and femoral neck in 251 women (mean age 62 +/- 14.5 years) when attending an osteoporosis clinic. The sensitivity and specificity for osteoporosis and osteopenia for the DXL measurements were calculated assuming a low T-score at the spine or femoral neck as the criterion for a correct diagnosis. The sensitivity was found to be 80% for osteoporosis and 82% for osteopenia and the specificity was 82% for osteoporosis and 89% for osteopenia. We conclude that DXL measurement at the heel bone, using a T-score threshold of -2.5 for classification of osteoporosis, is in concordance with the World Health Organization (WHO) definition of osteoporosis.


Targeting interleukin-21 in rheumatoid arthritis.
Interleukin-21 (IL-21) is a new member of the type I cytokine superfamily, which binds to a composite receptor that consists of a private receptor (IL-21R) and the common cytokine receptor γ chain. Recently, increasing evidence has shown that IL-21 contributes to the pathogenesis of chronic inflammatory and autoimmune diseases because of its pro-inflammatory and immune-mediated properties. IL-21 induced T-cell activation and pro-inflammatory cytokine secretion in rheumatoid arthritis (RA). IL-21R RNA transcripts were found in synovial tissue samples of patients with RA. In addition, blockade of the IL-21/IL-21R pathway ameliorated disease in animal models of RA and significantly inhibited inflammatory cytokine production in vitro. Moreover, IL-21R deficiency in the K/BxN mouse model of inflammatory arthritis was sufficient to block arthritis initiation completely. All theses findings suggest that IL-21 has important biological effects in autoimmunity that might be a promising therapeutic target for RA. In this review, we discuss the biological features of IL-21 and summarize recent advances in the role of IL-21 in the pathogenesis and treatment of RA.


'Silk Road', the virtual drug marketplace: a single case study of user experiences.
The online promotion of 'drug shopping' and user information networks is of increasing public health and law enforcement concern. An online drug marketplace called 'Silk Road' has been operating on the 'Deep Web' since February 2011 and was designed to revolutionise contemporary drug consumerism. A single case study approach explored a 'Silk Road' user's motives for online drug purchasing, experiences of accessing and using the website, drug information sourcing, decision making and purchasing, outcomes and settings for use, and perspectives around security. The participant was recruited following a lengthy relationship building phase on the 'Silk Road' chat forum. The male participant described his motives, experiences of purchasing processes and drugs used from 'Silk Road'. Consumer experiences on 'Silk Road' were described as 'euphoric' due to the wide choice of drugs available, relatively easy once navigating the Tor Browser (encryption software) and using 'Bitcoins' for transactions, and perceived as safer than negotiating illicit drug markets. Online researching of drug outcomes, particularly for new psychoactive substances was reported. Relationships between vendors and consumers were described as based on cyber levels of trust and professionalism, and supported by 'stealth modes', user feedback and resolution modes. The reality of his drug use was described as covert and solitary with psychonautic characteristics, which contrasted with his membership, participation and feelings of safety within the 'Silk Road' community. 'Silk Road' as online drug marketplace presents an interesting displacement away from 'traditional' online and street sources of drug supply. Member support and harm reduction ethos within this virtual community maximises consumer decision-making and positive drug experiences, and minimises potential harms and consumer perceived risks. Future research is necessary to explore experiences and backgrounds of other users.


Phenotypic heterogeneity of B cell chronic lymphocytic leukaemia.
The peripheral blood lymphocytes from 39 patients from the Latvian S.S.R.T., U.S.S.R. with chronic lymphocytic leukaemia (CLL) have been phenotyped with various monoclonal antibodies representing the major clusters of differentiation (CD) used for phenotyping B cells. A clear delineation of two groups of patients was evidenced. The major group (33/39) possessed leukaemic cells bearing surface immunoglobulins (SIg) at a low density, Class II HLA, and CD5, CD24 and CD37 molecules but not CD21, CD22 and CD35. CD23 antigen was seen only once under microscope examination, but could be visualized by flow cytometry. CD6 antibody reacted with cells from about 1/3 of this group of patients. In the six patients of the second group the leukaemic phenotype was SIg+, Class II HLA+, CD5+, 24+, 37+, 21+, 22+, 35+, 23+ and 6-. The main finding is the concomitant expression of CD22, CD21 (CR2) and CD35 (CR1) molecules, all involved in B cell activation. It is not yet known whether these observations correlate with different clinical evolutions of the disease.


Long-term effect of transurethral partial cystectomy with a 2-micrometer continuous-wave laser for non-muscle-invasive bladder cancer.
We have reported the efficacy and safety of 2-micrometer continuous-wave laser cystectomy of non-muscle invasive bladder tumor (NMIBC) (J Urol. 2009;182:66-9). In this study, we evaluated the long-term outcomes of patients with NMIBC who underwent transurethral partial cystectomy with a 2-micrometer continuous-wave laser, and explored the risk factors for tumor recurrence. This was a retrospective study of patients with NMIBC planned to undergo transurethral partial cystectomy with a 2-micrometer continuous-wave laser at the Fourth Medical Center of the PLA General Hospital between January 2012 and December 2014. The primary outcome was bladder cancer recurrence. A total of 75 patients were enrolled. Sixty-two (82.7%) were male. The patients were 59.8 ± 12.9 years of age. The mean operation time was 38.7 ± 20.4 min. No Clavien grade >2 complications occurred. The duration of catheter indwelling was 3.6 ± 1.8 days. The hospital stay was 6.0 ± 2.3 days. The median follow-up was 80 months. A total of 17 patients had a recurrence during follow-up, and the recurrence-free survival (RFS) rate was 77.3%. In the multivariable analysis, the tumor risk group were independently associated with the recurrence of NMIBC (p = 0.026). After TURBT with a 2-micrometer continuous-wave laser, RFS was 77.3% at the median follow-up of 80 months. All complications were mild. Only tumor risk group was independently associated with the recurrence of NMIBC.


Cell cycle phase-dependent effect of retinoic acid on the induction of granulocytic differentiation in HL-60 promyelocytic leukemia cells. Evidence for sphinganine potentiation of retinoic acid-induced differentiation.
The efficiency of retinoic acid (RA)-induced differentiation was dependent on the position of HL-60 cells in the cell cycle. Our results demonstrated that cells at the G1/S border were more efficiently induced to differentiate by short exposure to RA than cells at other phases of the cell cycle. Synchronization of cells in G1/S phase by aphidicolin (APH) or mimosine (MIMO) increased the sensitivity of cells to RA short exposure treatment. Pretreatment with sphinganine (SP), a protein kinase C (PKC) inhibitor, potentiated RA-induced cell differentiation. By cell cycle analysis, SP was found to block the cell progression through the G1/S phase. Consequently, cells accumulated in the G1/S phase of the cell cycle. The present data therefore suggest a possible mechanism of action of SP to enhance RA-induced differentiation.


Hypertrophic Cardiomyopathy: Genetic Foundations, Outcomes, Interconnections, and Their Modifiers.
Hypertrophic cardiomyopathy (HCM) is the most prevalent heritable cardiomyopathy. HCM is considered to be caused by mutations in cardiac sarcomeric protein genes. Recent research suggests that the genetic foundation of HCM is much more complex than originally postulated. The clinical presentations of HCM are very variable. Some mutation carriers remain asymptomatic, while others develop severe HCM, terminal heart failure, or sudden cardiac death. Heterogeneity regarding both genetic mutations and the clinical course of HCM hinders the establishment of universal genotype-phenotype correlations. However, some trends have been identified. The presence of a mutation in some genes encoding sarcomeric proteins is associated with earlier HCM onset, more severe left ventricular hypertrophy, and worse clinical outcomes. There is a diversity in the mechanisms implicated in the pathogenesis of HCM. They may be classified into groups, but they are interrelated. The lack of known supplementary elements that control the progression of HCM indicates that molecular mechanisms that exist between genotype and clinical presentations may be crucial. Secondary molecular changes in pathways implicated in HCM pathogenesis, post-translational protein modifications, and epigenetic factors affect HCM phenotypes. Cardiac loading conditions, exercise, hypertension, diet, alcohol consumption, microbial infection, obstructive sleep apnea, obesity, and environmental factors are non-molecular aspects that change the HCM phenotype. Many mechanisms are implicated in the course of HCM. They are mostly interconnected and contribute to some extent to final outcomes.


Types of Research Bias Encountered in IR.
Bias is a systemic error in studies that leads to inaccurate deductions. Relevant biases in the field of IR and interventional oncology were identified after reviewing articles published in the Journal of Vascular and Interventional Radiology and CardioVascular and Interventional Radiology. Biases cited in these articles were divided into three categories: preinterventional (health care access, participation, referral, and sample biases), periinterventional (contamination, investigator, and operator biases), and postinterventional (guarantee-time, lead time, loss to follow-up, recall, and reporting biases).


Age-dependent decrease in desflurane concentration for maintaining bispectral index below 50.
We examined the hypothesis that the minimum alveolar concentration of desflurane for maintaining bispectral index (BIS) below 50 (MACBIS 50 ) decreases with advance of age. Sixty young (20-30 year), middle-aged (31-65 year) and elderly (66-80 year) patients were included (n = 20, each group). Five minutes following the start of continuous intravenous administration of remifentanil at 0.25 μg/kg/min, general anaesthesia was induced with propofol 2 mg/kg and rocuronium 0.8 mg/kg to facilitate tracheal intubation. Infusion of remifentanil was stopped immediately after tracheal intubation. When BIS began to increase > 60, maintenance of anaesthesia was started with an end-tidal desflurane concentration of 4.0% and maintained for 10 min followed by 1-min assessment of BIS taken at 10-s intervals. MACBIS 50 of each age group was estimated by up-down methodology. MACBIS 50 of desflurane in young, middle-aged and elderly patients was 4.25% end-tidal (95% confidence intervals 4.04-4.46), 3.58% (3.38-3.79) and 2.75% (2.50-3.00) respectively. MACBIS 50 was higher (P = 0.011) in young patients and lower (P = 0.012) in elderly patients than those in middle-aged patients. Advance in age significantly decreased the concentrations of desflurane required to maintain BIS below 50. BIS reflected age-associated decrease in end-tidal concentrations of desflurane required for maintaining adequate depth of anaesthesia during resting state.


Morphological and molecular identification of epibiontic sessilid Epistylis semiciculus n. sp. (ciliophora, Peritrichia) from Procambarus clarkia (Crustacea, Decapoda) in China.
Data on sessilinasis from Procambarus clarkia are limited. This study investigates sessilid diversity in Hubei Province, China in 2016. Procambarus clarkia pereopods were covered by two sessilid morphotypes in April and May, and the gills were adhered by one of these two morphotypes (morphotype I) in January. Identifying the two morphotypes according to their morphological characters through live observations and protargol-stained method is difficult. Both morphotypes show almost identical morphological characteristics: zooids present vase-shaped, the length-to-width ratio is 2:1, the semicircle-shaped peristomial disk is evidently above the peristomial lip, single contractile vacuole is located below the peristomial lip, and the oral infraciliature shows identical arrangement which can be distinguished from other Epistylis. However, the morphometric data of the two morphotypes are significant different: body size of morphotype I is 78.9-103.8 × 32.1-54.6 μm, whereas that of morphotypes II is 136.7-171.5 × 60.9-88.0 μm. To further identify the two morphotypes, molecular regions including small subunit ribosomal DNA (SSU rDNA) sequences, large subunit ribosomal DNA (LSU rDNA) sequences, and ITS1-5.8S-ITS2 sequences were used. Results supported that the two morphotypes are single species of genus Epistylis rather than distinct species based in their distinct size ranges and temporal presence events. We assigned it the name E. semiciculus n. sp. with respect to the semicircular peristomial disk. Overall, these findings emphasized the importance of using molecular data to solve the identification confusion caused by ontogenetic processes. This study is the first morphological and molecular characterization of a sessilid isolated from P. clarkia under aquaculture conditions.


Terfenadine: a mixture of equipotent antihistamine enantiomers without a clear 'isomeric ballast'.
Terfenadine was the first non-sedating histamine H1 receptor antagonist and one of the most frequently prescribed H1 antihistamines. Terfenadine has one asymmetric centre in the molecule and is currently used as a racemate. Different methods and approaches for obtaining pure enantiomers of terfenadine are summarized and discussed in the present paper. Studies on antihistamine activity of the enantiomers, their side-effects on the central nervous system, calcium channel affinity and metabolism are also reviewed and analysed.


Modification of in vitro adherence of Streptococcus mutans by plant lectins.
1) Several plant lectins inhibit in vitro adherence of S. mutans to smooth surfaces. 2) Initial attachment of S. mutans appears to be independent of sucrose-derived glucans. 3) Blockage of adherence is possibly due to lectin interaction with basic amino acid residues on the cell surfaces.


Suspension culture combined with chemotherapeutic agents for sorting of breast cancer stem cells.
Cancer stem cell (CSC) hypothesis has not been well demonstrated by the lack of the most convincing evidence concerning a single cell capable of giving rise to a tumor. The scarcity in quantity and improper approaches for isolation and purification of CSCs have become the major obstacles for great development in CSCs. Here we adopted suspension culture combined with anticancer regimens as a strategy for screening breast cancer stem cells (BrCSCs). BrCSCs could survive and be highly enriched in non-adherent suspension culture while chemotherapeutic agents could destroy most rapidly dividing cancer cells and spare relatively quiescent BrCSCs. TM40D murine breast cancer cells were cultured in serum-free medium. The expression of CD44+CD24- was measured by flow cytometry. Cells of passage 10 were treated in combination with anticancer agents pacilitaxel and epirubicin at different peak plasma concentrations for 24 hours, and then maintained under suspension culture. The rate of apoptosis was examined by flow cytometry with Annexin-V fluorescein isothiocyanate (FITC)/propidium iodide (PI) double staining method. Selected cells in different amounts were injected subcutaneously into BALB/C mice to observe tumor formation. Cells of passage 10 in suspension culture had the highest percentage of CD44+CD24- (about 77 percent). A single tumor cell in 0.35 PPC could generate tumors in 3 of 20 BALB/C mice. Suspension culture combined with anticancer regimens provides an effective means of isolating, culturing and purifying BrCSCs.


Development of a Certified Reference Material for myeloperoxidase-anti-neutrophil cytoplasmic autoantibodies (MPO-ANCA).
A serum Certified Reference Material (CRM) for supporting reliable autoimmune diagnostics was recently released by the Institute for Reference Materials and Measurements (IRMM) of the Joint Research Centre of the European Commission. It was produced in collaboration with a Working Group on the Harmonisation of Autoimmune Tests of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC WG-HAT). This material is aimed at facilitating the standardisation of measurements of anti-myeloperoxidase immunoglobulin G antibodies. The CRM could be used as a common calibrant by clinicians and manufacturers thereby significantly improving the comparability of results from commercial immunoassays used for IgG anti-MPO measurements. This paper provides information on the new CRM and its intended use.


Single pellet grasping following cervical spinal cord injury in adult rat using an automated full-time training robot.
Task specific motor training is a common form of rehabilitation therapy in individuals with spinal cord injury (SCI). The single pellet grasping (SPG) task is a skilled forelimb motor task used to evaluate recovery of forelimb function in rodent models of SCI. The task requires animals to obtain food pellets located on a shelf beyond a slit at the front of an enclosure. Manually training and testing rats in the SPG task requires extensive time and often yields results with high outcome variability and small therapeutic windows (i.e., the difference between pre- and post-SCI success rates). Recent advances in automated SPG training using automated pellet presentation (APP) systems allow rats to train ad libitum 24h a day, 7 days a week. APP trained rats have improved success rates, require less researcher time, and have lower outcome variability compared to manually trained rats. However, it is unclear whether APP trained rats can perform the SPG task using the APP system after SCI. Here we show that rats with cervical SCI can successfully perform the SPG task using the APP system. We found that SCI rats with APP training performed significantly more attempts, had slightly lower and less variable final score success rates, and larger therapeutic windows than SCI rats with manual training. These results demonstrate that APP training has clear advantages over manual training for evaluating reaching performance of SCI rats and represents a new tool for investigating rehabilitative motor training following CNS injury.


Arginine vasopressin response to an osmotic stimulus in the fetal sheep.
Baseline plasma osmolality (pOsm) and plasma arginine vasopressin (pAVP) were measured in chronically catheterized fetal sheep. Mean baseline pAVP in fetuses from 101-120 days was 1.9 +/- 0.46 muU/ml (mean +/- SEM) with a pOsm of 293 +/- 1.8 mOsm/kg. In fetuses of 121-141 days of gestation, mean pAVP was significantly lower, 0.77 +/- 0.19 muU/ml (P less than 0.05), with a similar pOsm (293 +/- 1.9 mOsm/kg). The logarithmic baseline pAVP values were linearly correlated with pOsm for both groups. Hypertonic saline infusion resulted in a similar increase in the log pAVP corrected for the rise in pOsm in the 101-120-day fetuses and in 121-141-day fetuses. The slope of this response was similar to that of the steady state relationship. The data indicates that the fetal osmoreceptor system for control of arginine vasopressin secretion is fully functional in the last trimester of pregnancy.


Neural networks and the experience and cultivation of mind.
Hard core neural network research includes development of mathematical models of cognitive prediction and optimization aimed at dual use, both as models of what we see in brain circuits and behavior, and as useful general-purpose engineering technology. The pathway and principles now exist to let us someday replicate learning abilities as elevated as what we see in the brain of the mouse-but how can this help us today in understanding and maximizing the much greater potential of the human mind, as addressed by many schools of thought all over the world for centuries? This paper discusses how we might use what we have learned at a lower level to better illuminate key phenomena in first person and clinical human experience such as Freud's "psychic energy", the role of traumatic experience, the interpretation of dreams, creativity, the cultivation of sanity and sensitivity, and the biological foundations of language.


Increased number of cytotoxic T cells within CD4+8- T cells in beta 2-microglobulin, major histocompatibility complex class I-deficient mice.
Targeted disruption of beta 2-microglobulin gene results in deficient major histocompatibility complex class I expression and failure to develop CD4-8+ T cells. Despite this, beta 2 M-/- mice reject skin grafts and cope with most viral infections tested. We asked whether CD4+8- cytotoxic T cells would play a role in compensating for the defect in CD4-8+ cytotoxic T cell function. We found that the cytotoxic activity against class II+ targets is significantly higher among CD4+8- T cells of beta 2M-/- than among those of beta 2M+/+ mice. In the limiting dilution experiment, we showed that the precursor frequency for the cytotoxic, CD4+8-, class II-specific T cells is at least fivefold higher in beta 2M-/- than in beta 2M+/+ mice. These results suggest that CD4+8- cytotoxic T cells could play a major role in carrying out cytotoxic function in beta 2M-/- mice.


Glucocorticoids reduce alveolar and trabecular bone in mice.
Glucocorticoid (GC) treatment is the main cause of secondary osteoporosis. There are some controversies about the relationships between alveolar bone loss and bone loss at the appendicular and axial skeleton. To assess, in parallel, the effects of GCs on alveolar bone and on the tibia in a mice model. Five-month-old male Swiss-Webster mice were randomized into two groups. Pellets releasing 5 mg/kg/day of prednisolone or control pellets were subcutaneously implanted for 28 days. After euthanasia, the right tibia and the right hemimandible of each mouse were analyzed by histomorphometry and microcomputed tomography. Alveolar bone consists of a thin slab between the incisor and the molar roots connected with the alveolar processes. A 2D-frontal section was done through the pulp chamber of the first molar and was used to measure the thickness of the alveolar bone slab. A 2D-sagittal section was done through the pulp chamber of the three molars and was used to measure bone volume in the alveolar processes. At day 28, thickness and bone volume of alveolar bone were significantly decreased in the GC group (P<0.05). At the tibia, GCs decreased bone formation with a reduced mineral apposition rate and bone formation rate and a significant decrease in BV/TV and Tb.Th (P<0.05). Although the amount of alveolar bone is very low in the mouse, this study shows that GCs can induce an alveolar bone loss in long-term treated animals.


Characterization of Bordetella bronchiseptica strains using phenotypic and genotypic markers.
Thirty-five strains of Bordetella bronchiseptica, recovered primarily from pigs, rabbits, dogs, cats and humans, were characterized by phenotypic and genotypic markers. Biochemical typing only showed variation in the ability to reduce nitrate to nitrite. OMP profiles from virulent strains showed variations in the region of 85-95kDa, which lead us to describe five OMP-types alpha, beta, gamma, delta and epsilon. Genotypic markers included the presence of IS1001, and polymorphisms in the flagellin gene (flaA) and pertussis toxin (PT) promoter region. The IS1001 was detected in 16 isolates (2 from humans and 10 from pigs) but was absent in rabbit isolates. The restriction profiles of the flaA gene allowed us to differentiate the strains into types A-C. The PT types were characterized by an RFLP assay and could be typed through patterns III-V. There was no apparent association between the flaA or PT types and the origin of the isolates. Eleven groups of isolates were identified on the basis of specific combinations of the analyzed markers. The combination of phenotypic and genotypic tests used could be useful in characterizing isolates and differentiating between certain clonal types of B. bronchiseptica.


The small-cell variant of mycosis fungoides. A clinicopathological and quantitative electron microscopic study on 14 patients.
Small-cell variants of Sézary syndrome and mycosis fungoides (MF) have been described. However, in these studies the nuclear area of the small-cell variant of MF (SC-MF) as compared to histological classical MF (CL-MF) was not characterized objectively by quantitative electron microscopy. In a 14-year follow-up period, of a total of 76 patch/plaque stage MF patients seen in the Department of Dermatology of the University Hospital Utrecht, 14 (18%) had an infiltrate composed of atypical lymphocytes characterized by a distinctly smaller cell diameter and smaller, hyperchromatic, deeply indented nuclei as compared to the usual cell type of MF. The aim of the investigation was to confirm this observation objectively using quantitative electron microscopy (morphometry) and to define SC-MF as compared to CL-MF. The study was performed on the 14 patients with SC-MF, and 10 patients with clinical and histological CL-MF and 4 patients with chronic eczema. Electron micrographs of sections obtained from each biopsy were analysed by computer to produce the following data: a nuclear contour index (NCI), the mean nuclear area (MNA), the mean nuclear area of the cells above the 75th percentile (P75NA) and the percentage of cells larger than 30 microm2. The values of MNA differed significantly between patients with SC-MF and those with CL-MF (17.6 vs 23.2 microm2; P = 0.02), as did the values of P75NA (20.7 vs 27.9 microm2; P = 0.01). The NCI of the SC-MF and CL-MF patients were similar. These results are consistent with our observations that SC-MF does indeed exist.


A versatile image analysis approach for simultaneous chromosome identification and localization of FISH probes.
Modern cytogenetic techniques, such as comparative genomic hybridization (CGH) and the multi-color fluorescence in situ hybridization (FISH) techniques of multiplex fluorescence in situ hybridization (M-FISH) and spectral karyotyping (SKY), require a coordinated banding analysis to maximize their usefulness. All of the methods currently used, including Giemsa (G-) banding, Alu banding, and 4',6-diamidino-2-phenyl-indole (DAPI) banding, have serious drawbacks. A simple and effective method to band chromosomes concurrently with FISH is needed. To address this problem, we stained chromosomes with DAPI and chromomycin A3, and then used an image analysis program to generate banding by dividing the image taken with a DAPI excitation filter by the image taken with a chromomycin A3 excitation filter. The result was a metaphase spread in which the chromosomes possessed a banding pattern characteristic of R-banding. The image analysis program was then used to generate linescans of pixel intensity versus relative position along the length of chromosomes that were banded using this technique, which we have called D/C R-banding. Each chromosome in a genome was represented by a characteristic scan profile, which was unaffected by FISH signals. Reference linescans were prepared by karyotyping D/C R-banded chromosomes for a given species, and then drawing lines along the length of the known chromosomes. The linescans were combined into a spreadsheet database, which was linked by dynamic data exchange to the image analysis program and normalized for length and intensity. The linescan of an unknown chromosome was then transferred to the spreadsheet, where it was normalized for length and intensity and overlaid on the linescans of each chromosome in the genome. Unknown chromosomes were identified by comparison of their graphs with graphs in the standardized reference genome. We have used this approach to create reference linescan karyotypes of several species, and to identify chromosomes on which FISH was performed.


Functional Integrin Regulation Through Interactions with Tetraspanin CD9.
Integrins are adhesion receptors that mediate many intercellular and cell-extracellular matrix interactions with relevance in physiology and pathology. Unlike other cellular receptors, integrins critically require activation for ligand binding. Through interaction in cis with other molecules and the formation of tetraspanin-enriched membrane microdomains (TEMs), the tetraspanin CD9 regulates integrin activity and avidity. Here we present three techniques used to study CD9-integrin interactions and integrin activation.


Allele-specific restriction analysis of human platelet antigen system 4.
Diagnosis, and occasionally treatment, of disorders involving platelet-specific alloimmunization, including neonatal alloimmune thrombocytopenia and posttransfusion purpura, requires platelet allotyping. Allele-specific restriction analyses for convenient genotyping are available for the major human platelet antigen (HPA) systems except HPA-4. An allele-specific restriction analysis for HPA-4 was developed by designing a polymerase chain reaction primer containing a single-base substitution (A for T) at glycoprotein IIIa cDNA position 529. The resulting mismatch did not interfere with DNA amplification. Digestion of the polymerase chain reaction product with BsmI allowed differentiation of HPA-4a and HPA-4b alleles. A 126-bp polymerase chain reaction product was amplified with the novel primer. BsmI endonuclease cleaved product encoding HPA-4a into 104- and 22-bp fragments and left DNA encoding HPA-4b intact. This rapid allele-specific restriction analysis for genotyping the HPA-4 system complements similar methods for other platelet alloantigenic determinants.


Accuracy and role of contrast-enhanced CT in diagnosis and surgical planning in 88 soft tissue tumours of extremities.
Soft tissue tumours (STT) require accurate diagnosis in order to identify potential malignancies. Preoperative planning is fundamental to avoid inadequate treatments. The role of contrast-enhanced computed tomography (CT) for local staging remains incompletely assessed. Aims of the study were to evaluate CT accuracy in discriminating active from aggressive tumours compared to histology and evaluate the role of CT angiography (CTA) in surgical planning. This retrospective cohort series of 88 cases from 1200 patients (7 %) was locally studied by contrast-enhanced CT and CTA in a referral centre: 74 malignant tumours, 14 benign lesions. Contrast-enhancement patterns and relationship of the mass with major vessels and bone were compared with histology on surgically excised samples. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were evaluated in discriminating active from aggressive tumours. Sensitivity in differentiating aggressive tumours from active lesions was 89 %, specificity 84 %, PPV 90 %, NPV 82 %. The relationship between mass and major vessels/bone was fundamental for surgical strategy respectively in 40 % and in 58 % of malignant tumours. Contrast-enhanced CT and CTA are effective in differentiating aggressive masses from active lesions in soft tissue and in depicting the relationship between tumour and adjacent bones and major vessels. • Accurate delineation of vascular and bony involvement preoperatively is fundamental for a correct resection. • CT plays a critical role in differential diagnosis of soft tissue masses. • Contrast-enhanced CT and CT angiography are helpful in depicting tumoral vascular involvement. • CT is optimal for characterization of bone involvement in soft tissue malignancies.


Mesenchymal stem cells-derived exosomal microRNA-21-5p downregulates PDCD4 and ameliorates erectile dysfunction in a rat model of diabetes mellitus.
Erectile dysfunction (ED) is a common comorbidity in males with diabetes mellitus (DM), whose pathogenesis might be induced by dysregulation of corpus cavernosum smooth muscle cells (CCSMCs). Gene Expression Omnibus repository-based analysis identified the differentially expressed PDCD4 in DM rats. PDCD4 has also been determined as a putative gene under the regulatory control of microRNA-21-5p (miR-21-5p). This study aimed to further determine the functional role of miR-21-5p in CCSMCs in a rat model of diabetes mellitus-induced erectile dysfunction (DMED). CCSMCs were isolated from penile cavernous tissue and cultured in high glucose (HG) medium. The expression of miR-21-5p and/or PDCD4 was altered in CCSMCs, as directly or indirectly measured by CCK-8 assay, flow cytometry, and TUNEL assays. Furthermore, exosomes were isolated from mesenchymal stem cells (MSCs) transfected with miR-21-5p mimic or miR-21-5p inhibitor and co-cultured with CCSMCs. DMED rats were injected with lentivirus carrying PDCD4/siRNA-PDCD4 plasmids, or exosomes from MSCs containing miR-21-5p-agomir to explore their roles in vivo. The experimental data validated that PDCD4 was upregulated in cavernous tissue of DMED rats. miR-21-5p targeted and inhibited PDCD4. miR-21-5p was enriched in MSC-exosomes. Moreover, PDCD4 downregulation, miR-21-5p elevation or MSC-derived exosomal miR-21-5p reduced apoptosis and enhanced proliferation of CCSMCs cultured in HG medium. PDCD4 silencing or miR-21-5p-containing MSC-exosomes improved erectile function and smooth muscle density in DMED rats. Collectively, our findings suggested that MSC-derived exosomal miR-21-5p suppressed PDCD4 expression and ED in rats with DM.


Postoperative pain after cataract surgery.
Cataract extraction surgery is the most common surgical procedure, but knowledge of postoperative pain related to cataract surgery is sparse. In this systematic review, the incidence, prevalence, and management of pain after phacoemulsification surgery were identified using PubMed and Scopus. Selected studies were restricted to randomized controlled trials with interventions on postoperative inflammation and pain. Data from 105 articles were extracted and 21 studies met the final inclusion criteria. Most studies reported no or only mild postoperative pain, but some reported moderate and severe pain and pain lasting several weeks. The interventions consisted of drug therapy including topical nonsteroidal antiinflammatory drugs, corticosteroids, paracetamol, perioperative intraocular injections, eye pads used after surgery, and various surgical techniques. The reviewed literature indicates that cataract surgery is associated with significant postoperative pain in some patients, who should be provided with appropriate counseling and pain treatment.


The "disappearing" osteochondroma.
Spontaneous regression of a solitary osteochondroma is described. This regression apparently resulted from a cessation of growth of the osteochondroma prior to skeletal maturation, with subsequent incorporation of the lesion into the enlarging bony metaphysis.


Self-Assembled 2D VS2 /Ti3 C2 Tx MXene Nanostructures with Ultrafast Kinetics for Superior Electrochemical Sodium-Ion Storage.
Constructing nanostructures with high structural stability and ultrafast electrochemical reaction kinetics as anodes for sodium-ion batteries (SIBs) is a big challenge. Herein, the robust 2D VS2 / Ti3 C2 Tx MXene nanostructures with the strong Ti─S covalent bond synthesized by a one-pot self-assembly approach are developed. The strong interfacial interaction renders the material of good structural durability and enhanced reaction kinetics. Meanwhile, the enlarged and few-layered MXene nanosheets can be easily obtained according to this interaction, providing a conductive network for sufficient electrolyte penetration and rapid charge transfer. As predicted, the VS2 /MXene nanostructures exhibit an extremely low sodium diffusion barrier confirmed by DFT calculations and small charge transfer impedance evidenced by electrochemical impedance spectroscopy (EIS) analysis. Therefore, the SIBs based on the VS2 /MXene electrode present first-class electrochemical performance with the ultrahigh average initial columbic efficiency of 95.08% and excellent sodium-ion storage capacity of 424.6 mAh g-1 even at 10 A g-1 . It also shows an outstanding sodium-ion storage capacity of 514.2 mAh g-1 at 1 A g-1 with a capacity retention of nearly 100% within 500 times high-rate cycling. Such impressive performance demonstrates the successful synthesis strategy and the great potential of interfacial interactions for high-performance energy storage devices.


Vanadium uptake by biomass of Coprinus comatus and their effect on hyperglycemic mice.
The Vanadium uptake by Coprinus comatus and their co-effect on hyperglycemic mice were studied. By fermentation and AAS analysis, the optimal concentration of vanadium in medium was 0.4%, and the content of vanadium accumulated in the mycelia was 3,528.0 microg/g. At the concentration of 0.4%, the vanadium-associated toxicity was reduced, and its anti-diabetic effects were maintained.


Dihydrolipoic acid inhibits tetrachlorohydroquinone-induced tumor promotion through prevention of oxidative damage.
alpha-Lipoic acid (LA) has been intensely investigated as a therapeutic agent for several diseases, including hepatic disorder and diabetic polyneuropathy. However, the effects of LA or its reduced form, dihydrolipoic acid (DHLA), on cancer chemoprevention has seldom been studied. Tetrachlorohydroquinone (TCHQ) is a toxic metabolite of pentachlorophenol (PCP) that was proven to be a tumor promoter in our previous study. We recently reported that DHLA can inhibit DMBA/TPA-induced skin tumor formation through its anti-inflammatory and anti-oxidizing functions. In the present study, we further examined the effects of DHLA on DMBA/TCHQ-induced skin tumor formation and the possible mechanisms. We found that DHLA significantly inhibited tumor incidence and tumor multiplicity in DMBA/TCHQ-induced skin tumor formation. Administration of DHLA prevented ROS generation, cytotoxicity, genotoxicity and apoptotic cell death in cells treated with TCHQ. In addition, activation of JNK and p38 MAPK may be involved in TCHQ-mediated apoptosis. Nonetheless, the detailed mechanisms of DHLA in attenuating TCHQ-induced skin tumor promotion are still unclear and need to be further investigated. We conclude that DHLA may be a useful protective agent against TCHQ-induced toxicity in epithelial cells, and for reversing TCHQ-induced damage in mouse skin.


Development and evaluation of the effect of ethanol and surfactant in vesicular carriers on Lamivudine permeation through the skin.
The skin embodies a relatively large and readily accessible surface area to absorb a drug through a non-invasive procedure. The vesicular carrier systems such as liposomes, ethosomes, and transethosomes have been explored as non-invasive systems for transdermal delivery of drugs. In the present study, different vesicular carriers were prepared by the thin-film hydration method with modification, and various parameters like size, elasticity, and release profiles were evaluated. Ethosomes and transethosomes have shown the smaller size of 362.21 ± 55.76 and 314.34 ± 41.21 nm, with deformity of 19.34% and 25.04%, respectively, compared with liposomes. The FTIR study of the skin before and after the application of vesicular formulation was performed. The ethosomes and transethosomes changed the orthorhombic phase to the liquid crystalline phase to move the vesicular carrier with the drug to cross the stratum corneum (SC) of the skin. The thermotropic behaviour of drug and vesicular carrier ingredients was studied using differential scanning calorimetry (DSC). Fluorescence images of vesicular-skin permeation have revealed that ethosome and transethosome formulation have shown deeper penetration across the SC and epidermis. The in vitro drug release from the ethosomes and transethosomes has shown 93.34 ± 1.23% and 95.45 ± 2.67% of drug release using Franz diffusion cell and porcine skin as a membrane. The nanostructured flexible vesicular carrier containing ethanol alone and a combination of ethanol and edge activator is a perfect carrier for drug penetration to the deeper skin layer and maintaining the sustained release of drug for a prolonged time.


Endoplasmic reticulum calcium pool depletion-induced apoptosis is coupled with activation of the death receptor 5 pathway.
Thapsigargin (TG), by inducing perturbations in cellular Ca(2+) homeostasis, has been shown to induce apoptosis. The molecular mechanisms of Ca(2+) perturbation-induced apoptosis are not fully understood. In this study, we demonstrate for the first time that TG-mediated perturbations in Ca(2+) homeostasis are coupled with activation of the death receptor 5 (DR5)-dependent apoptotic pathway in human cancer cells. TG selectively upregulated DR5 but had no effect on the expression of the other TRAIL receptor, DR4. TG also upregulated the expression of the DR5 ligand TRAIL (tumor necrosis factor-related apoptosis inducing ligand), albeit in a cell-type specific manner. TG-induced apoptosis has been shown to be associated with activation of the mitochondrial pathway. We found that TG upregulation of DR5 and TRAIL was coupled with caspase 8 activation and Bid cleavage, suggesting that the TG-regulated DR5 pathway could be linked to the mitochondrial pathway. TG enhanced not only DR5 mRNA stability but also increased induction of the DR5 genomic promoter-reporter gene. The TG-induced increase in DR5 expression appeared to occur as a consequence of TG-induced endoplasmic reticulum (ER) Ca(2+) pool depletion. Thus, we report our novel findings that ER Ca(2+) pool depletion-induced apoptotic signals are mediated, at least in part, via a DR5-dependent apoptotic pathway and there appears to be a cross-talk between the death receptor and mitochondrial pathways.


Use of competition dialysis in the discovery of G-quadruplex selective ligands.
G-quadrplex DNA can exist in a rich variety of structural forms, ranging from unimolecular folded structures containing diverse types of loops and strand oreintations, to bimolecular dimeric structures, and finally to tetramolecular parallel-stranded structures. These diverse structures present numerous potential small molecule binding sites with distinctive properties. There is mounting evidence for important functional roles for G-quadruplex structures in biology. G-quadruplexes may participate in the maintenance of telomeres, in transcriptional regulation and, in mRNA, may act to modulate translation. G-quadruplexes thus represent an attractive target for new small-molecule therapeutic agents. Competition dialysis provides a useful tool for the discovery of small molecules that selectively recognize the unique structural features of G-quadruplexes. The principles and practice of the competition dialysis experiment are described here.


[Effect of Chinese herbal drugs and tetrandrine on TGF-beta1 signaling pathway].
To investigate the molecule mechanism of the anti-fibrotic effects of Chinese herbal drugs (Qidan granules) in rats. The male rats were randomly divided into four experimental groups: normal group, model group, Qidan group, tetrandrine group. Every group had 10 rats. Normal group were treated with physiologic saline while others were treated with silicon dioxide (50 mg/rat) by intratracheal instillation to induce silicosis. On 30th day Qidan group and Tetrandrine group were treated with Qidan granules (3125 mg/kg) or treated with tetrandrine (22 mg/kg) respectively. All the rats were scarified after 5 months. Lung/body coefficient was measured. Content of hydroxyproline was measured by alkaline hydrolysis. The gene expression of transforming growth factor-beta1 in bronchoalveolar lavage fluid was examined by using enzyme-linked immunosorbent assay (ELISA). The gene expressions of transforming growth factor-beta1, transcription factor Smad 3 and Smad 7 in lung were analyzed by using immunohistochemical technique (SP) and the image analysis. Model group mainly had Grade III approximately IV silicotic nodule while Qidan group and tetrandrine group had Grade II silicotic nodule. In Qidan group and tetrandrine group, lung/body coefficient and content of hydroxyproline and expression of transforming growth factor-beta1 and Smad3 in lung and expression of transforming growth factor-beta1 in bronchoalveolar lavage fluid were lower than those in model group (P < 0.05). Expression of Smad 7 in lung was higher than model group (P < 0.05). Injury of kidney occurred in tetrandrine group. Qidan granules and tetrandrine could inhibit expression of both Smad 7 and transforming growth factor-beta1 and promote expression of Smad 3. Qidan granules and tetrandrine could inhibit remarkably silicotic fibrosis in rats. Qidan granules are safer than tetrandrine.


Pattern-reversal visual evoked potentials in patients with chronic renal insufficiency.
Visual evoked potentials (VEPs) were recorded from 88 patients with chronic renal insufficiency twice at a 6 month interval. In dialysed patients statistically significant decreases in amplitudes and prolongations of VEP peak latencies were found. Azotaemic non-dialysed patients showed related, but smaller, changes in their VEPs. In patients after kidney transplantation the VEP amplitudes were normal but peak latencies were prolonged. No systematic significant relationship between the VEPs and creatinine and urea levels in the blood could be shown.


Revision of Neodeuterus Schaufuss and description of a new allied genus from Borneo (Coleoptera: Staphylinidae: Pselaphinae).
The Sumatran genus Neodeuterus is revised, and the two included species are synonymized (i.e., N. admirandus = N. alter syn. n.). In addition, Borneodeuterus gen. n. is erected to accommodate B. sannio sp. n. from Borneo.


Innate and mild Th17 cutaneous immune responses elicited by subcutaneous infection of immunocompetent mice with Cladosporium cladosporioides.
Cladosporium cladosporioides is a dematiaceous hyphomycete that is pathogenic in the superficial and deep tissues of both immunodeficient and immunocompetent humans and animals. Our aim was to evaluate the antifungal immune responses elicited by C. cladosporioides in immunocompetent mice. Hence, we subcutaneously injected suspensions of C. cladosporioides spores into immunocompetent mice to investigate the anti-fungal immune responses in the skin. We collected skin tissue samples for histopathological examination, immunofluorescence staining, and quantitative real-time polymerase chain reaction analysis. We observed subcutaneous abscesses in mice after subcutaneous injection of C. cladosporioides. A large number of inflammatory cells, including dendritic cells, macrophages, and neutrophils, infiltrated the focal abscess, with comparatively few infiltrating inflammatory cells in the epidermal and dermal layers of the skin. We detected the expression of CD54 in the abscesses and the skin. Gene expression of the pattern recognition receptors Dectin-1 and TLR-2 was higher in infected mice than in controls. Gene expression of the cytokines IL-6, IL-1β, and IL-17A also increased after infection, suggesting that the Th17 signaling pathway may be involved in the anti-fungal response. Although the pathogenicity of C. cladosporioides in healthy mice was weak after subcutaneous infection, resulting in few serious pathological phenomena, it appears that innate and Th17 immune responses play important roles in the cutaneous host response to C. cladosporioides. These findings lay a foundation for further study of the pathogenic mechanism and treatment of C. cladosporioides infection.


Peripheral versus central effect of intravenous moxonidine on rat carotid sinus baroreflex-mediated sympathetic arterial pressure regulation.
Moxonidine is a centrally acting antihypertensive agent with a selectivity to I1-imidazoline receptors higher than that to α2-adrenergic receptors. The present study aimed to quantify a peripheral effect of moxonidine on carotid sinus baroreflex-mediated sympathetic arterial pressure (AP) regulation separately from its central effect. In eight anesthetized Wistar rats, changes in efferent sympathetic nerve activity (SNA) and AP in response to a carotid sinus pressure input were compared before and during an intravenous administration of moxonidine (100μgkg-1 bolus followed by a continuous infusion at 200μg·kg-1·h-1). Moxonidine significantly narrowed the range of the AP response (55.3±5.8 to 39.1±6.1mmHg, P<0.05) without changing the minimum AP (77.2±6.4 to 80.7±5.1mmHg, not significant). In the neural arc, moxonidine reduced the minimum SNA (56.6±5.9 to 29.7±6.2%, P<0.05) without affecting the range of the SNA response (45.3±5.5 to 40.2±5.0%, not significant). In the peripheral arc, moxonidine increased the intercept (3.0±8.5 to 51.1±7.2mmHg, P<0.01) and reduced the slope (1.28±0.06 to 0.92±0.15mmHg/%, P<0.05). Moxonidine increased AP at any given SNA, suggesting that the peripheral vasoconstrictive effect is stronger than generally recognized. The peripheral vasoconstrictive effect of moxonidine may partly offset the vasodilatory effect attained by centrally-mediated sympathoinhibition.


Uniform-sized PLA nanoparticles: preparation by premix membrane emulsification.
Nanoparticle size is crucial to drug release behavior and biodistribution in vivo, but few studies have been performed on biodegradable nanoparticles with narrow size distribution. In this note, uniform-sized nanoparticles were prepared by a facile method combining emulsion-solvent removal and premix membrane emulsification for the first time. After preparation of coarse emulsions, additional premix membrane emulsification with very high pressure was occupied to achieve uniform-sized nanodroplets, and nanoparticles were formed by further solidification. Polylactide (PLA) was selected as a model polymer. Several factors played key roles to obtain uniform-sized PLA nanoparticles, including type of organic solvent, the volume ratio of oil phase and external water phase, pore size of the microporous membrane and transmembrane pressure. The coefficient of variation (CV) value of PLA nanoparticles could be controlled below 16.9% under an optimum condition. The novel method also has the advantages of high productivity, simplicity and easy scale-up. The uniform-sized nanoparticles prepared by this novel method have great potentials in drug delivery.


Developmental-stage specific single-cell human embryo dissociation.
Isolation of individual cells ensures detailed analysis of human embryos and promotes our understanding of molecular mechanisms driving embryo development and cell specification. Here, we present a protocol for the processing of human embryos for single-cell analysis. We describe steps for growing embryos and individualizing cells from the polar and the mural parts of trophectoderm at the blastocyst stage using laser dissection. We then detail embryo dissociation followed by steps to pick, wash, and dispense cells in plates.


Outcomes of Radiation-Associated Esophageal Squamous Cell Carcinoma: The MSKCC Experience.
Esophageal squamous cell carcinoma (ESCC-R) is a rarely encountered sequela of chest radiation. Treatment is limited by toxicity with reirradiation and complex surgical dissection in a previously radiated field. The clinical presentation, prognosis, and treatment selection of ESCC-R remain undefined. A retrospective review of patients with esophageal squamous cell carcinoma at a single institution between 2000 and 2017 was performed to identify patients with previous radiation therapy (≥ 5 years delay). Clinicopathologic characteristics, treatment, and outcomes of ESCC-R (n = 69) patients were compared to patients with primary esophageal squamous cell carcinoma (ESCC) (n = 827). Overall survival (OS) and cumulative incidence of recurrence (CIR) were compared using log-rank and Gray's tests, respectively. Median time from radiation to ESCC-R was 18.2 years. The majority of ESCC-R patients were female and presented with earlier disease and decreased behavioral risk factors. ESCC-R treated with surgery alone had worse OS than ESCC (5-year 15 vs 33%; p = 0.045). Patients with ESCC-R who received neoadjuvant treatment had higher risk of postoperative in-house mortality (16.7 vs 4.2%; p = 0.032). Patients with ESCC-R treated with surgery alone and definitive chemoradiation had higher recurrence risk than those with neoadjuvant + surgery (5-year recurrence 55 and 45 vs 15%; p = 0.101). Neoadjuvant chemotherapy or chemoradiation should be used whenever possible for ESCC-R as it is associated with lower risk of recurrence. The improved survival benefits of aggressive treatment must be weighed against the higher associated postoperative risks.


Intravitreal injection of mesenchymal stem cells evokes retinal vascular damage in rats.
The aim of this study is to investigate the vascular outcome after intravitreal mesenchymal stem cell (MSC) administration in rats without or with damage to the neurovascular unit [transgenic (TGR) rats]. Male Sprague-Dawley (SD) and TGR rats received an intravitreal injection of 2 × 104 rat bone marrow-derived MSCs (BMSCs) or human adipose-derived stem cells (ASCs) at postnatal d 30. After 4 wk, vasculature, neuronal function, and gene expression in the retinas were evaluated using retinal morphometry, electroretinography, immunofluorescence, Western blot, and quantitative PCR. Intravitreal administration of rat BMSCs and human ASCs in both SD and TGR eyes induced cataract, loss of pericytes, and increased formation of acellular capillaries. BMSCs remained in the vitreous cavity and did not migrate into the retinas. Intravitreal administration of BMSCs impacted retinal neuronal function in neither SD nor TGR rats. Retinal glial activation, elevation of IL-1β, C3, arginase 1, and heat shock protein 90 were detected in BMSC-injected SD rats. Intravitreal administration of MSCs induces cataract, retinal vasoregression, activation of retinal glial cells, and inflammatory response in rat eyes.-Huang, H., Kolibabka, M., Eshwaran, R., Chatterjee, A., Schlotterer, A., Willer, H., Bieback, K., Hammes, H.-P., Feng, Y. Intravitreal injection of mesenchymal stem cells evokes retinal vascular damage in rats.


Genome-wide characterization of integrin (ITG) gene family and their expression profiling in half-smooth tongue sole (Cynoglossus semilaevis) upon Vibrio anguillarum infection.
Integrins (ITGs) are transmembrane heterodimer receptors with ITGα subunit and ITGβ subunit, participating in various physiological processes, including immunity. At present, systematic research on ITGs in teleost is scarce, especially in half-smooth tongue sole (Cynoglossus semilaevis). In this study, a set of 28 ITG genes in half-smooth tongue sole have been identified and characterized. The phylogenetic analysis showed that ITGα and ITGβ subunits were respectively classified into five and two clusters, consistent with previous studies. The selection pressure analysis indicated that most of ITG genes were under purifying selection, except for ITGα11b and ITGαL with positive selection. The expression profiles of eight selected ITG genes, including ITGα1, ITGα5, ITGα8, ITGα11, ITGβ1, ITGβ2, ITGβ3, and ITGβ8, were analyzed in healthy tissues and after infection with Vibrio anguillarum, revealed their implications in immune response. The study provided a comprehensive characterization and expression analysis of ITG genes in half-smooth tongue sole, setting a solid foundation for further functional studies and promising potential in disease control.


Superspreading events of SARS-CoV-2 in Paris: A retrospective analysis of data from the first wave of COVID-19 in 2020.
The 2020 COVID-19 pandemic led to a strict lockdown in France from March 17 to May 11, 2020. After the lockdown, the French strategy to mitigate the impact of SARS-CoV-2 relied partly on investigations of all confirmed cases. Monitoring collective settings is particularly important since SARS-CoV-2 seems prone to superspreading events (SSEs). Our study is based on data gathered in Paris from May 11 to December 31, 2020, by the Ile-de-France Regional Health Agency (RHA) to investigate cases occurring in collective and high-risk settings. Specific events in high-risk settings were systematically transmitted to the RHA, and screenings were organized by the facilities, while other settings were reported when three cases were identified within a short period. These settings were more difficult to identify through the surveillance system since no systematic screening was organized by the facility, leaving screenings to rely on the national contact-tracing programme. No official superspreading threshold has been set for SARS-CoV-2. We defined a SSE as an event involving ten cases. We analysed 15,706 events associated with 38,670 cases, representing an average of 2.70 cases per event. Most clusters occurred in educational facilities, workplace environments, social care settings, and healthcare facilities. SSEs represented 3.4% but accounted for 28% of all cases reported. The highest number of SSEs occurred in college settings (12.6%), followed by hospitals and retirement homes. Educational facilities had the lowest number of SSEs, with around 1% in preschools and elementary schools. We observed different SSE rates in each setting. Preschools and primary schools represented the majority of events but experiencing very few SSEs. Colleges were prone to SSEs and were associated with a high number of secondary cases. These findings provide some insights on contact tracing activities and SARS-CoV-2 transmission in different settings.


Effectiveness of using a chatbot to promote adherence to home physiotherapy after total knee replacement, rationale and design of a randomized clinical trial.
Rehabilitation is essential to optimize outcomes after surgical procedures in musculoskeletal disorders. However, adherence to rehabilitation continues to be an important barrier, since compliance with the programs is not always as desired, which may have a negative impact on clinical results. Randomized controlled trial aimed at to determining the effectiveness of using a virtual assistant (i.e., chatbot) to promote adherence to home rehabilitation. Overall, seventy patients under 75, undergoing total knee replacement, who have a personal smartphone and are familiar with its use, will be assigned into the control (standard care) or the experimental (standard care plus virtual assistant) group. Adherence (primary outcome) will be assessed three months after surgery. The WOMAC questionnaire, knee pain and system usability scale will be also outcomes of interest at three months and one year. Overall, an analysis of variance will look for possible time, group and time*group interactions. The expected result is to determine whether the use of a chatbot that interacts with the patient can increase adherence to post-surgical home physiotherapy, and result in better clinical results (functional and pain) than standard care. clinicaltrials.gov id. NCT05363137.


Two molecular forms of (Na+ + K+)-stimulated ATPase in brain. Separation, and difference in affinity for strophanthidin.
The brain contains two distinct molecular forms of the (Na,K)-ATPase (sodium and potassium ion-stimulated adenosine triphosphatase). They can be resolved by gel electrophoresis in sodium dodecyl sulfate, and can be identified by sodium-dependent, potassium-sensitive phosphorylation by [gamma-32P]ATP. They are present in the brain of every animal species examined, while only one molecular form is detected in the other organs examined. They are located in different kinds of cells within the brain, and can be physically separated while fully active by gentle tissue fractionation procedures. One is the only (Na,K)-ATPase of brain non-neuronal cells (astrocytes), while the other is the only (Na,K)-ATPase of axolemma (plasma membrane of myelinated axons). They differ in at least one kinetic parameter: the affinity for the specific inhibitor strophanthidin. They have similar one-dimensional peptide maps, but differ in their sensitivity to digestion by trypsin and in the number or reactivity of sulfhydryl groups. It is anticipated that they will be found to play functionally different roles in the complex ion transport mechanisms of the brain.


Interaction of the mutagenic metabolite of sodium azide, synthesized in vitro, with DNA of barley embryos.
The in vitro synthesized sodium azide mutagenic metabolite (azidoalanine) produced single-strand breaks and proteinase K-sensitive sites in isolated, germinating barley embryos. In contrast with sodium azide, the efficiency of DNA damage induction was lower, and both types of DNA lesions were totally or partially repaired in the course of subsequent 24 h incubation of the embryos. The mutagenic azide metabolite did not inhibit DNA replication, while azide did so even at doses which are not highly mutagenic. The metabolite labelled with 14C at the amino acid residue was taken up with a similar efficiency both into barley embryos germinating for 2 days and into cells of Salmonella typhimurium TA100. The majority of the radioactivity was incorporated into proteins, less into RNA and a negligible amount into DNA.


Venous Stent Migration of the Right Ventricle.
Peripheral migration of a venous stent to the heart is a rare but known complication, with the heart being the most common site of landing. Echocardiographic modalities are essential in clinical diagnosis and management, particularly with limited data and consensus regarding the best management approach. (Level of Difficulty: Intermediate.).


Automated magnetic sorbent extraction based on octadecylsilane functionalized maghemite magnetic particles in a sequential injection system coupled with electrothermal atomic absorption spectrometry for metal determination.
A new automatic sequential injection (SI) system for on-line magnetic sorbent extraction coupled with electrothermal atomic absorption spectrometry (ETAAS) has been successfully developed for metal determination. In this work, we reported effective on-line immobilization of magnetic silica particles into a microcolumn by the external force of two strong neodymium iron boron (NdFeB) magnets across it, avoiding the use of frits. Octadecylsilane functionalized maghemite magnetic particles were used as sorbent material. The potentials of the system were demonstrated for trace cadmium determination in water samples. The method was based on the on-line complex formation with diethyldithiocarbamate (DDTC), retention of Cd-DDTC on the surface of the MPs and elution with isobutyl methyl ketone (IBMK). The formation mechanism of the magnetic solid phase packed column and all critical parameters (chemical, flow, graphite furnace) influencing the performance of the system were optimized and offered good analytical characteristics. For 5 mL sample volume, a detection limit of 3 ng L(-1), a relative standard deviation of 3.9% at 50 ng L(-1) level (n=11) and a linear range of 9-350 ng L(-1) were obtained. The column remained stable for more than 600 cycles keeping the cost down in routine analysis. The proposed method was evaluated by analyzing certified reference materials and natural waters.


Batch immunoextraction method for efficient purification of aromatic cytokinins.
A range of benzylaminopurines naturally occur in plants and exhibit high biological activity. Others have been synthesized, such as 6-(2-hydroxy-3-methoxybenzylamino)purine riboside (2OH3MeOBAPR), which has shown interesting anti-cancer activity under in vitro conditions. In order to study the biological activity of this interesting compound in more detail, a rapid and highly efficient method for its purification from complex samples (e.g. blood and plant extracts) is needed. Therefore, we prepared monoclonal antibodies against 2OH3MeOBAPR. The antibody had undetectable cross-reactivity with all natural isoprenoid cytokinins, but relatively high cross-reactivity with aromatic cytokinins as well as some synthetic di- and tri-substituted 6-benzylaminopurines and the corresponding ribosides. The antibody also showed strong responses and specificity in enzyme-linked immunoassays (ELISAs). In addition, it was used to prepare, for the first time, an immunoaffinity sorbent with high specificity and capacity for aromatic cytokinins. A batch immunoextraction method was then developed and optimized for the purification of 2OH3MeOBAPR from murine blood samples. The high efficacy and simplicity of this method (in off-line combination with HPLC-MS) for the isolation of target analytes from biological material is demonstrated in this study.


Comparative performance of four malaria rapid diagnostic tests, Vikia Malaria Pf/Pan, Meriline-Meriscreen Pf/Pv/Pan, Right Sign Malaria Pf/Pan, and Right Sign Malaria Pf, among febrile patients in Gabon.
Rapid diagnostic tests (RDTs) are selected based on their performances. Here, we compared the diagnostic performance of different malaria RDTs. Febrile patients were tested for malaria using Vikia Malaria Pf/Pan, Meriline-Meriscreen Pf/Pv/Pan, Right Sign Malaria Pf/Pan, and Right Sign Malaria Pf RDTs at Melen Regional Hospital in Gabon. In total, 120 of 274 tested children (43.8%) had malaria. The sensitivity was > 95% for all RDTs, while the specificity was > 85% for two tests. One test generated invalid tests (8%). Based on their performances, all tests except one may be recommended for malaria diagnosis.


Antibiotics for simple upper respiratory tract infections: a survey of academic, pediatric, and adult clinical allergists.
The Centers for Disease Control and Prevention (CDC), the American Academy of Family Practice, and the American Academy of Pediatrics published guidelines for judicious antibiotic use: antibiotics are injudicious for the treatment of short-term purulent rhinorrhea, otitis media with effusion, and acute wheezy bronchitis. To determine how academic, pediatric, and adult clinical allergists differed in use of antibiotics for upper respiratory tract infections (URIs). Surveys were sent to 424 allergists in private clinical practice and 156 allergists in academic settings. Three clinical pediatric vignettes were described. Questions about possible antibiotic use followed. Vignettes were as follows: simple URI in a toddler, the same child with short-duration green rhinorrhea, and the same child with otitis media with effusion. Of 580 mailed surveys, 358 were returned, for an overall response rate of 61.7%. Thirty-nine of these surveys did not meet inclusion criteria, reducing the response rate to 55.0%. Of these, 47.0% (n=150) were familiar with the guidelines: 85.3% answered that they usually adhered to them in practice. The academic allergist respondents demonstrated the best adherence to the guidelines for the 3 vignettes, followed closely by the clinical pediatric allergist respondents. For the population surveyed, adult clinical allergists were more likely than the other 2 groups to prescribe antibiotics for a simple URI (P < .001) and for a URI with short-duration green rhinorrhea (P = .004). Academic allergists adhered to the CDC guidelines more closely than did adult allergists. Pediatric allergists in clinical practice were in agreement with the academic allergists. Despite self-reported knowledge of the CDC guidelines, many adult allergists in clinical practice did not adhere to them in their answers to the questions after several vignettes.


The development of functional heterogeneity in the liver parenchyma of the golden hamster.
Prenatal and postnatal stages of the development of golden hamsters were studied histochemically and biochemically. It was shown that, beginning with the 12th gestational day, the fetal liver starts to store glycogen, and that this process reaches its maximum a birth. Glycogen phosphorylase and glucose-6-phosphatase (G6Pase)-activity increased drastically in the last two days before birth, glycogen phosphorylase preceding G6Pase. As a histochemical characteristic, an even distribution of glycogen, glycogen phosphorylase and G6Pase activity is found in the liver parenchyma at birth. During the first two postnatal weeks typical heterogeneous patterns of distribution developed: glycogen depletion could be demonstrated predominantly in zone 1 of the liver acinus, this being at the same time the area of highest glycogen phosphorylase and G6Pase-activity. The periportal zone 1 thus became characterized as the primary site of glycogenolysis (glycogen phosphorylase) and gluco(neo)genesis (G6Pase). "Metabolic Zonation" is interpreted as the chemomorphological equivalent of the regulatory function of the liver as a glucostat.


Purine nucleotide synthesis in normal and leukemic blood cells.
The present study was undertaken to obtain more precise information about the purine biosynthetic pathway in human blood cells. 5'phosphoribosyl-l-pyrophosphate (PP-ribose-P) amidotransferase was found in cell-free extracts from all leukemic cells and normal lymphocytes and therefore these cells could synthesize the first intermediate of the purine-de-novo-synthesis. Normal leucocytes, erythrocytes and bone marrow cells lack this enzyme system and have an absolute requirement for externally supplied purines via salvage pathway. Leukemic blast cells show different enzyme activities independent of their cell count. Kinetic studies with the crude enzymes showed sigmoidal substrate velocity curves for PP-ribose-P, whereas glutamine shows hyperbolic kinetics. The leukemic cell enzymes from all four donor types (ALL, CLL, AML and CML) are rapidly saturated with low concentrations of PP-ribose-P and less inhibited by the physiological feedback inhibitor, adenosine 5'monophosphate. The crude enzymes of normal spleen lymphocytes and leukemic cells were further purified (10 to 15-fold) and substrate velocity curves for PP-ribose-P and glutamine show now hyperbolic kinetics and double reciprocal plots were linear with and apparent Km for PP-ribose-P of 0.14 mM and for glutamine 2.0 mM. In the presence of different concentrations of AMP, the PP-ribose-P substrate velocity plot changed from a hyperbolic to a sigmoidal curve; no difference in the degree of the inhibition between both partially purified enzymes (normal spleen lymphocytes and leukemic cells from all four donor types) could now be observed.


Scaffolds for cartilage repair of the ankle joint: The impact on surgical practice.
Ideal management of osteochondral lesions in the ankle joint is still theme of debate. Scaffold-based repair is emerging as a new approach for regenerative treatment. Articles published in PubMed from 2000 to January 2012 addressing cartilage scaffold-based treatment were identified, including levels I-IV evidence clinical trials with measures of functional, clinical or imaging outcome. The analysis showed a progressively increasing number of articles from 2000. The number of selected papers was 19:15 focusing on two-step and 4 on one-step procedures; no randomized studies, 3 comparative studies, 11 case series and 5 case reports were identified. Regenerative surgical approach with scaffold-based procedures is emerging as a potential therapeutic option for the treatment of chondral lesions of the ankle. One step treatments simplify the procedure and the results reported are very close to the previous techniques. However, well-designed studies are lacking, and randomized long-term trials are necessary to confirm the potential of these techniques. Review - IV.


Spectrophotometric detection of the interaction between cytochrome c and heparin.
Heparin inhibits transport of electrons from reduced cytochrome c to cytochrome c oxidase. The effect is due to the interaction of heparin with cytochrome c. It has been observed that binding of heparin to the reduced or oxidized cytochrome c changes the spectrum of cytochrome c at the Soret region. Affinity chromatography of heparin in cytochrome c immobilized to thiol-Sepharose shows that commercial heparin is eluted in the low-affinity and high-affinity fractions. Both participate in the interaction with cytochrome c. Polylysine induces decay of the cytochrome c-heparin complex.


The presence of viral subpopulations in an infectious bronchitis virus vaccine with differing pathogenicity--a preliminary study.
There are currently four commercially available vaccines in Australia to protect chickens against infectious bronchitis virus (IBV). Predominantly, IBV causes clinical signs associated with respiratory or kidney disease, which subsequently cause an increase in mortality rate. Three of the current vaccines belong to the same subgroup (subgroup 1), however, the VicS vaccine has been reported to cause an increased vaccinal reaction compared to the other subgroup 1 vaccines. Molecular anomalies detected in VicS suggested the presence of two major subspecies, VicS-v and VicS-del, present in the commercial preparation of VicS. The most notable anomaly is the absence of a 40 bp sequence in the 3'UTR of VicS-del. In this investigation, the two subspecies were isolated and shown to grow independently and to similar titres in embryonated chicken eggs. An in vivo investigation involved 5 groups of 20 chickens each and found that VicS-del grew to a significantly lesser extent in the chicken tissues collected than did VicS-v. The group inoculated with an even ratio of the isolated subspecies scored the most severe clinical signs, with the longest duration. These results indicate the potential for a cooperative, instead of an expected competitive, relationship between VicS-v and VicS-del to infect a host, which is reminiscent of RNA viral quasi-species.


Efficacy and Safety of Lower-Sodium Oxybate in an Open-Label Titration Period of a Phase 3 Clinical Study in Adults with Idiopathic Hypersomnia.
To report the efficacy and safety of lower-sodium oxybate (LXB; Xywav®) during the open-label titration and optimization period (OLT) and stable-dose period (SDP) in a clinical study for the treatment of idiopathic hypersomnia. Data were collected during treatment titration and optimization in a phase 3 randomized withdrawal trial in adults (18-75 years of age) with idiopathic hypersomnia who took LXB treatment (once, twice, or thrice nightly, administered orally) in the OLT (10-14 weeks), followed by the 2-week, open-label SDP. Endpoints included the Epworth Sleepiness Scale (ESS), Idiopathic Hypersomnia Severity Scale (IHSS), Patient Global Impression of Change, Clinical Global Impression of Change, Functional Outcomes of Sleep Questionnaire (FOSQ)-10, and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP). The safety population included 154 participants; the modified intent-to-treat population comprised 115 participants. During open-label treatment, mean (SD) ESS scores improved (decreased) from 15.7 (3.8) at baseline to 6.1 (4.0) at end of SDP, and IHSS scores improved (decreased) from 31.6 (8.3) to 15.3 (8.5). Improvements were also observed during OLT in each individual IHSS item and in FOSQ-10 and WPAI:SHP scores. Thirty-five (22.7%) participants discontinued during OLT and SDP, 22 (14.3%) due to treatment-emergent adverse events (TEAEs) during OLT and SDP. The most frequent TEAEs in the first 4 weeks were nausea, headache, dizziness, and dry mouth; TEAE incidence decreased throughout OLT and SDP (weeks 1-4, n = 87 [56.5%]; weeks 13-16, n = 39 [31.7%]). During open-label treatment with LXB, participants showed clinically meaningful improvements in idiopathic hypersomnia symptoms and in quality of life and functional measures. TEAE incidence declined over LXB titration and optimization.


Association Between Pre-diagnostic Dietary Supplements Intake and Ovarian Cancer Survival: Findings From a Prospective Cohort Study in Chinese Women.
Background: As a result of a limited number of studies and inconsistent findings, there remains uncertainty in whether pre-diagnostic dietary supplements intake affects survival after ovarian cancer (OC) diagnosis. Methods: The association between pre-diagnostic dietary supplements intake and all-cause OC mortality was examined in the OC follow-up study, which included a hospital-based cohort (n = 703) of Chinese women diagnosed with OC between 2015 and 2020. Pre-diagnostic dietary supplements information was collected using self-administered questionnaires. Deaths were ascertained up to March 31, 2021, via death registry linkage. Cox proportional hazards were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the aforementioned association. Results: A total of 130 women died during the median follow-up of 37.2 months (interquartile: 24.7-50.2 months). We found no evidence that any pre-diagnostic dietary supplements intake compared with never is associated with OC survival (HR = 0.75, 95%CI: 0.47-1.18). Furthermore, our study suggested no association for ever supplements intakes of vitamin A (HR = 0.48, 95%CI: 0.07-3.46), vitamin C (HR = 0.64, 95%CI: 0.27-1.54), vitamin D (HR = 1.19, 95%CI: 0.28-5.03), vitamin E (HR = 0.47, 95%CI: 0.06-3.87), multivitamin (HR = 0.49, 95%CI: 0.14-1.67), calcium (HR = 0.96, 95%CI: 0.53-1.72), and fish oil/DHA (HR = 0.31, 95%CI: 0.04-2.37) with OC survival. Interestingly, we only found a detrimental effect of vitamin B supplementation intake (HR = 3.78, 95%CI: 1.33-0.69) on OC survival. Conclusions: We found no evidence that any pre-diagnostic dietary supplements intake is associated with OC survival. Considering lower exposure of dietary supplements before OC diagnosis in the present study, further studies are warranted to confirm these findings.


Peri-operative pulmonary dysfunction and protection.
Pulmonary complications are a major cause of peri-operative morbidity and mortality, but have been researched less thoroughly than cardiac complications. It is important to try and predict which patients are at risk of peri-operative pulmonary complications and to intervene to reduce this risk. Anaesthetists are in a unique position to do this during the whole peri-operative period. Pre-operative training, smoking cessation and lung ventilation with tidal volumes of 6-8 ml.kg(-1) and low positive end-expiratory pressure probably reduce postoperative pulmonary complications.


Burn wound pathophysiology and care.
The pathophysiology of the burn injury and treatment factors that influence burn depth are explained. Details of burn wound care, including indications for early excision, topical antimicrobials, and the most recent advances in skin substitutes, are described. Burn wound sepsis, the most common and serious complication, is discussed in regard to diagnosis and treatment.


Natural killer KIR3DS1 is closely associated with HCV viral clearance and sustained virological response in HIV/HCV patients.
To evaluate the influence of the presence of the killer cell immunoglobulin-like receptor (KIR) 3DS1 on HCV treatment response in HIV/HCV genotype 1 co-infected patients. HIV/HCV co-infected patients were included. KIR3DS1, their specific HLA-B ligands and IL28B gene were genotyped. Reductions of plasma HCV RNA levels between baseline and week 1, week 2 and week 4 were analyzed for IL28B genotype and KIR3DS1 (HLA Bw4 or Bw6). Rapid and sustained virological response (RVR and SVR) rates were also analyzed. Sixty HIV/HCV genotype 1 co-infected patients were included. Patients with KIR3DS1 and Bw4 had higher rates of HCV viral decline than those who were not carriers of KIR3DS1 (week 1: p = 0.01; week 2: p = 0.038; week 4: p = 0.03). Patients carrying KIR3DS1/Bw4 had higher rates of RVR and SVR than those who did not carry KIR3DS1 (RVR: 46.15% versus 17.02%, p = 0.012; SVR: 63.6% versus 13 26.5%, p = 0.031). With respect to patients carrying the IL28B-CC genotype, those with KIR3DS1/Bw4 had greater rates of HCV viral clearance (week 1: p<0.001; week 2: p = 0.01; week 4: p = 0.02), RVR (p = 0.015) and SVR (p = 0.029) than those not carrying KIR3DS1. Our results show that the KIR3DS1 genotype has a positive effect on HCV viral clearance during the first weeks of Peg-IFN/RBV treatment in HCV/HCV co-infected patients bearing genotype 1, and higher RVR and SVR rates.


Whole-body muscle MRI in McArdle disease.
This study describes muscle involvement on whole-body MRI (WB-MRI) scans at different stages of McArdle disease. WB-MRI was performed on fifteen genetically confirmed McArdle disease patients between ages 25 to 80. The degree of fatty substitution was scored for 60 muscles using Mercuri's classification. All patients reported an intolerance to exercise and episodes of rhabdomyolysis. A mild fixed muscle weakness was observed in 13/15 patients with neck flexor weakness in 7/15 cases, and proximal muscle weakness in 6/15 cases. A moderate scapular winging was observed in five patients. A careful review of the MRI scans, as well as hierarchical clustering of patients by Mercuri scores, pointed out recurrent muscle changes particularly in the subscapularis, anterior serratus, erector spinae and quadratus femoris muscles. WB-MRI imaging provides clinically relevant information and is a useful tool to orient toward the diagnosis of McArdle disease.


Myotoxicity of injections for acute muscle injuries: a systematic review.
Injection therapies are widely used for muscle injuries. As there is only limited evidence of their efficacy, physicians should be aware of the potential harmful effects of these injected preparations. The purpose of this review was to systematically review the literature on the myotoxic effects of intramuscular injection preparations commonly used for acute muscle injuries. The databases of PubMed, Embase, Web of Science, Cochrane Library, CINAHL and SportDiscus were searched in March 2013. Studies reporting histological evaluation or creatine kinase activity after intramuscular injection with local anaesthetics, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), platelet-rich plasma (PRP), Traumeel(®) and Actovegin(®), or combination preparations were eligible for inclusion. Two authors independently screened the search results and assessed the risk of bias. A best-evidence synthesis was used to identify the level of evidence. Forty-nine studies were included in this systematic review. There is strong to moderate evidence that intramuscularly injected local anaesthetics and NSAIDs are myotoxic, and there is conflicting evidence of the myotoxicity of PRP. There is limited evidence that single corticosteroid injections are not myotoxic but have a synergistic myotoxic effect when used together with local anaesthetics. There is no information to assess whether Actovegin(®) and Traumeel(®) are myotoxic. Local anaesthetics and NSAID injections are not recommended for the treatment of muscle injuries in athletes, as they are myotoxic. The possible myotoxic effects of corticosteroids, PRP, Traumeel(®) and Actovegin(®) should be assessed in future research.


Retrospective analysis of the occurrence of internal malignancy in patients treated with PUVA between 1986 and 1999 in South Warwickshire.
Concerns were raised in our department when four of our patients receiving PUVA treatment developed internal malignancy. We reviewed the medical and phototherapy case notes of patients who received either systemic or bath PUVA therapy in our department between 1986 and 1999. Among the 197 patients for whom we were able to trace the hospital records we identified five patients with internal malignancies. Over the same period (1986-1999) we calculated, using the Kaplan-Meier nonparametric estimator, that 4.6 cases of internal malignancy would have been anticipated in our study population. Therefore PUVA therapy did not appear to be a risk factor for internal malignancy.


Alcohol dehydrogenase in the mouse epididymis. Genetic variation and cellular localization.
The cellular localization of alcohol dehydrogenase (ADH) in the mouse epididymis was investigated using differential substrate specificities and genetic variation as a means of distinguishing these enzymes histochemically in tissue sections. ADH-C2 exhibited high activity in BALB/c epididymis and was observed as a discrete zone within duct epithelial cells near the nuclei. This isozyme exhibited no detectable activity in C57BL/6J epididymis extracts or histochemical sections.


Scalable water splitting on particulate photocatalyst sheets with a solar-to-hydrogen energy conversion efficiency exceeding 1.
Photocatalytic water splitting using particulate semiconductors is a potentially scalable and economically feasible technology for converting solar energy into hydrogen. Z-scheme systems based on two-step photoexcitation of a hydrogen evolution photocatalyst (HEP) and an oxygen evolution photocatalyst (OEP) are suited to harvesting of sunlight because semiconductors with either water reduction or oxidation activity can be applied to the water splitting reaction. However, it is challenging to achieve efficient transfer of electrons between HEP and OEP particles. Here, we present photocatalyst sheets based on La- and Rh-codoped SrTiO3 (SrTiO3:La, Rh; ref. ) and Mo-doped BiVO4 (BiVO4:Mo) powders embedded into a gold (Au) layer. Enhancement of the electron relay by annealing and suppression of undesirable reactions through surface modification allow pure water (pH 6.8) splitting with a solar-to-hydrogen energy conversion efficiency of 1.1% and an apparent quantum yield of over 30% at 419 nm. The photocatalyst sheet design enables efficient and scalable water splitting using particulate semiconductors.


Clinical course of breast cancer patients with isolated sternal and full-thickness chest wall recurrences treated with and without radical surgery.
The role and outcome of radical surgery in contemporary multidisciplinary management of breast cancer patients presenting with isolated sternal or fullthickness chest wall (SCW) recurrence are undefined compared with patients treated without surgery. Detailed analyses of all patients with isolated SCW recurrence treated from 1992 to 2011 at a large cancer institution were performed. Univariate and multivariate comparisons of clinicopathologic and treatment characteristics were analyzed. Overall and progression-free survival were compared using the Kaplan–Meier method. Seventy-six patients were identified, 44 treated surgically and 32 nonsurgically. Overall survival at 5 years was not statistically different between patients who underwent surgery and those who did not (30.6 and 49.6 %, respectively; P = 0.52) although patients selected for surgery presented with more advanced and biologically aggressive disease. Surgically treated patients were more likely to have triple-negative breast cancer at recurrence (52 vs. 17 %; P = 0.006). Among surgical patients, 95 % received preoperative systemic therapy. Clinical response with systemic therapy was significantly different, with surgically treated patients more likely to have responsive or stable disease (54 vs. 25 %, P = 0.04). Complications related to radical surgical resection occurred in 25 % of patients. For hormone receptor–positive recurrence, 5-year progression-free survival was significantly higher among surgical patients (46.3 vs. 14.5 %; P = 0.01). Among patients with isolated SCW recurrence, hormone receptor-positive recurrence is associated with improved survival. Systemic therapy should be the initial treatment, and clinical response can be used to help select patients who may benefit from radical resection.


Kinetic study of H-terminated silicon nanowires oxidation in very first stages.
Oxidation of silicon nanowires (Si NWs) is an undesirable phenomenon that has a detrimental effect on their electronic properties. To prevent oxidation of Si NWs, a deeper understanding of the oxidation reaction kinetics is necessary. In the current work, we study the oxidation kinetics of hydrogen-terminated Si NWs (H-Si NWs) as the starting surfaces for molecular functionalization of Si surfaces. H-Si NWs of 85-nm average diameter were annealed at various temperatures from 50°C to 400°C, in short-time spans ranging from 5 to 60 min. At high temperatures (T ≥ 200°C), oxidation was found to be dominated by the oxide growth site formation (made up of silicon suboxides) and subsequent silicon oxide self-limitation. Si-Si backbond oxidation and Si-H surface bond propagation dominated the process at lower temperatures (T < 200°C).


Detection of Leptospira in a forest fragmentation area in eastern Amazon: A unique health approach.
The objective of this study was to detect the presence of anti-Leptospira spp. in samples of humans and domestic animals of forest fragmentation areas in the Brazilian Amazon. A total of 208 samples from dogs, cats, and humans were collected during two expeditions within the same fragment. Detection of anti-Leptospira spp. antibodies was performed by the Microscopic Agglutination Test (MAT) using live antigens from 19 Leptospira spp. serogroups and DNA detection of Leptospira 16S rRNA gene was done using Polymerase Chain Reaction. After the analysis, we observed 24.03% (50/208) of reactive serum samples, where the most prevalent serogroups circulating in the human and animal population were Canicola, Djasiman, Cynopteri, and Serjoe. Leptospira DNA was detected only in the samples of 13 dogs, which demonstrated 100% identity with L. interrogans DNA deposited in the GenBank. We concluded that there is a circulation of Leptospira spp. in the studied fragment.


Dysplasia: a common finding in intractable pediatric temporal lobe epilepsy.
Risk factors for temporal lobe epilepsy (TLE) include history of CNS infection, family history of epilepsy, and history of febrile convulsions (FC). Pre-existing cortical dysplasia (CD) may also predispose to refractory TLE, independent of other risk factors for epilepsy. The authors reviewed the neuropathologic features of surgical tissue from temporal lobectomies of 33 pediatric patients with refractory TLE, with and without a history of epilepsy risk factors. CD was found in 64% (21/33) of all patients with refractory TLE, including 73% (11/15) patients with a history of FC, 66% (2/3) patients with CNS infections, and 83% (5/6) patients with a family history of epilepsy. Disrupted cortical lamination, dystrophic and maloriented neurons, and balloon cells characterized the CD found in the temporal neocortex. CD was seen in 21 of 33 surgical specimens from children with refractory TLE, including those with and without other epilepsy risk factors.


The cytochrome c3-[Fe]-hydrogenase electron-transfer complex: structural model by NMR restrained docking.
Cytochrome c(3) (M(r) 13000) is a low redox potential cytochrome specific of the anaerobic metabolism in sulfate-reducing bacteria. This tetrahemic cytochrome is an intermediate between the [Fe]-hydrogenase and the cytochrome Hmc in Desulfovibrio vulgaris Hildenborough strain. The present work describes the structural model of the cytochrome c(3)-[Fe]-hydrogenase complex obtained by nuclear magnetic resonance restrained docking. This model connects the distal cluster of the [Fe]-hydrogenase to heme 4 of the cytochrome, the same heme found in the interaction with cytochrome Hmc. This result gives evidence that cytochrome c(3) is an electron shuttle between the periplasmic hydrogenase and the Hmc membrane-bound complex.


Protein folding in the secretory pathway of animal cells.
The exit of newly-synthesized proteins from the lumen of the endoplasmic reticulum (ER) is the rate-determining step in protein secretion. Only correctly-folded and fully-assembled proteins exit the ER and progress along the secretory pathway. Folding and assembly in the ER are mediated by a variety of factors including folding catalysts and molecular chaperones. The properties of these factors, and the nature of their interactions with folding substrates, are beginning to be clarified. Little work has been done to characterize these processes and these factors in cell lines employed for large-scale cell culture. Manipulation of these process may permit improvement in yield or productivity of recombinant proteins by cultured animal cells.


Oral Candida carriage among individuals chewing betel-quid with and without tobacco.
The aim was to assess oral Candida carriage among individuals chewing betel-quid (BQ) with and without tobacco. A retrospective and comparative study of oral Candida carriage among individuals chewing BQ with and without tobacco. Oral yeast samples were collected from 103 BQ-chewers (52 chewing BQ with tobacco and 51 chewing BQ without tobacco) and 100 non-chewers. Candida strains were cultured in Sabouraud dextrose agar and identified using the API 32-C System and polymerase chain reaction-DNA sequencing. Tongue lesions were clinically identified and numbers of missing teeth were recorded. Unstimulated whole salivary flow rate was recorded. Oral Candida species were isolated from 72.7% BQ-chewers (73.1% in individuals chewing BQ with tobacco and 72.4% in individuals chewing BQ without tobacco) and 61% non-chewers. Chewing BQ (with or without tobacco) does not influence oral Candida carriage.


Treatment of sexually transmitted infections in women.
Sexually transmitted infections remain a major public health concern in the United States. An estimated 19 million infections occur each year. The economic burden imposed by sexually transmitted infections is impressive: direct medical costs are estimated to be as high as $15.5 billion annually. Women and infants disproportionately bear the long-term consequences of sexually transmitted diseases. This article briefly introduces various infections, reviews new diagnostic information, and presents the latest guidelines for therapy. All recommended and alternative regimens are drawn from the most recent Centers for Disease Control and Prevention treatment guidelines and recent updates.


Minimal-trauma ankle fractures predominate during pregnancy: a 17-year retrospective study.
This study assessed all fractures occurring in pregnancy at a tertiary referral centre over a 17-year period. Most fractures were due to minimal trauma, and those involving the ankle were the most common. Women tended to fracture during their second and third trimesters and most required surgical intervention during pregnancy. To characterise fractures in pregnancy over a 17-year period at a tertiary referral health service. Medical records at the Monash Health in Australia were examined from 2000-2016 for fractures in pregnancy using the birthing outcome system database and the tenth revision of the International Statistical Classification of Diseases and Related Health Problems coding. Site, mechanism, investigations, management and outcomes were documented. Of the 114,673 live births during this period, 33 women (mean age 30.3 ± 1.9 years) were identified with fracture in pregnancy (~ 2.9 maternal fractures/10,000 live births). Minimal-trauma fractures (MTFs) occurred in 28 women whilst 5 were due to motor vehicle accidents. Of the MTF, 2/28 (7.1%), 13/28 (46.4%) and 13/28 (46.4%) occurred in the first, second and third trimesters, respectively. MTF involved the lower limb (60.7%), upper limb (25.0%), ribs (10.7%) and clavicle (3.6%). The ankle was involved in 39.3% of MTFs. Diabetes (14.3%), asthma (10.7%) and thyroid dysfunction (7.1%) affected these women with MTF; vitamin D levels were not routinely measured. Surgical interventions requiring anaesthesia were required in 57.1% with MTF: 50.0% during their second, 31.3% in their third and 12.5% in their first trimesters; 6.3% had surgery post partum. Pre-term birth and emergency caesarean section complicated 6/28 (21.4%) of MTF pregnancies. One patient received post-partum bisphosphonate therapy; only two 2/32 (6.25%) received medical follow-up. Fractures in pregnancy are uncommon. Lower limb fractures are frequently due to minimal trauma, and surgical intervention is often required. The low rate of medical follow-up in MTF is of concern and reinforces the need for greater recognition of potential osteoporosis in this population.