Detection of SARS-CoV-2-Specific IgA in the Human Milk of COVID-19 Vaccinated Lactating Health Care Workers.
Background: In 2019, a deadly virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID-19), emerged. In December 2020, two mRNA-based COVID-19 vaccines were approved for use in the United States, which provide immunity to those receiving the vaccine. Maternally derived antibodies are a key element of infants' immunity. Certain vaccines given to pregnant and lactating mothers provide immunity to infants through transmission across the placenta, umbilical cord (IgG), and human milk (IgA). Human milk produced by mothers with a history of COVID-19 infection contains SARS-CoV-2 IgA and IgG. The purpose of this study is to determine whether SARS-CoV-2-specific immunoglobulins are found in human milk after the COVID-19 vaccination, and to characterize the types of immunoglobulins present. Methods: This is a prospective observational study conducted at Shands Hospital, University of Florida, from December 2020 to March 2021. Twenty-two lactating health care workers who received the SARS-CoV-2 mRNA vaccine (Pfizer/BioNTech or Moderna) made up the sample group. Plasma and human milk were collected at three time points (prevaccination, post-first vaccine dose, and post-second vaccine dose). SARS-CoV-2-specific IgA and IgG in human milk and in plasma were measured by enzyme-linked immunosorbent assay (ELISA). Maternal demographics were compiled. Results: We found significant secretion of SARS-CoV-2-specific IgA and IgG in human milk and plasma after SARS-CoV-2 vaccination. Conclusions: Our results show that the mRNA-based COVID-19 vaccines induce SARS-CoV-2-specific IgA and IgG secretion in human milk. Further studies are needed to determine the duration of this immune response, its capacity to neutralize the COVID-19 virus, the transfer of passive immunity to breastfeeding infants, and the potential therapeutic use of human milk IgA to combat SARS-CoV-2 infections and COVID-19.


Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain.
Voltage-gated sodium (Nav) channels initiate action potentials in most neurons, including primary afferent nerve fibres of the pain pathway. Local anaesthetics block pain through non-specific actions at all Nav channels, but the discovery of selective modulators would facilitate the analysis of individual subtypes of these channels and their contributions to chemical, mechanical, or thermal pain. Here we identify and characterize spider (Heteroscodra maculata) toxins that selectively activate the Nav1.1 subtype, the role of which in nociception and pain has not been elucidated. We use these probes to show that Nav1.1-expressing fibres are modality-specific nociceptors: their activation elicits robust pain behaviours without neurogenic inflammation and produces profound hypersensitivity to mechanical, but not thermal, stimuli. In the gut, high-threshold mechanosensitive fibres also express Nav1.1 and show enhanced toxin sensitivity in a mouse model of irritable bowel syndrome. Together, these findings establish an unexpected role for Nav1.1 channels in regulating the excitability of sensory nerve fibres that mediate mechanical pain.


A translational approach to micro-inflammation in end-stage renal disease: molecular effects of low levels of interleukin-6.
Inflammation plays a key role in the progression of cardiovascular disease, the leading cause of mortality in ESRD (end-stage renal disease). Over recent years, inflammation has been greatly reduced with treatment, but mortality remains high. The aim of the present study was to assess whether low (<2 pg/ml) circulating levels of IL-6 (interleukin-6) are necessary and sufficient to activate the transcription factor STAT3 (signal transducer and activator of transcription 3) in human hepatocytes, and if this micro-inflammatory state was associated with changes in gene expression of some acute-phase proteins involved in cardiovascular mortality in ESRD. Human hepatocytes were treated for 24 h in the presence and absence of serum fractions from ESRD patients and healthy subjects with different concentrations of IL-6. The specific role of the cytokine was also evaluated by cell experiments with serum containing blocked IL-6. Furthermore, a comparison of the effects of IL-6 from patient serum and rIL-6 (recombinant IL-6) at increasing concentrations was performed. Confocal microscopy and Western blotting demonstrated that STAT3 activation was associated with IL-6 cell-membrane-bound receptor overexpression only in hepatocytes cultured with 1.8 pg/ml serum IL-6. A linear activation of STAT3 and IL-6 receptor expression was also observed after incubation with rIL-6. Treatment of hepatocytes with 1.8 pg/ml serum IL-6 was also associated with a 31.6-fold up-regulation of hepcidin gene expression and a 8.9-fold down-regulation of fetuin-A gene expression. In conclusion, these results demonstrated that low (<2 pg/ml) circulating levels of IL-6, as present in non-inflamed ESRD patients, are sufficient to activate some inflammatory pathways and can differentially regulate hepcidin and fetuin-A gene expression.


Extended L-shaped Spreader Graft for Correction of Combined Dorsal and Caudal Nasal Septal Deviations.
Although a wide range of surgical techniques have been proposed to straighten the deviated cartilaginous nasal dorsum and maximize nasal function, recurrence is common because of cartilage memory and scar contractures. An extended L-shaped spreader graft, a permanent support, was developed to correct functional and aesthetic problems, to prevent recurrence, and to maintain the correction of the septum stable and strong. This technique was utilized in 16 cases of deviated cartilaginous dorsum. All patients were subjected to a detailed history, physical examination, CT scan of the nose, and photographic documentation preoperatively. The patients were followed up during a period of 3 months to 4 years. According to physical examination, postoperative photography, and patients' satisfaction, the final results were categorized as excellent, good, or poor. The results were as follows: 14 patients (87.5%) were classified as excellent, as their noses were completely straight, and this was consistent with physical examination and postoperative photographs. Two patients (12.5%) were classified as good because there was a minimal residual deviation according to either photographs or clinical examinations. This minimal deformity was not experienced by the patients. In conclusion, consistent, reproducible results were achieved with using the autologous extended L-shaped spreader graft for controlling and maintenance of the dorsal and caudal septal deviation after correction. It is one piece of L-shaped graft of autogenous cartilage fixed to the original septal L-strut. It is regarded as an anatomical graft that provides sustained cephalocaudal support, preserves pliability of the lobule, and maintains stability as an independent stabilizer for the native strut.


[Lymphedema of the arm after mastectomy--symptom of a recurrence?].
From 1972 to 1976, 488 women suffering from cancer of the female breast underwent uniform surgical treatment (Rotter-Halsted-operation), no postoperative irradiation. In 62 cases (12,7%) a lymphoedema could be observed. The author holds the opinion that the oedema of the equilateral arm is caused by dissemination of cancer cells and depends on tumour stage and not the specific kind of treatment.


Antichirality Emergent in Type-II Weyl Phononic Crystals.
Chiral anomaly as the hallmark feature lies in the heart of the researches for Weyl semimetal. It is rooted in the zeroth Landau level of the system with an applied magnetic field. Chirality or antichirality characterizes the propagation property of the one-way zeroth Landau level mode, and antichirality means an opposite group velocity compared to the case of chirality. Chirality is commonly observed for Weyl semimetals. Interestingly, the type-II Weyl point, with the overtilted dispersion, may flip the chirality to the antichirality, which, however, is yet to be evidenced despite numerous previous experimental efforts. Here, we implement the type-II Weyl point in sonic crystals, and by creating the pseudomagnetic fields with geometric deformation, the chirality flip of zeroth Landau levels is unambiguously demonstrated. Our Letter unveils the novel antichiral transport in the presence of time-reversal symmetry, and paves the way toward the state-of-the-art manipulation of sound waves.


Coaching tailored by stages: A valuable educational strategy to achieve independence in research.
This study presents an individualized coaching approach tailored to the stages of proximity of promising scientists interested in becoming independently funded researchers in the context of a minority-serving institution. This strategy defined the participant's stage of proximity by their number of first-author publications in peer-reviewed journals and their track record in submitting research grants. We argue that coaching tailored by stages is an asset to maintain the enthusiasm, persistence, and positive attitude of promising scientists as they try to reach independent investigator status. Furthermore, this valuable educational approach supports the development of management and leadership skills in defined scientific domains.


Therapeutic targeting of polycomb and BET bromodomain proteins in diffuse intrinsic pontine gliomas.
Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brainstem tumor characterized by rapid and uniform patient demise. A heterozygous point mutation of histone H3 occurs in more than 80% of these tumors and results in a lysine-to-methionine substitution (H3K27M). Expression of this histone mutant is accompanied by a reduction in the levels of polycomb repressive complex 2 (PRC2)-mediated H3K27 trimethylation (H3K27me3), and this is hypothesized to be a driving event of DIPG oncogenesis. Despite a major loss of H3K27me3, PRC2 activity is still detected in DIPG cells positive for H3K27M. To investigate the functional roles of H3K27M and PRC2 in DIPG pathogenesis, we profiled the epigenome of H3K27M-mutant DIPG cells and found that H3K27M associates with increased H3K27 acetylation (H3K27ac). In accordance with previous biochemical data, the majority of the heterotypic H3K27M-K27ac nucleosomes colocalize with bromodomain proteins at the loci of actively transcribed genes, whereas PRC2 is excluded from these regions; this suggests that H3K27M does not sequester PRC2 on chromatin. Residual PRC2 activity is required to maintain DIPG proliferative potential, by repressing neuronal differentiation and function. Finally, to examine the therapeutic potential of blocking the recruitment of bromodomain proteins by heterotypic H3K27M-K27ac nucleosomes in DIPG cells, we performed treatments in vivo with BET bromodomain inhibitors and demonstrate that they efficiently inhibit tumor progression, thus identifying this class of compounds as potential therapeutics in DIPG.


Reversible membrane permeabilization of mammalian cells treated with digitonin and its use for inducing nuclear reprogramming by Xenopus egg extracts.
Plasma membranes can be reversibly permeabilized by Streptolysin O. The permeabilized cells can be reprogrammed and partially dedifferentiated in the cell-free system from egg extracts. However, the permeabilizing activity of Streptolysin O is not stable, and therefore it is difficult to control its activity. An alternative method for reversible permeabilization is useful for establishing a cell-free system. Here, we used a nonionic detergent, digitonin, for permeabilization. A low concentration of digitonin induced reversible permeabilization of the plasma membrane in bovine, mouse, and porcine somatic cells. The permeabilized cells were treated with Xenopus laevis egg extracts. The treated cells showed exchange of nuclear proteins from extracts such as incorporation of Xenopus-specific histone B4 and Lamin LIII into nuclei. After resealing of the membrane, the cells showed upregulation of OCT4, SOX2, and NANOG expression. Our results suggest that reversible permeabilization with digitonin can be used to induce nuclear reprogramming and to activate pluripotent genes by a cell-free system.


Imbalanced Coagulation in the Airway of Type-2 High Asthma with Comorbid Obesity.
Asthma is a common, chronic airway inflammatory disease marked by airway hyperresponsiveness, inflammation, and remodeling. Asthma incidence has increased rapidly in the past few decades and recent multicenter analyses have revealed several unique asthma endotypes. Of these, type-2 high asthma with comorbid obesity presents a unique clinical challenge marked by increased resistance to standard therapies and exacerbated disease development. The extrinsic coagulation pathway plays a significant role in both type-2 high asthma and obesity. The type-2 high asthma airway is marked by increased procoagulant potential, which is readily activated following damage to airway tissue. In this review, we summarize the current understanding of the role the extrinsic coagulation pathway plays in the airway of type-2 high asthma with comorbid obesity. We propose that asthma control is worsened in obesity as a result of a systemic and local airway shift towards a procoagulant and anti-fibrinolytic environment. Lastly, we hypothesize bariatric surgery as a treatment for improved asthma management in type-2 high asthma with comorbid obesity, facilitated by normalization of systemic procoagulant and pro-inflammatory mediators. A better understanding of attenuated coagulation parameters in the airway following bariatric surgery will advance our knowledge of biomolecular pathways driving asthma pathobiology in patients with obesity.


Molecular modelling of the peroxisome proliferator-activated receptor alpha (PPAR alpha) from human, rat and mouse, based on homology with the human PPAR gamma crystal structure.
The generation of homology models of human, rat and mouse peroxisome proliferator-activated receptor alpha (PPAR alpha) are reported, based on the recently published crystal structure of the human PPAR gamma ligand-binding domain (LBD) with bound ligand, rosiglitazone. It is found that a template of peroxisome proliferating fibrate drugs and related compounds can fit within the putative ligand-binding site of rat PPAR alpha, via contacts with amino acid residues which are consistent with their biological potency for peroxisome proliferation, site-directed mutagenesis experiments and with quantitative structure-activity relationship (QSAR) analysis studies. The experimental binding affinity of leukotriene B(4) (LTB(4)) for the mouse PPAR alpha agrees closely with the calculated value based on the modelled interactions, whereas selective PPAR alpha ligands such as clofibric acid are able to fit the human PPAR alpha binding site in agreement with reported site-directed mutagenesis information.


Medial meniscus anterior horn cyst: arthroscopic decompression.
Meniscus cysts are mostly seen with meniscus tears, and arthroscopic decompression of cysts is gaining great importance in their treatment. In this study, we present a medial meniscus anterior horn cyst without an accompanying tear in the meniscus. A 33-year-old male patient was seen with pain and a palpable mass in his right knee. He complained that the severity of the pain had increased over the previous year. After the clinical and radiologic examinations, a painless, fixed soft tissue mass averaging 4 x 5 cm was located just medial to tuberositas tibia. The cyst was decompressed arthroscopically. In the 18th month of follow up, the mass had totally disappeared and the patient had no pain. Medial meniscus cysts are seen nine times fewer than lateral meniscus cysts. They are mostly accompanied with meniscal tears. Total meniscectomy with arthrotomy, isolated cyst excision, cyst excision, and partial meniscectomy with arthrotomy and arthroscopic partial meniscectomy with cyst decompression are treatment modalities. Arthroscopic meniscal cyst decompression is an important treatment choice and should always be taken into consideration with low morbidity, short recovery period, low recurrence rate, preservation of range of motion, and permission for early mobilization and rehabilitation of the joint.


Infraclusion of primary molars: reports of cases.
A review of twenty-five patients (nine boys and sixteen girls with a mean age of 13.6 years) with infraclusion of primary molars is reported. There were thirty-two infracluded teeth, twenty-one (65.6 percent) maxillary primary molars and eleven (34.4 percent) mandibular primary molars. The primary first molar was found to be in infraclusion in four (12.5 percent) cases and the primary second molar in twenty-eight (87.5 percent) cases. Submergence was mild in fifteen cases, moderate in five, and severe in twelve. The permanent successor was lacking in four (12.5 percent) infracluded teeth. Aplasia of a nonsuccedaneous tooth was observed in four patients (more than one aplasia in three of them). Sixty-five percent of the teeth distal to the infracluded tooth had some degree of mesioversion, and 34.4 percent showed a distoversion of the mesial tooth. Twenty-one patients underwent orthodontic therapy because of malocclusion induced by the submerged tooth or for other reasons. A total of twenty-five (78.1 percent) teeth had to be extracted (surgical extraction in seventeen cases). An alveolotomy made to help the succedaneous tooth to erupt was necessary in ten cases.


Sound propagation from a ridge wind turbine across a valley.
Sound propagation outdoors can be strongly affected by ground topography. The existence of hills and valleys between a source and receiver can lead to the shielding or focusing of sound waves. Such effects can result in significant variations in received sound levels. In addition, wind speed and air temperature gradients in the atmospheric boundary layer also play an important role. All of the foregoing factors can become especially important for the case of wind turbines located on a ridge overlooking a valley. Ridges are often selected for wind turbines in order to increase their energy capture potential through the wind speed-up effects often experienced in such locations. In this paper, a hybrid calculation method is presented to model such a case, relying on an analytical solution for sound diffraction around an impedance cylinder and the conformal mapping (CM) Green's function parabolic equation (GFPE) technique. The various aspects of the model have been successfully validated against alternative prediction methods. Example calculations with this hybrid analytical-CM-GFPE model show the complex sound pressure level distribution across the valley and the effect of valley ground type. The proposed method has the potential to include the effect of refraction through the inclusion of complex wind and temperature fields, although this aspect has been highly simplified in the current simulations.This article is part of the themed issue 'Wind energy in complex terrains'.


Identification and quantitative GLC determination of iproniazid in human urine.
A GLC method for the specific identification and quantitation of iproiazid, a potent monamine oxidase inhibitor drug, is described. The free drug isolated from urine samples by two-phase extraction reinforced with salting out. Identification and quantitative determination at the microgram level are done on aliquots of the chloroform extract by GLC, using the 2-butyl analog as an internal standard. Iproniazid and potentially interfering compounds present in the extracts are also identified by GLC-mass spectrometry and TLC for supporting evidence of the GLC method's specificity.


Low-dose-rate total lymphoid irradiation: a new method of rapid immunosuppression.
Total Lymphoid Irradiation (TLI) has been successful in inducing immunosuppression in experimental and clinical applications. However, both the experimental and clinical utility of TLI are hampered by the prolonged treatment courses required (23 days in rats and 30-60 days in humans). Low-dose-rate TLI has the potential of reducing overall treatment time while achieving comparable immunosuppression. This study examines the immunosuppressive activity and treatment toxicity of conventional-dose-rate (23 days) vs low-dose-rate (2-7 days) TLI. Seven groups of Lewis rats were given TLI with 60Co. One group was treated at conventional-dose-rates (80-110 cGy/min) and received 3400 cGy in 17 fractions over 23 days. Six groups were treated at low-dose-rate (7 cGy/min) and received total doses of 800, 1200, 1800, 2400, 3000, and 3400 cGy over 2-7 days. Rats treated at conventional-dose-rates over 23 days and at low-dose-rate over 2-7 days tolerated radiation with minimal toxicity. The level of immunosuppression was tested using allogeneic (Brown-Norway) skin graft survival. Control animals retained allogeneic skin grafts for a mean of 14 days (range 8-21 days). Conventional-dose-rate treated animals (3400 cGy in 23 days) kept their grafts 60 days (range 50-66 days) (p less than .001). Low-dose-rate treated rats (800 to 3400 cGy total dose over 2-7 days) also had prolongation of allogeneic graft survival times following TLI with a dose-response curve established. The graft survival time for the 3400 cGy low-dose-rate group (66 days, range 52-78 days) was not significantly different from the 3400 cGy conventional-dose-rate group (p less than 0.10). When the total dose given was equivalent, low-dose-rate TLI demonstrated an advantage of reduced overall treatment time compared to conventional-dose-rate TLI (7 days vs. 23 days) with no increase in toxicity. This was accomplished without compromise of the immunosuppressant activity of TLI as demonstrated by comparable allogeneic skin graft survival times between the two 3400 cGy treatment groups. This clinical advantage would prove to be beneficial where immediate suppression of the immune system is desirable.


Recombination hotspot associated factors specifically recognize novel target sequences at the site of interchromosomal rearrangements in T-ALL patients with t(8;14)(q24;q11) and t(1;14)(p32;q11).
A DNA binding protein was identified which binds to two novel target-like sequences: (i) at the 5' flanking site of the breakpoint junction of chromosome 8 in a patient with T-acute lymphoblastic leukemia (ALL) carrying the t(8;14)(q24;q11) rearrangement and (ii) on chromosome 1 in three of five T-ALL patients with the t(1;14)(p32;q11) rearrangement. This protein [provisionally called recombination hotspot associated factor (ReHF-1)] was also found to bind to a similar target sequence that is present immediately at the 3' end of the human V delta 3 gene segment. In a small number of lines tested, the ReHF-1 protein was expressed in gamma delta lineage T cells and in a number of B cell precursor ALLs whose TCR delta locus has been rearranged. The molecular weight of ReHF-1 protein was determined to be approximately 30 kDa by UV cross-linking analysis. Gel filtration chromatography and sedimentation velocity centrifugation analyses indicate that the ReHF-1 protein exists as a multimeric protein in its native form. These data might suggest a possible role for this protein in the rearrangement of the TCR delta locus. Furthermore, another protein, ReHF-2, that appears to have strict sequence specificity was found to bind only to the complementary single strand of the target sequence. The interaction of these proteins with a conserved target sequence at the chromosomal breakpoint junction might suggest that they are involved in a novel enzymatic mechanism reminiscent of the general features of DNA recombination or replication events in Escherichia coli or Saccharomyces cerevisiae.


Monoclonal antibody EG2 does not provide reliable immunohistochemical discrimination between resting and activated eosinophils.
The monoclonal antibody (mAb) EG2 has been considered to identify activated eosinophils and several immunohistochemical reports of EG2+ eosinophils in various allergic and other inflammatory disorders have suggested an important pathogenic role for such cells. This study showed that cellular EG2 reactivity, both in peripheral blood and mucosal tissue preparations, depends mainly on the method of sample preparation. Nearly 100% of blood eosinophils from normal individuals were strongly EG2+ when prepared by formalin fixation, whereas only a fraction reacted in the unfixed (64%) or acetone-fixed (60%) state. A significantly increased (p < 0.03) number of EG2+ cells were likewise detected in cryo-sections of inflamed nasal mucosa after formalin fixation compared with acetone fixation. Moreover, virtually all eosinophils were EG2+ in cryo-sections of normal jejunal mucosa fixed in periodate-lysine-(0.5%) paraformaldehyde prior to freezing. Conversely, EG2 reacted only weakly, or failed to react, with many eosinophils in cryo-material not subjected to such pre-fixation, in contrast to adjacent non-eosinophilic cells which were brightly stained. Two-colour immunofluorescence consistently revealed overlapping labelling with EG2 and mAb EG1 or a polyclonal antibody to eosinophil cationic protein in sections of formalin-fixed, paraffin-embedded normal gastrointestinal mucosa. Our findings thus showed that EG2 does not provide reliable immunohistochemical discrimination between resting and activated eosinophils. When optimal pre-fixation of tissue specimens was omitted, EG2 reactivity appeared to be caused, at least in part, by leached antigen adsorbed to adjacent non-eosinophilic cells.


Interacting ultracold bosons in disordered lattices: sensitivity of the dynamics to the initial state.
We study the dynamics of a nonlinear one-dimensional disordered system obtained by coupling the Anderson model with the Gross-Pitaevskii equation. We introduce a single quantity globally characterizing the localization of the system. This quantity obeys a scaling law with respect to the width of the initial state, which can be used to characterize the dynamics independently of the initial state.


Survival of Salmonella in Tea Under Different Storage Conditions and Brewing Methods.
Salmonella is one of the leading causes of bacterial gastroenteritis. High prevalence of Salmonella in environment is partially due to its ability to enter the "viable but non-culturable" (VBNC) state when they encounter unfavorable conditions. Dried teas are traditionally believed to have a low risk of causing salmonellosis. This study investigated the survival of Salmonella in four types of dried teas under different storage conditions and brewing methods. A method that coupled propidium monoazide (PMA) and quantitative PCR was optimized to quantify VBNC Salmonella cells to assess the risk of Salmonella contamination in teas after brewing. Each tea sample was inoculated with Salmonella at an 8 log CFU/ml concentration and stored at 4, 10, and 25°C. Under three storage conditions, the number of survived Salmonella was highest in teas stored at 4°C and lowest in teas stored at 25°C. After storage of 120 days, culturable Salmonella was detected from all samples ranging from 6-7 log CFU/g (4°C storage) to 3-4 log CFU/g (25°C storage). The effectiveness of brewing methods in inactivating Salmonella was assessed by brewing inoculated teas at room temperature, 55, 75, and 100°C for 10 min. Brewing teas at 75 and 100°C significantly (P < 0.05) reduced the number of viable Salmonella, but VBNC Salmonella formed when brewed at 75°C. Altogether, Salmonella can persist in dried teas for over 3 months at a temperature ranging from 4 to 25°C, and thermal treatment delivered during home brewing may not eradicate Salmonella in teas.


MOLECULAR INVESTIGATION OF HEMOTROPIC MYCOPLASMAS IN HUMAN BEINGS, DOGS AND HORSES IN A RURAL SETTLEMENT IN SOUTHERN BRAZIL.
The aims of this study were to determine the prevalence of hemoplasmas in a rural Brazilian settlement's population of human beings, their dogs and horses, highly exposed to tick bites; to identify the tick species parasitizing dogs and horses, and analyze factors associated with their infection. Blood samples from 132 dogs, 16 horses and 100 humans were screened using a pan-hemoplasma SYBR green real-time PCR assay followed by a species-specific TaqMan real-time PCR. A total of 59/132 (44.7%) dog samples were positive for hemoplasmas (21 Mycoplasma haemocanis alone, 12 ' Candidatus Mycoplasma haematoparvum' alone and 21 both). Only 1/100 (1.0%) human sample was positive by qPCR SYBR green, with no successful amplification of 16S rRNA or 23 rRNA genes despite multiple attempts. All horse samples were negative. Dogs >1 year of age were more likely to be positive for hemoplasmas ( p= 0.0014). In conclusion, although canine hemoplasma infection was highly prevalent, cross-species hemoplasma transmission was not observed, and therefore may not frequently occur despite overexposure of agents and vectors.


Prevention of postshunting ventricular asymmetry by transseptal placement of ventricular catheters. A randomized study.
Ventricular asymmetry is common after ventricular shunting, and occasionally isolation of the contralateral ventricle necessitates a second shunt. The following study was performed to determine whether contralateral placement of the ventricular catheter via ultrasound-guided perforation of the septum pellucidum would decrease the incidence of postshunting ventricular asymmetry which might predispose to symptomatic isolation of a lateral ventricle. Fifty-eight children with hydrocephalus and an open fontanel, who were having a ventriculo-peritoneal shunt via a parieto-occipital approach, were randomized to have the ventricular catheter tip placed into either the ipsilateral or the contralateral frontal horn. Ventricular asymmetry occurred in 23% of the patients with contralateral versus 54% with ipsilateral placement (chi 2 = 5.53; p = 0.019). In 7 patients with contralateral placement, in whom a special catheter with two sets of holes was used, such that holes were located in both ventricles, no shunt-related ventricular asymmetry occurred. In 2 children with ipsilateral placement, a second shunt was required for a symptomatic isolated lateral ventricle. Perforation of the septum pellucidum with placement of the ventricular catheter in the contralateral ventricle, using a specially designed catheter with two sets of holes, may decrease the incidence of postshunting ventricular asymmetry and symptomatic isolation of a lateral ventricle.


[Wilson disease: clinical and biological aspects].
Wilson disease is an autosomal recessive disorder of copper excess. This illness results from mutations of the ATP7B gene (chromosome 13, MIM# 277900). The discovery of the gene allowed a better understanding of cytosolic copper trafficking and its relationship with ceruloplasmin synthesis. Symptomatic patients may present with hepatic, neurologic or psychiatric forms. Clinical and phenotypic evidences provide only presumptive arguments for this disease which can be routinely assessed by molecular analysis. This genetic disease which can be efficiently treated was formerly biologically suspected after a careful but sometimes invasive study of copper metabolism. Genetic advances can now give a definite answer using linkage analysis and research for disease-causing mutations. However, this diagnosis strategy is limited since currently over 320 mutations and 80 polymorphisms have been currently identified.


Lack of effect of colony-stimulating factors, interleukins, interferons, and tumor necrosis factor on the growth and differentiation of cultured Reed-Sternberg cells. Comparison with effects of phorbol ester and retinoic acid.
The neoplastic Hodgkin's Reed-Sternberg (H-RS) cells in Hodgkin's disease are surrounded in vivo by abundant reactive cells, the function of which may be attributed in part to their elaboration of various cytokines. Thus, a study of the interaction of H-RS cells with exogenous cytokines may provide information as to the mechanism of the clinical and histopathologic changes observed in Hodgkin's disease. This study examined the effect of various cytokines, and of phorbol ester (TPA) and retinoic acid, on the differentiation and proliferation of cultured H-RS cells (cell lines HDLM-1 and KM-H2). In addition, it was determined whether these cells were able to secrete cytokines after being treated with exogenous cytokines. The cytokines used included various types of interleukins (1, 2, and 3), colony-stimulating factors (GM, G, and M), interferons (alpha, beta, and gamma), and tumor necrosis factor (alpha). It was found that these cytokines, used alone or in combination, were not effective in modulating the proliferation and differentiation of cells, or the production of cytokines, in cultured H-RS cells. In contrast, this study revealed that retinoic acid can potentiate TPA-induced growth inhibition in cultured H-RS cells. Retinoic acid, when used alone, exhibited a minimal effect on cell differentiation. No synergistic effects of cytokines and retinoic acid on H-RS cells were observed. The failure of cultured H-RS cells to respond to exogenous cytokines suggests that, during the course of neoplastic transformation, of progression of disease, or of establishment of the cells in culture, H-RS cells lose their dependence on cytokines, although they retain the capacity to produce various cytokines.


First report of carglumic acid in a patient with citrullinemia type 1 (argininosuccinate synthetase deficiency).
Carglumic acid is a structural analogue of human N-acetylglutamate, which has become an alternative therapeutic option for hyperammonaemia in organic acidaemias such as isovaleric acidaemia, methylmalonic acidaemia and propionic acidaemia, and it has been suggested in other urea cycle disorders such as ornithine transcarbamylase deficiency and carbamoyl phosphate synthetase 1 deficiency. A male newborn was diagnosed with citrullinemia after serum amino acid analyses revealed markedly elevated citrulline concentration together with homozygous p.Gly390Arg mutation in ASS1 gene. The ammonia concentration decreased and blood gas analysis normalized after peritoneal dialysis was performed for three days. Also, sodium benzoate, L-arginine and parenteral nutrition with glucose and lipid therapy were initiated. Until 1 year of age, low adherence to sodium benzoate therapy due to unpleasant taste caused hyperammonaemic episodes and obligated us to initiate carglumic acid (100 mg/kg/day) therapy. During treatment with carglumic acid, the median ammonia level was 45.6 µmol/L. The patient's treatment was switched from carglumic acid to sodium phenylbutyrate when he was 4.5 years old. Currently, the patient is 6.5 years old and remains under follow-up with sodium phenylbutyrate, L-arginine and protein-restricted diet. Plasma ornithine level was found to be significantly lower during the carglumic acid treatment compared to other treatments (P=.039). Also, glutamic acid was found to be higher during the sodium benzoate treatment period compared to other treatment periods (P=.024). To the best of our knowledge, this is the first report describing the long-term use of carglumic acid in a patient with argininosuccinate synthetase deficiency.


Investigations with monoclonal antibody drug (anthracycline) conjugates.
The development of monoclonal antibody-drug (anthracycline) conjugates (immunocytostatics) that has emerged during the last decade is briefly reviewed. Stress is layed on the various procedures that have been employed for the chemical attachment of daunorubicin (daunomycin) and doxorubicin (adriamycin) to spacers, high-molecular weight carrier molecules, and immunoglobulins. Anthracycline conjugates that have proved effective in mice with respect to the treatment of cancer are especially evaluated. Also a new method developed for the conjugation of rhodosaminyl anthracyclinones via a hydrolysable spacer, developed in our laboratories, is briefly communicated. Finally, import aspects for further developments of monoclonal antibody-drug conjugates are discussed.


Economic evaluation of urgent-start peritoneal dialysis versus urgent-start hemodialysis in the United States.
Patients presenting late in the course of kidney disease who require urgent initiation of dialysis have traditionally received temporary vascular catheters followed by hemodialysis. Recent changes in Medicare payment policy for dialysis in the USA incentivized the use of peritoneal dialysis (PD). Consequently, the use of more expeditious PD for late-presenting patients (urgent-start PD) has received new attention. Urgent-start PD has been shown to be safe and effective, and offers a mechanism for increasing PD utilization. However, there has been no assessment of the dialysis-related costs over the first 90 days of care. The objective of this study was to characterize the costs associated with urgent-start PD, urgent-start hemodialysis (HD), or a dual approach (urgent-start HD followed by urgent-start PD) over the first 90 days of treatment from a provider perspective. A survey of practitioners from 5 clinics known to use urgent-start PD was conducted to provide inputs for a cost model representing typical patients. Model inputs were obtained from the survey, literature review, and available cost data. Sensitivity analyses were also conducted. The estimated per patient cost over the first 90 days for urgent-start PD was $16,398. Dialysis access represented 15% of total costs, dialysis services 48%, and initial hospitalization 37%. For urgent-start HD, total per patient costs were $19,352, and dialysis access accounted for 27%, dialysis services 42%, and initial hospitalization 31%. The estimated cost for dual patients was $19,400. Urgent-start PD may offer a cost saving approach for the initiation of dialysis in eligible patients requiring an urgent-start to dialysis.


Waldenström Macroglobulinemia: Review of Pathogenesis and Management.
Waldenström macroglobulinemia (WM) is a low-grade B-cell clonal disorder characterized by lymphoplasmacytic bone marrow involvement associated with monoclonal immunoglobulin M. Although WM remains to be an incurable disease with a heterogeneous clinical course, the recent discovery of mutations in the MYD88 and CXCR4 genes further enhanced our understanding of its pathogenesis. Development of new therapies including monoclonal antibodies, proteasome inhibitors, and Bruton tyrosine kinase inhibitors have made the management of WM increasingly complex. Treatment should be tailored to the individual patient while considering many clinical factors. The clinical outcomes are expected to continue to improve, given the emergence of novel therapeutics and better understanding of the underlying pathogenesis.


Insights Into the Role of Collagen in Vocal Fold Health and Disease.
As one of the key fibrous proteins in the extracellular matrix, collagen plays a significant role in the structural and biomechanical characteristics of the vocal fold. Anchored fibrils of collagen create secure structural regions within the vocal folds and are strong enough to sustain vibratory impact and stretch during phonation. This contributes tensile strength, density, and organization to the vocal folds and influences health and pathogenesis. This review offers a comprehensive summary for a current understanding of collagen within normal vocal fold tissues throughout the life span as well as vocal pathology and wound repair. Further, collagen's molecular structure and biosynthesis are discussed. Finally, collagen alterations in tissue injury and repair and the incorporation of collagen-based biomaterials as a method of treating voice disorders are reviewed.


siRNA directed against survivin enhances pancreatic cancer cell gemcitabine chemosensitivity.
Survivin is known to be overexpressed in various human malignancies, including pancreatic cancer, and to cause resistance to radiation and chemotherapy, so the regulation of this molecule could be a new strategy for treating pancreatic cancer. In our study, a short interfering RNA (siRNA) plasmid expression vector against survivin was constructed and transfected into human pancreatic cancer cell lines of Panc-1 and BxPC3. The expression of survivin mRNA and protein among the stable transfected cells and the untransfected cells was detected by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot, respectively. Tumor cell growth in vitro was assessed by trypan blue exclusion. The cell cycle distribution and cell apoptosis were measured by flow cytometry. The cytotoxicity assay was measured by the MTT test. Our results showed that survivin siRNA treatment caused a specific and profound decrease of survivin mRNA and protein that was associated with decreased cell growth, spontaneous apoptosis, and a specific G0/G1 arrest. Furthermore, the suppression of survivin can enhance the chemosensitivity of pancreatic cancer cells to gemcitabine significantly. We suggest that the RNAi against survivin gene strategy would be a potential approach to chemosensitization therapy in human pancreatic cancer.


Directed Self-Assembly of Templatable Block Copolymers by Easily Accessible Magnetic Control.
Magnetic control has been a prosperous and powerful contactless approach in arraying materials into high-order nanostructures. However, it is tremendously difficult to control organic polymers in this way on account of the weak magnetic response. The preparation of block copolymers (BCPs) with high magnetostatic energy is reported here, relying on an effective electrostatic coupling between paramagnetic ions and polymer side chains. As a result, the BCPs undergo a magnetically directed self-assembly to form microphase-segregated nanostructures with long-range order. It is emphasized that such a precisely controlled alignment of the BCPs is performed upon a single commercial magnet with low-intensity field (0.35 Tesla). This strategy is profoundly easy-to-handle in contrast to routine electromagnetic methods with high-intensity field (5-10 Tesla). More significantly, the paramagnetic metal component in the BCP samples can be smartly removed, providing a template effect with a preservation of the directed self-assembled nanofeatures for patterning follow-up functionalized species through the original binding site.


[First experiences with the Visante apparatus].
The apparatus Visante (Zeiss) was tested on the group of 37 eyes with selected findings. This apparatus enables to visualize the anterior segment of the eye by means of OCT imaging. The main asset of the new imaging method is the accuracy of the image and the possibility to depict exactly the corneo-scleral angle and the artificial structures in the anterior chamber of the eye. The main advantage of the new apparatus is especially the imaging and measurement of the anterior segment structures of the eye in glaucoma and artificial structures in the anterior chamber and corneo-scleral angle of the eye


Efficacy and safety of apatinib plus docetaxel as the second or above line treatment in advanced nonsquamous NSCLC: A multi center prospective study.
Apatinib is an oral small-molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR-2). Some clinical trials have demonstrated that apatinib is efficacious against advanced nonsquamous NSCLC. This study aimed to probe efficacy and safety of apatinib plus docetaxel, as the second or above line treatment, in advanced nonsquamous NSCLC. Multicenter, prospective, single arm study. Three teaching hospitals centers in the Sichuan. Fourteen patients with stage IVA/B nonsquamous NSCLC had previously received at least 1 platinum-based chemotherapy regimen. Patients who were enrolled between November 2016 and January 2018 were given docetaxel (75 mg/m, i.v., d1) plus oral apatinib (250 mg/d), 4 weeks as one cycle, until disease progression or intolerance to adverse events (AE). The primary endpoint was progression-free survival (PFS). The secondary endpoints comprised objective response rate (ORR), disease control rate (DCR), overall survival (OS), and AE incidence rate. All patients carried adenocarcinoma by pathological type. The median follow-up duration was 9.76 months. Out of 14 cases, 12 were evaluable, showing ORR of 33.33%, DCR of 66.67%, DCR of 50% in cases with brain metastasis, median PFS of 2.92 months (95% CI: 1.38-4.48), and 6-month OS of 80%. Primary AEs encompassed: leukopenia in 7 cases (58.33%), hand-foot skin reaction in 5 cases (41.67%), and diarrhea in 4 cases (33.33%). Among them, grade 3 AEs were: leukopenia in 4 cases (33.33%), and hand-foot skin reaction in 1 case (8.33%). No grade 4/5 AEs were reported. Univariate and multivariate analysis were conducted respectively for PFS and OS. These factors encompassed: gender, age, gene mutations, clinical stage, ECOG scores, quantity of metastatic foci, brain metastasis, and hand-foot skin reaction. Results demonstrated zero risk factors for PFS or OS. Apatinib plus docetaxel, as the second or above line treatment, is effective and safe against advanced nonsquamous NSCLC, with good tolerance profile. NCT03416231.


A Novel Wheat C-bZIP Gene, TabZIP14-B, Participates in Salt and Freezing Tolerance in Transgenic Plants.
The group C-bZIP transcription factors (TFs) are involved in diverse biological processes, such as the regulation of seed storage protein (SSP) production and the responses to pathogen challenge and abiotic stress. However, our knowledge of the abiotic functions of group C-bZIP genes in wheat remains limited. Here, we present the function of a novel TabZIP14-B gene in wheat. This gene belongs to the group C-bZIP TFs and contains six exons and five introns; three haplotypes were identified among accessions of tetraploid and hexaploid wheat. A subcellular localization analysis indicated that TabZIP14-B was targeted to the nucleus of tobacco epidermal cells. A transactivation assay demonstrated that TabZIP14-B showed transcriptional activation ability and was capable of binding the abscisic acid (ABA) responsive element (ABRE) in yeast. RT-qPCR revealed that TabZIP14-B was expressed in the roots, stems, leaves, and young spikes and was up-regulated by exogenous ABA, salt, low-temperature, and polyethylene glycol (PEG) stress treatments. Furthermore, Arabidopsis plants overexpressing TabZIP14-B exhibited enhanced tolerance to salt, freezing stresses and ABA sensitivity. Overexpression of TabZIP14-B resulted in increased expression of the AtRD29A, AtCOR47, AtRD20, AtGSTF6, and AtRAB18 genes and changes in several physiological characteristics. These results suggest that TabZIP14-B could function as a positive regulator in mediating the abiotic stress response.


A study of impact of shift work on fatigue level of workers in a sanitary-ware factory using a fuzzy set model.
Work generally affects workers in terms of both physical and mental health. Workers must adapt their life pattern to match shift-work styles which can result in family problems, increased fatigue level, lower work efficiency, higher accident rate, illnesses, and lower productivity. The project obtained an entry permission to study the impact of shift work on fatigue level of workers in a sanitary-ware factory. The objectives were: 1) to evaluate fatigue levels of workers who worked in the morning shift and night shift, and 2) to prioritize contributing factors affecting fatigue levels using a model of fuzzy set theory. Twelve male workers participated in the study. Four subjects were recruited from each of 3 departments, i.e., glazing, baking and quality inspection. The measurement was conducted before and after the shift for both shifts. Variables included heart rate monitoring throughout the work shift, critical flicker fusion frequency, reaction time response, hand-grip strength, and wet-bulb globe temperature. Results were analyzed using a computerized statistical package. It was concluded from this study that mental fatigue from working in the morning shift was significantly higher than the one for working in the night shift. The same indication was also true in the case of physical fatigue, though it was not statistically significant. From the fuzzy set analysis, it was confirmed that working in the morning shift resulted in a higher fatigue level than working in the night shift and the temperature of the work environment was the most important factor contributing to the higher fatigue level.


Growth performance, immune response, and digestive enzyme activity in Pacific white shrimp, Penaeus vannamei Boone, 1931, fed dietary microbial lysozyme.
The present study investigates the effects of the dietary microbial lysozyme (ML) as an immunostimulant, on the growth performance, some immune parameters and digestive enzyme of Pacific white shrimp, Penaeus vannamei. Six hundred shrimps were obtained and randomly allocated into four groups as follows with three replicates. The shrimps were fed diets supplemented with 0 (control), 0.5, 1, and 2 g kg-1 ML for 4 months. The results indicated that dietary supplementation of ML significantly improved final weight, weight gain, average daily weight gain rate (ADG), feed conversion rate (FCR), and feed efficiency rate (FER) compared to the control (P ˂ 0.05). However, weight gain specific growth rate (SGR) and survival rate were not significantly affected by dietary ML (P ˃ 0.05). Dietary ML had a progressive effects on some immune parameters status including total antioxidant capacity (TAOC), superoxide dismutase (SOD), glutathione peroxidase (GPX), lysozyme (LYZ), alkaline phosphatase (ALP), phenoloxidase (PO) and acid phosphatase (ACP) activity as well as differential haemocyte count (DHC) and total haemocyte count (THC), in shrimps treated with the lysozyme than untreated shrimps (P ˂ 0.05). However, feeding with ML had no significant effect on plasma malondialdehyde (MDA) level (P ˃ 0.05). Furthermore, intestinal digestive enzymes (lipase, protease, and amylase) in shrimp fed with dietary ML were significantly (P ˂ 0.05) higher than those fed with non-supplemented control basal diet. Thus, the results indicate that oral administration of ML can be recommended for shrimp feed to improve immune response as well digestive enzymes activity modulation.


Protein restriction in hepatic encephalopathy is appropriate for selected patients: a point of view.
Since the late nineteenth century, protein restriction has been shown to improve hepatic encephalopathy. However, malnutrition has been described in up to 60 % of cirrhotic patients and is associated with increased mortality. Furthermore, emerging clinical evidence has revealed that a large proportion of cirrhotic patients may tolerate normal protein intake. However, approximately one third of cirrhotic patients with hepatic encephalopathy may need a short course of protein restriction, in addition to maximum medical therapy, to ameliorate the clinical course of their hepatic encephalopathy. For patients with chronic hepatic encephalopathy who are protein-sensitive, modifying their sources of nitrogen by using more vegetable protein, less animal protein, and branched-chain amino acids may improve their encephalopathy without further loss of lean body mass. In conclusion, among cirrhotics with hepatic encephalopathy, modulation of normal protein intake must take into account the patient's hepatic reserve, severity of hepatic encephalopathy, and current nutritional status.


Role of wet experiment design in data generation: from in vivo to in silico and back.
A thorough understanding of the in vivo kinetics of microorganisms requires the analysis of different data sets and therefore needs support from different sources of genome, transcriptome, proteome and metabolome data, as well as to generate new data in the laboratory to depict cell phenotypes in different scenarios. The value of dynamic metabolic data depends on the adequate design of wet experiments. In this paper a schematic representation of wet dynamic experiments to generate data is discussed. As a case study, the linking of the central metabolism with the carnitine secondary metabolism in E. coli is presented. The feed-back between the data generated and in silico modeling helps our understanding of the Escherichia coli expressed phenotype and permits new wet experiments to be designed to generate data concerning metabolic optimization.


Varenicline induces manic relapse in bipolar disorder.
Varenicline (Chantix) is commonly used to assist individuals with smoking cessation. This medication is known to affect mood and behavior. We report a patient with bipolar disorder who developed manic relapse after starting treatment with varenicline for tobacco dependence. Further research is necessary to establish the safety of using varenicline in individuals who have significant mental illness and want to stop smoking.


Persistent pain is common 1-2 years after shoulder replacement.
Persistent postsurgical pain is a well-recognized problem after various types of surgery such as amputation and thoracotomy. The prevalence of persistent pain, and the extent to which it involves neuropathic pain, is highly dependent on the type of surgery. We investigated the prevalence of, characteristics of, and risk factors for persistent pain 1-2 years after shoulder replacement. A questionnaire was sent to patients who underwent primary shoulder replacement between April 2011 and April 2012, and whose data were recorded in the Danish Shoulder Arthroplasty Register. Patients who had undergone reoperation or bilateral replacements were excluded. Persistent pain was defined as constant or daily pain within the last month, which interfered much or very much with daily activities. Multivariate logistic regression was used to assess risk factors. 538 patients were available for analysis. The prevalence of persistent pain was 22% (CI: 18-25), and the prevalence of presumed neuropathic pain was 13% (CI: 10-16). Persistent pain was more frequent in fracture patients (29%) than in osteoarthritis patients (16%), while the prevalence of neuropathic pain was similar. Severe pain during the first postoperative week increased the risk of persistent pain. Risk also increased with hemiprosthesis (as compared to total prosthesis) in osteoarthritis patients, and with previous osteosynthesis and pain elsewhere in fracture patients. Persistent pain after shoulder replacement is a daily burden for many patients. Further studies should address patient and prosthesis selection, postoperative pain management, and follow-up of these patients.


[A Case of Serous Retinal Detachment after Encorafenib, Binimetinib, and Cetuximab Treatment for BRAF V600E Mutant Colorectal Cancer].
The patient was a 72-year-old man with a chief complaint of abdominal pain. We performed laparoscopic left hemicolectomy of the colon after descending colon cancer ileus stenting, and postoperative pathology was pT4aN0M0, pStage Ⅱb. In 1.5 years postoperatively, 2 liver metastases and 1 lymph node metastasis were found, and each was resected. Chemotherapy was initiated for multiple lung metastases. Genetic testing was positive for BRAF V600E mutation, and the patient received 8 mFOLFOXIRI plus bevacizumab therapy courses. After 15 5-FU plus LV plus bevacizumab courses, the patient had a brain infarction and lung metastasis reincreased. Chemotherapy was changed to encorafenib plus binimetinib plus cetuximab. On day 2, visual impairment was observed, and serous retinal detachment CTCAE Grade 2 was diagnosed. On day 7, the symptoms improved and one-step dose reduction was resumed. On day 2 of re-treatment, serous retinal detachment recurred and treatment was discontinued. On day 4 of re-treatment, the symptoms improved, another dose reduction was performed, and treatment was resumed. Since subjective MEK inhibitor-induced ocular symptoms are often minor, conducting an interview and early ophthalmologic diagnosis is recommended.


Popliteal cyst before William Baker: first report in the Galenic Corpus.
A popliteal cyst, also known as Baker cyst, is a benign fluctuant swelling of the gastrocnemius-semimembranosus bursa in the popliteal fossa at the back of the knee. The cyst is named after William Morrant Baker, who is considered to have first described this fluid collection with new sac formation outside of the knee-joint in 1877. We herein present a short description contained in the Galenic Corpus that appears to match to what we now call the Baker cyst. Α thorough survey of Kühn's Galenic Corpus was performed. The 14th book of Kühn's edition contains a brief review of all the anatomical structures and pathologies. In the 17th chapter of this treatise, devoted to skin lesions, the author states that steatomas appear in the popliteal fossa. However, it is no more believed to reflect the Galenic teaching and is ascribed to Pseudo-Galen. With regard to the descriptions survived and the anatomy knowledge in the post-Galenic era time, the brief report of the ancient text of unknown origin, appears to match what we now describe as popliteal cyst.


Individual, contextual and network characteristics of blood donors and non-donors: a systematic review of recent literature.
The ageing population and recent migration flows may negatively affect the blood supply in the long term, increasing the importance of targeted recruitment and retention strategies to address donors. This review sought to identify individual, network and contextual characteristics related to blood donor status and behaviour, to systematically discuss differences between study results, and to identify possible factors to target in recruitment and retention efforts. The systematic review was conducted in accordance with a predefined PROSPERO protocol (CRD42016039591). After quality assessments by multiple independent raters, a final set of 66 peer-reviewed papers, published between October 2009 and January 2017, were included for review. Individual and contextual characteristics of blood donor status and behaviour were categorised into five main lines of research: donor demographics, motivations and barriers, adverse reactions and deferral, contextual factors, and blood centre factors. Results on donor demographics, motivations and barriers, and contextual factors were inconclusive, differing between studies, countries, and sample characteristics. Adverse reactions and deferral were negatively related to blood donor behaviour. Blood centre factors play an important role in donor management, e.g., providing information, reminders, and (non-)monetary rewards. No studies were found on network characteristics of (non-)donors. Although individual and contextual characteristics strongly relate to blood donor status and behaviour, mechanisms underlying these relations have not been studied sufficiently. We want to stress the importance of longitudinal studies in donor behaviour, exploring the role of life events and network characteristics within blood donor careers. Increased understanding of donor behaviour will assist policy makers of blood collection agencies, with the ultimate goal of safeguarding a sufficient and matching blood supply.


DNA-mediated transfection as a model for oncogenesis.
DNA transfer technology has greatly contributed to progress in understanding molecular biology and genetics. In recent years, great efforts have been expended to determine the oncogenic potential of single, defined genes or complex gene mixtures as a prelude to defining the role those genes may play in neoplastic transformation in vitro and tumor induction in vivo. This paper reviews the currently available DNA transfection techniques and their application toward understanding cancer initiation and progression, and how the in vitro and animal models may apply to human cancer.


Emissions of sulfur trioxide from coal-fired power plants.
Emissions of sulfur trioxide (SO3) are a key component of plume opacity and acid deposition. Consequently, these emissions need to be low enough to not cause opacity violations and acid deposition. Generally, a small fraction of sulfur (S) in coal is converted to SO3 in coal-fired combustion devices such as electric utility boilers. The emissions of SO3 from such a boiler depend on coal S content, combustion conditions, flue gas characteristics, and air pollution devices being used. It is well known that the catalyst used in the selective catalytic reduction (SCR) technology for nitrogen oxides control oxidizes a small fraction of sulfur dioxide in the flue gas to SO3. The extent of this oxidation depends on the catalyst formulation and SCR operating conditions. Gas-phase SO3 and sulfuric acid, on being quenched in plant equipment (e.g., air preheater and wet scrubber), result in fine acidic mist, which can cause increased plume opacity and undesirable emissions. Recently, such effects have been observed at plants firing high-S coal and equipped with SCR systems and wet scrubbers. This paper investigates the factors that affect acidic mist production in coal-fired electric utility boilers and discusses approaches for mitigating emission of this mist.


A supportive nursing care clinic: conceptions of patients with head and neck cancer.
Patients with head and neck cancer have complex long-lasting physical and psychosocial needs due to illness and treatment, and studies have shown deficiencies concerning support in these respects. The purpose of this study was to describe how head and neck cancer patients with eating problems conceived the significance of a supportive nursing care clinic before, during and after completion of radiotherapy. Thematic interviews were carried out in an open dialogue with 12 patients treated with radiotherapy for head and neck cancer. The phenomenologischer method was used in the analyses. The findings showed that the nurse clinic could meet head and neck cancer patients' needs of safety and security, which was especially important before and after completion of treatment when no other regular contacts in the health care system existed. The significance of the nurse clinic varied depending on where in the trajectory the patients were, what needs and problems they experienced, and how severe these were experienced by the individual patient. The supportive nursing care clinic could meet these patients' needs of knowledge, care and support both concerning practical measures related to the disease and its treatment, and emotional needs. This way of organising the care can contribute to these patients' health and wellbeing.


Broadband terahertz lasing in aligned molecules.
No broadband amplifying medium has been demonstrated yet for terahertz radiation. We present simulations showing that laser-aligned molecules can amplify broadband terahertz radiation, allowing high-energy amplification of few-cycle pulses at terahertz frequencies.


Periostin alters transcriptional profile in a rat model of isoproterenol-induced cardiotoxicity.
Periostin is an extracellular matrix protein from the fasciclin family that guides cellular trafficking and extracellular matrix organization. Periostin stimulates mature cardiomyocytes to reenter the cell cycle. The molecular mechanism behind such stimulation remains to be explored. A DNA microarray technology constituting 30,429 gene-level probe sets was utilized to investigate effects of recombinant murine periostin peptide on the gene expression pattern in a rat model of isoproterenol (ISO)-induced myocardial injury. The experiment was performed on 84 adult male Sprague-Dawley rats in four groups ( n = 21): (1) control group, (2) only periostin applied group, (3) ISO cardiotoxicity group, and (4) ISO + periostin group. The experiment was continued for 28 days, and rats were killed on days 1, 7, and 28 ( n = 7). Microarray analyses revealed that periostin significantly altered the expression of at least ±2-fold of 2474 genes in the ISO + periostin group compared to the ISO cardiotoxicity group of which 521 genes altered out of 30,429 gene-level probe sets. Ingenuity pathway analysis indicated that multiple pathway networks were affected by periostin, with predominant changes occurring in the expression of genes involved in oxidative phosphorylation, oxidative stress, fatty acid metabolism, and TNF-α NF-κB signaling pathways. These findings indicate that periostin alters gene expression profile in the ISO-induced myocardial injury and modulates local myocardial inflammation, possibly mitigating inflammation through TNF-α NF-κB signaling pathway along with a decreased Casp7 activity and apoptotic cell death.


Sudden hearing loss associated with peginterferon and ribavirin combination therapy during hepatitis C treatment.
Adverse effects associated with peginterferon and ribavirin during hepatitis C treatment are well known. Sudden hearing loss has rarely been reported. Possible mechanisms involved include direct ototoxicity of interferon, autoimmunity, and hematological changes. Hearing loss is frequently fully resolved after discontinuation of antiviral therapy. We report a 47-year-old man with chronic hepatitis C, genotype 2 ac who developed sudden hearing loss 22 wk after starting therapy with peginterferon alpha 2a at a dose of 180 microg/wk and ribavirin 800 mg per day. Since symptoms did not worsen, antiviral therapy was continued for 2 wk, according to the patient's wish. Hearing loss resolved within 2 wk after the end of treatment. Serum liver alanine aminotransferase remained normal during and after the end of antiviral therapy. HCV RNA was undetectable at the end of therapy and remained negative 24 wk later. Thus, patients should be aware that hearing loss may occur with peginterferon therapy, but the decision whether to continue or to stop the treatment is based on the clinical judgment of the physician and the wishes of the patient.


Rehabilitation of postural stability in ataxic/hemiplegic patients after stroke.
This study assesses the postural stability and the effect of balance training using a force platform visual biofeedback among outpatients with postural disturbances following stroke. A tilting multiaxial force platform was used to assess bilateral postural stability in 38 outpatients (mean age 69.50 +/- 8.57 years) with hemiplegia and/or ataxia after stroke. Stability indexes were obtained. Afterwards, a subgroup of 12 patients with the poorest overall stability index (OASI) started a balance training programme in the force platform. Postural control training consisted of a 30-min training session once a week for a 15-week period. The test was then repeated. In the 38 outpatients sample, the mean OASI was 4.7 +/- 2.0 and 42.1% of the patients used their hands for support. In the 12 outpatients group, the initial OASI was 5.8 +/- 2.3 and half of the patients used their hands for support. The final OASI was 3.3 +/- 1.0 (p = 0.005) and only two of the patients used their hands for support (p = 0.046). Our results suggest that a training programme using force platform visual biofeedback improves objective measures of bilateral postural stability in patients with hemiplegia and/or ataxia after stroke.


A multi-institutional assessment of eye lens dose in nuclear medicine clinics.
The endeavor was to measure the lens dose of actively working staff in nuclear medicine departments. This study was accomplished in three nuclear medicine sites. A total of 23 workers in nuclear medicine joined this work. Among them are 6 SPECT/ CT technologists, 6 PET/CT technologists, 3 PET/MRI technologists, 5 radiopharmacists, 2 physicists, and 1 physician. EXTDOSE Hp(3) OSL dosimeter with tissue equivalent beryllium-oxide crystal was used for lens dose measurement. All participants were asked to wear the lens dosimeter for 2 months as near to the eye level as possible. Pooling the dose measures together yielded an average lens dose of 1.48 ± 0.77 mSv for the radiopharmacy team, 1.44 ± 0.26 for PET/ CT technologists, 0.86 ± 0.45 mSv for SPECT/ CT technologists, 0.38 mSv for the sole physician administered 177Lu, and 0.45 ± 0.02 mSv for the physicists conducting 131I therapy. Moreover, normalizing the lens dose to the labeled activity led to a lens dose of 2.2 ± 1.4 µSv/GBq for the radiopharmacy team. Likewise, per administered activity: 23.8 ± 7.3 µSv/GBq for PET/CT and PET/MRI technologists, 12.2 ± 10.5 µSv/GBq 99mTc for SPECT/CT technologists, 6.0 ± 0.81 µSv/GBq 131I for physicists, and 3.0 µSv/GBq 177Lu for the physician. It was deduced that the annual occupational lens dose of the nuclear medicine workers varied from 2.3 to 11.5 mSv/year; however, one radiopharmacist projected annual lens dose as close to the lens equivalent dose limit (20 mSv/year) as 17.9 mSv.


Subtype-selective nicotinic acetylcholine receptor agonists enhance the responsiveness to citalopram and reboxetine in the mouse forced swim test.
Nicotine increases serotonergic and noradrenergic neuronal activity and facilitates serotonin and noradrenaline release. Accordingly, nicotine enhances antidepressant-like actions of reuptake inhibitors selective for serotonin or noradrenaline in the mouse forced swim test and the mouse tail suspension test. Both high-affinity α4β2 and low-affinity α7 nicotinic acetylcholine receptor subtypes are implicated in nicotine-mediated release of serotonin and noradrenaline. The present study therefore investigated whether selective agonism of α4β2 or α7 nicotinic acetylcholine receptors would affect the mouse forced swim test activity of two antidepressants with distinct mechanisms of action, namely the selective serotonin reuptake inhibitor citalopram and the noradrenaline reuptake inhibitor reboxetine. Subthreshold and threshold doses of citalopram (3 and 10 mg/kg) or reboxetine (10 and 20 mg/kg) were tested alone and in combination with the novel α4β2-selective partial nicotinic acetylcholine receptor agonist, NS3956 (0.3 and 1.0 mg/kg) or the α7-selective nicotinic acetylcholine receptor agonist, PNU-282987 (10 and 30 mg/kg). Alone, NS3956 and PNU-282987 were devoid of activity in the mouse forced swim test, but both 1.0 mg/kg NS3956 and 30 mg/kg PNU-282987 enhanced the effect of citalopram and also reboxetine. The data suggest that the activity of citalopram and reboxetine in the mouse forced swim test can be enhanced by agonists at either α4β2 or α7 nicotinic acetylcholine receptors, suggesting that both nicotinic acetylcholine receptor subtypes may be involved in the nicotine-enhanced action of antidepressants.


Prognostic features of large cell anaplastic carcinoma of the bronchus.
The clinical features of 208 patients with large cell anaplastic carcinoma of the bronchus are reviewed. Of the sample 47.6% had disseminated disease at presentation, and 95% were cigarette smokers. The median survival was 6.0 months and five-year survival was 5.9%. Twenty-seven per cent of the patients had surgical resection of tumour. The median survival of resected patients was 13.0 months and five-year-survival was 21%. Radiotherapy was ineffective in controlling the disease in this series.


Down-regulation of IKKβ expression in glioma-infiltrating microglia/macrophages is associated with defective inflammatory/immune gene responses in glioblastoma.
Glioblastoma (GBM) is an aggressive malignancy associated with profound host immunosuppression. Microglia and macrophages infiltrating GBM acquire the pro-tumorigenic, M2 phenotype and support tumor invasion, proliferation, survival, angiogenesis and block immune responses both locally and systematically. Mechanisms responsible for immunological deficits in GBM patients are poorly understood. We analyzed immune/inflammatory gene expression in five datasets of low and high grade gliomas, and performed Gene Ontology and signaling pathway analyses to identify defective transcriptional responses. The expression of many immune/inflammatory response and TLR signaling pathway genes was reduced in high grade gliomas compared to low grade gliomas. In particular, we found the reduced expression of the IKBKB, a gene coding for IKKβ, which phosphorylates IκB proteins and represents a convergence point for most signal transduction pathways leading to NFκB activation. The reduced IKBKB expression and IKKβ levels in GBM tissues were demonstrated by qPCR, Western blotting and immunohistochemistry. The IKKβ expression was down-regulated in microglia/macrophages infiltrating glioblastoma. NFκB activation, prominent in microglia/macrophages infiltrating low grade gliomas, was reduced in microglia/macrophages in glioblastoma tissues. Down-regulation of IKBKB expression and NFκB signaling in microglia/macrophages infiltrating glioblastoma correlates with defective expression of immune/inflammatory genes and M2 polarization that may result in the global impairment of anti-tumor immune responses in glioblastoma.


Propofol alters left atrial function evaluated with pressure-volume relations in vivo.
The effects of IV anesthetics on left atrial (LA) function in vivo are unknown. We tested the hypothesis that propofol alters LA mechanics evaluated with pressure-volume relations in barbiturate-anesthetized dogs (n = 9) instrumented for measurement of aortic, LA, and left ventricular (LV) pressures (micromanometers) and LA volume (epicardial orthogonal sonomicrometers). LA myocardial contractility (E(es)) and dynamic chamber stiffness were assessed with end-systolic and end-reservoir pressure-volume relations, respectively. Relaxation was determined from the slope of LA pressure decline after contraction corrected for peak LA pressure. LA stroke work and reservoir function were assessed by A and V loop area, respectively, from the steady-state pressure-volume diagram. LA-LV coupling was determined by the ratio of E(es) to LV elastance. Dogs received propofol (5, 10, 20, or 40 mg. kg(-1). h(-1)) in a random manner, and LA function was determined after a 15-min equilibration at each dose. Propofol decreased heart rate, mean arterial blood pressure, and the maximal rate of increase of LV pressure. Propofol caused dose-related reductions in E(es), dynamic chamber stiffness, and E(es)/LV elastance. An increase in V loop area and declines in LA stroke work, emptying fraction, and the active LA contribution to LV filling also occurred. Relaxation was unchanged. The results indicate that propofol depresses LA myocardial contractility, reduces dynamic chamber stiffness, maintains reservoir function, and impairs LA-LV coupling but does not alter LA relaxation in vivo. Propofol depresses contractile function of left atrial (LA) myocardium, impairs mechanical matching between the LA and the left ventricular (LV), and reduces the active LA contribution to LV filling in vivo. Compensatory decreases in chamber stiffness contribute to relative maintenance of LA reservoir function during the administration of propofol.


Should central venous catheter be systematically removed in patients with suspected catheter related infection?
Best clinical practice for patients with suspected catheter-related infection (CRI) remains unclear according to the latest Infectious Diseases Society of America (IDSA) guidelines. Thus, the objective of this study was to analyze clinical practice concerning the central venous catheter (CVC) and its impact on prognosis in patients with suspected CRI. We performed a prospective, multicenter, observational study in 18 Spanish Intensive Care Units (ICUs). Inclusion criteria were patients with CVC and suspected CRI. The following exclusion criteria were used: age less than 18 years; pregnancy; lactation; human immunodeficiency virus; neutropenia; solid or haematological tumor; immunosuppressive or radiation therapy; transplanted organ; intravascular foreign body; haemodynamic instability; suppuration or frank erythema/induration at the insertion site of the CVC, and patients with bacteremia or fungemia. The end-point of the study was mortality at 30 days of CRI suspicion. The study included 384 patients. In 214 (55.8%) patients, CVC was removed at the moment of CRI suspicion, in 114 (29.7%) CVC was removed later and in 56 (14.6%) CVC was not removed. We did not find significant differences between survivors (n =311) and non-survivors (n =73) at 30 days according to CVC decision (P =0.26). The rate of confirmed catheter-related bloodstream infection (CRBSI) was higher in survivors than in non-survivors (14.5% versus 4.1%; P =0.02). Mortality rate was lower in patients with CRBSI than in the group of patients whose clinical symptoms were due to other causes (3/48 (6.25%) versus 70/336 (20.8%); P =0.02). We did not find significant differences in mortality in patients with confirmed CRBSI according to CVC removal at the moment of CRI suspicion (n =38) or later (n =10) (7.9% versus 0; P =0.99). In patients with suspected CRI, immediate CVC removal may be not necessary in all patients. Other aspects should be taken into account in the decision-making, such as vascular accessibility, the risk of mechanical complications during new cannulation that may be life-threatening, and the possibility that the CVC may not be the origin of the suspected CRI.


Nuclear factor-kappaB and advanced glycation end-products expression in lacrimal glands of aging rats.
Advanced glycation end products (AGEs) increase with aging and induce signaling alterations that lead to inflammation and dysfunction in several tissues. Aging reduces function and insulin signaling in lacrimal glands (LGs). To evaluate whether AGE signaling and insulin secretion in LGs are altered in aging, 24- and 2-month-old male Wistar rats were compared. Immunohistochemistry with confocal microscopy was used to evaluate AGE, AGE receptor (RAGE) and nuclear factor-kappaB (NF-kappaB) expression in LGs. Basal tear secretion volume, insulin, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) levels in tears and LGs and peroxidase activity in LG tissue were measured. Insulin secretion from isolated LGs and pancreatic beta-cells was compared in the supernatant of aging and control rats in vitro by RIA after stimulation with 2.8-16.7 mM glucose, carbachol and KCl. AGE, RAGE and NF-kappaB expression was higher in LGs of aging compared with young rats. Basal tear secretion and peroxidase activity were significantly lower in the aging group (P=0.016 for both assays). IL-1beta and TNF-alpha levels were higher in tears of aging rats compared with young rats (P=0.007 and 0.05 respectively); however, even though aging rats were insulin-resistant (as confirmed by the insulin-tolerance test), the insulin levels in the tear film of aging and control rats were similar in vivo and in vitro. The higher expression of AGEs, RAGE and NF-kappaB in LGs of aging rats is accompanied by systemic insulin resistance and may be involved in LG and tear film alterations but does not affect insulin secretion in the tear film. These observations indicate that metabolic events may be related to LG and tear film dysfunctions in aging.


In vivo optimisation study for multi-baseline MR-based thermometry in the context of hyperthermia using MR-guided high intensity focused ultrasound for head and neck applications.
In this in vivo study, the feasibility to perform hyperthermia treatments in the head and neck using magnetic resonance image-guided high intensity focused ultrasound (MRgHIFU) was established using a porcine acute model. Porcine specimens with a weight between 17 and 18 kg were treated in the omohyoid muscle in the neck. Hyperthermia was applied with a target temperature of 41 °C for 30 min using a Sonalleve MRgHIFU system. MR-based thermometry was calculated using water-proton resonance frequency shift and multi-baseline look-up tables indexed by peak-to-peak displacement (Dpp) measurements using a pencil-beam navigator. Three hyperthermia experiments were conducted at different Dpp values of 0.2, 1.0 and 3.0 mm. An optimisation study was carried out to establish the optimal parameters controlling the multi-baseline method that ensured a minimisation of spatial-average peak-to-peak temperature (TSA-pp) and temperature direct current bias (TSA-DC). The multi-baseline technique reduced considerably the noise on both TSA-pp and TSA-DC. The reduction of noise was more important when Dpp was higher. For Dpp = 3 mm the average (±standard deviation (SD)) of TSA-pp and TSA-DC was reduced from 4.5 (± 2.5) and 2.5 (±0.6) °C, respectively, to 0.8 (± 0.7) and 0.09 (± 0.2) °C. This in vivo study showed the level of noise in PRFS-based thermometry introduced by respiratory motion in the context of MRgHIFU hyperthermia treatment for head and neck and the feasibility of reducing this noise using a multi-baseline technique.


Brainstem network disruption: A pathway to sudden unexplained death in epilepsy?
Observations in witnessed Sudden Unexpected Death in Epilepsy (SUDEP) suggest that a fatal breakdown of the central autonomic control could play a major role in SUDEP. A previous MR study found volume losses in the mesencephalon in focal epilepsy that were more severe and extended into the lower brainstem in two patients who later died of SUDEP. The aims of this study were to demonstrate an association (1) between brainstem volume loss and impaired autonomic control (reduced heart rate variability [HRV]); (2) between brainstem damage and time to SUDEP in patients who later died of SUDEP. Two populations were studied: (1) Autonomic system function population (ASF, 18 patients with focal epilepsy, 11 controls) with HRV measurements and standardized 3 T MR exams. (2) SUDEP population (26 SUDEP epilepsy patients) with clinical MRI 1-10 years before SUDEP. Deformation-based morphometry of the brainstem was used to generate profile similarity maps from the resulting Jacobian determinant maps that were further characterized by graph analysis to identify regions with excessive expansion indicating significant volume loss or atrophy. The total number of regions with excessive expansion in ASF was negatively correlated with HRV (r = -.37, p = .03), excessive volume loss in periaqueductal gray/medulla oblongata autonomic nuclei explained most of the HRV associated variation (r/r2 = -.82/.67, p < .001). The total number of regions with excessive expansion in SUDEP was negatively correlated with time to SUDEP (r = -.39, p = .03), excessive volume loss in the raphe/medulla oblongata at the obex level explained most of the variation of the time between MRI to SUDEP (r/r2 = -.60/.35,p = .001). Epilepsy is associated with brainstem atrophy that impairs autonomic control and can increase the risk for SUDEP if it expands into the mesencephalon.


Breast tuberculosis: report of eight cases.
Tuberculosis of the breast is an extremely rare disease, which is still present and is also misdiagnosed with carcinoma or bacterial abscesses. In this study, we reported on eight patients with mammary tuberculosis during a four-year period. The main signs and symptoms of the patients included a painful tender lump in the breast (n=4), a painless lump in the breast (n=3), a lump with sinus (n=1), a sinus without lump (n=1), and an ipsilateral axillary lymphadenopathy (n=1). The diagnosis was confirmed by fine-needle aspiration cytology or histology. Antitubercular therapy was the therapeutic mainstay. Surgical intervention was reserved for aspiration of cold abscesses, and excision of residual sinuses and masses.


Cutaneous leiomyoma: novel histologic findings for classification and diagnosis.
Smooth muscle tumors rather benign or malignant can arise wherever the muscular tissue presents but cutaneous leiomyoma is one of the rare benign tumors of the which even the diagnostic criteria from the malignant type of the tumor is still in doubt. This study was aimed to compare the subtypes of cutaneous leiomyoma from different histologic aspects in order to find unique criteria for better classification and diagnosis. The six year data base of our center was reviewed and 25 patients with cutaneous leiomyoma were included in this study. Of 25 patients, 5 were female and 20 were male. 5 patients had angioleiomyoma (ALM) and 20 had pilar leiomyoma (PLM). ALM had following characteristics: dilated vascular canals intermingled with compact smooth muscle bundles; well circumscribe counter and myxoid and hyaline changes through the tumor. In contrast, PLMs had following histologic features: poor defined outline, entrapped hair follicles and eccrine glands, acanthosis and elongated rete ridges with hyperpigmentation and smooth muscle bundles which are interdigitated with elongated rete ridges. Here we introduced some distinct histological features for each subtype of the cutaneous leiomyoma which can lead to create novel criteria for classification and diagnosis of the lesion.


Counterfactual thinking in Tourette's syndrome: a study using three measures.
Pathophysiological evidence suggests an involvement of frontostriatal circuits in Tourette syndrome (TS) and cognitive abnormalities have been detected in tasks sensitive to cognitive deficits associated with prefrontal damage (verbal fluency, planning, attention shifting, working memory, cognitive flexibility, and social reasoning). A disorder in counterfactual thinking (CFT), a behavioural executive process linked to the prefrontal cortex functioning, has not been investigated in TS. CFT refers to the generation of a mental simulation of alternatives to past factual events, actions, and outcomes. It is a pervasive cognitive feature in everyday life and it is closely related to decision-making, planning, problem-solving, and experience-driven learning-cognitive processes that involve wide neuronal networks in which prefrontal lobes play a fundamental role. Clinical observations in patients with focal prefrontal lobe damage or with neurological and psychiatric diseases related to frontal lobe dysfunction (e.g., Parkinson's disease, Huntington's disease, and schizophrenia) show counterfactual thinking impairments. In this work, we evaluate the performance of CFT in a group of patients with Tourette's syndrome compared with a group of healthy participants. Overall results showed no statistical differences in counterfactual thinking between TS patients and controls in the three counterfactual measures proposed. The possible explanations of this unexpected result are discussed below.


Metal-Free Photocatalytic CO2 Reduction to CH4 and H2 O2 under Non-sacrificial Ambient Conditions.
Photocatalytic CO2 reduction to CH4 requires photosensitizers and sacrificial agents to provide sufficient electrons and protons through metal-based photocatalysts, and the separation of CH4 from by-product O2 has poor applications. Herein, we successfully synthesize a metal-free photocatalyst of a novel electron-acceptor 4,5,9,10-pyrenetetrone (PT), to our best knowledge, this is the first time that metal-free catalyst achieves non-sacrificial photocatalytic CO2 to CH4 and easily separable H2 O2 . This photocatalyst offers CH4 product of 10.6 μmol ⋅ g-1 ⋅ h-1 under non-sacrificial ambient conditions (room temperature, and only water), which is two orders of magnitude higher than that of the reported metal-free photocatalysts. Comprehensive in situ characterizations and calculations reveal a multi-step reaction mechanism, in which the long-lived oxygen-centered radical in the excited PT provides as a site for CO2 activation, resulting in a stabilized cyclic carbonate intermediate with a lower formation energy. This key intermediate is thermodynamically crucial for the subsequent reduction to CH4 product with the electronic selectivity of up to 90 %. The work provides fresh insights on the economic viability of photocatalytic CO2 reduction to easily separable CH4 in non-sacrificial and metal-free conditions.


Productivity of outdoor algal cultures in enclosed tubular photobioreactor.
At quasi-steady-state outdoor cyclic fed batch cultures of Chlorella pyrenoidosa, the growth irradiance incidented on the tubular photobioreactor increased about fivefold between 9:00 a.m. and noon. Overheating of the cultures was observed, resulting in decreasing biomass output rate when culture temperature went above 40 degrees C. In cultures with temperature control, the quasi-steady-state output rate of all cultures increased throughout the day and leveled off in the late afternoon in high-density cultures. The daily area output rate was proportional to the density of the cultures. The specific growth rate of the light-limited cultures increased only marginally (20%) in the morning.


Functional brain networks assessed with surface electroencephalography for predicting motor recovery in a neural guided intervention for chronic stroke.
Predicting whether a chronic stroke patient is likely to benefit from a specific intervention can help patients establish reasonable expectations. It also provides the basis for candidates selecting for the intervention. Recent convergent evidence supports the value of network-based approach for understanding the relationship between dysfunctional neural activity and motor deficits after stroke. In this study, we applied resting-state brain connectivity networks to investigate intervention-specific predictive biomarkers of motor improvement in 22 chronic stroke participants who received either combined action observation with EEG-guided robot-hand training (Neural Guided-Action Observation Group, n = 12, age: 34-68 years) or robot-hand training without action observation and EEG guidance (non-Neural Guided-text group, n = 10, age: 42-57 years). The robot hand in Neural Guided-Action Observation training was activated only when significant mu suppression (8-12 Hz) was detected from participant's EEG signals in ipsilesional hemisphere while it was randomly activated in non-Neural Guided-text training. Only the Neural Guided-Action Observation group showed a significant long-term improvement in their upper-limb motor functions (P < 0.5). In contrast, no significant training effect on the paretic motor functions was found in the non-Neural Guided-text group (P > 0.5). The results of brain connectivity estimated via EEG coherence showed that the pre-training interhemispheric connectivity of delta, theta, alpha and contralesional connectivity of beta were motor improvement related in the Neural Guided-Action Observation group. They can not only differentiate participants with good and poor recovery (interhemispheric delta: P = 0.047, Hedges' g = 1.409; interhemispheric theta: P = 0.046, Hedges' g = 1.333; interhemispheric alpha: P = 0.038, Hedges' g = 1.536; contralesional beta: P = 0.027, Hedges' g = 1.613) but also significantly correlated with post-training intervention gains (interhemispheric delta: r = -0.901, P < 0.05; interhemispheric theta: r = -0.702, P < 0.05; interhemispheric alpha: r = -0.641, P < 0.05; contralesional beta: r = -0.729, P < 0.05). In contrast, no EEG coherence was significantly correlated with intervention gains in the non-Neural Guided-text group (all P s > 0.05 ). Partial least square regression showed that the combination of pre-training interhemispheric and contralesional local connectivity could precisely predict intervention gains in the Neural Guided-Action Observation group with a strong correlation between predicted and observed intervention gains (r = 0.82 r = 0.82 ) and between predicted and observed intervention outcomes (r = 0.90 r = 0.90 ). In summary, EEG-based resting-state brain connectivity networks may serve clinical decision-making by offering an approach to predicting Neural Guided-Action Observation training-induced motor improvement.


Subdural strip electrodes for localizing epileptogenic foci.
Surgical removal of epileptogenic brain is indicated for treatment of many medically refractory focal seizure disorders. One of the important factors in providing good results from surgery is the accuracy of identifying the epileptogenic focus. However, accurate localization may be difficult when only standard scalp recordings are used. Many epilepsy centers have used intracranial recording techniques to better define regions of cortical epileptogenicity . Although subdural strip electrodes were first utilized many years ago, the more popular method of intracranial recording has been by intracortical depth electrodes. The authors present their method of placing subdural strip electrodes for extensive recordings from the cortex. To date, this method has been used to provide continuous monitoring of the electrocorticogram in 28 patients for periods up to 3 weeks, with only two minor complications. This procedure is relatively safe and a valuable alternative to placing intracortical depth electrodes.


Discovering Ways to Mend Growing Bodies: The Bioengineering of Devices for the Youngest Patients Brings Unique Challenges and Rewards.
Some babies are born with a rare condition known as esophageal atresia, in which part of the connection between the throat and stomach is missing or nonfunctional. While this was once untreatable and fatal, in recent years surgeons have developed a method using traction to stretch the tissues out on each end until, over time, they are long enough to be sewn together and so substitute for the missing portion of the esophagus. The procedure has allowed many infant patients to go home with a full, normal life ahead of them. But the procedure, which costs US$500,000 and upwards, requires that the patient be fully sedated and unconscious in an intensive-care unit (ICU) for between one and two months to avoid any bodily motions that could tear out internal sutures.


Differential cell replication within the periosteum of the pig mandibular ramus.
The periosteum is anatomically and functionally divided into two layers. The inner osteoblastic layer contributes to local appositional bone growth. The outer fibroblastic layer receives the attachments of muscles and responds to bone growth by a more global enlargement. Coordinated growth of the layers could theoretically be produced by parallel replication rates in the layers followed by migration of fibroblastic layer cells. Alternatively, replication rates in the layers could differ, those in the osteoblastic layer reflecting local apposition and those in the fibroblastic layer responding to total bone growth. To test these alternatives, we compared two regions of the pig mandible, one appositional and one resorptive, equidistant from the major growth sites of the bone. Four 2-week-old pigs were injected i.p. with 5-bromo-2'-deoxyuridine (BrdU) to label replicating cells. Three hours subsequent to BrdU injection, animals were sacrificed. The mandibles were sectioned and processed immunocytochemically for BrdU. Periosteal cell mitotic activity was analyzed selectively at the level of the mandibular foramen on the medial and lateral ramal surfaces. The proportion of labeled cells was determined by grid-point analysis. Individual differences were minor but regional differences were striking. As expected, the osteoblastic layer of the lateral surface exhibited a greater proportion of mitotic cells than did the medial surface (p = 0.037). However, no such difference was seen in the fibroblastic layer, where medial and lateral sides exhibited identical replication activity. These results strongly support the second alternative, that cell division is differentially controlled in the two periosteal layers.


Preoperative magnetic resonance assessment of patellar tendon dimensions for graft selection in anterior cruciate ligament reconstruction.
A bone patellar tendon bone autograft is one of the standard graft choices for anterior cruciate ligament reconstruction. However, its use can be limited when the patellar tendon is too narrow or too long. A preoperative assessment of patellar tendon dimensions using magnetic resonance imaging would be accurate and reliable. Patients undergoing anterior cruciate ligament reconstruction would have wide ranges of patellar tendon dimensions, and a significant proportion of patients would have a too narrow and/or too long patellar tendon as the graft choice. There would be a demographic predictor to identify the patients with inappropriate patellar tendon dimensions. Cohort study (diagnosis); Level of evidence, 3. The accuracy and reliability of magnetic resonance assessments of patellar tendon dimensions were assessed by comparing the intraoperative measurements using a ruler in 55 knees and 10 knees, respectively. Data from the magnetic resonance assessments in 147 knees undergoing anterior cruciate ligament reconstruction were used for the normative documentation of the patellar tendon dimensions (width, thickness, and length) and identification of demographic predictors for the dimensions. Preoperative magnetic resonance assessments of the patellar tendon dimensions were accurate and reliable. Korean patients undergoing anterior cruciate ligament reconstruction had wide variations in patellar dimensions, and a significant portion of the patients had an inappropriate patellar tendon (longer than 5 cm in 4.1% and narrower than 27 mm at middle portion in 15.6%) for the graft source. Patient height was the predictor used for patellar tendon width. The mathematical equation used to estimate the width based on patient height was: tendon width at middle portion (mm) = 0.202 x patient height (cm) - 5.07. Preoperative magnetic resonance assessment of patellar tendon dimensions can be a valuable tool with satisfactory accuracy and reliability when the autologous patellar tendon is considered as the graft source for anterior cruciate ligament reconstruction.