Neuroprotection in preterm infants.
Preterm infants born before the 30th week of pregnancy are especially at risk of perinatal brain damage which is usually a result of cerebral ischemia or an ascending intrauterine infection. Prevention of preterm birth and early intervention given signs of imminent intrauterine infection can reduce the incidence of perinatal cerebral injury. It has been shown that administering magnesium intravenously to women at imminent risk of a preterm birth leads to a significant reduction in the likelihood of the infant developing cerebral palsy and motor skill dysfunction. It has also been demonstrated that delayed clamping of the umbilical cord after birth reduces the rate of brain hemorrhage among preterm infants by up to 50%. In addition, mesenchymal stem cells seem to have significant neuroprotective potential in animal experiments, as they increase the rate of regeneration of the damaged cerebral area. Clinical tests of these types of therapeutic intervention measures appear to be imminent. In the last trimester of pregnancy, the serum concentrations of estradiol and progesterone increase significantly. Preterm infants are removed abruptly from this estradiol and progesterone rich environment. It has been demonstrated in animal experiments that estradiol and progesterone protect the immature brain from hypoxic-ischemic lesions. However, this neuroprotective strategy has unfortunately not yet been subject to sufficient clinical investigation.


Augmentation therapy with minocycline in treatment-resistant depression patients with low-grade peripheral inflammation: results from a double-blind randomised clinical trial.
This study aimed to investigate the role of baseline levels of peripheral inflammation when testing the efficacy of antidepressant augmentation with minocycline in patients with treatment-resistant depression. We conducted a 4-week, placebo-controlled, randomised clinical trial of minocycline (200 mg/day) added to antidepressant treatment in 39 patients selected for elevated levels of serum C-reactive protein (CRP ≥ 1 mg/L), n = 18 randomised to minocycline (M) and n = 21 to placebo (P). The main outcome was the change in Hamilton Depression Rating Scale (HAM-D-17) score from baseline to week 4, expressed both as mean and as full or partial response, in the overall sample and after further stratification for baseline CRP≥3 mg/L. Secondary outcomes included changes in other clinical and inflammatory measures. Changes in HAM-D-17 scores and the proportion of partial responders did not differ between study arms. After stratification for CRP levels <3 mg/L (CRP-) or ≥3 mg/L (CRP+), CRP+/M patients showed the largest changes in HAM-D-17 scores (mean ± SD = 12.00 ± 6.45) compared with CRP-/M (2.42 ± 3.20, p < 0.001), CRP+/P (3.50 ± 4.34, p = 0.003) and CRP-/P (2.11 ± 3.26, p = 0.006) patients, and the largest proportion (83.3%, p = 0.04) of partial treatment response at week 4. The threshold point for baseline CRP to distinguish responders from non-responders to minocycline was 2.8 mg/L. Responders to minocycline had higher baseline IL-6 concentrations than non-responders (p = 0.03); IFNγ was significantly reduced after treatment with minocycline compared with placebo (p = 0.03). Our data show some evidence of efficacy of add-on treatment with minocycline in MDD patients but only in those with low-grade inflammation defined as CRP ≥3 mg/L.


Chondrocyte survival and differentiation in situ are integrin mediated.
Chondrocytes in specific areas of the chick sternum have different developmental fates. Cephalic chondrocytes become hypertrophic and secrete type X collagen into the extracellular matrix prior to bone deposition. Middle and caudal chondrocytes remain cartilaginous throughout development and continue to secrete collagen types II, IX, and XI. The interaction of integrin receptors with extracellular matrix molecules has been shown to affect cytoskeleton organization, proliferation, differentiation, and gene expression in other cell types. We hypothesized that chondrocyte survival and differentiation including the deposition into interstitial matrix of type X collagen may be integrin receptor mediated. To test this hypothesis, a serum-free organ culture sternal model that recapitulates normal development and maintains the three-dimensional relationships of the tissue was developed. We examined chondrocyte differentiation by five parameters: type X collagen deposition into interstitial matrix, sternal growth, actin distribution, cell shape, and cell diameter changes. Additional sterna were analyzed for apoptosis using a fragmented DNA assay. Sterna were organ cultured with blocking antibodies specific for integrin subunits (alpha2, alpha3, or beta1). In the presence of anti-beta1 integrin (25 microg/ml, clone W1B10), type X collagen deposition into interstitial matrix and sternal growth were significantly inhibited. In addition, all chondrocytes were significantly smaller, the actin was disrupted, and there was a significant increase in apoptosis throughout the specimens. Addition of anti-alpha2 (10 microg/ml, clone P1E6) or anti-alpha3 (10 microg/ml, clone P1B5) integrin partially inhibited type X collagen deposition into interstitial matrix; however, sternal growth and cell size were significantly decreased. These data are the first obtained from intact tissue and demonstrate that the interaction of chondrocytes with extracellular matrix is required for chondrocyte survival and differentiation.


Secreted Listeria adhesion protein (Lap) influences Lap-mediated Listeria monocytogenes paracellular translocation through epithelial barrier.
Listeria adhesion protein (Lap), an alcohol acetaldehyde dehydrogenase (lmo1634) promotes bacterial paracellular translocation through epithelial cell junctions during gastrointestinal phase of infection. Secreted Lap is critical for pathogenesis and is mediated by SecA2 system; however, if strain dependent variation in Lap secretion would affect L. monocytogenes paracellular translocation through epithelial barrier is unknown. Amounts of Lap secretion were examined in clinical isolates of L. monocytogenes by cell fractionation analysis using Western blot. Quantitative reverse transcriptase PCR (qRT-PCR) was used to verify protein expression profiles. Adhesion and invasion of isolates were analyzed by in vitro Caco-2 cell culture model and paracellular translocation was determined using a trans-well model pre-seeded with Caco-2 cells. Western blot revealed that expression of Lap in whole cell preparation of isolates was very similar; however, cell fractionation analysis indicated variable Lap secretion among isolates. The strains showing high Lap secretion in supernatant exhibited significantly higher adhesion (3.4 - 4.8% vs 1.5 - 2.3%, P < 0.05), invasion and paracellular translocation in Caco-2 cells than the low secreting isolates. In cell wall fraction, Lap level was mostly uniform for both groups, while Lap accumulated in cytosol in low secreting strains indicating that Lap distribution in cellular compartments is a strain-dependent phenomenon, which may be controlled by the protein transport system, SecA2. ΔsecA2 mutants showed significantly reduced paracellular translocation through epithelial barrier (0.48 ± 0.01 vs 0.24 ± 0.02, P < 0.05). qRT-PCR did not show any discernible variation in lap transcript levels in either high or low secreting isolates. This study revealed that secreted Lap is an important determinant in Lap-mediated L. monocytogenes translocation through paracellular route and may serve as an indicator for pathogenic potential of an isolate.


Should blood gas analysis be part of the diagnostic workup of short children? Auxological data and blood gas analysis in children with renal tubular acidosis.
Renal tubular acidosis (RTA) is a rare cause of growth failure, therefore it is uncertain whether routine screening with blood gas analysis of short infants and children is cost-effective. To investigate the clinical, growth and laboratory parameters in children with RTA to estimate the possible value of laboratory screening for this disorder in infants and children referred for short stature according to a recent guideline. Retrospective chart analysis of 30 children diagnosed between 1978 and 2005 in The Netherlands and 3 centers in Belgium. The current guideline for short stature detected 33% of children with RTA. Assuming a pre-test probability of RTA of 0.6 per 100,000 births, the likelihood ratio of poor growth was 58 and 17 below and above 3 years, respectively. Sensitivity was 17/30 and 12/24 for a -2.0 SDS cutoff for weight and body mass index, respectively. In infants and toddlers diagnosed before 3 years of age, the mean weight loss was 1.5 SD, and 0.8 SDS in older children. In short children >3 years RTA was extremely rare, always associated with clinical symptoms, and rarely detected by blood gas analysis. According to our data a decreasing weight SDS for age is a sufficient indication to perform blood gas analysis in children <3 years of age, particularly in the presence of additional clinical features, whereas it can be omitted in short children >3 years of age.


[Incidence of phlebitis in patients with intestinal inflammatory disease undergoing peripheral parenteral nutrition].
The aim of this study is to evaluate the incidence of phlebitis in patients with inflammatory bowel disease under parenteral nutrition treatment (700 mOsm/ml) via peripheral vein. Results will be used to develop an standar protocol. 30 patients were sampled and the cannulation was performed by nursery personnel. Daily, incidence of phlebitis was evaluated with a gradual scale ranging in 5 possible degrees from absence of signs to thrombophlebitis. 86.6% of the patients received the feeding through a Teflon catheter with a fine bore of 20 gauge. Cannulas were mostly situated in the basilic vein. Development of phlebitic signs was proportional to the duration of infusion. When phlebitic signs appeared, via of cannulation was not changed in 33% of those patients.


Relation between blood pressure variability and early renal damage in hypertensive patients.
The objective of the present study was to observe the relation between blood pressure variability (BPV) and early renal damage in hypertensive patients. A total of 118 hypertensive patients were consecutively selected. General parameters including sex, age, duration, and grade of hypertension, antihypertensive drugs taken, smoking status, blood sugar, blood lipid level, body mass index, indexes of 24-h ambulatory blood pressure monitoring and renal function including cystatin C (CysC), serum creatinine (SCr), angiotensin II (Ang II), microalbuminuria (mALb), and urine creatinine (UCr) were measured. Glomerular filtration rate (eGFR), endogenous creatinine clearance rate (Ccr), and urine albumin/creatinine ratio (UACR) were calculated by CysC level, SCr level, and mALb and UCr level respectively. The 24-h ambulatory blood pressure monitoring indexes included 24-h mean systolic blood pressure variability (24h-SBPV), 24-h mean diastolic blood pressure variability (24h-DBPV), day mean systolic blood pressure variability (d-SBPV), day mean diastolic blood pressure variability (d-DBPV), night mean systolic blood pressure variability (n-SBPV), and night mean diastolic blood pressure variability (n-DBPV). Sixty-four hypertensive patients (54.24%) were non-dipper, and the baseline data of the two groups were comparable. The 24h-SBPV, 24h-DBPV, d-DBPV, n-SBPV and SCr, eGFR, and Ccr of the two groups showed no significant differences. The d-SBPV, n-DBPV, CysC, and Ang II of the non-dipper group were significantly higher than those of the dipper group (p<0.05). The mALb in both groups increased and was more obvious in the non-dipper group. UACR of the non-dipper group was significantly higher than that of dipper group (p<0.05), while UCr showed no difference. By Pearson correlation, d-SBPV and n-DBPV correlated positively (p<0.05) with CysC, Ang II, mALb, and UACR. BPV of hypersensitive patients, especially the d-SBPV and n-DBPV, was closely related to indexes of early renal damage including CysC, Ang II, mALb, and UACR.


Discovery of an unusual copper homeostatic mechanism in yeast cells respiring on minimal medium and an unexpectedly diverse labile copper pool.
Copper is essential for all eukaryotic cells but many details of how it is trafficked within the cell and how it is homeostatically regulated remain uncertain. Here, we characterized the copper content of cytosol and mitochondria using liquid chromatography with ICP-MS detection. Chromatograms of cytosol exhibited over two dozen peaks due to copper proteins and coordination complexes. Yeast cells respiring on minimal media did not regulate copper import as media copper concentration increased; rather, they imported copper at increasing rates while simultaneously increasing the expression of metallothionein CUP1 which then sequestered most of the excessive imported copper. Peak intensities due to superoxide dismutase SOD1, other copper proteins, and numerous coordination complexes also increased, but not as drastically. The labile copper pool was unexpectedly diverse and divided into two groups. One group approximately comigrated with copper-glutathione, -cysteine, and -histidine standards; the other developed only at high media copper concentrations and at greater elution volumes. Most cytosolic copper arose from copper-bound proteins, especially CUP1. Cytosol contained an unexpectedly high percentage of apo-copper proteins and apo-coordination complexes. Copper-bound forms of non-CUP1 proteins and complexes coexisted with apo-CUP1 and with the chelator BCS. Both experiments suggest unexpectedly stable-binding copper proteins and coordination complexes in cytosol. COX17Δ cytosol chromatograms were like those of WT cells. Chromatograms of soluble mitochondrial extracts were obtained, and mitoplasting helped distinguish copper species in the intermembrane space versus in the matrix/inner membrane. Issues involving the yeast copperome, copper homeostasis, labile copper pool, and copper trafficking are discussed.


The role of thrombospondins 1 and 2 in the regulation of cell-matrix interactions, collagen fibril formation, and the response to injury.
Thrombospondins (TSPs) 1 and 2 are extracellular modular glycoproteins that are best known for their anti-angiogenic properties and their ability to modulate cell-matrix interactions. However, these proteins, and in particular TSP2, are pleiotropic in function and affect processes as disparate as bone growth and hemostasis. In recognition of their ability to influence a wide variety of cell functions, and in the absence of convincing evidence for their participation as integral components of extracellular structures, the term 'matricellular' has been applied to these and a small group of functionally related proteins. In this review, we focus on the role of TSP1 and 2 in two forms of injury in mice, excisional skin wounds and subcutaneously implanted biomaterials, and take advantage of mice with targeted disruptions of one or both genes to identify likely biochemical mechanisms that could account for the characteristics of the injury response in these knockout mice. In work that stems largely from our own laboratory, we show that pericellular levels of the matrix metalloproteinase, MMP2, are controlled to a large extent by TSP2 (and potentially also by TSP1), and that elevated levels of MMP2 are likely to account in part for defects as diverse as reduced cellular adhesion, abnormal collagen fibril structure, and increased endothelial cell and vascular proliferation.


Validation of Digital Pathology for Primary Histopathological Diagnosis of Routine, Inflammatory Dermatopathology Cases.
Digital pathology (DP) systems have been validated for routine, histopathological diagnosis by several investigators. The diagnostic matter in previous studies is composed mostly of neoplasms. However, in dermatopathology, inflammatory diseases constitute a greater proportion of cases and have been under-represented in this literature. Herein, we report the results of a prospective, DP side-by-side validation study comparing the histologic assessment of routine, clinical inflammatory dermatopathology cases by whole slide imaging (WSI) and traditional light microscopy (LM). Glass slides were digitized at ×40 magnification. Two dermatopathologists rendered diagnoses digitally and immediately thereafter by light microscopy. Additional recuts, special, and immunohistochemical stains obtained during workup were scanned and evaluated similarly. Morphological features used to make diagnoses and appreciable differences in histology were recorded. A total of 332 slides representing 93 cases were examined, including 157 hematoxylin & eosin sections, 132 special stains, and 43 immunohistochemical slides. In total, 333 microscopic features important for rendering inflammatory diagnoses were identified. Two discrepant instances were noted wherein Gram-positive cocci were identified using traditional microscopy but not by DP (×40 scan). Eosinophils, melanin granules, and mucin were identified on both modalities but were noted to have different appearances. Our findings indicate that DP is sufficient for primary diagnosis in inflammatory dermatopathology. Higher magnification scanning may be required to identify submicron features, such as microorganisms. Subtle differences in image quality between these 2 modalities may contribute to varied histologic interpretations of which pathologists should be aware when validating clinical DP systems.


A technique for longitudinally sampling individual adult Ixodes scapularis (Acari: Ixodidae).
The first technique for repeatedly sampling individual Ixodes scapularis adult ticks was developed and validated. Gut samples from the same individual ticks were removed and analyzed at weekly intervals. Multiple analyses were conducted on each gut sample (e.g., total protein concentration, presence of viable B. burgdorferi spirochetes, and concentration of outer surface protein A [OspA]). Female I. scapularis survived for up to 25 d after gut sampling. Seventy-five percent of females oviposited after the sampling procedure, with 14% of ticks laying >1,500 eggs. No significant differences in either fecundity or length of survival were found between B. burgdorferi-infected and uninfected I. scapularis. This technique will enable longitudinal studies on both tick-pathogen interactions and physiological studies that have hitherto not been attempted.


ASVCP guidelines: quality assurance for point-of-care testing in veterinary medicine.
Point-of-care testing (POCT) refers to any laboratory testing performed outside the conventional reference laboratory and implies close proximity to patients. Instrumental POCT systems consist of small, handheld or benchtop analyzers. These have potential utility in many veterinary settings, including private clinics, academic veterinary medical centers, the community (eg, remote area veterinary medical teams), and for research applications in academia, government, and industry. Concern about the quality of veterinary in-clinic testing has been expressed in published veterinary literature; however, little guidance focusing on POCT is available. Recognizing this void, the ASVCP formed a subcommittee in 2009 charged with developing quality assurance (QA) guidelines for veterinary POCT. Guidelines were developed through literature review and a consensus process. Major recommendations include (1) taking a formalized approach to POCT within the facility, (2) use of written policies, standard operating procedures, forms, and logs, (3) operator training, including periodic assessment of skills, (4) assessment of instrument analytical performance and use of both statistical quality control and external quality assessment programs, (5) use of properly established or validated reference intervals, (6) and ensuring accurate patient results reporting. Where possible, given instrument analytical performance, use of a validated 13s control rule for interpretation of control data is recommended. These guidelines are aimed at veterinarians and veterinary technicians seeking to improve management of POCT in their clinical or research setting, and address QA of small chemistry and hematology instruments. These guidelines are not intended to be all-inclusive; rather, they provide a minimum standard for maintenance of POCT instruments in the veterinary setting.


Immunologic responses in patients with lepromatous leprosy.
Immunologic responses were measured in 46 patients with lepromatous leprosy. These patients were not distinguishable from controls on the basis of responses to soluble intradermal antigens, sensitization to contactants, peripheral blood T- and B-cell percentages, in vitro lymphocyte responses to a mitogen, or the prevalence of autoantibodies. Generalized immunologic abnormalities in patients with lepromatous leprosy are neither predisposing causes nor necessary accompaniments of lepromatous leprosy, but are probably remote sequellae of the illness. By implication, the generalized immunologic abnormalities reported in other diseases are likely to be remote sequellae of the particular illness.


Streptococcus pneumoniae Colonization Is Required To Alter the Nasal Microbiota in Cigarette Smoke-Exposed Mice.
Smokers have nasal microbiota dysbiosis, with an increased frequency of colonizing bacterial pathogens. It is possible that cigarette smoke increases pathogen acquisition by perturbing the microbiota and decreasing colonization resistance. However, it is difficult to disentangle microbiota dysbiosis due to cigarette smoke exposure from microbiota changes caused by increased pathogen acquisition in human smokers. Using an experimental mouse model, we investigated the impact of cigarette smoke on the nasal microbiota in the absence and presence of nasal pneumococcal colonization. We observed that cigarette smoke exposure alone did not alter the nasal microbiota composition. The microbiota composition was also unchanged at 12 h following low-dose nasal pneumococcal inoculation, suggesting that the ability of the microbiota to resist initial nasal pneumococcal acquisition was not impaired in smoke-exposed mice. However, nasal microbiota dysbiosis occurred as a consequence of established high-dose nasal pneumococcal colonization at day 3 in smoke-exposed mice. Similar to clinical reports on human smokers, an enrichment of potentially pathogenic bacterial genera such as Fusobacterium, Gemella, and Neisseria was observed. Our findings suggest that cigarette smoke exposure predisposes to pneumococcal colonization independent of changes to the nasal microbiota and that microbiota dysbiosis observed in smokers may occur as a consequence of established pathogen colonization.


Emergence of RNA-guided transcription factors via domestication of transposon-encoded TnpB nucleases.
Transposon-encoded tnpB genes encode RNA-guided DNA nucleases that promote their own selfish spread through targeted DNA cleavage and homologous recombination 1-4 . This widespread gene family was repeatedly domesticated over evolutionary timescales, leading to the emergence of diverse CRISPR-associated nucleases including Cas9 and Cas12 5,6 . We set out to test the hypothesis that TnpB nucleases may have also been repurposed for novel, unexpected functions other than CRIS-PR-Cas. Here, using phylogenetics, structural predictions, comparative genomics, and functional assays, we uncover multiple instances of programmable transcription factors that we name TnpB-like nuclease-dead repressors (TldR). These proteins employ naturally occurring guide RNAs to specifically target conserved promoter regions of the genome, leading to potent gene repression in a mechanism akin to CRISPRi technologies invented by humans 7 . Focusing on a TldR clade found broadly in Enterobacteriaceae , we discover that bacteriophages exploit the combined action of TldR and an adjacently encoded phage gene to alter the expression and composition of the host flagellar assembly, a transformation with the potential to impact motility 8 , phage susceptibility 9 , and host immunity 10 . Col-lectively, this work showcases the diverse molecular innovations that were enabled through repeated exaptation of genes encoded by transposable elements, and reveals that RNA-guided transcription factors emerged long before the development of dCas9-based editors.


Selection criteria and long-term results of surgery in symptomatic rectocele.
The aim of this study was to confirm some selection criteria for the transrectal repair of the anterior rectocele and to compare our surgical results with those reported in the literature. From January 1992 to December 1999, 30 females (mean age 52.9 years, range 28-70 yrs) affected by anterior rectocele were prospectively evaluated with a standard questionnaire, clinical examination, proctosigmoidoscopy, colonic transit time, dynamic defecography, anal EMG, anal manometry. Then, they were submitted to transrectal repair of rectocele with anterior plication of the rectal muscular wall. Fourteen (46.6%) of them were also submitted to perineal levatorplasty. Patients were followed postoperatively (mean 25.7 months) with the same standard questionnaire, clinical examination, defecography, and manometry. Results were tested by Fisher's Exact text, Wilcoxon's test, and "t"-test. Rectal dyschezia, incomplete evacuation, digital help in defecating, mean stool frequency, and rectal bleeding significantly improved. After 3 months, 30% of patients had no complaints, 40% had only 1-2 episodes/month complaints, 13.3% had evacuation only using laxatives, and 16.6% were unchanged. Defecography showed a significant reduction of the rectocele in 70% of patients after 3 months. Manometric parameters were not significantly modified. Four (28.6%) out of 14 patients submitted to perineal levatorplasty complained of dyspareunia. Our surgical results were comparable with those reported in the literature, with more than 80% of successful outcome. Preoperative clinical data and defecography were confirmed to be basic parameters in selecting patients for surgery. Colonic transit time, anal EMG, and anorectal manometry demonstrated to be useful to recognize conditions as slow colonic transit time, peripheral denervation, and reduced voluntary contraction that could lead to a less satisfactory outcome after surgery, and might benefit with a postoperative perineal rehabilitation by biofeedback and anal electrostimulations. The perineal levatorplasty is not suitable in young females, due to the risk of dyspareunia.


Patterns of sexual dimorphism in Mexican alligator lizards, Barisia imbricata.
We compare morphological characteristics of male and female Barisia imbricata, Mexican alligator lizards, and find that mass, head length, coloration, incidence of scars from conspecifics, tail loss, and frequency of bearing the color/pattern of the opposite sex are all sexually dimorphic traits. Overall size (measured as snout-vent length), on the other hand, is not different between the two sexes. We use data on bite scar frequency and fecundity to evaluate competing hypotheses regarding the selective forces driving these patterns. We contend that sexual selection, acting through male-male competition, may favor larger mass and head size in males, whereas large females are likely favored by natural selection for greater fecundity. In addition, the frequency of opposite-sex patterning in males versus females may indicate that the costs of agonistic interactions among males are severe enough to allow for an alternative mating strategy. Finally, we discuss how sexual and natural selective forces may interact to drive or mask the evolution of sexually dimorphic traits.


Theophylline for the prevention of radiocontrast nephropathy: a meta-analysis.
Radiocontrast nephropathy is a common cause of acute renal failure in hospitalized patients. Several studies have examined the capacity of theophylline or aminophylline to prevent radiocontrast nephropathy, with conflicting results. We conducted a meta-analysis of published randomized controlled trials to determine if the pre-procedural administration of theophylline or aminophylline prevents radiocontrast-induced declines in kidney function. We searched MEDLINE, EMBASE, the Cochrane Collaboration Database, bibliographies of retrieved articles, and consulted with experts to identify relevant studies. Randomized controlled trials of theophylline or aminophylline in hospitalized patients receiving radiocontrast were included. Studies were excluded if they did not report changes in serum creatinine or creatinine clearance within 48 h after radiocontrast exposure. Seven randomized controlled trials satisfied all inclusion criteria and were included in the analysis (pooled sample size n = 480). The difference in mean change in serum creatinine was 11.5 micromol/l (95% confidence intervals 5.3-19.4 micromol/l, P = 0.004) lower in the theophylline- or aminophylline-treated groups than controls. One participant (0.6%) required dialysis. Prophylactic administration of theophylline or aminophylline appears to protect against radiocontrast-induced declines in kidney function. Whether these agents reduce the proportion of patients who experience large decrements in serum creatinine concentration, or require dialysis, is unknown.


Differential Effects of D-Cycloserine and ACBC at NMDA Receptors in the Rat Entorhinal Cortex Are Related to Efficacy at the Co-Agonist Binding Site.
Partial agonists at the NMDA receptor co-agonist binding site may have potential therapeutic efficacy in a number of cognitive and neurological conditions. The entorhinal cortex is a key brain area in spatial memory and cognitive processing. At synapses in the entorhinal cortex, NMDA receptors not only mediate postsynaptic excitation but are expressed in presynaptic terminals where they tonically facilitate glutamate release. In a previous study we showed that the co-agonist binding site of the presynaptic NMDA receptor is endogenously and tonically activated by D-serine released from astrocytes. In this study we determined the effects of two co-agonist site partial agonists on both presynaptic and postsynaptic NMDA receptors in layer II of the entorhinal cortex. The high efficacy partial agonist, D-cycloserine, decreased the decay time of postsynaptic NMDA receptor mediated currents evoked by electrical stimulation, but had no effect on amplitude or other kinetic parameters. In contrast, a lower efficacy partial agonist, 1-aminocyclobutane-1-carboxylic acid, decreased decay time to a greater extent than D-cycloserine, and also reduced the peak amplitude of the evoked NMDA receptor mediated postsynaptic responses. Presynaptic NMDA receptors, (monitored indirectly by effects on the frequency of AMPA receptor mediated spontaneous excitatory currents) were unaffected by D-cycloserine, but were reduced in effectiveness by 1-aminocyclobutane-1-carboxylic acid. We discuss these results in the context of the effect of endogenous regulation of the NMDA receptor co-agonist site on receptor gating and the potential therapeutic implications for cognitive disorders.


Comparison of GSTM polymorphisms and risk for oral cancer between African-Americans and Caucasians.
Two members of the mu class of glutathione S-transferase (GST) genes, GSTM1 and GSTM3, have polymorphic alleles which have been associated with altered levels of GST mu protein expression and may be linked to increased risk for several tobacco-related cancers. Oral cancer is a tobacco-related disease that affects African-American men at a significantly higher incidence than Caucasian men. To examine the potential role of GSTM polymorphisms in risk for oral cancer in African-Americans and Caucasians, the prevalences of the GSTM1 null and GSTM3 intron 6 polymorphisms were examined in 63 African-American and 101 Caucasian patients with histologically confirmed primary oral cancer, as well as in 133 African-American and 213 Caucasian matched control subjects. In African-Americans, the odds ratio for oral cancer associated with the GSTM1 (0/0) genotype was 3.1 [95% confidence interval (CI) = 1.1-8.5], with the association between the GSTM1 (0/0) genotype and oral cancer risk strongest in heavy smokers [i.e. > 24 pack-years; odds ratio (OR) = 5.4, 95% CI = 1.2-24]. Using the potentially most protective GSTM1 [+]/GSTM3 (B/B) genotype as the reference group, increased risk for oral cancer was observed in African-Americans with the GSTM1 [+]/GSTM3 [(A/A) + (A/B)] (OR = 2.2, 95% CI = 0.82-6.0), GSTM1 (0/0)/GSTM3 (B/B) (OR = 4.3, 95% CI = 1.1-16), and GSTM1 (0/0)/GSTM3 [(A/A) + (A/B)] (OR = 6.6, 95% CI = 1.2-38) genotypes (P < 0.01, trend test). No significant associations were observed between GSTM genotype and oral cancer risk in Caucasians. These results suggest that the GSTM1 null and GSTM3 intron 6 polymorphisms play an important role in risk for oral cancer among African-Americans and implicates the mu class of GSTs as important tobacco carcinogen detoxifying enzymes in this population.


[Psychiatric disorders and illnesses after childbirth].
After childbirth, from about a quarter up to nearly one half of all puerperae develop a short-lasting, mild affective distress, the so called blues. During the first months after delivery, about 10-15% of all young mothers suffer from a longstanding depression which is so severe that they are in need of treatment. In one or two out of 1000 women even a psychotic disorder becomes manifest. These postpartal disturbances and diseases are often not diagnosed by doctors-on the one hand because the women concerned often hide their complaints due to shame and a sense guilt regarding their supposed failure as a good mother, on the other hand because these syndromes until now have not found enough attention in German-as opposed to Angloamerican-medicine. Yet, these disorders-apart from the blues-are very serious ones with potentially severe consequences for the mother, the baby and possibly the whole family. Women with mental disorders in their family history and especially their own history are at an increased risk. They should be informed about this and, in certain cases, be treated preventively. Women with depressive and psychotic disorders are, especially in the postpartal time, in urgent need of treatment which, depending on type and severity of the disorder, should consist of psychotherapy, frequently also pharmacotherapy, and social care. Special needs of the postpartal period such as breast-feeding or the mother-infant relationship have to be considered which often requires close cooperation of the psychiatrist/psychotherapist, the gynaecologist and the pediatrician.


An evaluation of empagliflozin and it's applicability to hypertension as a therapeutic option.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors such as Empagliflozin are novel antihyperglycemic drugs approved for the treatment of type 2 diabetes (T2D). In addition to its glucose-lowering effects, Empagliflozin promotes weight loss, blood pressure reduction, and other beneficial metabolic benefits. This review outlines the pharmacokinetics, pharmacodynamics, safety, and tolerability of Empagliflozin and discusses its role in diabetes-associated hypertension. Empagliflozin was the first in class to not only demonstrate safety of SGLT2 inhibition but also cardio- and reno-protective effects in an adequately powered cardiovascular outcome trial. The EMPA-REG study showed significant reductions in mortality from cardiovascular causes, hospitalization for heart failure, and progression of diabetic kidney disease. These benefits cannot be attributed to glycemic control alone, suggesting the involvement of other SGLT2 inhibition-mediated mechanisms. Recent data suggests the potential utility of SGLT2 inhibition in other conditions including type 1 diabetes (T1D) and non-diabetic heart failure patients with clinical trials currently being conducted. In concert with ongoing pre-clinical investigations to unravel the mechanisms contributing to cardiorenal protection, the full therapeutic potential of SGLT2 inhibition will become apparent over the next few years and promises to be one of the major success stories in clinical medicine. T1D: type 1 diabetes; T2D: type 2 diabetes; SGLT2: sodium-glucose cotransporter 2; CVD: cardiovascular disease; SBP: systolic blood pressure; DBP: diastolic blood pressure; SNS: sympathetic nervous system; BP: blood pressure; CV: cardiovascular; ZDF: Zucker diabetic fatty; CKD: chronic kidney disease; FDA: Food and Drug Administration.


Proton microprobe analysis in biology.
This paper is intended as an introduction to the field of proton microprobe analysis with special emphasis on applications in biological sciences. It is mainly intended for users of electron microscopes equipped with microprobes or other analytical equipment. The basic principles of Particle Induced X-ray Emission analysis are discussed as well as the instrumental requirements for the proton microprobe. The analytical characteristics including quantification procedures are compared with those of the electron microprobe and a review is given of various analytical applications of the proton microprobe within biology and medicine.


Treatment of childhood and adolescent depression with mianserin.
The efficacy of mianserin in treating adult depression is now well established. Since there are no publications concerning the use of mianserin in children, the authors set up an open pilot study of 110 depressed children and adolescents aged 8-19 years. The average dose of mianserin was 1 mg/kg/day. Efficacy of treatment was noticeable by the end of the first week and was maintained throughout the 60 day study period. Evaluation was based on both clinical observations and changes in scores obtained from 80 subjects. Side-effects were minimal leading to temporary withdrawal of treatment in only seven cases. The profile of mianserin in children and adolescents is similar to that of adults. It is an antidepressant with an anxiolytic component, and has a regulating effect on sleep. In view of its efficacy, compliance, and the very low incidence of side-effects, mianserin appears to be a useful treatment for depression in children and adolescents. The results of this open study justify the development of further controlled studies.


Brain mechanisms underlying the emotion processing bias in treatment-resistant depression.
Depression is associated with a cognitive bias towards negative information and away from positive information. This biased emotion processing may underlie core depression symptoms, including persistent feelings of sadness or low mood and a reduced capacity to experience pleasure. The neural mechanisms responsible for this biased emotion processing remain unknown. Here, we had a unique opportunity to record stereotactic electroencephalography (sEEG) signals in the amygdala and prefrontal cortex (PFC) from 5 treatment-resistant depression (TRD) patients and 12 epilepsy patients (as control) while they participated in an affective bias task in which happy and sad faces were rated. First, compared with the control group, patients with TRD showed increased amygdala responses to sad faces in the early stage (around 300 ms) and decreased amygdala responses to happy faces in the late stage (around 600 ms) following the onset of faces. Further, during the late stage of happy face processing, alpha-band activity in PFC as well as alpha-phase locking between the amygdala and PFC were significantly greater in TRD patients compared to the controls. Second, after deep brain stimulation (DBS) delivered to bilateral subcallosal cingulate (SCC) and ventral capsule/ventral striatum (VC/VS), atypical amygdala and PFC processing of happy faces in TRD patients remitted toward the normative pattern. The increased amygdala activation during the early stage of sad face processing suggests an overactive bottom-up processing system in TRD. Meanwhile, the reduced amygdala response during the late stage of happy face processing could be attributed to inhibition by PFC through alpha-band oscillation, which can be released by DBS in SCC and VC/VS.


Fostering hope in the patient with cancer.
When a patient is diagnosed with cancer, feelings such as fear, anxiety, and hopelessness can negatively affect a person's frame of mind. Hope can help a patient decrease anxiety and increase quality of life. Nurses should assess hope, provide interventions, be empathetic, listen, and treat patients with dignity to help improve hope and quality of life. This article features how hope can have a positive impact and provides specific information about how nurses can promote and foster hope in patients with cancer.


Antioxidant enzyme activity is up-regulated after unilateral resistance exercise training in older adults.
Cellular antioxidant capacity and oxidative stress are postulated to be critical factors in the aging process. The effects of resistance exercise training on the level of skeletal muscle oxidative stress and antioxidant capacity have not previously been examined in older adults. Muscle biopsies from both legs were obtained from the vastus lateralis muscle of 12 men 71 +/- 7 years of age. Subjects then engaged in a progressive resistance exercise-training program with only one leg for 12 weeks. After 12 weeks, the nontraining leg underwent an acute bout of exercise (exercise session identical to that of the trained leg at the same relative intensity) at the same time as the last bout of exercise in the training leg. Muscle biopsies were collected from the vastus lateralis of both legs 48 h after the final exercise bout. Electron transport chain enzyme activity was unaffected by resistance training and acute resistance exercise (p < 0.05). Training resulted in a significant increase in CuZnSOD (pre--7.2 +/- 4.2, post--12.6 +/- 5.6 U.mg protein(-1); p = 0.02) and catalase (pre--8.2 +/- 2.3, post--14.9 +/- 7.6 micromol.min(-1).mg protein(-1); p = 0.02) but not MnSOD activity, whereas acute exercise had no effect on the aforementioned antioxidant enzyme activities. Furthermore, basal muscle total protein carbonyl content did not change as a result of exercise training or acute exercise. In conclusion, unilateral resistance exercise training is effective in enhancing the skeletal muscle cellular antioxidant capacity in older adults. The potential long-term benefits of these adaptations remain to be evaluated.


Low skeletal muscle capillarization limits muscle adaptation to resistance exercise training in older adults.
Adequate muscle perfusion supports the transport of nutrients, oxygen and hormones into muscle fibers. Aging is associated with a substantial decrease in skeletal muscle capillarization, fiber size and oxidative capacity, which may be improved with regular physical activity. The aim of this study was to investigate the relationship between muscle capillarization and indices of muscle hypertrophy (i.e. lean mass; fiber cross sectional area (CSA)) in older adults before and after 12 weeks of progressive resistance exercise training (RET). Interventional study SETTING AND PARTICIPANTS: 19 subjects (10 male and 9 female; 71.1 ± 4.3 years; 27.6 ± 3.2 BMI) were enrolled in the study and performed a whole body RET program for 12 weeks. Subjects where then retrospectively divided into a LOW or HIGH group, based on their pre-RET capillary-to-fiber perimeter exchange index (CFPE). Physical activity level, indices of capillarization (capillaries-to-fiber ratio, C:Fi; CFPE index and capillary-to-fiber interface, LC-PF index), muscle hypertrophy, muscle protein turnover and mitochondrial function were assessed before and after RET. Basal capillarization (C:Fi; CFPE and LP-CF index) correlates with daily physical activity level (C:Fi, r = 0.57, p = 0.019; CFPE index, r = 0.55, p = 0.024; LC-PF index, r = 0.56, p = 0.022) and CFPE and LC-PF indices were also positively associated with oxidative capacity (respectively r = 0.45, p = 0.06; r = 0.67, p = 0.004). Following RET, subjects in the HIGH group underwent hypertrophy with significant improvements in muscle protein synthesis and muscle fiber CSA (p < 0.05). However, RET did not promote muscle hypertrophy in the LOW group, but RET significantly increased muscle capillary density (p < 0.05). Muscle fiber capillarization before starting an exercise training program may be predictive of the muscle hypertrophic response to RET in older adults. Increases in muscle fiber size following RET appear to be blunted when muscle capillarization is low, suggesting that an adequate initial capillarization is critical to achieve a meaningful degree of muscle adaptation to RET.


Proton transfer in wild-type GFP and S205V mutant is reduced by conformational changes of residues in the proton wire.
To study the dynamics and mechanisms of the proton wire of wild type green fluorescence protein (wt-GFP) and its S205V mutant, we applied molecular dynamics (MD) simulations and compared the results with the X-ray structures of both proteins and with the proton transfer kinetics of these proteins studied by the time-resolved emission technique. The MD simulations for the wt-GFP show that, in the proton wire, the Ser205 exists in two conformations with similar probabilities. One conformation supports the proton transfer, and the other does not. The fluctuation between the two conformers is relatively slow. This result may explain the time-resolved emission spectrum's long-time fluorescence tail of the wt-GFP chromophore's protonated form. The MD simulations of the S205V mutant show that the water molecule in the proton wire is replaced by other bulk water molecules along the simulations of 60 ns. Furthermore, as in the wt-GFP, the Thr203 also exists in two conformations in which only one conformation supports the proton transfer. These two findings give an insight into the relatively slow proton transfer rate in the S205V mutant in comparison to the wt-GFP.


Semantic interoperability in Czech healthcare environment supported by HL7 version 3.
The data interchange in the Czech healthcare environment is mostly based on national standards. This paper describes a utilization of international standards and nomenclatures for building a pilot semantic interoperability platform (SIP) that would serve to exchange information among electronic health record systems (EHR-Ss) in Czech healthcare. The work was performed by the national research project of the "Information Society" program. At the beginning of the project a set of requirements the SIP should meet was formulated. Several communication standards (openEHR, HL7 v3, DICOM) were analyzed and HL7 v3 was selected to exchange health records in our solution. Two systems were included in our pilot environment: WinMedicalc 2000 and ADAMEKj EHR. HL7-based local information models were created to describe the information content of both systems. The concepts from our original information models were mapped to coding systems supported by HL7 (LOINC, SNOMED CT and ICD-10) and the data exchange via HL7 v3 messages was implemented and tested by querying patient administration data. As a gateway between local EHR systems and the HL7 message-based infrastructure, a configurable HL7 Broker was developed. A nationwide implementation of a full-scale SIP based on HL7 v3 would include adopting and translating appropriate international coding systems and nomenclatures, and developing implementation guidelines facilitating the migration from national standards to international ones. Our pilot study showed that our approach is feasible but it would demand a huge effort to fully integrate the Czech healthcare system into the European e-health context.


Genes for low-molecular-weight heat shock proteins of soybeans: sequence analysis of a multigene family.
Soybeans, Glycine max, synthesize a family of low-molecular-weight heat shock (HS) proteins in response to HS. The DNA sequences of two genes encoding 17.5- and 17.6-kilodalton HS proteins were determined. Nuclease S1 mapping of the corresponding mRNA indicated multiple start termini at the 5' end and multiple stop termini at the 3' end. These two genes were compared with two other soybean HS genes of similar size. A comparison among the 5' flanking regions encompassing the presumptive HS promoter of the soybean HS-protein genes demonstrated this region to be extremely homologous. Analysis of the DNA sequences in the 5' flanking regions of the soybean genes with the corresponding regions of Drosophila melanogaster HS-protein genes revealed striking similarity between plants and animals in the presumptive promoter structure of thermoinducible genes. Sequences related to the Drosophila HS consensus regulatory element were found 57 to 62 base pairs 5' to the start of transcription in addition to secondary HS consensus elements located further upstream. Comparative analysis of the deduced amino acid sequences of four soybean HS proteins illustrated that these proteins were greater than 90% homologous. Comparison of the amino acid sequence for soybean HS proteins with other organisms showed much lower homology (less than 20%). Hydropathy profiles for Drosophila, Xenopus, Caenorhabditis elegans, and G. max HS proteins showed a similarity of major hydrophilic and hydrophobic regions, which suggests conservation of functional domains for these proteins among widely dispersed organisms.


Basic/Translational Development of Forthcoming Opioid- and Nonopioid-Targeted Pain Therapeutics.
Opioids represent an efficacious therapeutic modality for some, but not all pain states. Singular reliance on opioid therapy for pain management has limitations, and abuse potential has deleterious consequences for patient and society. Our understanding of pain biology has yielded insights and opportunities for alternatives to conventional opioid agonists. The aim is to have efficacious therapies, with acceptable side effect profiles and minimal abuse potential, which is to say an absence of reinforcing activity in the absence of a pain state. The present work provides a nonexclusive overview of current drug targets and potential future directions of research and development. We discuss channel activators and blockers, including sodium channel blockers, potassium channel activators, and calcium channel blockers; glutamate receptor-targeted agents, including N-methyl-D-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, and metabotropic receptors. Furthermore, we discuss therapeutics targeted at γ-aminobutyric acid, α2-adrenergic, and opioid receptors. We also considered antagonists of angiotensin 2 and Toll receptors and agonists/antagonists of adenosine, purine receptors, and cannabinoids. Novel targets considered are those focusing on lipid mediators and anti-inflammatory cytokines. Of interest is development of novel targeting strategies, which produce long-term alterations in pain signaling, including viral transfection and toxins. We consider issues in the development of druggable molecules, including preclinical screening. While there are examples of successful translation, mechanistically promising preclinical candidates may unexpectedly fail during clinical trials because the preclinical models may not recapitulate the particular human pain condition being addressed. Molecular target characterization can diminish the disconnect between preclinical and humans' targets, which should assist in developing nonaddictive analgesics.


Racial differences in patient consent policy preferences for electronic health information exchange.
This study aimed to explore the association between demographic variables, such as race and gender, and patient consent policy preferences for health information exchange as well as self-report by VHA enrollees of information continuity between Veterans Health Administration (VHA) and community non-VHA heath care providers. Data were collected between March 25, 2016 and August 22, 2016 in an online survey of 19 567 veterans. Three questions from the 2016 Commonwealth Fund International Health Policy Survey, which addressed care continuity, were included. The survey also included questions about consent policy preference regarding opt-out, opt-in, and "break the glass" consent policies. VHA enrollees had comparable proportions of unnecessary laboratory testing and conflicting information from providers when compared with the United States sample in the Commonwealth Survey. However, they endorsed medical record information being unavailable between organizations more highly. Demographic variables were associated with gaps in care continuity as well as consent policy preferences, with 56.8% of Whites preferring an opt-out policy as compared with 40.3% of Blacks, 44.9% of Hispanic Latinos, 48.3% of Asian/Pacific Islanders, and 38.3% of Native Americans (P < .001). Observed large differences by race and ethnicity in privacy preferences for electronic health information exchange should inform implementation of these programs to ensure cultural sensitivity. Veterans experienced care continuity comparable to a general United States sample, except for less effective exchange of health records between heath care organizations. VHA followed an opt-in consent policy at the time of this survey which may underlie this gap.


The role of proprioceptive afferents in the control of respiratory muscles.
Building largely on the results of previous studies of motor control in respiration the role of proprioceptive control of respiratory movements is discussed with particular reference to the significance of the following points: (i) The co-activation of fusimotor and alpha motoneurons in load compensation and in the control of velocity and force of the respiratory movements. (ii) The convergence onto the same intercostal spindle of fusimotor fibres for respiratory movements and for postural activity. (iii) The difference between proprioceptive control of intercostal muscles on the one hand and the diaphragm on the other, and of the control of the phrenic motoneuron pool exerted by intercostal proprioceptors. (iv) The cerebellar control both of the fusimotor-alpha balance between the indirect drive of the intercostal motoneurons and of the responsiveness of the phrenic motoneuron pool to respiratory and reflex influences. (v) Results suggesting spinobulbar reflex effects on the control of rate and depth of respiration from muscle and joint receptors of the thoracic wall.


[Mesenchymal stem cells. Basic science and future clinical use].
Mesenchymal stem cells can be obtained from a bone marrow aspirate taken from the iliac crest of adult humans. The cells can be ex vivo expanded to large numbers and retain the ability of differentiate to cardiac, bone, adipocytes and muscle cells in vitro and in vivo. Undifferentiated mesenchymal stem cells produce large numbers of growth factors that control hematopoiesis and modulate lymphocyte function. Mesenchymal stem cells are well tolerated when transplanted to humans and animals. After transplantation, the differentiation appears to be controlled by local factors in the respective tissues. When co-transplanted together with hematopoietic cells in a stem-cell transplantation setting, mesenchymal stem cells appear to enhance engraftment of the hematopoietic cells as well as reduced the incidence and severity of graft-versus-host disease.


The lure of rationality: Why does the deficit model persist in science communication?
Science communication has been historically predicated on the knowledge deficit model. Yet, empirical research has shown that public communication of science is more complex than what the knowledge deficit model suggests. In this essay, we pose four lines of reasoning and present empirical data for why we believe the deficit model still persists in public communication of science. First, we posit that scientists' training results in the belief that public audiences can and do process information in a rational manner. Second, the persistence of this model may be a product of current institutional structures. Many graduate education programs in science, technology, engineering, and math (STEM) fields generally lack formal training in public communication. We offer empirical evidence that demonstrates that scientists who have less positive attitudes toward the social sciences are more likely to adhere to the knowledge deficit model of science communication. Third, we present empirical evidence of how scientists conceptualize "the public" and link this to attitudes toward the deficit model. We find that perceiving a knowledge deficit in the public is closely tied to scientists' perceptions of the individuals who comprise the public. Finally, we argue that the knowledge deficit model is perpetuated because it can easily influence public policy for science issues. We propose some ways to uproot the deficit model and move toward more effective science communication efforts, which include training scientists in communication methods grounded in social science research and using approaches that engage community members around scientific issues.


Effect of prior exercise above and below critical power on exercise to exhaustion.
The aim of the present study was to ascertain whether the intensity of prior exercise altered the time to exhaustion at critical power (CP). Eleven participants volunteered to take part in the study (mean +/- SD: VO2max 4.1 +/- 0.5 L x min(-1); age 30.1 +/- 7.2 yr; body mass 74.6 +/- 9.1 kg) and completed three trials to exhaustion at their CP under differing prior exercise conditions: 1) a control trial (CON); 2) a trial preceded by three 60-s efforts at 110% CP (severe); and 3) a trial preceded by three 73-s efforts at 90% CP (heavy). All trials followed a 5-min baseline at 50 W. Time to exhaustion was significantly lengthened after prior heavy exercise (1071 +/- 18 s) when compared with CON (973 +/- 16 s, F = 9.53, P = 0.006). However, there was no effect on TTE after prior severe exercise (967 +/- 16 s). Oxygen deficit was significantly reduced from that in CON (3.8 +/- 0.2 L) after prior heavy (3.2 +/- 0.3 L) and prior severe exercise (3.1 +/- 0.3 L, F = 10.95, P = 0.001). Concurrently, there was a significant reduction in the magnitude of the VO2 slow component (SC) in the trials with prior exercise (197 +/- 34 and 126 +/- 19 mL x min(-1) after heavy and severe exercise, respectively) when compared with CON (223 +/- 31 mL x min(-1), F = 9.62, P = 0.006). Prior heavy exercise does appear to improve the time to exhaustion at CP by approximately 10% and is associated with a reduction in the VO2 SC. However, the reduction in the SC, with no change in performance after prior severe exercise, suggests that a reduced SC may not necessarily lead to improved TTE.


Colorectal cancer screening: low health literacy and limited English proficiency among Asians and Whites in California.
The authors examined the relationship between low health literacy (LHL), limited English proficiency (LEP), and meeting current U.S. Preventive Service Task Force colorectal cancer (CRC) screening guidelines for Asians and Whites in California. For 1,478 Asian and 14,410 White respondents 50-75 years of age in the 2007 California Health Interview Survey, the authors examined meeting CRC screening guidelines using multivariable logistic models by LEP and LHL separately and in combination. Analyses were run with the full sample, then separately for Whites and Asians controlling for demographics and insurance. For those with LEP, patient-provider language concordance and CRC screening was examined. Overall, respondents with LEP and LHL were the least likely to meet CRC screening guidelines (36%) followed by LEP-only (45%), LHL-only (51%), and those with neither LHL nor LEP (59%), a hierarchy that remained significant in multivariable models. For Whites, LHL-only was associated with screening, whereas LEP-only and LEP and LHL were significant for Asians. Having a language concordant provider was not significantly associated with CRC screening among those with LEP. Health literacy is associated with CRC screening, but English proficiency is also critical to consider. Asians with both LEP and LHL appear particularly vulnerable to cancer screening disparities.


Implementation of supported employment for homeless veterans with psychiatric or addiction disorders: two-year outcomes.
There has been growing interest in the dissemination of supported employment, but few studies have used a control group to examine the benefits of multisite dissemination efforts for clients or have addressed the needs of homeless persons with psychiatric disorders, addiction disorders, or both. This study examined a low-intensity training approach for implementing the individual placement and support (IPS) model at nine Department of Veterans Affairs (VA) programs and compared client outcomes before (phase 1) and after (phase 2) the program was implemented (phase 1). Special funds and sustained training, which was based primarily on teleconferencing, were used to support implementation of the IPS model of supported employment at nine VA programs for homeless veterans. A comparison cohort (phase 1) (N=308) was recruited from the nine sites before IPS was implemented. A postimplementation cohort (phase 2) (N=321) was recruited at the same sites and offered IPS. Mixed models were used to compare quarterly employment outcomes over two years in phase 1 and phase 2, adjusting for significant baseline differences (N=629). Measures of both client-level service delivery and site-level fidelity to IPS suggest that implementation was successful at most, but not all, sites. Overall, compared with veterans in the phase 1 group, those in the phase 2 group had a better long-term work history at the time of program entry. When the analyses controlled for baseline differences, the mean number of competitive employment days per month over the two-year follow-up period was 15% higher for veterans in phase 2 (8.4 days compared with 7.3 days; p<.001) and the mean number of days housed during follow-up was also higher in phase 2 (34.1 days compared with 29.8 days; p=.04), but there were no differences for other outcome measures. A sustained training program can be used to implement IPS in systems that have had little past experience with this approach. This effort was associated with improved employment outcomes and more rapid housing placement.


Sendai-viral HN and F glycoproteins as probes of plasma-membrane protein catabolism in HTC cells. Studies with fusogenic reconstituted Sendai-viral envelopes.
Reconstituted Sendai-viral envelopes (RSVE) were produced by the method of Vainstein, Hershkovitz, Israel & Loyter [(1984) Biochim. Biophys. Acta 773, 181-188]. RSVE are fusogenic unilamellar vesicles containing two transmembrane glycoproteins: the HN (haemagglutinin-neuraminidase) protein and the F (fusion) factor. The fate of the viral proteins after fusion-mediated transplantation of RSVE into hepatoma (HTC) cell plasma membranes was studied to probe plasma-membrane protein degradation. Both protein species are degraded at similar, relatively slow, rates (t1/2 = 67 h) in HTC cells fused with RSVE in suspension. Even slower degradation rates for HN and F proteins (t1/2 = 93 h) were measured when RSVE were fused with HTC cells in monolayer. Lysosomal degradation of the transplanted viral proteins is strongly implicated by the finding that degradation of HN and F proteins is sensitive to inhibition by 10 mM-NH4Cl (81%) and by 50 micrograms of leupeptin/ml (70%).


Cytosolic calcium and the action of vasopressin in toad urinary bladder.
The effects of experimental procedures believed to increase cytosolic calcium on basal and vasopressin-stimulated osmotic water flow and transepithelial sodium transport were examined in the toad urinary bladder. Exposure of isolated toad bladders to quinidine, calcium ionophores (A23187, X537A), or low-sodium or potassium-free serosal solutions resulted in a dose-dependent decrease in the hydrosmotic response to vasopressin or exogenous adenosine 3',5'-cyclic monophosphate (cAMP). The degree of inhibition of cAMP-induced water flow induced by low-sodium or potassium-free serosal bathing media varied, and in a similar manner, with the serosal calcium concentration. The effects of quinidine sulfate (2 X 10-4 M), X537A (2 X 10(-5) M), and low serosal sodium (20 mM), but not that of A23187 (10(-5) M), were readily reversible. Exposure to quinidine (4 X 10(-4) M), A23187 (10(-5) M), X537A (5 X 10(-6) M), or low serosal sodium (2 mM) also inhibited the basal short-circuit current (SCC). Vasopressin, 4-20 mU/ml, completely overcame the inhibition of the SCC induced by quinidine, A23187, or low serosal sodium, but a submaximal dose of hormone (4 mU/ml) failed to fully reverse the inhibitory effect of X537A, 5 X 10(-6) M. These results are consistent with the view that 1) a Na-Ca exchange process operates across the basolateral surface of the granular epithelial cells of the toad urinary bladder in vivo, and 2) the level of free calcium in the granular cell cytosol plays a modulatory role in the control of apical membrane water and sodium permeability by vasopressin, and in the regulation of the basal rate of transepithelial sodium transport.


Evaluation of maternal serum alpha-foetoprotein assay using dry blood spot samples.
The quantification of alpha-foetoprotein in dry blood spots from pregnant women was evaluated, using a conventional radioimmunoassay (RIA) with a monospecific antibody. The stability of alpha-foetoprotein in dry blood spots on filter paper was evaluated with respect to mailing, distances travelled, and the existence of high summer temperatures in our region. The results obtained show that the blood alpha-foetoprotein is stable on dry filter spots sent by mail and is stable for up to four weeks at 4, 25 and 37 degrees C. The analytical method used has a minimal detectable concentration of 10 +/- 1.9 international kilo-units/l. Both inter- and intra-assay variabilities are smaller than 10% and this method can provide results comparable with those of conventional serum assays. Results from dry blood spots and serum samples (the latter analysed by both RIA and two-site enzyme immunoassay) exhibited a good correlation (r = 0.98 and r = 0.97, p less than 0.001). The design of the assay and the nature of the samples make this method suitable for a screening programmes for the antenatal detection of open neural tube defects.


Self-seeded lasing in ionized air pumped by 800 nm femtosecond laser pulses.
We report on the lasing in air and pure nitrogen gas pumped by a single 800 nm femtosecond laser pulse. Depending on gas pressure, incident laser power and beam convergence, different lasing lines are observed in the forward direction with rapid change of their relative intensities. The lines are attributed to transitions between vibrational and rotational levels of the first negative band of the singly charged nitrogen molecule-ion. We show that self-seeding plays an important role in the observed intensity changes.


Smoking and smoking cessation during early pregnancy and its effect on adverse pregnancy outcomes and fetal growth.
Maternal smoking during pregnancy is a significant threat to the fetus. We examined the association between active maternal smoking and smoking cessation during early pregnancy with newborn somatometrics and adverse pregnancy outcomes including preterm delivery, low birth weight, and fetal growth restriction. One thousand four hundred mother-child pairs with extensive questionnaire data were followed up until delivery, within the context of a population-based mother-child cohort study (Rhea study), in Crete, Greece, 2007-2008. Comparing smokers to nonsmokers, the adjusted odds ratio (OR) was 2.8 [95% confidence interval (CI), 1.7, 4.6] for low birth weight and 2.6 (95%CI: 1.6, 4.2) for fetal growth restriction. This corresponded to a 119-g reduction in birth weight, a 0.53-cm reduction in length, and a 0.35-cm reduction in head circumference. Smoking cessation early during pregnancy modified significantly these pregnancy outcomes indicating the necessity for primary smoking prevention.


Quantitative Assessment of Point-of-Care 3D-Printed Patient-Specific Polyetheretherketone (PEEK) Cranial Implants.
Recent advancements in medical imaging, virtual surgical planning (VSP), and three-dimensional (3D) printing have potentially changed how today's craniomaxillofacial surgeons use patient information for customized treatments. Over the years, polyetheretherketone (PEEK) has emerged as the biomaterial of choice to reconstruct craniofacial defects. With advancements in additive manufacturing (AM) systems, prospects for the point-of-care (POC) 3D printing of PEEK patient-specific implants (PSIs) have emerged. Consequently, investigating the clinical reliability of POC-manufactured PEEK implants has become a necessary endeavor. Therefore, this paper aims to provide a quantitative assessment of POC-manufactured, 3D-printed PEEK PSIs for cranial reconstruction through characterization of the geometrical, morphological, and biomechanical aspects of the in-hospital 3D-printed PEEK cranial implants. The study results revealed that the printed customized cranial implants had high dimensional accuracy and repeatability, displaying clinically acceptable morphologic similarity concerning fit and contours continuity. From a biomechanical standpoint, it was noticed that the tested implants had variable peak load values with discrete fracture patterns and failed at a mean (SD) peak load of 798.38 ± 211.45 N. In conclusion, the results of this preclinical study are in line with cranial implant expectations; however, specific attributes have scope for further improvements.


Catch, bycatch and discards of the Galapagos Marine Reserve small-scale handline fishery.
Fisheries bycatch is a significant marine conservation issue as valuable fish are wasted and protected species harmed with potential negative ecological and socio-economic consequences. Even though there are indications that the small-scale handline fishery of the Galapagos Marine Reserve has a low selectivity, information on its bycatch has never been published. We used onboard monitoring and interview data to assess the bycatch of the Galapagos handline fishery by estimating the bycatch ratio, determining species compositions of landings and bycatch, identifying fishers' reasons for discarding certain individuals, and revealing historical trends in the bycatch ratio. The estimated bycatch ratio as a function of biomass of 0.40 and a diverse species composition of target catch and bycatch confirmed the low selectivity of this fishery. Most individuals were not landed for economic motivations, either because species (77.4%) or sizes (17.7%) are unmarketable or for regulatory reasons (5.9%). We found that bycatch contributes to growth overfishing of some target species because they are discarded or used as bait before reaching their first maturity. Moreover, over half of interviewees perceived a historical decrease in bycatch ratios that was explained by a diversification of the target catch due to the reduction in abundance of the traditionally most important target species. As some target species show signs of overfishing and to date there are no specific regulations for the finfish fishery species in place, we recommend the implementation of a series of management measures to protect critical life stages of overexploited species and to improve the selectivity of the Galapagos handline fishery.


The Possible Role of Helicobacter pylori Infection in Non-alcoholic Fatty Liver Disease.
Helicobacter pylori (H. pylori) which colonizes the stomach can cause a wide array of gastric disorders, including chronic gastritis, peptic ulcer, and gastric cancer. Recently, accumulating evidence has implicated H. pylori infection in extragastrointestinal diseases such as cardiovascular diseases, neurological disorders, and metabolic diseases. At the same time, many scholars have noted the relationship between H. pylori infection and non-alcoholic fatty liver disease (NAFLD). Despite the positive association between H. pylori and NAFLD reported in some researches, there are opposite perspectives denying their relationship. Due to high prevalence, unclear etiology and difficult treatment of NAFLD, confirming the pathogenicity of H. pylori infection in NAFLD will undoubtedly provide insights for novel treatment strategies for NAFLD. This paper will review the relationship between H. pylori infection and NAFLD and the possible pathogenic mechanisms.


Intracellular superoxide level controlled by manganese superoxide dismutases affects trichothecene production in Fusarium graminearum.
The intracellular superoxide level is a clue to clarification of the regulatory mechanism for mycotoxin production in Fusarium graminearum. In this study, we focused on two manganese superoxide dismutases (SODs) of the fungus, FgSOD2 and FgSOD3, to investigate the relationship of the superoxide level to trichothecene production. Recombinant FgSOD2 and FgSOD3 showed SOD activity, and they were localized mainly in the mitochondria and cytoplasm, respectively. Trichothecene production and mRNA levels of Tri5 and Tri6, which encode a trichothecene biosynthetic enzyme and a key regulator of trichothecene production, respectively, were greatly reduced in gene-deletion mutants of FgSod2 and FgSod3 (ΔFgSod2 and ΔFgSod3). Significant increases in the cytosolic and mitochondrial superoxide levels were observed in ΔFgSod2 and ΔFgSod3, respectively. These results suggested that the cellular superoxide level affects trichothecene production in F. graminearum.


Enzymatically-crosslinked injectable hydrogels based on biomimetic dextran-hyaluronic acid conjugates for cartilage tissue engineering.
Polysaccharide hybrids consisting of hyaluronic acid (HA) grafted with a dextran-tyramine conjugate (Dex-TA) were synthesized and investigated as injectable biomimetic hydrogels for cartilage tissue engineering. The design of these hybrids (denoted as HA-g-Dex-TA) is based on the molecular structure of proteoglycans present in the extracellular matrix of native cartilage. Hydrogels of HA-g-Dex-TA were rapidly formed within 2 min via enzymatic crosslinking of the tyramine residues in the presence of horseradish peroxidase and hydrogen peroxide. The gelation time, equilibrium swelling and storage modulus could be adjusted by varying the degree of substitution of tyramine residues and polymer concentration. Bovine chondrocytes incorporated in the HA-g-Dex-TA hydrogels remained viable, as shown by the Live-dead assay. Moreover, enhanced chondrocyte proliferation and matrix production were observed in the HA-g-Dex-TA hydrogels compared to Dex-TA hydrogels. These results suggest that HA-g-Dex-TA hydrogels have a high potential as injectable scaffolds for cartilage tissue engineering.


Acetyl-L-carnitine enhances the response of PC12 cells to nerve growth factor.
We have demonstrated that treatment of rat pheochromocytoma (PC12) cells with acetyl-L-carnitine (ALCAR) stimulates the synthesis of nerve growth factor receptors (NGFR). ALCAR has also been reported to prevent some age-related impairments of the central nervous system (CNS). In particular, ALCAR reduces the loss of NGFR in the hippocampus and basal forebrain of aged rodents. On these bases, a study on the effect of NGF on the PC12 cells was carried out to ascertain whether ALCAR induction of NGFR resulted in an enhancement of NGF action. Treatment of PC12 cells for 6 days with ALCAR (10 mM) stimulated [125I]NGF PC12 cell uptake, consistent with increased NGFR levels. Also, neurite outgrowth elicited in PC12 cells by NGF (100 ng/ml) was greatly augmented by ALCAR pretreatment. When PC12 cells were treated with 10 mM ALCAR and then exposed to NGF (1 ng/ml), an NGF concentration that is insufficient to elicit neurite outgrowth under these conditions, there was an ALCAR effect on neurite outgrowth. The concentration of NGF necessary for survival of serum-deprived PC12 cells was 100-fold lower for ALCAR-treated cells as compared to controls. The minimal effective dose of ALCAR here was between 0.1 and 0.5 mM. This is similar to the reported minimal concentration of ALCAR that stimulates the synthesis of NGFR in these cells. The data here presented indicate that one mechanism by which ALCAR rescues aged neurons may be by increasing their responsiveness to neuronotrophic factors in the CNS.


Excessive copper induces the production of reactive oxygen species, which is mediated by phospholipase D, nicotinamide adenine dinucleotide phosphate oxidase and antioxidant systems.
Tobacco BY-2 suspension cells were used to study the chemical damage and its associated mechanisms caused by Cu2+. Treatment with 100 micromol/L Cu2+ generated a large amount of H2O2 and thiobarbituric acid-reactive substances (TBARS) in cells. Using phospholipase D (PLD) specific inhibitor (1-butanol) or phosphatidic acid (PA), we demonstrated that PLD plays an important role in the generation of H2O2 and TBARS. Semi-quantitative reverse-transcriptase polymerase chain reaction and enzyme activity assays with wild type and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-overexpressing BY-2 cells revealed that PLD and PA are the key factors leading to NADPH oxidase activation, which is responsible for H2O2 and TBARS production induced by Cu2+. Moreover, the content of ascorbic acid (AsA), an effective antioxidant, was sharply reduced in BY-2 cells exposed to excessive Cu2+. Furthermore, a significant downregulation of the enzymes of AsA biosynthesis and the antioxidant system was found. This evidence suggests that excessive Cu2+-elevated reactive oxygen species (ROS) production is caused by upregulated PLD that elevates the activity of NADPH oxidase and its collapsed antioxidant systems that scavenges ROS.


Probing the Surface of a Parasite Drug Target Thioredoxin Glutathione Reductase Using Small Molecule Fragments.
Fragment screening is a powerful drug discovery approach particularly useful for enzymes difficult to inhibit selectively, such as the thiol/selenol-dependent thioredoxin reductases (TrxRs), which are essential and druggable in several infectious diseases. Several known inhibitors are reactive electrophiles targeting the selenocysteine-containing C-terminus and thus often suffering from off-target reactivity in vivo. The lack of structural information on the interaction modalities of the C-terminus-targeting inhibitors, due to the high mobility of this domain and the lack of alternative druggable sites, prevents the development of selective inhibitors for TrxRs. In this work, fragments selected from actives identified in a large screen carried out against Thioredoxin Glutathione Reductase from Schistosoma mansoni (SmTGR) were probed by X-ray crystallography. SmTGR is one of the most promising drug targets for schistosomiasis, a devastating, neglected disease. Utilizing a multicrystal method to analyze electron density maps, structural analysis, and functional studies, three binding sites were characterized in SmTGR: two sites are close to or partially superposable with the NADPH binding site, while the third one is found between two symmetry related SmTGR subunits of the crystal lattice. Surprisingly, one compound bound to this latter site stabilizes, through allosteric effects mediated by the so-called guiding bar residues, the crucial redox active C-terminus of SmTGR, making it finally visible at high resolution. These results further promote fragments as small molecule probes for investigating functional aspects of the target protein, exemplified by the allosteric effect on the C-terminus, and providing fundamental chemical information exploitable in drug discovery.


In Vivo Repeatability and Multiscanner Reproducibility of MRI Radiomics Features in Patients With Monoclonal Plasma Cell Disorders: A Prospective Bi-institutional Study.
Despite the extensive number of publications in the field of radiomics, radiomics algorithms barely enter large-scale clinical application. Supposedly, the low external generalizability of radiomics models is one of the main reasons, which hinders the translation from research to clinical application. The objectives of this study were to investigate reproducibility of radiomics features (RFs) in vivo under variation of patient positioning, magnetic resonance imaging (MRI) sequence, and MRI scanners, and to identify a subgroup of RFs that shows acceptable reproducibility across all different acquisition scenarios. Between November 30, 2020 and February 16, 2021, 55 patients with monoclonal plasma cell disorders were included in this prospective, bi-institutional, single-vendor study. Participants underwent one reference scan at a 1.5 T MRI scanner and several retest scans: once after simple repositioning, once with a second MRI protocol, once at another 1.5 T scanner, and once at a 3 T scanner. Radiomics feature from the bone marrow of the left hip bone were extracted, both from original scans and after different image normalizations. Intraclass correlation coefficient (ICC) was used to assess RF repeatability and reproducibility. Fifty-five participants (mean age, 59 ± 7 years; 36 men) were enrolled. For T1-weighted images after muscle normalization, in the simple test-retest experiment, 110 (37%) of 295 RFs showed an ICC ≥0.8: 54 (61%) of 89 first-order features (FOFs), 35 (95%) of 37 volume and shape features, and 21 (12%) of 169 texture features (TFs). When the retest was performed with different technical settings, even after muscle normalization, the number of FOF/TF with an ICC ≥0.8 declined to 58/13 for the second protocol, 29/7 for the second 1.5 T scanner, and 49/7 for the 3 T scanner, respectively. Twenty-five (28%) of the 89 FOFs and 6 (4%) of the 169 TFs from muscle-normalized T1-weighted images showed an ICC ≥0.8 throughout all repeatability and reproducibility experiments. In vivo, only few RFs are reproducible with different MRI sequences or different MRI scanners, even after application of a simple image normalization. Radiomics features selected by a repeatability experiment only are not necessarily suited to build radiomics models for multicenter clinical application. This study isolated a subset of RFs, which are robust to variations in MRI acquisition observed in scanners from 1 vendor, and therefore are candidates to build reproducible radiomics models for monoclonal plasma cell disorders for multicentric applications, at least when centers are equipped with scanners from this vendor.


JAPANESE QUAIL EGG EMBRYO AS A HOST FOR VIRUSES.
Rauscher, Frank J. (National Cancer Institute, Bethesda, Md.), James A. Reyniers, and Miriam R. Sacksteder. Japanese quail egg embryo as a host for viruses. J. Bacteriol. 84:1134-1139. 1962.-The egg embryo of Japanese quail (Coturnix coturnix japonica, Temminck and Schlegel) was found to support readily the growth of a wide range of viruses known to infect chicken eggs. Methods commonly used in studying viruses in chicken eggs were modified and adapted to the quail egg. The procedures are described in detail. The sensitivity of quail eggs to representative viruses of the myxo and pox groups was found to be equal to that of chicken eggs. Preliminary observations of the different responses of quail eggs to standard chicken tumor and to quail-adapted Rous sarcoma virus are described. Viruses known not to grow or induce an observable response in chicken eggs (e.g., the agents of mouse hepatitis, murine leukemias, and visceral lymphomatosis of chickens) also failed to produce such responses in quail eggs.


An approximation algorithm for the Noah's Ark problem with random feature loss.
The phylogenetic diversity (PD) of a set of species is a measure of their evolutionary distinctness based on a phylogenetic tree. PD is increasingly being adopted as an index of biodiversity in ecological conservation projects. The Noah's Ark Problem (NAP) is an NP-Hard optimization problem that abstracts a fundamental conservation challenge in asking to maximize the expected PD of a set of taxa given a fixed budget, where each taxon is associated with a cost of conservation and a probability of extinction. Only simplified instances of the problem, where one or more parameters are fixed as constants, have as of yet been addressed in the literature. Furthermore, it has been argued that PD is not an appropriate metric for models that allow information to be lost along paths in the tree. We therefore generalize the NAP to incorporate a proposed model of feature loss according to an exponential distribution and term this problem NAP with Loss (NAPL). In this paper, we present a pseudopolynomial time approximation scheme for NAPL.


Investigation of micronized titanium dioxide penetration in human skin xenografts and its effect on cellular functions of human skin-derived cells.
Titanium dioxide (TiO2) nanoparticles are ubiquitously used materials in everyday life (e.g. paints,household products and plastic goods). However, despite the wide array of common applications, their pathogenetic role was also suggested under certain conditions (e.g. pulmonary neoplasias and lung fibrosis). From a dermatological point of view, it is also of great importance that TiO2 also serves as a physical photoprotective agent in sunscreens and is widely used in various cosmetic products. However, the effect of TiO2 on human cutaneous functions is still unknown. Therefore, in the current study, we investigated the in vivo penetration of TiO2 via human skin transplanted to immunodeficient mice and,furthermore, we measured the in vitro effects of nanoparticles on various functional properties of numerous epidermal and dermal cells in culture. Hereby, using various nuclear microscopy methods, we provide the first evidence that TiO2nanoparticles in vivo do not penetrate through the intact epidermal barrier. However, we also report that TiO2, when exposed directly to cell cultures in vitro, exerts significant and cell-type dependent effects on such cellular functions as viability, proliferation, apoptosis and differentiation. Therefore, our novel findings will hopefully inspire one to systemically explore in future, clinically oriented trials whether there is indeed a risk from micronized TiO2-containing products on skin with an impaired stratum corneum barrier function.


Increased Clinical and Economic Burden Associated With Peripheral Intravenous Catheter-Related Complications: Analysis of a US Hospital Discharge Database.
The burden of complications associated with peripheral intravenous use is underevaluated, in part, due to the broad use, inconsistent coding, and lack of mandatory reporting of these devices. This study aimed to analyze the clinical and economic impact of peripheral intravenous-related complications on hospitalized patients. This analysis of Premier Perspective® Database US hospital discharge records included admissions occurring between July 1, 2013 and June 30, 2015 for pneumonia, chronic obstructive pulmonary disease, myocardial infarction, congestive heart failure, chronic kidney disease, diabetes with complications, and major trauma (hip, spinal, cranial fractures). Admissions were assumed to include a peripheral intravenous. Admissions involving surgery, dialysis, or central venous lines were excluded. Multivariable analyses compared inpatient length of stay, cost, admission to intensive care unit, and discharge status of patients with versus without peripheral intravenous-related complications (bloodstream infection, cellulitis, thrombophlebitis, other infection, or extravasation). Models were conducted separately for congestive heart failure, chronic obstructive pulmonary disease, diabetes with complications, and overall (all 7 diagnoses) and adjusted for demographics, comorbidities, and hospital characteristics. We identified 588 375 qualifying admissions: mean (SD), age 66.1 (20.6) years; 52.4% female; and 95.2% urgent/emergent admissions. Overall, 1.76% of patients (n = 10 354) had peripheral intravenous-related complications. In adjusted analyses between patients with versus without peripheral intravenous complications, the mean (95% confidence interval) inpatient length of stay was 5.9 (5.8-6.0) days versus 3.9 (3.9-3.9) days; mean hospitalization cost was $10 895 ($10 738-$11 052) versus $7009 ($6988-$7031). Patients with complications were less likely to be discharged home versus those without (62.4% [58.6%-66.1%] vs 77.6% [74.6%-80.5%]) and were more likely to have died (3.6% [2.9%-4.2%] vs 0.7% [0.6%-0.9%]). Models restricted to single admitting diagnosis were consistent with overall results. Patients with peripheral intravenous-related complications have longer length of stay, higher costs, and greater risk of death than patients without such complications; this is true across diagnosis groups of interest. Future research should focus on reducing these complications to improve clinical and economic outcomes.


Digital Health Needs of Women With Postpartum Depression: Focus Group Study.
Although approximately 10% of new mothers in Canada develop postpartum depression (PPD), they face many barriers when accessing care. eHealth offers a unique opportunity to provide psychosocial skills and support to new mothers; however, patient populations are not consistently engaged in eHealth development processes. Thus, the diversity of women's backgrounds and needs are often not reflected in existing tools. This study aims to engage women from a variety of backgrounds and locations around British Columbia (BC) who have previously experienced PPD to determine the unmet psychoeducational needs of women with PPD and how a web-enabled platform used to deliver psychosocial skills and education to assist in the management of PPD could fulfill those needs. Focus groups were conducted in 7 cities across BC with a total of 31 women (mean age 34.5 years, SD 4.9), with each group ranging from 2-7 participants. Focus groups were cofacilitated by the study coordinator and a local service provider in each community using a semistructured guide to discuss participants' needs, ideas, and opinions as they relate to the use of technology in PPD management. Transcripts were approached inductively using thematic analysis to identify themes and qualitative description to frame what was observed in the data. A total of 5 themes were identified: bridging gaps to meet needs; providing validation to combat stigma; nurturing capacity to cope, manage, and/or reach wellness; empowering people to take ownership over their mental health; and offering customization to ensure relevance. Each theme identified a need (eg, combatting stigma) and a way to address that need using a web-enabled intervention (eg, providing validation). At the intersection of these themes was the overarching value of promoting agency for women experiencing PPD. Ultimately, new mothers require accessible mental health care that promotes their agency in mental health care decision making. Our participants believed that a web-enabled intervention could help meet this need. These data will be used to guide the design of such an intervention, with the eventual implementation of this resource as a first-line management option for PPD.


Are physicians required during winch rescue missions in an Australian helicopter emergency medical service?
A helicopter emergency medical service (HEMS) capable of winching offers several advantages over standard rescue operations. Little is known about the benefit of physician winching in addition to a highly trained paramedic. To analyse the mission profiles and interventions performed during rescues involving the winching of a physician in the Greater Sydney Area HEMS (GSA-HEMS). All winch missions involving a physician from August 2009 to January 2012 were identified from the prospectively completed GSA-HEMS electronic database. A structured case sheet review for a predetermined list of demographic data and physician-only interventions (POIs) was conducted. We identified 130 missions involving the winching of a physician, of which 120 case sheets were available for analysis. The majority of patients were traumatically injured (90%) and male (85%) with a median age of 37 years. Seven patients were pronounced dead at the scene. A total of 63 POIs were performed on 48 patients. Administration of advanced analgesia was the most common POI making up 68.3% of interventions. Patients with abnormal RTSc(2) scores were more likely to receive a POI than those with normal RTSc(2) (84.8% vs 15.2%; p=0.03). The performance of a POI had no effect on median scene times (45 vs 43 min; p=0.51). Our high POI rate of 40% (48/120) coupled with long rescue times and the occasional severe injuries support the argument for winching Physicians. Not doing so would deny a significant proportion of patients time-critical interventions, advanced analgesia and procedural sedation.


Laser hair removal: comparison of long-pulsed Nd:YAG, long-pulsed alexandrite, and long-pulsed diode lasers.
Advances in laser technology over the past several years have led to the development of numerous lasers for the treatment of unwanted hair. Laser wavelength is a key factor influencing treatment efficacy and complication rates. To compare the efficacy and safety of laser hair removal using three different laser systems. A retrospective study of 805 consecutive laser-assisted hair removal treatments, conducted on 75 patients by means of either a long-pulsed Nd:YAG, a long-pulsed alexandrite, or a long-pulsed diode laser is reported. All patients were evaluated at least 3 months after the last treatment, and their present conditions were compared with the 1st-day photographs. The mean hair reduction was 42.4%, 65.6%, and 46.9% in Nd:YAG, alexandrite, and diode lasers, respectively. When the number of treatment sessions was taken into account, the efficacy of alexandrite and diode lasers was not significantly different, whereas both systems were more efficacious than Nd:YAG. Neither of the laser systems showed better results for a particular skin type. The occurrence of side effects was not significantly different between three laser systems. Both long-pulsed alexandrite and long-pulsed diode laser systems are effective in the treatment of unwanted hair, and they are more efficacious than Nd:YAG laser.


[Treatment of acute brain edema].
To review the basic concepts and mechanisms of cerebral edema and to analyze current management of this complex clinical problem. Cerebral edema is a stereotyped reaction of the brain to any aggression and is a very common complication in patients with alterations of the blood-brain barrier. The cerebral edema should be recognized and treated early and aggressively to avoid disastrous results such as cerebral herniation. The most important types of edema are the vasogenic and cytotoxic. The first implies primary alterations of the blood-brain barrier, whilst in the second they are of cellular homeostasis. We have reviewed how various pro-inflammatory substances interact to stimulate the mechanisms causing edema, and also the importance of cerebrovascular autoregulation for maintenance of a normal intracranial volume. The measures necessary for good cerebral reanimation are the following: evaluation of the airway, controlled hyperventilation, maintenance of the cerebral perfusion pressure > 70 mmHg, suitable position of the head, administration of hypertonic solutions, dexamethasone, and possibly barbiturates. We have shown that a body temperature > 37.5 degrees C and blood glucose > 150 mg/dl are related to worsening of the cerebral edema. Finally, we have reviewed other experimental treatments which seem promising, such as hemicraniectomy, hypertonic saline solutions, hypothermia and other neuroprotector agents. All patients with acute cerebral edema should be evaluated early and treated with therapy which will solve the underlying pathological problem. Good medical management of these patients is of vital importance to assure a satisfactory clinical outcome. Recently new, effective therapy has been evaluated which may substantially change current concepts of the treatment of patients with acute cerebral edema.


[Common antigens of stable group A streptococcal L forms and muscle fibers of human myocardium].
The immunofluorescence method was used to demonstrate that the antigens of stable streptococcus L-forms and of the cytoplasmic membrane of human myocardium muscle fibers were common. The common antigen was included into the composition of the surface membrane of the muscle cell adjacent to the sarcolemma, and of the transverse tubule membranes of the sarcoplasma reticulum passing in the Z-band region of the muscle fiber sarcomeres. The reactions is completely prevented by the exhaustion of the anti-serum to the antigen of the L-forms with the homogenate of human myocardium tissues or a suspension of the L-form cultures grown both on meat and on casein media. Exhaustion with tissue homogenate of other organs (the liver) or with concentrated nutrient medium practically failed to influence the extent of this reaction. The authors believe that the commonnes of the antigens of stable L-forms of streptococcus, group A, cultures and of the myocardium could serve as one of the causes of prolonged persistence of L-forms in human and animal organism.


New mathematical approach for the evaluation of drug binding to human serum albumin by high-performance liquid affinity chromatography.
A novel mathematical approach for investigation of drug-human serum albumin (HSA) interactions by means of high-performance liquid affinity chromatography is developed. The model is based on the assumption that two types of competitive binding sites exist on the HSA molecule. The widely used single-site binding equation is extended and a proper mathematical analysis is proposed allowing the determination of the major parameters characterizing the multisite binding (cobinding) process. The utility of the new approach is proved by competitive studies on HSA binding of two model drugs, diazepam and diclofenac.


[Role of peptide complexes from the kidney and thymus in the regulation of apoptosis in lymphoid cells].
Using morphological and electrophoresis methods special features of apoptosis induction by peptide complexes from kidney and thymus were analyzed in thymocytes and peripheral blood lymphocytes of pigs. It was shown that peptide complexes both from kidney and thymus induced thymocytes apoptosis in an allogenic system. In these conditions, genetic distinctions between individuals and a degree of thymocyte maturation determined the level of apoptosis.