DNA synthesis and endomitoses in the giant nuclei of the silkgland of Bombyx mori.
At the first symptoms of organisation of the silkgland in the embryo, mitoses stop and nuclei start to grow. Through autoradiographic studies, performed after sequenced labeling with [3H] and [14C] thymidine, the durations of the different phases of DNA synthesis cycles (T = 42 to 48 h, S = 22 to 25 h, G = 20 to 23 h) are established. These durations are in fact identical during the second and the third instar, and the same, whatever region is concerned : posterior, middle or anterior parts. A model has been established to account for the distribution of the S phases during the second and third instars. The DNA synthesis in all nuclei of a given region has been followed during the first four instars by labelling with [3H]thymidine. The activity goes through maxima and minima, depending on the percent of nuclei synthesizing DNA and their synchronism, both being characteristic of each region; long resting periods are observed during the molting stages of the first three instars in the middle and the anterior parts. The coincidence is obvious between the maxima and minima and respectively the S and G phases of the model. DNA assays agree with the distribution of cycles established by autoradiography if one admits that each cycle does lead to a doubling of the amount of DNA. The overall DNA synthesis from the diploid value is estimated to correspond to 18-19 endomitoic cycles in the nucleic of the posterior part, 19-20 cycles of those of the middle part and 13 in those of the anterior part. The analysis of chromosome structures, by squashing the nuclear content, shows that existence of a complete endomitotic cycle: the doubling of chromosomes is associated with condensed structures, alternating with a decondensed state of chromatin, responsible for the DNA synthesis. The female heterochromatin undergoes a restricted morphological cycle delayed with respect to bulk chromatin. It is characterized by a late DNA duplication and by non dispersed daughter chromosomes. Some of these aspects are, to a lesser extent, reproduced in groups of autosomic chromosomes.


Embolization of Urinary Tract Fistulae Using an AMPLATZER Vascular Plug and Glue.
Six patients (mean age, 57.7 y ± 19.7) with persistent urinary fistulae underwent 7 urinary tract embolizations with AMPLATZER Vascular Plugs (AVPs) and glue: 5 with concomitant cavity obliteration with glue and 2 without. A single procedure was successful in resolving urinary leakage in 5 patients (71%) at a mean follow-up of 27.3 wk ± 31.5 (median, 9.7 wk; range, 4.9-80 wk). Repeat cavity embolization was required in 2 instances to achieve clinical success. Mean survival was 42.3 wk (median, 16.4 wk; range, 11.7-104 wk). Combined AVP and glue embolization may prove to be a primary approach in the control of persistent fistulae.


Placental GPI-PLD is of maternal origin and its GPI substrate is absent from placentae of pregnancies associated with pre-eclampsia.
Pre-eclampsia (PE) is a disorder affecting 5-10% of all pregnancies and is characterised by abnormal trophoblast invasion, maternal endothelial cell dysfunction and a systemic maternal response. A unifying factor responsible for eliciting these effects remains unknown. However, levels of the autocrine insulin mediators, inositolphosphoglycans (IPG), are elevated 3-fold in pre-eclamptic placentae compared with controls and are also elevated 3-fold in maternal urine of pre-eclamptic women, suggesting an abnormal paracrine role of the mediator in the systemic maternal response. At the placental level, IPGs are metabolic second messengers capable of eliciting some of the characteristic features of PE, such as the 10-fold increase in glycogen synthesis and 16-fold increase in the activity of the IPG-dependent enzyme glycogen synthase. IPGs are derived from their lipidic precursors, the glycosylphosphatidylinositols (GPI), in membrane associated caveolae by the action of a GPI-specific phospholipase D whose activity is regulated by its membrane microenvironment. We show that the lipidic GPI precursor was detected in total placental membrane and microvillous membrane from normal placentae. The presence of GPI could not be detected in PE placentae, suggesting that the GPI/IPG signalling system is dysregulated in this disorder. Equivalent amounts of a proteolytically-cleaved 50 kDa GPI-PLD protein is detected in both normal and PE placentae. However, GPI-PLD mRNA is absent, suggesting a mechanism of uptake from maternal serum. Since GPI-PLD, whose presence is required for hydrolysis of GPI and release of free IPG, is detectable with equal activity in both normal and PE placentae, we postulate that dysregulation of the tubular caveolar structure of the microvilli in pre-eclamptic placentae provides an environment which promotes the unregulated hydrolysis of GPI in this disorder.


Ultrasensitive Label-Free Detection of Protein-Membrane Interaction Exemplified by Toxin-Liposome Insertion.
Measuring the high-affinity binding of proteins to liposome membranes remains a challenge. Here, we show an ultrasensitive and direct detection of protein binding to liposome membranes using high throughput second harmonic scattering (SHS). Perfringolysin O (PFO), a pore-forming toxin, with a highly membrane selective insertion into cholesterol-rich membranes is used. PFO inserts only into liposomes with a cholesterol concentration >30%. Twenty mole-percent cholesterol results in neither SHS-signal deviation nor pore formation as seen by cryo-electron microscopy of PFO and liposomes. PFO inserts into cholesterol-rich membranes of large unilamellar vesicles in an aqueous solution with Kd = (1.5 ± 0.2) × 10-12 M. Our results demonstrate a promising approach to probe protein-membrane interactions below sub-picomolar concentrations in a label-free and noninvasive manner on 3D systems. More importantly, the volume of protein sample is ultrasmall (<10 μL). These findings enable the detection of low-abundance proteins and their interaction with membranes.


A New Trend in Social Media and Medicine: The Poor Quality of Videos Related to Ankle Sprain Exercises on TikTok.
Social media platforms, like TikTok, have become popular options for the distribution of health care information. Because of the lack of scientific oversight, the quality of health care-related videos has become a focus of the current literature. However, orthopaedic surgery has lagged behind other fields in acknowledging the widespread utilization of TikTok videos for medical information consumption. This study aims to assess the quality and educational benefits of ankle sprain-related TikTok videos. TikTok was queried using the hashtag "#anklesprainexercises." One hundred videos were included after applying the exclusion criteria. The number of views, likes, shares, comments, and favorites was recorded. The content was graded using DISCERN (a well-validated informational analysis tool) and ASEES (a self-designed tool for exercise evaluation). We hypothesized that information on TikTok related to ankle sprain exercises would be poor in quality. The total number of views of the 100 videos was 6 483 412, with a median of 5377.5 (IQR = 1074-20 275). The videos collectively received 385 847 likes, 3642 comments, 55 574 favorites, and 14 918 shares with a median of 267.5 (IQR = 41.5-1678.0), 4.0 (IQR = 0.0-23.0), 42.0 (IQR = 4.8-264.5), and 13.0 (IQR = 1.8-67.8), respectively. General users had a higher percentage of their videos graded as "very poor" (61.8%) in comparison to the number of videos uploaded by health care professionals deemed "very poor" (34.4%). Neither general user nor health care professionals had videos graded as "good" or "excellent." There were significant differences between the 2 groups for DISCERN 1, 3, and ASSES scores. Although TikTok is a powerful tool for information distribution, the educational value of the videos related to ankle sprain injury exercises was poor. With only 2% of videos receiving a grade of "fair," and no videos reaching a score of "good" or "excellent," health care professionals should be aware of the low-quality content easily accessible on TikTok. Level III, cross-sectional study.


The interaction of the von Hippel-Lindau tumor suppressor and heterochromatin protein 1.
Inactivation of the von Hippel-Lindau (VHL) tumor suppressor is associated with renal carcinoma, hemangioblastoma and pheochromocytoma. The VHL protein is a component of a ubiquitin ligase complex that ubiquitinates and degrades hypoxia inducible factor-α (HIF-α). Degradation of HIF-α by VHL is proposed to suppress tumorigenesis and tumor angiogenesis. Several lines of evidence also suggest important roles for HIF-independent VHL functions in tumor suppression and other biological processes. Using GST-VHL pull-down experiment and mass spectrometry, we detected an interaction between VHL and heterochromatin protein 1 (HP1). We identified a conserved HP1-binding motif (PXVXL) in the β domain of VHL, which is disrupted in a renal carcinoma-associated P81S mutant. We show that the VHL P81S mutant displays reduced binding to HP1, yet retains the ability to interact with elongin B, elongin C, and cullin 2 and is fully capable of degrading HIF-α. We also demonstrate that HP1 increases the chromatin association of VHL. These results suggest a role for the VHL-HP1 interaction in VHL chromatin targeting.


The impact of isolation precautions on caregiver-infant interactions in the neonatal intensive care unit: A case-control study.
This case-control study investigated the association between isolation precautions and the frequency of infant-caregiver interaction in the NICU. Interactions were discretely counted; cases and controls were matched by isolation status. Cases had fewer interactions than controls (median, 4 vs 8; P < .0001). Further research is needed to determine whether this reduction impacts patient outcomes.


Innate immunity in the CNS: redefining the relationship between the CNS and Its environment.
The concept of the CNS as an immune-privileged organ has led to a common misunderstanding that it is not an active immunological organ, guarded from its surroundings by the blood-brain barrier (BBB). Recent advances in this field clearly demonstrate that the CNS is a highly immunologically active organ, with complex immune responses mostly based on innate immune processes. Such responses implicate a continuum of heterogeneous cell types both inside the CNS, in the periphery, and at their interface, the BBB. This Review aims to discuss the importance of the BBB as the first line of defense against brain infections and injuries of the CNS and the main molecular mechanisms involved in the control of the innate immune system of the CNS. We also review the central role of the neurovascular unit in diseases of the CNS and how it can be targeted for novel therapeutic strategies.


Immediate radiological management of disasters.
During the past 13 years, 93 civil disasters have been dealt with by the Accident and Emergency (A/E) department of the Royal Victorial Hospital, Belfast. The average number of patients requiring hospital treatment was 30 per incident. Most of these needed some form of radiographic examination. The radiological work-load in one major disaster is described. The need for senior radiological, radiographic and clerical staff at such times is emphasised. The rapid and efficient management of patients is essential to avoid life-threatening delays. Radiological priorities in the immediate phase of trauma are discussed. Chest, spinal and pelvic X-rays usually take precedence. A review of 100 patients with significant intra-abdominal trauma showed a poor correlation with the plain-film appearances. Early resort to more accurate diagnostic methods, such as angiography and computed tomography, is suggested. The need for more active participation by radiologists in the A/E department is stressed.


Biosynthesis, processing, and extracellular release of alpha-L-fucosidase in lymphoid cell lines of different genetic origins.
In humans, the quantity of alpha-L-fucosidase in serum is determined by heredity. The mechanism controlling levels of the enzyme in serum is unknown. Lymphoid cell lines derived from individuals with either low, intermediate, or high alpha-L-fucosidase in serum were established. Steady-state levels of intracellular and extracellular alpha-L-fucosidase as well as rates of synthesis and secretion of enzyme overlapped among the cell lines. Thus, in vivo serum phenotypes were not expressed in this system. No appreciable differences in the qualitative processing of newly made alpha-L-fucosidase were observed among these lymphoid cell lines. Cells pulse-labeled with 35S-methionine from 0.25 to 2 hr had an intracellular form of enzyme with a Mr = 58,000. Cells pulsed for 1.5 hr and chased for 21 hr with unlabeled methionine had an intracellular form of Mr = 60,000 and an extracellular form of Mr = 62,000. All three enzyme forms were glycoproteins with a common polypeptide chain of Mr = 52,000 but with different carbohydrate moieties. No evidence for a high molecular mass precursor form of alpha-L-fucosidase was found. Fucosidosis is a rare, inherited disease in which alpha-L-fucosidase activity in tissues and body fluids is low or absent. The mutations for fucosidosis and the serum polymorphism map separately. Lymphoid cells from two siblings with fucosidosis had 8-fold to 341-fold less intracellular alpha-L-fucosidase protein with 11-fold to 56-fold lower specific activities than control cells. Residual mutant enzyme was a glycoprotein with a polypeptide chain virtually the same size (Mr = 52,000) as control enzyme. However, residual mutant enzyme was hypoglycosylated and hypersecreted as compared to control enzyme.


Prognostic analysis and nomogram establishment in patients with early esophageal cancer receiving endoscopic therapy: a population-based study.
The growing numbers of early esophageal cancer (EEC) have increased the demand for endoscopic therapy. To clarify the influential factors for the prognosis of patients with EEC receiving endoscopic surgery, and to construct a nomogram to evaluate the prognostic value of endoscopic therapy. Prognostic analysis study. Clinical data of EEC patients who received endoscopic therapy between 2004 and 2015 were collected from the Surveillance, Epidemiology, and End Results database and used to construct the nomogram. The prognosis was analyzed by R language; the nomogram was constructed by Cox survival analysis; and the accuracy of the nomogram was verified by C index and the receiver operating characteristic (ROC) and calibration curves. X-Tile software was used to stratify the risk of patients. Our study constructed the nomogram of the prognosis of patients with EEC treated by endoscopic surgery, including 1118 patients and 5 independent prognostic factors of esophageal cancer-specific survival. The C index and the area under the ROC curve (AUC) of the training and verification cohorts were all >0.75. The calibration curve also reflected the good consistency of the model in predicting survival. Significant difference in the risk of patients from different stratifications with the same T staging existed, and the model had a better C index than that of the T staging. Our study reports potential influential factors affecting the prognosis of EEC patients who received endoscopic therapy and establishes a reliable nomogram to predict the risk and prognosis, which has certain advantages compared with traditional TNM staging system.


Plant RNA-mediated gene regulatory network.
Not all transcribed RNAs are protein-coding. Some non-coding RNAs (ncRNAs) seem to be non-functional and are resulted from spurious transcription. Many others have a significant function in the translation process. Gene expressions depend on complex networks of diverse gene regulatory pathways. Several ncRNAs, as major elements, regulate gene expression in a sequence-specific system either at the transcriptional level or post-transcriptional level. RNA-mediated gene regulation machinery is evolutionarily ancient and pretty complex. In this review, the current knowledge in the field of RNA-mediated gene silencing have been summarized.


Primary central nervous system lymphoma: monocenter, long-term, intent-to-treat analysis.
This retrospective, single-center study assessed the feasibility, outcome, and late side effects of the treatment of immunocompetent patients with primary central nervous system lymphoma (PCNSL) at the authors' institution. All 72 consecutive patients diagnosed with PCNSL between January 1994 and February 2005 were scheduled to receive high-dose methotrexate (HDMTX)-based chemotherapy. The median age of the patients was 62 years and the median Karnofsky performance score (KPS) was 70. Twelve patients did not receive HDMTX-based chemotherapy because of poor physical condition or renal insufficiency. Of the 60 patients treated with HDMTX-based chemotherapy, the treatment of 9 was followed with whole-brain irradiation. Of 54 patients who were evaluable for response, 35 (65%) responded (52% with a complete response and 13% with a partial response), and 19 patients (35%) did not. At a median follow-up of 58.7 months, the median progression-free survival was 9 months and the median overall survival (OAS) was 41.4 months. According to the Memorial Sloan-Kettering Cancer Center (MSKCC) prognosis score, patients could be divided into 3 groups with significantly different OAS: 52.9 months for patients aged <50 years, 42.4 months for patients aged >or= 50 years and with a KPS >70, and 5.2 months for patients aged >or= 50 years and with a KPS <70 (P= .009, log-rank test). Promising long-term results could be achieved with HDMTX-based chemotherapy in patients with PCNSL in this monocenter study. The MSKCC score proved useful for predicting survival.


Floating assembly of diatom Coscinodiscus sp. microshells.
Diatoms have silica frustules with transparent and delicate micro/nano scale structures, two dimensional pore arrays, and large surface areas. Although, the diatom cells of Coscinodiscus sp. live underwater, we found that their valves can float on water and assemble together. Experiments show that the convex shape and the 40 nm sieve pores of the valves allow them to float on water, and that the buoyancy and the micro-range attractive forces cause the valves to assemble together at the highest point of water. As measured by AFM calibrated glass needles fixed in manipulator, the buoyancy force on a single floating valve may reach up to 10 μN in water. Turning the valves over, enlarging the sieve pores, reducing the surface tension of water, or vacuum pumping may cause the floating valves to sink. After the water has evaporated, the floating valves remained in their assembled state and formed a monolayer film. The bonded diatom monolayer may be valuable in studies on diatom based optical devices, biosensors, solar cells, and batteries, to better use the optical and adsorption properties of frustules. The floating assembly phenomenon can also be used as a self-assembly method for fabricating monolayer of circular plates.


Water and sediment quality, partial mass budget and effluent N loading in coastal brackishwater shrimp farms in Bangladesh.
The present study aimed to quantify the water and sediment quality and growth and production parameters and to establish nutrient budgets for an average of five selected semi-intensive shrimp ponds in Bangladesh over a growing cycle. Physico-chemical parameters of water and sediments were measured and analyzed by standard methods. Gross yield (kg ha-1) of shrimp was calculated from the stocking and harvesting data. Finally, a partial nutrient mass budget for N and P was calculated. Most of the parameters of water and sediments correlated significantly with each other suggesting a high degree of interactions between different parameters in the system. Significantly higher concentrations of all species of nitrogenous nutrients were recorded in the effluent waters than that entering into the ponds. Therefore, a high loading and net output of nitrogenous nutrients in effluent waters was documented. The study also indicated a net discharge of solids and minerals through effluent loading. However, significantly lower concentrations of phosphorus in the effluent water indicated a net retention and trapping of phosphatic nutrients in the environment. Total production ranged between 532.0 and 697.0 kg ha-1 cycle-1 and P. monodon production between 484.0 and 562.0 kg ha-1 cycle-1. Ponds gained nitrogen primarily from intake water (55%) and fertilizers (29%), and nitrogen was lost primarily from water exchange (78%) and harvested shrimp (12%). Phosphorus gain occurred mostly from intake water (52%) and fertilizers (25%), and phosphorus was lost primarily from water exchange (52%) and harvested shrimp (3.3%). About 10% of input nitrogen and 44% of phosphorus were not accounted for in measured losses, and presumably were fixed or metabolized in the system. On average, 78 g N was discharged to and 25 g P was removed from the surrounding water by the system for each kilogram of shrimp produced. Mean conversion of feed nitrogen and phosphorus to shrimp flesh averaged 74% and 40%, respectively. It was concluded that semi-intensive systems serve as net supplier of N to and net remover of P from the surrounding water.


Theoretical studies on beta-lactam antibiotics. I. Conformational similarity of penicillins and cephalosporins to X-D-alanyl-D-alanine and correlation of their structure with activity.
The substrate analogue hypothesis proposed for the mechanism of the action of penicillins and cephalosporins is examined by stereochemical criteria. These beta-lactam antibiotics assume conformation similar to X-D-alanyl-D-alanine due to the presence of the lactam ring; this disagrees with the assumption made by Tipper & Strominger that L and D amino acid residues take similar conformation. The model proposed in this study for the activity of these antibiotics differs considerably from the earlier models, mainly in phi2 rotational angle which determines the conformation of the aminoacyl group. The inactivity of C6 or C7 epimers and the effect of various substitutions at 6alpha or 7alpha and C2 positions of penicillins and cephalosporins on the biological activity are explained.


Metanephric mesenchyme-derived Foxd1+ mesangial precursor cells alleviate mesangial proliferative glomerulonephritis.
Mesangial proliferative glomerulonephritis (MsPGN) is a glomerular disease characterized by the proliferation of mesangial cells and the accumulation of mesangial matrix. No effective treatment is currently able to stop or reverse the disease process. Here, we isolated metanephric mesenchyme-derived Foxd1+ mesangial precursor cells from E13.5 Foxd1Cre; DTRflox double transgenic embryo mice. The Foxd1+ cells showed the cell-specific expression of high levels of Foxd1 without Six2 and manifested specific cell surface markers of mesenchymal stem cells while retaining their differentiation potential. Next, an anti-Thy1 MsPGN rat model was established, and the Foxd1+ cells were injected into the tail veins 24 h later. We found that the Foxd1+ cells could improve the pathological changes to the kidney and significantly reduce proteinuria by inhibiting the sonic hedgehog pathway. Moreover, the Foxd1+ cells could inhibit PDGF-BB-induced activation of mesangial cells by secreting multiple cytokines, including hepatocyte growth factor. Our study uncovered the novel function of Foxd1+ mesangial precursor cells in repairing the damaged mesangium, stabilizing the structure and function of mesangial cells, and restoring their therapeutic effect on the MsPGN. KEY MESSAGES: It is viable to isolate highly purified metanephric mesenchyme-derived Foxd1+ mesangial precursor cells using transgenic mice. Foxd1+ cells could alleviate experimental mesangial proliferative glomerulonephritis and PDGF-induced mesangial cell proliferation through a variety of mechanisms including inhibiting the sonic hedgehog pathway and secreting multiple cytokines. As the progenitor cells of mesangial cells, Foxd1+ cells could stabilize the structure and function of mesangial cells that had undergone pathological changes.


Myelin basic protein in cerebrospinal fluid from children.
Forty-one cerebrospinal fluid (CSF) specimens from children were investigated with a radioimmunoassay for their content of myelin basic protein (BP). Eight specimens were regarded as BP-positive (BP is greater than or equal to 1.0 ng/ml). Twenty-nine were BP-negative and 4 could not be analyzed because of an excessive protein content. The BP-positive samples were from 6 children with evidence of severe acute brain damage leading to death in 5 cases: i.e., 2 term newborns with perinatal asphyxia, a 4 week-old child with severe convulsions, a 3 year-old boy with hypoxia due to laryngitis, and a 12 year-old girl with encephalitis. One preterm baby survived severe hypoxia and developed hydrocephalus shortly afterwards. We conclude that BP becomes detectable in CSF of newborns and older children under certain pathological conditions, and that the presence of BP in CSF may be associated with severe brain tissue destruction.


Glycerol valorization using Colombian olivine as a catalyst.
The biodiesel industry currently generates large amounts of crude glycerol that are not marketed, thus accumulating, and causing environmental problems. This study evaluates the catalytic potential of Colombian olivine, using glycerol steam reforming to assess valorization alternatives for this by-product. The analyzed olivine was thermally treated at 1200 °C and reduced at 900 °C, then producing nanometer-sized Fe compounds. The catalyst was characterized by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) surface area, scanning electron microscopy (SEM), temperature-programmed reduction (TPR), and transmission electron microscopy (TEM). Calcined olivine increased glycerol conversion at 600 °C from 43% (without catalyst) to 96% with the formation of liquid-phase products such as aldehydes and carboxylic acids. In addition, syngas with H2/CO ratios of 1.1 and 1.5 was generated at reaction temperatures of 700 °C and 800 °C, respectively, with low CH4 content. Finally, it was established that olivine from Medellín, under the conditions used for glycerol steam reforming, is a viable and interesting alternative to valorize glycerol into gas- or liquid-phase products.


Factors associated with adoption of robotic surgical technology in US hospitals and relationship to radical prostatectomy procedure volume.
Robotic technology has diffused rapidly despite high costs and limited additive reimbursement by major payers. We aimed to identify the factors associated with hospitals' decisions to adopt robotic technology and the consequences of these decisions. This observational study used data on hospitals and market areas from 2005 to 2009. Included were hospitals in census-based statistical areas within states in the State Inpatient Database that participated in the American Hospital Association annual surveys and performed radical prostatectomies. The likelihood that a hospital would acquire a robotic facility and the rates of radical prostatectomy relative to the prevalence of robots in geographic market areas were assessed using multivariable analysis. Hospitals in areas where a higher proportion of other hospitals had already acquired a robot were more likely to acquire one (P=0.012), as were those with more than 300 beds (P<0.0001) and teaching hospitals (P<0.0001). There was a significant association between years with a robot and the change in the number of radical prostatectomies (P<0.0001). More radical prostatectomies were performed in areas where the number of robots per 100,000 men was higher (P<0.0001). Adding a single robot per 100,000 men in an area was associated with a 30% increase in the rate of radical prostatectomies. Local area robot competition was associated with the rapid spread of robot technology in the United States. Significantly more radical prostatectomies were performed in hospitals with robots and in market areas of hospitals with robotic technology.


Amygdala response in patients with acute PTSD to masked and unmasked emotional facial expressions.
This study used functional magnetic resonance imaging to investigate amygdala response in patients with acute posttraumatic stress disorder (PTSD) to emotional expressions. Thirteen medication-free individuals with acute PTSD and no axis I psychiatric comorbidity were scanned while viewing pictures of fearful or happy faces, presented above or below consciousness, with backward masking. There was a significant positive correlation between the severity of PTSD and the difference in amygdala responses between masked fearful and happy faces and a corresponding negative correlation for the difference between unmasked fearful and happy faces. These findings suggest that functional abnormalities in brain responses to emotional stimuli observed in chronic PTSD are already apparent in its acute phase.


Release of zirconia nanoparticles at the metal stem-bone cement interface in implant loosening of total hip replacements.
In a previous failure analysis performed on femoral components of cemented total hip replacements, we determined high volumes of abraded bone cement. Here, we describe the topography of the polished surface of polymethyl methacrylate (PMMA) bone cement containing zirconia radiopacifier, analyzed by scanning electron microscopy and vertical scanning interferometry. Zirconia spikes protruded about 300nm from the PMMA matrix, with pits of former crystal deposition measuring about 400nm in depth. We deduced that the characteristically mulberry-shaped agglomerates of zirconia crystals are ground and truncated into flat surfaces and finally torn out of the PMMA matrix. Additionally, evaluation of in vitro PMMA-on-PMMA articulation confirmed that crystal agglomerations of zirconia were exposed to grain pullout, fatigue, and abrasion. In great quantities, micron-sized PMMA wear and zirconia nanoparticles accumulate in the cement-bone interface and capsular tissues, thereby contributing to osteolysis. Dissemination of nanoparticles to distant lymph nodes and organs of storage has been reported. As sufficient information is lacking, foreign body reactions to accumulated nanosized zirconia in places of long-term storage should be investigated. The production of wear particles of PMMA bone cement in the interface to joint replacement devices, presents a local challenge. The presence of zirconia particles results in frustrated digestion attempts by macrophages, liberation of inflammatory mediators, and necrosis leading to aseptic inflammation and osteolyses. Attempts to minimize wear of articulating joints reduced the attention to the deterioration of cement cuffs. We therefore investigated polished surfaces of retrieved cuffs to demonstrate their morphology and to measure surface roughness. Industrially admixed agglomerates of the radiopacifier are abraded to micron and nano-meter sized particles. The dissemination of zirconia particles in the reticulo-endothelial system to storage organs is a possible burden. Research to replace the actual contrast media by non-particulate material deserves more attention.


CXCL9 and its Receptor CXCR3, an Important Link Between Inflammation and Cardiovascular Risks in RA Patients.
Cardiovascular disease (CVD) is the most common cause of mortality in rheumatoid arthritis (RA), and Inflammation has a decisive role in its pathogenesis. CXCL9 contributes to multi aspects of inflammatory reactions associated with the pathogenesis of CVD. In the current study, we evaluated the association of plasma CXCL9 and CXCR3 gene expression with Cardiovascular risk factors in RA patients for the first time. Thirty newly diagnosed, 30 on-treatment RA patients, and 30 healthy subjects were recruited in this study. The plasma concentration of CXCL9 and CXCR3 gene expression were measured using ELISA and Real-Time PCR, respectively. The CVD risk was evaluated using Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE). The plasma levels of CXCL9 were significantly higher in the newly diagnosed and on-treatment RA patients compared to the control group (P < 0.0001 and P < 0.001, respectively). Also, The CXCR3 gene expression was strongly elevated in newly diagnosed and on-treatment patients (P < 0.001 and P < 0.01, respectively). The CXCL9 and CXCR3 were significantly associated with RA disease activity (P = 0.0005, r = 0.436; P = 0.0002, r = 0.463, respectively). The FRS was remarkably higher in newly diagnosed and on-treatment patients (P = 0.014 and P = 0.035, respectively). The CXCR3 gene expression significantly correlated with age, systolic blood pressure, FRS, and SCORE (P = 0.020, r = 0.298; P = 0.006, r = 0.346; P = 0.006, r = 0.349; P = 0.007, r = 0.341, respectively). The CXCL9 plasma concentration had a significant negative correlation with plasma HDL and LDL levels (P = 0.033, r = -0.275; P = 0.021, r = -0.296, respectively). CXCL9 and CXCR3 correlates with different variables of CVD in RA.


Exploring Influences of Eating Behaviors Among Emerging Adults in the Military.
Identify factors influencing eating behaviors among emerging adults in the military. Focused ethnography using interviews, observations, and artifacts for data. Three US Naval installations. Thirty-two active-duty Sailors aged 18-25 years. Qualitative data were organized in NVivo and analyzed sequentially to categorize culturally relevant domains and themes using a social ecological model (SEM). Descriptive statistics were used to describe questionnaire data in SPSS (version 27.0, IBM, 2020). Leaders encouraged healthy eating through policies and messages, but cultural contradictions and environmental barriers undermined Sailors' efforts to eat healthily. Stress and resource constraints (intrapersonal), peer pressure (social), unhealthy food environments and lack of access to food preparation (environmental), and eating on the go because of mission-first norms (cultural) promoted unhealthy eating behaviors. Nutrition and culinary literacy (intrapersonal); peer support and leadership engagement (social); access to healthy, convenient, and low-cost foods (environmental); and indoctrination to healthy eating during recruit training (cultural) positively influenced eating behaviors. The eating behaviors of service members are influenced by many modifiable factors. Targeted education, leadership engagement, and policies that make nutritious foods easily accessible, appealing, and preferred are needed.


Moonlighting genes harbor antisense ORFs that encode potential membrane proteins.
Moonlighting genes encode for single polypeptide molecules that perform multiple and often unrelated functions. These genes occur across all domains of life. Their ubiquity and functional diversity raise many questions as to their origins, evolution, and role in the cell cycle. In this study, we present a simple bioinformatics probe that allows us to rank genes by antisense translation potential, and we show that this probe enriches, reliably, for moonlighting genes across a variety of organisms. We find that moonlighting genes harbor putative antisense open reading frames (ORFs) rich in codons for non-polar amino acids. We also find that moonlighting genes tend to co-locate with genes involved in cell wall, cell membrane, or cell envelope production. On the basis of this and other findings, we offer a model in which we propose that moonlighting gene products are likely to escape the cell through gaps in the cell wall and membrane, at wall/membrane construction sites; and we propose that antisense ORFs produce "membrane-sticky" protein products, effectively binding moonlighting-gene DNA to the cell membrane in porous areas where intensive cell-wall/cell-membrane construction is underway. This leads to high potential for escape of moonlighting proteins to the cell surface. Evolutionary and other implications of these findings are discussed.


The northern population development; colonization and mortality in Swedish Sápmi, 1776-1895.
The aim of the Consequence of Colonization project is to study population development and mortality in Swedish Sápmi. This article, the first to be drawn from our research, compares these changes between Sami and non-Sami, South and North Sami. Study design. Longitudinal individual based data from computerized records ofthe Glillivare, Undersåker and Frostviken parishes, divided into 2 40-year periods: 1776-1815 and 1856-1895. The main source material used for the present study was a set of data files from the Demographic Data Base (DDB) at Umeå University, the largest historical database in Europe. A Sami cohort was created by indicators of ethnicity in the parish registers, and was later extended with automatic linkages to children and parents. Sami mortality rates show great fluctuations during the period 1776-1815, almost always peaking at a higher rate than in the rest of Sweden. The non-Sami group had lower mortality rates compared with both Sweden as a whole and the Sami in the parish. Between 1856 and 1895, the non-Sami experienced a very small reduction in their mortality rates and the Sami experienced overall improvement in their health status. Significant differences in age-specific mortality appear when the South and North Sami are compared, showing that the South Sami had far lower child mortality rates. The Sami population's health status improved during the nineteenth century. This indicates that they had advanced in the epidemiologic transition model. A corresponding change is not found for the non-Sami group.


Pituitary metastasis of a breast ductal adenocarcinoma.
Pituitary metastases are rare, a primary tumor of the breasts or lungs are frequently found. The clinical picture is very variable, they can be accidental discovery or revealed by a pituitary dysfunction. The prognosis is generally poor and depends on the anatomopathological type. We report the observation of a patient with a pituitary metastasis of a breast cancer evolving for 4 years, the diagnosis was suspected in front of pituitary macroadenoma images, a transphenoidal endoscopic biopsy and an anatomopathological confirmation revealing an infiltrating breast adenocarcinoma.


Emergency Department Visits by and Hospitalizations of Senior Diabetics in the Three Years Following Hurricanes Katrina and Rita.
While prior studies have investigated health care utilization immediately following disasters, few have examined utilization beyond that period. We use individual-level U.S. Medicare claims data for three years prior to (2002-2004) and after (2006-2008) Hurricanes Katrina and Rita to investigate whether senior diabetics affected by the storms had a greater number of emergency department visits and days hospitalized in the three years following the storms. An event study was conducted using regression analysis that controlled for all fixed individual characteristics. While the 2006 and 2007 rates of increase in utilization were relatively similar across the control group and the two affected groups, in 2008 the affected groups exhibited substantially greater increases in both emergency department visits and days hospitalized. The differences correspond to an additional 380,907 days hospitalized and 21,583 emergency department visits in 2008. The results indicate that, in addition to short term effects previously estimated, disasters may have longer term effects on utilization of healthcare services. These potential effects suggest that improved post-disaster care may significantly reduce the healthcare costs of disasters.


European experience on the practical use of levosimendan in patients with acute heart failure syndromes.
The novel calcium sensitizer and ATP-dependent potassium channel opener levosimendan has been introduced for routine use in several European countries. Recent reports on clinical experience confirm the positive hemodynamic results and beneficial clinical effects described in the initial dose-finding and randomized comparative therapeutic trials in patients with severe low-output heart failure. In addition, studies in small series of patients with cardiogenic shock after myocardial infarction and/or surgical interventions and post-interventional myocardial dysfunction (stunning) indicate that the inotropic and vasodilating actions of levosimendan may be of value in a wider range of indications. Dose recommendations, combination with other drugs, and potential side effects are discussed in this overview.


Pulmonary lavage in the treatment of alveolar proteinosis.
Alveolar proteinosis is a rare disease characterized by the accumulation of a proteinoseous material inside the alveolus. Various forms of treatment have been tried without much success. Pulmonary lavage has been found effective in bringing relief to patients as well as objective amelioration. This presentation describes the technique used and the problems encountered.


Ischaemia-induced vascular vulnerability resulting in intracerebral haemorrhage with ipsilateral internal carotid artery occlusion.
Intracerebral haemorrhage accompanied with cervical internal carotid artery (ICA) occlusion on the same side without moyamoya-like vessels is rare. A 73-year-old man with left ICA occlusion and no presence of moyamoya disease criteria underwent xenon-enhanced computed tomography with acetazolamide challenge test. The findings showed hypoperfusion and no vasoreactivity in the territory of the left middle cerebral artery. During follow-up he suffered bleeding in the left frontoparietal lobe. Cerebral angiography showed left ICA occlusion and cross flow via the anterior communicating artery without moyamoya vessels. Long-term ischaemia would make perforating or anastomotic arteries vulnerable. These arteries were easily ruptured by hypertension, resulting in intracerebral haemorrhage.


Pancreas Transplantation from Donors after Circulatory Death: an Irrational Reluctance?
Beta-cell replacement is the best therapeutic option for patients with type 1 diabetes. Because of donor scarcity, more extended criteria donors are used for transplantation. Donation after circulatory death donors (DCD) are not commonly used for pancreas transplantation, because of the supposed higher risk of complications. This review gives an overview on the pathophysiology, risk factors, and outcome in DCD transplantation and discusses different preservation methods. Studies on outcomes of DCD pancreata show similar results compared with those of donation after brain death (DBD), when accumulation of other risk factors is avoided. Hypothermic machine perfusion is shown to be a safe method to improve graft viability in experimental settings. DCD should not be the sole reason to decline a pancreas for transplantation. Adequate donor selection and improved preservation techniques can lead to enhanced pancreas utilization and outcome.


Chemically modified maize cobs waste with enhanced adsorption properties upon methyl orange and arsenic.
The surface chemistry of maize naturasorbent was altered in this work by the modifying agents: phosphoric acid and different amines (triethanolamine, diethylenetriamine and 1,4-diaminobutane). Removal of methyl orange (25 mg l(-1)) was <50% by maize corn cobs modified by phosphorylation and higher by the quaternized samples: 68% with the 1,4-diaminobutane and 73% with the diethylenetriamine modificators. Adsorption of arsenite by the samples modified with phosphoric acid/ammonia was 11 microg g(-1), which corresponds to 98% removal from a 550 microg As l(-1) solution for an adsorbent dose of 50 mg ml(-1). The samples modified by phosphoric acid/urea removed 0.4 microg g(-1) arsenate from a 300 mug As l(-1) solution. Adsorption of methyl orange, arsenite and arsenate was superior by the chemically modified maize cobs judged against the initial naturasorbent. For comparison, removal by the commercial anion exchanger was 100% for methyl orange, 45% (5 microg g(-1)) for arsenite and 99% (5 microg g(-1)) for arsenate.


Seroprevalence of IgG antibodies against SARS-CoV-2 in India, March 2020 to August 2021: a systematic review and meta-analysis.
India experienced 2 waves of COVID-19 pandemic caused by SARS-CoV-2 and reported the second highest caseload globally. Seroepidemiologic studies were done to track the course of the pandemic. We systematically reviewed and synthesized the seroprevalence of SARS-CoV-2 in the Indian population. We included studies reporting seroprevalence of IgG antibodies against SARS-CoV-2 from March 1, 2020 to August 11, 2021 and excluded studies done only among patients with COVID-19 and vaccinated individuals. We searched published databases, preprint servers, and government documents using a combination of keywords and medical subheading (MeSH) terms of "Seroprevalence AND SARS-CoV-2 AND India". We assessed risk of bias using the Newcastle-Ottawa scale, the appraisal tool for cross-sectional studies (AXIS), the Joanna Briggs Institute (JBI) critical appraisal tool, and WHO's statement on the Reporting of Seroepidemiological Studies for SARS-CoV-2 (ROSES-S). We calculated pooled seroprevalence along with 95% Confidence Intervals (CI) during the first (March 2020 to February 2021) and second wave (March to August 2021). We also estimated seroprevalence by selected demographic characteristics. We identified 3821 studies and included 53 studies with 905379 participants after excluding duplicates, screening of titles and abstracts and full-text screening. Of the 53, 20 studies were of good quality. Some of the reviewed studies did not report adequate information on study methods (sampling = 24% (13/53); laboratory = 83% [44/53]). Studies of 'poor' quality had more than one of the following issues: unjustified sample size, nonrepresentative sample, nonclassification of nonrespondents, results unadjusted for demographics and methods insufficiently explained to enable replication. Overall pooled seroprevalence was 20.7% in the first (95% CI = 16.1 to 25.3) and 69.2% (95% CI = 64.5 to 73.8) in the second wave. Seroprevalence did not differ by age in first wave, whereas in the second, it increased with age. Seroprevalence was slightly higher among women in the second wave. In both the waves, the estimate was higher in urban than in rural areas. Seroprevalence increased by 3-fold between the 2 waves of the pandemic in India. Our review highlights the need for designing and reporting studies using standard protocols.


Adenovirus expressing both thymidine kinase and soluble PD1 enhances antitumor immunity by strengthening CD8 T-cell response.
Adenoviruses harboring the herpes simplex virus thymidine kinase (HSVtk) gene under the regulation of a trans-splicing ribozyme targeting human telomerase reverse transcriptase (hTERT-TR) show marked and specific antitumor activity. In addition to inducing tumor cell death by direct cytotoxicity, it is becoming clear that HSVtk also induces antitumor immunity. Programmed death ligand 1 (PD-L1) expressed on tumor cell surfaces mediates tumor-induced immunoresistance by inhibiting PD1-expressing tumor-infiltrating T cells. Here, we explored whether a soluble form of PD1 (sPD1-Ig), which blocks PD-L1, could synergize with TERT-TR-regulated HSVtk to enhance the adenoviral therapeutic efficacy by boosting antitumor immunity. Tumor antigen released by HSVtk-transduced tumors successfully primed tumor antigen-specific CD8 T cells via dendritic cells (DC). Regression of murine tumors was markedly enhanced when sPD1-Ig was incorporated into the adenovirus as compared with a single-module adenovirus expressing only HSVtk. This effect was abolished by CD8 T-cell depletion. Consistent with this, following adoptive transfer of tumor antigen-specific CD8 T cells into tumor-bearing Rag1(-/-) mice, dual-module adenovirus significantly enhanced CD8 T cell-mediated tumor rejection. In addition, secondary tumor challenge at a distal site was completely suppressed in mice treated with a dual-module adenovirus. These results suggest that a dual-targeting strategy to elicit both tumor antigen priming and tumor-induced immunoresistance enhances CD8 T cell-mediated antitumor immunity.


[Lateral tracheal indentation or compression by the brachiocephalic arterial trunk in children].
Three cases of compression of the right wall of the trachea by buckling of the innominate artery in childhood are described. A coarctation of the thoracic aorta is associated in two cases, and a left cervical aortic arch in the third one. In one case, a severe tracheomalacia occurs following the surgical repair of the associated coarctation. This lateral indentation of the trachea is suggestive of right aortic arch but the absence of posterior oesophageal indentation excludes the diagnosis. Angiography is helpful and echography is unable to demonstrate the vascular origin of the tracheal compression. The authors analyse the correct diagnostic approach, emphasize the risk of tracheomalacia and the high rate of associated cardio-vascular malformations.


Predictors of total and low-density lipoprotein cholesterol change after partial ileal bypass.
POSCH is a prospective, randomized secondary intervention trial examining the effect of maximal lipoprotein modification achieved by partial ileal bypass on overall mortality and the course of coronary heart disease. In the initial 189 surgical patients, total cholesterol levels decreased from 256.7 +/- 2.6 mg/dl to 166.6 +/- 2 mg/dl, and low-density lipoprotein cholesterol levels decreased from 181.5 +/- 2.7 mg/dl to 94.1 +/- 1.7 mg/dl 3 months after operation. These significant decreases were sustained through 5 years of follow-up (p less than 0.001). The total cholesterol level was 29.2 +/- 0.9 percent lower and the low-density lipoprotein cholesterol level was 43.2 +/- 1 percent lower at 5 years compared with the baseline level. Decreases of similar magnitude were seen in each of the common WHO lipoprotein phenotypes. The baseline total cholesterol level was the only significant independent preoperative predictor of the 5 year total cholesterol level (correlation coefficient 0.547; p less than 0.001), and the baseline low-density lipoprotein cholesterol level was the only significant independent preoperative determinant of the 5 year low-density lipoprotein cholesterol level (correlation coefficient 0.599; p less than 0.001). These relationships are expressed by the following equations: 5 year total cholesterol = 0.54 X baseline total cholesterol + 42.3, and 5 year low-density lipoprotein cholesterol = 0.455 X baseline low-density lipoprotein cholesterol + 19.2. The decrease in total and low-density lipoprotein cholesterol levels after partial ileal bypass are greater than reported by any trial of drug or diet intervention, including the Lipid Research Clinics Coronary Primary Prevention Trial which examined cholestyramine. Estimation of the change in total and low-density lipoprotein cholesterol levels after partial ileal bypass can be made based on preoperative lipid analysis and is essential in comparing different therapeutic modalities and assessing the role of partial ileal bypass among strategies aimed at lowering coronary heart disease risk.


Concomitant Gleason Score ≥ 7 prostate cancer is an independent prognosticator for poor survival in nonmetastatic bladder cancer patients undergoing radical cystoprostatectomy.
In bladder cancer (BCa) patients undergoing radical cystoprostatectomy (RCPx), concomitant prostate cancer (PCa) is a common finding. Up to now there is no clear evidence to suggest that concomitant PCa is a predictor of outcome in these patients. Aim of this study was to assess incidence and clinicopathologic characteristics of concomitant PCa in RCPx specimen and correlate it to survival parameters from a single-centre material over two decades. All men who had undergone RCPx for BCa at our institution between 1994 and 2013 were included in this study. Clinicopathologic parameters for BCa and PCa were evaluated and correlated with outcome parameters. Survival analysis was performed for the subgroup of nonmetastatic organ-confined BCa to evaluate the role of concomitant Gleason Score (GS) ≥7 PCa. Of 945 men who had undergone RCPx for BCa, concomitant PCa was present in 237 patients (25.1 %). There was a significant increase in PCa incidence from 18.9 to 32.3 % between 1994 and 2013 (p = 0.009). Concomitant PCa represented a more aggressive phenotype at the end of the study (p = 0.037). In nonmetastatic organ-confined BCa, concomitant GS ≥7 PCa (HR 3.09; p = 0.0001) and age > 68 (HR 1.80; p = 0.0004) were independent negative predictors for overall survival. Concomitant PCa in RCPx specimen of BCa patients is a common finding. The incidence of concomitant PCa has significantly increased within 2 decades, presenting a more aggressive phenotype. Age and in particular concomitant GS ≥7 PCa are independent prognosticators for poor survival in patients with nonmetastatic organ-confined BCa.


The combined prognostic potential of serum high-sensitivity cardiac troponin I and N-terminal pro-B-type natriuretic peptide concentrations in dogs with degenerative mitral valve disease.
Identification of factors associated with decreased survival in dogs with degenerative mitral valve disease (DMVD) will allow more accurate prognosis. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is negatively associated with survival in dogs with DMVD. In human patients, multimarker strategies provide superior risk stratification compared with single markers. High-sensitivity cardiac troponin I (hscTnI) and other clinical variables will be associated with survival time in dogs with DMVD. Measuring hscTnI and NT-proBNP in combination will be prognostically superior to measurement of either marker alone. The rate of change of these markers will vary according to cause of death. Client-owned dogs (n = 202) with DMVD of varying severity and age-matched healthy control dogs (n = 30) recruited from first opinion private practice. Prospective cohort study relating clinical variables at enrollment in dogs with DMVD to survival time (all-cause, cardiac, and noncardiac mortality). Multivariable Cox regression analysis was used to identify factors associated with survival. Measurements were obtained approximately every 6 months. Repeated measures models were constructed to assess changes over time. hscTnI, LVEDDN, heart rate, and age were independently associated with decreased survival time (all-cause mortality). Survival times were shortest in dogs in which both serum hscTnI and NT-proBNP were increased. hscTnI and NT-proBNP increased more rapidly in dogs that died of cardiac disease. Serum hscTnI has prognostic value in dogs with DMVD. Measurement of NT-proBNP and hscTnI is prognostically superior to measuring either alone. Serial measurement strategies provide additional prognostic information.


The use of contralateral free extended latissimus dorsi myocutaneous flap for a tertiary failed breast reconstruction: Is it still an option?
Unsuccessful breast reconstruction management represents a complex challenge for the plastic surgeon. Although these events rarely occur, many patients are not suitable candidates for conventional flaps, because of either previous donor-site surgery or lack of sufficient tissue. In this study, a contralateral free latissimus dorsi musculocutaneous flap (CL-LDMF) was planned for correction of major lesions in the anterior chest wall. Twelve patients underwent secondary/tertiary breast reconstruction with CL-LDMF with a customized shape (horizontal, oblique, or "fleur-de-lis") depending on the amount of tissue necessary. The technique was indicated in patients with large thoracic defects who lacked a donor site and had undergone previous unsuccessful pedicled LDMF. The mean follow-up time was 42.5 months (range: 18-72 months). Five local complications occurred in four of the 12 patients. Dorsal dehiscence was observed in one, local wound infection in one, small partial CL-LDMF necrosis in one, and dorsal seroma in one patient. All cases of complications were limited and treated with a conservative approach except for one implant extrusion 4 months after reconstruction. No total flap loss was reported. All patients achieved a satisfactory thoracic and breast reconstruction. The results of this study demonstrate that free CL-LDMF is a reliable technique and should be considered in selected cases of tertiary reconstructions. The majority of complications were immediate, minor, and comparable to other reconstructive techniques. We believe that in selected patients, especially those who do not have available donor-site areas, free CL-LDMF is advantageous and should be part of the armamentarium of all plastic surgeons who deal with tertiary breast reconstructions.


The reliability of laboratory data from blood samples collected through pulmonary artery catheters.
Blood samples obtained through quadruple-lumen Swan-Ganz catheters in ten critically ill patients provided reliable results after withdrawal of a total of 2.2 mL (including 1.2 mL of dead space) for hematocrit tests and 3.2 mL (including 1.2 mL of dead space) for plasma sodium tests.


Congenital mediastinal dumbbell neuroblastoma with spontaneous regression of liver metastases.
We report a patient with a congenital mediastinal dumbbell neuroblastoma (NB) presenting as respiratory distress at birth rather than a neurologic deficit. The tumor did not respond to low-dose chemotherapy, but radiotherapy and surgery were effective. The patient was observed postoperatively without further therapeutic intervention considering the favorable biologic factors despite the appearance of liver metastases, which ultimately regressed spontaneously. The authors believe that most congenital NBs have favorable outcomes with a possibility of spontaneous regression, and that an understanding of the biologic features of tumors is important to avoid overtreatment of lesions with a favorable prognosis. Keywords Congenital neuroblastoma. Dumbbell tumor. Liver metastasis. Spontaneous regression


Expression, glycosylation, and intracellular distribution of human beta-galactosidase in recombinant baculovirus-infected Spodoptera frugiperda cells.
A full-length cDNA encoding human acid beta-galactosidase was inserted into the baculovirus genome under transcriptional regulation of the viral polyhedrin gene promoter. The Spodoptera frugiperda cells infected with the recombinant virus expressed the beta-galactosidase activity 300-fold higher than human fibroblasts. Immunoblot analysis revealed an 82-kDa protein band, which was modified in molecular size by deglycosylating enzymes; an 80-kDa band appeared after N-glycanase digestion, and two bands (80-kDa and 81-kDa) appeared after endoglycosidase H digestion. This result suggested that the enzyme molecule was glycosylated, partly with high-mannose type oligosaccharides. The intracellular distribution of the enzyme observed by indirect immunofluorescence staining was perinuclear or diffusely cytoplasmic, and not characteristic of lysosomes; the enzyme was secreted to the culture medium in large quantities, and not translocated to lysosomes. Possible application of this expression system to the studies of the structure and function of normal and mutant human beta-galactosidases was discussed.


Evidence for an essential arginine residue in the active site of Escherichia coli 2-keto-4-hydroxyglutarate aldolase. Modification with 1,2-cyclohexanedione.
Treatment of homogeneous preparations of Escherichia coli 2-keto-4-hydroxyglutarate aldolase with 1,2-cyclohexanedione, 2,3-butanedione, phenylglyoxal, or 2,4-pentanedione results in a time- and concentration-dependent loss of enzymatic activity; the kinetics of inactivation are pseudo-first order. Cyclohexanedione is the most effective modifier; a plot of log (1000/t 1/2) versus log [cyclohexanedione] gives a straight line with slope = 1.1, indicating that one molecule of modifier reacts with each active unit of enzyme. The kinetics of inactivation are first order with respect to cyclohexanedione, suggesting that the loss of activity is due to modification of 1 arginine residue/subunit. Controls establish that this inactivation is not due to modifier-induced dissociation or photoinduced structural alteration of the aldolase. The same Km but decreased Vmax values are obtained when partially inactivated enzyme is compared with native. Amino acid analyses of 95% inactivated aldolase show the loss of 1 arginine/subunit with no significant change in other amino acid residues. Considerable protection against inactivation is provided by the substrates 2-keto-4-hydroxyglutarate and pyruvate (75 and 50%, respectively) and to a lesser extent (40 and 35%, respectively) by analogs like 2-keto-4-hydroxybutyrate and 2-keto-3-deoxyarabonate. In contrast, formaldehyde or glycolaldehyde (analogs of glyoxylate) under similar conditions show no protective effect. These results indicate that an arginine residue is required for E. coli 2-keto-4-hydroxyglutarate aldolase activity; it most likely participates in the active site of the enzyme by interacting with the carboxylate anion of the pyruvate-forming moiety of 2-keto-4-hydroxyglutarate.


Laser guided ionic wind.
We report on a method to experimentally generate ionic wind by coupling an external large electric field with an intense femtosecond laser induced air plasma channel. The measured ionic wind velocity could be as strong as >4 m/s. It could be optimized by increasing the strength of the applied electric field and the volume of the laser induced plasma channel. The experimental observation was qualitatively confirmed by a numerical simulation of spatial distribution of the electric field. The ionic wind can be generated outside a high-voltage geometry, even at remote distances.


Transforming growth factor-β induces vascular endothelial growth factor-C expression leading to lymphangiogenesis in rat unilateral ureteral obstruction.
Inflammation is recognized as an important contributor to lymphangiogenesis; however, in tubulointerstitial lesions in human chronic kidney diseases, this process is better correlated with the presence of myofibroblasts rather than macrophages. As little is known about the interaction between lymphangiogenesis and renal fibrosis, we utilized the rat unilateral ureteral obstruction model to analyze inflammation, fibrosis, lymphangiogenesis, and growth factor expression. Additionally, we determined the relationship between vascular endothelial growth factor-C (VEGF-C), an inducer of lymphangiogenesis, and the profibrotic factor, transforming growth factor-β1 (TGF-β1). The expression of both TGF-β1 and VEGF-C was detected in tubular epithelial and mononuclear cells, and gradually increased, peaking 14 days after ureteral obstruction. The kinetics and localization of VEGF-C were similar to those of TGF-β1, and the expression of these growth factors and lymphangiogenesis were linked with the progression of fibrosis. VEGF-C expression was upregulated by TGF-β1 in cultured proximal tubular epithelial cells, collecting duct cells, and macrophages. Both in vitro and in vivo, the induction of VEGF-C along with the overall appearance of lymphatics in vivo was specifically suppressed by the TGF-β type I receptor inhibitor LY364947. Thus, TGF-β1 induces VEGF-C expression, which leads to lymphangiogenesis.


Round-Robin test for the histological diagnosis of acute colonic Graft-versus-Host disease validating established histological criteria and grading systems.
Histomorpholgy is one of the mainstays of acute Graft-versus-host disease (GvHD) diagnosis. However, concerns about reproducibility and the most appropriate grading system question its usefulness. Our aim was to assess histomorphological parameters and previously reported grading systems for GvHD regarding reproducibility and validity. Moreover, we propose that sum scores, derived by combining separately scored morphological parameters into a total score, might provide a simplified but equally effective means to grade GvHD. A total of 123 colon biopsies were assessed across four pathologists for intestinal GvHD using a Round-Robin test and results were correlated with clinical findings. Interobserver reproducibility was high for histological parameters that were evaluated as indicators of acute GvHD. Published grading systems were moderately reproducible (ICC 0.679-0.769) while simplified sum scores, in comparison, showed better interrater reliability (ICC 0.818-0.896). All grading systems and sum scores were associated with clinical signs of GvHD and in part with therapy response and survival. However, they were not able to stratify patients according to the clinical severity of GvHD. In a hot-spot analysis 1 crypt apoptotic body (CAB) in 10 crypts was a reasonable cut-off value for minimal diagnostic criteria of GvHD. In conclusion, histology can contribute to the diagnosis of GvHD and is reproducible. Published grading systems are able to reflect clinical findings as are simplified sum scores, which showed improved reproducibility and might be easier to handle as they are based on adding up histological parameters rather than transferring histological findings into a separate grading system. Sum scores will have to be further tested in a prospective setting.


The healing of freeze-dried rabbit flexor tendon in a synovial fluid environment.
Deep flexor tendons from the forepaws of rabbits were removed and cut into two segments, sutured and freeze-dried. About one week later each tendon was placed in a knee joint of the same rabbit from which the tendon had been removed. At one, two, three and six weeks the tendons were retrieved and examined grossly, histologically and by electron microscopy. For comparison a control group using non freeze-dried tendons was also studied. Although there was evidence of central necrosis, superficial healing of the freeze-dried tendons occurred and was presumably due to cells from the synovial fluid.


Mental illness among the homeless: prevalence study in a Dublin homeless hostel.
To determine the prevalence of mental illness among the residents of a homeless hostel in inner city Dublin. A cross-sectional survey was carried out among hostel residents, as previous studies have indicated that homeless hostel-dwelling men in Dublin constitute the largest single grouping of homeless Irish people. All agreeable residents were interviewed by the authors over an eight-week period using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) Clinical Version. For each disorder, the current (30-day) and past prevalence was determined. A total of 38 residents were interviewed, resulting in a response rate of 39.2% for the study. A total of 81.6% of residents had a current Axis I diagnosis; this number increased to 89.5% when combining current and past diagnoses. Only four residents had no diagnosis. There was considerable comorbidity between disorders, with a significant number of residents experiencing both mental illness and substance use problems. When considering lifetime diagnoses, 31.6% had a single diagnosis only; 57.9% had two/more diagnoses. Twelve residents (31.6%) had been admitted to a psychiatric hospital during their lifetime. The most prevalent disorders during the past month were Alcohol Dependence (23.7%), Opioid Dependence and Major Depressive Disorder (both 18.4%), Opioid Abuse and Alcohol-Induced Depression (both 7.9%). Only 23.7% of interviewed residents were attending psychiatric or addiction services. A significant number of residents who did not wish to participate in the study were identified by hostel staff as having a confirmed psychiatric diagnosis. The survey demonstrated a very high prevalence of mental disorders among homeless hostel residents. The high prevalence of dual diagnosis highlights the need for greater collaboration between psychiatric services and addiction services. The outcome also points to the importance of providing mental health training to emergency shelter/hostel staff. Research into the mental health status of the homeless should be undertaken regularly if services are to be planned to meet the needs of this vulnerable group.


Left ventricular noncompaction and myocardial fibrosis: a case report.
Left ventricular noncompaction (LVNC) is a rare congenital abnormality. It is currently classified as a genetic cardiomyopathy and results from early arrest of endomyocardial morphogenesis. The pathophysiology of left ventricular dysfunction, which becomes apparent beyond the 4th decade of life, is unclear. We report a case of 60-year-old woman who presented with shortness of breath and showed noncompacted endocardium on echocardiography. Cardiac catheterization and viral studies were unremarkable. Histology revealed endomyocardial fibrosis without disarray. She was subsequently diagnosed with LVNC and treated with medications. Cardiologists and other physicians should be aware of LVNC due to its high likelihood of misdiagnosis and associated high complication rates. Early diagnosis, intervention and screening among family members can decrease the morbidity and mortality associated with LVNC.


Comparison of blood glucose concentrations measured by enzymatic and reflectance photometric methods in fasting piglets.
During a metabolic study of 22 fasting newborn piglets, blood glucose concentrations were measured by enzymatic and reflectance photometric methods. Use of the reflectance photometer is an accurate method of determining blood glucose levels even in hypoglycaemic range. In addition, the minimal quantity of blood needed for measurement allows the use of the same newborn piglets in longitudinal studies in which samples must be taken frequently.


Island-sharing by archipelago species.
Diamond (1975) formulated "assembly rules" for avian species on islands in an archipelago, which made a successful colonisation depend essentially on which other species were present. Critically examining these rules, Connor and Simberloff (1979) maintained that, in the Vanuatu (New Hebrides) archipelago, the field data on species distribution was quite compatible with a null hypothesis, in which species colonise at random with no species interaction. Their work was in turn criticised (Diamond and Gilpin (1982), Gilpin and Diamond (1982)) and a vigorous controversy has ensued.Here we contribute a method in which a simple but hitherto neglected statistic is used as a probe: the number of islands shared by a pair of species, with its first and second moments. The matrix of these sharing values is given as a simple product of the incidence matrix, and its properties are examined - first, for the field data, and then in the random ensemble used by Connor and Simberloff (1979). It is shown that their constraints hold constant the mean number shared, so that any fall in the number that one pair of species share, due to their excluding each other, must imply a rise in the number shared by some other species pair-i.e., an aggregation.Turning to the second moment of the numbers shared, it is shown that its value in the Vanuatu field data exceeds the largest value to be found in a sample of 1000 matrices, these latter being constructed so that they obey the Connor and Simberloff constraints but are otherwise random. This indicates that exclusion and/or aggregation effects are present in the actual distribution of species, which are not catered for by the null hypothesis.The observed distribution thus emerges as much more exceptional than found by Connor and Simberloff (1979), and even by Diamond and Gilpin (1982), when examining the same ensemble. The reason for this disagreement are sought, and some cautions are offered, supported by numerical evidence, concerning the use of the chi-square test when the data points involved are mutually dependent.


Molecularly engineered organic copolymers as high capacity cathode materials for aqueous proton battery operating at sub-zero temperatures.
High-performance aqueous all-organic rechargeable batteries are promising candidates for cost-effective, safe, and environment-friendly next-generation energy storage devices. Herein, two organic copolymers with nanorod-like morphology (AN-TA, and AN-PA), composed of different tertiary amines, are synthesized as the cathode material for an aqueous proton battery. The individual copolymer electrodes possess the dominated diffusion-controlled electrode kinetics resulting from the proton insertion/de-insertion along with the surface-controlled processes in 2 M HCl and 2 M H2SO4. Among the two copolymers, AN-PA exhibits the maximum specific capacity of 145 mAh g-1 at 1 A g-1 and then, even at the higher current density of 10 A g-1, it possesses the capacity as 110 mAh g-1 in 2 M HCl. The assembled aqueous proton battery comprising of AN-PA as a cathode delivers the capacity of 80 mAh g-1 at 1 A g-1 in 2 M HCl. The maximum deliverable energy density of 33.9 Wh kg-1 is achieved at the power density of 423 W kg-1. Notably, our proton battery can well operate at the sub-zero temperature of -25 °C with a cell voltage of 1.1 V. More importantly, the device retains 84 % of the initial capacity after 1000 cycles at 2 A g-1 and exhibits the retention of specific capacity of about > 93% when compared to that of room temperature.


Association study of CRP gene polymorphism and hypertension in Han Chinese population.
Serum C-reactive protein (CRP) and genetic variation of CRP gene have been reported as a strong, independent predictor of myocardial infarction and stroke. But there is rare association evidence of CRP genetic variation and hypertension (HT). A community-based case-control study including 1331 cases with HT and 1400 controls was used to evaluate the association of tagSNPs covered CRP gene, CRPP1 gene and 40kb upstream with HT in a Chinese Han population. Haplotypes and stratification analysis were applied to further evaluate relationships between the screened SNPs and HT and general linear model (GLM) was applied to compare blood pressure levels between genotypes. In stage 1, five SNPs had positive association with HT (P<0.05) and entered stage 2 and two SNPs rs876537 and rs10737175 polymorphisms showed significant association with HT in joint sample. Haplotype analysis showed that comparing with common haplotype T-C which was constructed by rs6677719 and rs10737175, haplotype T-T significantly associated with HT after adjusted covariates. Stratification analysis found significant associations of HT for rs876537, rs2808630, rs6677719 and rs10737175 in ≥50years group, rs876537, rs10737175 in female, rs876537 and rs10737175 in non-smoking and non-drinking populations as well as rs2808630 in non-drinking population. Furthermore, quantitative trait analysis indicated significant differences of SBP and DBP between the genotypes of rs10737175, rs876537 and rs2808630 in non-treatment hypertensive cases and control population. The findings of this study support that CRP gene polymorphisms have significant association with genetic susceptibility of HT and quantitative traits of blood pressure.


Minimally Invasive Trigeminal Ablation: Transoral Approach for Targeting V2.
Trigeminal neuralgia (TN) is a chronic orofacial pain syndrome, which manifests as severe pain in the distribution of any trigeminal nerve branch. Though traditionally responsive to anticonvulsant therapy, TN can become refractory to medications and require surgical intervention. We present a case of V2 TN that was treated with minimally invasive trigeminal ablation. The patient presented with a 6-year history of type 1 TN and had failed the maximum tolerated doses of carbamazepine and gabapentin. There was no evidence of vascular compression on neuroimaging. After the patient refused stereotactic radiosurgery, she was offered minimally invasive trigeminal ablation. At 5 months postoperatively the patient reported complete alleviation of pain with tolerable sensorineural numbness. The endoscopic approach allows for precise targeting of V2, which is ideal in patients undergoing targeted neuroablation for pain. This is the first documented case of a transoral endoscopic approach toward ablative V2 TN management.


Endoscopic Transfontanellar Approach of a Cyst Anterior to the Brainstem Crossing the Foramen Magnum-Part I: Failure of Unique Fenestration: 2-Dimensional Operative Video.
Premature infants with severe germinal matrix intraventricular hemorrhage (IVH) are at high risk of posthemorrhagic ventricular dilation and hydrocephalus (Video 1). We report the case of a 3-month-old premature infant referred for posthemorrhagic multilocated hydrocephalus. He presented with somnolence, hypotonia, and a bulging fontanelle. His past medical history included an IVH grade III with hydrocephalus initially treated by temporary ventriculosubgaleal shunting. Magnetic resonance imaging (MRI) showed persistent hydrocephalus associated to a cyst extending anteriorly from the mesencephalon to the posterior wall of the sixth cervical vertebra, causing severe brainstem and spinal cord compression. A two-step surgery was performed, consisting of an endoscopic procedure and a ventriculo peritoneal shunt placement, to achieve hydrocephalus treatment and cyst fenestration. A right transfontanellar approach with the head flexed was chosen, using a straight 30-degree endoscope. The procedure and surgical technique are explained in a step-by-step fashion in the original conditions. A large unique fenestration was performed with no postoperative complications and improvement of the neurological status. One month later the patient presented again with symptomatic intracranial hypertension with compatible clinical and imagery findings. MRI showed cyst recurrence and hydrocephalus. We therefore revised our strategy and performed an additional procedure, which is detailed in the second part of the video (Part II: Success of Multiple Fenestrations). Our report underlines the high risk of recurrence of such cysts in post-hemorrhagic arachnoiditis. Cyst recurrence may be explained by the absence of crossing flow when a unique perforation is made.


3D Virtual Reality Rehabilitation Therapy for Patients with Vertigo Due to Peripheral Vestibular Dysfunction.
This study aimed to evaluate 3D virtual reality rehabilitation therapy in patients with vertigo due to peripheral vestibular dysfunction. The subjects were 20 patients with peripheral vestibular dysfunction confirmed by Videonystagmography, Divided into 2 groups: Group 1 (study group) underwent vestibular rehabilitation therapy using 3D virtual reality in a customised VR lab with specific headset (Oculus rift and htc vive) with software application, which allows vestibular rehabilitation treatment using high quality immersive virtual reality console in which environment appears real and in 3D. The exercises are designed for gaze stability, increase postural stability, improve vertigo and daily activities, through sensory stimuli and in addition to conventional Cawthorne-Choksey exercises. Group 2 (control group) are treated by conventional Cawthorne-Choksey exercises alone. A VSS-SF (Vertigo Symptom Scale-short form) questionnaire and VAS (Visual Analog Scale) were used to assess the levels of patient satisfaction compared before and after each treatment session in both groups. A significant higher level of subjective satisfaction was observed in patients who underwent 3D virtual reality rehabilitation therapy with conventional therapy (group 1) compared to patients who underwent conventional cawthorne-Choksey exercises alone (group 2). The study gave a substantial subjective satisfaction in patients using 3D virtual reality rehabilitation therapy with conventional therapy (group1) than conventional Cawthorne-Choksey exercises alone (group 2). Future of VR rehabilitation therapy brings a revolutionary novelty in field of rehabilitation therapy were it involves real time stimulation and interaction between sensory, motor and cognitive channels.


Mometasone Furoate Use for Recurrent Adenoid Hypertrophy: Randomized Controlled Clinical Trial.
Background& Objective: Adenoid hypertrophy (AH) in children is one of the most causes of nasal obstruction and is associated with many nasal and respiratory symptoms. Till now, surgery is the main option for managing the associated symptom of AH. The intranasal steroid has an effective role in the control of allergic rhinitis and associated AH. This work aimed to assess the effects of local mometasone on recurrent AH in children. Patients& Methods: A randomized controlled trial enrolled 39 patients aged between 2 and 15 years with recurrent AH. Those patients were randomly subdivided into three groups; group (A) received topical mometasone furoate (MF), group (B) did not receive any medication, and group (C) received topical normal saline. All groups were followed up for 8 weeks. Results: Patients who received Mometasone furoate had temporary relief of adenoid hypertrophy-related symptoms (84.6%) in comparison to the control group and placebo group during the duration of treatment. After cessation of treatment with local steroids, all cases experienced symptoms caused by adenoid hypertrophy, and by the end of the third month of follow up all cases underwent adenoidectomy. Conclusion: Mometasone furoate can temporarily reduce the adenoid size, reducing symptoms related to adenoid hypertrophy.


Differential potency and trans-activation of normal and mutant T24 human H-ras1 gene promoters.
We have employed a short-term transfection assay system in which we monitored the transient expression of the chloramphenicol acetyltransferase (CAT) gene linked to the promoter region of the normal and mutant T24 H-ras1 gene or the human epsilon-globin gene in Chinese hamster lung (CHL) cells or cells derived from them which carry and express one or the other of the polyoma virus early genes. Our findings can be summarized as follows: (i) The mutant T24 H-ras1 promoter region behaves as a stronger promoter than the H-ras1 gene in all these types of cells as well as in rat 208F fibroblast cells. (ii) In CHL cells expressing the polyoma large T antigen the normal and mutant T24 Ha-ras1 promoters are not trans-activated in these cells and only a 2.5-fold activation of the epsilon-globin promoter is observed. (iii) In cells expressing the polyoma middle T antigen both the normal and mutant H-ras1 are trans-activated whereas transcription from the epsilon-globin promoter is not affected when compared to the normal CHL cells. (iv) In cells expressing the polyoma small T antigen the normal and mutant H-ras1 as well as the epsilon-globin promoters are trans-activated. We suggest from these data that a tissue-specific element exists in the promoter region of the H-ras1 gene and that the polyoma middle and small T antigens trigger the expression of proteins that trans-activate these promoters.


Progression of Vasculopathy in Young Individuals with Turner Syndrome.
Vasculopathy has been identified in young individuals with Turner syndrome (TS). No studies in young individuals with TS have investigated whether this vasculopathy progresses over time. The objective of this study is to describe the changes in vasculopathy over time in a cohort of young individuals with TS. Repeat ultrasound and SphygmoCor CPV® (AtCor Medical) measurements of carotid thickness and peripheral arterial stiffness were performed. Vascular measurements were compared at baseline and follow-up. Follow-up measurements were also compared to historical lean (L) and obese (O) age-, race-, and sex-matched non-TS controls. Thirty-five individuals with TS were studied at a mean age of 19.4 years (range, 13.9-27.5). Mean time to follow-up was 7.2 years (range, 7.1-7.8). Carotid intima media thickness increased by 0.03 ± 0.07 mm (p < 0.01) over time, but was less than L and O controls at follow-up. Pulse wave velocity carotid-femoral increased by 0.51 ± 0.86 m/s (p < 0.01) over time, but was similar to L and less than O controls at follow-up. Augmentation index (AIx) remained unchanged (p = 0.09) over time, but was significantly higher at follow-up than both control groups (p < 0.01 for both). There were no identified differences between 45,X and other TS genotypes. We demonstrate evidence of vascular thickening and stiffening over 7 years in a cohort of young individuals with TS, as well as a persistently increased augmentation index compared to L and O non-TS controls. It is unclear whether the increase in vascular structure and function are related to normal aging or if TS is a risk factor. Higher body mass index seems to be a risk factor. Early estrogen replacement and longer exposure to growth hormone therapy need to be further explored as potential protective factors.


The potential effect of patulin on mice bearing melanoma cells: an anti-tumour or carcinogenic effect?
Mycotoxins are bioactive compounds that are noxious to human. Their effects on oncogenesis have been satisfactorily elucidated, and some of mycotoxins have been classified as carcinogenic to humans. Nevertheless, patulin (PAT) is considered by the International Agency of Research on Cancer as 'not carcinogenic to humans'. The present study was designed to understand the effect of this mycotoxin on melanoma cells (B16F10) by measuring cell proliferation and assessing the anti-tumour effect in vivo in Balb/c mice. Our results revealed that intraperitoneally administration of PAT for 20 days significantly induces tumour regression in B16F10 cell-implanted mice. This effect was evidenced by the activation of apoptosis which is supported by the increase in p53 and Bax expressions, the downregulation of the protein levels of Bcl2, and the increase in caspase-3 activity. Moreover, systemic toxicity analysis demonstrated that there is no potential toxicity following PAT treatment unlike untreated melanoma mice which suffer from anaemia, inflammation and liver dysfunction. Remarkably, this is the first published report demonstrating the therapeutic efficacy of PAT in vivo models.


The prognostic significance of X-ray changes at presentation and reassessment in patients with multiple myeloma.
The relationship between presenting skeletal X-ray findings and survival in multiple myeloma was assessed in 172 consecutive patients treated at this institute. All patients were investigated, treated and followed up according to one protocol. The shortest survival was seen in those with normal X-rays (3-year actuarial 11 per cent) and the longest in those with minimal lytic changes (3-year actuarial 44 per cent). Patients with osteoporosis alone and those with extensive lytic lesions had intermediate survivals of 32 per cent and 33 per cent respectively. Of the other major prognostic features only anaemia demonstrated a significant correlation with X-ray findings in terms of survival (p less than 0.001) suggesting that those with normal X-rays may have a more diffuse marrow involvement accounting for their poor prognosis. The response on bone X-rays in 102 patients who completed nine cycles of chemotherapy was also analysed. Patients with evidence of healing had a 3-year actuarial survival of 37 per cent, those with progression 36 per cent and those with stable X-rays 65 per cent (p less than 0.01). Normal bone X-rays at presentation and radiological evidence of healing following therapy appear to be bad prognostic signs in multiple myeloma.


Identification of human herpesvirus 6 variants A and B by primer-specific real-time PCR may help to revisit their respective role in pathology.
Human herpesvirus 6 (HHV-6) isolates are classified into two variants, termed HHV-6A and HHV-6B, on the basis of distinct genetic, antigenic and biological characteristics, but the specific pathogenicity of each variant remains poorly understood. To design a rapid, sensitive and specific real-time variant-specific PCR (VS-PCR) method to differentiate both variants in biological specimens. The VS-PCR was adapted from a real-time PCR assay, based on TaqMan technology, previously developed for the genome quantitation of both HHV-6 variants [Gautheret-Dejean A, Manichanh C, Thien-Ah-Koon F, Fillet AM, Mangeney N, Vidaud M, et al. Development of a real-time polymerase chain reaction assay for the diagnosis of human herpesvirus-6 infection and application to bone marrow transplant patients. J Virol Meth 2002;100:27-35], a consensual reverse primer (Taq2) being changed into two variant-specific primers named H6A and H6B. This method was applied to a large set of biological specimens obtained in different pathological contexts. The sensitivity threshold was about 10 copies/well for HHV-6A-specific PCR (PCR-A) and 1 copy/well for HHV-6B-specific PCR (PCR-B). Both assays showed a linear dynamic range from 10 to 100,000 copies of HHV-6 DNA. Regarding the specificity and the capacity of discrimination of each assay, one variant could be detected and identified in the presence of more than 1000 times higher concentrations of the other variant in virus mixtures. The comparison of the results obtained with this VS-PCR with those previously obtained with a classic PCR method allowed us to validate our new technique on a wide panel of biological samples, including numerous patients with severe HHV-6-related symptoms. The high prevalence of HHV-6B was confirmed in healthy individuals and immunocompromised patients. HHV-6A was identified in distinct samples from several patients exhibiting neurological disorders. We developed a new VS-PCR assay, able to differentiate HHV-6A and HHV-6B in biological samples, even in the case of mixed infections. Our study confirms the wide prevalence of HHV-6B and highlights the potential greater neuropathogenic role of HHV-6A in immunocompromised patients and young infants.


Emergency use of uncrossmatched red cells in neonatal intensive care infants.
In very rare situations, a newborn will be delivered with severe unrecognized life-threatening anemia. Two infants with severe anemia with differing etiologies were deemed to require emergency uncrossmatched O-negative blood. In one infant, the blood transfused was incompatible for the minor antigen that had caused the isoimmune hemolytic anemia. We report on the indications, potential risks and benefits in giving uncrossmatched O-negative blood to term infants with life-threatening anemia.


Anomalous effect of the aging degree on the ionic permeability of silica shells.
We present a systematic study on the ionic permeability and protective ability of silica shells with different aging degrees by using the acid etching of silica-coated iron oxide nanoparticles as the model reaction. Contradictory to common impressions, we found that the ionic permeability of silica shells increased rather than decreased with the increasing aging degree. This trend may be explained by the chemical nature of the sol-gel silica shell that affects the wettability and, thereby, the transportation of water molecules and hydrated ions. Our study provides novel insights into the protective ability of sol-gel derived silica, which enables us to design thin but low-permeability shells for the stability of inner nanoparticles under harsh conditions without scarifying the performance of core-shell nanostructures.


Quality assurance in ambulatory care.
This article is one example of how a more simplified audit system for evaluating patient outcomes can be implemented and can be applied to an ambulatory care setting. Quality assurance activities are here to stay, either as a result of our feeling a professional obligation to monitor our own practice in relationship to the public we serve, or as a result of pressure from consumers and third-party payers. I prefer to believe that as professionals, we do recognize our obligation to be accountable for our actions, and that only we can set the standards of practice to which we will be held accountable. Through the development of criteria for care, we are able to establish these standards of practice. In complex care settings such as our Ambulatory Care Service, the CMA/CHA audit process is a reasonable approach to assuring quality by looking at patient outcomes. This process supports the team approach to patient care, is a less expensive method because less time is required to orient personnel to the audit process, and meets JCAH requirements for accreditation.


Implantation and Establishment of Pregnancy in Ruminants.
The establishment of pregnancy in ruminants occurs during the peri-implantation period and involves the suppression of the endometrial luteolytic mechanism to maintain progesterone production by the corpus luteum (CL). Reciprocal interactions between the elongating conceptus (embryo/fetus and associated extraembryonic membranes) and endometrium culminate in implantation. Antiluteolytic effects of the conceptus are due to the production of interferon tau (IFNT) by the trophoblast that has a paracrine effect to inhibit the upregulation of oxytocin receptors in the endometrial epithelia, thereby disrupting uterine release of luteolytic prostaglandin F2 alpha (PGF) pulses. Additionally, IFNT is released into the uterine vein and has endocrine actions to induce ISGs in peripheral tissues. For example, IFNT may induce luteal resistance to PGF, thereby ensuring survival of the CL and maintenance of pregnancy. Survival of the blastocyst and elongation of the conceptus requires embryotrophic factors from the epithelia of the uterus, and those embryotrophic factors are regulated by ovarian progesterone as well as conceptus-derived factors including IFNT and prostaglandins. This review provides new concepts on mechanisms of the establishment of pregnancy and implantation in ruminants with emphasis on conceptus-maternal signaling associated with elongation of the blastocyst and endometrial responses to the presence of a conceptus.


Ageing of radiation-sterilized polypropylene: changes in semicrystallinity.
Studies on radiation sterilization of isotactic polypropylene intended for biomedical applications were carried out for uncovered and covered samples. The effect of ageing on these samples was studied by determining the changes in relative crystallinity. The semicrystalline nature of the polymer is responsible for the changes in crystallinity. The transitions between short- and long-range order and short- and long-duration stiffness in both covered and uncovered samples, reflected in changes in relative crystallinity, were highly affected by the formation of branches in the backbone of the polymer. The high degree of branching in covered samples resulted in greater long-duration stiffness in the transition between short- and long-duration stiffness. The high degree of branching in covered samples was attributed to the high diffusion of energized oxygen into the polymer matrix compared with uncovered samples. The changes in relative crystallinity were rapid in uncovered samples (70% max; 34% min) but rather slow in covered samples (87% max; 43% min).


Monocytes/macrophages activation contributes to b-gamma-glutamyltransferase accumulation inside atherosclerotic plaques.
Gamma-glutamyltransferase (GGT) is a well-established independent risk factor for cardiovascular mortality related to atherosclerotic disease. Four GGT fractions have been identified in plasma, but only b-GGT fraction accumulates in atherosclerotic plaques, and correlates with other histological markers of vulnerability. The present study was aimed to evaluate whether macrophagic lineage cells may provide a source of b-GGT within the atherosclerotic plaque. GGT expression and release were studied in human monocytes isolated from peripheral blood of healthy donors. The growth factors GM-CSF and M-CSF were used to induce differentiation into M1-like and M2-like macrophages, respectively. Plaque GGT was investigated in tissue samples obtained from patients undergoing carotid endoarterectomy. We found that M1-like macrophages express higher levels of GGT as compared to M2-like, and that both monocytes and M1-like macrophages-but not M2-like-are able to release the b-GGT fraction upon activation with pro-inflammatory stimuli. Western blot analysis of b-GGT extracted from plaques confirmed the presence of a GGT immunoreactive peptide coincident with that of macrophages. Our data indicate that macrophages characterized by a pro-inflammatory phenotype may contribute to intra-plaque accumulation of b-GGT, which in turn may play a role in the progression of atherosclerosis by modulating inflammatory processes and favouring plaque instability.


YBX1 as an oncogenic factor in T-cell acute lymphoblastic leukemia.
Y-box-binding protein 1 (YBX1), a member of the RNA-binding protein family, is a critical regulator of cell survival in various solid tumors and acute myeloid leukemia. However, the function of YBX1 in T-cell acute lymphoblastic leukemia (T-ALL) remains elusive. Here, we found that YBX1 was upregulated in patients with T-ALL, T-ALL cell lines, and NOTCH1-induced T-ALL mice. Furthermore, depletion of YBX1 dramatically reduced cell proliferation, induced cell apoptosis, and induced G0/G1 phase arrest in vitro. Moreover, YBX1 depletion significantly decreased the leukemia burden in the human T-ALL xenograft and NOTCH1-induced T-ALL mice model in vivo. Mechanistically, downregulation of YBX1 markedly inhibited the expression of total AKT serine/threonine kinase (AKT), p-AKT, total extracellular signal-regulated kinase (ERK), and p-ERK in T-ALL cells. Taken together, our results uncovered a critical role of YBX1 in the leukemogenesis of T-ALL, which may have great potential as a biomarker and therapeutic target in T-ALL.